Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment.

PubMed

Bayer, T A; Wirths, O

2008-02-01

Accumulating evidence points to an important role of intraneuronal Abeta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Abeta instead of extracellular Abeta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Abeta42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.

Effector-triggered immunity: from pathogen perception to robust defense.

PubMed

Cui, Haitao; Tsuda, Kenichi; Parker, Jane E

2015-01-01

In plant innate immunity, individual cells have the capacity to sense and respond to pathogen attack. Intracellular recognition mechanisms have evolved to intercept perturbations by pathogen virulence factors (effectors) early in host infection and convert it to rapid defense. One key to resistance success is a polymorphic family of intracellular nucleotide-binding/leucine-rich-repeat (NLR) receptors that detect effector interference in different parts of the cell. Effector-activated NLRs connect, in various ways, to a conserved basal resistance network in order to transcriptionally boost defense programs. Effector-triggered immunity displays remarkable robustness against pathogen disturbance, in part by employing compensatory mechanisms within the defense network. Also, the mobility of some NLRs and coordination of resistance pathways across cell compartments provides flexibility to fine-tune immune outputs. Furthermore, a number of NLRs function close to the nuclear chromatin by balancing actions of defense-repressing and defense-activating transcription factors to program cells dynamically for effective disease resistance.

Robust Water Supply Infrastructure Development Pathways: What, When and Where Matters the Most? (INVITED)

NASA Astrophysics Data System (ADS)

Reed, Patrick; Zeff, Harrison; Characklis, Gregory

2017-04-01

Water supply adaptation frameworks that seek robustness must adaptively trigger actions that are contextually appropriate to emerging system observations and avoid long term high regret lock-ins. As an example, emerging water scarcity concerns in southeastern United States are associated with several deeply uncertain factors, including rapid population growth, limited coordination across adjacent municipalities and the increasing risks for sustained regional droughts. Managing these uncertainties will require that regional water utilities identify regionally coordinated, scarcity-mitigating infrastructure development pathways that trigger time appropriate actions. Mistakes can lead to water shortages, overbuilt stranded assets and possibly financial failures. This presentation uses the Research Triangle area of North Carolina to illustrate the key concerns and challenges that emerged when helping Raleigh, Durham, Cary and Chapel Hill develop their long term water supply infrastructure pathways through 2060. This example shows how the region's water utilities' long term infrastructure pathways are strongly shaped by their short term conservation policies (i.e., reacting to evolving demands) and their ability to consider regional water transfers (i.e., reacting to supply imbalances). Cooperatively developed, shared investments across the four municipalities expand their capacity to use short term transfers to better manage severe droughts with fewer investments in irreversible infrastructure options. Cooperative pathways are also important for avoiding regional robustness conflicts, where one party benefits strongly at the expense of one or more the others. A significant innovation of this work is the exploitation of weekly and annual dynamic risk-of-failure action triggers that exploit evolving feedbacks between co-evolving human demands and regional supplies. These dynamic action triggers provide high levels of adaptivity, tailor actions to their specific context, and motivate the value of joint human—natural system observation systems. The insights from this work have general merit globally for urban regions where adjacent municipalities can benefit from cooperative planning.

VHDL implementation of feature-extraction algorithm for the PANDA electromagnetic calorimeter

NASA Astrophysics Data System (ADS)

Guliyev, E.; Kavatsyuk, M.; Lemmens, P. J. J.; Tambave, G.; Löhner, H.; Panda Collaboration

2012-02-01

A simple, efficient, and robust feature-extraction algorithm, developed for the digital front-end electronics of the electromagnetic calorimeter of the PANDA spectrometer at FAIR, Darmstadt, is implemented in VHDL for a commercial 16 bit 100 MHz sampling ADC. The source-code is available as an open-source project and is adaptable for other projects and sampling ADCs. Best performance with different types of signal sources can be achieved through flexible parameter selection. The on-line data-processing in FPGA enables to construct an almost dead-time free data acquisition system which is successfully evaluated as a first step towards building a complete trigger-less readout chain. Prototype setups are studied to determine the dead-time of the implemented algorithm, the rate of false triggering, timing performance, and event correlations.

Enzymatically triggered rupture of polymersomes.

PubMed

Jang, Woo-Sik; Park, Seung Chul; Reed, Ellen H; Dooley, Kevin P; Wheeler, Samuel F; Lee, Daeyeon; Hammer, Daniel A

2016-01-28

Polymersomes are robust vesicles made from amphiphilic block co-polymers. Large populations of uniform giant polymersomes with defined, entrapped species can be made by templating of double-emulsions using microfluidics. In the present study, a series of two enzymatic reactions, one inside and the other outside of the polymersome, were designed to induce rupture of polymersomes. We measured how the kinetics of rupture were affected by altering enzyme concentration. These results suggest that protocells with entrapped enzymes can be engineered to secrete contents on cue.

On the robustness of SAC silencing in closed mitosis

NASA Astrophysics Data System (ADS)

Ruth, Donovan; Liu, Jian

Mitosis equally partitions sister chromatids to two daughter cells. This is achieved by properly attaching these chromatids via their kinetochores to microtubules that emanate from the spindle poles. Once the last kinetochore is properly attached, the spindle microtubules pull the sister chromatids apart. Due to the dynamic nature of microtubules, however, kinetochore-microtubule attachment often goes wrong. When this erroneous attachment occurs, it locally activates an ensemble of proteins, called the spindle assembly checkpoint proteins (SAC), which halts the mitotic progression until all the kinetochores are properly attached by spindle microtubules. The timing of SAC silencing thus determines the fidelity of chromosome segregation. We previously established a spatiotemporal model that addresses the robustness of SAC silencing in open mitosis for the first time. Here, we focus on closed mitosis by examining yeast mitosis as a model system. Though much experimental work has been done to study the SAC in cells undergoing closed mitosis, the processes responsible are not well understood. We leverage and extend our previous model to study SAC silencing mechanism in closed mitosis. We show that a robust signal of the SAC protein accumulation at the spindle pole body can be achieved. This signal is a nonlinear increasing function of number of kinetochore-microtubule attachments, and can thus serve as a robust trigger to time the SAC silencing. Together, our mechanism provides a unified framework across species that ensures robust SAC silencing and fidelity of chromosome segregation in mitosis. Intramural research program in NHLBI at NIH.

Modeling and analyzing cascading dynamics of the Internet based on local congestion information

NASA Astrophysics Data System (ADS)

Zhu, Qian; Nie, Jianlong; Zhu, Zhiliang; Yu, Hai; Xue, Yang

2018-06-01

Cascading failure has already become one of the vital issues in network science. By considering realistic network operational settings, we propose the congestion function to represent the congested extent of node and construct a local congestion-aware routing strategy with a tunable parameter. We investigate the cascading failures on the Internet triggered by deliberate attacks. Simulation results show that the tunable parameter has an optimal value that makes the network achieve a maximum level of robustness. The robustness of the network has a positive correlation with tolerance parameter, but it has a negative correlation with the packets generation rate. In addition, there exists a threshold of the attacking proportion of nodes that makes the network achieve the lowest robustness. Moreover, by introducing the concept of time delay for information transmission on the Internet, we found that an increase of the time delay will decrease the robustness of the network rapidly. The findings of the paper will be useful for enhancing the robustness of the Internet in the future.

PROPELLER for motion-robust imaging of in vivo mouse abdomen at 9.4 T.

PubMed

Teh, Irvin; Golay, Xavier; Larkman, David J

2010-11-01

In vivo high-field MRI in the abdomen of small animals is technically challenging because of the small voxel sizes, short T(2) and physiological motion. In standard Cartesian sampling, respiratory and gastrointestinal motion can lead to ghosting artefacts. Although respiratory triggering and navigator echoes can either avoid or compensate for motion, they can lead to variable TRs, require invasive intubation and ventilation, or extend TEs. A self-navigated fast spin echo (FSE)-based periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) acquisition was implemented at 9.4 T to enable high-resolution in vivo MRI of mouse abdomen without the use of additional navigators or triggering. T(2)-weighted FSE-PROPELLER data were compared with single-shot FSE and multi-shot FSE data with and without triggering. Single-shot methods, although rapid and robust to motion, demonstrated strong blurring. Multi-shot FSE data showed better resolution, but suffered from marked blurring in the phase-encoding direction and motion in between shots, leading to ghosting artefacts. When respiratory triggering was used, motion artefacts were largely avoided. However, TRs and acquisition times were lengthened by up to approximately 20%. The PROPELLER data showed a 25% and 61% improvement in signal-to-noise ratio and contrast-to-noise ratio, respectively, compared with multi-shot FSE data, together with a 35% reduction in artefact power. A qualitative comparison between acquisition methods using diffusion-weighted imaging was performed. The results were similar, with the exception that respiratory triggering was unable to exclude major motion artefacts as a result of the sensitisation to motion by the diffusion gradients. The PROPELLER data were of consistently higher quality. Considerations specific to the use of PROPELLER at high field are discussed, including the selection of practical blade widths and the effects on contrast, resolution and artefacts.

Suicidality in Bipolar Disorder: The Role of Emotion-Triggered Impulsivity

PubMed Central

Johnson, Sheri L.; Carver, Charles S.; Tharp, Jordan A.

2018-01-01

A growing body of research suggests that impulsive responses to emotion more robustly predict suicidality than do other forms of impulsivity. This issue has not yet been examined within bipolar disorder, however. Participants diagnosed with bipolar I disorder (n = 133) and control participants (n = 110) diagnosed with no mood or psychotic disorder completed self-report measures of emotion-triggered impulsivity (Negative and Positive Urgency Scales) and interviews concerning lifetime suicidality. Analyses examined the effects of emotion-triggered impulsivity alone and in combination with gender, age of onset, depression severity, comorbid anxiety, comorbid substance use, and medication. A history of suicide ideation and attempts, as well as self-harm, were significantly more common in the bipolar disorder group compared with the control group. Impulsive responses to positive emotions related to suicide ideation, attempts, and self-harm within the bipolar group. Findings extend research on the importance of emotion-triggered impulsivity to a broad range of key outcomes within bipolar disorder. The discussion focuses on limitations and potential clinical implications. PMID:27406282

Event-triggered resilient filtering with stochastic uncertainties and successive packet dropouts via variance-constrained approach

NASA Astrophysics Data System (ADS)

Jia, Chaoqing; Hu, Jun; Chen, Dongyan; Liu, Yurong; Alsaadi, Fuad E.

2018-07-01

In this paper, we discuss the event-triggered resilient filtering problem for a class of time-varying systems subject to stochastic uncertainties and successive packet dropouts. The event-triggered mechanism is employed with hope to reduce the communication burden and save network resources. The stochastic uncertainties are considered to describe the modelling errors and the phenomenon of successive packet dropouts is characterized by a random variable obeying the Bernoulli distribution. The aim of the paper is to provide a resilient event-based filtering approach for addressed time-varying systems such that, for all stochastic uncertainties, successive packet dropouts and filter gain perturbation, an optimized upper bound of the filtering error covariance is obtained by designing the filter gain. Finally, simulations are provided to demonstrate the effectiveness of the proposed robust optimal filtering strategy.

Room temperature solid-state quantum emitters in the telecom range.

PubMed

Zhou, Yu; Wang, Ziyu; Rasmita, Abdullah; Kim, Sejeong; Berhane, Amanuel; Bodrog, Zoltán; Adamo, Giorgio; Gali, Adam; Aharonovich, Igor; Gao, Wei-Bo

2018-03-01

On-demand, single-photon emitters (SPEs) play a key role across a broad range of quantum technologies. In quantum networks and quantum key distribution protocols, where photons are used as flying qubits, telecom wavelength operation is preferred because of the reduced fiber loss. However, despite the tremendous efforts to develop various triggered SPE platforms, a robust source of triggered SPEs operating at room temperature and the telecom wavelength is still missing. We report a triggered, optically stable, room temperature solid-state SPE operating at telecom wavelengths. The emitters exhibit high photon purity (~5% multiphoton events) and a record-high brightness of ~1.5 MHz. The emission is attributed to localized defects in a gallium nitride (GaN) crystal. The high-performance SPEs embedded in a technologically mature semiconductor are promising for on-chip quantum simulators and practical quantum communication technologies.

The evolution of the Trigger and Data Acquisition System in the ATLAS experiment

NASA Astrophysics Data System (ADS)

Krasznahorkay, A.; Atlas Collaboration

2014-06-01

The ATLAS experiment, aimed at recording the results of LHC proton-proton collisions, is upgrading its Trigger and Data Acquisition (TDAQ) system during the current LHC first long shutdown. The purpose of the upgrade is to add robustness and flexibility to the selection and the conveyance of the physics data, simplify the maintenance of the infrastructure, exploit new technologies and, overall, make ATLAS data-taking capable of dealing with increasing event rates. The TDAQ system used to date is organised in a three-level selection scheme, including a hardware-based first-level trigger and second- and third-level triggers implemented as separate software systems distributed on separate, commodity hardware nodes. While this architecture was successfully operated well beyond the original design goals, the accumulated experience stimulated interest to explore possible evolutions. We will also be upgrading the hardware of the TDAQ system by introducing new elements to it. For the high-level trigger, the current plan is to deploy a single homogeneous system, which merges the execution of the second and third trigger levels, still separated, on a unique hardware node. Prototyping efforts already demonstrated many benefits to the simplified design. In this paper we report on the design and the development status of this new system.

Robust calibration of an optical-lattice depth based on a phase shift

NASA Astrophysics Data System (ADS)

Cabrera-Gutiérrez, C.; Michon, E.; Brunaud, V.; Kawalec, T.; Fortun, A.; Arnal, M.; Billy, J.; Guéry-Odelin, D.

2018-04-01

We report on a method to calibrate the depth of an optical lattice. It consists of triggering the intrasite dipole mode of the cloud by a sudden phase shift. The corresponding oscillatory motion is directly related to the interband frequencies on a large range of lattice depths. Remarkably, for a moderate displacement, a single frequency dominates the oscillation of the zeroth and first orders of the interference pattern observed after a sufficiently long time of flight. The method is robust against atom-atom interactions and the exact value of the extra weak external confinement superimposed to the optical lattice.

Highlight on Supernova Early Warning at Daya Bay

NASA Astrophysics Data System (ADS)

Wei, Hanyu

Providing an early warning of supernova burst neutrinos is of importance in studying both supernova dynamics and neutrino physics. The Daya Bay Reactor Neutrino Experiment, with a unique feature of multiple liquid scintillator detectors, is sensitive to the full energy spectrum of supernova burst electron-antineutrinos. By utilizing 8 Antineutrino Detectors (ADs) in the three different experimental halls which are about 1 km's apart from each other, we obtain a powerful and prompt rejection of muon spallation background than single-detector experiments with the same target volume. A dedicated trigger system embedded in the data acquisition system has been installed to allow the detection of a coincidence of neutrino signals of all ADs via an inverse beta-decay (IBD) within a 10-second window, thus providing a robust early warning of a supernova occurrence within the Milky Way. An 8-AD associated supernova trigger table has been established theoretically to tabulate the 8-AD event counts' coincidence vs. the trigger rate. As a result, a golden trigger threshold, i.e. with a false alarm rate < 1/3-months, can be set as low as 6 candidates among the 8 detectors, leading to a 100% detection probability for all 1987A type supernova bursts at the distance to the Milky Way center and a 96% detection probability to those at the edge of the Milky Way.

Stability of the Effect of a Standardized Meal on QTc.

PubMed

Täubel, Jörg; Fernandes, Sara; Ferber, Georg

2017-01-01

The assessment of QTc changes after the intake of a standardized meal has been proposed as an alternative approach to prove assay sensitivity when the proarrhythimic potential of a drug is to be excluded in either TQT or intensive Phase I QT studies. In this article, an analysis of the food effect at baseline across periods in two different studies is presented to support the robustness of the method. The results show that the time-effect attributed to food is stable over different study periods demonstrating consistency of the physiological response triggered by food. Stability and reproducibility of the effect is comparable with moxifloxacin. © 2016 Wiley Periodicals, Inc.

A hardware fast tracker for the ATLAS trigger

NASA Astrophysics Data System (ADS)

Asbah, Nedaa

2016-09-01

The trigger system of the ATLAS experiment is designed to reduce the event rate from the LHC nominal bunch crossing at 40 MHz to about 1 kHz, at the design luminosity of 1034 cm-2 s-1. After a successful period of data taking from 2010 to early 2013, the LHC already started with much higher instantaneous luminosity. This will increase the load on High Level Trigger system, the second stage of the selection based on software algorithms. More sophisticated algorithms will be needed to achieve higher background rejection while maintaining good efficiency for interesting physics signals. The Fast TracKer (FTK) is part of the ATLAS trigger upgrade project. It is a hardware processor that will provide, at every Level-1 accepted event (100 kHz) and within 100 microseconds, full tracking information for tracks with momentum as low as 1 GeV. Providing fast, extensive access to tracking information, with resolution comparable to the offline reconstruction, FTK will help in precise detection of the primary and secondary vertices to ensure robust selections and improve the trigger performance. FTK exploits hardware technologies with massive parallelism, combining Associative Memory ASICs, FPGAs and high-speed communication links.

Online track detection in triggerless mode for INO

NASA Astrophysics Data System (ADS)

Jain, A.; Padmini, S.; Joseph, A. N.; Mahesh, P.; Preetha, N.; Behere, A.; Sikder, S. S.; Majumder, G.; Behera, S. P.

2018-03-01

The India based Neutrino Observatory (INO) is a proposed particle physics research project to study the atmospheric neutrinos. INO-Iron Calorimeter (ICAL) will consist of 28,800 detectors having 3.6 million electronic channels expected to activate with 100 Hz single rate, producing data at a rate of 3 GBps. Data collected contains a few real hits generated by muon tracks and the remaining noise-induced spurious hits. Estimated reduction factor after filtering out data of interest from generated data is of the order of 103. This makes trigger generation critical for efficient data collection and storage. Trigger is generated by detecting coincidence across multiple channels satisfying trigger criteria, within a small window of 200 ns in the trigger region. As the probability of neutrino interaction is very low, track detection algorithm has to be efficient and fast enough to process 5 × 106 events-candidates/s without introducing significant dead time, so that not even a single neutrino event is missed out. A hardware based trigger system is presently proposed for on-line track detection considering stringent timing requirements. Though the trigger system can be designed with scalability, a lot of hardware devices and interconnections make it a complex and expensive solution with limited flexibility. A software based track detection approach working on the hit information offers an elegant solution with possibility of varying trigger criteria for selecting various potentially interesting physics events. An event selection approach for an alternative triggerless readout scheme has been developed. The algorithm is mathematically simple, robust and parallelizable. It has been validated by detecting simulated muon events for energies of the range of 1 GeV-10 GeV with 100% efficiency at a processing rate of 60 μs/event on a 16 core machine. The algorithm and result of a proof-of-concept for its faster implementation over multiple cores is presented. The paper also discusses about harnessing the computing capabilities of multi-core computing farm, thereby optimizing number of nodes required for the proposed system.

Triggering and Quenching: simulations and mock observations of Active Galactic Nuclei and their hosts

NASA Astrophysics Data System (ADS)

Choi, Ena

2015-10-01

The lives of galaxies and their supermassive black holes (SMBH) are probably intimately linked. Deep multi-wavelength surveys with HST are now providing detailed imaging of a statistically robust sample of obscured and unobscured AGN hosts, along with control samples of inactive galaxies, giving us an unprecedented opportunity to study the relationship between AGN and their hosts. However, so far these observations have uncovered more puzzles than they have resolved. Although mergers are considered a promising triggering mechanism for AGN activity, numerous studies have shown that AGN hosts are no more likely to appear morphologically disturbed than inactive galaxies. Studies of whether AGN hosts exhibit enhanced or suppressed star formation have also yielded conflicting results. We propose to run a suite of state-of-the-art simulations to study the AGN-host galaxy connection. These simulations will be post-processed with a radiative transfer code, a sub-grid model for torus-scale obscuration, and short timescale AGN variability. Using mock images created from the simulations, we will study the predicted morphologies and stellar populations of AGN hosts and normal galaxies with similar stellar masses. We will use our simulations to address two major science questions: (1) how is SMBH growth fueled and fed, and what triggers rapid feeding, and (2) how does AGN feedback regulate BH growth and the growth of the host galaxy? In addition, we will release our simulation outputs and mock images and catalogs to the community through MAST.

Roles of small RNAs in plant disease resistance.

PubMed

Yang, Li; Huang, Hai

2014-10-01

The interaction between plants and pathogens represents a dynamic competition between a robust immune system and efficient infectious strategies. Plant innate immunity is composed of complex and highly regulated molecular networks, which can be triggered by the perception of either conserved or race-specific pathogenic molecular signatures. Small RNAs are emerging as versatile regulators of plant development, growth and response to biotic and abiotic stresses. They act in different tiers of plant immunity, including the pathogen-associated molecular pattern-triggered and the effector-triggered immunity. On the other hand, pathogens have evolved effector molecules to suppress or hijack the host small RNA pathways. This leads to an arms race between plants and pathogens at the level of small RNA-mediated defense. Here, we review recent advances in small RNA-mediated defense responses and discuss the challenging questions in this area. © 2014 Institute of Botany, Chinese Academy of Sciences.

Room temperature solid-state quantum emitters in the telecom range

PubMed Central

Bodrog, Zoltán; Adamo, Giorgio; Gali, Adam

2018-01-01

On-demand, single-photon emitters (SPEs) play a key role across a broad range of quantum technologies. In quantum networks and quantum key distribution protocols, where photons are used as flying qubits, telecom wavelength operation is preferred because of the reduced fiber loss. However, despite the tremendous efforts to develop various triggered SPE platforms, a robust source of triggered SPEs operating at room temperature and the telecom wavelength is still missing. We report a triggered, optically stable, room temperature solid-state SPE operating at telecom wavelengths. The emitters exhibit high photon purity (~5% multiphoton events) and a record-high brightness of ~1.5 MHz. The emission is attributed to localized defects in a gallium nitride (GaN) crystal. The high-performance SPEs embedded in a technologically mature semiconductor are promising for on-chip quantum simulators and practical quantum communication technologies. PMID:29670945

Autocalibrating motion-corrected wave-encoding for highly accelerated free-breathing abdominal MRI.

PubMed

Chen, Feiyu; Zhang, Tao; Cheng, Joseph Y; Shi, Xinwei; Pauly, John M; Vasanawala, Shreyas S

2017-11-01

To develop a motion-robust wave-encoding technique for highly accelerated free-breathing abdominal MRI. A comprehensive 3D wave-encoding-based method was developed to enable fast free-breathing abdominal imaging: (a) auto-calibration for wave-encoding was designed to avoid extra scan for coil sensitivity measurement; (b) intrinsic butterfly navigators were used to track respiratory motion; (c) variable-density sampling was included to enable compressed sensing; (d) golden-angle radial-Cartesian hybrid view-ordering was incorporated to improve motion robustness; and (e) localized rigid motion correction was combined with parallel imaging compressed sensing reconstruction to reconstruct the highly accelerated wave-encoded datasets. The proposed method was tested on six subjects and image quality was compared with standard accelerated Cartesian acquisition both with and without respiratory triggering. Inverse gradient entropy and normalized gradient squared metrics were calculated, testing whether image quality was improved using paired t-tests. For respiratory-triggered scans, wave-encoding significantly reduced residual aliasing and blurring compared with standard Cartesian acquisition (metrics suggesting P < 0.05). For non-respiratory-triggered scans, the proposed method yielded significantly better motion correction compared with standard motion-corrected Cartesian acquisition (metrics suggesting P < 0.01). The proposed methods can reduce motion artifacts and improve overall image quality of highly accelerated free-breathing abdominal MRI. Magn Reson Med 78:1757-1766, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Transcriptomic analysis reveals tomato genes whose expression is induced specifically during effector-triggered immunity and identifies the Epk1 protein kinase which is required for the host response to three bacterial effector proteins.

PubMed

Pombo, Marina A; Zheng, Yi; Fernandez-Pozo, Noe; Dunham, Diane M; Fei, Zhangjun; Martin, Gregory B

2014-01-01

Plants have two related immune systems to defend themselves against pathogen attack. Initially,pattern-triggered immunity is activated upon recognition of microbe-associated molecular patterns by pattern recognition receptors. Pathogenic bacteria deliver effector proteins into the plant cell that interfere with this immune response and promote disease. However, some plants express resistance proteins that detect the presence of specific effectors leading to a robust defense response referred to as effector-triggered immunity. The interaction of tomato with Pseudomonas syringae pv. tomato is an established model system for understanding the molecular basis of these plant immune responses. We apply high-throughput RNA sequencing to this pathosystem to identify genes whose expression changes specifically during pattern-triggered or effector-triggered immunity. We then develop reporter genes for each of these responses that will enable characterization of the host response to the large collection of P. s. pv. tomato strains that express different combinations of effectors. Virus-induced gene silencing of 30 of the effector-triggered immunity-specific genes identifies Epk1 which encodes a predicted protein kinase from a family previously unknown to be involved in immunity. Knocked-down expression of Epk1 compromises effector-triggered immunity triggered by three bacterial effectors but not by effectors from non-bacterial pathogens. Epistasis experiments indicate that Epk1 acts upstream of effector-triggered immunity-associated MAP kinase signaling. Using RNA-seq technology we identify genes involved in specific immune responses. A functional genomics screen led to the discovery of Epk1, a novel predicted protein kinase required for plant defense activation upon recognition of three different bacterial effectors.

Event-triggered fault detection for a class of discrete-time linear systems using interval observers.

PubMed

Zhang, Zhi-Hui; Yang, Guang-Hong

2017-05-01

This paper provides a novel event-triggered fault detection (FD) scheme for discrete-time linear systems. First, an event-triggered interval observer is proposed to generate the upper and lower residuals by taking into account the influence of the disturbances and the event error. Second, the robustness of the residual interval against the disturbances and the fault sensitivity are improved by introducing l 1 and H ∞ performances. Third, dilated linear matrix inequalities are used to decouple the Lyapunov matrices from the system matrices. The nonnegative conditions for the estimation error variables are presented with the aid of the slack matrix variables. This technique allows considering a more general Lyapunov function. Furthermore, the FD decision scheme is proposed by monitoring whether the zero value belongs to the residual interval. It is shown that the information communication burden is reduced by designing the event-triggering mechanism, while the FD performance can still be guaranteed. Finally, simulation results demonstrate the effectiveness of the proposed method. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Suicidality in Bipolar Disorder: The Role of Emotion-Triggered Impulsivity.

PubMed

Johnson, Sheri L; Carver, Charles S; Tharp, Jordan A

2017-04-01

A growing body of research suggests that impulsive responses to emotion more robustly predict suicidality than do other forms of impulsivity. This issue has not yet been examined within bipolar disorder, however. Participants diagnosed with bipolar I disorder (n = 133) and control participants (n = 110) diagnosed with no mood or psychotic disorder completed self-report measures of emotion-triggered impulsivity (Negative and Positive Urgency Scales) and interviews concerning lifetime suicidality. Analyses examined the effects of emotion-triggered impulsivity alone and in combination with gender, age of onset, depression severity, comorbid anxiety, comorbid substance use, and medication. A history of suicide ideation and attempts, as well as self-harm, were significantly more common in the bipolar disorder group compared with the control group. Impulsive responses to positive emotions related to suicide ideation, attempts, and self-harm within the bipolar group. Findings extend research on the importance of emotion-triggered impulsivity to a broad range of key outcomes within bipolar disorder. The discussion focuses on limitations and potential clinical implications. © 2016 The American Association of Suicidology.

An open repository of earthquake-triggered ground-failure inventories

USGS Publications Warehouse

Schmitt, Robert G.; Tanyas, Hakan; Nowicki Jessee, M. Anna; Zhu, Jing; Biegel, Katherine M.; Allstadt, Kate E.; Jibson, Randall W.; Thompson, Eric M.; van Westen, Cees J.; Sato, Hiroshi P.; Wald, David J.; Godt, Jonathan W.; Gorum, Tolga; Xu, Chong; Rathje, Ellen M.; Knudsen, Keith L.

2017-12-20

Earthquake-triggered ground failure, such as landsliding and liquefaction, can contribute significantly to losses, but our current ability to accurately include them in earthquake-hazard analyses is limited. The development of robust and widely applicable models requires access to numerous inventories of ground failures triggered by earthquakes that span a broad range of terrains, shaking characteristics, and climates. We present an openly accessible, centralized earthquake-triggered groundfailure inventory repository in the form of a ScienceBase Community to provide open access to these data with the goal of accelerating research progress. The ScienceBase Community hosts digital inventories created by both U.S. Geological Survey (USGS) and non-USGS authors. We present the original digital inventory files (when available) as well as an integrated database with uniform attributes. We also summarize the mapping methodology and level of completeness as reported by the original author(s) for each inventory. This document describes the steps taken to collect, process, and compile the inventories and the process for adding additional ground-failure inventories to the ScienceBase Community in the future.

Dynamic Triggering of Seismic Events and Their Relation to Slow Slip in Interior Alaska

NASA Astrophysics Data System (ADS)

Sims, N. E.; Holtkamp, S. G.

2017-12-01

We conduct a search for dynamically triggered events in the Minto Flats Fault Zone (MFFZ), a left-lateral strike-slip zone expressed as multiple, partially overlapping faults, in central Alaska. We focus on the MFFZ because we have observed slow slip processes (earthquake swarms and Very Low Frequency Earthquakes) and interaction between earthquake swarms and larger main-shock (MS) events in this area before. We utilize the Alaska Earthquake Center catalog to identify potential earthquake swarms and dynamically triggered foreshock and mainshock events along the fault zone. We find 30 swarms occurring in the last two decades, five of which we classify as foreshock (FS) swarms due to their close proximity in both time and space to MS events. Many of the earthquake swarms cluster around 15-20 km depth, which is near the seismic-aseismic transition along this fault zone. Additionally, we observe instances of large teleseismic events such as the M8.6 2012 Sumatra earthquake and M7.4 2012 Guatemala earthquake triggering seismic events within the MFFZ, with the Sumatra earthquake triggering a mainshock event that was preceded by an ongoing earthquake swarm and the Guatemala event triggering earthquake swarms that subsequently transition into a larger mainshock event. In both cases an earthquake swarm transitioned into a mainshock-aftershock event and activity continued for several days after the teleseismic waves had passed, lending some evidence to delayed dynamic triggering of seismic events. We hypothesize that large dynamic transient strain associated with the passage of teleseismic surface waves is triggering slow slip processes near the base of the seismogenic zone. These triggered aseismic transient events result in earthquake swarms, which sometimes lead to the nucleation of larger earthquakes. We utilize network matched filtering to build more robust catalogs of swarm earthquake families in this region to search for additional swarm-like or triggered activity in response to teleseismic surface waves, and to test dynamic triggering hypotheses.

Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.

PubMed

Nikolaev, Yury A; Dosen, Peter J; Laver, Derek R; van Helden, Dirk F; Hamill, Owen P

2015-05-22

The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)

Hypoxia triggers short term potentiation of phrenic motoneuron discharge after chronic cervical spinal cord injury

PubMed Central

Lee, Kun-Ze; Sandhu, Milapjit S.; Dougherty, Brendan J.; Reier, Paul J.; Fuller, David D.

2014-01-01

Repeated exposure to hypoxia can induce spinal neuroplasticity as well as respiratory and somatic motor recovery after spinal cord injury (SCI). The purpose of the present study was to define the capacity for a single bout of hypoxia to trigger short-term plasticity in phrenic output after cervical SCI, and to determine the phrenic motoneuron (PhrMN) bursting and recruitment patterns underlying the response. Hypoxia-induced short term potentiation (STP) of phrenic motor output was quantified in anesthetized rats 11 wks following lateral spinal hemisection at C2 (C2Hx). A 3-min hypoxic episode (12–14% O2) always triggered STP of inspiratory burst amplitude, the magnitude of which was greater in phrenic bursting ipsilateral vs. contralateral to C2Hx. We next determined if STP could be evoked in recruited (silent) PhrMNs ipsilateral to C2Hx. Individual PhrMN action potentials were recorded during and following hypoxia using a “single fiber” approach. STP of bursting activity did not occur in cells initiating bursting at inspiratory onset, but was robust in recruited PhrMNs as well as previously active cells initiating bursting later in the inspiratory effort. We conclude that following chronic C2Hx, a single bout of hypoxia triggers recruitment of PhrMNs in the ipsilateral spinal cord with bursting that persists beyond the hypoxic exposure. The results provide further support for the use of short bouts of hypoxia as a neurorehabilitative training modality following SCI. PMID:25448009

An alert system for triggering different levels of coastal management urgency: Tunisia case study using rapid environmental assessment data.

PubMed

Price, A R G; Jaoui, K; Pearson, M P; Jeudy de Grissac, A

2014-03-15

Rapid environmental assessment (REA) involves scoring abundances of ecosystems/species groups and magnitude of pressures, concurrently, using the same logarithmic (0-6) assessment scale. We demonstrate the utility of REA data for an alert system identifying different levels of coastal management concern. Thresholds set for abundances/magnitudes, when crossed, trigger proposed responses. Kerkennah, Tunisia, our case study, has significant natural assets (e.g. exceptional seagrass and invertebrate abundances), subjected to varying levels of disturbance and management concern. Using REA thresholds set, fishing, green algae/eutrophication and oil occurred at 'low' levels (scores 0-1): management not (currently) necessary. Construction and wood litter prevailed at 'moderate' levels (scores 2-4): management alerted for (further) monitoring. Solid waste densities were 'high' (scores 5-6): management alerted for action; quantities of rubbish were substantial (20-200 items m⁻¹ beach) but not unprecedented. REA is considered a robust methodology and complementary to other rapid assessment techniques, environmental frameworks and indicators of ecosystem condition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic adaptation to historical pathogen burdens.

PubMed

Fedderke, Johannes W; Klitgaard, Robert E; Napolioni, Valerio

2017-10-01

Historical pathogen burdens are examined as possible triggers for genetic adaptation. Evidence of adaptation emerges for the acid phosphatase locus 1 (ACP1), interleukin-6 (IL6), interleukin-10 (IL10 ), human leukocyte antigen (HLA) polymorphisms, along with a measure of heterozygosity over 783 alleles. Results are robust to controlling for the physical and historical environment humans faced, and to endogeneity of the historical pathogen burden measure. The present study represents a proof-of-concept which may pave the way to the analysis of future aggregate measures coming from whole-genome sequencing/genotyping data. Copyright © 2017 Elsevier B.V. All rights reserved.

Modifiable factors associated with changes in postpartum depressive symptoms.

PubMed

Howell, Elizabeth A; Mora, Pablo A; DiBonaventura, Marco D; Leventhal, Howard

2009-04-01

Up to 50% of mothers report postpartum depressive symptoms yet providers do a poor job predicting and preventing their occurrence. Our goal was to identify modifiable factors (situational triggers and buffers) associated with postpartum depressive symptoms. Observational prospective cohort telephone study of 563 mothers interviewed at 2 weeks and 6 months postpartum. Mothers reported on demographic factors, physical and emotional symptoms, daily function, infant behaviors, social support, and skills in managing infant and household. Mothers were categorized into four groups based on the presence of depressive symptoms at 2 weeks and at 6 months postpartum: never, always, late onset, and remission groups. Fifty-two percent did not have depressive symptoms at 2 weeks or at 6 months (never group), 14% had symptoms at both time points (always group), 10% had late onset, and 24% had early onset of symptoms with remission. As compared with women in the never group, women in the always and late onset groups had high-risk characteristics (e.g., past history of depression), more situational triggers (e.g., physical symptoms), and less robust social and personal buffers (i.e., social support and self-efficacy). As compared with the never group, mothers in the remission group had more situational triggers and fewer buffers initially. Changes in situational triggers and buffers were different for the four groups and were correlated with group membership. Situational triggers such as physical symptoms and infant colic, and low levels of social support and self-efficacy in managing situational demands are associated with postpartum depressive symptoms. Further research is needed to investigate whether providing education about the physical consequences of childbirth, providing social support, and teaching skills to enhance self-efficacy will reduce the incidence of postpartum symptoms of depression.

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery.

PubMed

Niedermayer, Stefan; Weiss, Veronika; Herrmann, Annika; Schmidt, Alexandra; Datz, Stefan; Müller, Katharina; Wagner, Ernst; Bein, Thomas; Bräuchle, Christoph

2015-05-07

A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.

Integrated action of pheromone signals in promoting courtship behavior in male mice

PubMed Central

Haga-Yamanaka, Sachiko; Ma, Limei; He, Jie; Qiu, Qiang; Lavis, Luke D; Looger, Loren L; Yu, C Ron

2014-01-01

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior. DOI: http://dx.doi.org/10.7554/eLife.03025.001 PMID:25073926

Emotional stress as a trigger of falls leading to hip or pelvic fracture. Results from the ToFa study - a case-crossover study among elderly people in Stockholm, Sweden.

PubMed

Möller, Jette; Hallqvist, Johan; Laflamme, Lucie; Mattsson, Fredrik; Ponzer, Sari; Sadigh, Siv; Engström, Karin

2009-02-09

Sudden emotions may interfere with mechanisms for keeping balance among the elderly. The aim of this study is to analyse if emotional stress and specifically feelings of anger, sadness, worries, anxiety or stress, can trigger falls leading to hip or pelvic fracture among autonomous older people. The study applied the case-crossover design and was based on data gathered by face to face interviews carried out in Stockholm between November 2004 and January 2006 at the emergency wards of two hospitals. Cases (n = 137) were defined as persons aged 65 and older admitted for at least one night due to a fall-related hip or pelvic fracture (ICD10: S72 or S32) and meeting a series of selection criteria. Results are presented as relative risks with 95% confidence intervals. There was an increased risk for fall and subsequent hip or pelvic fracture for up to one hour after emotional stress. For anger there was an increased relative risk of 12.2 (95% CI 2.7-54.7), for sadness of 5.7 (95% CI 1.1-28.7), and for stress 20.6 (95% CI 4.5-93.5) compared to periods with no such feelings. Emotional stress seems to have the potential to trigger falls and subsequent hip or pelvic fracture among autonomous older people. Further studies are needed to clarify how robust the findings are - as the number of exposed cases is small - and the mechanisms behind them - presumably balance and vision impairment in stress situation.

A binary link tracker for the BaBar level 1 trigger system

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

Berenyi, A.; Chen, H.K.; Dao, K.

1999-08-01

The BaBar detector at PEP-II will operate in a high-luminosity e{sup +}e{sup {minus}} collider environment near the {Upsilon}(4S) resonance with the primary goal of studying CP violation in the B meson system. In this environment, typical physics events of interest involve multiple charged particles. These events are identified by counting these tracks in a fast first level (Level 1) trigger system, by reconstructing the tracks in real time. For this purpose, a Binary Link Tracker Module (BLTM) was designed and fabricated for the BaBar Level 1 Drift Chamber trigger system. The BLTM is responsible for linking track segments, constructed bymore » the Track Segment Finder Modules (TSFM), into complete tracks. A single BLTM module processes a 360 MBytes/s stream of segment hit data, corresponding to information from the entire Drift Chamber, and implements a fast and robust algorithm that tolerates high hit occupancies as well as local inefficiencies of the Drift Chamber. The algorithms and the necessary control logic of the BLTM were implemented in Field Programmable Gate Arrays (FPGAs), using the VHDL hardware description language. The finished 9U x 400 mm Euro-format board contains roughly 75,000 gates of programmable logic or about 10,000 lines of VHDL code synthesized into five FPGAs.« less

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.

Programmable single-cell mammalian biocomputers.

PubMed

Ausländer, Simon; Ausländer, David; Müller, Marius; Wieland, Markus; Fussenegger, Martin

2012-07-05

Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms. Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits. Using trigger-controlled transcription factors, which independently control gene expression, and RNA-binding proteins that inhibit the translation of transcripts harbouring specific RNA target motifs, we have designed a set of synthetic transcription–translation control devices that could be rewired in a plug-and-play manner. Here we show that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells. Functional interconnection of two N-IMPLY variants resulted in bitwise intracellular XOR operations, and a combinatorial arrangement of three logic gates enabled independent cells to perform programmable half-subtractor and half-adder calculations. Individual mammalian cells capable of executing basic molecular arithmetic functions isolated or coordinated to metabolic activities in a predictable, precise and robust manner may provide new treatment strategies and bio-electronic interfaces in future gene-based and cell-based therapies.

UV-Triggered Self-Healing of a Single Robust SiO2 Microcapsule Based on Cationic Polymerization for Potential Application in Aerospace Coatings.

PubMed

Guo, Wanchun; Jia, Yin; Tian, Kesong; Xu, Zhaopeng; Jiao, Jiao; Li, Ruifei; Wu, Yuehao; Cao, Ling; Wang, Haiyan

2016-08-17

UV-triggered self-healing of single microcapsules has been a good candidate to enhance the life of polymer-based aerospace coatings because of its rapid healing process and healing chemistry based on an accurate stoichiometric ratio. However, free radical photoinitiators used in single microcapsules commonly suffer from possible deactivation due to the presence of oxygen in the space environment. Moreover, entrapment of polymeric microcapsules into coatings often involves elevated temperature or a strong solvent, probably leading to swelling or degradation of polymer shell, and ultimately the loss of active healing species into the host matrix. We herein describe the first single robust SiO2 microcapsule self-healing system based on UV-triggered cationic polymerization for potential application in aerospace coatings. On the basis of the similarity of solubility parameters of the active healing species and the SiO2 precursor, the epoxy resin and cationic photoinitiator are successfully encapsulated into a single SiO2 microcapsule via a combined interfacial/in situ polymerization. The single SiO2 microcapsule shows solvent resistance and thermal stability, especially a strong resistance for thermal cycling in a simulated space environment. In addition, the up to 89% curing efficiency of the epoxy resin in 30 min, and the obvious filling of scratches in the epoxy matrix demonstrate the excellent UV-induced healing performance of SiO2 microcapsules, attributed to a high load of healing species within the capsule (up to 87 wt %) and healing chemistry based on an accurate stoichiometric ratio of the photoinitiator and epoxy resin at 9/100. More importantly, healing chemistry based on a UV-triggered cationic polymerization mechanism is not sensitive to oxygen, extremely facilitating future embedment of this single SiO2 microcapsule in spacecraft coatings to achieve self-healing in a space environment with abundant UV radiation and oxygen.

Signaling mechanisms underlying the robustness and tunability of the plant immune network

PubMed Central

Kim, Yungil; Tsuda, Kenichi; Igarashi, Daisuke; Hillmer, Rachel A.; Sakakibara, Hitoshi; Myers, Chad L.; Katagiri, Fumiaki

2014-01-01

Summary How does robust and tunable behavior emerge in a complex biological network? We sought to understand this for the signaling network controlling pattern-triggered immunity (PTI) in Arabidopsis. A dynamic network model containing four major signaling sectors, the jasmonate, ethylene, PAD4, and salicylate sectors, which together explain up to 80% of the PTI level, was built using data for dynamic sector activities and PTI levels under exhaustive combinatorial sector perturbations. Our regularized multiple regression model had a high level of predictive power and captured known and unexpected signal flows in the network. The sole inhibitory sector in the model, the ethylene sector, was central to the network robustness via its inhibition of the jasmonate sector. The model's multiple input sites linked specific signal input patterns varying in strength and timing to different network response patterns, indicating a mechanism enabling tunability. PMID:24439900

Passive broadband targeted energy transfers and control of self-excited vibrations

NASA Astrophysics Data System (ADS)

Lee, Young S.

This work consists of the three main parts---Nonlinear energy pumping (that is, passive broadband targeted energy transfers---TETs), and its applications to theoretical and experimental suppression of aeroelastic instabilities. In the first part, nonlinear energy pumping (or TETs) in coupled oscillators is studied. The system is composed of a primary linear subsystem coupled through an essentially nonlinear stiffness and a linear viscous damper to an additional mass (which is called, as a whole, a nonlinear energy sink---NES). By considering the linear damping as a perturbation to the system, periodic solutions of the underlying Hamiltonian system are formulated by means of the non-smooth temporal transformation and solved numerically by a shooting method. The special periodic orbits, which are corresponding to the impulsive initial conditions for the primary subsystem, bear their importance as baits for initiating localized transfers of a significant portion of energy to the NES. The second part theoretically deals with suppression of limit cycle oscillations (LCOs) in self-excited systems by means of passive energy localizations. As a pilot scheme, suppression or even complete elimination of the LCO in a van der Pol (VDP) oscillator coupled with two types of NESS---grounded and ungrounded---is studied. Computational parametric study proves the efficacy of LCO elimination by means of passive nonlinear energy pumping from the VDP oscillator to appropriately designed NESs. The numerical study of the transient dynamics of the system showed that the dynamical mechanism for LCO suppression is a series of 1:1 and 1:3 transient resonance captures, with the damped transient dynamics following closely corresponding resonant manifolds of the underlying Hamiltonian system. It is through the TRCs that energy gets transferred from the VDP oscillator to the NES, thus causing LCO suppression. By performing an additional bifurcation analysis of the steady state responses through a numerical continuation of equilibria and periodic solutions, the parameter dependence and bifurcations of the steady-state solutions are examined. It is also proved that a Hopf bifurcation is the global dynamical mechanism for generation and elimination of the LCOs in the configurations considered. The bifurcation analysis revealed that it is possible to design grounded or ungrounded NESs that robustly and completely eliminate the LCO instability of the system. This should be possible when the system parameters are chosen such that a subcritical Hopf bifurcation occurs, thus assuring the existence of a unique global trivial attractor of the dynamics in the parameter ranges of interest. Then, triggering mechanisms of aeroelastic instability is investigated for a two-DOF rigid wing model in subsonic flow with cubic nonlinear stiffnesses at the support. Based on the observation of the instability triggering, a single-degree-of-freedom (SDOF) NES is applied to the wing model. The NES is attached at an offset from the elastic axis for its additional interaction with the pitch mode, as well as being parallel with the heave mode, primarily to hinder initial triggering of the heave mode by the flow. It is shown that it is feasible to partially or even completely suppress aeroelastic instabilities of the wing by passively transferring vibration energy from the wing to the NES in a one-way irreversible fashion. Moreover, this aeroelastic instability suppression is performed by partially or completely eliminating the triggering mechanists for aeroelastic suppression. Through numerical parametric studies three main mechanisms for suppressing aeroelastic instability are identified: (i) Recurring burst-out and suppression; (ii) intermediate suppression; (iii) complete elimination of instability. In general, the relative occurrence of one of the two limit point cycle (LPC) bifurcations with respect to the Hopf bifurcation decides whether or not the suppression mechanisms are robust. In order to improve robustness of instability suppression, several types of multi-DOF NES configurations are introduced. In the last part, experimental suppression of aeroelastic instability by means of targeted energy transfers is investigated. In order to gain insights into the experiments, theoretical triggering mechanism of the aeroelastic instability in the nonlinear aeroelastic test apparatus (NATA) in a low-speed wind tunnel at Texas A&M University is studied. Finally, experimental results are presented in connection to the theoretical investigation, and all the predictions on the instability suppression mechanisms are demonstrated experimentally. It is also revealed that the dry friction affects only the robustness of an instability suppression by changing the unstable trivial equilibrium into an equilibrium set. (Abstract shortened by UMI.)

Paying To Belong: When Does Rejection Trigger Ingratiation?

PubMed Central

Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S.; Rodriguez, Sylvia; Cavanaugh, Timothy J.; Pelayo, Rosemary

2010-01-01

Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction with robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual’s self-definition. Four studies tested the hypothesis that people high in rejection sensitivity, and therefore dispositionally concerned about rejection, will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In three studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a fourth study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly. PMID:20649367

Robustness of the filamentation instability for asymmetric plasma shells collision in arbitrarily oriented magnetic field

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

Bret, A.

2013-10-15

The filamentation instability triggered when two counter streaming plasma shells overlap appears to be the main mechanism by which collisionless shocks are generated. It has been known for long that a flow aligned magnetic field can completely suppress this instability. In a recent paper [Phys. Plasmas 18, 080706 (2011)], it was demonstrated in two dimensions that for the case of two cold, symmetric, relativistically colliding shells, such cancellation cannot occur if the field is not perfectly aligned. Here, this result is extended to the case of two asymmetric shells. The filamentation instability appears therefore as an increasingly robust mechanism tomore » generate shocks.« less

Mimicking subsecond neurotransmitter dynamics with femtosecond laser stimulated nanosystems.

PubMed

Nakano, Takashi; Chin, Catherine; Myint, David Mo Aung; Tan, Eng Wui; Hale, Peter John; Krishna M, Bala Murali; Reynolds, John N J; Wickens, Jeff; Dani, Keshav M

2014-06-23

Existing nanoscale chemical delivery systems target diseased cells over long, sustained periods of time, typically through one-time, destructive triggering. Future directions lie in the development of fast and robust techniques capable of reproducing the pulsatile chemical activity of living organisms, thereby allowing us to mimic biofunctionality. Here, we demonstrate that by applying programmed femtosecond laser pulses to robust, nanoscale liposome structures containing dopamine, we achieve sub-second, controlled release of dopamine--a key neurotransmitter of the central nervous system--thereby replicating its release profile in the brain. The fast delivery system provides a powerful new interface with neural circuits, and to the larger range of biological functions that operate on this short timescale.

ESD robustness improving for the low-voltage triggering silicon-controlled rectifier by adding NWell at cathode

NASA Astrophysics Data System (ADS)

Jin, Xiangliang; Zheng, Yifei; Wang, Yang; Guan, Jian; Hao, Shanwan; Li, Kan; Luo, Jun

2018-01-01

The low-voltage triggering silicon-controlled rectifier (LVTSCR) device is widely used in on-chip electrostatic discharge (ESD) protection owing to its low trigger voltage and strong current-tolerating capability per area. In this paper, an improved LVTSCR by adding a narrow NWell (NW2) under the source region of NMOS is discussed, which is realized in a 0.5-μm CMOS process. A 2-dimension (2D) device simulation platform and a transmission line pulse (TLP) testing system are used to predict and characterize the proposed ESD protection devices. According to the measurement results, compared with the preliminary LVTSCR, the improved LVTSCR elevates the second breakdown current (It2) from 2.39 A to 5.54 A and increases the holding voltage (Vh) from 3.04 V to 4.09 V without expanding device area or sacrificing any ESD performances. Furthermore, the influence of the size of the narrow NWell under the source region of NMOS on holding voltage is also discussed.

The food additive vanillic acid controls transgene expression in mammalian cells and mice.

PubMed

Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

2012-03-01

Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

Heterogeneous autoregressive model with structural break using nearest neighbor truncation volatility estimators for DAX.

PubMed

Chin, Wen Cheong; Lee, Min Cherng; Yap, Grace Lee Ching

2016-01-01

High frequency financial data modelling has become one of the important research areas in the field of financial econometrics. However, the possible structural break in volatile financial time series often trigger inconsistency issue in volatility estimation. In this study, we propose a structural break heavy-tailed heterogeneous autoregressive (HAR) volatility econometric model with the enhancement of jump-robust estimators. The breakpoints in the volatility are captured by dummy variables after the detection by Bai-Perron sequential multi breakpoints procedure. In order to further deal with possible abrupt jump in the volatility, the jump-robust volatility estimators are composed by using the nearest neighbor truncation approach, namely the minimum and median realized volatility. Under the structural break improvements in both the models and volatility estimators, the empirical findings show that the modified HAR model provides the best performing in-sample and out-of-sample forecast evaluations as compared with the standard HAR models. Accurate volatility forecasts have direct influential to the application of risk management and investment portfolio analysis.

Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

PubMed

Goggins, Sean; Marsh, Barrie J; Lubben, Anneke T; Frost, Christopher G

2015-08-01

Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.

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.

Reducing regional vulnerabilities and multi-city robustness conflicts using many-objective optimization under deep uncertainty

NASA Astrophysics Data System (ADS)

Reed, Patrick; Trindade, Bernardo; Jonathan, Herman; Harrison, Zeff; Gregory, Characklis

2016-04-01

Emerging water scarcity concerns in southeastern US are associated with several deeply uncertain factors, including rapid population growth, limited coordination across adjacent municipalities and the increasing risks for sustained regional droughts. Managing these uncertainties will require that regional water utilities identify regionally coordinated, scarcity-mitigating strategies that trigger the appropriate actions needed to avoid water shortages and financial instabilities. This research focuses on the Research Triangle area of North Carolina, seeking to engage the water utilities within Raleigh, Durham, Cary and Chapel Hill in cooperative and robust regional water portfolio planning. Prior analysis of this region through the year 2025 has identified significant regional vulnerabilities to volumetric shortfalls and financial losses. Moreover, efforts to maximize the individual robustness of any of the mentioned utilities also have the potential to strongly degrade the robustness of the others. This research advances a multi-stakeholder Many-Objective Robust Decision Making (MORDM) framework to better account for deeply uncertain factors when identifying cooperative management strategies. Results show that the sampling of deeply uncertain factors in the computational search phase of MORDM can aid in the discovery of management actions that substantially improve the robustness of individual utilities as well as the overall region to water scarcity. Cooperative water transfers, financial risk mitigation tools, and coordinated regional demand management must be explored jointly to decrease robustness conflicts between the utilities. The insights from this work have general merit for regions where adjacent municipalities can benefit from cooperative regional water portfolio planning.

Reducing regional vulnerabilities and multi-city robustness conflicts using many-objective optimization under deep uncertainty

NASA Astrophysics Data System (ADS)

Trindade, B. C.; Reed, P. M.; Herman, J. D.; Zeff, H. B.; Characklis, G. W.

2015-12-01

Emerging water scarcity concerns in southeastern US are associated with several deeply uncertain factors, including rapid population growth, limited coordination across adjacent municipalities and the increasing risks for sustained regional droughts. Managing these uncertainties will require that regional water utilities identify regionally coordinated, scarcity-mitigating strategies that trigger the appropriate actions needed to avoid water shortages and financial instabilities. This research focuses on the Research Triangle area of North Carolina, seeking to engage the water utilities within Raleigh, Durham, Cary and Chapel Hill in cooperative and robust regional water portfolio planning. Prior analysis of this region through the year 2025 has identified significant regional vulnerabilities to volumetric shortfalls and financial losses. Moreover, efforts to maximize the individual robustness of any of the mentioned utilities also have the potential to strongly degrade the robustness of the others. This research advances a multi-stakeholder Many-Objective Robust Decision Making (MORDM) framework to better account for deeply uncertain factors when identifying cooperative management strategies. Results show that the sampling of deeply uncertain factors in the computational search phase of MORDM can aid in the discovery of management actions that substantially improve the robustness of individual utilities as well as of the overall region to water scarcity. Cooperative water transfers, financial risk mitigation tools, and coordinated regional demand management should be explored jointly to decrease robustness conflicts between the utilities. The insights from this work have general merit for regions where adjacent municipalities can benefit from cooperative regional water portfolio planning.

Emotional stress as a trigger of falls leading to hip or pelvic fracture. Results from the ToFa study – a case-crossover study among elderly people in Stockholm, Sweden

PubMed Central

Möller, Jette; Hallqvist, Johan; Laflamme, Lucie; Mattsson, Fredrik; Ponzer, Sari; Sadigh, Siv; Engström, Karin

2009-01-01

Background Sudden emotions may interfere with mechanisms for keeping balance among the elderly. The aim of this study is to analyse if emotional stress and specifically feelings of anger, sadness, worries, anxiety or stress, can trigger falls leading to hip or pelvic fracture among autonomous older people. Methods The study applied the case-crossover design and was based on data gathered by face to face interviews carried out in Stockholm between November 2004 and January 2006 at the emergency wards of two hospitals. Cases (n = 137) were defined as persons aged 65 and older admitted for at least one night due to a fall-related hip or pelvic fracture (ICD10: S72 or S32) and meeting a series of selection criteria. Results are presented as relative risks with 95% confidence intervals. Results There was an increased risk for fall and subsequent hip or pelvic fracture for up to one hour after emotional stress. For anger there was an increased relative risk of 12.2 (95% CI 2.7–54.7), for sadness of 5.7 (95% CI 1.1–28.7), and for stress 20.6 (95% CI 4.5–93.5) compared to periods with no such feelings. Conclusion Emotional stress seems to have the potential to trigger falls and subsequent hip or pelvic fracture among autonomous older people. Further studies are needed to clarify how robust the findings are – as the number of exposed cases is small – and the mechanisms behind them – presumably balance and vision impairment in stress situation. PMID:19203356

VEGF-induced intracellular Ca2+ oscillations are down-regulated and do not stimulate angiogenesis in breast cancer-derived endothelial colony forming cells

PubMed Central

Ruffinatti, Federico Alessandro; Poletto, Valentina; Massa, Margherita; Tancredi, Richard; Zuccolo, Estella; Khdar, Dlzar Alì; Riccardi, Alberto; Biggiogera, Marco; Rosti, Vittorio; Guerra, Germano; Moccia, Francesco

2017-01-01

Endothelial colony forming cells (ECFCs) represent a population of truly endothelial precursors that promote the angiogenic switch in solid tumors, such as breast cancer (BC). The intracellular Ca2+ toolkit, which drives the pro-angiogenic response to VEGF, is remodelled in tumor-associated ECFCs such that they are seemingly insensitive to this growth factor. This feature could underlie the relative failure of anti-VEGF therapies in cancer patients. Herein, we investigated whether and how VEGF uses Ca2+ signalling to control angiogenesis in BC-derived ECFCs (BC-ECFCs). Although VEGFR-2 was normally expressed, VEGF failed to induce proliferation and in vitro tubulogenesis in BC-ECFCs. Likewise, VEGF did not trigger robust Ca2+ oscillations in these cells. Similar to normal cells, VEGF-induced intracellular Ca2+ oscillations were triggered by inositol-1,4,5-trisphosphate-dependent Ca2+ release from the endoplasmic reticulum (ER) and maintained by store-operated Ca2+ entry (SOCE). However, InsP3-dependent Ca2+ release was significantly lower in BC-ECFCs due to the down-regulation of ER Ca2+ levels, while there was no remarkable difference in the amplitude, pharmacological profile and molecular composition of SOCE. Thus, the attenuation of the pro-angiogenic Ca2+ response to VEGF was seemingly due to the reduction in ER Ca2+ concentration, which prevents VEGF from triggering robust intracellular Ca2+ oscillations. However, the pharmacological inhibition of SOCE prevented BC-ECFC proliferation and in vitro tubulogenesis. These findings demonstrate for the first time that BC-ECFCs are insensitive to VEGF, which might explain at cellular and molecular levels the failure of anti-VEGF therapies in BC patients, and hint at SOCE as a novel molecular target for this disease. PMID:29221123

Atrx promotes heterochromatin formation at retrotransposons

PubMed Central

Sadic, Dennis; Schmidt, Katharina; Groh, Sophia; Kondofersky, Ivan; Ellwart, Joachim; Fuchs, Christiane; Theis, Fabian J; Schotta, Gunnar

2015-01-01

More than 50% of mammalian genomes consist of retrotransposon sequences. Silencing of retrotransposons by heterochromatin is essential to ensure genomic stability and transcriptional integrity. Here, we identified a short sequence element in intracisternal A particle (IAP) retrotransposons that is sufficient to trigger heterochromatin formation. We used this sequence in a genome-wide shRNA screen and identified the chromatin remodeler Atrx as a novel regulator of IAP silencing. Atrx binds to IAP elements and is necessary for efficient heterochromatin formation. In addition, Atrx facilitates a robust and largely inaccessible heterochromatin structure as Atrx knockout cells display increased chromatin accessibility at retrotransposons and non-repetitive heterochromatic loci. In summary, we demonstrate a direct role of Atrx in the establishment and robust maintenance of heterochromatin. PMID:26012739

Pulse Detecting Genetic Circuit – A New Design Approach

PubMed Central

Inniss, Mara; Iba, Hitoshi; Way, Jeffrey C.

2016-01-01

A robust cellular counter could enable synthetic biologists to design complex circuits with diverse behaviors. The existing synthetic-biological counters, responsive to the beginning of the pulse, are sensitive to the pulse duration. Here we present a pulse detecting circuit that responds only at the falling edge of a pulse–analogous to negative edge triggered electric circuits. As biological events do not follow precise timing, use of such a pulse detector would enable the design of robust asynchronous counters which can count the completion of events. This transcription-based pulse detecting circuit depends on the interaction of two co-expressed lambdoid phage-derived proteins: the first is unstable and inhibits the regulatory activity of the second, stable protein. At the end of the pulse the unstable inhibitor protein disappears from the cell and the second protein triggers the recording of the event completion. Using stochastic simulation we showed that the proposed design can detect the completion of the pulse irrespective to the pulse duration. In our simulation we also showed that fusing the pulse detector with a phage lambda memory element we can construct a counter which can be extended to count larger numbers. The proposed design principle is a new control mechanism for synthetic biology which can be integrated in different circuits for identifying the completion of an event. PMID:27907045

Pulse Detecting Genetic Circuit - A New Design Approach.

PubMed

Noman, Nasimul; Inniss, Mara; Iba, Hitoshi; Way, Jeffrey C

2016-01-01

A robust cellular counter could enable synthetic biologists to design complex circuits with diverse behaviors. The existing synthetic-biological counters, responsive to the beginning of the pulse, are sensitive to the pulse duration. Here we present a pulse detecting circuit that responds only at the falling edge of a pulse-analogous to negative edge triggered electric circuits. As biological events do not follow precise timing, use of such a pulse detector would enable the design of robust asynchronous counters which can count the completion of events. This transcription-based pulse detecting circuit depends on the interaction of two co-expressed lambdoid phage-derived proteins: the first is unstable and inhibits the regulatory activity of the second, stable protein. At the end of the pulse the unstable inhibitor protein disappears from the cell and the second protein triggers the recording of the event completion. Using stochastic simulation we showed that the proposed design can detect the completion of the pulse irrespective to the pulse duration. In our simulation we also showed that fusing the pulse detector with a phage lambda memory element we can construct a counter which can be extended to count larger numbers. The proposed design principle is a new control mechanism for synthetic biology which can be integrated in different circuits for identifying the completion of an event.

Ionization-induced star formation - IV. Triggering in bound clusters

NASA Astrophysics Data System (ADS)

Dale, J. E.; Ercolano, B.; Bonnell, I. A.

2012-12-01

We present a detailed study of star formation occurring in bound star-forming clouds under the influence of internal ionizing feedback from massive stars across a spectrum of cloud properties. We infer which objects are triggered by comparing our feedback simulations with control simulations in which no feedback was present. We find that feedback always results in a lower star formation efficiency and usually but not always results in a larger number of stars or clusters. Cluster mass functions are not strongly affected by feedback, but stellar mass functions are biased towards lower masses. Ionization also affects the geometrical distribution of stars in ways that are robust against projection effects, but may make the stellar associations more or less subclustered depending on the background cloud environment. We observe a prominent pillar in one simulation which is the remains of an accretion flow feeding the central ionizing cluster of its host cloud and suggest that this may be a general formation mechanism for pillars such as those observed in M16. We find that the association of stars with structures in the gas such as shells or pillars is a good but by no means foolproof indication that those stars have been triggered and we conclude overall that it is very difficult to deduce which objects have been induced to form and which formed spontaneously simply from observing the system at a single time.

Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells.

PubMed

Thankamony, Sai P; Sackstein, Robert

2011-02-08

According to the multistep model of cell migration, chemokine receptor engagement (step 2) triggers conversion of rolling interactions (step 1) into firm adhesion (step 3), yielding transendothelial migration. We recently reported that glycosyltransferase-programmed stereosubstitution (GPS) of CD44 on human mesenchymal stem cells (hMSCs) creates the E-selectin ligand HCELL (hematopoietic cell E-selectin/L-selectin ligand) and, despite absence of CXCR4, systemically administered HCELL(+)hMSCs display robust osteotropism visualized by intravital microscopy. Here we performed studies to define the molecular effectors of this process. We observed that engagement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesion to ligand VCAM-1. This VLA-4 activation is mediated via a Rac1/Rap1 GTPase signaling pathway, resulting in transendothelial migration on stimulated human umbilical vein endothelial cells without chemokine input. These findings indicate that hMSCs coordinately integrate CD44 ligation and integrin activation, circumventing chemokine-mediated signaling, yielding a step 2-bypass pathway of the canonical multistep paradigm of cell migration.

Nifurpirinol: A more potent and reliable substrate compared to metronidazole for nitroreductase-mediated cell ablations.

PubMed

Bergemann, David; Massoz, Laura; Bourdouxhe, Jordane; Carril Pardo, Claudio A; Voz, Marianne L; Peers, Bernard; Manfroid, Isabelle

2018-04-17

The zebrafish is a popular animal model with well-known regenerative capabilities. To study regeneration in this fish, the nitroreductase/metronidazole-mediated system is widely used for targeted ablation of various cell types. Nevertheless, we highlight here some variability in ablation efficiencies with the metronidazole prodrug that led us to search for a more efficient and reliable compound. Herein, we present nifurpirinol, another nitroaromatic antibiotic, as a more potent prodrug compared to metronidazole to trigger cell-ablation in nitroreductase expressing transgenic models. We show that nifurpirinol induces robust and reliable ablations at concentrations 2,000 fold lower than metronidazole and three times below its own toxic concentration. We confirmed the efficiency of nifurpirinol in triggering massive ablation of three different cell types: the pancreatic beta cells, osteoblasts, and dopaminergic neurons. Our results identify nifurpirinol as a very potent prodrug for the nitroreductase-mediated ablation system and suggest that its use could be extended to many other cell types, especially if difficult to ablate, or when combined pharmacological treatments are desired. © 2018 by the Wound Healing Society.

Spliced X-box Binding Protein 1 Couples the Unfolded Protein Response to Hexosamine Biosynthetic Pathway

PubMed Central

Wang, Zhao V.; Deng, Yingfeng; Gao, Ningguo; Pedrozo, Zully; Li, Dan L.; Morales, Cyndi R.; Criollo, Alfredo; Luo, Xiang; Tan, Wei; Jiang, Nan; Lehrman, Mark A.; Rothermel, Beverly A.; Lee, Ann-Hwee; Lavandero, Sergio; Mammen, Pradeep P.A.; Ferdous, Anwarul; Gillette, Thomas G.; Scherer, Philipp E.; Hill, Joseph A.

2014-01-01

SUMMARY The hexosamine biosynthetic pathway (HBP) generates UDP-GlcNAc (uridine diphosphate N-acetylglucosamine) for glycan synthesis and O-linked GlcNAc (O-GlcNAc) protein modifications. Despite the established role of the HBP in metabolism and multiple diseases, regulation of the HBP remains largely undefined. Here, we show that spliced X-box binding protein 1 (Xbp1s), the most conserved signal transducer of the unfolded protein response (UPR), is a direct transcriptional activator of the HBP. We demonstrate that the UPR triggers HBP activation via Xbp1s-dependent transcription of genes coding for key, rate-limiting enzymes. We further establish that this previously unrecognized UPR-HBP axis is triggered in a variety of stress conditions. Finally, we demonstrate a physiologic role for the UPR-HBP axis, by showing that acute stimulation of Xbp1s in heart by ischemia/reperfusion confers robust cardioprotection in part through induction of the HBP. Collectively, these studies reveal that Xbp1s couples the UPR to the HBP to protect cells under stress. PMID:24630721

Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway.

PubMed

Wang, Zhao V; Deng, Yingfeng; Gao, Ningguo; Pedrozo, Zully; Li, Dan L; Morales, Cyndi R; Criollo, Alfredo; Luo, Xiang; Tan, Wei; Jiang, Nan; Lehrman, Mark A; Rothermel, Beverly A; Lee, Ann-Hwee; Lavandero, Sergio; Mammen, Pradeep P A; Ferdous, Anwarul; Gillette, Thomas G; Scherer, Philipp E; Hill, Joseph A

2014-03-13

The hexosamine biosynthetic pathway (HBP) generates uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) for glycan synthesis and O-linked GlcNAc (O-GlcNAc) protein modifications. Despite the established role of the HBP in metabolism and multiple diseases, regulation of the HBP remains largely undefined. Here, we show that spliced X-box binding protein 1 (Xbp1s), the most conserved signal transducer of the unfolded protein response (UPR), is a direct transcriptional activator of the HBP. We demonstrate that the UPR triggers HBP activation via Xbp1s-dependent transcription of genes coding for key, rate-limiting enzymes. We further establish that this previously unrecognized UPR-HBP axis is triggered in a variety of stress conditions. Finally, we demonstrate a physiologic role for the UPR-HBP axis by showing that acute stimulation of Xbp1s in heart by ischemia/reperfusion confers robust cardioprotection in part through induction of the HBP. Collectively, these studies reveal that Xbp1s couples the UPR to the HBP to protect cells under stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Parafoveal preview benefit in reading is only obtained from the saccade goal.

PubMed

McDonald, Scott A

2006-12-01

Previous research has demonstrated that reading is less efficient when parafoveal visual information about upcoming words is invalid or unavailable; the benefit from a valid preview is realised as reduced reading times on the subsequently foveated word, and has been explained with reference to the allocation of attentional resources to parafoveal word(s). This paper presents eyetracking evidence that preview benefit is obtained only for words that are selected as the saccade target. Using a gaze-contingent display change paradigm (Rayner, K. (1975). The perceptual span and peripheral cues in reading. Cognitive Psychology, 7, 65-81), the position of the triggering boundary was set near the middle of the pretarget word. When a refixation saccade took the eye across the boundary in the pretarget word, there was no reliable effect of the validity of the target word preview. However, when the triggering boundary was positioned just after the pretarget word, a robust preview benefit was observed, replicating previous research. The current results complement findings from studies of basic visual function, suggesting that for the case of preview benefit in reading, attentional and oculomotor processes are obligatorily coupled.

What Experiences in Medical School Trigger Professional Identity Development?

PubMed

Kay, Denise; Berry, Andrea; Coles, Nicholas A

2018-04-02

Phenomenon: This qualitative inquiry used conceptual change theory as a theoretical lens to illuminate experiences in medical school that trigger professional identity formation. According to conceptual change theory, changes in personal conceptualizations are initiated when cognitive disequilibrium is introduced. We sought to identify the experiences that trigger cognitive disequilibrium and to subsequently describe students' perceptions of self-in-profession prior to the experience; the nature of the experience; and, when applicable, the outcomes of the experience. This article summarizes findings from portions of data collected in a larger qualitative study conducted at a new medical school in the United States that utilizes diverse pedagogies and experiences to develop student knowledge, clinical skills, attitudes, and dispositions. Primary data sources included focus groups and individual interviews with students across the 4 years of the curriculum (audio data). Secondary data included students' comments from course and end-of-year evaluations for the 2013-2017 classes (text data). Data treatment tools available in robust qualitative software, NVivo 10, were utilized to expedite coding of both audio and text data. Content analysis was adopted as the analysis method for both audio and text data. We identified four experiences that triggered cognitive disequilibrium in relationship to students' perceptions of self-in-profession: (a) transition from undergraduate student to medical student, (b) clinical experiences in the preclinical years, (c) exposure to the business of medicine, and (d) exposure to physicians in clinical practice. Insights: We believe these experiences represent vulnerable periods of professional identity formation during medical school. Educators interested in purposefully shaping curriculum to encourage adaptive professional identity development during medical school may find it useful to integrate educational interventions that assist students with navigating the disequilibrium that is introduced during these periods.

MicroRNA-155 Is Required for Mycobacterium bovis BCG-Mediated Apoptosis of Macrophages

PubMed Central

Ghorpade, Devram Sampat; Leyland, Rebecca; Kurowska-Stolarska, Mariola; Patil, Shripad A.

2012-01-01

Pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium bovis, cause significant morbidity and mortality worldwide. However, the vaccine strain Mycobacterium bovis BCG, unlike virulent strains, triggers extensive apoptosis of infected macrophages, a step necessary for the elicitation of robust protective immunity. We here demonstrate that M. bovis BCG triggers Toll-like receptor 2 (TLR2)-dependent microRNA-155 (miR-155) expression, which involves signaling cross talk among phosphatidylinositol 3-kinase (PI3K), protein kinase Cδ (PKCδ), and mitogen-activated protein kinases (MAPKs) and recruitment of NF-κB and c-ETS to miR-155 promoter. Genetic and signaling perturbations presented the evidence that miR-155 regulates PKA signaling by directly targeting a negative regulator of PKA, protein kinase inhibitor alpha (PKI-α). Enhanced activation of PKA signaling resulted in the generation of PKA C-α; phosphorylation of MSK1, cyclic AMP response element binding protein (CREB), and histone H3; and recruitment of phospho-CREB to the apoptotic gene promoters. The miR-155-triggered activation of caspase-3, BAK1, and cytochrome c translocation involved signaling integration of MAPKs and epigenetic or posttranslational modification of histones or CREB. Importantly, M. bovis BCG infection-induced apoptosis was severely compromised in macrophages derived from miR-155 knockout mice. Gain-of-function and loss-of-function studies validated the requirement of miR-155 for M. bovis BCG's ability to trigger apoptosis. Overall, M. bovis BCG-driven miR-155 dictates cell fate decisions of infected macrophages, strongly implicating a novel role for miR-155 in orchestrating cellular reprogramming during immune responses to mycobacterial infection. PMID:22473996

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.

Robust patterning of gene expression based on internal coordinate system of cells.

PubMed

Ogawa, Ken-ichiro; Miyake, Yoshihiro

2015-06-01

Cell-to-cell communication in multicellular organisms is established through the transmission of various kinds of chemical substances such as proteins. It is well known that gene expression triggered by a chemical substance in individuals has stable spatial patterns despite the individual differences in concentration patterns of the chemical substance. This fact reveals an important property of multicellular organisms called "robustness", which allows the organisms to generate their forms while maintaining proportion. Robustness has been conventionally accounted for by the stability of solutions of dynamical equations that represent a specific interaction network of chemical substances. However, any biological system is composed of autonomous elements. In general, an autonomous element does not merely accept information on the chemical substance from the environment; instead, it accepts the information based on its own criteria for reaction. Therefore, this phenomenon needs to be considered from the viewpoint of cells. Such a viewpoint is expected to allow the consideration of the autonomy of cells in multicellular organisms. This study aims to explain theoretically the robust patterning of gene expression from the viewpoint of cells. For this purpose, we introduced a new operator for transforming a state variable of a chemical substance from an external coordinate system to an internal coordinate system of each cell, which describes the observation of the chemical substance by cells. We then applied this operator to the simplest reaction-diffusion model of the chemical substance to investigate observation effects by cells. Our mathematical analysis of this extended model indicates that the robust patterning of gene expression against individual differences in concentration pattern of the chemical substance can be explained from the viewpoint of cells if there is a regulation field that compensates for the difference between cells seen in the observation results. This result provides a new insight into the investigation of the mechanism of robust patterning in biological systems composed of individual elements. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Unbiased and robust quantification of synchronization between spikes and local field potential.

PubMed

Li, Zhaohui; Cui, Dong; Li, Xiaoli

2016-08-30

In neuroscience, relating the spiking activity of individual neurons to the local field potential (LFP) of neural ensembles is an increasingly useful approach for studying rhythmic neuronal synchronization. Many methods have been proposed to measure the strength of the association between spikes and rhythms in the LFP recordings, and most existing measures are dependent upon the total number of spikes. In the present work, we introduce a robust approach for quantifying spike-LFP synchronization which performs reliably for limited samples of data. The measure is termed as spike-triggered correlation matrix synchronization (SCMS), which takes LFP segments centered on each spike as multi-channel signals and calculates the index of spike-LFP synchronization by constructing a correlation matrix. The simulation based on artificial data shows that the SCMS output almost does not change with the sample size. This property is of crucial importance when making comparisons between different experimental conditions. When applied to actual neuronal data recorded from the monkey primary visual cortex, it is found that the spike-LFP synchronization strength shows orientation selectivity to drifting gratings. In comparison to another unbiased method, pairwise phase consistency (PPC), the proposed SCMS behaves better for noisy spike trains by means of numerical simulations. This study demonstrates the basic idea and calculating process of the SCMS method. Considering its unbiasedness and robustness, the measure is of great advantage to characterize the synchronization between spike trains and rhythms present in LFP. Copyright © 2016 Elsevier B.V. All rights reserved.

The dose can make the poison: lessons learned from adverse in vivo toxicities caused by RNAi overexpression.

PubMed

Grimm, Dirk

2011-10-26

For the past five years, evidence has accumulated that vector-mediated robust RNA interference (RNAi) expression can trigger severe side effects in small and large animals, from cytotoxicity and accelerated tumorigenesis to organ failure and death. The recurring notions in these studies that a critical parameter is the strength of RNAi expression and that Exportin-5 and the Argonaute proteins are rate-limiting mammalian RNAi, strongly imply dose-dependent saturation of the endogenous miRNA pathway as one of the underlying mechanisms. This minireview summarizes the relevant work and data leading to this intriguing model and highlights potential avenues by which to alleviate RNAi-induced toxicities in future clinical applications.

Fetal and Placental DNA Stimulation of TLR9: A Mechanism Possibly Contributing to the Pro-inflammatory Events During Parturition.

PubMed

Goldfarb, Ilona Telefus; Adeli, Sharareh; Berk, Tucker; Phillippe, Mark

2018-05-01

While there is evidence for a relationship between cell-free fetal DNA (cffDNA) and parturition, questions remain regarding whether cffDNA could trigger a pro-inflammatory response on the pathway to parturition. We hypothesized that placental and/or fetal DNA stimulates toll-like receptor 9 (TLR9) leading to secretion of pro-inflammatory cytokines by macrophage cells. Four in vitro DNA stimulation studies were performed using RAW 264.7 mouse peritoneal macrophage cells incubated in media containing the following DNA particles: an oligodeoxynucleotide (ODN2395), intact genomic DNA (from mouse placentas, fetuses and adult liver), mouse DNA complexed with DOTAP (a cationic liposome forming compound), and telomere-depleted mouse DNA. Interleukin 6 (IL6) secretion was measured in the media by enzyme-linked immunosorbent assay; and the cell pellet was homogenized for protein content (picograms IL6/mg protein). Robust IL6 secretion was observed in response to ODN2395 (a CpG-rich TLR9 agonist), mouse DNA-DOTAP complexes, and telomere-depleted mouse DNA in concentrations of 5 to 15 μg/mL. In contrast, ODN A151 (containing telomere sequence motifs), intact genomic mouse DNA, and restriction enzyme-digested DNA had no effect on IL6 secretion. The IL6 response was significantly inhibited by chloroquine (10 μg/mL), thereby confirming the important role for TLR9 in the response by macrophage cells. DNA derived from mouse placentas and fetuses, and depleted of telomeric sequences, stimulates a robust pro-inflammatory response by macrophage cells, thereby supporting the hypothesis that cffDNA is able to stimulate an innate immune response that could trigger the onset of parturition. These findings are of clinical importance, as we search for effective treatment/prevention of preterm parturition.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Role of Innate Immunity in a Model of Histidyl-tRNA Synthetase (Jo-1)-mediated Myositis

PubMed Central

Soejima, Makoto; Kang, Eun Ha; Gu, Xinyan; Katsumata, Yasuhiro; Clemens, Paula R.; Ascherman, Dana P.

2010-01-01

Objectives Previous work in humans and in animal models supports a key role for histidyl-tRNA synthetase (HRS=Jo-1) in the pathogenesis of idiopathic inflammatory myopathy. While most investigations have focused on the ability of HRS to trigger adaptive immune responses, in vitro studies clearly indicate that HRS possesses intrinsic chemokine-like properties capable of activating the innate immune system. The purpose of this study was therefore to examine the ability of HRS to direct innate immune responses in a murine model of myositis. Methods Following intramuscular immunization with soluble HRS in the absence of exogenous adjuvant, selected strains of mice were evaluated at different time points for histopathologic evidence of myositis. ELISA-based assessment of autoantibody formation and CFSE proliferation studies provided complementary measures of B and T cell responses triggered by HRS immunization. Results Compared to appropriate control proteins, a murine HRS fusion protein induced robust, statistically significant muscle inflammation in multiple congenic strains of C57BL/6 and NOD mice. Time course experiments revealed that this inflammatory response occurred as early as 7 days post immunization and persisted for up to 7 weeks. Parallel immunization strategies in DO11.10/Rag2−/− and C3H/HeJ (TLR4−/−) mice indicated that the ability of murine HRS to drive muscle inflammation was not dependent on B cell receptor or T cell receptor recognition and did not require TLR4 signaling. Conclusion Collectively, these experiments support a model in which HRS can trigger both innate and adaptive immune responses which culminate in severe muscle inflammation that is the hallmark of idiopathic inflammatory myopathy. PMID:21280002

Sensitivity of Coulomb stress changes to slip models of source faults: A case study for the 2011 Mw 9.0 Tohoku-oki earthquake

NASA Astrophysics Data System (ADS)

Wang, J.; Xu, C.; Furlong, K.; Zhong, B.; Xiao, Z.; Yi, L.; Chen, T.

2017-12-01

Although Coulomb stress changes induced by earthquake events have been used to quantify stress transfers and to retrospectively explain stress triggering among earthquake sequences, realistic reliable prospective earthquake forecasting remains scarce. To generate a robust Coulomb stress map for earthquake forecasting, uncertainties in Coulomb stress changes associated with the source fault, receiver fault and friction coefficient and Skempton's coefficient need to be exhaustively considered. In this paper, we specifically explore the uncertainty in slip models of the source fault of the 2011 Mw 9.0 Tohoku-oki earthquake as a case study. This earthquake was chosen because of its wealth of finite-fault slip models. Based on the wealth of those slip models, we compute the coseismic Coulomb stress changes induced by this mainshock. Our results indicate that nearby Coulomb stress changes for each slip model can be quite different, both for the Coulomb stress map at a given depth and on the Pacific subducting slab. The triggering rates for three months of aftershocks of the mainshock, with and without considering the uncertainty in slip models, differ significantly, decreasing from 70% to 18%. Reliable Coulomb stress changes in the three seismogenic zones of Nanki, Tonankai and Tokai are insignificant, approximately only 0.04 bar. By contrast, the portions of the Pacific subducting slab at a depth of 80 km and beneath Tokyo received a positive Coulomb stress change of approximately 0.2 bar. The standard errors of the seismicity rate and earthquake probability based on the Coulomb rate-and-state model (CRS) decay much faster with elapsed time in stress triggering zones than in stress shadows, meaning that the uncertainties in Coulomb stress changes in stress triggering zones would not drastically affect assessments of the seismicity rate and earthquake probability based on the CRS in the intermediate to long term.

DNS of Supersonic Turbulent Flows in a DLR Scramjet Intake

NASA Astrophysics Data System (ADS)

Li, Xinliang; Yu, Changping

2014-11-01

Direct numerical simulation (DNS) of supersonic/hypersonic flow through a DLR scramjet intake GK01 is performed. The free stream Mach numbers are 3, 5 and 7, and the angle of attack is zero degree. The DNS cases are performed by using an optimized MP scheme with adaptive dissipation (OMP-AD) developed by the authors, and the blow-and-suction perturbations near the leading edge are used to trigger the transition. To stabilize the simulation, locally non-linear flittering is used in high-Mach-number case. The transition, separation, and shock-turbulent boundary layer interaction are studied by using both flow visualization and statistical analysis. A new method, OMP-AD, is also addressed in this paper. The OMP-AD scheme is developed by using joint MP method and optimized technique, and the coefficients in the scheme are flexible to show low dissipation in the smoothing region, and to show high robust (but high dissipation) in the large gradient region. Numerical tests show that the OMP-AD is more robust than the original MP schemes, and the numerical dissipation of OMP-AD is very low.

Synaptically Driven Phosphorylation of Ribosomal Protein S6 Is Differentially Regulated at Active Synapses versus Dendrites and Cell Bodies by MAPK and PI3K/mTOR Signaling Pathways

ERIC Educational Resources Information Center

Pirbhoy, Patricia Salgado; Farris, Shannon; Steward, Oswald

2017-01-01

High-frequency stimulation of the medial perforant path triggers robust phosphorylation of ribosomal protein S6 (rpS6) in activated dendritic domains and granule cell bodies. Here we dissect the signaling pathways responsible for synaptically driven rpS6 phosphorylation in the dentate gyrus using pharmacological agents to inhibit PI3-kinase/mTOR…

AE Recorder Characteristics and Development.

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

Partridge, Michael E.; Curtis, Shane Keawe; McGrogan, David Paul

2016-11-01

The Anomalous Environment Recorder (AE Recorder) provides a robust data recording capability for multiple high-shock applications including earth penetrators. The AE Recorder, packaged as a 2.4" di ameter cylinder 3" tall, acquires 12 accelerometer, 2 auxiliary, and 6 discrete signal channels at 250k samples / second. Recording depth is 213 seconds plus 75ms of pre-trigger data. The mechanical, electrical, and firmware are described as well as support electro nics designed for the first use of the recorder.

secHsp70 as a tool to approach amyloid-β42 and other extracellular amyloids.

PubMed

De Mena, Lorena; Chhangani, Deepak; Fernandez-Funez, Pedro; Rincon-Limas, Diego E

2017-07-03

Self-association of amyloidogenic proteins is the main pathological trigger in a wide variety of neurodegenerative disorders. These aggregates are deposited inside or outside the cell due to hereditary mutations, environmental exposures or even normal aging. Cumulative evidence indicates that the heat shock chaperone Hsp70 possesses robust neuroprotection against various intracellular amyloids in Drosophila and mouse models. However, its protective role against extracellular amyloids was largely unknown as its presence outside the cells is very limited. Our recent manuscript in PNAS revealed that an engineered form of secreted Hsp70 (secHsp70) is highly protective against toxicity induced by extracellular deposition of the amyloid-β42 (Aβ42) peptide. In this Extra View article, we extend our analysis to other members of the heat shock protein family. We created PhiC31-based transgenic lines for human Hsp27, Hsp40, Hsp60 and Hsp70 and compared their activities in parallel against extracellular Aβ42. Strikingly, only secreted Hsp70 exhibits robust protection against Aβ42-triggered toxicity in the extracellular milieu. These observations indicate that the ability of secHsp70 to suppress Aβ42 insults is quite unique and suggest that targeted secretion of Hsp70 may represent a new therapeutic approach against Aβ42 and other extracellular amyloids. The potential applications of this engineered chaperone are discussed.

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.

Fluctuating hydrodynamics of multispecies nonreactive mixtures

DOE PAGES

Balakrishnan, Kaushik; Garcia, Alejandro L.; Donev, Aleksandar; ...

2014-01-22

In this study we discuss the formulation of the fluctuating Navier-Stokes equations for multispecies, nonreactive fluids. In particular, we establish a form suitable for numerical solution of the resulting stochastic partial differential equations. An accurate and efficient numerical scheme, based on our previous methods for single species and binary mixtures, is presented and tested at equilibrium as well as for a variety of nonequilibrium problems. These include the study of giant nonequilibrium concentration fluctuations in a ternary mixture in the presence of a diffusion barrier, the triggering of a Rayleigh-Taylor instability by diffusion in a four-species mixture, as well asmore » reverse diffusion in a ternary mixture. Finally, good agreement with theory and experiment demonstrates that the formulation is robust and can serve as a useful tool in the study of thermal fluctuations for multispecies fluids.« less

Letter and symbol identification: No evidence for letter-specific crowding mechanisms.

PubMed

Castet, Eric; Descamps, Marine; Denis-Noël, Ambre; Colé, Pascale

2017-09-01

It has been proposed that letters, as opposed to symbols, trigger specialized crowding processes, boosting identification of the first and last letters of words. This hypothesis is based on evidence that single-letter accuracy as a function of within-string position has a W shape (the classic serial position function [SPF] in psycholinguistics) whereas an inverted V shape is obtained when measured with symbols. Our main goal was to test the robustness of the latter result. Our hypothesis was that any letter/symbol difference might result from short-term visual memory processes (due to the partial report [PR] procedures used in SPF studies) rather than from crowding. We therefore removed the involvement of short-term memory by precueing target-item position and compared SPFs with precueing and postcueing. Perimetric complexity was stringently matched between letters and symbols. In postcueing conditions similar to previous studies, we did not reproduce the inverted V shape for symbols: Clear-cut W shapes were observed with an overall smaller accuracy for symbols compared to letters. This letter/symbol difference was dramatically reduced in precueing conditions in keeping with our prediction. Our results are not consistent with the claim that letter strings trigger specialized crowding processes. We argue that PR procedures are not fit to isolate crowding processes.

Role of hormones and neurosteroids in epileptogenesis

PubMed Central

Reddy, Doodipala Samba

2013-01-01

This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis. PMID:23914154

Type I Interferon Responses by HIV-1 Infection: Association with Disease Progression and Control.

PubMed

Soper, Andrew; Kimura, Izumi; Nagaoka, Shumpei; Konno, Yoriyuki; Yamamoto, Keisuke; Koyanagi, Yoshio; Sato, Kei

2017-01-01

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome and its infection leads to the onset of several disorders such as the depletion of peripheral CD4 + T cells and immune activation. HIV-1 is recognized by innate immune sensors that then trigger the production of type I interferons (IFN-Is). IFN-Is are well-known cytokines eliciting broad anti-viral effects by inducing the expression of anti-viral genes called interferon-stimulated genes (ISGs). Extensive in vitro studies using cell culture systems have elucidated that certain ISGs such as APOBEC3G, tetherin, SAM domain and HD domain-containing protein 1, MX dynamin-like GTPase 2, guanylate-binding protein 5, and schlafen 11 exert robust anti-HIV-1 activity, suggesting that IFN-I responses triggered by HIV-1 infection are detrimental for viral replication and spread. However, recent studies using animal models have demonstrated that at both the acute and chronic phase of infection, the role of IFN-Is produced by HIV or SIV infection in viral replication, spread, and pathogenesis, may not be that straightforward. In this review, we describe the pluses and minuses of HIV-1 infection stimulated IFN-I responses on viral replication and pathogenesis, and further discuss the possibility for therapeutic approaches.

Simultaneous Event-Triggered Fault Detection and Estimation for Stochastic Systems Subject to Deception Attacks.

PubMed

Li, Yunji; Wu, QingE; Peng, Li

2018-01-23

In this paper, a synthesized design of fault-detection filter and fault estimator is considered for a class of discrete-time stochastic systems in the framework of event-triggered transmission scheme subject to unknown disturbances and deception attacks. A random variable obeying the Bernoulli distribution is employed to characterize the phenomena of the randomly occurring deception attacks. To achieve a fault-detection residual is only sensitive to faults while robust to disturbances, a coordinate transformation approach is exploited. This approach can transform the considered system into two subsystems and the unknown disturbances are removed from one of the subsystems. The gain of fault-detection filter is derived by minimizing an upper bound of filter error covariance. Meanwhile, system faults can be reconstructed by the remote fault estimator. An recursive approach is developed to obtain fault estimator gains as well as guarantee the fault estimator performance. Furthermore, the corresponding event-triggered sensor data transmission scheme is also presented for improving working-life of the wireless sensor node when measurement information are aperiodically transmitted. Finally, a scaled version of an industrial system consisting of local PC, remote estimator and wireless sensor node is used to experimentally evaluate the proposed theoretical results. In particular, a novel fault-alarming strategy is proposed so that the real-time capacity of fault-detection is guaranteed when the event condition is triggered.

So little source, so much sink: requirements for afterdepolarizations to propagate in tissue.

PubMed

Xie, Yuanfang; Sato, Daisuke; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

2010-09-08

How early (EADs) and delayed afterdepolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mechanisms of change of a novel weight loss programme provided by a third sector organisation: a qualitative interview study.

PubMed

McMahon, Naoimh E; Visram, Shelina; Connell, Louise A

2016-05-10

There is a need for theory-driven studies that explore the underlying mechanisms of change of complex weight loss programmes. Such studies will contribute to the existing evidence-base on how these programmes work and thus inform the future development and evaluation of tailored, effective interventions to tackle overweight and obesity. This study explored the mechanisms by which a novel weight loss programme triggered change amongst participants. The programme, delivered by a third sector organisation, addressed both diet and physical activity. Over a 26 week period participants engaged in three weekly sessions (education and exercise in a large group, exercise in a small group and a one-to-one education and exercise session). Novel aspects included the intensity and duration of the programme, a competitive selection process, milestone physical challenges (e.g. working up to a 5 K and 10 K walk/run during the programme), alumni support (face-to-face and online) and family attendance at exercise sessions. Data were collected through interviews with programme providers (n = 2) and focus groups with participants (n = 12). Discussions were audio-recorded, transcribed and analysed using NVivo10. Published behaviour change frameworks and behaviour change technique taxonomies were used to guide the coding process. Clients' interactions with components of the weight loss programme brought about a change in their commitment, knowledge, beliefs about capabilities and social and environmental contexts. Intervention components that generated these changes included the competitive selection process, group and online support, family involvement and overcoming milestone challenges over the 26 week programme. The mechanisms by which these components triggered change differed between participants. There is an urgent need to establish robust interventions that can support people who are overweight and obese to achieve a healthy weight and maintain this change. Third sector organisations may be a feasible alternative to private and public sector weight loss programmes. We have presented findings from one example of a novel community-based weight loss programme and identified how the programme components resulted in change amongst the participants. Further research is needed to robustly test the effectiveness, and cost-effectiveness, of this programme.

Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Aguilar-Hidalgo, D.; Lemos, M. C.; Córdoba, A.

2015-03-01

During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.

Cytokinin signalling inhibitory fields provide robustness to phyllotaxis

NASA Astrophysics Data System (ADS)

Besnard, Fabrice; Refahi, Yassin; Morin, Valérie; Marteaux, Benjamin; Brunoud, Géraldine; Chambrier, Pierre; Rozier, Frédérique; Mirabet, Vincent; Legrand, Jonathan; Lainé, Stéphanie; Thévenon, Emmanuel; Farcot, Etienne; Cellier, Coralie; Das, Pradeep; Bishopp, Anthony; Dumas, Renaud; Parcy, François; Helariutta, Ykä; Boudaoud, Arezki; Godin, Christophe; Traas, Jan; Guédon, Yann; Vernoux, Teva

2014-01-01

How biological systems generate reproducible patterns with high precision is a central question in science. The shoot apical meristem (SAM), a specialized tissue producing plant aerial organs, is a developmental system of choice to address this question. Organs are periodically initiated at the SAM at specific spatial positions and this spatiotemporal pattern defines phyllotaxis. Accumulation of the plant hormone auxin triggers organ initiation, whereas auxin depletion around organs generates inhibitory fields that are thought to be sufficient to maintain these patterns and their dynamics. Here we show that another type of hormone-based inhibitory fields, generated directly downstream of auxin by intercellular movement of the cytokinin signalling inhibitor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 6 (AHP6), is involved in regulating phyllotactic patterns. We demonstrate that AHP6-based fields establish patterns of cytokinin signalling in the meristem that contribute to the robustness of phyllotaxis by imposing a temporal sequence on organ initiation. Our findings indicate that not one but two distinct hormone-based fields may be required for achieving temporal precision during formation of reiterative structures at the SAM, thus indicating an original mechanism for providing robustness to a dynamic developmental system.

How robust are distributed systems

NASA Technical Reports Server (NTRS)

Birman, Kenneth P.

1989-01-01

A distributed system is made up of large numbers of components operating asynchronously from one another and hence with imcomplete and inaccurate views of one another's state. Load fluctuations are common as new tasks arrive and active tasks terminate. Jointly, these aspects make it nearly impossible to arrive at detailed predictions for a system's behavior. It is important to the successful use of distributed systems in situations in which humans cannot provide the sorts of predictable realtime responsiveness of a computer, that the system be robust. The technology of today can too easily be affected by worn programs or by seemingly trivial mechanisms that, for example, can trigger stock market disasters. Inventors of a technology have an obligation to overcome flaws that can exact a human cost. A set of principles for guiding solutions to distributed computing problems is presented.

Hyperbranched Hybridization Chain Reaction for Triggered Signal Amplification and Concatenated Logic Circuits.

PubMed

Bi, Sai; Chen, Min; Jia, Xiaoqiang; Dong, Ying; Wang, Zonghua

2015-07-06

A hyper-branched hybridization chain reaction (HB-HCR) is presented herein, which consists of only six species that can metastably coexist until the introduction of an initiator DNA to trigger a cascade of hybridization events, leading to the self-sustained assembly of hyper-branched and nicked double-stranded DNA structures. The system can readily achieve ultrasensitive detection of target DNA. Moreover, the HB-HCR principle is successfully applied to construct three-input concatenated logic circuits with excellent specificity and extended to design a security-mimicking keypad lock system. Significantly, the HB-HCR-based keypad lock can alarm immediately if the "password" is incorrect. Overall, the proposed HB-HCR with high amplification efficiency is simple, homogeneous, fast, robust, and low-cost, and holds great promise in the development of biosensing, in the programmable assembly of DNA architectures, and in molecular logic operations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Frequent floods in the European Alps coincide with cooler periods of the past 2500 years.

PubMed

Glur, Lukas; Wirth, Stefanie B; Büntgen, Ulf; Gilli, Adrian; Haug, Gerald H; Schär, Christoph; Beer, Jürg; Anselmetti, Flavio S

2013-09-26

Severe floods triggered by intense precipitation are among the most destructive natural hazards in Alpine environments, frequently causing large financial and societal damage. Potential enhanced flood occurrence due to global climate change would thus increase threat to settlements, infrastructure, and human lives in the affected regions. Yet, projections of intense precipitation exhibit major uncertainties and robust reconstructions of Alpine floods are limited to the instrumental and historical period. Here we present a 2500-year long flood reconstruction for the European Alps, based on dated sedimentary flood deposits from ten lakes in Switzerland. We show that periods with high flood frequency coincide with cool summer temperatures. This wet-cold synchronism suggests enhanced flood occurrence to be triggered by latitudinal shifts of Atlantic and Mediterranean storm tracks. This paleoclimatic perspective reveals natural analogues for varying climate conditions, and thus can contribute to a better understanding and improved projections of weather extremes under climate change.

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.

Accounting for sequential trial effects in the flanker task: conflict adaptation or associative priming?

PubMed

Nieuwenhuis, Sander; Stins, John F; Posthuma, Danielle; Polderman, Tinca J C; Boomsma, Dorret I; de Geus, Eco J

2006-09-01

The conflict-control loop theory proposes that the detection of conflict in information processing triggers an increase in cognitive control, resulting in improved performance on the subsequent trial. This theory seems consistent with the robust finding that conflict susceptibility is reduced following correct trials associated with high conflict: the conflict adaptation effect. However, despite providing favorable conditions for eliciting and detecting conflict-triggered performance adjustments, none of the five experiments reported here provide unequivocal evidence of such adjustments. Instead, the results corroborate and extend earlier findings by demonstrating that the conflict adaptation effect, at least in the flanker task, is only present for a specific subset of trial sequences that is characterized by a response repetition. This pattern of results provides strong evidence that the conflict adaptation effect reflects associative stimulus-response priming instead of conflict-driven adaptations in cognitive control.

The spread of Ras activity triggered by activation of a single dendritic spine.

PubMed

Harvey, Christopher D; Yasuda, Ryohei; Zhong, Haining; Svoboda, Karel

2008-07-04

In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.

Scout-MRM: Multiplexed Targeted Mass Spectrometry-Based Assay without Retention Time Scheduling Exemplified by Dickeya dadantii Proteomic Analysis during Plant Infection.

PubMed

Rougemont, Blandine; Bontemps Gallo, Sébastien; Ayciriex, Sophie; Carrière, Romain; Hondermarck, Hubert; Lacroix, Jean Marie; Le Blanc, J C Yves; Lemoine, Jérôme

2017-02-07

Targeted mass spectrometry of a surrogate peptide panel is a powerful method to study the dynamics of protein networks, but chromatographic time scheduling remains a major limitation for dissemination and implementation of robust and large multiplexed assays. We unveil a Multiple Reaction Monitoring method (Scout-MRM) where the use of spiked scout peptides triggers complex transition lists, regardless of the retention time of targeted surrogate peptides. The interest of Scout-MRM method regarding the retention time independency, multiplexing capability, reproducibility, and putative interest in facilitating method transfer was illustrated by a 782-peptide-plex relative assay targeting 445 proteins of the phytopathogen Dickeya dadantii during plant infection.

Three-dimensional simulations of the orientation and structure of reconnection X-lines

NASA Astrophysics Data System (ADS)

Schreier, R.; Swisdak, M.; Drake, J. F.; Cassak, P. A.

2010-11-01

This letter employs Hall magnetohydrodynamic simulations to study X-lines formed during the reconnection of magnetic fields with differing strengths and orientations embedded in plasmas of differing densities. Although random initial perturbations trigger the growth of X-lines with many orientations, a few robust X-lines sharing an orientation consistent with the direction of maximal outflow speed, as predicted by Swisdak and Drake [Geophys. Res. Lett. 34, L11106 (2007)] eventually dominate the system. Reconnection in the geometry examined here contradicts the suggestion of Sonnerup [J. Geophys. Res. 79, 1546 (1974)] that it occurs in a plane normal to the equilibrium current. At late time, the X-lines' growth stagnates, leaving them shorter than the simulation domain.

Nutrient depletion in Bacillus subtilis biofilms triggers matrix production

NASA Astrophysics Data System (ADS)

Zhang, Wenbo; Seminara, Agnese; Suaris, Melanie; Brenner, Michael P.; Weitz, David A.; Angelini, Thomas E.

2014-01-01

Many types of bacteria form colonies that grow into physically robust and strongly adhesive aggregates known as biofilms. A distinguishing characteristic of bacterial biofilms is an extracellular polymeric substance (EPS) matrix that encases the cells and provides physical integrity to the colony. The EPS matrix consists of a large amount of polysaccharide, as well as protein filaments, DNA and degraded cellular materials. The genetic pathways that control the transformation of a colony into a biofilm have been widely studied, and yield a spatiotemporal heterogeneity in EPS production. Spatial gradients in metabolites parallel this heterogeneity in EPS, but nutrient concentration as an underlying physiological initiator of EPS production has not been explored. Here, we study the role of nutrient depletion in EPS production in Bacillus subtilis biofilms. By monitoring simultaneously biofilm size and matrix production, we find that EPS production increases at a critical colony thickness that depends on the initial amount of carbon sources in the medium. Through studies of individual cells in liquid culture we find that EPS production can be triggered at the single-cell level by reducing nutrient concentration. To connect the single-cell assays with conditions in the biofilm, we calculate carbon concentration with a model for the reaction and diffusion of nutrients in the biofilm. This model predicts the relationship between the initial concentration of carbon and the thickness of the colony at the point of internal nutrient deprivation.

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

A complete methodology towards accuracy and lot-to-lot robustness in on-product overlay metrology using flexible wavelength selection

NASA Astrophysics Data System (ADS)

Bhattacharyya, Kaustuve; den Boef, Arie; Noot, Marc; Adam, Omer; Grzela, Grzegorz; Fuchs, Andreas; Jak, Martin; Liao, Sax; Chang, Ken; Couraudon, Vincent; Su, Eason; Tzeng, Wilson; Wang, Cathy; Fouquet, Christophe; Huang, Guo-Tsai; Chen, Kai-Hsiung; Wang, Y. C.; Cheng, Kevin; Ke, Chih-Ming; Terng, L. G.

2017-03-01

The optical coupling between gratings in diffraction-based overlay triggers a swing-curve1,6 like response of the target's signal contrast and overlay sensitivity through measurement wavelengths and polarizations. This means there are distinct measurement recipes (wavelength and polarization combinations) for a given target where signal contrast and overlay sensitivity are located at the optimal parts of the swing-curve that can provide accurate and robust measurements. Some of these optimal recipes can be the ideal choices of settings for production. The user has to stay away from the non-optimal recipe choices (that are located on the undesirable parts of the swing-curve) to avoid possibilities to make overlay measurement error that can be sometimes (depending on the amount of asymmetry and stack) in the order of several "nm". To accurately identify these optimum operating areas of the swing-curve during an experimental setup, one needs to have full-flexibility in wavelength and polarization choices. In this technical publication, a diffraction-based overlay (DBO) measurement tool with many choices of wavelengths and polarizations is utilized on advanced production stacks to study swing-curves. Results show that depending on the stack and the presence of asymmetry, the swing behavior can significantly vary and a solid procedure is needed to identify a recipe during setup that is robust against variations in stack and grating asymmetry. An approach is discussed on how to use this knowledge of swing-curve to identify recipe that is not only accurate at setup, but also robust over the wafer, and wafer-to-wafer. KPIs are reported in run-time to ensure the quality / accuracy of the reading (basically acting as an error bar to overlay measurement).

Influence of Different Coupling Modes on the Robustness of Smart Grid under Targeted Attack.

PubMed

Kang, WenJie; Hu, Gang; Zhu, PeiDong; Liu, Qiang; Hang, Zhi; Liu, Xin

2018-05-24

Many previous works only focused on the cascading failure of global coupling of one-to-one structures in interdependent networks, but the local coupling of dual coupling structures has rarely been studied due to its complex structure. This will result in a serious consequence that many conclusions of the one-to-one structure may be incorrect in the dual coupling network and do not apply to the smart grid. Therefore, it is very necessary to subdivide the dual coupling link into a top-down coupling link and a bottom-up coupling link in order to study their influence on network robustness by combining with different coupling modes. Additionally, the power flow of the power grid can cause the load of a failed node to be allocated to its neighboring nodes and trigger a new round of load distribution when the load of these nodes exceeds their capacity. This means that the robustness of smart grids may be affected by four factors, i.e., load redistribution, local coupling, dual coupling link and coupling mode; however, the research on the influence of those factors on the network robustness is missing. In this paper, firstly, we construct the smart grid as a two-layer network with a dual coupling link and divide the power grid and communication network into many subnets based on the geographical location of their nodes. Secondly, we define node importance ( N I ) as an evaluation index to access the impact of nodes on the cyber or physical network and propose three types of coupling modes based on N I of nodes in the cyber and physical subnets, i.e., Assortative Coupling in Subnets (ACIS), Disassortative Coupling in Subnets (DCIS), and Random Coupling in Subnets (RCIS). Thirdly, a cascading failure model is proposed for studying the effect of local coupling of dual coupling link in combination with ACIS, DCIS, and RCIS on the robustness of the smart grid against a targeted attack, and the survival rate of functional nodes is used to assess the robustness of the smart grid. Finally, we use the IEEE 118-Bus System and the Italian High-Voltage Electrical Transmission Network to verify our model and obtain the same conclusions: (I) DCIS applied to the top-down coupling link is better able to enhance the robustness of the smart grid against a targeted attack than RCIS or ACIS, (II) ACIS applied to a bottom-up coupling link is better able to enhance the robustness of the smart grid against a targeted attack than RCIS or DCIS, and (III) the robustness of the smart grid can be improved by increasing the tolerance α . This paper provides some guidelines for slowing down the speed of the cascading failures in the design of architecture and optimization of interdependent networks, such as a top-down link with DCIS, a bottom-up link with ACIS, and an increased tolerance α .

Thermoacoustics of solids: A pathway to solid state engines and refrigerators

NASA Astrophysics Data System (ADS)

Hao, Haitian; Scalo, Carlo; Sen, Mihir; Semperlotti, Fabio

2018-01-01

Thermoacoustic oscillations have been one of the most exciting discoveries of the physics of fluids in the 19th century. Since its inception, scientists have formulated a comprehensive theoretical explanation of the basic phenomenon which has later found several practical applications to engineering devices. To date, all studies have concentrated on the thermoacoustics of fluid media where this fascinating mechanism was exclusively believed to exist. Our study shows theoretical and numerical evidence of the existence of thermoacoustic instabilities in solid media. Although the underlying physical mechanism exhibits some interesting similarities with its counterpart in fluids, the theoretical framework highlights relevant differences that have important implications on the ability to trigger and sustain the thermoacoustic response. This mechanism could pave the way to the development of highly robust and reliable solid-state thermoacoustic engines and refrigerators.

RATIR Follow-up of LIGO/Virgo Gravitational Wave Events

NASA Astrophysics Data System (ADS)

Golkhou, V. Zach; Butler, Nathaniel R.; Strausbaugh, Robert; Troja, Eleonora; Kutyrev, Alexander; Lee, William H.; Román-Zúñiga, Carlos G.; Watson, Alan M.

2018-04-01

We have recently witnessed the first multi-messenger detection of colliding neutron stars through gravitational waves (GWs) and electromagnetic (EM) waves (GW 170817) thanks to the joint efforts of LIGO/Virgo and Space/Ground-based telescopes. In this paper, we report on the RATIR follow-up observation strategies and show the results for the trigger G194575. This trigger is not of astrophysical interest; however, it is of great interest to the robust design of a follow-up engine to explore large sky-error regions. We discuss the development of an image-subtraction pipeline for the six-color, optical/NIR imaging camera RATIR. Considering a two-band (i and r) campaign in the fall of 2015, we find that the requirement of simultaneous detection in both bands leads to a factor ∼10 reduction in false alarm rate, which can be further reduced using additional bands. We also show that the performance of our proposed algorithm is robust to fluctuating observing conditions, maintaining a low false alarm rate with a modest decrease in system efficiency that can be overcome utilizing repeat visits. Expanding our pipeline to search for either optical or NIR detections (three or more bands), considering separately the optical riZ and NIR YJH bands, should result in a false alarm rate ≈1% and an efficiency ≈90%. RATIR’s simultaneous optical/NIR observations are expected to yield about one candidate transient in the vast 100 deg2 LIGO error region for prioritized follow-up with larger aperture telescopes.

Computational Software for Fitting Seismic Data to Epidemic-Type Aftershock Sequence Models

NASA Astrophysics Data System (ADS)

Chu, A.

2014-12-01

Modern earthquake catalogs are often analyzed using spatial-temporal point process models such as the epidemic-type aftershock sequence (ETAS) models of Ogata (1998). My work introduces software to implement two of ETAS models described in Ogata (1998). To find the Maximum-Likelihood Estimates (MLEs), my software provides estimates of the homogeneous background rate parameter and the temporal and spatial parameters that govern triggering effects by applying the Expectation-Maximization (EM) algorithm introduced in Veen and Schoenberg (2008). Despite other computer programs exist for similar data modeling purpose, using EM-algorithm has the benefits of stability and robustness (Veen and Schoenberg, 2008). Spatial shapes that are very long and narrow cause difficulties in optimization convergence and problems with flat or multi-modal log-likelihood functions encounter similar issues. My program uses a robust method to preset a parameter to overcome the non-convergence computational issue. In addition to model fitting, the software is equipped with useful tools for examining modeling fitting results, for example, visualization of estimated conditional intensity, and estimation of expected number of triggered aftershocks. A simulation generator is also given with flexible spatial shapes that may be defined by the user. This open-source software has a very simple user interface. The user may execute it on a local computer, and the program also has potential to be hosted online. Java language is used for the software's core computing part and an optional interface to the statistical package R is provided.

Control of CA3 output by feedforward inhibition despite developmental changes in the excitation-inhibition balance.

PubMed

Torborg, Christine L; Nakashiba, Toshiaki; Tonegawa, Susumu; McBain, Chris J

2010-11-17

In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.

MICCA: a complete and accurate software for taxonomic profiling of metagenomic data.

PubMed

Albanese, Davide; Fontana, Paolo; De Filippo, Carlotta; Cavalieri, Duccio; Donati, Claudio

2015-05-19

The introduction of high throughput sequencing technologies has triggered an increase of the number of studies in which the microbiota of environmental and human samples is characterized through the sequencing of selected marker genes. While experimental protocols have undergone a process of standardization that makes them accessible to a large community of scientist, standard and robust data analysis pipelines are still lacking. Here we introduce MICCA, a software pipeline for the processing of amplicon metagenomic datasets that efficiently combines quality filtering, clustering of Operational Taxonomic Units (OTUs), taxonomy assignment and phylogenetic tree inference. MICCA provides accurate results reaching a good compromise among modularity and usability. Moreover, we introduce a de-novo clustering algorithm specifically designed for the inference of Operational Taxonomic Units (OTUs). Tests on real and synthetic datasets shows that thanks to the optimized reads filtering process and to the new clustering algorithm, MICCA provides estimates of the number of OTUs and of other common ecological indices that are more accurate and robust than currently available pipelines. Analysis of public metagenomic datasets shows that the higher consistency of results improves our understanding of the structure of environmental and human associated microbial communities. MICCA is an open source project.

MICCA: a complete and accurate software for taxonomic profiling of metagenomic data

PubMed Central

Albanese, Davide; Fontana, Paolo; De Filippo, Carlotta; Cavalieri, Duccio; Donati, Claudio

2015-01-01

The introduction of high throughput sequencing technologies has triggered an increase of the number of studies in which the microbiota of environmental and human samples is characterized through the sequencing of selected marker genes. While experimental protocols have undergone a process of standardization that makes them accessible to a large community of scientist, standard and robust data analysis pipelines are still lacking. Here we introduce MICCA, a software pipeline for the processing of amplicon metagenomic datasets that efficiently combines quality filtering, clustering of Operational Taxonomic Units (OTUs), taxonomy assignment and phylogenetic tree inference. MICCA provides accurate results reaching a good compromise among modularity and usability. Moreover, we introduce a de-novo clustering algorithm specifically designed for the inference of Operational Taxonomic Units (OTUs). Tests on real and synthetic datasets shows that thanks to the optimized reads filtering process and to the new clustering algorithm, MICCA provides estimates of the number of OTUs and of other common ecological indices that are more accurate and robust than currently available pipelines. Analysis of public metagenomic datasets shows that the higher consistency of results improves our understanding of the structure of environmental and human associated microbial communities. MICCA is an open source project. PMID:25988396

WRKY Transcription Factors Phosphorylated by MAPK Regulate a Plant Immune NADPH Oxidase in Nicotiana benthamiana[OPEN

PubMed Central

Adachi, Hiroaki; Nakano, Takaaki; Miyagawa, Noriko; Ishihama, Nobuaki; Yoshioka, Miki; Katou, Yuri; Yaeno, Takashi

2015-01-01

Pathogen attack sequentially confers pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) after sensing of pathogen patterns and effectors by plant immune receptors, respectively. Reactive oxygen species (ROS) play pivotal roles in PTI and ETI as signaling molecules. Nicotiana benthamiana RBOHB, an NADPH oxidase, is responsible for both the transient PTI ROS burst and the robust ETI ROS burst. Here, we show that RBOHB transactivation mediated by MAPK contributes to R3a/AVR3a-triggered ETI (AVR3a-ETI) ROS burst. RBOHB is markedly induced during the ETI and INF1-triggered PTI (INF1-PTI), but not flg22-tiggered PTI (flg22-PTI). We found that the RBOHB promoter contains a functional W-box in the R3a/AVR3a and INF1 signal-responsive cis-element. Ectopic expression of four phospho-mimicking mutants of WRKY transcription factors, which are MAPK substrates, induced RBOHB, and yeast one-hybrid analysis indicated that these mutants bind to the cis-element. Chromatin immunoprecipitation assays indicated direct binding of the WRKY to the cis-element in plants. Silencing of multiple WRKY genes compromised the upregulation of RBOHB, resulting in impairment of AVR3a-ETI and INF1-PTI ROS bursts, but not the flg22-PTI ROS burst. These results suggest that the MAPK-WRKY pathway is required for AVR3a-ETI and INF1-PTI ROS bursts by activation of RBOHB. PMID:26373453

Zinc triggers microglial activation.

PubMed

Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

2008-05-28

Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

Cascade defense via routing in complex networks

NASA Astrophysics Data System (ADS)

Xu, Xiao-Lan; Du, Wen-Bo; Hong, Chen

2015-05-01

As the cascading failures in networked traffic systems are becoming more and more serious, research on cascade defense in complex networks has become a hotspot in recent years. In this paper, we propose a traffic-based cascading failure model, in which each packet in the network has its own source and destination. When cascade is triggered, packets will be redistributed according to a given routing strategy. Here, a global hybrid (GH) routing strategy, which uses the dynamic information of the queue length and the static information of nodes' degree, is proposed to defense the network cascade. Comparing GH strategy with the shortest path (SP) routing, efficient routing (ER) and global dynamic (GD) routing strategies, we found that GH strategy is more effective than other routing strategies in improving the network robustness against cascading failures. Our work provides insight into the robustness of networked traffic systems.

Accelerated 4D self-gated MRI of tibiofemoral kinematics.

PubMed

Mazzoli, Valentina; Schoormans, Jasper; Froeling, Martijn; Sprengers, Andre M; Coolen, Bram F; Verdonschot, Nico; Strijkers, Gustav J; Nederveen, Aart J

2017-11-01

Anatomical (static) magnetic resonance imaging (MRI) is the most useful imaging technique for the evaluation and assessment of internal derangement of the knee, but does not provide dynamic information and does not allow the study of the interaction of the different tissues during motion. As knee pain is often only experienced during dynamic tasks, the ability to obtain four-dimensional (4D) images of the knee during motion could improve the diagnosis and provide a deeper understanding of the knee joint. In this work, we present a novel approach for dynamic, high-resolution, 4D imaging of the freely moving knee without the need for external triggering. The dominant knee of five healthy volunteers was scanned during a flexion/extension task. To evaluate the effects of non-uniform motion and poor coordination skills on the quality of the reconstructed images, we performed a comparison between fully free movement and movement instructed by a visual cue. The trigger signal for self-gating was extracted using principal component analysis (PCA), and the images were reconstructed using a parallel imaging and compressed sensing reconstruction pipeline. The reconstructed 4D movies were scored for image quality and used to derive bone kinematics through image registration. Using our method, we were able to obtain 4D high-resolution movies of the knee without the need for external triggering hardware. The movies obtained with and without instruction did not differ significantly in terms of image scoring and quantitative values for tibiofemoral kinematics. Our method showed to be robust for the extraction of the self-gating signal even for uninstructed motion. This can make the technique suitable for patients who, as a result of pain, may find it difficult to comply exactly with instructions. Furthermore, bone kinematics can be derived from accelerated MRI without the need for additional hardware for triggering. Copyright © 2017 John Wiley & Sons, Ltd.

Measure of robustness for complex networks

NASA Astrophysics Data System (ADS)

Youssef, Mina Nabil

Critical infrastructures are repeatedly attacked by external triggers causing tremendous amount of damages. Any infrastructure can be studied using the powerful theory of complex networks. A complex network is composed of extremely large number of different elements that exchange commodities providing significant services. The main functions of complex networks can be damaged by different types of attacks and failures that degrade the network performance. These attacks and failures are considered as disturbing dynamics, such as the spread of viruses in computer networks, the spread of epidemics in social networks, and the cascading failures in power grids. Depending on the network structure and the attack strength, every network differently suffers damages and performance degradation. Hence, quantifying the robustness of complex networks becomes an essential task. In this dissertation, new metrics are introduced to measure the robustness of technological and social networks with respect to the spread of epidemics, and the robustness of power grids with respect to cascading failures. First, we introduce a new metric called the Viral Conductance (VCSIS ) to assess the robustness of networks with respect to the spread of epidemics that are modeled through the susceptible/infected/susceptible (SIS) epidemic approach. In contrast to assessing the robustness of networks based on a classical metric, the epidemic threshold, the new metric integrates the fraction of infected nodes at steady state for all possible effective infection strengths. Through examples, VCSIS provides more insights about the robustness of networks than the epidemic threshold. In addition, both the paradoxical robustness of Barabasi-Albert preferential attachment networks and the effect of the topology on the steady state infection are studied, to show the importance of quantifying the robustness of networks. Second, a new metric VCSIR is introduced to assess the robustness of networks with respect to the spread of susceptible/infected/recovered (SIR) epidemics. To compute VCSIR, we propose a novel individual-based approach to model the spread of SIR epidemics in networks, which captures the infection size for a given effective infection rate. Thus, VCSIR quantitatively integrates the infection strength with the corresponding infection size. To optimize the VCSIR metric, a new mitigation strategy is proposed, based on a temporary reduction of contacts in social networks. The social contact network is modeled as a weighted graph that describes the frequency of contacts among the individuals. Thus, we consider the spread of an epidemic as a dynamical system, and the total number of infection cases as the state of the system, while the weight reduction in the social network is the controller variable leading to slow/reduce the spread of epidemics. Using optimal control theory, the obtained solution represents an optimal adaptive weighted network defined over a finite time interval. Moreover, given the high complexity of the optimization problem, we propose two heuristics to find the near optimal solutions by reducing the contacts among the individuals in a decentralized way. Finally, the cascading failures that can take place in power grids and have recently caused several blackouts are studied. We propose a new metric to assess the robustness of the power grid with respect to the cascading failures. The power grid topology is modeled as a network, which consists of nodes and links representing power substations and transmission lines, respectively. We also propose an optimal islanding strategy to protect the power grid when a cascading failure event takes place in the grid. The robustness metrics are numerically evaluated using real and synthetic networks to quantify their robustness with respect to disturbing dynamics. We show that the proposed metrics outperform the classical metrics in quantifying the robustness of networks and the efficiency of the mitigation strategies. In summary, our work advances the network science field in assessing the robustness of complex networks with respect to various disturbing dynamics.

Gaze cueing by pareidolia faces.

PubMed

Takahashi, Kohske; Watanabe, Katsumi

2013-01-01

Visual images that are not faces are sometimes perceived as faces (the pareidolia phenomenon). While the pareidolia phenomenon provides people with a strong impression that a face is present, it is unclear how deeply pareidolia faces are processed as faces. In the present study, we examined whether a shift in spatial attention would be produced by gaze cueing of face-like objects. A robust cueing effect was observed when the face-like objects were perceived as faces. The magnitude of the cueing effect was comparable between the face-like objects and a cartoon face. However, the cueing effect was eliminated when the observer did not perceive the objects as faces. These results demonstrated that pareidolia faces do more than give the impression of the presence of faces; indeed, they trigger an additional face-specific attentional process.

Gaze cueing by pareidolia faces

PubMed Central

Takahashi, Kohske; Watanabe, Katsumi

2013-01-01

Visual images that are not faces are sometimes perceived as faces (the pareidolia phenomenon). While the pareidolia phenomenon provides people with a strong impression that a face is present, it is unclear how deeply pareidolia faces are processed as faces. In the present study, we examined whether a shift in spatial attention would be produced by gaze cueing of face-like objects. A robust cueing effect was observed when the face-like objects were perceived as faces. The magnitude of the cueing effect was comparable between the face-like objects and a cartoon face. However, the cueing effect was eliminated when the observer did not perceive the objects as faces. These results demonstrated that pareidolia faces do more than give the impression of the presence of faces; indeed, they trigger an additional face-specific attentional process. PMID:25165505

Interdependent networks - Topological percolation research and application in finance

NASA Astrophysics Data System (ADS)

Zhou, Di

This dissertation covers the two major parts of my Ph.D. research: i) developing a theoretical framework of complex networks and applying simulation and numerical methods to study the robustness of the network system, and ii) applying statistical physics concepts and methods to quantitatively analyze complex systems and applying the theoretical framework to study real-world systems. In part I, we focus on developing theories of interdependent networks as well as building computer simulation models, which includes three parts: 1) We report on the effects of topology on failure propagation for a model system consisting of two interdependent networks. We find that the internal node correlations in each of the networks significantly changes the critical density of failures, which can trigger the total disruption of the two-network system. Specifically, we find that the assortativity within a single network decreases the robustness of the entire system. 2) We study the percolation behavior of two interdependent scale-free (SF) networks under random failure of 1-p fraction of nodes. We find that as the coupling strength q between the two networks reduces from 1 (fully coupled) to 0 (no coupling), there exist two critical coupling strengths q1 and q2 , which separate the behaviors of the giant component as a function of p into three different regions, and for q2 < q < q 1 , we observe a hybrid order phase transition phenomenon. 3) We study the robustness of n interdependent networks with partially support-dependent relationship both analytically and numerically. We study a starlike network of n Erdos-Renyi (ER), SF networks and a looplike network of n ER networks, and we find for starlike networks, their phase transition regions change with n, but for looplike networks the phase regions change with average degree k . In part II, we apply concepts and methods developed in statistical physics to study economic systems. We analyze stock market indices and foreign exchange daily returns for 60 countries over the period of 1999-2012. We build a multi-layer network model based on different correlation measures, and introduce a dynamic network model to simulate and analyze the initializing and spreading of financial crisis. Using different computational approaches and econometric tests, we find atypical behavior of the cross correlations and community formations in the financial networks that we study during the financial crisis of 2008. For example, the overall correlation of stock market increases during crisis while the correlation between stock market and foreign exchange market decreases. The dramatic increase in correlations between a specific nation and other nations may indicate that this nation could trigger a global financial crisis. Specifically, core countries that have higher correlations with other countries and larger Gross Domestic Product (GDP) values spread financial crisis quite effectively, yet some countries with small GDPs like Greece and Cyprus are also effective in propagating systemic risk and spreading global financial crisis.

A fast, robust and tunable synthetic gene oscillator.

PubMed

Stricker, Jesse; Cookson, Scott; Bennett, Matthew R; Mather, William H; Tsimring, Lev S; Hasty, Jeff

2008-11-27

One defining goal of synthetic biology is the development of engineering-based approaches that enable the construction of gene-regulatory networks according to 'design specifications' generated from computational modelling. This approach provides a systematic framework for exploring how a given regulatory network generates a particular phenotypic behaviour. Several fundamental gene circuits have been developed using this approach, including toggle switches and oscillators, and these have been applied in new contexts such as triggered biofilm development and cellular population control. Here we describe an engineered genetic oscillator in Escherichia coli that is fast, robust and persistent, with tunable oscillatory periods as fast as 13 min. The oscillator was designed using a previously modelled network architecture comprising linked positive and negative feedback loops. Using a microfluidic platform tailored for single-cell microscopy, we precisely control environmental conditions and monitor oscillations in individual cells through multiple cycles. Experiments reveal remarkable robustness and persistence of oscillations in the designed circuit; almost every cell exhibited large-amplitude fluorescence oscillations throughout observation runs. The oscillatory period can be tuned by altering inducer levels, temperature and the media source. Computational modelling demonstrates that the key design principle for constructing a robust oscillator is a time delay in the negative feedback loop, which can mechanistically arise from the cascade of cellular processes involved in forming a functional transcription factor. The positive feedback loop increases the robustness of the oscillations and allows for greater tunability. Examination of our refined model suggested the existence of a simplified oscillator design without positive feedback, and we construct an oscillator strain confirming this computational prediction.

Blood pressure control with selective vagal nerve stimulation and minimal side effects

NASA Astrophysics Data System (ADS)

Plachta, Dennis T. T.; Gierthmuehlen, Mortimer; Cota, Oscar; Espinosa, Nayeli; Boeser, Fabian; Herrera, Taliana C.; Stieglitz, Thomas; Zentner, Joseph

2014-06-01

Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson's disease.

PubMed

Sugama, Shuei; Sekiyama, Kazunari; Kodama, Tohru; Takamatsu, Yoshiki; Takenouchi, Takato; Hashimoto, Makoto; Bruno, Conti; Kakinuma, Yoshihiko

2016-01-01

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and, to a lesser extent, in the noradrenergic neurons of the locus coeruleus (LC). Most cases of PD are idiopathic and sporadic and are believed to be the result of both environmental and genetic factors. Here, to the best of our knowledge, we report the first evidence that chronic restraint stress (8h/day, 5days/week) substantially reduces nigral DA and LC noradrenergic neuronal cell numbers in rats. Loss of DA neurons in the SNpc was evident after 2weeks of stress and progressed in a time-dependent manner, reaching up to 61% at 16weeks. This reduction was accompanied by robust microglial activation and oxidative stress and was marked by nitrotyrosine in the SNpc and LC of the midbrain. These results indicate that chronic stress triggers DA and noradrenergic neurodegeneration by increasing oxidative stress, and that activated microglia in the substantia nigra and LC may play an important role in modulating the neurotoxic effects of oxidative stress. Taken together, these data suggest that exposure to chronic stress triggers DA and noradrenergic neurodegeneration, which is a cause of PD. Copyright © 2015 Elsevier Inc. All rights reserved.

In situ formation of magnetopolymersomes via electroporation for MRI

NASA Astrophysics Data System (ADS)

Bain, Jennifer; Ruiz-Pérez, Lorena; Kennerley, Aneurin J.; Muench, Stephen P.; Thompson, Rebecca; Battaglia, Giuseppe; Staniland, Sarah S.

2015-09-01

As the development of diagnostic/therapeutic (and combined: theranostic) nanomedicine grows, smart drug-delivery vehicles become ever more critical. Currently therapies consist of drugs tethered to, or encapsulated within nanoparticles or vesicles. There is growing interest in functionalising them with magnetic nanoparticles (MNPs) to target the therapeutics by localising them using magnetic fields. An alternating magnetic field induces remote heating of the particles (hyperthermia) triggering drug release or cell death. Furthermore, MNPs are diagnostic MRI contrast agents. There is considerable interest in MNP embedded vehicles for nanomedicine, but their development is hindered by difficulties producing consistently monodisperse MNPs and their reliable loading into vesicles. Furthermore, it is highly advantageous to "trigger" MNP production and to tune the MNP's size and magnetic response. Here we present the first example of a tuneable, switchable magnetic delivery vehicle for nanomedical application. These are comprised of robust, tailored polymer vesicles (polymersomes) embedded with superparamagnetic magnetite MNPs (magnetopolymersomes) which show good MRI contrast (R2* = 148.8 s-1) and have a vacant core for loading of therapeutics. Critically, the magnetopolymersomes are produced by a pioneering nanoreactor method whereby electroporation triggers the in situ formation of MNPs within the vesicle membrane, offering a switchable, tuneable magnetic responsive theranostic delivery vehicle.

How to assess the efficiency of synchronization experiments in tokamaks

NASA Astrophysics Data System (ADS)

Murari, A.; Craciunescu, T.; Peluso, E.; Gelfusa, M.; Lungaroni, M.; Garzotti, L.; Frigione, D.; Gaudio, P.; Contributors, JET

2016-07-01

Control of instabilities such as ELMs and sawteeth is considered an important ingredient in the development of reactor-relevant scenarios. Various forms of ELM pacing have been tried in the past to influence their behavior using external perturbations. One of the main problems with these synchronization experiments resides in the fact that ELMs are periodic or quasi-periodic in nature. Therefore, after any pulsed perturbation, if one waits long enough, an ELM is always bound to occur. To evaluate the effectiveness of ELM pacing techniques, it is crucial to determine an appropriate interval over which they can have a real influence and an effective triggering capability. In this paper, three independent statistical methods are described to address this issue: Granger causality, transfer entropy and recurrence plots. The obtained results for JET with the ITER-like wall (ILW) indicate that the proposed techniques agree very well and provide much better estimates than the traditional heuristic criteria reported in the literature. Moreover, their combined use allows for the improvement of the time resolution of the assessment and determination of the efficiency of the pellet triggering in different phases of the same discharge. Therefore, the developed methods can be used to provide a quantitative and statistically robust estimate of the triggering efficiency of ELM pacing under realistic experimental conditions.

Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses.

PubMed

Roux, Jonathan; Bard, Denis; Le Pabic, Estelle; Segala, Claire; Reis, Jacques; Ongagna, Jean-Claude; de Sèze, Jérôme; Leray, Emmanuelle

2017-07-01

Seasonal variation of relapses in multiple sclerosis (MS) suggests that season-dependent factors, such as ambient air pollution, may trigger them. However, only few studies have considered possible role of air pollutants as relapse's risk factor. We investigated the effect of particulate matter of aerodynamic diameter smaller than 10µm (PM 10 ) on MS relapses. In total, 536 relapsing MS patients from Strasbourg city (France) were included, accounting for 2052 relapses over 2000-2009 period. A case-crossover design was used with cases defined as the days of relapse and controls being selected in the same patient at plus and minus 35 days. Different lags from 0 to 30 days were considered. Conditional logistic regressions, adjusted on meteorological parameters, school and public holidays, were used and exposure was considered first as a quantitative variable and second, as a binary variable. The natural logarithm of the average PM 10 concentration lagged from 1 to 3 days before relapse onset was significantly associated with relapse risk (OR =1.40 [95% confidence interval 1.08-1.81]) in cold season. Consistent results were observed when considering PM 10 as a binary variable, even if not significant. With an appropriate study design and robust ascertainment of neurological events and exposure, the present study highlights the effect of PM 10 on the risk of relapse in MS patients, probably through oxidative stress mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative biochemical studies of fresh frozen plasma and pooled solvent/detergent-treated plasma (octaplasLG® ) with focus on protein S and its impact in different thrombin generation assay set-ups.

PubMed

Heger, A; Janisch, S; Pock, K; Römisch, J

2016-10-01

The solvent/detergent treatment enables effective and robust inactivation of all lipid-enveloped viruses, but also inactivates partly sensitive plasma proteins such as protein S. The aim of this study was to investigate the thrombin generation capacity of octaplasLG ® , in particular focusing on the function of protein S in thrombin generation assay and the impact of assay settings. Sixteen octaplasLG ® batches and 32 units of single donor fresh frozen plasma (FFP) were investigated. For protein S, both functional activity and free antigen levels were measured. Thrombin generation assay was performed using two fluorogenic tests with different triggers. Finally, rotational thromboelastometry was performed. Mean protein S levels were lower in octaplasLG ® , but a wider range of values was found for FFP. Clotting parameters and thrombin generation capacities overlapped between the two plasma groups as demonstrated using both thrombin generation assays and different triggers. Spiking studies with protein S-depleted plasma, human purified protein S or antibodies against protein S confirmed a correlation between protein S and thrombin generation capacity under specific assay conditions, especially in an assay with low tissue factor concentration. Correlation between protein S and thrombin generation capacity was demonstrated in the TGA. Due to higher variability in protein S content in the FFP group, overlapping haemostatic potentials of the two plasma groups were found. © 2016 International Society of Blood Transfusion.

Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light.

PubMed

Chen, Xianjun; Li, Ting; Wang, Xue; Du, Zengmin; Liu, Renmei; Yang, Yi

2016-04-07

Programmable transcription factors can enable precise control of gene expression triggered by a chemical inducer or light. To obtain versatile transgene system with combined benefits of a chemical inducer and light inducer, we created various chimeric promoters through the assembly of different copies of the tet operator and Gal4 operator module, which simultaneously responded to a tetracycline-responsive transcription factor and a light-switchable transactivator. The activities of these chimeric promoters can be regulated by tetracycline and blue light synergistically or antagonistically. Further studies of the antagonistic genetic circuit exhibited high spatiotemporal resolution and extremely low leaky expression, which therefore could be used to spatially and stringently control the expression of highly toxic protein Diphtheria toxin A for light regulated gene therapy. When transferring plasmids engineered for the gene switch-driven expression of a firefly luciferase (Fluc) into mice, the Fluc expression levels of the treated animals directly correlated with the tetracycline and light input program. We suggest that dual-input genetic circuits using TET and light that serve as triggers to achieve expression profiles may enable the design of robust therapeutic gene circuits for gene- and cell-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Regional dry-season climate changes due to three decades of Amazonian deforestation

NASA Astrophysics Data System (ADS)

Khanna, Jaya; Medvigy, David; Fueglistaler, Stephan; Walko, Robert

2017-02-01

More than 20% of the Amazon rainforest has been cleared in the past three decades, triggering important hydroclimatic changes. Small-scale (a few kilometres) deforestation in the 1980s has caused thermally triggered atmospheric circulations that increase regional cloudiness and precipitation frequency. However, these circulations are predicted to diminish as deforestation increases. Here we use multi-decadal satellite records and numerical model simulations to show a regime shift in the regional hydroclimate accompanying increasing deforestation in Rondônia, Brazil. Compared with the 1980s, present-day deforested areas in downwind western Rondônia are found to be wetter than upwind eastern deforested areas during the local dry season. The resultant precipitation change in the two regions is approximately +/-25% of the deforested area mean. Meso-resolution simulations robustly reproduce this transition when forced with increasing deforestation alone, showing that large-scale climate variability plays a negligible role. Furthermore, deforestation-induced surface roughness reduction is found to play an essential role in the present-day dry-season hydroclimate. Our study illustrates the strong scale sensitivity of the climatic response to Amazonian deforestation and suggests that deforestation is sufficiently advanced to have caused a shift from a thermally to a dynamically driven hydroclimatic regime.

Green fluorescent protein (GFP): is seeing believing and is that enough?

PubMed

Shorter, Susan A; Pettit, Marie W; Dyer, Paul D R; Coakley Youngs, Emma; Gorringe-Pattrick, Monique A M; El-Daher, Samer; Richardson, Simon

Intracellular compartmentalisation is a significant barrier to the successful nucleocytosolic delivery of biologics. The endocytic system has been shown to be responsible for compartmentalisation, providing an entry point, and trigger(s) for the activation of drug delivery systems. Consequently, many of the technologies used to understand endocytosis have found utility within the field of drug delivery. The use of fluorescent proteins as markers denoting compartmentalisation within the endocytic system has become commonplace. Several of the limitations associated with the use of green fluorescent protein (GFP) within the context of drug delivery have been explored here by asking a series of related questions: (1) Are molecules that regulate fusion to a specific compartment (i.e. Rab- or SNARE-GFP fusions) a good choice of marker for that compartment? (2) How reliable was GFP-marker overexpression when used to define a given endocytic compartment? (3) Can glutathione-s-transferase (GST) fused in frame with GFP (GST-GFP) act as a fluid phase endocytic probe? (4) Was GFP fluorescence a robust indicator of (GFP) protein integrity? This study concluded that there are many appropriate and useful applications for GFP; however, thought and an understanding of the biological and physicochemical character of these markers are required for the generation of meaningful data.

Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

PubMed Central

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H.; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID:22073316

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

PubMed

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Virus infection, antiviral immunity, and autoimmunity

PubMed Central

Getts, Daniel R.; Chastain, Emily M. L.; Terry, Rachael L.; Miller, Stephen D.

2014-01-01

Summary As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity. PMID:23947356

Effect-based trigger values for in vitro bioassays: Reading across from existing water quality guideline values.

PubMed

Escher, Beate I; Neale, Peta A; Leusch, Frederic D L

2015-09-15

Cell-based bioassays are becoming increasingly popular in water quality assessment. The new generations of reporter-gene assays are very sensitive and effects are often detected in very clean water types such as drinking water and recycled water. For monitoring applications it is therefore imperative to derive trigger values that differentiate between acceptable and unacceptable effect levels. In this proof-of-concept paper, we propose a statistical method to read directly across from chemical guideline values to trigger values without the need to perform in vitro to in vivo extrapolations. The derivation is based on matching effect concentrations with existing chemical guideline values and filtering out appropriate chemicals that are responsive in the given bioassays at concentrations in the range of the guideline values. To account for the mixture effects of many chemicals acting together in a complex water sample, we propose bioanalytical equivalents that integrate the effects of groups of chemicals with the same mode of action that act in a concentration-additive manner. Statistical distribution methods are proposed to derive a specific effect-based trigger bioanalytical equivalent concentration (EBT-BEQ) for each bioassay of environmental interest that targets receptor-mediated toxicity. Even bioassays that are indicative of the same mode of action have slightly different numeric trigger values due to differences in their inherent sensitivity. The algorithm was applied to 18 cell-based bioassays and 11 provisional effect-based trigger bioanalytical equivalents were derived as an illustrative example using the 349 chemical guideline values protective for human health of the Australian Guidelines for Water Recycling. We illustrate the applicability using the example of a diverse set of water samples including recycled water. Most recycled water samples were compliant with the proposed triggers while wastewater effluent would not have been compliant with a few. The approach is readily adaptable to any water type and guideline or regulatory framework and can be expanded from the protection goal of human health to environmental protection targets. While this work constitutes a proof of principle, the applicability remains limited at present due to insufficient experimental bioassay data on individual regulated chemicals and the derived effect-based trigger values are of course only provisional. Once the experimental database is expanded and made more robust, the proposed effect-based trigger values may provide guidance in a regulatory context. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rationales for the Lightning Launch Commit Criteria

NASA Technical Reports Server (NTRS)

Willett, John C. (Editor); Merceret, Francis J. (Editor); Krider, E. Philip; O'Brien, T. Paul; Dye, James E.; Walterscheid, Richard L.; Stolzenburg, Maribeth; Cummins, Kenneth; Christian, Hugh J.; Madura, John T.

2016-01-01

Since natural and triggered lightning are demonstrated hazards to launch vehicles, payloads, and spacecraft, NASA and the Department of Defense (DoD) follow the Lightning Launch Commit Criteria (LLCC) for launches from Federal Ranges. The LLCC were developed to prevent future instances of a rocket intercepting natural lightning or triggering a lightning flash during launch from a Federal Range. NASA and DoD utilize the Lightning Advisory Panel (LAP) to establish and develop robust rationale from which the criteria originate. The rationale document also contains appendices that provide additional scientific background, including detailed descriptions of the theory and observations behind the rationales. The LLCC in whole or part are used across the globe due to the rigor of the documented criteria and associated rationale. The Federal Aviation Administration (FAA) adopted the LLCC in 2006 for commercial space transportation and the criteria were codified in the FAA's Code of Federal Regulations (CFR) for Safety of an Expendable Launch Vehicle (Appendix G to 14 CFR Part 417, (G417)) and renamed Lightning Flight Commit Criteria in G417.

Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens. [Corrected].

PubMed

Wu, Liang; Chen, Huan; Curtis, Chad; Fu, Zheng Qing

2014-01-01

Plant resistance (R) proteins perceive specific pathogen effectors from diverse plant pathogens to initiate defense responses, designated effector-triggered immunity (ETI). Plant R proteins are mostly nucleotide binding-leucine rich repeat (NB-LRR) proteins, which recognize pathogen effectors directly or indirectly through sophisticated mechanisms. Upon activation by effector proteins, R proteins elicit robust defense responses, including a rapid burst of reactive oxygen species (ROS), induced biosynthesis and accumulation of salicylic acid (SA), a rapid programmed cell death (PCD) called hypersensitive response (HR) at the infection sites, and increased expression of pathogenesis-related (PR) genes. Initiation of ETI is correlated with a complex network of defense signaling pathways, resulting in defensive cellular responses and large-scale transcriptional reprogramming events. In this review, we highlight important recent advances on the recognition of effectors, regulation and activation of plant R proteins, dynamic intracellular trafficking of R proteins, induction of cell death, and transcriptional reprogramming associated with ETI. Current knowledge gaps and future research directions are also discussed in this review.

Triggering signaling pathways using F-actin self-organization.

PubMed

Colin, A; Bonnemay, L; Gayrard, C; Gautier, J; Gueroui, Z

2016-10-04

The spatiotemporal organization of proteins within cells is essential for cell fate behavior. Although it is known that the cytoskeleton is vital for numerous cellular functions, it remains unclear how cytoskeletal activity can shape and control signaling pathways in space and time throughout the cell cytoplasm. Here we show that F-actin self-organization can trigger signaling pathways by engineering two novel properties of the microfilament self-organization: (1) the confinement of signaling proteins and (2) their scaffolding along actin polymers. Using in vitro reconstitutions of cellular functions, we found that both the confinement of nanoparticle-based signaling platforms powered by F-actin contractility and the scaffolding of engineered signaling proteins along actin microfilaments can drive a signaling switch. Using Ran-dependent microtubule nucleation, we found that F-actin dynamics promotes the robust assembly of microtubules. Our in vitro assay is a first step towards the development of novel bottom-up strategies to decipher the interplay between cytoskeleton spatial organization and signaling pathway activity.

Triggering signaling pathways using F-actin self-organization

PubMed Central

Colin, A.; Bonnemay, L.; Gayrard, C.; Gautier, J.; Gueroui, Z.

2016-01-01

The spatiotemporal organization of proteins within cells is essential for cell fate behavior. Although it is known that the cytoskeleton is vital for numerous cellular functions, it remains unclear how cytoskeletal activity can shape and control signaling pathways in space and time throughout the cell cytoplasm. Here we show that F-actin self-organization can trigger signaling pathways by engineering two novel properties of the microfilament self-organization: (1) the confinement of signaling proteins and (2) their scaffolding along actin polymers. Using in vitro reconstitutions of cellular functions, we found that both the confinement of nanoparticle-based signaling platforms powered by F-actin contractility and the scaffolding of engineered signaling proteins along actin microfilaments can drive a signaling switch. Using Ran-dependent microtubule nucleation, we found that F-actin dynamics promotes the robust assembly of microtubules. Our in vitro assay is a first step towards the development of novel bottom-up strategies to decipher the interplay between cytoskeleton spatial organization and signaling pathway activity. PMID:27698406

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.

Frequent floods in the European Alps coincide with cooler periods of the past 2500 years

PubMed Central

Glur, Lukas; Wirth, Stefanie B.; Büntgen, Ulf; Gilli, Adrian; Haug, Gerald H.; Schär, Christoph; Beer, Jürg; Anselmetti, Flavio S.

2013-01-01

Severe floods triggered by intense precipitation are among the most destructive natural hazards in Alpine environments, frequently causing large financial and societal damage. Potential enhanced flood occurrence due to global climate change would thus increase threat to settlements, infrastructure, and human lives in the affected regions. Yet, projections of intense precipitation exhibit major uncertainties and robust reconstructions of Alpine floods are limited to the instrumental and historical period. Here we present a 2500-year long flood reconstruction for the European Alps, based on dated sedimentary flood deposits from ten lakes in Switzerland. We show that periods with high flood frequency coincide with cool summer temperatures. This wet-cold synchronism suggests enhanced flood occurrence to be triggered by latitudinal shifts of Atlantic and Mediterranean storm tracks. This paleoclimatic perspective reveals natural analogues for varying climate conditions, and thus can contribute to a better understanding and improved projections of weather extremes under climate change. PMID:24067733

An open-source, extensible system for laboratory timing and control

NASA Astrophysics Data System (ADS)

Gaskell, Peter E.; Thorn, Jeremy J.; Alba, Sequoia; Steck, Daniel A.

2009-11-01

We describe a simple system for timing and control, which provides control of analog, digital, and radio-frequency signals. Our system differs from most common laboratory setups in that it is open source, built from off-the-shelf components, synchronized to a common and accurate clock, and connected over an Ethernet network. A simple bus architecture facilitates creating new and specialized devices with only moderate experience in circuit design. Each device operates independently, requiring only an Ethernet network connection to the controlling computer, a clock signal, and a trigger signal. This makes the system highly robust and scalable. The devices can all be connected to a single external clock, allowing synchronous operation of a large number of devices for situations requiring precise timing of many parallel control and acquisition channels. Provided an accurate enough clock, these devices are capable of triggering events separated by one day with near-microsecond precision. We have achieved precisions of ˜0.1 ppb (parts per 109) over 16 s.

Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways.

PubMed

Bijangi-Vishehsaraei, Khadijeh; Reza Saadatzadeh, M; Wang, Haiyan; Nguyen, Angie; Kamocka, Malgorzata M; Cai, Wenjing; Cohen-Gadol, Aaron A; Halum, Stacey L; Sarkaria, Jann N; Pollok, Karen E; Safa, Ahmad R

2017-12-01

OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.

Zinc triggers microglial activation

PubMed Central

Kauppinen, Tiina M.; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A.

2009-01-01

Microglia are resident immune cells of the central nervous system. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, “amoeboid” morphology and release matrix metalloproteinases, reactive oxygen species, and other pro-inflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here we show that zinc directly triggers microglial activation. Microglia transfected with an NF-kB reporter gene showed a several-fold increase in NF-kB activity in response to 30 μM zinc. Cultured mouse microglia exposed to 15 – 30 μM zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-κB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-κB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders. PMID:18509044

Robust Denaturation of Villin Headpiece by MoS2 Nanosheet: Potential Molecular Origin of the Nanotoxicity

NASA Astrophysics Data System (ADS)

Gu, Zonglin; Yang, Zaixing; Kang, Seung-Gu; Yang, Jerry R.; Luo, Judong; Zhou, Ruhong

2016-06-01

MoS2 nanosheet, a new two-dimensional transition metal dichalcogenides nanomaterial, has attracted significant attentions lately due to many potential promising biomedical applications. Meanwhile, there is also a growing concern on its biocompatibility, with little known on its interactions with various biomolecules such as proteins. In this study, we use all-atom molecular dynamics simulations to investigate the interaction of a MoS2 nanosheet with Villin Headpiece (HP35), a model protein widely used in protein folding studies. We find that MoS2 exhibits robust denaturing capability to HP35, with its secondary structures severely destroyed within hundreds of nanosecond simulations. Both aromatic and basic residues are critical for the protein anchoring onto MoS2 surface, which then triggers the successive protein unfolding process. The main driving force behind the adsorption process is the dispersion interaction between protein and MoS2 monolayer. Moreover, water molecules at the interface between some key hydrophobic residues (e.g. Trp-64) and MoS2 surface also help to accelerate the process driven by nanoscale drying, which provides a strong hydrophobic force. These findings might have shed new light on the potential nanotoxicity of MoS2 to proteins with atomic details, which should be helpful in guiding future biomedical applications of MoS2 with its nanotoxicity mitigated.

Development of an aversive Pavlovian-to-instrumental transfer task in rat

PubMed Central

Campese, Vincent; McCue, Margaret; Lázaro-Muñoz, Gabriel; LeDoux, Joseph E.; Cain, Christopher K.

2013-01-01

Pavlovian-to-instrumental transfer (PIT) is an effect whereby a classically conditioned stimulus (CS) enhances ongoing instrumental responding. PIT has been extensively studied with appetitive conditioning but barely at all with aversive conditioning. Although it's been argued that conditioned suppression is a form of aversive PIT, this effect is fundamentally different from appetitive PIT because the CS suppresses, instead of facilitates, responding. Five experiments investigated the importance of a variety of factors on aversive PIT in a rodent Sidman avoidance paradigm in which ongoing shuttling behavior (unsignaled active avoidance or USAA) was facilitated by an aversive CS. Experiment 1 demonstrated a basic PIT effect. Experiment 2 found that a moderate amount of USAA extinction produces the strongest PIT with shuttling rates best at around 2 responses per minute prior to the CS. Experiment 3 tested a protocol in which the USAA behavior was required to reach the 2-response per minute mark in order to trigger the CS presentation and found that this produced robust and reliable PIT. Experiment 4 found that the Pavlovian conditioning US intensity was not a major determinant of PIT strength. Experiment 5 demonstrated that if the CS and US were not explicitly paired during Pavlovian conditioning, PIT did not occur, showing that CS-US learning is required. Together, these studies demonstrate a robust, reliable and stable aversive PIT effect that is amenable to analysis of neural circuitry. PMID:24324417

Lipopolysaccharide hyporesponsiveness: protective or damaging response to the brain?

PubMed

Pardon, Marie Christine

2015-01-01

Lipopolysaccharide (LPS) endotoxins are widely used as experimental models of systemic bacterial infection and trigger robust inflammation by potently activating toll-like receptors 4 (TLR4) expressed on innate immune cells. Their ability to trigger robust neuroinflammation despite poor brain penetration can prove useful for the understanding of how inflammation induced by viral infections contributes to the pathogenesis of neurodegenerative diseases. A single LPS challenge often result in a blunted inflammatory response to subsequent stimulation by LPS and other TLR ligands, but the extent to which endotoxin tolerance occur in the brain requires further clarification. LPS is also thought to render the brain transiently resistant to subsequent brain injuries by attenuating the concomitant pro-inflammatory response. While LPS hyporesponsiveness and preconditioning are classically seen as protective mechanisms limiting the toxic effects of sustained inflammation, recent research casts doubt as to whether they have beneficial or detrimental roles on the brain and in neurodegenerative disease. These observations suggest that spatio-temporal aspects of the immune responses to LPS and the disease status are determinant factors. Endotoxin tolerance may lead to a late pro-inflammatory response with potential harmful consequences. And while reduced TLR4 signaling reduces the risk of neurodegenerative diseases, up-regulation of anti-inflammatory cytokines associated with LPS hyporesponsiveness can have deleterious consequences to the brain by inhibiting the protective phenotype of microglia, aggravating the progression of some neurodegenerative conditions such as Alzheimer's disease. Beneficial effects of LPS preconditioning, however appear to require a stimulation of anti-inflammatory mediators rather than an attenuation of the pro-inflammatory response.

An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death.

PubMed

Garcia-Belinchón, Mercè; Sánchez-Osuna, María; Martínez-Escardó, Laura; Granados-Colomina, Carla; Pascual-Guiral, Sònia; Iglesias-Guimarais, Victoria; Casanelles, Elisenda; Ribas, Judit; Yuste, Victor J

2015-08-21

Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as "apoptosis-necrosis continuum." To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death*

PubMed Central

Garcia-Belinchón, Mercè; Sánchez-Osuna, María; Martínez-Escardó, Laura; Granados-Colomina, Carla; Pascual-Guiral, Sònia; Iglesias-Guimarais, Victoria; Casanelles, Elisenda; Ribas, Judit; Yuste, Victor J.

2015-01-01

Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as “apoptosis-necrosis continuum.” To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death. PMID:26124276

Sparse graph regularization for robust crop mapping using hyperspectral remotely sensed imagery with very few in situ data

NASA Astrophysics Data System (ADS)

Xue, Zhaohui; Du, Peijun; Li, Jun; Su, Hongjun

2017-02-01

The generally limited availability of training data relative to the usually high data dimension pose a great challenge to accurate classification of hyperspectral imagery, especially for identifying crops characterized with highly correlated spectra. However, traditional parametric classification models are problematic due to the need of non-singular class-specific covariance matrices. In this research, a novel sparse graph regularization (SGR) method is presented, aiming at robust crop mapping using hyperspectral imagery with very few in situ data. The core of SGR lies in propagating labels from known data to unknown, which is triggered by: (1) the fraction matrix generated for the large unknown data by using an effective sparse representation algorithm with respect to the few training data serving as the dictionary; (2) the prediction function estimated for the few training data by formulating a regularization model based on sparse graph. Then, the labels of large unknown data can be obtained by maximizing the posterior probability distribution based on the two ingredients. SGR is more discriminative, data-adaptive, robust to noise, and efficient, which is unique with regard to previously proposed approaches and has high potentials in discriminating crops, especially when facing insufficient training data and high-dimensional spectral space. The study area is located at Zhangye basin in the middle reaches of Heihe watershed, Gansu, China, where eight crop types were mapped with Compact Airborne Spectrographic Imager (CASI) and Shortwave Infrared Airborne Spectrogrpahic Imager (SASI) hyperspectral data. Experimental results demonstrate that the proposed method significantly outperforms other traditional and state-of-the-art methods.

Improving Multi-Objective Management of Water Quality Tipping Points: Revisiting the Classical Shallow Lake Problem

NASA Astrophysics Data System (ADS)

Quinn, J. D.; Reed, P. M.; Keller, K.

2015-12-01

Recent multi-objective extensions of the classical shallow lake problem are useful for exploring the conceptual and computational challenges that emerge when managing irreversible water quality tipping points. Building on this work, we explore a four objective version of the lake problem where a hypothetical town derives economic benefits from polluting a nearby lake, but at the risk of irreversibly tipping the lake into a permanently polluted state. The trophic state of the lake exhibits non-linear threshold dynamics; below some critical phosphorus (P) threshold it is healthy and oligotrophic, but above this threshold it is irreversibly eutrophic. The town must decide how much P to discharge each year, a decision complicated by uncertainty in the natural P inflow to the lake. The shallow lake problem provides a conceptually rich set of dynamics, low computational demands, and a high level of mathematical difficulty. These properties maximize its value for benchmarking the relative merits and limitations of emerging decision support frameworks, such as Direct Policy Search (DPS). Here, we explore the use of DPS as a formal means of developing robust environmental pollution control rules that effectively account for deeply uncertain system states and conflicting objectives. The DPS reformulation of the shallow lake problem shows promise in formalizing pollution control triggers and signposts, while dramatically reducing the computational complexity of the multi-objective pollution control problem. More broadly, the insights from the DPS variant of the shallow lake problem formulated in this study bridge emerging work related to socio-ecological systems management, tipping points, robust decision making, and robust control.

A comprehensive pathophysiology of dandruff and seborrheic dermatitis - towards a more precise definition of scalp health.

PubMed

Schwartz, James R; Messenger, Andrew G; Tosti, Antonella; Todd, Gail; Hordinsky, Maria; Hay, Roderick J; Wang, Xuemin; Zachariae, Claus; Kerr, Kathy M; Henry, James P; Rust, Rene C; Robinson, Michael K

2013-03-27

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Discrepancy and Disliking Do Not Induce Negative Opinion Shifts

PubMed Central

Flache, Andreas; Mäs, Michael

2016-01-01

Both classical social psychological theories and recent formal models of opinion differentiation and bi-polarization assign a prominent role to negative social influence. Negative influence is defined as shifts away from the opinion of others and hypothesized to be induced by discrepancy with or disliking of the source of influence. There is strong empirical support for the presence of positive social influence (a shift towards the opinion of others), but evidence that large opinion differences or disliking could trigger negative shifts is mixed. We examine positive and negative influence with controlled exposure to opinions of other individuals in one experiment and with opinion exchange in another study. Results confirm that similarities induce attraction, but results do not support that discrepancy or disliking entails negative influence. Instead, our findings suggest a robust positive linear relationship between opinion distance and opinion shifts. PMID:27333160

Evaluation of the clinical efficacy of the PeTrack motion tracking system for respiratory gating in cardiac PET imaging

NASA Astrophysics Data System (ADS)

Manwell, Spencer; Chamberland, Marc J. P.; Klein, Ran; Xu, Tong; deKemp, Robert

2017-03-01

Respiratory gating is a common technique used to compensate for patient breathing motion and decrease the prevalence of image artifacts that can impact diagnoses. In this study a new data-driven respiratory gating method (PeTrack) was compared with a conventional optical tracking system. The performance of respiratory gating of the two systems was evaluated by comparing the number of respiratory triggers, patient breathing intervals and gross heart motion as measured in the respiratory-gated image reconstructions of rubidium-82 cardiac PET scans in test and control groups consisting of 15 and 8 scans, respectively. We found evidence suggesting that PeTrack is a robust patient motion tracking system that can be used to retrospectively assess patient motion in the event of failure of the conventional optical tracking system.

Bursting of sensitive polymersomes induced by curling

PubMed Central

Mabrouk, Elyes; Cuvelier, Damien; Brochard-Wyart, Françoise; Nassoy, Pierre; Li, Min-Hui

2009-01-01

Polymersomes, which are stable and robust vesicles made of block copolymer amphiphiles, are good candidates for drug carriers or micro/nanoreactors. Polymer chemistry enables almost unlimited molecular design of responsive polymersomes whose degradation upon environmental changes has been used for the slow release of active species. Here, we propose a strategy to remotely trigger instantaneous polymersome bursting. We have designed asymmetric polymer vesicles, in which only one leaflet is composed of responsive polymers. In particular, this approach has been successfully achieved by using a UV-sensitive liquid-crystalline copolymer. We study experimentally and theoretically this bursting mechanism and show that it results from a spontaneous curvature of the membrane induced by the remote stimulus. The versatility of this mechanism should broaden the range of applications of polymersomes in fields such as drug delivery, cosmetics and material chemistry. PMID:19383800

Influence of Climate Oscillations on Extreme Precipitation in Texas

NASA Astrophysics Data System (ADS)

Bhatia, N.; Singh, V. P.; Srivastav, R. K.

2016-12-01

Much research in the field of hydroclimatology is focusing on the impact of climate variability on hydrologic extremes. Recent studies show that the unique geographical location and the enormous areal extent, coupled with extensive variations in climate oscillations, have intensified the regional hydrologic cycle of Texas. The state-wide extreme precipitation events can actually be attributed to sea-surface pressure and temperature anomalies, such as Bermuda High and Jet Streams, which are further triggered by such climate oscillations. This study aims to quantify the impact of five major Atlantic and Pacific Ocean related climate oscillations: (i) Atlantic Multidecadal Oscillation (AMO), (ii) North Atlantic Oscillation (NAO), (iii) Pacific Decadal Oscillation (PDO), (iv) Pacific North American Pattern (PNA), and (v) Southern Oscillation Index (SOI), on extreme precipitation in Texas. Their respective effects will be determined for both climate divisions delineated by the National Climatic Data Centre (NCDC) and climate regions defined by the Köppen Climate Classification System. This study will adopt a weighted correlation approach to attain the robust correlation coefficients while addressing the regionally variable data outliers for extreme precipitation. Further, the variation of robust correlation coefficients across Texas is found to be related to the station elevation, historical average temperature, and total precipitation in the months of extremes. The research will shed light on the relationship between precipitation extremes and climate variability, thus aiding regional water boards in planning, designing, and managing the respective systems as per the future climate change.

Predictive performance of rainfall thresholds for shallow landslide triggering in Switzerland from daily gridded precipitation data

NASA Astrophysics Data System (ADS)

Leonarduzzi, E.; Molnar, P.; McArdell, B. W.

2017-12-01

In Switzerland floods are responsible for most of the damage caused by rainfall-triggered natural hazards (89%), followed by landslides (6%, almost 600 M USD) as reported in Hilker et al. (2009) for the period 1972-2007. A high-resolution gridded daily precipitation dataset is combined with a landslide inventory containing over 2000 events in the period 1972-2012 to analyze rainfall thresholds that lead to landsliding in Switzerland. First triggering rainfall and landslides are co-located obtaining the distributions of triggering and non-triggering rainfall event properties at the scale of the precipitation data (2*2 km2) and considering 1 day as the interarrival time to separate events. Then rainfall thresholds are obtained by maximizing true positives (accurate predictions) while minimizing false negatives (false alarms), using the True Skill Statistic. The best predictive performance is obtained by the intensity-duration ID threshold curve, followed by peak daily intensity (Imax) and mean event intensity (Imean). Event duration by itself has very low predictive power. In addition to country-wide thresholds, local ones are also defined by regionalization based on surface erodibility and local long-term climate (mean daily precipitation). Different Imax thresholds are determined for each of the regions separately. It is found that wetter local climate and lower erodibility lead to significantly higher rainfall thresholds required to trigger landslides. However, the improvement in model performance due to regionalization is marginal and much lower than what can be achieved by having a high quality landslide database. In order to validate the performance of the Imax rainfall threshold model, reference cases will be presented in which the landslide locations and timing are randomized and the landslide sample size is reduced. Jack-knife and cross-validation experiments demonstrate that the model is robust. The results highlight the potential of using rainfall I-D threshold curves and Imax threshold values for predicting the occurrence of landslides on a country or regional scale even with daily precipitation data, with possible applications in landslide warning systems.

Cascading failures in interdependent systems under a flow redistribution model

NASA Astrophysics Data System (ADS)

Zhang, Yingrui; Arenas, Alex; Yaǧan, Osman

2018-02-01

Robustness and cascading failures in interdependent systems has been an active research field in the past decade. However, most existing works use percolation-based models where only the largest component of each network remains functional throughout the cascade. Although suitable for communication networks, this assumption fails to capture the dependencies in systems carrying a flow (e.g., power systems, road transportation networks), where cascading failures are often triggered by redistribution of flows leading to overloading of lines. Here, we consider a model consisting of systems A and B with initial line loads and capacities given by {LA,i,CA ,i} i =1 n and {LB,i,CB ,i} i =1 n, respectively. When a line fails in system A , a fraction of its load is redistributed to alive lines in B , while remaining (1 -a ) fraction is redistributed equally among all functional lines in A ; a line failure in B is treated similarly with b giving the fraction to be redistributed to A . We give a thorough analysis of cascading failures of this model initiated by a random attack targeting p1 fraction of lines in A and p2 fraction in B . We show that (i) the model captures the real-world phenomenon of unexpected large scale cascades and exhibits interesting transition behavior: the final collapse is always first order, but it can be preceded by a sequence of first- and second-order transitions; (ii) network robustness tightly depends on the coupling coefficients a and b , and robustness is maximized at non-trivial a ,b values in general; (iii) unlike most existing models, interdependence has a multifaceted impact on system robustness in that interdependency can lead to an improved robustness for each individual network.

Cascading failures in interdependent systems under a flow redistribution model.

PubMed

Zhang, Yingrui; Arenas, Alex; Yağan, Osman

2018-02-01

Robustness and cascading failures in interdependent systems has been an active research field in the past decade. However, most existing works use percolation-based models where only the largest component of each network remains functional throughout the cascade. Although suitable for communication networks, this assumption fails to capture the dependencies in systems carrying a flow (e.g., power systems, road transportation networks), where cascading failures are often triggered by redistribution of flows leading to overloading of lines. Here, we consider a model consisting of systems A and B with initial line loads and capacities given by {L_{A,i},C_{A,i}}_{i=1}^{n} and {L_{B,i},C_{B,i}}_{i=1}^{n}, respectively. When a line fails in system A, a fraction of its load is redistributed to alive lines in B, while remaining (1-a) fraction is redistributed equally among all functional lines in A; a line failure in B is treated similarly with b giving the fraction to be redistributed to A. We give a thorough analysis of cascading failures of this model initiated by a random attack targeting p_{1} fraction of lines in A and p_{2} fraction in B. We show that (i) the model captures the real-world phenomenon of unexpected large scale cascades and exhibits interesting transition behavior: the final collapse is always first order, but it can be preceded by a sequence of first- and second-order transitions; (ii) network robustness tightly depends on the coupling coefficients a and b, and robustness is maximized at non-trivial a,b values in general; (iii) unlike most existing models, interdependence has a multifaceted impact on system robustness in that interdependency can lead to an improved robustness for each individual network.

High-efficiency robust perovskite solar cells on ultrathin flexible substrates

PubMed Central

Li, Yaowen; Meng, Lei; Yang, Yang (Michael); Xu, Guiying; Hong, Ziruo; Chen, Qi; You, Jingbi; Li, Gang; Yang, Yang; Li, Yongfang

2016-01-01

Wide applications of personal consumer electronics have triggered tremendous need for portable power sources featuring light-weight and mechanical flexibility. Perovskite solar cells offer a compelling combination of low-cost and high device performance. Here we demonstrate high-performance planar heterojunction perovskite solar cells constructed on highly flexible and ultrathin silver-mesh/conducting polymer substrates. The device performance is comparable to that of their counterparts on rigid glass/indium tin oxide substrates, reaching a power conversion efficiency of 14.0%, while the specific power (the ratio of power to device weight) reaches 1.96 kW kg−1, given the fact that the device is constructed on a 57-μm-thick polyethylene terephthalate based substrate. The flexible device also demonstrates excellent robustness against mechanical deformation, retaining >95% of its original efficiency after 5,000 times fully bending. Our results confirmed that perovskite thin films are fully compatible with our flexible substrates, and are thus promising for future applications in flexible and bendable solar cells. PMID:26750664

Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes

NASA Astrophysics Data System (ADS)

Wibroe, Peter Popp; Anselmo, Aaron C.; Nilsson, Per H.; Sarode, Apoorva; Gupta, Vivek; Urbanics, Rudolf; Szebeni, Janos; Hunter, Alan Christy; Mitragotri, Samir; Mollnes, Tom Eirik; Moghimi, Seyed Moein

2017-07-01

Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.

Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth

PubMed Central

Awal, Mehraj R.; Shay, James; McLoed, Melissa M.; Mazur, Eric; Gabel, Christopher V.

2016-01-01

During development, a neuron transitions from a state of rapid growth to a stable morphology, and neurons within the adult mammalian CNS lose their ability to effectively regenerate in response to injury. Here, we identify a novel form of neuronal regeneration, which is remarkably independent of DLK-1/DLK, KGB-1/JNK, and other MAPK signaling factors known to mediate regeneration in Caenorhabditis elegans, Drosophila, and mammals. This DLK-independent regeneration in C. elegans has direct genetic and molecular links to a well-studied form of endogenous activity-dependent ectopic axon outgrowth in the same neuron type. Both neuron outgrowth types are triggered by physical lesion of the sensory dendrite or mutations disrupting sensory activity, calcium signaling, or genes that restrict outgrowth during neuronal maturation, such as SAX-1/NDR kinase or UNC-43/CaMKII. These connections suggest that ectopic outgrowth represents a powerful platform for gene discovery in neuronal regeneration. Moreover, we note numerous similarities between C. elegans DLK-independent regeneration and lesion conditioning, a phenomenon producing robust regeneration in the mammalian CNS. Both regeneration types are triggered by lesion of a sensory neurite via reduction of neuronal activity and enhanced by disrupting L-type calcium channels or elevating cAMP. Taken as a whole, our study unites disparate forms of neuronal outgrowth to uncover fresh molecular insights into activity-dependent control of the adult nervous system’s intrinsic regenerative capacity. PMID:27078101

Regulatory Forum opinion piece: New testing paradigms for reproductive and developmental toxicity--the NTP modified one generation study and OECD 443.

PubMed

Foster, Paul M D

2014-12-01

The National Toxicology Program (NTP) has developed a new flexible study design, termed the modified one generation (MOG) reproduction study. The MOG study will encompass measurements of developmental and reproductive toxicity parameters as well as enable the setting of appropriate dose levels for a cancer bioassay through evaluation of target organ toxicity that is based on test article exposure that starts during gestation. This study design is compared and contrasted with the new Organization for Economic Co-operation and Development (OECD) 443 test guideline, the extended one generation reproduction study. The MOG study has a number of advantages, with a focus on F 1 animals, the generation of adequately powered, robust data sets that include both pre and postnatal developmental toxicity information, and the measurement of effects on reproductive structure and function in the same animals. This new study design does not employ the use of internal triggers in the design structure for the use of animals already on test and is also consistent with the principles of the 3R's. © 2014 by The Author(s).

Insights into the Streaming Instability in Protoplanetary Disks

NASA Astrophysics Data System (ADS)

Youdin, Andrew N.; Lin, Min-Kai; Li, Rixin

2017-10-01

The streaming instability is a leading mechanism to concentrate particles in protoplanetary disks, thereby triggering planetesimal formation. I will present recent analytical and numerical work on the origin of the streaming instability and its robustness. Our recent analytic work examines the origin of, and relationship between, a variety of drag-induced instabilities, including the streaming instability as well as secular gravitational instabilities, a drag instability driven by self-gravity. We show that drag instabilities are powered by a specific phase relationship between gas pressure and particle concentrations, which power the instability via pressure work. This mechanism is analogous to pulsating instabilities in stars. This mechanism differs qualitatively from other leading particle concentration mechanisms in pressure bumps and vortices. Our recent numerical work investigates the numerical robustness of non-linear particle clumping by the streaming instability, especially with regard to the location and boundary condition of vertical boundaries. We find that particle clumping is robust to these choices in boxes that are not too short. However, hydrodynamic activity away from the particle-dominated midplane is significantly affected by vertical boundary conditions. This activity affects the observationally significant lofting of small dust grains. We thus emphasize the need for larger scale simulations which connect disk surface layers, including outflowing winds, to the planet-forming midplane.

High fluid pressure and triggered earthquakes in the enhanced geothermal system in Basel, Switzerland

NASA Astrophysics Data System (ADS)

Terakawa, T.; Miller, S. A.; Deichmann, N.

2011-12-01

We estimate the pore fluid pressure field of the stimulated region during the fluid injection experiment in Basel, Switzerland by analyzing 118 well-constrained focal mechanisms. This technique, termed focal mechanism tomography (FMT), uses the orientations of the slip planes within the prevailing regional stress field as indicator of the fluid pressure along the plane at the time of slip. Elevated pore fluid pressures were concentrated within 500 m of the open hole section, and we find average earthquake triggering excess pressures of about 10MPa, with a peak value of 19.3 MPa, consistent with the known wellhead pressure applied at the borehole. Our results demonstrate that FMT is a robust approach, being validated at the macroscopic scale of the Basel stimulation experiment. Over-pressurized fluids induced many small events (M < 3) along faults unfavourably-oriented relative to the tectonic stress pattern, while larger events tended to occur along optimally-oriented faults. This suggests that small-scale hydraulic networks, developed from the high pressure stimulation, interact to load (hydraulically isolated) high strength bridges that produce the larger events. The triggering pore fluid pressures are substantially higher than that predicted from a linear pressure diffusion process from the source boundary, showing that the system is highly permeable along flow paths, allowing fast pressure diffusion to the boundaries of the stimulated region.

Physical instrumental vetoes for gravitational-wave burst triggers

NASA Astrophysics Data System (ADS)

Ajith, P.; Hewitson, M.; Smith, J. R.; Grote, H.; Hild, S.; Strain, K. A.

2007-08-01

We present a robust strategy to veto certain classes of instrumental glitches that appear at the output of interferometric gravitational-wave detectors. This veto method is “physical” in the sense that, in order to veto a burst trigger, we make use of our knowledge of the coupling of different detector subsystems to the main detector output. The main idea behind this method is that the noise in an instrumental channel X can be transferred to the detector output (channel H) using the transfer function from X to H, provided the noise coupling is linear and the transfer function is unique. If a nonstationarity in channel H is causally related to one in channel X, the two have to be consistent with the transfer function. We formulate two methods for testing the consistency between the burst triggers in channel X and channel H. One method makes use of the null stream constructed from channel H and the transferred channel X, and the second involves cross correlating the two. We demonstrate the efficiency of the veto by “injecting” instrumental glitches in the hardware of the GEO 600 detector. The veto safety is demonstrated by performing gravitational-wave like hardware injections. We also show an example application of this method using 5 days of data from the fifth science run of GEO 600. The method is found to have very high veto efficiency with a very low accidental veto rate.

Geomagnetic storms can trigger stroke: evidence from 6 large population-based studies in Europe and Australasia.

PubMed

Feigin, Valery L; Parmar, Priya G; Barker-Collo, Suzanne; Bennett, Derrick A; Anderson, Craig S; Thrift, Amanda G; Stegmayr, Birgitta; Rothwell, Peter M; Giroud, Maurice; Bejot, Yannick; Carvil, Phillip; Krishnamurthi, Rita; Kasabov, Nikola

2014-06-01

Although the research linking cardiovascular disorders to geomagnetic activity is accumulating, robust evidence for the impact of geomagnetic activity on stroke occurrence is limited and controversial. We used a time-stratified case-crossover study design to analyze individual participant and daily geomagnetic activity (as measured by Ap Index) data from several large population-based stroke incidence studies (with information on 11 453 patients with stroke collected during 16 031 764 person-years of observation) in New Zealand, Australia, United Kingdom, France, and Sweden conducted between 1981 and 2004. Hazard ratios and corresponding 95% confidence intervals (CIs) were calculated. Overall, geomagnetic storms (Ap Index 60+) were associated with 19% increase in the risk of stroke occurrence (95% CI, 11%-27%). The triggering effect of geomagnetic storms was most evident across the combined group of all strokes in those aged <65 years, increasing stroke risk by >50%: moderate geomagnetic storms (60-99 Ap Index) were associated with a 27% (95% CI, 8%-48%) increased risk of stroke occurrence, strong geomagnetic storms (100-149 Ap Index) with a 52% (95% CI, 19%-92%) increased risk, and severe/extreme geomagnetic storms (Ap Index 150+) with a 52% (95% CI, 19%-94%) increased risk (test for trend, P<2×10(-16)). Geomagnetic storms are associated with increased risk of stroke and should be considered along with other established risk factors. Our findings provide a framework to advance stroke prevention through future investigation of the contribution of geomagnetic factors to the risk of stroke occurrence and pathogenesis. © 2014 American Heart Association, Inc.

Meta-Cognitions in Tourette Syndrome, Tic Disorders, and Body-Focused Repetitive Disorder

PubMed Central

O’Connor, Kieron; St-Pierre-Delorme, Marie-Ève; Leclerc, Julie; Lavoie, Marc; Blais, Mélodie T

2014-01-01

Objective To explore if self-reported presence of thinking about tics or body-focused repetitive behaviours (BFRBs; gests) are direct triggers of tic or gest onset in 3 groups: Tourette syndrome (TS; n =18), persistent chronic tic disorders (TDs; n = 42), and a comparison group with BFRB (n = 36). Method: The 3 groups completed a thinking about tics inventory, listing 22 items derived from clinician consensus that asked whether thoughts always, sometimes, or never exclusively triggered tic onset. Other questionnaires measured mood, perfectionism, impulsivity, premonitory urge, and self-rated tension. Sixty-three participants completed the inventory twice, and the inventory was completed pre- and post-behavioural intervention by a further 54. Results: The ranking of the thoughts reported as likely to trigger tics or gests was positively correlated across TD and BFRB groups. Exploratory principal components analysis of a reduced 12-item set (the thinking about tics inventory) in TS and TD groups revealed that such thoughts could be grouped into 3 separate subscales: thoughts about the interference of tics or gests, thoughts anticipating tics or gests, and thoughts about whether the person has permission to perform the tic or the gest. The 3 sets of subscales showed good and acceptable internal consistency and overall score showed good test–retest reliability, suggesting thoughts about tics or gests are robust and measurable. The subscales correlated with impulsivity, tic or behaviour severity, and ratings of frequency decreased post-behavioural treatment. Conclusions: Thinking about tics or gests is reported as triggering tics or gests in both TD and BFRB, and meta-cognition seems independent of premonitory sensations and relates to distinct clinical characteristics in each clinical group. PMID:25161066

Meta-cognitions in tourette syndrome, tic disorders, and body-focused repetitive disorder.

PubMed

O'Connor, Kieron; St-Pierre-Delorme, Marie-Ève; Leclerc, Julie; Lavoie, Marc; Blais, Mélodie T

2014-08-01

To explore if self-reported presence of thinking about tics or body-focused repetitive behaviours (BFRBs; gests) are direct triggers of tic or gest onset in 3 groups: Tourette syndrome (TS; n =18), persistent chronic tic disorders (TDs; n = 42), and a comparison group with BFRB (n = 36). The 3 groups completed a thinking about tics inventory, listing 22 items derived from clinician consensus that asked whether thoughts always, sometimes, or never exclusively triggered tic onset. Other questionnaires measured mood, perfectionism, impulsivity, premonitory urge, and self-rated tension. Sixty-three participants completed the inventory twice, and the inventory was completed pre- and post-behavioural intervention by a further 54. The ranking of the thoughts reported as likely to trigger tics or gests was positively correlated across TD and BFRB groups. Exploratory principal components analysis of a reduced 12-item set (the thinking about tics inventory) in TS and TD groups revealed that such thoughts could be grouped into 3 separate subscales: thoughts about the interference of tics or gests, thoughts anticipating tics or gests, and thoughts about whether the person has permission to perform the tic or the gest. The 3 sets of subscales showed good and acceptable internal consistency and overall score showed good test-retest reliability, suggesting thoughts about tics or gests are robust and measurable. The subscales correlated with impulsivity, tic or behaviour severity, and ratings of frequency decreased post-behavioural treatment. Thinking about tics or gests is reported as triggering tics or gests in both TD and BFRB, and meta-cognition seems independent of premonitory sensations and relates to distinct clinical characteristics in each clinical group.

High frequency pacing of edge localized modes by injection of lithium granules in DIII-D H-mode discharges

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

Bortolon, A.; Maingi, R.; Mansfield, D. K.

A newly installed Lithium Granule Injector (LGI) was used to pace edge localized modes (ELM) in DIII-D. ELM pacing efficiency was studied injecting lithium granules of nominal diameter 0.3–0.9mm, speed of 50–120 m s -1 and average injection rates up to 100 Hz for 0.9mm granules and up to 700 Hz for 0.3mm granules. The efficiency of ELM triggering was found to depend strongly on size of the injected granules, with triggering efficiency close to 100% obtained with 0.9mm diameter granules, lower with smaller sizes, and weakly depending on granule velocity. Robust ELM pacing was demonstrated in ITER-like plasmas formore » the entire shot length, at ELM frequencies 3–5 times larger than the ‘natural’ ELM frequency observed in reference discharges. Within the range of ELM frequencies obtained, the peak ELM heat flux at the outer strike point was reduced with increasing pacing frequency. The peak heat flux reduction at the inner strike point appears to saturate at high pacing frequency. Lithium was found in the plasma core, with a concurrent reduction of metallic impurities and carbon. Altogether, high frequency ELM pacing using the lithium granule injection appears to be compatible with both H-mode energy confinement and attractive H-mode pedestal characteristics, but further assessment is need« less

USGS approach to real-time estimation of earthquake-triggered ground failure - Results of 2015 workshop

USGS Publications Warehouse

Allstadt, Kate E.; Thompson, Eric M.; Wald, David J.; Hamburger, Michael W.; Godt, Jonathan W.; Knudsen, Keith L.; Jibson, Randall W.; Jessee, M. Anna; Zhu, Jing; Hearne, Michael; Baise, Laurie G.; Tanyas, Hakan; Marano, Kristin D.

2016-03-30

The U.S. Geological Survey (USGS) Earthquake Hazards and Landslide Hazards Programs are developing plans to add quantitative hazard assessments of earthquake-triggered landsliding and liquefaction to existing real-time earthquake products (ShakeMap, ShakeCast, PAGER) using open and readily available methodologies and products. To date, prototype global statistical models have been developed and are being refined, improved, and tested. These models are a good foundation, but much work remains to achieve robust and defensible models that meet the needs of end users. In order to establish an implementation plan and identify research priorities, the USGS convened a workshop in Golden, Colorado, in October 2015. This document summarizes current (as of early 2016) capabilities, research and operational priorities, and plans for further studies that were established at this workshop. Specific priorities established during the meeting include (1) developing a suite of alternative models; (2) making use of higher resolution and higher quality data where possible; (3) incorporating newer global and regional datasets and inventories; (4) reducing barriers to accessing inventory datasets; (5) developing methods for using inconsistent or incomplete datasets in aggregate; (6) developing standardized model testing and evaluation methods; (7) improving ShakeMap shaking estimates, particularly as relevant to ground failure, such as including topographic amplification and accounting for spatial variability; and (8) developing vulnerability functions for loss estimates.

High frequency pacing of edge localized modes by injection of lithium granules in DIII-D H-mode discharges

DOE PAGES

Bortolon, A.; Maingi, R.; Mansfield, D. K.; ...

2016-04-08

A newly installed Lithium Granule Injector (LGI) was used to pace edge localized modes (ELM) in DIII-D. ELM pacing efficiency was studied injecting lithium granules of nominal diameter 0.3–0.9mm, speed of 50–120 m s -1 and average injection rates up to 100 Hz for 0.9mm granules and up to 700 Hz for 0.3mm granules. The efficiency of ELM triggering was found to depend strongly on size of the injected granules, with triggering efficiency close to 100% obtained with 0.9mm diameter granules, lower with smaller sizes, and weakly depending on granule velocity. Robust ELM pacing was demonstrated in ITER-like plasmas formore » the entire shot length, at ELM frequencies 3–5 times larger than the ‘natural’ ELM frequency observed in reference discharges. Within the range of ELM frequencies obtained, the peak ELM heat flux at the outer strike point was reduced with increasing pacing frequency. The peak heat flux reduction at the inner strike point appears to saturate at high pacing frequency. Lithium was found in the plasma core, with a concurrent reduction of metallic impurities and carbon. Altogether, high frequency ELM pacing using the lithium granule injection appears to be compatible with both H-mode energy confinement and attractive H-mode pedestal characteristics, but further assessment is need« less

Neuronal somatic ATP release triggers neuron–satellite glial cell communication in dorsal root ganglia

PubMed Central

Zhang, X.; Chen, Y.; Wang, C.; Huang, L.-Y. M.

2007-01-01

It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca2+ entry is required for the release. FM1–43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca2+ channels completely eliminates the neuron–glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-α (TNFα) from satellite cells. TNFα in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell–cell signaling. PMID:17525149

Crystalline metamaterials for topological properties at subwavelength scales

PubMed Central

Yves, Simon; Fleury, Romain; Berthelot, Thomas; Fink, Mathias; Lemoult, Fabrice; Lerosey, Geoffroy

2017-01-01

The exciting discovery of topological condensed matter systems has lately triggered a search for their photonic analogues, motivated by the possibility of robust backscattering-immune light transport. However, topological photonic phases have so far only been observed in photonic crystals and waveguide arrays, which are inherently physically wavelength scaled, hindering their application in compact subwavelength systems. In this letter, we tackle this problem by patterning the deep subwavelength resonant elements of metamaterials onto specific lattices, and create crystalline metamaterials that can develop complex nonlocal properties due to multiple scattering, despite their very subwavelength spatial scale that usually implies to disregard their structure. These spatially dispersive systems can support subwavelength topological phases, as we demonstrate at microwaves by direct field mapping. Our approach gives a straightforward tabletop platform for the study of photonic topological phases, and allows to envision applications benefiting the compactness of metamaterials and the amazing potential of topological insulators. PMID:28719573

Evolution and Extinction Dynamics in Rugged Fitness Landscapes

NASA Astrophysics Data System (ADS)

Sibani, Paolo; Brandt, Michael; Alstrøm, Preben

After an introductory section summarizing the paleontological data and some of their theoretical descriptions, we describe the "reset" model and its (in part analytically soluble) mean field version, which have been briefly introduced in Letters.1,2 Macroevolution is considered as a problem of stochastic dynamics in a system with many competing agents. Evolutionary events (speciations and extinctions) are triggered by fitness records found by random exploration of the agents' fitness landscapes. As a consequence, the average fitness in the system increases logarithmically with time, while the rate of extinction steadily decreases. This non-stationary dynamics is studied by numerical simulations and, in a simpler mean field version, analytically. We also consider the effect of externally added "mass" extinctions. The predictions for various quantities of paleontological interest (life-time distribution, distribution of event sizes and behavior of the rate of extinction) are robust and in good agreement with available data.

Cloud Formation and Water Transport on Mars after Major Outflow Events

NASA Technical Reports Server (NTRS)

Santiago, D. L.; Colaprete, A.; Kreslavsky, M.; Kahre, M. A.; Asphaug, E.

2012-01-01

The triggering of a robust water cycle on Mars might have been caused by the gigantic flooding events evidenced by outflow channels. We use the Ames Mars General Circulation Model (MGCM) to test this hypothesis, studying how these presumably abrupt eruptions of water might have affected the climate of Mars in the past. We model where the water ultimately went as part of a transient atmospheric water cycle, to answer questions including: (1) Can sudden introductions of large amounts of water on the Martian surface lead to a new equilibrated water cycle? (2) What are the roles of water vapor and water ice clouds to sudden changes in the water cycle on Mars? (3) How are radiative feedbacks involved with this? (4) What is the ultimate fate of the outflow water? (5) Can we tie certain geological features to outflow water redistributed by the atmosphere?

The bacterial skin microbiome in psoriatic arthritis, an unexplored link in pathogenesis: challenges and opportunities offered by recent technological advances.

PubMed

Castelino, Madhura; Eyre, Stephen; Upton, Mathew; Ho, Pauline; Barton, Anne

2014-05-01

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both the skin and gastrointestinal tract as sources of microbial triggers for PsA. In parallel with genetic studies, characterization of the host microbiota may benefit our understanding of the microbial contribution to disease pathogenesis-knowledge that may eventually inform the development of novel therapeutics.

Quality Control of Wind Data from 50-MHz Doppler Radar Wind Profiler

NASA Technical Reports Server (NTRS)

Vacek, Austin

2016-01-01

Upper-level wind profiles obtained from a 50-MHz Doppler Radar Wind Profiler (DRWP) instrument at Kennedy Space Center are incorporated in space launch vehicle design and day-of-launch operations to assess wind effects on the vehicle during ascent. Automated and manual quality control (QC) techniques are implemented to remove spurious data in the upper-level wind profiles caused from atmospheric and non-atmospheric artifacts over the 2010-2012 period of record (POR). By adding the new quality controlled profiles with older profiles from 1997-2009, a robust database will be constructed of upper-level wind characteristics. Statistical analysis will determine the maximum, minimum, and 95th percentile of the wind components from the DRWP profiles over recent POR and compare against the older database. Additionally, this study identifies specific QC flags triggered during the QC process to understand how much data is retained and removed from the profiles.

Quality Control of Wind Data from 50-MHz Doppler Radar Wind Profiler

NASA Technical Reports Server (NTRS)

Vacek, Austin

2015-01-01

Upper-level wind profiles obtained from a 50-MHz Doppler Radar Wind Profiler (DRWP) instrument at Kennedy Space Center are incorporated in space launch vehicle design and day-of-launch operations to assess wind effects on the vehicle during ascent. Automated and manual quality control (QC) techniques are implemented to remove spurious data in the upper-level wind profiles caused from atmospheric and non-atmospheric artifacts over the 2010-2012 period of record (POR). By adding the new quality controlled profiles with older profiles from 1997-2009, a robust database will be constructed of upper-level wind characteristics. Statistical analysis will determine the maximum, minimum, and 95th percentile of the wind components from the DRWP profiles over recent POR and compare against the older database. Additionally, this study identifies specific QC flags triggered during the QC process to understand how much data is retained and removed from the profiles.

Camera Concepts for the Advanced Gamma-Ray Imaging System (AGIS)

NASA Astrophysics Data System (ADS)

Nepomuk Otte, Adam

2009-05-01

The Advanced Gamma-Ray Imaging System (AGIS) is a concept for the next generation observatory in ground-based very high energy gamma-ray astronomy. Design goals are ten times better sensitivity, higher angular resolution, and a lower energy threshold than existing Cherenkov telescopes. Each telescope is equipped with a camera that detects and records the Cherenkov-light flashes from air showers. The camera is comprised of a pixelated focal plane of blue sensitive and fast (nanosecond) photon detectors that detect the photon signal and convert it into an electrical one. The incorporation of trigger electronics and signal digitization into the camera are under study. Given the size of AGIS, the camera must be reliable, robust, and cost effective. We are investigating several directions that include innovative technologies such as Geiger-mode avalanche-photodiodes as a possible detector and switched capacitor arrays for the digitization.

Crystalline metamaterials for topological properties at subwavelength scales

NASA Astrophysics Data System (ADS)

Yves, Simon; Fleury, Romain; Berthelot, Thomas; Fink, Mathias; Lemoult, Fabrice; Lerosey, Geoffroy

2017-07-01

The exciting discovery of topological condensed matter systems has lately triggered a search for their photonic analogues, motivated by the possibility of robust backscattering-immune light transport. However, topological photonic phases have so far only been observed in photonic crystals and waveguide arrays, which are inherently physically wavelength scaled, hindering their application in compact subwavelength systems. In this letter, we tackle this problem by patterning the deep subwavelength resonant elements of metamaterials onto specific lattices, and create crystalline metamaterials that can develop complex nonlocal properties due to multiple scattering, despite their very subwavelength spatial scale that usually implies to disregard their structure. These spatially dispersive systems can support subwavelength topological phases, as we demonstrate at microwaves by direct field mapping. Our approach gives a straightforward tabletop platform for the study of photonic topological phases, and allows to envision applications benefiting the compactness of metamaterials and the amazing potential of topological insulators.

Thermal force approach to molecular evolution.

PubMed

Braun, Dieter; Libchaber, Albert

2004-06-01

Recent experiments are discussed where temperature gradients across mesoscopic pores are shown to provide essential mechanisms for autonomous molecular evolution. On the one hand, laminar thermal convection can drive DNA replication as the molecules are continuously cycled between hot and cold regions of a chamber. On the other hand, thermophoresis can accumulate charged biopolymers in similar convection settings. The experiments show that temperature differences analogous to those across porous rocks present a robust nonequilibrium boundary condition to feed the replication and accumulation of evolving molecules. It is speculated that similar nonequilibrium conditions near porous submarine hydrothermal mounds could have triggered the origin of life. In such a scenario, the encapsulation of cells with membranes would be a later development. It is expected that detailed studies of mesoscopic boundary conditions under nonequilibrium conditions will reveal new connecting pieces in the fascinating puzzle of the origins of life.

Galaxy Interactions and AGN-triggering to z~1: an unprecedented new view from the Hyper Suprime-Cam Survey

NASA Astrophysics Data System (ADS)

Goulding, Andy D.; Greene, Jenny E.; Bezanson, Rachel; Greco, Johnny; Johnson, Sean; Medezinski, Elinor; Strauss, Michael A.; HSC Collaboration

2017-01-01

Collisions and interactions between galaxies are thought to be pivotal stages in their formation and evolution, causing the rapid production of new stars, and may also serve as a mechanism for fueling supermassive black holes (BH). Harnessing the exquisite spatial resolution (0.3—0.7 arcsec) afforded by the new 1400 deg2 Hyper Suprime-Cam (HSC) Survey, we present our new constraints on the importance of major and minor mergers in growing BHs throughout the last ~7 Gyrs. Utilizing the first ~170 deg2 of the HSC Survey, and mid-infrared observations in the WISE All-Sky survey, we have robustly selected active galactic nuclei (AGN), starburst, and mass-matched control galaxy samples, totaling ~120,000 spectroscopically confirmed systems at i<22 mag. We identify galaxy interactions using a novel machine-learning technique, and use these data to map the growth of BHs as a function of interaction-stage, redshift and AGN luminosity, ultimately providing the necessary large-number statistics required to investigate merger—AGN triggering in the context of galaxy evolution out to z~1.

Eosinophils subvert host resistance to an intracellular pathogen by instigating non-protective IL-4 in CCR2-/- mice.

PubMed

Verma, A H; Bueter, C L; Rothenberg, M E; Deepe, G S

2017-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases; however, their influence on intracellular pathogens is less clear. We previously reported that CCR2 -/- mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated interleukin (IL)-4 response. We sought to identify the cellular source promulgating IL-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2 -/- animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity.

Localized scleroderma.

PubMed

Kreuter, Alexander

2012-01-01

Localized scleroderma (also called morphea) is a term encompassing a spectrum of sclerotic autoimmune diseases that primarily affect the skin, but also might involve underlying structures such as the fat, fascia, muscle, and bones. Its exact pathogenesis is still unknown, but several trigger factors in genetically predisposed individuals might initially lead to an immunologically triggered release of pro-inflammatory cytokines, resulting in a profound dysregulation of the connective tissue metabolism and ultimately to induction of fibrosis. To date, there are no specific serological markers available for localized scleroderma. Within the last years, several validated clinical scores have been introduced as potential outcome measures for the disease. Given the rarity of localized scleroderma, only few evidence-based therapeutical treatment options exist. So far, the most robust data is available for ultraviolet A1 phototherapy in disease that is restricted to the skin, and methotrexate alone or in combination with systemic corticosteroids in more severe disease that additionally affects extracutaneous structures. This practical review summarizes relevant information on the epidemiology, pathogenesis, clinical subtypes and classifications, differential diagnoses, clinical scores and outcome measures, and current treatment strategies of localized scleroderma. © 2012 Wiley Periodicals, Inc.

The unfolded protein response in melanocytes: activation in response to chemical stressors of the endoplasmic reticulum and tyrosinase misfolding.

PubMed

Manga, Prashiela; Bis, Sabina; Knoll, Kristen; Perez, Beremis; Orlow, Seth J

2010-10-01

Accumulation of proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), comprising three signaling pathways initiated by Ire1, Perk and Atf6 respectively. Unfolded protein response activation was compared in chemically stressed murine wildtype melanocytes and mutant melanocytes that retain tyrosinase in the ER. Thapsigargin, an ER stressor, activated all pathways in wildtype melanocytes, triggering Caspase 12-mediated apoptosis at toxic doses. Albino melanocytes expressing mutant tyrosinase showed evidence of ER stress with increased Ire1 expression, but the downstream effector, Xbp1, was not activated even following thapsigargin treatment. Attenuation of Ire1 signaling was recapitulated in wildtype melanocytes treated with thapsigargin for 8 days, with diminished Xbp1 activation observed after 4 days. Atf6 was also activated in albino melanocytes, with no response to thapsigargin, while the Perk pathway was not activated and thapsigargin treatment elicited robust expression of the downstream effector CCAAT-enhancer-binding protein homologous protein. Thus, melanocytes adapt to ER stress by attenuating two UPR pathways.

Optimization of ultrasound parameters of myocardial cavitation microlesions for therapeutic application.

PubMed

Miller, Douglas L; Dou, Chunyan; Owens, Gabe E; Kripfgans, Oliver D

2014-06-01

Intermittent high intensity ultrasound scanning with contrast microbubbles can induce scattered cavitation microlesions in the myocardium, which may be of value for tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5 MHz focused ultrasound pulses, guided by an 8 MHz imaging transducer. The relative efficacy with 2 or 4 MPa pulses, 1:4 or 1:8 trigger intervals and 5 or 10 cycle pulses was explored in six groups. Electrocardiogram premature complexes (PCs) induced by the triggered pulse bursts were counted, and Evans blue stained cardiomyocyte scores (SCSs) were obtained. The increase from 2 to 4 MPa produced significant increases in PCs and SCSs and eliminated an anticipated decline in the rate of PC induction with time, which might hinder therapeutic efficacy. Increased intervals and pulse durations did not yield significant increases in the effects. The results suggest that cavitation microlesion production can be refined and potentially lead to a clinically robust therapeutic method. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

A quantitative metabolomics study of high sodium response in Clostridium acetobutylicum ATCC 824 acetone-butanol-ethanol (ABE) fermentation

PubMed Central

Zhao, Xinhe; Condruz, Stefan; Chen, Jingkui; Jolicoeur, Mario

2016-01-01

Hemicellulose hydrolysates, sugar-rich feedstocks used in biobutanol refinery, are normally obtained by adding sodium hydroxide in the hydrolyze process. However, the resulting high sodium concentration in the hydrolysate inhibits ABE (acetone-butanol-ethanol) fermentation, and thus limits the use of these low-cost feedstocks. We have thus studied the effect of high sodium on the metabolic behavior of Clostridium acetobutyricum ATCC 824, with xylose as the carbon source. At a threshold sodium concentration of 200 mM, a decrease of the maximum cell dry weight (−19.50 ± 0.85%) and of ABE yield (−35.14 ± 3.50% acetone, −33.37 ± 0.74% butanol, −22.95 ± 1.81% ethanol) were observed compared to control culture. However, solvents specific productivities were not affected by supplementing sodium. The main effects of high sodium on cell metabolism were observed in acidogenesis, during which we observed the accumulation of ATP and NADH, and the inhibition of the pentose phosphate (PPP) and the glycolytic pathways with up to 80.73 ± 1.47% and 68.84 ± 3.42% decrease of the associated metabolic intermediates, respectively. However, the NADP+-to-NADPH ratio was constant for the whole culture duration, a phenomenon explaining the robustness of solvents specific productivities. Therefore, high sodium, which inhibited biomass growth through coordinated metabolic effects, interestingly triggered cell robustness on solvents specific productivity. PMID:27321153

An improved SWAT vegetation growth module and its evaluation for four tropical ecosystems

NASA Astrophysics Data System (ADS)

Alemayehu, Tadesse; van Griensven, Ann; Taddesse Woldegiorgis, Befekadu; Bauwens, Willy

2017-09-01

The Soil and Water Assessment Tool (SWAT) is a globally applied river basin ecohydrological model used in a wide spectrum of studies, ranging from land use change and climate change impacts studies to research for the development of the best water management practices. However, SWAT has limitations in simulating the seasonal growth cycles for trees and perennial vegetation in the tropics, where rainfall rather than temperature is the dominant plant growth controlling factor. Our goal is to improve the vegetation growth module of SWAT for simulating the vegetation variables - such as the leaf area index (LAI) - for tropical ecosystems. Therefore, we present a modified SWAT version for the tropics (SWAT-T) that uses a straightforward but robust soil moisture index (SMI) - a quotient of rainfall (P) and reference evapotranspiration (ETr) - to dynamically initiate a new growth cycle within a predefined period. Our results for the Mara Basin (Kenya/Tanzania) show that the SWAT-T-simulated LAI corresponds well with the Moderate Resolution Imaging Spectroradiometer (MODIS) LAI for evergreen forest, savanna grassland and shrubland. This indicates that the SMI is reliable for triggering a new annual growth cycle. The water balance components (evapotranspiration and streamflow) simulated by the SWAT-T exhibit a good agreement with remote-sensing-based evapotranspiration (ET-RS) and observed streamflow. The SWAT-T model, with the proposed vegetation growth module for tropical ecosystems, can be a robust tool for simulating the vegetation growth dynamics in hydrologic models in tropical regions.

Autophagy triggered by magnolol derivative negatively regulates angiogenesis

PubMed Central

Kumar, S; Guru, S K; Pathania, A S; Kumar, A; Bhushan, S; Malik, F

2013-01-01

Angiogenesis has a key role in the tumor progression and metastasis; targeting endothelial cell proliferation has emerged as a promising therapeutic strategy for the prevention of cancer. Previous studies have revealed a complex association between the process of angiogenesis and autophagy and its outcome on tumorigenesis. Autophagy, also known as type-II cell death, has been identified as an alternative way of cell killing in apoptotic-resistant cancer cells. However, its involvement in chemoresistance and tumor promotion is also well known. In this study, we used a derivate of natural product magnolol (Ery5), a potent autophagy inducer, to study the association between the autophagy and angiogenesis in both in vitro and in vivo model system. We found that the robust autophagy triggered by Ery5, inhibited angiogenesis and caused cell death independent of the apoptosis in human umbilical cord vein endothelial cells and PC-3 cells. Ery5 induced autophagy effectively inhibited cell proliferation, migration, invasion and tube formation. We further demonstrated that Ery5-mediated autophagy and subsequent inhibition of angiogenesis was reversed when autophagy was inhibited through 3-methyl adenine and knocking down of key autophagy proteins ATG7 and microtubule-associated protein light chain 3. While evaluating the negative regulation of autophagy on angiogenesis, it was interesting to find that angiogenic environment produced by the treatment of VEGF and CoCl2 remarkably downregulated the autophagy and autophagic cell death induced by Ery5. These studies, while disclosing the vital role of autophagy in the regulation of angiogenesis, also suggest that the potent modulators of autophagy can lead to the development of effective therapeutics in apoptosis-resistant cancer. PMID:24176847

Regional hydro-climatic impacts of contemporary Amazonian deforestation

NASA Astrophysics Data System (ADS)

Khanna, Jaya

More than 17% of the Amazon rainforest has been cleared in the past three decades triggering important climatological and societal impacts. This thesis is devoted to identifying and explaining the regional hydroclimatic impacts of this change employing multidecadal satellite observations and numerical simulations providing an integrated perspective on this topic. The climatological nature of this study motivated the implementation and application of a cloud detection technique to a new geostationary satellite dataset. The resulting sub daily, high spatial resolution, multidecadal time series facilitated the detection of trends and variability in deforestation triggered cloud cover changes. The analysis was complemented by satellite precipitation, reanalysis and ground based datasets and attribution with the variable resolution Ocean-Land-Atmosphere-Model. Contemporary Amazonian deforestation affects spatial scales of hundreds of kilometers. But, unlike the well-studied impacts of a few kilometers scale deforestation, the climatic response to contemporary, large scale deforestation is neither well observed nor well understood. Employing satellite datasets, this thesis shows a transition in the regional hydroclimate accompanying increasing scales of deforestation, with downwind deforested regions receiving 25% more and upwind deforested regions receiving 25% less precipitation from the deforested area mean. Simulations robustly reproduce these shifts when forced with increasing deforestation alone, suggesting a negligible role of large-scale decadal climate variability in causing the shifts. Furthermore, deforestation-induced surface roughness variations are found necessary to reproduce the observed spatial patterns in recent times illustrating the strong scale-sensitivity of the climatic response to Amazonian deforestation. This phenomenon, inconsequential during the wet season, is found to substantially affect the regional hydroclimate in the local dry and parts of transition seasons, hence occurring in atmospheric conditions otherwise less conducive to thermal convection. Evidence of this phenomenon is found at two large scale deforested areas considered in this thesis. Hence, the 'dynamical' mechanism, which affects the seasons most important for regional ecology, emerges as an impactful convective triggering mechanism. The phenomenon studied in this thesis provides context for thinking about the climate of a future, more patchily forested Amazonia, by articulating relationships between climate and spatial scales of deforestation.

Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

Ultrafast time-resolved electron diffraction revealing the nonthermal dynamics of near-UV photoexcitation-induced amorphization in Ge2Sb2Te5.

PubMed

Hada, Masaki; Oba, Wataru; Kuwahara, Masashi; Katayama, Ikufumi; Saiki, Toshiharu; Takeda, Jun; Nakamura, Kazutaka G

2015-08-28

Because of their robust switching capability, chalcogenide glass materials have been used for a wide range of applications, including optical storages devices. These phase transitions are achieved by laser irradiation via thermal processes. Recent studies have suggested the potential of nonthermal phase transitions in the chalcogenide glass material Ge2Sb2Te5 triggered by ultrashort optical pulses; however, a detailed understanding of the amorphization and damage mechanisms governed by nonthermal processes is still lacking. Here we performed ultrafast time-resolved electron diffraction and single-shot optical pump-probe measurements followed by femtosecond near-ultraviolet pulse irradiation to study the structural dynamics of polycrystalline Ge2Sb2Te5. The experimental results present a nonthermal crystal-to-amorphous phase transition of Ge2Sb2Te5 initiated by the displacements of Ge atoms. Above the fluence threshold, we found that the permanent amorphization caused by multi-displacement effects is accompanied by a partial hexagonal crystallization.

Ultrafast time-resolved electron diffraction revealing the nonthermal dynamics of near-UV photoexcitation-induced amorphization in Ge2Sb2Te5

PubMed Central

Hada, Masaki; Oba, Wataru; Kuwahara, Masashi; Katayama, Ikufumi; Saiki, Toshiharu; Takeda, Jun; Nakamura, Kazutaka G.

2015-01-01

Because of their robust switching capability, chalcogenide glass materials have been used for a wide range of applications, including optical storages devices. These phase transitions are achieved by laser irradiation via thermal processes. Recent studies have suggested the potential of nonthermal phase transitions in the chalcogenide glass material Ge2Sb2Te5 triggered by ultrashort optical pulses; however, a detailed understanding of the amorphization and damage mechanisms governed by nonthermal processes is still lacking. Here we performed ultrafast time-resolved electron diffraction and single-shot optical pump-probe measurements followed by femtosecond near-ultraviolet pulse irradiation to study the structural dynamics of polycrystalline Ge2Sb2Te5. The experimental results present a nonthermal crystal-to-amorphous phase transition of Ge2Sb2Te5 initiated by the displacements of Ge atoms. Above the fluence threshold, we found that the permanent amorphization caused by multi-displacement effects is accompanied by a partial hexagonal crystallization. PMID:26314613

An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine

PubMed Central

Schmauss, C.

2015-01-01

Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of fluoxetine, suggesting that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy. PMID:25639887

Using SSTAs (Significant Sequences of TIR Anomalies) to trigger Natural Time Analysis: a Long Term Study on Earthquakes (M>4) occurred over Greece in 2004-2013

NASA Astrophysics Data System (ADS)

Tramutoli, V.; Eleftheriou, A.; Filizzola, C.; Genzano, N.; Lacava, T.; Lisi, M.; Paciello, R.; Pergola, N.; Vallianatos, F.

2016-12-01

From an appropriate identification and real-time integration of independent observations we expect to significantly improve our present capability of dynamically assess Seismic Hazard. Sometime one specific observation (e.g. anomaly in one parameter) can be used as a trigger or as a reference point (in the space and/or time domain) for activating/improving analysis on other independent parameters (e.g. b-value computation and/or Natural Time Analysis on seismic data) whose systematic computation could result otherwise very computationally expensive or impossible. In this paper one of these parameter (the Earth's emitted radiation in the Thermal Infra-Red spectral region) will be used to drive the application of Natural Time Analysis of seismic data in order to verify possible improvements in the forecast of earthquakes (with M≥4) occurred in Greece in the 10 years period 2004-2013. The RST (Robust Satellite Technique) data analysis approach and RETIRA (Robust Estimator of TIR Anomalies) index were used to preliminarily define, and then to identify, Significant Sequences of TIR Anomalies (SSTAs) in 10 years (2004-2013) of daily TIR images acquired by the Spinning Enhanced Visible and Infrared Imager (SEVIRI) on board the Meteosat Second Generation (MSG) satellite. A previous paper already demonstrated that more than 93% of all identified SSTAs occurred in a pre-fixed space-time window around earthquakes time (30 days before up to 15 after) and location (within 150 km or Dorbrovolsky distance) with a false positive rate smaller than 7%. In this paper just the barycenter of (and not all the alerted area) SSTAs is used to define the center of the circular area from which collect seismic data required for NTA analysis. Changes in the quality of earthquake forecast achieved by using each individual parameter in different configurations as well as the improvement rising by their joint use will be presented with reference to the 10 years considered period and to several recent events occurred in Greece.

Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

NASA Astrophysics Data System (ADS)

Bernal-Martínez, Juan; Ortega Soto, Arturo

2004-09-01

Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

Pacific western boundary currents and their roles in climate.

PubMed

Hu, Dunxin; Wu, Lixin; Cai, Wenju; Gupta, Alex Sen; Ganachaud, Alexandre; Qiu, Bo; Gordon, Arnold L; Lin, Xiaopei; Chen, Zhaohui; Hu, Shijian; Wang, Guojian; Wang, Qingye; Sprintall, Janet; Qu, Tangdong; Kashino, Yuji; Wang, Fan; Kessler, William S

2015-06-18

Pacific Ocean western boundary currents and the interlinked equatorial Pacific circulation system were among the first currents of these types to be explored by pioneering oceanographers. The widely accepted but poorly quantified importance of these currents-in processes such as the El Niño/Southern Oscillation, the Pacific Decadal Oscillation and the Indonesian Throughflow-has triggered renewed interest. Ongoing efforts are seeking to understand the heat and mass balances of the equatorial Pacific, and possible changes associated with greenhouse-gas-induced climate change. Only a concerted international effort will close the observational, theoretical and technical gaps currently limiting a robust answer to these elusive questions.

Effect of groove width of modified current collector on internal short circuit of abused lithium-ion battery

NASA Astrophysics Data System (ADS)

Wang, Meng; Shi, Yang; Noelle, Daniel J.; Le, Anh V.; Qiao, Yu

2017-10-01

In a lithium-ion battery (LIB), mechanical abuse often leads to internal short circuits (ISC) that trigger thermal runaway. We investigated a thermal-runaway mitigation (TRM) technique using a modified current collector. By generating surface grooves on the current collector, the area of electrodes directly involved in ISC could be largely reduced, which decreased the ISC current. The TRM mechanism took effect immediately after the LIB was damaged. The testing data indicate that the groove width is a critical factor. With optimized groove width, this technique may enable robust and multifunctional design of LIB cells for large-scale energy-storage units.

Triggers of oral lichen planus flares and the potential role of trigger avoidance in disease management.

PubMed

Chen, Hannah X; Blasiak, Rachel; Kim, Edwin; Padilla, Ricardo; Culton, Donna A

2017-09-01

Many patients with oral lichen planus (OLP) report triggers of flares, some of which overlap with triggers of other oral diseases, including oral allergy syndrome and oral contact dermatitis. The purpose of this study was to evaluate the prevalence of commonly reported triggers of OLP flares, their overlap with triggers of other oral diseases, and the potential role of trigger avoidance as a management strategy. Questionnaire-based survey of 51 patients with biopsy-proven lichen planus with oral involvement seen in an academic dermatology specialty clinic and/or oral pathology clinic between June 2014 and June 2015. Of the participants, 94% identified at least one trigger of their OLP flares. Approximately half of the participants (51%) reported at least one trigger that overlapped with known triggers of oral allergy syndrome, and 63% identified at least one trigger that overlapped with known triggers of oral contact dermatitis. Emotional stress was the most commonly reported trigger (77%). Regarding avoidance, 79% of the study participants reported avoiding their known triggers in daily life. Of those who actively avoided triggers, 89% reported an improvement in symptoms and 70% reported a decrease in the frequency of flares. Trigger identification and avoidance can play a potentially effective role in the management of OLP. Copyright © 2017 Elsevier Inc. All rights reserved.

Microglia in Glia-Neuron Co-cultures Exhibit Robust Phagocytic Activity Without Concomitant Inflammation or Cytotoxicity.

PubMed

Adams, Alexandra C; Kyle, Michele; Beaman-Hall, Carol M; Monaco, Edward A; Cullen, Matthew; Vallano, Mary Lou

2015-10-01

A simple method to co-culture granule neurons and glia from a single brain region is described, and microglia activation profiles are assessed in response to naturally occurring neuronal apoptosis, excitotoxin-induced neuronal death, and lipopolysaccharide (LPS) addition. Using neonatal rat cerebellar cortex as a tissue source, glial proliferation is regulated by omission or addition of the mitotic inhibitor cytosine arabinoside (AraC). After 7-8 days in vitro, microglia in AraC(-) cultures are abundant and activated based on their amoeboid morphology, expressions of ED1 and Iba1, and ability to phagocytose polystyrene beads and the majority of neurons undergoing spontaneous apoptosis. Microglia and phagocytic activities are sparse in AraC(+) cultures. Following exposure to excitotoxic kainate concentrations, microglia in AraC(-) cultures phagocytose most dead neurons within 24 h without exacerbating neuronal loss or mounting a strong or sustained inflammatory response. LPS addition induces a robust inflammatory response, based on microglial expressions of TNF-α, COX-2 and iNOS proteins, and mRNAs, whereas these markers are essentially undetectable in control cultures. Thus, the functional effector state of microglia is primed for phagocytosis but not inflammation or cytotoxicity even after kainate exposure that triggers death in the majority of neurons. This model should prove useful in studying the progressive activation states of microglia and factors that promote their conversion to inflammatory and cytotoxic phenotypes.

HIV-1-Tat excites cardiac parasympathetic neurons of nucleus ambiguus and triggers prolonged bradycardia in conscious rats

PubMed Central

Brailoiu, Eugen; Deliu, Elena; Sporici, Romeo A.; Benamar, Khalid

2014-01-01

The mechanisms of autonomic imbalance and subsequent cardiovascular manifestations in HIV-1-infected patients are poorly understood. We report here that HIV-1 transactivator of transcription (Tat, fragment 1–86) produced a concentration-dependent increase in cytosolic Ca2+ in cardiac-projecting parasympathetic neurons of nucleus ambiguus retrogradely labeled with rhodamine. Using store-specific pharmacological agents, we identified several mechanisms of the Tat-induced Ca2+ elevation: 1) lysosomal Ca2+ mobilization, 2) Ca2+ release via inositol 1,4,5-trisphosphate-sensitive endoplasmic reticulum pools, and 3) Ca2+ influx via transient receptor potential vanilloid type 2 (TRPV2) channels. Activation of TRPV2, nonselective cation channels, induced a robust and prolonged neuronal membrane depolarization, thus triggering an additional P/Q-mediated Ca2+ entry. In vivo microinjection studies indicate a dose-dependent, prolonged bradycardic effect of Tat administration into the nucleus ambiguus of conscious rats, in which neuronal TRPV2 played a major role. Our results support previous studies, indicating that Tat promotes bradycardia and, consequently, may be involved in the QT interval prolongation reported in HIV-infected patients. In the context of an overall HIV-dependent autonomic dysfunction, these Tat-mediated mechanisms may account for the higher prevalence of sudden cardiac death in HIV-1-infected patients compared with general population with similar risk factors. Our results may be particularly relevant in view of the recent findings that significant Tat levels can still be identified in the cerebrospinal fluid of HIV-infected patients with viral load suppression due to efficient antiretroviral therapy. PMID:24694382

A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

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

Zhang, Guozhu, E-mail: gzhang6@ncsu.edu

Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weightedmore » Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.« less

High fluid pressure and triggered earthquakes in the enhanced geothermal system in Basel, Switzerland

NASA Astrophysics Data System (ADS)

Terakawa, Toshiko; Miller, Stephen A.; Deichmann, Nicholas

2012-07-01

We analyzed 118 well-constrained focal mechanisms to estimate the pore fluid pressure field of the stimulated region during the fluid injection experiment in Basel, Switzerland. This technique, termed focal mechanism tomography (FMT), uses the orientations of slip planes within the prevailing regional stress field as an indicator of the fluid pressure along the plane at the time of slip. The maximum value and temporal change of excess pore fluid pressures are consistent with the known history of the wellhead pressure applied at the borehole. Elevated pore fluid pressures were concentrated within 500 m of the open hole section, which are consistent with the spatiotemporal evolution of the induced microseismicity. Our results demonstrate that FMT is a robust approach, being validated at the meso-scale of the Basel stimulation experiment. We found average earthquake triggering excess pore fluid pressures of about 10 MPa above hydrostatic. Overpressured fluids induced many small events (M < 3) along faults unfavorably oriented relative to the tectonic stress pattern, while the larger events tended to occur along optimally oriented faults. This suggests that small-scale hydraulic networks, developed from the high pressure stimulation, interact to load (hydraulically isolated) high strength bridges that produce the larger events. The triggering pore fluid pressures are substantially higher than that predicted from a linear pressure diffusion process from the source boundary, and shows that the system is highly permeable along flow paths that allow fast pressure diffusion to the boundaries of the stimulated region.

Predictive performance of rainfall thresholds for shallow landslides in Switzerland from gridded daily data

NASA Astrophysics Data System (ADS)

Leonarduzzi, Elena; Molnar, Peter; McArdell, Brian W.

2017-08-01

A high-resolution gridded daily precipitation data set was combined with a landslide inventory containing over 2000 events in the period 1972-2012 to analyze rainfall thresholds which lead to landsliding in Switzerland. We colocated triggering rainfall to landslides, developed distributions of triggering and nontriggering rainfall event properties, and determined rainfall thresholds and intensity-duration ID curves and validated their performance. The best predictive performance was obtained by the intensity-duration ID threshold curve, followed by peak daily intensity Imax and mean event intensity Imean. Event duration by itself had very low predictive power. A single country-wide threshold of Imax = 28 mm/d was extended into space by regionalization based on surface erodibility and local climate (mean daily precipitation). It was found that wetter local climate and lower erodibility led to significantly higher rainfall thresholds required to trigger landslides. However, we showed that the improvement in model performance due to regionalization was marginal and much lower than what can be achieved by having a high-quality landslide database. Reference cases in which the landslide locations and timing were randomized and the landslide sample size was reduced showed the sensitivity of the Imax rainfall threshold model. Jack-knife and cross-validation experiments demonstrated that the model was robust. The results reported here highlight the potential of using rainfall ID threshold curves and rainfall threshold values for predicting the occurrence of landslides on a country or regional scale with possible applications in landslide warning systems, even with daily data.

Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells.

PubMed

Wang, Xiuling; Liu, Zhongchun; Wang, Peigang; Li, Shan; Zeng, Jie; Tu, Xiaoning; Yan, Qiujin; Xiao, Zheman; Pan, Mengxian; Zhu, Fan

2018-01-01

Schizophrenia is a devastating psychiatric disorder that impacts on social functioning and quality of life, and there is accumulating evidence that inflammation is a potential pathogenic mechanism of schizophrenia. However, the mechanism of inflammation possibly occurred in schizophrenia has not been well understood. The endogenous retroviral protein syncytin-1 and inflammatory marker CRP are both abnormally expressed in schizophrenia patients. CRP is one of the markers of bacterial infection generally. Less clear is whether virus or viral protein can trigger the activation of CRP. Here, we detected a robust increase of the levels of syncytin-1 and CRP in schizophrenia patients, and displayed a positive correlation and marked consistency between expressions of syncytin-1 and CRP in schizophrenia patients. Furthermore, overexpression of syncytin-1 significantly elevated the levels of CRP, TLR3, and IL-6 in both human microglia and astrocytes. TLR3 deficiency impaired the expressions of CRP and IL-6 induced by syncytin-1. Importantly, we observed a cellular co-localization and a direct interaction between syncytin-1 and TLR3. Additionally, knockdown of IL-6 inhibited the syncytin-1-induced CRP expression. Thus, the totality of these results showed that viral protein syncytin-1 could trigger the activation of CRP, which might explain the elevated CRP in sterile inflammation and exhibit a novel mechanism for regulation of inflammation by syncytin-1 in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Observations of bi-directional leader development in a triggered lightning flash

NASA Technical Reports Server (NTRS)

Laroche, P.; Idone, V.; Eybert-Berard, A.; Barret, L.

1991-01-01

Observations of a modified form of rocket triggered lightning are described. A flash triggered during the summer of 1989 is studied as part of an effort to model bidirectional discharge. It is suggested that the altitude triggering technique provides a realistic means of studying the attachment process.

Contribution of Cell Elongation to the Biofilm Formation of Pseudomonas aeruginosa during Anaerobic Respiration

PubMed Central

Park, Yongjin; Yoon, Sang Sun

2011-01-01

Pseudomonas aeruginosa, a gram-negative bacterium of clinical importance, forms more robust biofilm during anaerobic respiration, a mode of growth presumed to occur in abnormally thickened mucus layer lining the cystic fibrosis (CF) patient airway. However, molecular basis behind this anaerobiosis-triggered robust biofilm formation is not clearly defined yet. Here, we identified a morphological change naturally accompanied by anaerobic respiration in P. aeruginosa and investigated its effect on the biofilm formation in vitro. A standard laboratory strain, PAO1 was highly elongated during anaerobic respiration compared with bacteria grown aerobically. Microscopic analysis demonstrated that cell elongation likely occurred as a consequence of defective cell division. Cell elongation was dependent on the presence of nitrite reductase (NIR) that reduces nitrite (NO2 −) to nitric oxide (NO) and was repressed in PAO1 in the presence of carboxy-PTIO, a NO antagonist, demonstrating that cell elongation involves a process to respond to NO, a spontaneous byproduct of the anaerobic respiration. Importantly, the non-elongated NIR-deficient mutant failed to form biofilm, while a mutant of nitrate reductase (NAR) and wild type PAO1, both of which were highly elongated, formed robust biofilm. Taken together, our data reveal a role of previously undescribed cell biological event in P. aeruginosa biofilm formation and suggest NIR as a key player involved in such process. PMID:21267455

Where do we stand after twenty years of dynamic triggering studies? (Invited)

NASA Astrophysics Data System (ADS)

Prejean, S. G.; Hill, D. P.

2013-12-01

In the past two decades, remote dynamic triggering of earthquakes by other earthquakes has been explored in a variety of physical environments with a wide array of observation and modeling techniques. These studies have significantly refined our understanding of the state of the crust and the physical conditions controlling earthquake nucleation. Despite an ever growing database of dynamic triggering observations, significant uncertainties remain and vigorous debate in almost all aspects of the science continues. For example, although dynamic earthquake triggering can occur with peak dynamic stresses as small as 1 kPa, triggering thresholds and their dependence on local stress state, hydrological environment, and frictional properties of faults are not well understood. Some studies find a simple threshold based on the peak amplitude of shaking while others find dependencies on frequency, recharge time, and other parameters. Considerable debate remains over the range of physical processes responsible for dynamic triggering, and the wide variation in dynamic triggering responses and time scales suggests triggering by multiple physical processes. Although Coulomb shear failure with various friction laws can often explain dynamic triggering, particularly instantaneous triggering, delayed dynamic triggering may be dependent on fluid transport and other slowly evolving aseismic processes. Although our understanding of the global distribution of dynamic triggering has improved, it is far from complete due to spatially uneven monitoring. A major challenge involves establishing statistical significance of potentially triggered earthquakes, particularly if they are isolated events or time-delayed with respect to triggering stresses. Here we highlight these challenges and opportunities with existing data. We focus on environmental dependence of dynamic triggering by large remote earthquakes particularly in volcanic and geothermal systems, as these systems often have high rates of background seismicity. In many volcanic and geothermal systems, such as the Geysers in Northern California, dynamic triggering of micro-earthquakes is frequent and predictable. In contrast, most active and even erupting volcanoes in Alaska (with the exception of the Katmai Volcanic Cluster) do not experience dynamic triggering. We explore why.

Nanocomposite capsules with directional, pulsed nanoparticle release.

PubMed

Udoh, Christiana E; Cabral, João T; Garbin, Valeria

2017-12-01

The precise spatiotemporal delivery of nanoparticles from polymeric capsules is required for applications ranging from medicine to materials science. These capsules derive key performance aspects from their overall shape and dimensions, porosity, and internal microstructure. To this effect, microfluidics provide an exceptional platform for emulsification and subsequent capsule formation. However, facile and robust approaches for nanocomposite capsule fabrication, exhibiting triggered nanoparticle release, remain elusive because of the complex coupling of polymer-nanoparticle phase behavior, diffusion, phase inversion, and directional solidification. We investigate a model system of polyelectrolyte sodium poly(styrene sulfonate) and 22-nm colloidal silica and demonstrate a robust capsule morphology diagram, achieving a range of internal morphologies, including nucleated and bicontinuous microstructures, as well as isotropic and non-isotropic external shapes. Upon dissolution in water, we find that capsules formed with either neat polymers or neat nanoparticles dissolve rapidly and isotropically, whereas bicontinuous, hierarchical, composite capsules dissolve via directional pulses of nanoparticle clusters without disrupting the scaffold, with time scales tunable from seconds to hours. The versatility, facile assembly, and response of these nanocomposite capsules thus show great promise in precision delivery.

Powered ankle-foot prosthesis to assist level-ground and stair-descent gaits.

PubMed

Au, Samuel; Berniker, Max; Herr, Hugh

2008-05-01

The human ankle varies impedance and delivers net positive work during the stance period of walking. In contrast, commercially available ankle-foot prostheses are passive during stance, causing many clinical problems for transtibial amputees, including non-symmetric gait patterns, higher gait metabolism, and poorer shock absorption. In this investigation, we develop and evaluate a myoelectric-driven, finite state controller for a powered ankle-foot prosthesis that modulates both impedance and power output during stance. The system employs both sensory inputs measured local to the external prosthesis, and myoelectric inputs measured from residual limb muscles. Using local prosthetic sensing, we first develop two finite state controllers to produce biomimetic movement patterns for level-ground and stair-descent gaits. We then employ myoelectric signals as control commands to manage the transition between these finite state controllers. To transition from level-ground to stairs, the amputee flexes the gastrocnemius muscle, triggering the prosthetic ankle to plantar flex at terminal swing, and initiating the stair-descent state machine algorithm. To transition back to level-ground walking, the amputee flexes the tibialis anterior muscle, triggering the ankle to remain dorsiflexed at terminal swing, and initiating the level-ground state machine algorithm. As a preliminary evaluation of clinical efficacy, we test the device on a transtibial amputee with both the proposed controller and a conventional passive-elastic control. We find that the amputee can robustly transition between the finite state controllers through direct muscle activation, allowing rapid transitioning from level-ground to stair walking patterns. Additionally, we find that the proposed finite state controllers result in a more biomimetic ankle response, producing net propulsive work during level-ground walking and greater shock absorption during stair descent. The results of this study highlight the potential of prosthetic leg controllers that exploit neural signals to trigger terrain-appropriate, local prosthetic leg behaviors.

RhMKK9, a rose MAP KINASE KINASE gene, is involved in rehydration-triggered ethylene production in rose gynoecia.

PubMed

Chen, Jiwei; Zhang, Qian; Wang, Qigang; Feng, Ming; Li, Yang; Meng, Yonglu; Zhang, Yi; Liu, Guoqin; Ma, Zhimin; Wu, Hongzhi; Gao, Junping; Ma, Nan

2017-02-23

Flower opening is an important process in the life cycle of flowering plants and is influenced by various endogenous and environmental factors. Our previous work demonstrated that rose (Rosa hybrida) flowers are highly sensitive to dehydration during flower opening and the water recovery process after dehydration induced ethylene production rapidly in flower gynoecia. In addition, this temporal- and spatial-specific ethylene production is attributed to a transient but robust activation of the rose MAP KINASE6-ACC SYNTHASE1 (RhMPK6-RhACS1) cascade in gynoecia. However, the upstream component of RhMPK6-RhACS1 is unknown, although RhMKK9 (MAP KINASE KINASE9), a rose homologue of Arabidopsis MKK9, could activate RhMPK6 in vitro. In this study, we monitored RhMKK2/4/5/9 expression, the potential upstream kinase to RhMPK6, in rose gynoecia during dehydration and rehydration. We found only RhMKK9 was rapidly and strongly induced by rehydration. Silencing of RhMKK9 significantly decreased rehydration-triggered ethylene production. Consistently, the expression of several ethylene-responsive genes was down regulated in the petals of RhMKK9-silenced flowers. Moreover, we detected the DNA methylation level in the promoter and gene body of RhMKK9 by Chop-PCR. The results showed that rehydration specifically elevated the DNA methylation level on the RhMKK9 gene body, whereas it resulted in hypomethylation in its promoter. Our results showed that RhMKK9 possibly acts as the upstream component of the RhMKK9-RhMPK6-RhACS1 cascade and is responsible for water recovery-triggered ethylene production in rose gynoecia, and epigenetic DNA methylation is involved in the regulation of RhMKK9 expression by rehydration.

Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox

PubMed Central

Parker, Scott; Chen, Nanhai G.; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E.; Schriewer, Jill; Buller, R. Mark

2013-01-01

The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analogue of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is 4 or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection – thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. PMID:22381921

Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox.

PubMed

Parker, Scott; Chen, Nanhai G; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E; Schriewer, Jill; Mark Buller, R

2012-04-01

The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection - thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. Copyright © 2012 Elsevier B.V. All rights reserved.

Simulation studies on the differences between spontaneous and triggered seismicity and on foreshock probabilities

NASA Astrophysics Data System (ADS)

Zhuang, J.; Vere-Jones, D.; Ogata, Y.; Christophersen, A.; Savage, M. K.; Jackson, D. D.

2008-12-01

In this study we investigate the foreshock probabilities calculated from earthquake catalogs from Japan, Southern California and New Zealand. Unlike conventional studies on foreshocks, we use a probability-based declustering method to separate each catalog into stochastic versions of family trees, such that each event is classified as either having been triggered by a preceding event, or being a spontaneous event. The probabilities are determined from parameters that provide the best fit of the real catalogue using a space- time epidemic-type aftershock sequence (ETAS) model. The model assumes that background and triggered earthquakes have the same magnitude dependent triggering capability. A foreshock here is defined as a spontaneous event that has one or more larger descendants, and a triggered foreshock is a triggered event that has one or more larger descendants. The proportion of foreshocks in spontaneous events of each catalog is found to be lower than the proportion of triggered foreshocks in triggered events. One possibility is that this is due to different triggering productivity in spontaneous versus triggered events, i.e., a triggered event triggers more children than a spontaneous events of the same magnitude. To understand what causes the above differences between spontaneous and triggered events, we apply the same procedures to several synthetic catalogs simulated by using different models. The first simulation is done by using the ETAS model with parameters and spontaneous rate fitted from the JMA catalog. The second synthetic catalog is simulated by using an adjusted ETAS model that takes into account the triggering effect from events lower than the magnitude. That is, we simulated the catalog with a low magnitude threshold with the original ETAS model, and then we remove the events smaller than a higher magnitude threshold. The third model for simulation assumes that different triggering behaviors exist between spontaneous event and triggered events. We repeat the fitting and reconstruction procedures to all those simulated catalogs. The reconstruction results for the first synthetic catalog do not show the difference between spontaneous events and triggered event or the differences in foreshock probabilities. On the other hand, results from the synthetic catalogs simulated with the second and the third models clearly reconstruct such differences. In summary our results implies that one of the causes of such differences may be neglecting the triggering effort from events smaller than the cut-off magnitude or magnitude errors. For the objective of forecasting seismicity, we can use a clustering model in which spontaneous events trigger child events in a different way from triggered events to avoid over-predicting earthquake risks with foreshocks. To understand the physical implication of this study, we need further careful studies to compare the real seismicity and the adjusted ETAS model, which takes the triggering effect from events below the cut-off magnitude into account.

Reliability of physical examination for diagnosis of myofascial trigger points: a systematic review of the literature.

PubMed

Lucas, Nicholas; Macaskill, Petra; Irwig, Les; Moran, Robert; Bogduk, Nikolai

2009-01-01

Trigger points are promoted as an important cause of musculoskeletal pain. There is no accepted reference standard for the diagnosis of trigger points, and data on the reliability of physical examination for trigger points are conflicting. To systematically review the literature on the reliability of physical examination for the diagnosis of trigger points. MEDLINE, EMBASE, and other sources were searched for articles reporting the reliability of physical examination for trigger points. Included studies were evaluated for their quality and applicability, and reliability estimates were extracted and reported. Nine studies were eligible for inclusion. None satisfied all quality and applicability criteria. No study specifically reported reliability for the identification of the location of active trigger points in the muscles of symptomatic participants. Reliability estimates varied widely for each diagnostic sign, for each muscle, and across each study. Reliability estimates were generally higher for subjective signs such as tenderness (kappa range, 0.22-1.0) and pain reproduction (kappa range, 0.57-1.00), and lower for objective signs such as the taut band (kappa range, -0.08-0.75) and local twitch response (kappa range, -0.05-0.57). No study to date has reported the reliability of trigger point diagnosis according to the currently proposed criteria. On the basis of the limited number of studies available, and significant problems with their design, reporting, statistical integrity, and clinical applicability, physical examination cannot currently be recommended as a reliable test for the diagnosis of trigger points. The reliability of trigger point diagnosis needs to be further investigated with studies of high quality that use current diagnostic criteria in clinically relevant patients.

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.

Active photosynthetic inhibition mediated by MPK3/MPK6 is critical to effector-triggered immunity

PubMed Central

Su, Jianbin; Yang, Liuyi; Zhu, Qiankun; Wu, Hongjiao; He, Yi; Liu, Yidong; Xu, Juan; Jiang, Dean

2018-01-01

Extensive research revealed tremendous details about how plants sense pathogen effectors during effector-triggered immunity (ETI). However, less is known about downstream signaling events. In this report, we demonstrate that prolonged activation of MPK3 and MPK6, two Arabidopsis pathogen-responsive mitogen-activated protein kinases (MPKs), is essential to ETI mediated by both coiled coil-nucleotide binding site-leucine rich repeats (CNLs) and toll/interleukin-1 receptor nucleotide binding site-leucine rich repeats (TNLs) types of R proteins. MPK3/MPK6 activation rapidly alters the expression of photosynthesis-related genes and inhibits photosynthesis, which promotes the accumulation of superoxide (O2•−) and hydrogen peroxide (H2O2), two major reactive oxygen species (ROS), in chloroplasts under light. In the chemical-genetically rescued mpk3 mpk6 double mutants, ETI-induced photosynthetic inhibition and chloroplastic ROS accumulation are compromised, which correlates with delayed hypersensitive response (HR) cell death and compromised resistance. Furthermore, protection of chloroplasts by expressing a plastid-targeted cyanobacterial flavodoxin (pFLD) delays photosynthetic inhibition and compromises ETI. Collectively, this study highlights a critical role of MPK3/MPK6 in manipulating plant photosynthetic activities to promote ROS accumulation in chloroplasts and HR cell death, which contributes to the robustness of ETI. Furthermore, the dual functionality of MPK3/MPK6 cascade in promoting defense and inhibiting photosynthesis potentially allow it to orchestrate the trade-off between plant growth and defense in plant immunity. PMID:29723186

Transforming Growth Factor β-1 Stimulates Profibrotic Epithelial Signaling to Activate Pericyte-Myofibroblast Transition in Obstructive Kidney Fibrosis

PubMed Central

Wu, Ching-Fang; Chiang, Wen-Chih; Lai, Chun-Fu; Chang, Fan-Chi; Chen, Yi-Ting; Chou, Yu-Hsiang; Wu, Ting-Hui; Linn, Geoffrey R.; Ling, Hong; Wu, Kwan-Dun; Tsai, Tun-Jun; Chen, Yung-Ming; Duffield, Jeremy S.; Lin, Shuei-Liong

2014-01-01

Pericytes have been identified as the major source of precursors of scar-producing myofibroblasts during kidney fibrosis. The underlying mechanisms triggering pericyte-myofibroblast transition are poorly understood. Transforming growth factor β-1 (TGF-β1) is well recognized as a pluripotent cytokine that drives organ fibrosis. We investigated the role of TGF-β1 in inducing profibrotic signaling from epithelial cells to activate pericyte-myofibroblast transition. Increased expression of TGF-β1 was detected predominantly in injured epithelium after unilateral ureteral obstruction, whereas downstream signaling from the TGF-β1 receptor increased in both injured epithelium and pericytes. In mice with ureteral obstruction that were treated with the pan anti–TGF-β antibody (1D11) or TGF-β receptor type I inhibitor (SB431542), kidney pericyte-myofibroblast transition was blunted. The consequence was marked attenuation of fibrosis. In addition, epithelial cell cycle G2/M arrest and production of profibrotic cytokines were both attenuated. Although TGF-β1 alone did not trigger pericyte proliferation in vitro, it robustly induced α smooth muscle actin (α-SMA). In cultured kidney epithelial cells, TGF-β1 stimulated G2/M arrest and production of profibrotic cytokines that had the capacity to stimulate proliferation and transition of pericytes to myofibroblasts. In conclusion, this study identified a novel link between injured epithelium and pericyte-myofibroblast transition through TGF-β1 during kidney fibrosis. PMID:23142380

Triggering sporulation in Bacillus subtilis with artificial two-component systems reveals the importance of proper Spo0A activation dynamics.

PubMed

Vishnoi, Monika; Narula, Jatin; Devi, Seram Nganbiton; Dao, Hoang-Anh; Igoshin, Oleg A; Fujita, Masaya

2013-10-01

Sporulation initiation in Bacillus subtilis is controlled by the phosphorylated form of the master regulator Spo0A which controls transcription of a multitude of sporulation genes. In this study, we investigated the importance of temporal dynamics of phosphorylated Spo0A (Spo0A∼P) accumulation by rewiring the network controlling its phosphorylation. We showed that simultaneous induction of KinC, a kinase that can directly phosphorylate Spo0A, and Spo0A itself from separately controlled inducible promoters can efficiently trigger sporulation even under nutrient rich conditions. However, the sporulation efficiency in this artificial two-component system was significantly impaired when KinC and/or Spo0A induction was too high. Using mathematical modelling, we showed that gradual accumulation of Spo0A∼P is essential for the proper temporal order of the Spo0A regulon expression, and that reduction in sporulation efficiency results from the reversal of that order. These insights led us to identify premature repression of DivIVA as one possible explanation for the adverse effects of accelerated accumulation of Spo0A∼P on sporulation. Moreover, we found that positive feedback resulting from autoregulation of the native spo0A promoter leads to robust control of Spo0A∼P accumulation kinetics. Thus we propose that a major function of the conserved architecture of the sporulation network is controlling Spo0A activation dynamics. © 2013 John Wiley & Sons Ltd.

Evaluation of accuracy of IHI Trigger Tool in identifying adverse drug events: a prospective observational study.

PubMed

das Dores Graciano Silva, Maria; Martins, Maria Auxiliadora Parreiras; de Gouvêa Viana, Luciana; Passaglia, Luiz Guilherme; de Menezes, Renata Rezende; de Queiroz Oliveira, João Antonio; da Silva, Jose Luiz Padilha; Ribeiro, Antonio Luiz Pinho

2018-06-06

Adverse drug events (ADEs) can seriously compromise the safety and quality of care provided to hospitalized patients, requiring the adoption of accurate methods to monitor them. We sought to prospectively evaluate the accuracy of the triggers proposed by the Institute for Healthcare Improvement (IHI) for identifying ADEs. A prospective study was conducted in a public university hospital, in 2015, with patients ≥18 years. Triggers proposed by IHI and clinical alterations suspected to be ADEs were searched daily. The number of days in which the patient was hospitalized was considered as unit of measure to evaluate the accuracy of each trigger. Three hundred patients were included in this study. Mean age was 56.3 years (standard deviation (SD) 16.0), and 154 (51.3%) were female. The frequency of patients with ADEs was 24.7% and with at least one trigger was 53.3%. From those patients who had at least one trigger, the most frequent triggers were antiemetics (57.5%) and "abrupt medication stop" (31.8%). Triggers' sensitivity ranged from 0.3 to11.8 % and the positive predictive value ranged from 1.2 to 27.3%. Specificity and negative predictive value were greater than 86%. Most patients identified by the presence of triggers did not have ADEs (64.4%). No triggers were identified in 40 (38.5%) ADEs. IHI Trigger Tool did not show good accuracy in detecting ADEs in this prospective study. The adoption of combined strategies could enhance effectiveness in identifying patient safety flaws. Further discussion might contribute to improve trigger usefulness in clinical practice. This article is protected by copyright. All rights reserved.

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.

Proposal of a trigger tool to assess adverse events in dental care.

PubMed

Corrêa, Claudia Dolores Trierweiler Sampaio de Oliveira; Mendes, Walter

2017-11-21

The aim of this study was to propose a trigger tool for research of adverse events in outpatient dentistry in Brazil. The tool was elaborated in two stages: (i) to build a preliminary set of triggers, a literature review was conducted to identify the composition of trigger tools used in other areas of health and the principal adverse events found in dentistry; (ii) to validate the preliminarily constructed triggers a panel of experts was organized using the modified Delphi method. Fourteen triggers were elaborated in a tool with explicit criteria to identify potential adverse events in dental care, essential for retrospective patient chart reviews. Studies on patient safety in dental care are still incipient when compared to other areas of health care. This study intended to contribute to the research in this field. The contribution by the literature and guidance from the expert panel allowed elaborating a set of triggers to detect adverse events in dental care, but additional studies are needed to test the instrument's validity.

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

Etude et simulation du protocole TTEthernet sur un sous-systeme de gestion de vols et adaptation de la planification des tâches a des fins de simulation

NASA Astrophysics Data System (ADS)

Abidi, Dhafer

TTEthernet is a deterministic network technology that makes enhancements to Layer 2 Quality-of-Service (QoS) for Ethernet. The components that implement its services enrich the Ethernet functionality with distributed fault-tolerant synchronization, robust temporal partitioning bandwidth and synchronous communication with fixed latency and low jitter. TTEthernet services can facilitate the design of scalable, robust, less complex distributed systems and architectures tolerant to faults. Simulation is nowadays an essential step in critical systems design process and represents a valuable support for validation and performance evaluation. CoRE4INET is a project bringing together all TTEthernet simulation models currently available. It is based on the extension of models of OMNeT ++ INET framework. Our objective is to study and simulate the TTEthernet protocol on a flight management subsystem (FMS). The idea is to use CoRE4INET to design the simulation model of the target system. The problem is that CoRE4INET does not offer a task scheduling tool for TTEthernet network. To overcome this problem we propose an adaptation for simulation purposes of a task scheduling approach based on formal specification of network constraints. The use of Yices solver allowed the translation of the formal specification into an executable program to generate the desired transmission plan. A case study allowed us at the end to assess the impact of the arrangement of Time-Triggered frames offsets on the performance of each type of the system traffic.

Functionality of Triggers for Epilepsy Patients Assessed by Text and Data Mining of Medical and Nursing Records.

PubMed

Kivekäs, Eija; Kinnunen, Ulla-Mari; Paananen, Pekka; Kälviäinen, Reetta; Haatainen, Kaisa; Saranto, Kaija

2016-01-01

A trigger is a powerful tool for identifying adverse events to measure the level of any kind of harm caused in patient care. Studies with epilepsy patients have illustrated that using triggers as a methodology with data mining may increase patient well-being. The purpose of this study is to test the functionality and validity of the previously defined triggers to describe the status of epilepsy patient's well-being. In both medical and nursing data, the triggers described patients' well-being comprehensively. The narratives showed that there was overlapping in triggers. The preliminary results of triggers encourage us to develop some reminders to the documentation of epilepsy patient well-being. These provide healthcare professionals with further and more detailed information when necessary.

Holocene Glacier Fluctuations in the Peruvian Andes Indicate Northern Climate Linkages

NASA Astrophysics Data System (ADS)

Licciardi, Joseph M.; Schaefer, Joerg M.; Taggart, Jean R.; Lund, David C.

2009-09-01

The role of the tropics in triggering, transmitting, and amplifying interhemispheric climate signals remains a key debate in paleoclimatology. Tropical glacier fluctuations provide important insight on regional paleoclimatic trends and forcings, but robust chronologies are scarce. Here, we report precise moraine ages from the Cordillera Vilcabamba (13°20‧S) of southern Peru that indicate prominent glacial events and associated climatic shifts in the outer tropics during the early Holocene and late in the “Little Ice Age” period. Our glacier chronologies differ from the New Zealand record but are broadly correlative with well-dated glacial records in Europe, suggesting climate linkages between the tropics and the North Atlantic region.

The Disability Discrimination Act in the UK: helping or hindering employment among the disabled?

PubMed

Bell, David; Heitmueller, Axel

2009-03-01

The enactment of the Americans with Disabilities Act (ADA) in 1990 triggered a substantial academic debate about its consequences on employment rates of disabled people. In contrast, the employment provision of the 1996 Disability Discrimination Act (DDA) in Britain has received little attention. Exploiting both pooled and longitudinal data, this paper provides robust evidence that, similar to the ADA in the USA, the DDA has had no impact on the employment rate of disabled people or possibly worsened it. Possible reasons for this are higher uncertainty around litigation costs, low levels of general awareness about the Act among disabled people and employers, and a lack of financial support.

Stress-induced EGFR trafficking: mechanisms, functions, and therapeutic implications

PubMed Central

Tan, Xiaojun; Lambert, Paul F.; Rapraeger, Alan C.; Anderson, Richard A.

2016-01-01

Epidermal growth factor receptor (EGFR) has fundamental roles in normal physiology and in cancer, making it a rational target for cancer therapy. Surprisingly, however, inhibitors that target canonical, ligand-stimulated EGFR signaling have proven to be largely ineffective in treating many EGFR-dependent cancers. Recent evidence indicates that both intrinsic and therapy-induced cellular stress triggers robust, non-canonical pathways of ligand-independent EGFR trafficking and signaling, which provides cancer cells with a survival advantage and resistance to therapeutics. Here we review the mechanistic regulation of non-canonical EGFR trafficking and signaling, the pathological and therapeutic stresses that activate it, and discuss the implications of this pathway in clinical treatment of EGFR-overexpressing cancers. PMID:26827089

Monostable superrepellent materials

NASA Astrophysics Data System (ADS)

Li, Yanshen; Quéré, David; Lv, Cunjing; Zheng, Quanshui

2017-03-01

Superrepellency is an extreme situation where liquids stay at the tops of rough surfaces, in the so-called Cassie state. Owing to the dramatic reduction of solid/liquid contact, such states lead to many applications, such as antifouling, droplet manipulation, hydrodynamic slip, and self-cleaning. However, superrepellency is often destroyed by impalement transitions triggered by environmental disturbances whereas inverse transitions are not observed without energy input. Here we show through controlled experiments the existence of a “monostable” region in the phase space of surface chemistry and roughness, where transitions from Cassie to (impaled) Wenzel states become spontaneously reversible. We establish the condition for observing monostability, which might guide further design and engineering of robust superrepellent materials.

JP3D compressed-domain watermarking of volumetric medical data sets

NASA Astrophysics Data System (ADS)

Ouled Zaid, Azza; Makhloufi, Achraf; Olivier, Christian

2010-01-01

Increasing transmission of medical data across multiple user systems raises concerns for medical image watermarking. Additionaly, the use of volumetric images triggers the need for efficient compression techniques in picture archiving and communication systems (PACS), or telemedicine applications. This paper describes an hybrid data hiding/compression system, adapted to volumetric medical imaging. The central contribution is to integrate blind watermarking, based on turbo trellis-coded quantization (TCQ), to JP3D encoder. Results of our method applied to Magnetic Resonance (MR) and Computed Tomography (CT) medical images have shown that our watermarking scheme is robust to JP3D compression attacks and can provide relative high data embedding rate whereas keep a relative lower distortion.

Fully localised nonlinear energy growth optimals in pipe flow

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

Pringle, Chris C. T.; Willis, Ashley P.; Kerswell, Rich R.

A new, fully localised, energy growth optimal is found over large times and in long pipe domains at a given mass flow rate. This optimal emerges at a threshold disturbance energy below which a nonlinear version of the known (streamwise-independent) linear optimal [P. J. Schmid and D. S. Henningson, “Optimal energy density growth in Hagen-Poiseuille flow,” J. Fluid Mech. 277, 192–225 (1994)] is selected and appears to remain the optimal up until the critical energy at which transition is triggered. The form of this optimal is similar to that found in short pipes [Pringle et al., “Minimal seeds for shearmore » flow turbulence: Using nonlinear transient growth to touch the edge of chaos,” J. Fluid Mech. 702, 415–443 (2012)], but now with full localisation in the streamwise direction. This fully localised optimal perturbation represents the best approximation yet of the minimal seed (the smallest perturbation which is arbitrarily close to states capable of triggering a turbulent episode) for “real” (laboratory) pipe flows. Dependence of the optimal with respect to several parameters has been computed and establishes that the structure is robust.« less

Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses.

PubMed

Mohamadzadeh, Mansour; Coberley, Sadie S; Olinger, Gene G; Kalina, Warren V; Ruthel, Gordon; Fuller, Claudette L; Swenson, Dana L; Pratt, William D; Kuhns, Douglas B; Schmaljohn, Alan L

2006-07-01

Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections.

Innate immune signaling in Drosophila is regulated by transforming growth factor β (TGFβ)-activated kinase (Tak1)-triggered ubiquitin editing

PubMed Central

Chen, Li; Paquette, Nicholas; Mamoor, Shahan; Rus, Florentina; Nandy, Anubhab; Leszyk, John; Shaffer, Scott A.; Silverman, Neal

2017-01-01

Coordinated regulation of innate immune responses is necessary in all metazoans. In Drosophila the Imd pathway detects Gram-negative bacterial infections through recognition of diaminopimelic acid (DAP)-type peptidoglycan and activation of the NF-κB precursor Relish, which drives robust antimicrobial peptide gene expression. Imd is a receptor-proximal adaptor protein homologous to mammalian RIP1 that is regulated by proteolytic cleavage and Lys-63-polyubiquitination. However, the precise events and molecular mechanisms that control the post-translational modification of Imd remain unclear. Here, we demonstrate that Imd is rapidly Lys-63-polyubiquitinated at lysine residues 137 and 153 by the sequential action of two E2 enzymes, Ubc5 and Ubc13-Uev1a, in conjunction with the E3 ligase Diap2. Lys-63-ubiquitination activates the TGFβ-activated kinase (Tak1), which feeds back to phosphorylate Imd, triggering the removal of Lys-63 chains and the addition of Lys-48 polyubiquitin. This ubiquitin-editing process results in the proteasomal degradation of Imd, which we propose functions to restore homeostasis to the Drosophila immune response. PMID:28377500

Eosinophils Subvert Host Resistance to an Intracellular Pathogen by Instigating Non-Protective IL-4 in CCR2−/− Mice

PubMed Central

Verma, Akash H.; Bueter, Chelsea L.; Rothenberg, Marc E.; Deepe, George S.

2016-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases, however, their influence on intracellular pathogens is less clear. We previously reported that CCR2−/− mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated IL-4 response. We sought to identify the cellular source promulgating interleukin (IL)-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2−/− animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity. PMID:27049063

Wireless Synchronization of a Multi-Pinhole Small Animal SPECT Collimation Device With a Clinical Scanner

NASA Astrophysics Data System (ADS)

DiFilippo, Frank P.; Patel, Sagar

2009-06-01

A multi-pinhole collimation device for small animal single photon emission computed tomography (SPECT) uses the gamma camera detectors of a standard clinical SPECT scanner. The collimator and animal bed move independently of the detectors, and therefore their motions must be synchronized. One approach is manual triggering of the SPECT acquisition simultaneously with a programmed motion sequence for the device. However, some data blurring and loss of image quality result, and true electronic synchronization is preferred. An off-the-shelf digital gyroscope with integrated Bluetooth interface provides a wireless solution to device synchronization. The sensor attaches to the SPECT gantry and reports its rotational speed to a notebook computer controlling the device. Software processes the rotation data in real-time, averaging the signal and issuing triggers while compensating for baseline drift. Motion commands are sent to the collimation device with minimal delay, within approximately 0.5 second of the start of SPECT gantry rotation. Test scans of a point source demonstrate an increase in true counts and a reduction in background counts compared to manual synchronization. The wireless rotation sensor provides robust synchronization of the collimation device with the clinical SPECT scanner and enhances image quality.

Biomolecular Photovoltaics and Artificial Sight

NASA Astrophysics Data System (ADS)

Greenbaum, Elias; Kuritz, Tanya; Lee, Ida; Owens, Elizabeth T.; Humayun, Mark

2004-11-01

The goal of this project is insertion of purified Photosystem I (PSI) reaction centers or other photoactive agents into retinal cells where they will restore photoreceptor function to people who suffer from age-related macular degeneration (AMD) or retinitis pigmentosa (RP), diseases that are the leading causes of blindness world-wide. Although the neural ``wiring'' from eye to brain is intact, these patients lack photoreceptor activity. It is the ultimate goal of this project to restore photoreceptor activity to these patients using PSI as the optical trigger. In principle, the approach should work. PSI is a robust integral membrane molecular photovoltaic device. Depending on orientation, it can depolarize or hyperpolarize the cell membrane with sufficient voltage to trigger an action potential. The first objective of this work, reported here, is to impart photoreceptor activity to mammalian cells using the previously determined molecular photovoltaic properties of isolated Photosystem I reaction centers. Incubation of WERI-Rb-1 retinoblastoma cells with functional PSI reaction centers that were isolated from spinach leaves and reconstituted into proteoliposomes resulted in a light-induced PSI-dependent increase in intracellular Ca^2+. The increase, due to Ca^2+ uptake, was dependent on the presence of extracellular Ca^2+ ions.

Molecular Photovoltaics and Artificial Sight

NASA Astrophysics Data System (ADS)

Greenbaum, Elias

2005-03-01

The goal of this project is insertion of purified Photosystem I (PSI) reaction centers or other photoactive agents into retinal cells where they will restore photoreceptor function to people who suffer from age-related macular degeneration (AMD) or retinitis pigmentosa (RP), diseases that are the leading causes of blindness world-wide. Although the neural ``wiring'' from eye to brain is intact, these patients lack photoreceptor activity. It is the ultimate goal of this project to restore photoreceptor activity to these patients using PSI as the optical trigger. In principle, the approach should work. PSI is a robust integral membrane molecular photovoltaic device. Depending on orientation, it can depolarize or hyperpolarize the cell membrane with sufficient voltage to trigger an action potential. The first objective of this work, reported here, is to impart photoreceptor activity to mammalian cells using the previously determined molecular photovoltaic properties of isolated Photosystem I reaction centers. Incubation of WERI-Rb-1 retinoblastoma cells with functional PSI reaction centers that were isolated from spinach leaves and reconstituted into proteoliposomes resulted in a light-induced PSI-dependent increase in intracellular Ca^2+. The increase, due to Ca^2+ uptake, was dependent on the presence of extracellular Ca^2+ ions.

Responsive block copolymer photonics triggered by protein-polyelectrolyte coacervation.

PubMed

Fan, Yin; Tang, Shengchang; Thomas, Edwin L; Olsen, Bradley D

2014-11-25

Ionic interactions between proteins and polyelectrolytes are demonstrated as a method to trigger responsive transitions in block copolymer (BCP) photonic gels containing one neutral hydrophobic block and one cationic hydrophilic block. Poly(2-vinylpyridine) (P2VP) blocks in lamellar poly(styrene-b-2-vinylpyridine) block copolymer thin films are quaternized with primary bromides to yield swollen gels that show strong reflectivity peaks in the visible range; exposure to aqueous solutions of various proteins alters the swelling ratios of the quaternized P2VP (QP2VP) gel layers in the PS-QP2VP materials due to the ionic interactions between proteins and the polyelectrolyte. Parameters such as charge density, hydrophobicity, and cross-link density of the QP2VP gel layers as well as the charge and size of the proteins play significant roles on the photonic responses of the BCP gels. Differences in the size and pH-dependent charge of proteins provide a basis for fingerprinting proteins based on their temporal and equilibrium photonic response. The results demonstrate that the BCP gels and their photonic effect provide a robust and visually interpretable method to differentiate different proteins.

Suicide triggers as sex-specific threats in domains of evolutionary import: negative correlation between global male-to-female suicide ratios and average per capita gross national income.

PubMed

Saad, Gad

2007-01-01

From an evolutionary perspective, suicide is a paradoxical phenomenon given its fatal consequences on one's reproductive fitness. That fact notwithstanding, evolutionists have typically used kin and group selection arguments in proposing that suicide might indeed be viewed as an adaptive behavioral response. The current paper posits that in some instances, suicide might be construed as the ultimate maladaptive response to "crushing defeats" in domains of great evolutionary import (e.g., mating). Specifically, it is hypothesized that numerous sex-specific triggers of suicide are universally consistent because they correspond to dire sex-specific attacks on one's reproductive fitness (e.g., loss of occupational status is much more strongly linked to male suicides). More generally, it is proposed that many epidemiological aspects of suicide are congruent with Darwinian-based frameworks. These include the near-universal finding that men are much more likely to commit suicide (sexual selection theory), the differential motives that drive men and women to commit suicide (evolutionary psychology), and the shifting patterns of suicide across the life span (life-history theory). Using data from the World Health Organization and the World Bank, several evolutionary-informed hypotheses, regarding the correlation between male-to-female suicide ratios and average per capita Gross National Income, are empirically tested. Overall, the findings are congruent with Darwinian-based expectations namely as economic conditions worsen the male-to-female suicide ratio is exacerbated, with the negative correlation being the strongest for the "working age" brackets. The hypothesized evolutionary outlook provides a consilient framework in comprehending universal sex-specific triggers of suicide. Furthermore, it allows suicidologists to explore new research avenues that might remain otherwise untapped if one were to restrict their research interests on the identification of proximate causes of suicide. Global clinical and epidemiological data emphasizing other universally robust triggers of suicide would afford additional support for the postulated framework.

Dimethylated H3K27 Is a Repressive Epigenetic Histone Mark in the Protist Entamoeba histolytica and Is Significantly Enriched in Genes Silenced via the RNAi Pathway*

PubMed Central

Foda, Bardees M.; Singh, Upinder

2015-01-01

RNA interference (RNAi) is a fundamental biological process that plays a crucial role in regulation of gene expression in many organisms. Transcriptional gene silencing (TGS) is one of the important nuclear roles of RNAi. Our previous data show that Entamoeba histolytica has a robust RNAi pathway that links to TGS via Argonaute 2-2 (Ago2-2) associated 27-nucleotide small RNAs with 5′-polyphosphate termini. Here, we report the first repressive histone mark to be identified in E. histolytica, dimethylation of H3K27 (H3K27Me2), and demonstrate that it is enriched at genes that are silenced by RNAi-mediated TGS. An RNAi-silencing trigger can induce H3K27Me2 deposits at both episomal and chromosomal loci, mediating gene silencing. Our data support two phases of RNAi-mediated TGS: an active silencing phase where the RNAi trigger is present and both H3K27Me2 and Ago2-2 concurrently enrich at chromosomal loci; and an established silencing phase in which the RNAi trigger is removed, but gene silencing with H3K27Me2 enrichment persist independently of Ago2-2 deposition. Importantly, some genes display resistance to chromosomal silencing despite induction of functional small RNAs. In those situations, the RNAi-triggering plasmid that is maintained episomally gets partially silenced and has H3K27Me2 enrichment, but the chromosomal copy displays no repressive histone enrichment. Our data are consistent with a model in which H3K27Me2 is a repressive histone modification, which is strongly associated with transcriptional repression. This is the first example of an epigenetic histone modification that functions to mediate RNAi-mediated TGS in the deep-branching eukaryote E. histolytica. PMID:26149683

A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

PubMed

Calder, P C; Ahluwalia, N; Albers, R; Bosco, N; Bourdet-Sicard, R; Haller, D; Holgate, S T; Jönsson, L S; Latulippe, M E; Marcos, A; Moreines, J; M'Rini, C; Müller, M; Pawelec, G; van Neerven, R J J; Watzl, B; Zhao, J

2013-01-01

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

Acute triggers of myocardial infarction: A case-crossover study.

PubMed

Ghiasmand, Maryam; Moghadamnia, Mohammad Taghi; Pourshaikhian, Majid; Kazemnejad Lili, Ehsan

2017-12-01

Acute myocardial infarction (AMI) is one of the most preventable non-communicable diseases in human. Identifying triggers of myocardial infarction (MI) and prevention ways of exposure-induced complications can reduce morbidity and mortality in people at risk. The aim of this study was to identify the emotional, environmental, physical and chemical dimensions of acute triggers in patients with AMI. This case-crossover study was conducted on 269 patients with AMI, hospitalized at two remedial centers in Rasht in 2015. The study samples were selected by convenient sampling method. Data were collected using researcher-made questionnaire through interviews. Hazard and control periods for each trigger and its effects on the development of MI were studied. The collected data were analyzed using descriptive and analytical statistical methods, Cochran test, and generalized estimating equation (GEE) model with logistics function default in SPSS version 21, and p  < 0.05 was considered statistically significant. The results showed that quarrel ( P  = 0.008, OR = 2.01) and hearing the sudden news ( P  = 0.001, OR = 2.19) were the most common emotional triggers. Respiratory infections ( P  = 0.0001, OR = 6.78) and exposure to hot or cold weather ( P  = 0.005, OR = 2.19) were the most frequent environmental triggers. Doing heavy activities ( P  = 0.005, OR = 1.66) and sexual activities ( P  = 0.003, OR = 2.36) were among the most common physical triggers. High-fat foods consumption and overeating ( P  = 0.0001, OR = 3.79) were the most frequent chemical triggers of AMI. It seems that given the importance of the triggers in the incidence of AMI, planning is necessary to train vulnerable individuals to reduce exposure to triggers.

Combined Electrocardiography- and Respiratory-Triggered CT of the Lung to Reduce Respiratory Misregistration Artifacts between Imaging Slabs in Free-Breathing Children: Initial Experience.

PubMed

Goo, Hyun Woo; Allmendinger, Thomas

2017-01-01

Cardiac and respiratory motion artifacts degrade the image quality of lung CT in free-breathing children. The aim of this study was to evaluate the effect of combined electrocardiography (ECG) and respiratory triggering on respiratory misregistration artifacts on lung CT in free-breathing children. In total, 15 children (median age 19 months, range 6 months-8 years; 7 boys), who underwent free-breathing ECG-triggered lung CT with and without respiratory-triggering were included. A pressure-sensing belt of a respiratory gating system was used to obtain the respiratory signal. The degree of respiratory misregistration artifacts between imaging slabs was graded on a 4-point scale (1, excellent image quality) on coronal and sagittal images and compared between ECG-triggered lung CT studies with and without respiratory triggering. A p value < 0.05 was considered significant. Lung CT with combined ECG and respiratory triggering showed significantly less respiratory misregistration artifacts than lung CT with ECG triggering only (1.1 ± 0.4 vs. 2.2 ± 1.0, p = 0.003). Additional respiratory-triggering reduces respiratory misregistration artifacts on ECG-triggered lung CT in free-breathing children.

Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses.

PubMed

Wagner, Julia A; Berrien-Elliott, Melissa M; Rosario, Maximillian; Leong, Jeffrey W; Jewell, Brea A; Schappe, Timothy; Abdel-Latif, Sara; Fehniger, Todd A

2017-03-01

Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown. We investigated this interaction using killer cell immunoglobulin-like receptor- and HLA-genotyped primary human NK cells. Memory-like differentiation resulted in enhanced IFN-γ production triggered by leukemia targets or FcγRIIIa ligation within licensed NK cells, which exhibited the highest functionality of the NK cell subsets interrogated. IFN-γ production by unlicensed memory-like NK cells was also enhanced to a level comparable with that of licensed control NK cells. Mechanistically, differences in responses to FcγRIIIa-based triggering were not explained by alterations in key signaling intermediates, indicating that the underlying biology of memory-like NK cells is distinct from that of adaptive NK cells in human cytomegalovirus-positive individuals. Additionally, memory-like NK cells responded robustly to cytokine receptor restimulation with no impact of licensing status. These results demonstrate that both licensed and unlicensed memory-like NK cell populations have enhanced functionality, which may be translated to improve leukemia immunotherapy. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Event-Triggered Model Predictive Control for Embedded Artificial Pancreas Systems.

PubMed

Chakrabarty, Ankush; Zavitsanou, Stamatina; Doyle, Francis J; Dassau, Eyal

2018-03-01

The development of artificial pancreas (AP) technology for deployment in low-energy, embedded devices is contingent upon selecting an efficient control algorithm for regulating glucose in people with type 1 diabetes mellitus. In this paper, we aim to lower the energy consumption of the AP by reducing controller updates, that is, the number of times the decision-making algorithm is invoked to compute an appropriate insulin dose. Physiological insights into glucose management are leveraged to design an event-triggered model predictive controller (MPC) that operates efficiently, without compromising patient safety. The proposed event-triggered MPC is deployed on a wearable platform. Its robustness to latent hypoglycemia, model mismatch, and meal misinformation is tested, with and without meal announcement, on the full version of the US-FDA accepted UVA/Padova metabolic simulator. The event-based controller remains on for 18 h of 41 h in closed loop with unannounced meals, while maintaining glucose in 70-180 mg/dL for 25 h, compared to 27 h for a standard MPC controller. With meal announcement, the time in 70-180 mg/dL is almost identical, with the controller operating a mere 25.88% of the time in comparison with a standard MPC. A novel control architecture for AP systems enables safe glycemic regulation with reduced processor computations. Our proposed framework integrated seamlessly with a wide variety of popular MPC variants reported in AP research, customizes tradeoff between glycemic regulation and efficacy according to prior design specifications, and eliminates judicious prior selection of controller sampling times.

Exploring the Web : The Active Galaxy Population in the ORELSE Survey

NASA Astrophysics Data System (ADS)

Lubin, Lori

What are the physical processes that trigger starburst and nuclear activity in galaxies and drive galaxy evolution? Studies aimed at understanding this complex issue have largely focused on the cores of galaxy clusters or on field surveys, leaving underexplored intermediate-density regimes where rapid evolution occurs. As a result, we are conducting the ORELSE survey, a search for structure on scales > 10 Mpc around 18 clusters at 0.6 < z < 1.3. The survey covers 5 sq. deg., all targeted at high-density regions, making it comparable to field surveys such as DEEP2 and COSMOS. ORELSE is unmatched, with no other cluster survey having comparable breadth, depth, precision, and multi-band coverage. As such, ORELSE overcomes critical problems with previous high-redshift studies, including cosmic variance, restricted environmental ranges, sparse cluster samples, inconsistent star formation rate measures, and limited spectroscopy. From its initial spectral and photometric components, ORELSE already contains wellmeasured properties such as redshift, color, stellar mass, and star formation rate for a statistical sample of 7000 field+cluster galaxies. Because X-ray and mid-IR observations are crucial for a complete census of the active galaxy population, we propose to use the wealth of archival Chandra, Spitzer, and Herschel data in the ORELSE fields to map AGN and starburst galaxies over large scales. When complete, our sample will exceed by more than an order of magnitude the current samples of spectroscopically-confirmed active galaxies in high-redshift clusters and their environs. Combined with our numerical simulations plus galaxy formation models, we will provide a robust census of the active galaxy population in intermediate and high-density environments at z = 1, constrain the physical processes (e.g., merging, intracluster gas interactions, AGN feedback) responsible for triggering/quenching starburst and nuclear activity, and estimate their associated timescales.

The ocean-atmosphere response to wind-induced thermocline changes in the tropical South Western Indian Ocean

NASA Astrophysics Data System (ADS)

Manola, Iris; Selten, F. M.; de Ruijter, W. P. M.; Hazeleger, W.

2015-08-01

In the Indian Ocean basin the sea surface temperatures (SSTs) are most sensitive to changes in the oceanic depth of the thermocline in the region of the Seychelles Dome. Observational studies have suggested that the strong SST variations in this region influence the atmospheric evolution around the basin, while its impact could extend far into the Pacific and the extra-tropics. Here we study the adjustments of the coupled atmosphere-ocean system to a winter shallow doming event using dedicated ensemble simulations with the state-of-the-art EC-Earth climate model. The doming creates an equatorial Kelvin wave and a pair of westward moving Rossby waves, leading to higher SST 1-2 months later in the Western equatorial Indian Ocean. Atmospheric convection is strengthened and the Walker circulation responds with reduced convection over Indonesia and cooling of the SST in that region. The Pacific warm pool convection shifts eastward and an oceanic Kelvin wave is triggered at thermocline depth. The wave leads to an SST warming in the East Equatorial Pacific 5-6 months after the initiation of the Seychelles Dome event. The atmosphere responds to this warming with weak anomalous atmospheric convection. The changes in the upper tropospheric divergence in this sequence of events create large-scale Rossby waves that propagate away from the tropics along the atmospheric waveguides. We suggest to repeat these types of experiments with other models to test the robustness of the results. We also suggest to create the doming event in June so that the East-Pacific warming occurs in November when the atmosphere is most sensitive to SST anomalies and El Niño could possibly be triggered by the doming event under suitable conditions.

Uncertainty Estimation in Tsunami Initial Condition From Rapid Bayesian Finite Fault Modeling

NASA Astrophysics Data System (ADS)

Benavente, R. F.; Dettmer, J.; Cummins, P. R.; Urrutia, A.; Cienfuegos, R.

2017-12-01

It is well known that kinematic rupture models for a given earthquake can present discrepancies even when similar datasets are employed in the inversion process. While quantifying this variability can be critical when making early estimates of the earthquake and triggered tsunami impact, "most likely models" are normally used for this purpose. In this work, we quantify the uncertainty of the tsunami initial condition for the great Illapel earthquake (Mw = 8.3, 2015, Chile). We focus on utilizing data and inversion methods that are suitable to rapid source characterization yet provide meaningful and robust results. Rupture models from teleseismic body and surface waves as well as W-phase are derived and accompanied by Bayesian uncertainty estimates from linearized inversion under positivity constraints. We show that robust and consistent features about the rupture kinematics appear when working within this probabilistic framework. Moreover, by using static dislocation theory, we translate the probabilistic slip distributions into seafloor deformation which we interpret as a tsunami initial condition. After considering uncertainty, our probabilistic seafloor deformation models obtained from different data types appear consistent with each other providing meaningful results. We also show that selecting just a single "representative" solution from the ensemble of initial conditions for tsunami propagation may lead to overestimating information content in the data. Our results suggest that rapid, probabilistic rupture models can play a significant role during emergency response by providing robust information about the extent of the disaster.

A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers.

PubMed

Williams, Paige L; Seage, George R; Van Dyke, Russell B; Siberry, George K; Griner, Raymond; Tassiopoulos, Katherine; Yildirim, Cenk; Read, Jennifer S; Huo, Yanling; Hazra, Rohan; Jacobson, Denise L; Mofenson, Lynne M; Rich, Kenneth

2012-05-01

The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.

The ALICE data quality monitoring system

NASA Astrophysics Data System (ADS)

von Haller, B.; Telesca, A.; Chapeland, S.; Carena, F.; Carena, W.; Chibante Barroso, V.; Costa, F.; Denes, E.; Divià, R.; Fuchs, U.; Simonetti, G.; Soós, C.; Vande Vyvre, P.; ALICE Collaboration

2011-12-01

ALICE (A Large Ion Collider Experiment) is the heavy-ion detector designed to study the physics of strongly interacting matter and the quark-gluon plasma at the CERN Large Hadron Collider (LHC). The online Data Quality Monitoring (DQM) is a key element of the Data Acquisition's software chain. It provide shifters with precise and complete information to quickly identify and overcome problems, and as a consequence to ensure acquisition of high quality data. DQM typically involves the online gathering, the analysis by user-defined algorithms and the visualization of monitored data. This paper describes the final design of ALICE'S DQM framework called AMORE (Automatic MOnitoRing Environment), as well as its latest and coming features like the integration with the offline analysis and reconstruction framework, a better use of multi-core processors by a parallelization effort, and its interface with the eLogBook. The concurrent collection and analysis of data in an online environment requires the framework to be highly efficient, robust and scalable. We will describe what has been implemented to achieve these goals and the procedures we follow to ensure appropriate robustness and performance. We finally review the wide range of usages people make of this framework, from the basic monitoring of a single sub-detector to the most complex ones within the High Level Trigger farm or using the Prompt Reconstruction and we describe the various ways of accessing the monitoring results. We conclude with our experience, before and after the LHC startup, when monitoring the data quality in a challenging environment.

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.

Immobility reactions under threat: A contribution to human defensive cascade and PTSD.

PubMed

Volchan, E; Rocha-Rego, V; Bastos, A F; Oliveira, J M; Franklin, C; Gleiser, S; Berger, W; Souza, G G L; Oliveira, L; David, I A; Erthal, F S; Pereira, M G; Figueira, I

2017-05-01

Violence exacts a burden on public health. Gun violence is a major trigger for motor defensive reactions in humans and post-traumatic stress disorder (PTSD) is its main psychiatric sequela. However, studies of the human defensive cascade, especially the motor reactions, are at an early stage. This review focuses on studies that employ stabilometry, a methodology that assesses whole body motor reactions, to address defensive behaviors to violence-related threats. Special attention is given to three reactions: "attentive immobility", "immobility under attack" and "tonic immobility", with emphasis on the latter - a peritraumatic reaction which has been strongly associated with the severity of PTSD. These reactions are characterized by reduced body sway and bradycardia, except tonic immobility that presents robust tachycardia. The advances made by investigations into the immobility reactions of the human defensive cascade contribute to helping to bridge the gap between human and non-human species. Furthermore, progresses in basic research to objectively monitor motor defensive reactions under threat can help to develop a dimensional, trans-diagnostic approach to PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between Stock Market Gains and Losses and Google Searches

PubMed Central

Arditi, Eli; Yechiam, Eldad; Zahavi, Gal

2015-01-01

Experimental studies in the area of Psychology and Behavioral Economics have suggested that people change their search pattern in response to positive and negative events. Using Internet search data provided by Google, we investigated the relationship between stock-specific events and related Google searches. We studied daily data from 13 stocks from the Dow-Jones and NASDAQ100 indices, over a period of 4 trading years. Focusing on periods in which stocks were extensively searched (Intensive Search Periods), we found a correlation between the magnitude of stock returns at the beginning of the period and the volume, peak, and duration of search generated during the period. This relation between magnitudes of stock returns and subsequent searches was considerably magnified in periods following negative stock returns. Yet, we did not find that intensive search periods following losses were associated with more Google searches than periods following gains. Thus, rather than increasing search, losses improved the fit between people’s search behavior and the extent of real-world events triggering the search. The findings demonstrate the robustness of the attentional effect of losses. PMID:26513371

Engineering design of the PLX- α coaxial gun

NASA Astrophysics Data System (ADS)

Cruz, Edward; Brockington, Samuel; Case, Andrew; Luna, Marco; Witherspoon, Douglas; Langendorf, Samuel

2016-10-01

We describe the engineering and technical aspects of the coaxial gun designed for the 60-gun scaling study of spherically imploding plasma liners as a standoff driver for plasma-jet-driven magneto-inertial fusion. Each coaxial gun incorporates a fast, dense gas injection and triggering system, a compact low-weight pfn with integral sparkgap switching, and a contoured gap designed to suppress the blow-by instability. Alpha1 and Alpha2 guns are compared, with emphasis on the improvements on Alpha2, which include a faster more robust gas valve, an improved electrode contour, a custom 600- μF, 5-kV pfn, and a set of six inline sparkgap switches operated in parallel. The switch and pfn configurations are mounted directly to the back of the gun, and are designed to reduce inductance, cost, and complexity, maximize efficiency and system reliability, and ensure symmetric current flow. We will provide a detailed overview of the design choices made for the PLX- α coaxial gun. This work supported by the ARPA-E ALPHA Program.

C/EBPβ LIP augments cell death by inducing osteoglycin.

PubMed

Wassermann-Dozorets, Rina; Rubinstein, Menachem

2017-04-06

Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates the expression of Ogn. C/EBPβ is expressed as a full-length, active form (LAP) and as a truncated, dominant-negative form (LIP), and the LIP/LAP ratio is positively correlated with the extent of cell death under stress. For example, we reported that drug-resistant tumor cells lack LIP altogether, and its supplementation abolished their resistance to chemotherapy and to endoplasmic reticulum (ER) stress. Here we further show that elevated LIP/LAP ratio robustly increased Ogn expression and cell death under stress by modulating the mitogen-activated protein kinase/activator protein 1 pathway (MAPK/AP-1). Our findings suggest that LIP deficiency renders tumor cell resistant to ER stress by preventing the induction of Ogn.

Synoptic GNIRS XD Spectra ToO Novae

NASA Astrophysics Data System (ADS)

Woodward, Chick; Helton, Andrew; Spitzer/Chandra Team

2007-02-01

Novae are important contributors to galactic chemical enrichment on local scales. NIR spectroscopy of novae provides information about the elemental abundances of the gas and dust in the ejecta dispersing into the ISM as well as kinematic information related to the outburst. We propose to obtain synoptic GNIRS spectra of select Target of Opportunity (ToO) novae in the Magellanic Clouds (MC) and the galaxy to study the dynamics of the ejecta, to determine the temporal evolution of coronal lines and recombination lines (measuring their strength and velocity profiles), and to determine abundances. Being all equidistant, MC nova permit a more robust analysis of distant-dependent physical parameters of outburst than is generally possible for Galactic novae. The GNIRS data will provide critical spectral coverage and synoptic data to complement extant Spitzer and Chandra nova programs. Triggering of the GNIRS program will occur when a nova becomes brighter than V=12 mag, (assuming that adequate PWFS guide stars exist) as reported in the IAUC or CBET.

Environmental Exposures and the Development of Systemic Lupus Erythematosus

PubMed Central

Barbhaiya, Medha; Costenbader, Karen H.

2016-01-01

Purpose of Review This review examines evidence relating environmental factors to the development of systemic lupus erythematosus (SLE). Recent findings The strongest epidemiologic evidence exists for the associations of silica, cigarette smoking, oral contraceptives, postmenopausal hormone therapy, and endometriosis, with SLE incidence. Recent studies have also provided robust evidence of the association between alcohol consumption and decreased SLE risk. There are preliminary, conflicting or unsubstantiated data that other factors, including air pollution, ultraviolet light, infections, vaccinations, solvents, pesticides, and heavy metals such as mercury, are related to SLE risk. Biologic mechanisms linking environmental exposures and SLE risk include increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal triggers, as well as epigenetic modifications resulting from exposure that could lead to SLE. Summary Identifying the environmental risk factors related to risk of SLE is essential as it will lead to increased understanding of pathogenesis of this complex disease and will also make risk factor modification possible for those at increased risk. PMID:27428889

Modelling an advanced ManPAD with dual band detectors and a rosette scanning seeker head

NASA Astrophysics Data System (ADS)

Birchenall, Richard P.; Richardson, Mark A.; Butters, Brian; Walmsley, Roy

2012-01-01

Man Portable Air Defence Systems (ManPADs) have been a favoured anti aircraft weapon since their appearance on the military proliferation scene in the mid 1960s. Since this introduction there has been a 'cat and mouse' game of Missile Countermeasures (CMs) and the aircraft protection counter counter measures (CCMs) as missile designers attempt to defeat the aircraft platform protection equipment. Magnesium Teflon Viton (MTV) flares protected the target aircraft until the missile engineers discovered the art of flare rejection using techniques including track memory and track angle bias. These early CCMs relied upon CCM triggering techniques such as the rise rate method which would just sense a sudden increase in target energy and assume that a flare CM had been released by the target aircraft. This was not as reliable as was first thought as aspect changes (bringing another engine into the field of view) or glint from the sun could inadvertently trigger a CCM when not needed. The introduction of dual band detectors in the 1980s saw a major advance in CCM capability allowing comparisons between two distinct IR bands to be made thus allowing the recognition of an MTV flare to occur with minimal false alarms. The development of the rosette scan seeker in the 1980s complemented this advancement allowing the scene in the missile field of view (FOV) to be scanned by a much smaller (1/25) instantaneous FOV (IFOV) with the spectral comparisons being made at each scan point. This took the ManPAD from a basic IR energy detector to a pseudo imaging system capable of analysing individual elements of its overall FOV allowing more complex and robust CCM to be developed. This paper continues the work published in [1,2] and describes the method used to model an advanced ManPAD with a rosette scanning seeker head and robust CCMs similar to the Raytheon Stinger RMP.

Stress/strain changes and triggered seismicity following the MW7.3 Landers, California, earthquake

USGS Publications Warehouse

Gomberg, J.

1996-01-01

Calculations of dynamic stresses and strains, constrained by broadband seismograms, are used to investigate their role in generating the remotely triggered seismicity that followed the June 28, 1992, MW7.3 Landers, California earthquake. I compare straingrams and dynamic Coulomb failure functions calculated for the Landers earthquake at sites that did experience triggered seismicity with those at sites that did not. Bounds on triggering thresholds are obtained from analysis of dynamic strain spectra calculated for the Landers and MW,6.1 Joshua Tree, California, earthquakes at various sites, combined with results of static strain investigations by others. I interpret three principal results of this study with those of a companion study by Gomberg and Davis [this issue]. First, the dynamic elastic stress changes themselves cannot explain the spatial distribution of triggered seismicity, particularly the lack of triggered activity along the San Andreas fault system. In addition to the requirement to exceed a Coulomb failure stress level, this result implies the need to invoke and satisfy the requirements of appropriate slip instability theory. Second, results of this study are consistent with the existence of frequency- or rate-dependent stress/strain triggering thresholds, inferred from the companion study and interpreted in terms of earthquake initiation involving a competition of processes, one promoting failure and the other inhibiting it. Such competition is also part of relevant instability theories. Third, the triggering threshold must vary from site to site, suggesting that the potential for triggering strongly depends on site characteristics and response. The lack of triggering along the San Andreas fault system may be correlated with the advanced maturity of its fault gouge zone; the strains from the Landers earthquake were either insufficient to exceed its larger critical slip distance or some other critical failure parameter; or the faults failed stably as aseismic creep events. Variations in the triggering threshold at sites of triggered seismicity may be attributed to variations in gouge zone development and properties. Finally, these interpretations provide ready explanations for the time delays between the Landers earthquake and the triggered events.

Comparison of Triggering and Nontriggering Factors in ST-Segment Elevation Myocardial Infarction and Extent of Coronary Arterial Narrowing.

PubMed

Ben-Shoshan, Jeremy; Segman-Rosenstveig, Yafit; Arbel, Yaron; Chorin, Ehud; Barkagan, Michael; Rozenbaum, Zach; Granot, Yoav; Finkelstein, Ariel; Banai, Shmuel; Keren, Gad; Shacham, Yacov

2016-04-15

Various physical, emotional, and extrinsic triggers have been attributed to acute coronary syndrome. Whether a correlation can be drawn between identifiable ischemic triggers and the nature of coronary artery disease (CAD) still remains unclear. In the present study, we evaluated the correlation between triggered versus nontriggered ischemic symptoms and the extent of CAD in patients with ST-segment elevation myocardial infarction (STEMI). We conducted a retrospective, single-center observational study including 1,345 consecutive patients with STEMI, treated with primary percutaneous coronary intervention. Acute physical and emotional triggers were identified in patients' historical data. Independent predictors of multivessel CAD were determined using a logistic regression model. A potential trigger was identified in 37% of patients. Physical exertion was found to be the most dominant trigger (65%) followed by psychological stress (16%) and acute illness (12%). Patients with nontriggered STEMI tended to be older and more likely to have co-morbidities. Patients with nontriggered STEMI showed a higher rate of multivessel CAD (73% vs 30%, p <0.001). In a multivariate regression model, nontriggered symptoms emerged as an independent predictor of multivessel CAD (odds ratio 8.33, 95% CI 5.74 to 12.5, p = 0.001). No specific trigger was found to predict independently the extent of CAD. In conclusion, symptoms onset without a recognizable trigger is associated with multivessel CAD in STEMI. Further studies will be required to elucidate the putative mechanisms underlying ischemic triggering. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome: a retrospective cohort study

PubMed Central

2013-01-01

Background Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implantation rates can be sustained. The objective of this study was to assess the live-birth rate and incidence of OHSS after GnRHa trigger and intensive luteal steroid support compared to traditional hCG trigger and conventional luteal support in OHSS high risk Asian patients. Methods We conducted a retrospective cohort study of 363 women exposed to GnRHa triggering with intensive luteal support compared with 257 women exposed to conventional hCG triggering. Women at risk of OHSS were defined by ovarian response ≥15 follicles ≥12 mm on the day of the trigger. Results Live-birth rates were similar in both groups GnRHa vs hCG; 29.8% vs 29.2% (p = 0.69). One late onset severe OHSS case was observed in the GnRHa trigger group (0.3%) compared to 18 cases (7%) after hCG trigger. Conclusions GnRHa trigger combined with intensive luteal steroid support in this group of OHSS high risk Asian patients can facilitate fresh embryo transfer, however, in contrast to previous reports the occurrence of late onset OHSS was not completely eliminated. PMID:24369069

Studies of the stability of water-soluble polypeptoid helices and investigation of synthetic, biomimetic substrates for the development of a thermally triggered, enzymatically crosslinked hydrogel for biomedical applications

NASA Astrophysics Data System (ADS)

Sanborn, Tracy Joella

Due to the unique 3D structures of proteins, these biopolymers are able to perform a myriad of vital functions and activities in vivo. Peptidomimetic oligomers are being synthesized to mimic the structure and function of natural peptides. We have examined the stability of secondary structure of a poly-N-substituted glycine (peptoid) and developed synthetic substrates for transglutaminase enzymes. We synthesized an amphipathic, helical, 36 residue peptoid to study the stability of peptoid secondary structure using circular dichroism. We saw no significant dependence of helical structure on concentration, solvent, or temperature. The extraordinary resistance of these peptoid helices to denaturation is consistent with a dominant role, of steric forces in their structural stabilization. The structured polypeptoids studied here have potential as robust mimics of helical polypeptides of therapeutic interest. The ability of transglutaminases to crosslink peptidomimetic substrates was also investigated. There is a medical need for robust, biocompatible hydrogels that can be rapidly crosslinked in situ, for application as surgical adhesives, bone-inductive materials, or for drug delivery. We have taken an enzymatic approach to the creation of a novel gelation system that fits these requirements, utilizing transglutaminase enzymes, thermo-responsive liposomes, and a biomimetic enzyme substrate based on a peptide-polymer conjugate. At room temperature, the hydrogel system is a solution. Upon heating to 37°C, the calcium-loaded liposomes release calcium that activates Factor XIII in the presence of thrombin, producing a gel within 9 minutes. Rheological studies demonstrated that the hydrogel behaves as a robust, elastic solid, while scanning electron microscopy studies revealed that the hydrogel has a very dense morphology overall. We also investigated the ability of transglutaminases to crosslink non-natural, peptoid-based substrates. The activity of five lysine-containing peptoid substrates and two glutamine-containing peptoid substrates with proteinogenic side chains were compared to their peptide analogs. Lysine-containing peptoid substrates were crosslinked by the transglutaminase but at a much lower rate, producing at most 28% of the crosslinked product that its peptide counterpart produced. Of the two glutamine-containing peptoid substrates investigated, one did not show any crosslinked product formation, while the other was insoluble in aqueous solution.

Combined Electrocardiography- and Respiratory-Triggered CT of the Lung to Reduce Respiratory Misregistration Artifacts between Imaging Slabs in Free-Breathing Children: Initial Experience

PubMed Central

Allmendinger, Thomas

2017-01-01

Objective Cardiac and respiratory motion artifacts degrade the image quality of lung CT in free-breathing children. The aim of this study was to evaluate the effect of combined electrocardiography (ECG) and respiratory triggering on respiratory misregistration artifacts on lung CT in free-breathing children. Materials and Methods In total, 15 children (median age 19 months, range 6 months–8 years; 7 boys), who underwent free-breathing ECG-triggered lung CT with and without respiratory-triggering were included. A pressure-sensing belt of a respiratory gating system was used to obtain the respiratory signal. The degree of respiratory misregistration artifacts between imaging slabs was graded on a 4-point scale (1, excellent image quality) on coronal and sagittal images and compared between ECG-triggered lung CT studies with and without respiratory triggering. A p value < 0.05 was considered significant. Results Lung CT with combined ECG and respiratory triggering showed significantly less respiratory misregistration artifacts than lung CT with ECG triggering only (1.1 ± 0.4 vs. 2.2 ± 1.0, p = 0.003). Conclusion Additional respiratory-triggering reduces respiratory misregistration artifacts on ECG-triggered lung CT in free-breathing children. PMID:28860904

Causality and headache triggers

PubMed Central

Turner, Dana P.; Smitherman, Todd A.; Martin, Vincent T.; Penzien, Donald B.; Houle, Timothy T.

2013-01-01

Objective The objective of this study was to explore the conditions necessary to assign causal status to headache triggers. Background The term “headache trigger” is commonly used to label any stimulus that is assumed to cause headaches. However, the assumptions required for determining if a given stimulus in fact has a causal-type relationship in eliciting headaches have not been explicated. Methods A synthesis and application of Rubin’s Causal Model is applied to the context of headache causes. From this application the conditions necessary to infer that one event (trigger) causes another (headache) are outlined using basic assumptions and examples from relevant literature. Results Although many conditions must be satisfied for a causal attribution, three basic assumptions are identified for determining causality in headache triggers: 1) constancy of the sufferer; 2) constancy of the trigger effect; and 3) constancy of the trigger presentation. A valid evaluation of a potential trigger’s effect can only be undertaken once these three basic assumptions are satisfied during formal or informal studies of headache triggers. Conclusions Evaluating these assumptions is extremely difficult or infeasible in clinical practice, and satisfying them during natural experimentation is unlikely. Researchers, practitioners, and headache sufferers are encouraged to avoid natural experimentation to determine the causal effects of headache triggers. Instead, formal experimental designs or retrospective diary studies using advanced statistical modeling techniques provide the best approaches to satisfy the required assumptions and inform causal statements about headache triggers. PMID:23534872

Root assays to study pattern-triggered immunity in plant-nematode interactions

USDA-ARS?s Scientific Manuscript database

Plants employ extracellular immune receptors to perceive conserved pathogen-associated molecular patterns (PAMPs), triggering the first layer of defense known as pattern-triggered immunity (PTI). The understanding of PTI is mainly based on the studies focusing on leaves. Plants are vulnerable to att...

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.

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

Comparison of the origin and coupling interval between ectopy with and without atrial fibrillation initiation.

PubMed

Kanda, Takashi; Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2018-01-01

Differentiation of atrial fibrillation (AF) trigger ectopy from other ectopy is often difficult. The purpose of this study was to compare the origin and coupling intervals (CI) between AF-trigger and non-AF-trigger ectopy. This study consisted of 120 patients with AF who underwent an initial ablation. Isoproterenol was infused up to 20μg/min to provoke ectopy and AF. We measured the CI of all ectopy provoked by an isoproterenol infusion. The %CI was calculated as the CI of the ectopy/P-P interval of the preceding 2 beats. A total of 117 patients had at least one ectopy, and AF was induced in 56 (47%) patients. Of the 276 ectopies observed in this study, 211 (76%) originated from pulmonary veins and 77 (28%) were AF-trigger ectopy. AF-trigger ectopy more frequently originated from pulmonary veins (PVs) (74 vs. 3, p<0.001) and had a significantly shorter CI (201±70ms vs. 365±147ms, p<0.001) and lower %CI (29±11% vs. 55±14%, p<0.001) than that of non-AF-trigger ectopy. A receiver operating characteristics analysis revealed that a %CI of 40% was the best cut-off value for differentiating whether it was an AF-trigger or not. The identified trigger group, including patients with provoked AF-trigger ectopy or ectopy with a low %CI (<40%), had a significantly better AF recurrence-free survival rate than the other group (88% vs. 65%, p=0.004). AF-trigger ectopy predominantly originated from PVs and had a short CI. These findings may be useful for estimating whether ectopies are an AF-trigger or not. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The effect of trigger point management by positional release therapy on tension type headache.

PubMed

Ghanbari, Ali; Rahimijaberi, Abbas; Mohamadi, Marzieh; Abbasi, Leila; Sarvestani, Fahimeh Kamali

2012-01-01

The aim of this study was to compare the effectiveness of trigger points' management by Positional Release Therapy (PRT) and routine medical therapy in treatment of Tension Type Headache. Tension Type Headache is the most frequent headache with the basis of myofascial and trigger point disorders. PRT is an indirect technique that treats trigger points. 30 Patients with active trigger points in cervical muscles entered to the study. They were randomly assigned to PRT or medical therapy group. Headache frequency, intensity and duration and tablet count were recorded by use of a daily headache diary. Sensitivity of trigger points was assessed by numeric pain intensity and by use of a digital force gauge (FG 5020). Both groups showed significant reduction in headache frequency and duration and tablet count after treatment phase. However, the reduction of study variables was persisted only in PRT group after follow up phase. There was no significant reduction in headache intensity, neither in PRT and nor in medication group. Sensitivity of trigger points was significantly reduced. In comparison of the two study groups, there was no significant difference in headache frequency, intensity, duration and tablet count (p> 0.05). Both procedures were equally effective according to the study. Thus, PRT can be a treatment choice for patients with T.T.H.

Computational Software to Fit Seismic Data Using Epidemic-Type Aftershock Sequence Models and Modeling Performance Comparisons

NASA Astrophysics Data System (ADS)

Chu, A.

2016-12-01

Modern earthquake catalogs are often analyzed using spatial-temporal point process models such as the epidemic-type aftershock sequence (ETAS) models of Ogata (1998). My work implements three of the homogeneous ETAS models described in Ogata (1998). With a model's log-likelihood function, my software finds the Maximum-Likelihood Estimates (MLEs) of the model's parameters to estimate the homogeneous background rate and the temporal and spatial parameters that govern triggering effects. EM-algorithm is employed for its advantages of stability and robustness (Veen and Schoenberg, 2008). My work also presents comparisons among the three models in robustness, convergence speed, and implementations from theory to computing practice. Up-to-date regional seismic data of seismic active areas such as Southern California and Japan are used to demonstrate the comparisons. Data analysis has been done using computer languages Java and R. Java has the advantages of being strong-typed and easiness of controlling memory resources, while R has the advantages of having numerous available functions in statistical computing. Comparisons are also made between the two programming languages in convergence and stability, computational speed, and easiness of implementation. Issues that may affect convergence such as spatial shapes are discussed.

The development of a standardised diet history tool to support the diagnosis of food allergy.

PubMed

Skypala, Isabel J; Venter, Carina; Meyer, Rosan; deJong, Nicolette W; Fox, Adam T; Groetch, Marion; Oude Elberink, J N; Sprikkelman, Aline; Diamandi, Louiza; Vlieg-Boerstra, Berber J

2015-01-01

The disparity between reported and diagnosed food allergy makes robust diagnosis imperative. The allergy-focussed history is an important starting point, but published literature on its efficacy is sparse. Using a structured approach to connect symptoms, suspected foods and dietary intake, a multi-disciplinary task force of the European Academy of Allergy and Clinical Immunology developed paediatric and adult diet history tools. Both tools are divided into stages using traffic light labelling (red, amber and green). The red stage requires the practitioner to gather relevant information on symptoms, atopic history, food triggers, foods eaten and nutritional issues. The amber stage facilitates interpretation of the responses to the red-stage questions, thus enabling the practitioner to prepare to move forward. The final green stage provides a summary template and test algorithm to support continuation down the diagnostic pathway. These tools will provide a standardised, practical approach to support food allergy diagnosis, ensuring that all relevant information is captured and interpreted in a robust manner. Future work is required to validate their use in diverse age groups, disease entities and in different countries, in order to account for differences in health care systems, food availability and dietary norms.

Sam68 Is Required for DNA Damage Responses via Regulating Poly(ADP-ribosyl)ation

PubMed Central

Hodgson, Andrea; Wier, Eric M.; Wen, Matthew G.; Kamenyeva, Olena; Xia, Xue; Koo, Lily Y.

2016-01-01

The rapid and robust synthesis of polymers of adenosine diphosphate (ADP)-ribose (PAR) chains, primarily catalyzed by poly(ADP-ribose) polymerase 1 (PARP1), is crucial for cellular responses to DNA damage. However, the precise mechanisms through which PARP1 is activated and PAR is robustly synthesized are not fully understood. Here, we identified Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel signaling molecule in DNA damage responses (DDRs). In the absence of Sam68, DNA damage-triggered PAR production and PAR-dependent DNA repair signaling were dramatically diminished. With serial cellular and biochemical assays, we demonstrated that Sam68 is recruited to and significantly overlaps with PARP1 at DNA lesions and that the interaction between Sam68 and PARP1 is crucial for DNA damage-initiated and PARP1-conferred PAR production. Utilizing cell lines and knockout mice, we illustrated that Sam68-deleted cells and animals are hypersensitive to genotoxicity caused by DNA-damaging agents. Together, our findings suggest that Sam68 plays a crucial role in DDR via regulating DNA damage-initiated PAR production. PMID:27635653

eqMAXEL: A new automatic earthquake location algorithm implementation for Earthworm

NASA Astrophysics Data System (ADS)

Lisowski, S.; Friberg, P. A.; Sheen, D. H.

2017-12-01

A common problem with automated earthquake location systems for a local to regional scale seismic network is false triggering and false locations inside the network caused by larger regional to teleseismic distance earthquakes. This false location issue also presents a problem for earthquake early warning systems where societal impacts of false alarms can be very expensive. Towards solving this issue, Sheen et al. (2016) implemented a robust maximum-likelihood earthquake location algorithm known as MAXEL. It was shown with both synthetics and real-data for a small number of arrivals, that large regional events were easily identifiable through metrics in the MAXEL algorithm. In the summer of 2017, we collaboratively implemented the MAXEL algorithm into a fully functional Earthworm module and tested it in regions of the USA where false detections and alarming are observed. We show robust improvement in the ability of the Earthworm system to filter out regional and teleseismic events that would have falsely located inside the network using the traditional Earthworm hypoinverse solution. We also explore using different grid sizes in the implementation of the MAXEL algorithm, which was originally designed with South Korea as the target network size.

Zombie Vortex Instability: Effects of Non-uniform Stratification & Thermal Cooling

NASA Astrophysics Data System (ADS)

Barranco, Joseph; Pei, Suyang; Marcus, Phil; Jiang, Chung-Hsiang

2015-11-01

The Zombie Vortex Instability (ZVI) is a nonlinear instability in rotating, stratified, shear flows, such as in protoplanetary disks (PPD) of gas and dust orbiting new stars. The instability mechanism is the excitation of baroclinic critical layers, leading to vorticity amplification and nonlinear evolution into anticyclonic vortices and cyclonic sheets. ZVI is most robust when the Coriolis frequency, shear rate, and Brunt-Väisälä (BV) frequency are of the same order. Previously, we investigated ZVI with uniform stratification and without thermal cooling. Here, we explore the role of non-uniform stratification as would be found in PPDs in which the BV frequency is zero in the disk midplane, and increases away from the midplane. We find that ZVI is vigorous 1-3 pressure scale heights away from the midplane, but the non-isotropic turbulence generated by ZVI can penetrate into the midplane. We also explore the effect of thermal cooling and find that ZVI is still robust for cooling times as short as 5 orbital periods. ZVI may play important roles in transporting angular momentum in PPDs, and in trapping dust grains, which may trigger gravitational clumping into planetesimals.

Distinct retinal pathways drive spatial orientation behaviors in zebrafish navigation.

PubMed

Burgess, Harold A; Schoch, Hannah; Granato, Michael

2010-02-23

Navigation requires animals to adjust ongoing movements in response to pertinent features of the environment and select between competing target cues. The neurobiological basis of navigational behavior in vertebrates is hard to analyze, partly because underlying neural circuits are experience dependent. Phototaxis in zebrafish is a hardwired navigational behavior, performed at a stage when larvae swim by using a small repertoire of stereotyped movements. We established conditions to elicit robust phototaxis behavior and found that zebrafish larvae deploy directional orienting maneuvers and regulate forward swimming speed to navigate toward a target light. Using genetic analysis and targeted laser ablations, we show that retinal ON and OFF pathways play distinct roles during phototaxis. The retinal OFF pathway controls turn movements via retinotectal projections and establishes correct orientation by causing larvae to turn away from nontarget areas. In contrast, the retinal ON pathway activates the serotonergic system to trigger rapid forward swimming toward the target. Computational simulation of phototaxis with an OFF-turn, ON-approach algorithm verifies that our model accounts for key features of phototaxis and provides a simple and robust mechanism for behavioral choice between competing targets. Copyright 2010 Elsevier Ltd. All rights reserved.

Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.

PubMed

Diguet, Nicolas; Trammell, Samuel A J; Tannous, Cynthia; Deloux, Robin; Piquereau, Jérôme; Mougenot, Nathalie; Gouge, Anne; Gressette, Mélanie; Manoury, Boris; Blanc, Jocelyne; Breton, Marie; Decaux, Jean-François; Lavery, Gareth G; Baczkó, István; Zoll, Joffrey; Garnier, Anne; Li, Zhenlin; Brenner, Charles; Mericskay, Mathias

2018-05-22

Myocardial metabolic impairment is a major feature in chronic heart failure. As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, nicotinamide adenine dinucleotide (NAD + ) is emerging as a metabolic target in a number of diseases including heart failure. Little is known on the mechanisms regulating homeostasis of NAD + in the failing heart. To explore possible alterations of NAD + homeostasis in the failing heart, we quantified the expression of NAD + biosynthetic enzymes in the human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by Serum Response Factor transcription factor depletion in the heart (SRF HKO ) or of cardiac hypertrophy triggered by transverse aorta constriction. We studied the impact of NAD + precursor supplementation on cardiac function in both mouse models. We observed a 30% loss in levels of NAD + in the murine failing heart of both DCM and transverse aorta constriction mice that was accompanied by a decrease in expression of the nicotinamide phosphoribosyltransferase enzyme that recycles the nicotinamide precursor, whereas the nicotinamide riboside kinase 2 (NMRK2) that phosphorylates the nicotinamide riboside precursor is increased, to a higher level in the DCM (40-fold) than in transverse aorta constriction (4-fold). This shift was also observed in human failing heart biopsies in comparison with nonfailing controls. We show that the Nmrk2 gene is an AMP-activated protein kinase and peroxisome proliferator-activated receptor α responsive gene that is activated by energy stress and NAD + depletion in isolated rat cardiomyocytes. Nicotinamide riboside efficiently rescues NAD + synthesis in response to FK866-mediated inhibition of nicotinamide phosphoribosyltransferase and stimulates glycolysis in cardiomyocytes. Accordingly, we show that nicotinamide riboside supplementation in food attenuates the development of heart failure in mice, more robustly in DCM, and partially after transverse aorta constriction, by stabilizing myocardial NAD + levels in the failing heart. Nicotinamide riboside treatment also robustly increases the myocardial levels of 3 metabolites, nicotinic acid adenine dinucleotide, methylnicotinamide, and N1-methyl-4-pyridone-5-carboxamide, that can be used as validation biomarkers for the treatment. The data show that nicotinamide riboside, the most energy-efficient among NAD precursors, could be useful for treatment of heart failure, notably in the context of DCM, a disease with few therapeutic options. © 2017 American Heart Association, Inc.

Atypical Gaze Cueing Pattern in a Complex Environment in Individuals with ASD

ERIC Educational Resources Information Center

Zhao, Shuo; Uono, Shota; Yoshimura, Sayaka; Kubota, Yasutaka; Toichi, Motomi

2017-01-01

Clinically, social interaction, including gaze-triggered attention, has been reported to be impaired in autism spectrum disorder (ASD), but psychological studies have generally shown intact gaze-triggered attention in ASD. These studies typically examined gaze-triggered attention under simple environmental conditions. In real life, however, the…

MinD directly interacting with FtsZ at the H10 helix suggests a model for robust activation of MinC to destabilize FtsZ polymers.

PubMed

Taviti, Ashoka Chary; Beuria, Tushar Kant

2017-09-07

Cell division in bacteria is a highly controlled and regulated process. FtsZ, a bacterial cytoskeletal protein, forms a ring-like structure known as the Z-ring and recruits more than a dozen other cell division proteins. The Min system oscillates between the poles and inhibits the Z-ring formation at the poles by perturbing FtsZ assembly. This leads to an increase in the FtsZ concentration at the mid-cell and helps in Z-ring positioning. MinC, the effector protein, interferes with Z-ring formation through two different mechanisms mediated by its two domains with the help of MinD. However, the mechanism by which MinD triggers MinC activity is not yet known. We showed that MinD directly interacts with FtsZ with an affinity stronger than the reported MinC-FtsZ interaction. We determined the MinD-binding site of FtsZ using computational, mutational and biochemical analyses. Our study showed that MinD binds to the H10 helix of FtsZ. Single-point mutations at the charged residues in the H10 helix resulted in a decrease in the FtsZ affinity towards MinD. Based on our findings, we propose a novel model for MinCD-FtsZ interaction, where MinD through its direct interaction with FtsZ would trigger MinC activity to inhibit FtsZ functions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The Management of Long-Term Sickness Absence in Large Public Sector Healthcare Organisations: A Realist Evaluation Using Mixed Methods.

PubMed

Higgins, Angela; O'Halloran, Peter; Porter, Sam

2015-09-01

The success of measures to reduce long-term sickness absence (LTSA) in public sector organisations is contingent on organisational context. This realist evaluation investigates how interventions interact with context to influence successful management of LTSA. Multi-method case study in three Health and Social Care Trusts in Northern Ireland comprising realist literature review, semi-structured interviews (61 participants), Process-Mapping and feedback meetings (59 participants), observation of training, analysis of documents. Important activities included early intervention; workplace-based occupational rehabilitation; robust sickness absence policies with clear trigger points for action. Used appropriately, in a context of good interpersonal and interdepartmental communication and shared goals, these are able to increase the motivation of staff to return to work. Line managers are encouraged to take a proactive approach when senior managers provide support and accountability. Hindering factors: delayed intervention; inconsistent implementation of policy and procedure; lack of resources; organisational complexity; stakeholders misunderstanding each other's goals and motives. Different mechanisms have the potential to encourage common motivations for earlier return from LTSA, such as employees feeling that they have the support of their line manager to return to work and having the confidence to do so. Line managers' proactively engage when they have confidence in the support of seniors and in their own ability to address LTSA. Fostering these motivations calls for a thoughtful, diagnostic process, taking into account the contextual factors (and whether they can be modified) and considering how a given intervention can be used to trigger the appropriate mechanisms.

Ultrasound-triggered effects of the microbubbles coupled to GDNF- and Nurr1-loaded PEGylated liposomes in a rat model of Parkinson's disease.

PubMed

Yue, Peijian; Gao, Lin; Wang, Xuejing; Ding, Xuebing; Teng, Junfang

2018-06-01

The purpose of this study was to investigate ultrasound-triggered effects of the glial cell line-derived neurotrophic factor (GDNF) + nuclear receptor-related factor 1 (Nurr1)-polyethylene glycol (PEG)ylated liposomes-coupled microbubbles (PLs-GDNF + Nurr1-MBs) on behavioral impairment and neuron loss in a rat model of Parkinson's disease (PD). The unloaded PEGylated liposomes-coupled microbubbles (PLs-MBs) were characterized for zeta potential, particle size, and concentration. 6-hydroxydopamine (6-OHDA) was used to establish the PD rat model. Rotational, climbing pole, and suspension tests were used to detect behavioral impairment. The immunohistochemical staining of tyrosine hydroxylase (TH) and dopamine transporter (DAT) was used to assess the neuron loss. Western blot and quantitative real-time PCR (qRT-PCR) analysis were used to measure the expression levels of GDNF and Nurr1. The particle size of PLs-MBs was gradually increased, while the concentration and absolute zeta potential were gradually decreased as the time prolongs. 6-OHDA increased amphetamine-induced rotations and loss of dopaminergic neurons as compared to sham group. Interestingly, PLs-GDNF-MBs or PLs-Nurr1-MBs decreased rotations and increased the TH and DAT immunoreactivity. Combined of both genes resulted in a robust reduction in the rotations and a greater increase of the dopaminergic neurons. The delivery of PLs-GDNF + Nurr1-MBs into the brains using magnetic resonance imaging (MRI)-guided focused ultrasound may be more efficacious for the treatment of PD than the single treatment. © 2017 Wiley Periodicals, Inc.

Sleep Deprivation in Pigeons and Rats Using Motion Detection

PubMed Central

Newman, Sarah M.; Paletz, Elliott M.; Obermeyer, William H.; Benca, Ruth M.

2009-01-01

Study Objectives: Forced sleep deprivation results in substantial behavioral and physiologic effects in mammals. The disk-over-water (DOW) method produces a syndrome characterized by increased energy expenditure and a robust preferentially rapid-eye-movement sleep rebound upon recovery or eventual death after several weeks of sleep deprivation. The DOW has been used successfully only in rats. This paper presents a method to enforce long-term controlled sleep deprivation across species and to compare its effects in rats and pigeons. Design and Intervention: A conveyor was substituted for the DOW disk. Behavior rather than electroencephalography was used to trigger arousal stimuli, as in gentle-handling deprivation. Rats and pigeons were deprived using this apparatus, and the were compared with each other and with published reports. Measurements and Results: The physiologic consequences and recovery sleep in rats were like those published for DOW rats. Magnitude of sleep loss and recovery patterns in pigeons were similar to those seen in rats, but expected symptoms of the sleep deprivation syndrome were absent in pigeons. The use of a motion trigger allowed us to measure and, thus, to assess the quality and impact of the procedure. Conclusion: Prolonged and controlled sleep deprivation can be enforced using automated motion detection and a conveyor-over-water system. Pigeons and rats, deprived of sleep to the same extent, showed similar patterns of recovery sleep, but pigeons did not exhibit the hyperphagia, weight loss, and debilitation seen in rats. Citation: Newman SM; Paletz EM; Obermeyer WH; Benca RM. Sleep Deprivation In Pigeons And Rats Using Motion Detection. SLEEP 2009;32(10):1299-1312. PMID:19848359

Detecting Periprocedural Myocardial Infarction in Contemporary Percutaneous Coronary Intervention Trials.

PubMed

Spitzer, Ernest; de Vries, Ton; Cavalcante, Rafael; Tuinman, Marieke; Rademaker-Havinga, Tessa; Alkema, Maaike; Morel, Marie-Angele; Soliman, Osama I; Onuma, Yoshinobu; van Es, Gerrit-Anne; Tijssen, Jan G P; McFadden, Eugene; Serruys, Patrick W

2017-04-10

This study sought to investigate the differences in detecting (e.g., triggering) periprocedural myocardial infarction (PMI) among 3 current definitions. PMI is a frequent component of primary endpoints in coronary device trials. Identification of all potential suspected events is critical for accurate event ascertainment. Automatic triggers based on study databases prevent underreporting of events. We generated automated algorithms to trigger PMI based on each definition and compared results using data from the RESOLUTE all comers trial. The operationalization of current PMI definitions was achieved by defining programmable algorithms used to interrogate the study database. From a total of 636 PMI triggers, we identified 234 for the World Health Organization extended definition, 382 for the Third Universal definition, and 216 for the Society for Cardiovascular Angiography and Interventions definition. Differences among the biomarkers used, different cutoff values, and in the hierarchy among biomarkers within definitions, yielded a different number of triggers, and identified unique triggers for each definition. Only 38 triggers were consistently identified by all definitions. Availability of ECG data, eCRF data on clinical presentation, and the reporting of >2 post-procedural values of the same biomarker influenced considerably the number of PMI triggers identified. PMI definitions are not interchangeable. The number of triggers identified and consequently the potential number of events varies significantly, highlighting the importance of rigorous methodology when PMI is a component of a powered endpoint. Emphasis on collection of biomarkers, ECG data, and clinical status at baseline may improve the correct identification of PMI triggers. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Dual trigger of triptorelin and HCG optimizes clinical outcome for high ovarian responder in GnRH-antagonist protocols.

PubMed

Li, Saijiao; Zhou, Danni; Yin, Tailang; Xu, Wangming; Xie, Qingzhen; Cheng, Dan; Yang, Jing

2018-01-12

In this paper, a retrospective cohort study was conducted to the high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. The purpose of the study is to investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) can improve the clinical outcome compared with traditional dose (10000IU) HCG trigger and low-dose (8000IU) HCG trigger for high ovarian responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Our study included 226 couples with high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. Standard dosage of HCG trigger (10000 IU of recombinant HCG) versus dual trigger (0.2 mg of triptorelin and 2000 IU of recombinant HCG) and low-dose HCG trigger (8000IU of recombinant HCG) were used for final oocyte maturation. Our main outcome measures were high quality embryo rate, the number of usable embryos, the risk of OHSS, duration of hospitalization and incidence rate of complications. Our evidence demonstrated that dual trigger is capable of preventing severe OHSS while still maintaining excellent high quality embryo rate in in high ovarian responders of GnRH-antagonist protocols.

Endotoxins in Environmental and Clinical Samples Assessed by GC-Tandem MS

NASA Astrophysics Data System (ADS)

Szponar, Bogumila

Bacteria appeared on the Earth millions years before us and human evolution was triggered by the constant presence of pathogenic and symbiotic microorganisms in our surroundings. Interplay occurred between higher organism and microbial consortia residing in the host organs and on the epithelial surfaces; another natural space of bacteria-human interaction is the indoor environment where we spend the majority of our lifetime. Indoor microbial exposure affects our well-being and can result in respiratory symptoms, such as allergies and asthma, since both dead and live microorganisms and their cell constituents, including lipopolysaccharides (LPS, endotoxins), interact with our immune system. Thus, there is a demand for robust tools for qualitative and quantitative determination of the microbial communities that we are exposed to.

Reconfigurable ultra-thin film GDNMOS device for ESD protection in 28 nm FD-SOI technology

NASA Astrophysics Data System (ADS)

Athanasiou, Sotirios; Legrand, Charles-Alexandre; Cristoloveanu, Sorin; Galy, Philippe

2017-02-01

We propose a novel ESD protection device (GDNMOS: Gated Diode merged NMOS) fabricated with 28 nm UTBB FD-SOI high-k metal gate technology. By modifying the combination of the diode and transistor gate stacks, the robustness of the device is optimized, achieving a maximum breakdown voltage (VBR) of 4.9 V. In addition, modifications of the gate length modulate the trigger voltage (Vt1) with a minimum value of 3.5 V. Variable electrostatic doping (gate-induced) in diode and transistor body enables reconfigurable operation. A lower doping of the base enhances the bipolar gain, leading to thyristor behavior. This innovative architecture demonstrates excellent capability for high-voltage protection while maintaining a latch-up free behavior.

Self-Replicating Cracks: A Collaborative Fracture Mode in Thin Films

NASA Astrophysics Data System (ADS)

Marthelot, Joël; Roman, Benoît; Bico, José; Teisseire, Jérémie; Dalmas, Davy; Melo, Francisco

2014-08-01

Straight cracks are observed in thin coatings under residual tensile stress, resulting into the classical network pattern observed in china crockery, old paintings, or dry mud. Here, we present a novel fracture mechanism where delamination and propagation occur simultaneously, leading to the spontaneous self-replication of an initial template. Surprisingly, this mechanism is active below the standard critical tensile load for channel cracks and selects a robust interaction length scale on the order of 30 times the film thickness. Depending on triggering mechanisms, crescent alleys, spirals, or long bands are generated over a wide range of experimental parameters. We describe with a simple physical model, the selection of the fracture path and provide a configuration diagram displaying the different failure modes.

Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

PubMed

Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

2016-11-01

This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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.

Tidal Triggering of Microearthquakes Over an Eruption Cycle at 9°50'N East Pacific Rise

NASA Astrophysics Data System (ADS)

Tan, Yen Joe; Tolstoy, Maya; Waldhauser, Felix; Bohnenstiehl, DelWayne R.

2018-02-01

Studies have found that earthquake timing often correlates with tides at mid-ocean ridges and some terrestrial settings. Studies have also suggested that tidal triggering may preferentially happen when a region is critically stressed, making it a potential tool to forecast earthquakes and volcanic eruptions. We examine tidal triggering of ˜100,000 microearthquakes near 9°50'N East Pacific Rise recorded between October 2003 and January 2007, which encompasses an eruption in January 2006. This allows us to look at how tidal triggering signal varies over an eruption cycle to examine its utility as a forecasting tool. We find that tidal triggering signal is strong but does not vary systematically in the 2+ years leading up to the eruption. However, tidal triggering signal disappears immediately posteruption. Our findings suggest that tidal triggering variation may not be useful for forecasting mid-ocean ridge eruptions over a 2+ year timescale but might be useful over a longer timescale.

Systematic Detection of Remotely Triggered Seismicity in Africa Following Recent Large Earthquakes

NASA Astrophysics Data System (ADS)

Ayorinde, A. O.; Peng, Z.; Yao, D.; Bansal, A. R.

2016-12-01

It is well known that large distant earthquakes can trigger micro-earthquakes/tectonic tremors during or immediately following their surface waves. Globally, triggered earthquakes have been mostly found in active plate boundary regions. It is not clear whether they could occur within stable intraplate regions in Africa as well as the active East African Rift Zone. In this study we conduct a systematic study of remote triggering in Africa following recent large earthquakes, including the 2004 Mw9.1 Sumatra and 2012 Mw8.6 Indian Ocean earthquakes. In particular, the 2012 Indian Ocean earthquake is the largest known strike slip earthquake and has triggered a global increase of magnitude larger than 5.5 earthquakes as well as numerous micro-earthquakes/tectonic tremors around the world. The entire Africa region was examined for possible remotely triggered seismicity using seismic data downloaded from the Incorporated Research Institutes for Seismology (IRIS) Data Management Center (DMC) and GFZ German Research Center for Geosciences. We apply a 5-Hz high-pass-filter to the continuous waveforms and visually identify high-frequency signals during and immediately after the large amplitude surface waves. Spectrograms are computed as additional tools to identify triggered seismicities and we further confirm them by statistical analysis comparing the high-frequency signals before and after the distant mainshocks. So far we have identified possible triggered seismicity in Botswana and northern Madagascar. This study could help to understand dynamic triggering in diverse tectonic settings of the African continent.

Metabolic phenotyping of a model of adipocyte differentiation

PubMed Central

Roberts, Lee D.; Virtue, Sam; Vidal-Puig, Antonio; Nicholls, Andrew W.

2009-01-01

The 3T3-L1 murine cell line is a robust and widely used model for the study of adipogenesis and processes occurring in mature adipocytes. The fibroblastic like cells can be induced by hormones to differentiate into mature adipocytes. In this study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell line has been studied using gas chromatography-mass spectrometry, 1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct infusion-mass spectrometry, and 13C substrate labeling in conjunction with multivariate statistics. The changes in metabolite concentrations at distinct periods during differentiation have been defined including alterations in the TCA cycle, glycolysis, the production of odd chain fatty acids by α-oxidation, fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, and trans-esterification to produce complex lipids. The metabolic changes induced during differentiation of the 3T3-L1 cell line were then compared with the metabolic differences between pre- and postdifferentiation primary adipocytes. These metabolic alterations reflect the changing role of the 3T3-L1 cells during differentiation, as well as possibly providing metabolic triggers to stimulate the processes which occur during differentiation. PMID:19602617

Exploration of the Kinetics of Toehold-Mediated Strand Displacement via Plasmon Rulers.

PubMed

Li, Mei-Xing; Xu, Cong-Hui; Zhang, Nan; Qian, Guang-Sheng; Zhao, Wei; Xu, Jing-Juan; Chen, Hong-Yuan

2018-04-24

DNA/RNA strand displacement is one of the most fundamental reactions in DNA and RNA circuits and nanomachines. In this work, we reported an exploration of the dynamic process of the toehold-mediated strand displacement via core-satellite plasmon rulers at the single-molecule level. Applying plasmon rulers with unlimited lifetime, single-strand displacement triggered by the invader that resulted in stepwise leaving of satellite from the core was continuously monitored by changes of scattering signal for hours. The kinetics of strand displacement in vitro with three different toehold lengths have been investigated. Also, the study revealed the difference in the kinetics of strand displacement between DNA/RNA and DNA/DNA duplexes. For the kinetics study in vivo, influence from the surrounding medium has been evaluated using both phosphate buffer and cell lysate. Applying core-satellite plasmon rulers with high signal/noise ratio, kinetics study in living cells proceeded for the first time, which was not possible by conventional methods with a fluorescent reporter. The plasmon rulers, which are flexible, easily constructed, and robust, have proven to be effective tools in exploring the dynamical behaviors of biochemical reactions in vivo.

Quantifying the impact of Teleconnections on Hydrologic Regimes in Texas

NASA Astrophysics Data System (ADS)

Bhatia, N.; Singh, V. P.; Srivastav, R. K.

2016-12-01

Climate change is being alleged to have led to the increased frequency of extreme flooding events and the resulting damages are severe, especially where the flood-plain population densities are higher. Much research in the field of hydroclimatology is focusing on improving real-time flood forecasting models. Recent studies show that, in the state of Texas, extreme regional floods are actually triggered by abruptly higher precipitation intensities. Such intensities are further driven by sea-surface temperature and pressure anomalies, defined by certain patterns of teleconnections. In this study, climate variability is defined on the basis of five major Atlantic and Pacific Ocean related teleconnections: (i) Atlantic Multidecadal Oscillation (AMO), (ii) North Atlantic Oscillation (NAO), (iii) Pacific Decadal Oscillation (PDO), (iv) Pacific North American Pattern (PNA), and (v) Southern Oscillation Index (SOI). Hydrologic extremes will be modeled using probabilistic distributions. Leave-One-Out-Test (LOOT) will be employed to address the outliers in the extremes, and to eventually obtain the robust correlation coefficient. The variation in the effect of most correlated teleconnection with respect to hydrologic attributes will be investigated for the entire state. This study will attempt to identify potential teleconnection inputs for data-driven hydrologic models under varying climatic conditions.

Analysis of Trigger Factors in Episodic Migraineurs Using a Smartphone Headache Diary Applications

PubMed Central

Park, Jeong-Wook; Chu, Min Kyung; Kim, Jae-Moon; Park, Sang-Gue; Cho, Soo-Jin

2016-01-01

Background Various stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application. Method Episodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors. Results Sixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches) were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (p<0.001), headache-related disability (p<0.001), abortive medication use (p = 0.02), and the proportion of migraine (p < 0.001), relative to those without trigger factors. Traveling (odd ratios [OR]: 6.4), hormonal changes (OR: 3.5), noise (OR: 2.8), alcohol (OR: 2.5), overeating (OR: 2.4), and stress (OR:1.8) were significantly associated with migraines compared to non-migraine headaches. The headaches that were associated with hormonal changes or noise were more often migraines, regardless of the preventive medication. The headaches due to stress, overeating, alcohol, and traveling were more often migraines without preventive medication, but it was not evident with preventive medication. Conclusion Smartphone headache diary application is an effective tool to assess migraine trigger factors. The headaches with trigger factors had greater severity or migraine features. The type of triggers and the presence of preventive medication influenced the headache characteristics; hence, an investigation of trigger factors would be helpful in understanding migraine occurrences. PMID:26901341

Analysis of Trigger Factors in Episodic Migraineurs Using a Smartphone Headache Diary Applications.

PubMed

Park, Jeong-Wook; Chu, Min Kyung; Kim, Jae-Moon; Park, Sang-Gue; Cho, Soo-Jin

2016-01-01

Various stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application. Episodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors. Sixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches) were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (p<0.001), headache-related disability (p<0.001), abortive medication use (p = 0.02), and the proportion of migraine (p < 0.001), relative to those without trigger factors. Traveling (odd ratios [OR]: 6.4), hormonal changes (OR: 3.5), noise (OR: 2.8), alcohol (OR: 2.5), overeating (OR: 2.4), and stress (OR:1.8) were significantly associated with migraines compared to non-migraine headaches. The headaches that were associated with hormonal changes or noise were more often migraines, regardless of the preventive medication. The headaches due to stress, overeating, alcohol, and traveling were more often migraines without preventive medication, but it was not evident with preventive medication. Smartphone headache diary application is an effective tool to assess migraine trigger factors. The headaches with trigger factors had greater severity or migraine features. The type of triggers and the presence of preventive medication influenced the headache characteristics; hence, an investigation of trigger factors would be helpful in understanding migraine occurrences.

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.

Transformation in the pharmaceutical industry--a systematic review of the literature.

PubMed

Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J; Mouzughi, Yusra

2013-01-01

The evolutionary development of pharmaceutical transformation was studied through systematic review of the literature. Fourteen triggers were identified that will affect the pharmaceutical business, regulatory science, and enabling technologies in future years. The relative importance ranking of the transformation triggers was computed based on their prevalence within the articles studied. The four main triggers with the strongest literature evidence were Fully Integrated Pharma Network, Personalized Medicine, Translational Research, and Pervasive Computing. The theoretical quality risks for each of the four main transformation triggers are examined, and the remaining ten triggers are described. The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities (this is termed pharmaceutical transformation). The impact of these changes on the approaches to quality risk management requires more understanding. In this paper, a comprehensive review of the academic, regulatory, and industry literature were used to identify 14 triggers that influence pharmaceutical transformation. The four main triggers, namely Fully Integrated Pharma Network, Personalized Medicine, Translational Research, and Pervasive Computing, were selected as the most important based on the strength of the evidence found during the literature review activity described in this paper. Theoretical quality risks for each of the four main transformation triggers are examined, and the remaining ten triggers are described.

An efficient approach to detection of weak seismic events at the Groningen gas field in the Netherlands

NASA Astrophysics Data System (ADS)

Wyer, P.; Zurek, B.

2017-12-01

Extensive additions to the Royal Dutch Meteorological Institute (KNMI) seismic monitoring network over recent years have yielded corresponding gains in detection of low magnitude seismicity induced by production of the Groningen gas field. A review of the weakest events in the seismic catalog demonstrates that waveforms from individual stations in the 30 x 35 km network area overlap sufficiently for normalized analytic envelopes to be constructively stacked without compensation for moveout, detection of individual station triggers or the need for more advanced approaches such as template matching. This observation opens the possibility of updating the historical catalog to current detection levels without having to implement more computationally expensive steps when reprocessing the legacy continuous data. A more consistent long term catalog would better constrain the frequency-size distribution (Gutenberg-Richter relationship) and provide a richer dataset for calibration of geomechanical and seismological models. To test the viability of a direct stacking approach, normalized waveform envelopes are partitioned by station into two discrete RMS stacks. Candidate seismic events are then identified as simultaneous STA/LTA triggers on both stacks. This partitioning has a minor impact on signal, but avoids the majority of false detections otherwise obtained on a single stack. Undesired detection of anthropogenic sources and earthquakes occurring outside the field can be further minimized by tuning the waveform frequency filters and trigger configuration. After minimal optimization, data from as few as 14 legacy stations are sufficient for robust automatic detection of known events approaching ML0 from the recent catalog. Ongoing work will determine residual false detection rates and whether previously unknown past events can be detected with sensitivities comparable to the modern KNMI catalog.

Cytosolic proteins can exploit membrane localization to trigger functional assembly

PubMed Central

2018-01-01

Cell division, endocytosis, and viral budding would not function without the localization and assembly of protein complexes on membranes. What is poorly appreciated, however, is that by localizing to membranes, proteins search in a reduced space that effectively drives up concentration. Here we derive an accurate and practical analytical theory to quantify the significance of this dimensionality reduction in regulating protein assembly on membranes. We define a simple metric, an effective equilibrium constant, that allows for quantitative comparison of protein-protein interactions with and without membrane present. To test the importance of membrane localization for driving protein assembly, we collected the protein-protein and protein-lipid affinities, protein and lipid concentrations, and volume-to-surface-area ratios for 46 interactions between 37 membrane-targeting proteins in human and yeast cells. We find that many of the protein-protein interactions between pairs of proteins involved in clathrin-mediated endocytosis in human and yeast cells can experience enormous increases in effective protein-protein affinity (10–1000 fold) due to membrane localization. Localization of binding partners thus triggers robust protein complexation, suggesting that it can play an important role in controlling the timing of endocytic protein coat formation. Our analysis shows that several other proteins involved in membrane remodeling at various organelles have similar potential to exploit localization. The theory highlights the master role of phosphoinositide lipid concentration, the volume-to-surface-area ratio, and the ratio of 3D to 2D equilibrium constants in triggering (or preventing) constitutive assembly on membranes. Our simple model provides a novel quantitative framework for interpreting or designing in vitro experiments of protein complexation influenced by membrane binding. PMID:29505559

In situ amplified electrochemical aptasensing for sensitive detection of adenosine triphosphate by coupling target-induced hybridization chain reaction with the assembly of silver nanotags.

PubMed

Zhou, Qian; Lin, Youxiu; Lin, Yuping; Wei, Qiaohua; Chen, Guonan; Tang, Dianping

2016-01-01

Biomolecular immobilization and construction of the sensing platform are usually crucial for the successful development of a high-efficiency detection system. Herein we report on a novel and label-free signal-amplified aptasensing for sensitive electrochemical detection of small molecules (adenosine triphosphate, ATP, used in this case) by coupling with target-induced hybridization chain reaction (HCR) and the assembly of electroactive silver nanotags. The system mainly consisted of two alternating hairpin probes, a partial-pairing trigger-aptamer duplex DNA and a capture probe immobilized on the electrode. Upon target ATP introduction, the analyte attacked the aptamer and released the trigger DNA, which was captured by capture DNA immobilized on the electrode to form a newly partial-pairing double-stranded DNA. Thereafter, the exposed domain at trigger DNA could be utilized as the initator strand to open the hairpin probes in sequence, and propagated a chain reaction of hybridization events between two alternating hairpins to form a long nicked double-helix. The electrochemical signal derived from the assembled silver nanotags on the nicked double-helix. Under optimal conditions, the electrochemical aptasensor could exhibit a high sensitivity and a low detection limit, and allowed the detection of ATP at a concentration as low as 0.03 pM. Our design showed a high selectivity for target ATP against its analogs because of the high-specificity ATP-aptamer reaction, and its applicable for monitoring ATP in the spiking serum samples. Improtantly, the distinct advantages of the developed aptasensor make it hold a great potential for the development of simple and robust sensing strategies for the detection of other small molecules by controlling the apatmer sequence. Copyright © 2015 Elsevier B.V. All rights reserved.

Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages.

PubMed

Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto; Becker, María Inés

2016-06-01

Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5 Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. Copyright © 2016 by The American Association of Immunologists, Inc.

Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages

PubMed Central

Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto

2016-01-01

Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5. Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. PMID:27183578

Headache triggers in the US military.

PubMed

Theeler, Brett J; Kenney, Kimbra; Prokhorenko, Olga A; Fideli, Ulgen S; Campbell, William; Erickson, Jay C

2010-05-01

Headaches can be triggered by a variety of factors. Military service members have a high prevalence of headache but the factors triggering headaches in military troops have not been identified. The objective of this study is to determine headache triggers in soldiers and military beneficiaries seeking specialty care for headaches. A total of 172 consecutive US Army soldiers and military dependents (civilians) evaluated at the headache clinics of 2 US Army Medical Centers completed a standardized questionnaire about their headache triggers. A total of 150 (87%) patients were active-duty military members and 22 (13%) patients were civilians. In total, 77% of subjects had migraine; 89% of patients reported at least one headache trigger with a mean of 8.3 triggers per patient. A wide variety of headache triggers was seen with the most common categories being environmental factors (74%), stress (67%), consumption-related factors (60%), and fatigue-related factors (57%). The types of headache triggers identified in active-duty service members were similar to those seen in civilians. Stress-related triggers were significantly more common in soldiers. There were no significant differences in trigger types between soldiers with and without a history of head trauma. Headaches in military service members are triggered mostly by the same factors as in civilians with stress being the most common trigger. Knowledge of headache triggers may be useful for developing strategies that reduce headache occurrence in the military.

Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

PubMed Central

An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-01-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

Impacts of ESD Reliability by Different Layout Engineering in the 0.25-μm 60-V High-Voltage LDMOS Devices

NASA Astrophysics Data System (ADS)

Chen, Shen-Li; Lin, Chun-Ju; Yu-Ting, Huang

2018-02-01

How to effectively enhance the reliability robustness in high-voltage (HV) BCD [(bipolar) complementary metal-oxide semiconductor (CMOS) diffusion metaloxide semiconductor (DMOS)] processes is an important issue. Influences of layouttype dependences on anti-electrostatic discharge (ESD) robustness in a 0.25-μm 60-V process will be studied in this chapter, which includes, in part (1), the traditional striped-type n-channel lateral-diffused MOSFET (nLDMOS), waffle-type nLDMOS, and nLDMOS embedded with a "p-n-p"-arranged silicon-controlled rectifier (SCR) devices in the drain side; and in part (2) a p-channel LDMOS (pLDMOS) with an embedded "p-n-p-n-p"-arranged-type SCR in the drain side (diffusion regions of the drain side is P+-N+-P+-N+-P+). Then, these LDMOS devices are used to evaluate the influence of layout architecture on trigger voltage (Vt1), holding voltage (Vh), and secondary breakdown current (It2). Eventually, the sketching of the layout pattern of a HV LDMOS is a very important issue in the anti-ESD consideration. Also, in part (1), the waffle-type nLDMOS DUT contributes poorly to It2 robustness due to the non-uniform turned-on phenomenon and a narrow channel width per unit finger. Therefore, the It2 robustness of a waffle-type nLDMOS device is decreased about 17% as compared to a traditional striped-type nLDMOS device (reference DUT-1). The ESD abilities of traditional stripedtype and waffle-type nLDMOS devices with an embedded SCR ("p-n-p"-manner arrangement in the drain side) are better than a traditional nLDMOS 224.4% in average. Noteworthy, the nLDMOS-SCR with the "p-n-p" -arranged-type in the drainend is a good structure for the anti-ESD reliability especially in HV usages. Furthermore, in part (2) this layout manner of P+ discrete-island distributions in the drain-side have some impacts on the anti-ESD and anti-latch-up (LU) immunities. All of their It2 values have reached above 6 A; however, the major repercussion is that the Vh value will be decreased about 66.7 73.7%.

Study on the plasma generation characteristics of an induction-triggered coaxial pulsed plasma thruster

NASA Astrophysics Data System (ADS)

Weisheng, CUI; Wenzheng, LIU; Jia, TIAN; Xiuyang, CHEN

2018-02-01

At present, spark plugs are used to trigger discharge in pulsed plasma thrusters (PPT), which are known to be life-limiting components due to plasma corrosion and carbon deposition. A strong electric field could be formed in a cathode triple junction (CTJ) to achieve a trigger function under vacuum conditions. We propose an induction-triggered electrode structure on the basis of the CTJ trigger principle. The induction-triggered electrode structure could increase the electric field strength of the CTJ without changing the voltage between electrodes, contributing to a reduction in the electrode breakdown voltage. Additionally, it can maintain the plasma generation effect when the breakdown voltage is reduced in the discharge experiments. The induction-triggered electrode structure could ensure an effective trigger when the ablation distance of Teflon increases, and the magnetic field produced by the discharge current could further improve the plasma density and propagation velocity. The induction-triggered coaxial PPT we propose has a simplified trigger structure, and it is an effective attempt to optimize the micro-satellite thruster.

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.

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.

Robust Representation of Integrated Surface-subsurface Hydrology at Watershed Scales

NASA Astrophysics Data System (ADS)

Painter, S. L.; Tang, G.; Collier, N.; Jan, A.; Karra, S.

2015-12-01

A representation of integrated surface-subsurface hydrology is the central component to process-rich watershed models that are emerging as alternatives to traditional reduced complexity models. These physically based systems are important for assessing potential impacts of climate change and human activities on groundwater-dependent ecosystems and water supply and quality. Integrated surface-subsurface models typically couple three-dimensional solutions for variably saturated flow in the subsurface with the kinematic- or diffusion-wave equation for surface flows. The computational scheme for coupling the surface and subsurface systems is key to the robustness, computational performance, and ease-of-implementation of the integrated system. A new, robust approach for coupling the subsurface and surface systems is developed from the assumption that the vertical gradient in head is negligible at the surface. This tight-coupling assumption allows the surface flow system to be incorporated directly into the subsurface system; effects of surface flow and surface water accumulation are represented as modifications to the subsurface flow and accumulation terms but are not triggered until the subsurface pressure reaches a threshold value corresponding to the appearance of water on the surface. The new approach has been implemented in the highly parallel PFLOTRAN (www.pflotran.org) code. Several synthetic examples and three-dimensional examples from the Walker Branch Watershed in Oak Ridge TN demonstrate the utility and robustness of the new approach using unstructured computational meshes. Representation of solute transport in the new approach is also discussed. Notice: This manuscript has been authored by UT-Battelle, LLC, under Contract No. DE-AC0500OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for the United States Government purposes.

How to Minimize the Attack Rate during Multiple Influenza Outbreaks in a Heterogeneous Population

PubMed Central

Fung, Isaac Chun-Hai; Antia, Rustom; Handel, Andreas

2012-01-01

Background If repeated interventions against multiple outbreaks are not feasible, there is an optimal level of control during the first outbreak. Any control measures above that optimal level will lead to an outcome that may be as sub-optimal as that achieved by an intervention that is too weak. We studied this scenario in more detail. Method An age-stratified ordinary-differential-equation model was constructed to study infectious disease outbreaks and control in a population made up of two groups, adults and children. The model was parameterized using influenza as an example. This model was used to simulate two consecutive outbreaks of the same infectious disease, with an intervention applied only during the first outbreak, and to study how cumulative attack rates were influenced by population composition, strength of inter-group transmission, and different ways of triggering and implementing the interventions. We assumed that recovered individuals are fully immune and the intervention does not confer immunity. Results/Conclusion The optimal intervention depended on coupling between the two population sub-groups, the length, strength and timing of the intervention, and the population composition. Population heterogeneity affected intervention strategies only for very low cross-transmission between groups. At more realistic values, coupling between the groups led to synchronization of outbreaks and therefore intervention strategies that were optimal in reducing the attack rates for each subgroup and the population overall coincided. For a sustained intervention of low efficacy, early intervention was found to be best, while at high efficacies, a delayed start was better. For short interventions, a delayed start was always advantageous, independent of the intervention efficacy. For most scenarios, starting the intervention after a certain cumulative proportion of children were infected seemed more robust in achieving close to optimal outcomes compared to a strategy that used a specified duration after an outbreak’s beginning as the trigger. PMID:22701558

Use of Archival Sources to Improve Water-Related Hazard Assessments at Volcán de Agua, Guatemala

NASA Astrophysics Data System (ADS)

Hutchison, A. A.; Cashman, K. V.; Rust, A.; Williams, C. A.

2013-12-01

This interdisciplinary study focuses on the use of archival sources from the 18th Century Spanish Empire to develop a greater understanding of mudflow trigger mechanisms at Volcán de Agua in Guatemala. Currently, hazard assessments of debris flows at Volcán de Agua are largely based on studies of analogous events, such as the mudflow at Casita Volcano in 1998 caused by excessive rainfall generated by Hurricane Mitch. A preliminary investigation of Spanish archival sources, however, indicates that a damaging mudflow from the volcano in 1717 may have been triggered by activity at the neighbouring Volcán de Fuego. A VEI 4 eruption of Fuego in late August 1717 was followed by 33 days of localized 'retumbos' and then a major local earthquake with accompanying mudflows from several 'bocas' on the southwest flank of Agua. Of particular importance for this study is an archival source from Archivos Generales de Centro América (AGCA) that consists of a series of letters, petitions and witness statements that were written and gathered following the catastrophic events of 1717. Their purpose was to argue for royal permission to relocate the capital city, which at the time was located on the lower flanks of Volcán de Agua. Within these documents there are accounts of steaming 'avenidas' of water with sulphurous smells, and quantitative descriptions that suggest fissure formation related to volcanic activity at Volcán de Fuego. Clear evidence for volcano-tectonic activity at the time, combined with the fact there is no mention of rainfall in the documents, suggest that outbursts of mud from Agua's south flank may have been caused by a volcanic perturbation of a hydrothermal system. This single example suggests that further analysis of archival documents will provide a more accurate and robust assessment of water related hazards at Volcán de Agua than currently exists.

Landslide triggering thresholds for Switzerland based on a new gridded precipitation dataset

NASA Astrophysics Data System (ADS)

Leonarduzzi, Elena; Molnar, Peter; McArdell, Brian W.

2017-04-01

In Switzerland floods are responsible for most of the damage caused by rainfall-triggered natural hazards (89%), followed by landslides (6%, ca. 520 M Euros) as reported in Hilker et al. (2009) for the period 1972-2007. The prediction of landslide occurrence is particularly challenging because of their wide distribution in space and the complex interdependence of predisposing and triggering factors. The overall goal of our research is to develop an Early Warning System for landsliding in Switzerland based on hydrological modelling and rainfall forecasts. In order to achieve this, we first analyzed rainfall triggering thresholds for landslides from a new gridded daily precipitation dataset (RhiresD, MeteoSwiss) for Switzerland combined with landslide events recorded in the Swiss Damage Database (Hilker et al.,2009). The high-resolution gridded precipitation dataset allows us to collocate rainfall and landslides accurately in space, which is an advantage over many previous studies. Each of the 2272 landslides in the database in the period 1972-2012 was assigned to the corresponding 2x2 km precipitation cell. For each of these cells, precipitation events were defined as series of consecutive rainy days and the following event parameters were computed: duration (day), maximum and mean daily intensity (mm/day), total rainfall depth (mm) and maximum daily intensity divided by Mean Daily Precipitation (MDP). The events were classified as triggering or non-triggering depending on whether a landslide was recorded in the cell during the event. This classification of observations was compared to predictions based on a threshold for each of the parameters. The predictive power of each parameter and the best threshold value were quantified by ROC analysis and statistics such as AUC and the True Skill Statistic (TSS). Event parameters based on rainfall intensity were found to have similarly high predictive power (TSS=0.54-0.59, AUC=0.85-0.86), while rainfall duration had a significantly lower predictive power (TSS=0.24 and AUC=0.65). Slightly better performances were obtained when considering a typical power law intensity-duration curve as threshold (TSS=0.6). The analysis was repeated for sub-regions of the country based on erosivity and climate, using MDP and erodibility (Kuehni and Pfiffner, 2001), or a combination thereof, in the classification. When defining regional maximum intensity thresholds, the performances were further improved in all cases: for erodibility (TSS +1.3%), for MDP (TSS +3%), and for a combination of the two (TSS +5.1%). The regional maximum daily intensity thresholds varied greatly among classes, with differences of up to 43 mm/day, and they increased with decreasing erodibility and increasing MDP. This result was confirmed by considering the conditional probability of a landslide, which showed that for a given rainfall intensity the probability of a landslide in a region with wetter climate (higher MDP) is lower than that in a drier climate (lower MDP). This suggests the existence of a landscape balance between climate, erosion and soil formation. In order to demonstrate the quality and robustness of the results, we also show reference cases obtained by randomization of landslides in space and time, and resampling the data to equal sample size between triggering and non-triggering events (prevalence). Hilker, N., Badoux, A., & Hegg, C. (2009). The swiss flood and landslide damage database 1972-2007. Natural Hazards and Earth System Science, 9(3), 913-925. https://doi.org/10.1002/asl.183 Kühni, A., & Pfiffner, O. A. (2001). The relief of the Swiss Alps and adjacent areas and its relation to lithology and structure: Topographic analysis from a 250-m DEM. Geomorphology, 41(4), 285-307. https://doi.org/10.1016/S0169-555X(01)00060-5

Influence of supraliminal reward information on unconsciously triggered response inhibition.

PubMed

Diao, Liuting; Ding, Cody; Qi, Senqing; Zeng, Qinghong; Huang, Bo; Xu, Mengsi; Fan, Lingxia; Yang, Dong

2014-01-01

Although executive functions (e.g., response inhibition) are often thought to interact consciously with reward, recent studies have demonstrated that they can also be triggered by unconscious stimuli. Further research has suggested a close relationship between consciously and unconsciously triggered response inhibition. To date, however, the effect of reward on unconsciously triggered response inhibition has not been explored. To address this issue, participants in this study performed runs of a modified Go/No-Go task during which they were exposed to both high and low value monetary rewards presented both supraliminally and subliminally. Participants were informed that they would earn the reward displayed if they responded correctly to each trial of the run. According to the results, when rewards were presented supraliminally, a greater unconsciously triggered response inhibition was observed for high-value rewards than for low-value rewards. In contrast, when rewards were presented subliminally, no enhanced unconsciously triggered response inhibition was observed. Results revealed that supraliminal and subliminal rewards have distinct effects on unconsciously triggered response inhibition. These findings have important implications for extending our understanding of the relationship between reward and response inhibition.

Influence of Supraliminal Reward Information on Unconsciously Triggered Response Inhibition

PubMed Central

Diao, Liuting; Ding, Cody; Qi, Senqing; Zeng, Qinghong; Huang, Bo; Xu, Mengsi; Fan, Lingxia; Yang, Dong

2014-01-01

Although executive functions (e.g., response inhibition) are often thought to interact consciously with reward, recent studies have demonstrated that they can also be triggered by unconscious stimuli. Further research has suggested a close relationship between consciously and unconsciously triggered response inhibition. To date, however, the effect of reward on unconsciously triggered response inhibition has not been explored. To address this issue, participants in this study performed runs of a modified Go/No-Go task during which they were exposed to both high and low value monetary rewards presented both supraliminally and subliminally. Participants were informed that they would earn the reward displayed if they responded correctly to each trial of the run. According to the results, when rewards were presented supraliminally, a greater unconsciously triggered response inhibition was observed for high-value rewards than for low-value rewards. In contrast, when rewards were presented subliminally, no enhanced unconsciously triggered response inhibition was observed. Results revealed that supraliminal and subliminal rewards have distinct effects on unconsciously triggered response inhibition. These findings have important implications for extending our understanding of the relationship between reward and response inhibition. PMID:25268227

Triggers of acute attacks of gout, does age of gout onset matter? A primary care based cross-sectional study.

PubMed

Abhishek, Abhishek; Valdes, Ana M; Jenkins, Wendy; Zhang, Weiya; Doherty, Michael

2017-01-01

To determine the proportion of people with gout who self-report triggers of acute attacks; identify the commonly reported triggers, and examine the disease and demographic features associated with self-reporting any trigger(s) of acute attacks of gout. Individuals with gout were asked to fill a questionnaire enquiring about triggers that precipitated their acute gout attacks. Binary logistic regression was used to compute odds ratio (OR) and 95% confidence intervals (CI) to examine the association between having ≥1 self-reported trigger of acute gout and disease and demographic risk factors and to adjust for covariates. All statistical analyses were performed using STATA. 550 participants returned completed questionnaires. 206 (37.5%) reported at least one trigger of acute attacks, and less than 5% reported >2 triggers. Only 28.73% participants reported that their most recent gout attack was triggered by dietary or lifestyle risk factors. The most frequently self-reported triggers were alcohol intake (14.18%), red-meat or sea-food consumption (6%), dehydration (4.91%), injury or excess activity (4.91%), and excessively warm or cold weather (4.36% and 5.45%). Patients who had onset of gout before the age of 50 years were significantly more likely to identify a trigger for precipitating their acute gout attacks (aOR (95%CI) 1.73 (1.12-2.68) after adjusting for covariates. Most people with gout do not identify any triggers for acute attacks, and identifiable triggers are more common in those with young onset gout. Less than 20% people self-reported acute gout attacks from conventionally accepted triggers of gout e.g. alcohol, red-meat intake, while c.5% reported novel triggers such as dehydration, injury or physical activity, and weather extremes.

Triggers of acute attacks of gout, does age of gout onset matter? A primary care based cross-sectional study

PubMed Central

Valdes, Ana M.; Jenkins, Wendy; Zhang, Weiya; Doherty, Michael

2017-01-01

Objectives To determine the proportion of people with gout who self-report triggers of acute attacks; identify the commonly reported triggers, and examine the disease and demographic features associated with self-reporting any trigger(s) of acute attacks of gout. Methods Individuals with gout were asked to fill a questionnaire enquiring about triggers that precipitated their acute gout attacks. Binary logistic regression was used to compute odds ratio (OR) and 95% confidence intervals (CI) to examine the association between having ≥1 self-reported trigger of acute gout and disease and demographic risk factors and to adjust for covariates. All statistical analyses were performed using STATA. Results 550 participants returned completed questionnaires. 206 (37.5%) reported at least one trigger of acute attacks, and less than 5% reported >2 triggers. Only 28.73% participants reported that their most recent gout attack was triggered by dietary or lifestyle risk factors. The most frequently self-reported triggers were alcohol intake (14.18%), red-meat or sea-food consumption (6%), dehydration (4.91%), injury or excess activity (4.91%), and excessively warm or cold weather (4.36% and 5.45%). Patients who had onset of gout before the age of 50 years were significantly more likely to identify a trigger for precipitating their acute gout attacks (aOR (95%CI) 1.73 (1.12–2.68) after adjusting for covariates. Conclusion Most people with gout do not identify any triggers for acute attacks, and identifiable triggers are more common in those with young onset gout. Less than 20% people self-reported acute gout attacks from conventionally accepted triggers of gout e.g. alcohol, red-meat intake, while c.5% reported novel triggers such as dehydration, injury or physical activity, and weather extremes. PMID:29023487

Headaches: a Review of the Role of Dietary Factors.

PubMed

Zaeem, Zoya; Zhou, Lily; Dilli, Esma

2016-11-01

Dietary triggers are commonly reported by patients with a variety of headaches, particularly those with migraines. The presence of any specific dietary trigger in migraine patients varies from 10 to 64 % depending on study population and methodology. Some foods trigger headache within an hour while others develop within 12 h post ingestion. Alcohol (especially red wine and beer), chocolate, caffeine, dairy products such as aged cheese, food preservatives with nitrates and nitrites, monosodium glutamate (MSG), and artificial sweeteners such as aspartame have all been studied as migraine triggers in the past. This review focuses the evidence linking these compounds to headache and examines the prevalence of these triggers from prior population-based studies. Recent literature surrounding headache related to fasting and weight loss as well as elimination diets based on serum food antibody testing will also be summarized to help physicians recommend low-risk, non-pharmacological adjunctive therapies for patients with debilitating headaches.

Electronics for CMS Endcap Muon Level-1 Trigger System Phase-1 and HL LHC upgrades

NASA Astrophysics Data System (ADS)

Madorsky, A.

2017-07-01

To accommodate high-luminosity LHC operation at a 13 TeV collision energy, the CMS Endcap Muon Level-1 Trigger system had to be significantly modified. To provide robust track reconstruction, the trigger system must now import all available trigger primitives generated by the Cathode Strip Chambers and by certain other subsystems, such as Resistive Plate Chambers (RPC). In addition to massive input bandwidth, this also required significant increase in logic and memory resources. To satisfy these requirements, a new Sector Processor unit has been designed. It consists of three modules. The Core Logic module houses the large FPGA that contains the track-finding logic and multi-gigabit serial links for data exchange. The Optical module contains optical receivers and transmitters; it communicates with the Core Logic module via a custom backplane section. The Pt Lookup table (PTLUT) module contains 1 GB of low-latency memory that is used to assign the final Pt to reconstructed muon tracks. The μ TCA architecture (adopted by CMS) was used for this design. The talk presents the details of the hardware and firmware design of the production system based on Xilinx Virtex-7 FPGA family. The next round of LHC and CMS upgrades starts in 2019, followed by a major High-Luminosity (HL) LHC upgrade starting in 2024. In the course of these upgrades, new Gas Electron Multiplier (GEM) detectors and more RPC chambers will be added to the Endcap Muon system. In order to keep up with all these changes, a new Advanced Processor unit is being designed. This device will be based on Xilinx UltraScale+ FPGAs. It will be able to accommodate up to 100 serial links with bit rates of up to 25 Gb/s, and provide up to 2.5 times more logic resources than the device used currently. The amount of PTLUT memory will be significantly increased to provide more flexibility for the Pt assignment algorithm. The talk presents preliminary details of the hardware design program.

Nonlinear analysis of electromyogram following gait training with myoelectrically triggered neuromuscular electrical stimulation in stroke survivors

NASA Astrophysics Data System (ADS)

Dutta, Anirban; Khattar, Bhawna; Banerjee, Alakananda

2012-12-01

Neuromuscular electrical stimulation (NMES) facilitates ambulatory function after paralysis by activating the muscles of the lower extremities. The NMES-assisted stepping can either be triggered by a heel-switch (switch-trigger), or by an electromyogram (EMG)-based gait event detector (EMG-trigger). The command sources—switch-trigger or EMG-trigger—were presented to each group of six chronic (>6 months post-stroke) hemiplegic stroke survivors. The switch-trigger group underwent transcutaneous NMES-assisted gait training for 1 h, five times a week for 2 weeks, where the stimulation of the tibialis anterior muscle of the paretic limb was triggered with a heel-switch detecting heel-rise of the same limb. The EMG-trigger group underwent transcutaneous NMES-assisted gait training of the same duration and frequency where the stimulation was triggered with surface EMG from medial gastrocnemius (MG) of the paretic limb in conjunction with a heel-switch detecting heel-rise of the same limb. During the baseline and post-intervention surface EMG assessment, a total of 10 s of surface EMG was recorded from bilateral MG muscle while the subjects tried to stand steady on their toes. A nonlinear tool—recurrence quantification analysis (RQA)—was used to analyze the surface EMG. The objective of this study was to find the effect of NMES-assisted gait training with switch-trigger or EMG-trigger on two RQA parameters—the percentage of recurrence (%Rec) and determinism (%Det), which were extracted from surface EMG during fatiguing contractions of the paretic muscle. The experimental results showed that during fatiguing contractions, (1) %Rec and %Det have a higher initial value for paretic muscle than the non-paretic muscle, (2) the rate of change in %Rec and %Det was negative for the paretic muscle but positive for the non-paretic muscle, (3) the rate of change in %Rec and %Det significantly increased from baseline for the paretic muscle after EMG-triggered NMES-assisted gait training. Therefore, the study showed an improvement in paretic muscle function during a fatiguing task following gait training with EMG-triggered NMES. This study also showed that RQA parameters—%Rec and %Det—were sensitive to changes in paretic/non-paretic muscle properties due to gait training and can be used for non-invasive muscle monitoring in stroke survivors undergoing rehabilitation.

Comparative study of hadron- and γ-triggered azimuthal correlations in relativistic heavy-ion collisions

DOE PAGES

Ma, Guo -Lang; Wang, Xin -Nian

2012-01-01

In the framework of a multi-phase transport model, initial fluctuations in the transverse parton density lead to all orders of harmonic flows. Hadron-triggered azimuthal correlations include all contributions from harmonic flows, hot spots, and jet-medium excitations, which are isolated by using different initial conditions. We found that different physical components dominate different pseudorapidity ranges of dihadron correlations. Because γ-triggered azimuthal correlations can only be caused by jet-medium interactions, a comparative study of hadron- and γ -triggered azimuthal correlations can reveal more dynamics about jet-medium interactions.

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

A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: II. Probabilistic Guarantees on Constraint Satisfaction

PubMed Central

Li, Zukui; Floudas, Christodoulos A.

2012-01-01

Probabilistic guarantees on constraint satisfaction for robust counterpart optimization are studied in this paper. The robust counterpart optimization formulations studied are derived from box, ellipsoidal, polyhedral, “interval+ellipsoidal” and “interval+polyhedral” uncertainty sets (Li, Z., Ding, R., and Floudas, C.A., A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: I. Robust Linear and Robust Mixed Integer Linear Optimization, Ind. Eng. Chem. Res, 2011, 50, 10567). For those robust counterpart optimization formulations, their corresponding probability bounds on constraint satisfaction are derived for different types of uncertainty characteristic (i.e., bounded or unbounded uncertainty, with or without detailed probability distribution information). The findings of this work extend the results in the literature and provide greater flexibility for robust optimization practitioners in choosing tighter probability bounds so as to find less conservative robust solutions. Extensive numerical studies are performed to compare the tightness of the different probability bounds and the conservatism of different robust counterpart optimization formulations. Guiding rules for the selection of robust counterpart optimization models and for the determination of the size of the uncertainty set are discussed. Applications in production planning and process scheduling problems are presented. PMID:23329868

A SINFONI view of circum-nuclear star-forming rings in spiral galaxies

NASA Astrophysics Data System (ADS)

Falcón-Barroso, Jesús; Böker, Torsten; Schinnerer, Eva; Knapen, Johan H.; Ryder, Stuart

2008-07-01

We present near-infrared (H- and K-band) SINFONI integral-field observations of the circumnuclear star formation rings in five nearby spiral galaxies. We made use of the relative intensities of different emission lines (i.e. [FeII], HeI, Brγ) to age date the stellar clusters present along the rings. This qualitative, yet robust, method allows us to discriminate between two distinct scenarios that describe how star formation progresses along the rings. Our findings favour a model where star formation is triggered predominantly at the intersection between the bar major axis and the inner Lindblad resonance and then passively evolves as the clusters rotate around the ring (‘Pearls on a string’ scenario), although models of stochastically distributed star formation (‘Popcorn’ model) cannot be completely ruled out.

Collagen implants equipped with 'fish scale'-like nanoreservoirs of growth factors for bone regeneration.

PubMed

Eap, Sandy; Ferrand, Alice; Schiavi, Jessica; Keller, Laetitia; Kokten, Tunay; Fioretti, Florence; Mainard, Didier; Ladam, Guy; Benkirane-Jessel, Nadia

2014-01-01

Implants triggering rapid, robust and durable tissue regeneration are needed to shorten recovery times and decrease risks of postoperative complications for patients. Here, we describe active living collagen implants with highly promising bone regenerative properties. Bioactivity of the implants is obtained through the protective and stabilizing layer-by-layer immobilization of a protein growth factor in association with a polysaccharide (chitosan), within the form of nanocontainers decorating the collagen nanofibers. All components of the implants are US FDA approved. From both in vitro and in vivo evaluations, the sophisticated strategy described here should enhance, at a reduced cost, the safety and efficacy of the therapeutic implants in terms of large bone defects repair compared with current simplistic approaches based on the soaking of the implants with protein growth factor.

Rational design and evolutional fine tuning of Saccharomyces cerevisiae for biomass breakdown.

PubMed

Hasunuma, Tomohisa; Ishii, Jun; Kondo, Akihiko

2015-12-01

Conferring biomass hydrolysis activity on yeast through genetic engineering has paved the way for the development of groundbreaking processes for producing liquid fuels and commodity chemicals from lignocellulosic biomass. However, the overproduction and misfolding of heterologous and endogenous proteins can trigger cellular stress, increasing the metabolic burden and retarding growth. Improving the efficiency of lignocellulosic breakdown requires engineering of yeast secretory pathway based on system-wide metabolic analysis as well as DNA constructs for enhanced cellulase gene expression with advanced molecular biology tools. Also, yeast is subjected to severe stress due to toxic compounds generated during lignocellulose pretreatment in consolidated saccharification and fermentation processes. The prospect for development of robust yeast strains makes combining evolutionary and rational engineering strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. Objectives To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 × 109/L); standard trigger (10 × 109/L); higher trigger (20 × 109/L, 30 × 109/L, 50 × 109/L); or alternative platelet trigger (for example platelet mass)). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 × 109/L) versus a higher trigger (20 × 109/L or 30 × 109/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations. The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review. Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence). One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors’ own results; low-quality evidence). Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence). Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence). Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence). Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference −2.09, 95% CI −3.20 to −0.99; low-quality evidence). One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09). None of the studies reported on quality of life. Authors’ conclusions In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 × 109/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 × 109/L or 30 × 109/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 × 109/L or 30 × 109/L). Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 × 109/L) in the absence of other risk factors for bleeding. PMID:26576687

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.

PubMed

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-11-18

Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 x 10(9)/L); standard trigger (10 x 10(9)/L); higher trigger (20 x 10(9)/L, 30 x 10(9)/L, 50 x 10(9)/L); or alternative platelet trigger (for example platelet mass)). We used the standard methodological procedures expected by Cochrane. Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 x 10(9)/L) versus a higher trigger (20 x 10(9)/L or 30 x 10(9)/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations.The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review.Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence).One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors' own results; low-quality evidence).Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence).Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence).Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence).Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference -2.09, 95% CI -3.20 to -0.99; low-quality evidence).One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09).None of the studies reported on quality of life. In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 x 10(9)/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L).Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 x 10(9)/L) in the absence of other risk factors for bleeding.

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.

Redox rhythm reinforces the circadian clock to gate immune response.

PubMed

Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

2015-07-23

Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

Relativistic MHD simulations of collision-induced magnetic dissipation in poynting-flux-dominated jets/outflows

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

Deng, Wei; Li, Hui; Zhang, Bing

We perform 3D relativistic ideal MHD simulations to study the collisions between high-σ (Poynting- ux-dominated) blobs which contain both poloidal and toroidal magnetic field components. This is meant to mimic the interactions inside a highly variable Poynting- ux-dominated jet. We discover a significant electromagnetic field (EMF) energy dissipation with an Alfvenic rate with the efficiency around 35%. Detailed analyses show that this dissipation is mostly facilitated by the collision-induced magnetic reconnection. Additional resolution and parameter studies show a robust result that the relative EMF energy dissipation efficiency is nearly independent of the numerical resolution or most physical parameters in themore » relevant parameter range. The reconnection outflows in our simulation can potentially form the multi-orientation relativistic mini-jets as needed for several analytical models. We also find a linear relationship between the σ values before and after the major EMF energy dissipation process. In conclusion, our results give support to the proposed astrophysical models that invoke signi cant magnetic energy dissipation in Poynting- ux-dominated jets, such as the internal collision-induced magnetic reconnection and turbulence (ICMART) model for GRBs, and reconnection triggered mini-jets model for AGNs.« less

Development of an in vitro PIG-A gene mutation assay in human cells

PubMed Central

Rees, Benjamin J; Tate, Matthew; Lynch, Anthony M; Thornton, Catherine A; Jenkins, Gareth J; Walmsley, Richard M; Johnson, George E

2017-01-01

Abstract Mutagens can be carcinogens, and traditionally, they have been identified in vitro using the Salmonella ‘Ames’ reverse mutation assay. However, prokaryotic DNA packaging, replication and repair systems are mechanistically very different to those in the humans we inevitably seek to protect. Therefore, for many years, mammalian cell line genotoxicity assays that can detect eukaryotic mutagens as well as clastogens and aneugens have been used. The apparent lack of specificity in these largely rodent systems, due partly to their mutant p53 status, has contributed to the use of animal studies to resolve data conflicts. Recently, silencing mutations at the PIG-A locus have been demonstrated to prevent glycophosphatidylinositol (GPI) anchor synthesis and consequentially result in loss of GPI-anchored proteins from the cell’s extracellular surface. The successful exploitation of this mutant phenotype in animal studies has triggered interest in the development of an analogous in vitro PIG-A mutation screening assay. This article describes the development of a robust assay design using metabolically active human cells. The assay includes viability and cell membrane integrity assessment and conforms to the future ideas of the 21st-century toxicology testing. PMID:28057708

Relativistic MHD simulations of collision-induced magnetic dissipation in poynting-flux-dominated jets/outflows

DOE PAGES

Deng, Wei; Li, Hui; Zhang, Bing; ...

2015-05-29

We perform 3D relativistic ideal MHD simulations to study the collisions between high-σ (Poynting- ux-dominated) blobs which contain both poloidal and toroidal magnetic field components. This is meant to mimic the interactions inside a highly variable Poynting- ux-dominated jet. We discover a significant electromagnetic field (EMF) energy dissipation with an Alfvenic rate with the efficiency around 35%. Detailed analyses show that this dissipation is mostly facilitated by the collision-induced magnetic reconnection. Additional resolution and parameter studies show a robust result that the relative EMF energy dissipation efficiency is nearly independent of the numerical resolution or most physical parameters in themore » relevant parameter range. The reconnection outflows in our simulation can potentially form the multi-orientation relativistic mini-jets as needed for several analytical models. We also find a linear relationship between the σ values before and after the major EMF energy dissipation process. In conclusion, our results give support to the proposed astrophysical models that invoke signi cant magnetic energy dissipation in Poynting- ux-dominated jets, such as the internal collision-induced magnetic reconnection and turbulence (ICMART) model for GRBs, and reconnection triggered mini-jets model for AGNs.« less

West African Sorghum bicolor Leaf Sheaths Have Anti-Inflammatory and Immune-Modulating Properties In Vitro

PubMed Central

Benson, Kathleen F.; Beaman, Joni L.; Ou, Boxin; Okubena, Ademola; Okubena, Olajuwon

2013-01-01

Abstract The impact of chronic inflammatory conditions on immune function is substantial, and the simultaneous application of anti-inflammatory and immune modulating modalities has potential for reducing inflammation-induced immune suppression. Sorghum-based foods, teas, beers, and extracts are used in traditional medicine, placing an importance on obtaining an increased understanding of the biological effects of sorghum. This study examined selected anti-inflammatory and immune-modulating properties in vitro of Jobelyn™, containing the polyphenol-rich leaf sheaths from a West African variant of Sorghum bicolor (SBLS). Freshly isolated primary human polymorphonuclear (PMN) and mononuclear cell subsets were used to test selected cellular functions in the absence versus presence of aqueous and ethanol extracts of SBLS. Both aqueous and nonaqueous compounds contributed to reduced reactive oxygen species formation by inflammatory PMN cells, and reduced the migration of these cells in response to the inflammatory chemoattractant leukotriene B4. Distinct effects were seen on lymphocyte and monocyte subsets in cultures of peripheral blood mononuclear cells. The aqueous extract of SBLS triggered robust upregulation of the CD69 activation marker on CD3− CD56+ natural killer (NK) cells, whereas the ethanol extract of SBLS triggered similar upregulation of CD69 on CD3+ CD56+ NKT cells, CD3+ T lymphocytes, and monocytes. This was accompanied by many-fold increases in the chemokines RANTES/CCL5, Mip-1α/CCL3, and MIP-1β/CCL4. Both aqueous and nonaqueous compounds contribute to anti-inflammatory effects, combined with multiple effects on immune cell activation status. These observations may help suggest mechanisms of action that contribute to the traditional use of sorghum-based products, beverages, and extracts for immune support. PMID:23289787

Temporal changes in myocardial infarction incidence rates are associated with periods of perceived psychosocial stress: A SWEDEHEART national registry study.

PubMed

Wallert, John; Held, Claes; Madison, Guy; Olsson, Erik Mg

2017-09-01

Psychosocial stress might trigger myocardial infarction (MI). Increased MI incidence coincides with recurrent time periods during the year perceived as particularly stressful in the population. A stress-triggering hypothesis on the risk of MI onset was investigated with Swedish population data on MI hospital admission date and symptom onset date (N=156,690; 148,176) as registered from 2006 through 2013 in the national quality registry database Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Poisson regression was applied to analyze daily MI rates during days belonging to the Christmas and New Year holidays, turns of the month, Mondays, weekends, and summer vacation in July compared with remaining control days. Adjusted incidence rate ratios (IRRs) for MI rates were higher during Christmas and New Year holidays (IRR=1.07 [1.04-1.09], P<.001) and on Mondays (IRR=1.11 [1.09-1.13], P<.001) and lower in July (IRR=0.92 [0.90-0.94], P<.001) and over weekends (IRR=0.88 [0.87-0.89], P<.001), yet not during the turns of the month (IRR=1.01 [1.00-1.02], P=.891). These findings were also predominantly robust with symptom onset as alternative outcome, when adjusting for both established and some suggested-but-untested confounders, and in 8 subgroups. Fluctuations in daily MI incidence rates are systematically related to time periods of presumed psychosocial stress. Further research might clarify mechanisms that are amenable to clinical alteration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Thermal Detection Thresholds of Aδ- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin

PubMed Central

Churyukanov, Maxim; Plaghki, Léon; Legrain, Valéry; Mouraux, André

2012-01-01

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively. PMID:22558230

A Trigger-based Design for Evaluating the Safety of In Utero Antiretroviral Exposure in Uninfected Children of Human Immunodeficiency Virus-Infected Mothers

PubMed Central

Williams, Paige L.; Seage, George R.; Van Dyke, Russell B.; Siberry, George K.; Griner, Raymond; Tassiopoulos, Katherine; Yildirim, Cenk; Read, Jennifer S.; Huo, Yanling; Hazra, Rohan; Jacobson, Denise L.; Mofenson, Lynne M.; Rich, Kenneth

2012-01-01

The Pediatric HIV/AIDS Cohort Study’s Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a “trigger-based” design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or “triggers” undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios. PMID:22491086

Structural exploration for the refinement of anticancer matrix metalloproteinase-2 inhibitor designing approaches through robust validated multi-QSARs

NASA Astrophysics Data System (ADS)

Adhikari, Nilanjan; Amin, Sk. Abdul; Saha, Achintya; Jha, Tarun

2018-03-01

Matrix metalloproteinase-2 (MMP-2) is a promising pharmacological target for designing potential anticancer drugs. MMP-2 plays critical functions in apoptosis by cleaving the DNA repair enzyme namely poly (ADP-ribose) polymerase (PARP). Moreover, MMP-2 expression triggers the vascular endothelial growth factor (VEGF) having a positive influence on tumor size, invasion, and angiogenesis. Therefore, it is an urgent need to develop potential MMP-2 inhibitors without any toxicity but better pharmacokinetic property. In this article, robust validated multi-quantitative structure-activity relationship (QSAR) modeling approaches were attempted on a dataset of 222 MMP-2 inhibitors to explore the important structural and pharmacophoric requirements for higher MMP-2 inhibition. Different validated regression and classification-based QSARs, pharmacophore mapping and 3D-QSAR techniques were performed. These results were challenged and subjected to further validation to explain 24 in house MMP-2 inhibitors to judge the reliability of these models further. All these models were individually validated internally as well as externally and were supported and validated by each other. These results were further justified by molecular docking analysis. Modeling techniques adopted here not only helps to explore the necessary structural and pharmacophoric requirements but also for the overall validation and refinement techniques for designing potential MMP-2 inhibitors.

Auditory Responses and Stimulus-Specific Adaptation in Rat Auditory Cortex are Preserved Across NREM and REM Sleep

PubMed Central

Nir, Yuval; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Banks, Matthew I.; Tononi, Giulio

2015-01-01

Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic “gate,” which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8% between states). The processing of deviant tones was also compared in sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13–20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas. PMID:24323498

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

PubMed Central

Noguera-Ortega, Estela; Blanco-Cabra, Núria; Rabanal, Rosa Maria; Sánchez-Chardi, Alejandro; Roldán, Mónica; Guallar-Garrido, Sandra; Torrents, Eduard; Luquin, Marina; Julián, Esther

2016-01-01

The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer. PMID:27265565

Bioinspired Layer-by-Layer Microcapsules Based on Cellulose Nanofibers with Switchable Permeability.

PubMed

Paulraj, Thomas; Riazanova, Anastasia V; Yao, Kun; Andersson, Richard L; Müllertz, Anette; Svagan, Anna J

2017-04-10

Green, all-polysaccharide based microcapsules with mechanically robust capsule walls and fast, stimuli-triggered, and switchable permeability behavior show great promise in applications based on selective and timed permeability. Taking a cue from nature, the build-up and composition of plant primary cell walls inspired the capsule wall assembly, because the primary cell walls in plants exhibit high mechanical properties despite being in a highly hydrated state, primarily owing to cellulose microfibrils. The microcapsules (16 ± 4 μm in diameter) were fabricated using the layer-by-layer technique on sacrificial CaCO 3 templates, using plant polysaccharides (pectin, cellulose nanofibers, and xyloglucan) only. In water, the capsule wall was permeable to labeled dextrans with a hydrodynamic diameter of ∼6.6 nm. Upon exposure to NaCl, the porosity of the capsule wall quickly changed allowing larger molecules (∼12 nm) to permeate. However, the porosity could be restored to its original state by removal of NaCl, by which permeants became trapped inside the capsule's core. The high integrity of cell wall was due to the CNF and the ON/OFF alteration of the permeability properties, and subsequent loading/unloading of molecules, could be repeated several times with the same capsule demonstrating a robust microcontainer with controllable permeability properties.

Divergent forms of endoplasmic reticulum stress trigger a robust unfolded protein response in honey bees.

PubMed

Johnston, Brittany A; Hooks, Katarzyna B; McKinstry, Mia; Snow, Jonathan W

2016-03-01

Honey bee colonies in the United States have suffered from an increased rate of die-off in recent years, stemming from a complex set of interacting stresses that remain poorly described. While we have some understanding of the physiological stress responses in the honey bee, our molecular understanding of honey bee cellular stress responses is incomplete. Thus, we sought to identify and began functional characterization of the components of the UPR in honey bees. The IRE1-dependent splicing of the mRNA for the transcription factor Xbp1, leading to translation of an isoform with more transactivation potential, represents the most conserved of the UPR pathways. Honey bees and other Apoidea possess unique features in the Xbp1 mRNA splice site, which we reasoned could have functional consequences for the IRE1 pathway. However, we find robust induction of target genes upon UPR stimulation. In addition, the IRE1 pathway activation, as assessed by splicing of Xbp1 mRNA upon UPR, is conserved. By providing foundational knowledge about the UPR in the honey bee and the relative sensitivity of this species to divergent stresses, this work stands to improve our understanding of the mechanistic underpinnings of honey bee health and disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential proxy responses to late Allerød and early Younger Dryas climatic change recorded in varved sediments of the Trzechowskie palaeolake in Northern Poland

NASA Astrophysics Data System (ADS)

Słowiński, Michał; Zawiska, Izabela; Ott, Florian; Noryśkiewicz, Agnieszka M.; Plessen, Birgit; Apolinarska, Karina; Rzodkiewicz, Monika; Michczyńska, Danuta J.; Wulf, Sabine; Skubała, Piotr; Kordowski, Jarosław; Błaszkiewicz, Mirosław; Brauer, Achim

2017-02-01

High-resolution biological proxies (pollen, macrofossils, Cladocera and diatoms), geochemical data (μ-XRF element scans, TOC, C/N ratios, δ18Ocarb and δ13Corg values) and a robust chronology based on varve counting, AMS 14C dating and tephrochronology were applied to reconstruct lake system responses to rapid climatic and environmental changes of the Trzechowskie palaeolake (TRZ; Northern Poland) during the late Allerød - Younger Dryas (YD) transition. Palaeoecological and geochemical data at 5-15 years temporal resolution allowed tracing the dynamics of short-term shifts of the ecosystem triggered by abrupt climate change. The robust age control together with the high-resolution sampling allowed the detection of leads and lags between different proxies to the climate shift at the Allerød-Younger Dryas transition. Our results indicate (1) a water level decrease and an increase in wind activities during the late Allerød and the Allerød-YD transition, which caused intensified erosion in the catchment, (2) a two-decades delayed vegetation response in comparison to the lake depositional system. Comparison with the Lake Meerfelder Maar record revealed slightly different vegetation responses of the Trzechowskie palaeolake at the YD onset.

A Photogate Flash Trigger and a Demonstration of Inertia.

ERIC Educational Resources Information Center

Winters, Loren

1992-01-01

Describes a photogate electronic flash trigger that synchronizes flash discharge with high-speed events. Presents a photographic study of a high-speed collision demonstrating the passage of a BB through an elastic strip. Provides the schematic of the delay circuit utilized in the trigger. (MDH)

Smart Bandwidth Assignation in an Underlay Cellular Network for Internet of Vehicles.

PubMed

de la Iglesia, Idoia; Hernandez-Jayo, Unai; Osaba, Eneko; Carballedo, Roberto

2017-09-27

The evolution of the IoT (Internet of Things) paradigm applied to new scenarios as VANETs (Vehicular Ad Hoc Networks) has gained momentum in recent years. Both academia and industry have triggered advanced studies in the IoV (Internet of Vehicles), which is understood as an ecosystem where different types of users (vehicles, elements of the infrastructure, pedestrians) are connected. How to efficiently share the available radio resources among the different types of eligible users is one of the important issues to be addressed. This paper briefly analyzes various concepts presented hitherto in the literature and it proposes an enhanced algorithm for ensuring a robust co-existence of the aforementioned system users. Therefore, this paper introduces an underlay RRM (Radio Resource Management) methodology which is capable of (1) improving cellular spectral efficiency while making a minimal impact on cellular communications and (2) ensuring the different QoS (Quality of Service) requirements of ITS (Intelligent Transportation Systems) applications. Simulation results, where we compare the proposed algorithm to the other two RRM, show the promising spectral efficiency performance of the proposed RRM methodology.

Smart Bandwidth Assignation in an Underlay Cellular Network for Internet of Vehicles

PubMed Central

de la Iglesia, Idoia; Hernandez-Jayo, Unai

2017-01-01

The evolution of the IoT (Internet of Things) paradigm applied to new scenarios as VANETs (Vehicular Ad Hoc Networks) has gained momentum in recent years. Both academia and industry have triggered advanced studies in the IoV (Internet of Vehicles), which is understood as an ecosystem where different types of users (vehicles, elements of the infrastructure, pedestrians) are connected. How to efficiently share the available radio resources among the different types of eligible users is one of the important issues to be addressed. This paper briefly analyzes various concepts presented hitherto in the literature and it proposes an enhanced algorithm for ensuring a robust co-existence of the aforementioned system users. Therefore, this paper introduces an underlay RRM (Radio Resource Management) methodology which is capable of (1) improving cellular spectral efficiency while making a minimal impact on cellular communications and (2) ensuring the different QoS (Quality of Service) requirements of ITS (Intelligent Transportation Systems) applications. Simulation results, where we compare the proposed algorithm to the other two RRM, show the promising spectral efficiency performance of the proposed RRM methodology. PMID:28953256

Do Decapod Crustaceans Have Nociceptors for Extreme pH?

PubMed Central

Puri, Sakshi; Faulkes, Zen

2010-01-01

Background Nociception is the physiological detection of noxious stimuli. Because of its obvious importance, nociception is expected to be widespread across animal taxa and to trigger robust behaviours reliably. Nociception in invertebrates, such as crustaceans, is poorly studied. Methodology/Principal Findings Three decapod crustacean species were tested for nociceptive behaviour: Louisiana red swamp crayfish (Procambarus clarkii), white shrimp (Litopenaeus setiferus), and grass shrimp (Palaemonetes sp.). Applying sodium hydroxide, hydrochloric acid, or benzocaine to the antennae caused no change in behaviour in the three species compared to controls. Animals did not groom the stimulated antenna, and there was no difference in movement of treated individuals and controls. Extracellular recordings of antennal nerves in P. clarkii revealed continual spontaneous activity, but no neurons that were reliably excited by the application of concentrated sodium hydroxide or hydrochloric acid. Conclusions/Significance Previously reported responses to extreme pH are either not consistently evoked across species or were mischaracterized as nociception. There was no behavioural or physiological evidence that the antennae contained specialized nociceptors that responded to pH. PMID:20422026

Blast-induced tinnitus and hyperactivity in the auditory cortex of rats.

PubMed

Luo, Hao; Pace, Edward; Zhang, Jinsheng

2017-01-06

Blast exposure can cause tinnitus and hearing impairment by damaging the auditory periphery and direct impact to the brain, which trigger neural plasticity in both auditory and non-auditory centers. However, the underlying neurophysiological mechanisms of blast-induced tinnitus are still unknown. In this study, we induced tinnitus in rats using blast exposure and investigated changes in spontaneous firing and bursting activity in the auditory cortex (AC) at one day, one month, and three months after blast exposure. Our results showed that spontaneous activity in the tinnitus-positive group began changing at one month after blast exposure, and manifested as robust hyperactivity at all frequency regions at three months after exposure. We also observed an increased bursting rate in the low-frequency region at one month after blast exposure and in all frequency regions at three months after exposure. Taken together, spontaneous firing and bursting activity in the AC played an important role in blast-induced chronic tinnitus as opposed to acute tinnitus, thus favoring a bottom-up mechanism. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Drosophila larvae food intake cessation following exposure to Erwinia contaminated media requires odor perception, Trpa1 channel and evf virulence factor.

PubMed

Keita, Seydou; Masuzzo, Ambra; Royet, Julien; Kurz, C Leopold

2017-05-01

When exposed to microorganisms, animals use several protective strategies. On one hand, as elegantly exemplified in Drosophila melanogaster, the innate immune system recognizes microbial compounds and triggers an antimicrobial response. On the other hand, behaviors preventing an extensive contact with the microbes and thus reducing the risk of infection have been described. However, these reactions ranging from microbes aversion to intestinal transit increase or food intake decrease have been rarely defined at the molecular level. In this study, we set up an experimental system that allowed us to rapidly identify and quantify food intake decreases in Drosophila larvae exposed to media contaminated with bacteria. Specifically, we report a robust dose-dependent food intake decrease following exposure to the bacteria Erwinia carotovora carotovora strain Ecc15. We demonstrate that this response does not require Imd innate immune pathway, but rather the olfactory neuronal circuitry, the Trpa1 receptor and the evf virulence factor. Finally, we show that Ecc15 induce the same behavior in the invasive pest insect Drosophila suzukii. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coherent instability in wall-bounded turbulence

NASA Astrophysics Data System (ADS)

Hack, M. J. Philipp

2017-11-01

Hairpin vortices are commonly considered one of the major classes of coherent fluid motions in shear layers, even as their significance in the grand scheme of turbulence has remained an openly debated question. The statistical prevalence of the dynamic process that gives rise to the hairpins across different types of flows suggests an origin in a robust common mechanism triggered by conditions widespread in wall-bounded shear layers. This study seeks to shed light on the physical process which drives the generation of hairpin vortices. It is primarily facilitated through an algorithm based on concepts developed in the field of computer vision which allows the topological identification and analysis of coherent flow processes across multiple scales. Application to direct numerical simulations of boundary layers enables the time-resolved sampling and exploration of the hairpin process in natural flow. The analysis yields rich statistical results which lead to a refined characterization of the hairpin process. Linear stability theory offers further insight into the flow physics and especially into the connection between the hairpin and exponential amplification mechanisms. The results also provide a sharpened understanding of the underlying causality of events.

Endocytic pathways downregulate the L1-type cell adhesion molecule neuroglian to promote dendrite pruning in Drosophila.

PubMed

Zhang, Heng; Wang, Yan; Wong, Jack Jing Lin; Lim, Kah-Leong; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei

2014-08-25

Pruning of unnecessary axons and/or dendrites is crucial for maturation of the nervous system. However, little is known about cell adhesion molecules (CAMs) that control neuronal pruning. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites. Here, we report that Rab5/ESCRT-mediated endocytic pathways are critical for dendrite pruning. Loss of Rab5 or ESCRT function leads to robust accumulation of the L1-type CAM Neuroglian (Nrg) on enlarged endosomes in ddaC neurons. Nrg is localized on endosomes in wild-type ddaC neurons and downregulated prior to dendrite pruning. Overexpression of Nrg alone is sufficient to inhibit dendrite pruning, whereas removal of Nrg causes precocious dendrite pruning. Epistasis experiments indicate that Rab5 and ESCRT restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study demonstrates the cell-surface molecule that controls dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning. Copyright © 2014 Elsevier Inc. All rights reserved.

Sickling of red blood cells through rapid oxygen exchange in microfluidic drops.

PubMed

Abbyad, Paul; Tharaux, Pierre-Louis; Martin, Jean-Louis; Baroud, Charles N; Alexandrou, Antigoni

2010-10-07

We have developed a microfluidic approach to study the sickling of red blood cells associated with sickle cell anemia by rapidly varying the oxygen partial pressure within flowing microdroplets. By using the perfluorinated carrier oil as a sink or source of oxygen, the oxygen level within the water droplets quickly equilibrates through exchange with the surrounding oil. This provides control over the oxygen partial pressure within an aqueous drop ranging from 1 kPa to ambient partial pressure, i.e. 21 kPa. The dynamics of the oxygen exchange is characterized through fluorescence lifetime measurements of a ruthenium compound dissolved in the aqueous phase. The gas exchange is shown to occur primarily during and directly after droplet formation, in 0.1 to 0.5 s depending on the droplet diameter and speed. The controlled deoxygenation is used to trigger the polymerization of hemoglobin within sickle red blood cells, encapsulated in drops. This process is observed using polarization microscopy, which yields a robust criterion to detect polymerization based on transmitted light intensity through crossed polarizers.

Identification of MAPK Substrates Using Quantitative Phosphoproteomics.

PubMed

Zhang, Tong; Schneider, Jacqueline D; Zhu, Ning; Chen, Sixue

2017-01-01

Activation of mitogen-activated protein kinases (MAPKs) under diverse biotic and abiotic factors and identification of an array of downstream MAPK target proteins are hot topics in plant signal transduction. Through interactions with a plethora of substrate proteins, MAPK cascades regulate many physiological processes in the course of plant growth, development, and response to environmental factors. Identification and quantification of potential MAPK substrates are essential, but have been technically challenging. With the recent advancement in phosphoproteomics, here we describe a method that couples metal dioxide for phosphopeptide enrichment with tandem mass tags (TMT) mass spectrometry (MS) for large-scale MAPK substrate identification and quantification. We have applied this method to a transient expression system carrying a wild type (WT) and a constitutive active (CA) version of a MAPK. This combination of genetically engineered MAPKs and phosphoproteomics provides a high-throughput, unbiased analysis of MAPK-triggered phosphorylation changes on the proteome scale. Therefore, it is a robust method for identifying potential MAPK substrates and should be applicable in the study of other kinase cascades in plants as well as in other organisms.

Topologically protected bound states in one-dimensional Floquet acoustic waveguide systems

NASA Astrophysics Data System (ADS)

Peng, Yu-Gui; Geng, Zhi-Guo; Zhu, Xue-Feng

2018-03-01

Topological manipulation of sound has recently been a hot spot in acoustics due to the fascinating property of defect immune transport. To the best of our knowledge, the studies on one-dimensional (1D) topological acoustic systems hitherto mainly focus on the case of the Su-Schrieffer-Heeger model. Here, we show that topologically protected bound states may also exist in 1D periodically modulated acoustic waveguide systems, viz., 1D Floquet topological insulators. The results show that tuning the coupling strength in a waveguide lattice could trigger topological phase transition, which gives rise to topologically protected interface states as we put together two waveguide lattices featured with different topological phases or winding numbers. However, for the combined lattice, input at the waveguides other than the interfacial ones will excite bulk states. We have further verified the robustness of interface bound states against the variation of coupling strengths between the two distinct waveguide lattices. This work extends the scope of topological acoustics and may promote potential applications for acoustic devices with topological functionalities.

The role of predictive uncertainty in the operational management of reservoirs

NASA Astrophysics Data System (ADS)

Todini, E.

2014-09-01

The present work deals with the operational management of multi-purpose reservoirs, whose optimisation-based rules are derived, in the planning phase, via deterministic (linear and nonlinear programming, dynamic programming, etc.) or via stochastic (generally stochastic dynamic programming) approaches. In operation, the resulting deterministic or stochastic optimised operating rules are then triggered based on inflow predictions. In order to fully benefit from predictions, one must avoid using them as direct inputs to the reservoirs, but rather assess the "predictive knowledge" in terms of a predictive probability density to be operationally used in the decision making process for the estimation of expected benefits and/or expected losses. Using a theoretical and extremely simplified case, it will be shown why directly using model forecasts instead of the full predictive density leads to less robust reservoir management decisions. Moreover, the effectiveness and the tangible benefits for using the entire predictive probability density instead of the model predicted values will be demonstrated on the basis of the Lake Como management system, operational since 1997, as well as on the basis of a case study on the lake of Aswan.

Overload cascading failure on complex networks with heterogeneous load redistribution

NASA Astrophysics Data System (ADS)

Hou, Yueyi; Xing, Xiaoyun; Li, Menghui; Zeng, An; Wang, Yougui

2017-09-01

Many real systems including the Internet, power-grid and financial networks experience rare but large overload cascading failures triggered by small initial shocks. Many models on complex networks have been developed to investigate this phenomenon. Most of these models are based on the load redistribution process and assume that the load on a failed node shifts to nearby nodes in the networks either evenly or according to the load distribution rule before the cascade. Inspired by the fact that real power-grid tends to place the excess load on the nodes with high remaining capacities, we study a heterogeneous load redistribution mechanism in a simplified sandpile model in this paper. We find that weak heterogeneity in load redistribution can effectively mitigate the cascade while strong heterogeneity in load redistribution may even enlarge the size of the final failure. With a parameter θ to control the degree of the redistribution heterogeneity, we identify a rather robust optimal θ∗ = 1. Finally, we find that θ∗ tends to shift to a larger value if the initial sand distribution is homogeneous.

Theory of Liquid Film Growth and Wetting Instabilities on Graphene

NASA Astrophysics Data System (ADS)

Sengupta, Sanghita; Nichols, Nathan S.; Del Maestro, Adrian; Kotov, Valeri N.

2018-06-01

We investigate wetting phenomena near graphene within the Dzyaloshinskii-Lifshitz-Pitaevskii theory for light gases of hydrogen, helium, and nitrogen in three different geometries where graphene is either affixed to an insulating substrate, submerged or suspended. We find that the presence of graphene has a significant effect in all configurations. When placed on a substrate, the polarizability of graphene can increase the strength of the total van der Waals force by a factor of 2 near the surface, enhancing the propensity towards wetting. In a suspended geometry unique to two-dimensional materials, where graphene is able to wet on only one side, liquid film growth becomes arrested at a critical thickness, which may trigger surface instabilities and pattern formation analogous to spinodal dewetting. The existence of a mesoscopic critical film with a tunable thickness provides a platform for the study of a continuous wetting transition, as well as the engineering of custom liquid coatings. These phenomena are robust to some mechanical deformations and are also universally present in doped graphene and other two-dimensional materials, such as monolayer dichalcogenides.

Triggering Events and New Daily Persistent Headache: Age and Gender Differences and Insights on Pathogenesis-A Clinic-Based Study.

PubMed

Rozen, Todd D

2016-01-01

To define what are the age and gender differences for new daily persistent headache (NDPH) triggering events and how this may relate to the pathogenesis of NDPH. To describe several new triggering events for NDPH. All patients were diagnosed with primary NDPH at a headache specialty clinic during the time period of 01/2009 through 01/2013. This was a retrospective analysis of patient medical records utilizing an electronic medical record system. Ninety-seven patients were diagnosed with primary NDPH (65 women and 32 men). The mean average age of onset was younger in women than men 32.4 years vs 35.8 years. Fifty one of ninety seven NDPH patients (53%) did not recognize a triggering event while an infection or flu-like illness triggered NDPH in 22%, a stressful life event in 9%, a procedure (surgical) in 9%, and some "other" recognized trigger in 7%. All of the NDPH patients who developed new onset headache after an invasive surgical procedure were intubated. There was no significant difference in frequency for any of the triggering events between genders. The youngest age of onset was for a post stressful life event trigger while the oldest age of onset was in the post-surgical subgroup. Women developed NDPH at a younger age of onset for all recognized triggers, but there was no significant difference in ages of onset between the genders. There was no significant difference in the number of NDPH patients who had a history of migraine or no history and if they developed NDPH after any triggered event vs no triggering event. However, the majority of patients who developed NDPH after a stressful life event did have a precedent migraine history (67%). Newly noted triggers include: hormonal manipulation with progesterone, medication exposure, chemical/pesticide exposure, massage treatment, and immediately post a syncopal event. More than 50% of NDPH sufferers do not recognize a triggering event to their headaches. A key finding from the present study is the recognition that of those patients who developed NDPH after an invasive surgical procedure all required intubation and we speculate a cervicogenic origin to their headaches. The fact that both genders had an almost equal rate of occurrence for most NDPH triggers and almost the same age of onset suggests a common underlying pathogenesis for similar triggering events. A precedent history of migraine did not enhance the frequency of triggered vs nontriggered NDPH except possibly for a stressful life event. © 2015 American Headache Society.

GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis.

PubMed

Haahr, Thor; Roque, Matheus; Esteves, Sandro C; Humaidan, Peter

2017-01-01

The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm). CRD42016051091.

Dry needling — peripheral and central considerations

PubMed Central

Dommerholt, Jan

2011-01-01

Dry needling is a common treatment technique in orthopedic manual physical therapy. Although various dry needling approaches exist, the more common and best supported approach targets myofascial trigger points. This article aims to place trigger point dry needling within the context of pain sciences. From a pain science perspective, trigger points are constant sources of peripheral nociceptive input leading to peripheral and central sensitization. Dry needling cannot only reverse some aspects of central sensitization, it reduces local and referred pain, improves range of motion and muscle activation pattern, and alters the chemical environment of trigger points. Trigger point dry needling should be based on a thorough understanding of the scientific background of trigger points, the differences and similarities between active and latent trigger points, motor adaptation, and central sensitize application. Several outcome studies are included, as well as comments on dry needling and acupuncture. PMID:23115475

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.

Spark gaps synchronization using electrical trigger pulses

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

Agarwal, Ritu; Saroj, P.C.; Sharma, Archana

In pulse power systems, it is required to have synchronized triggering of two or more high voltage spark gaps capable of switching large currents, using electrical trigger pulses. This paper intends to study the synchronization of spark gaps using electrical trigger. The trigger generator consists of dc supply, IGBT switch and driver circuit which generates 8kV, 400ns (FWHM) pulses. The experiment was carried out using two 0.15uF/50kV energy storage capacitors charged to 12kV and discharged through stainless steel spark gaps of diameter 9 mm across 10 ohm non inductive load. The initial experiment shows that synchronization has been achieved withmore » jitter of 50 to 100ns. Further studies carried out to reduce the jitter time by varying various electrical parameters will be presented. (author)« less

Workshop on data acquisition and trigger system simulations for high energy physics

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

NONE

1992-12-31

This report discusses the following topics: DAQSIM: A data acquisition system simulation tool; Front end and DCC Simulations for the SDC Straw Tube System; Simulation of Non-Blocklng Data Acquisition Architectures; Simulation Studies of the SDC Data Collection Chip; Correlation Studies of the Data Collection Circuit & The Design of a Queue for this Circuit; Fast Data Compression & Transmission from a Silicon Strip Wafer; Simulation of SCI Protocols in Modsim; Visual Design with vVHDL; Stochastic Simulation of Asynchronous Buffers; SDC Trigger Simulations; Trigger Rates, DAQ & Online Processing at the SSC; Planned Enhancements to MODSEM II & SIMOBJECT -- anmore » Overview -- R.; DAGAR -- A synthesis system; Proposed Silicon Compiler for Physics Applications; Timed -- LOTOS in a PROLOG Environment: an Algebraic language for Simulation; Modeling and Simulation of an Event Builder for High Energy Physics Data Acquisition Systems; A Verilog Simulation for the CDF DAQ; Simulation to Design with Verilog; The DZero Data Acquisition System: Model and Measurements; DZero Trigger Level 1.5 Modeling; Strategies Optimizing Data Load in the DZero Triggers; Simulation of the DZero Level 2 Data Acquisition System; A Fast Method for Calculating DZero Level 1 Jet Trigger Properties and Physics Input to DAQ Studies.« less

Germination of Aspergillus niger conidia is triggered by nitrogen compounds related to L-amino acids.

PubMed

Hayer, Kimran; Stratford, Malcolm; Archer, David B

2014-10-01

Conidial germination is fundamentally important to the growth and dissemination of most fungi. It has been previously shown (K. Hayer, M. Stratford, and D. B. Archer, Appl. Environ. Microbiol. 79:6924-6931, 2013, http://dx.doi.org/10.1128/AEM.02061-13), using sugar analogs, that germination is a 2-stage process involving triggering of germination and then nutrient uptake for hyphal outgrowth. In the present study, we tested this 2-stage germination process using a series of nitrogen-containing compounds for the ability to trigger the breaking of dormancy of Aspergillus niger conidia and then to support the formation of hyphae by acting as nitrogen sources. Triggering and germination were also compared between A. niger and Aspergillus nidulans using 2-deoxy-D-glucose (trigger), D-galactose (nontrigger in A. niger but trigger in A. nidulans), and an N source (required in A. niger but not in A. nidulans). Although most of the nitrogen compounds studied served as nitrogen sources for growth, only some nitrogen compounds could trigger germination of A. niger conidia, and all were related to L-amino acids. Using L-amino acid analogs without either the amine or the carboxylic acid group revealed that both the amine and carboxylic acid groups were essential for an L-amino acid to serve as a trigger molecule. Generally, conidia were able to sense and recognize nitrogen compounds that fitted into a specific size range. There was no evidence of uptake of either triggering or nontriggering compounds over the first 90 min of A. niger conidial germination, suggesting that the germination trigger sensors are not located within the spore. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Stress/strain changes and triggered seismicity at The Geysers, California

USGS Publications Warehouse

Gomberg, J.; Davis, S.

1996-01-01

The principal results of this study of remotely triggered seismicity in The Geysers geothermal field are the demonstration that triggering (initiation of earthquake failure) depends on a critical strain threshold and that the threshold level increases with decreasing frequency or equivalently, depends on strain rate. This threshold function derives from (1) analyses of dynamic strains associated with surface waves of the triggering earthquakes, (2) statistically measured aftershock zone dimensions, and (3) analytic functional representations of strains associated with power production and tides. The threshold is also consistent with triggering by static strain changes and implies that both static and dynamic strains may cause aftershocks. The observation that triggered seismicity probably occurs in addition to background activity also provides an important constraint on the triggering process. Assuming the physical processes underlying earthquake nucleation to be the same, Gomberg [this issue] discusses seismicity triggered by the MW 7.3 Landers earthquake, its constraints on the variability of triggering thresholds with site, and the implications of time delays between triggering and triggered earthquakes. Our results enable us to reject the hypothesis that dynamic strains simply nudge prestressed faults over a Coulomb failure threshold sooner than they would have otherwise. We interpret the rate-dependent triggering threshold as evidence of several competing processes with different time constants, the faster one(s) facilitating failure and the other(s) inhibiting it. Such competition is a common feature of theories of slip instability. All these results, not surprisingly, imply that to understand earthquake triggering one must consider not only simple failure criteria requiring exceedence of some constant threshold but also the requirements for generating instabilities.

Stress/strain changes and triggered seismicity at The Geysers, California

NASA Astrophysics Data System (ADS)

Gomberg, Joan; Davis, Scott

1996-01-01

The principal results of this study of remotely triggered seismicity in The Geysers geothermal field are the demonstration that triggering (initiation of earthquake failure) depends on a critical strain threshold and that the threshold level increases with decreasing frequency, or, equivalently, depends on strain rate. This threshold function derives from (1) analyses of dynamic strains associated with surface waves of the triggering earthquakes, (2) statistically measured aftershock zone dimensions, and (3) analytic functional representations of strains associated with power production and tides. The threshold is also consistent with triggering by static strain changes and implies that both static and dynamic strains may cause aftershocks. The observation that triggered seismicity probably occurs in addition to background activity also provides an important constraint on the triggering process. Assuming the physical processes underlying earthquake nucleation to be the same, Gomberg [this issue] discusses seismicity triggered by the MW 7.3 Landers earthquake, its constraints on the variability of triggering thresholds with site, and the implications of time delays between triggering and triggered earthquakes. Our results enable us to reject the hypothesis that dynamic strains simply nudge prestressed faults over a Coulomb failure threshold sooner than they would have otherwise. We interpret the rate-dependent triggering threshold as evidence of several competing processes with different time constants, the faster one(s) facilitating failure and the other(s) inhibiting it. Such competition is a common feature of theories of slip instability. All these results, not surprisingly, imply that to understand earthquake triggering one must consider not only simple failure criteria requiring exceedence of some constant threshold but also the requirements for generating instabilities.

Activation of Pax7-Positive Cells in a Non-Contractile Tissue Contributes to Regeneration of Myogenic Tissues in the Electric Fish S. macrurus

PubMed Central

Weber, Christopher M.; Martindale, Mark Q.; Tapscott, Stephen J.; Unguez, Graciela A.

2012-01-01

The ability to regenerate tissues is shared across many metazoan taxa, yet the type and extent to which multiple cellular mechanisms come into play can differ across species. For example, urodele amphibians can completely regenerate all lost tissues, including skeletal muscles after limb amputation. This remarkable ability of urodeles to restore entire limbs has been largely linked to a dedifferentiation-dependent mechanism of regeneration. However, whether cell dedifferentiation is the fundamental factor that triggers a robust regeneration capacity, and whether the loss or inhibition of this process explains the limited regeneration potential in other vertebrates is not known. Here, we studied the cellular mechanisms underlying the repetitive regeneration of myogenic tissues in the electric fish S. macrurus. Our in vivo microinjection studies of high molecular weight cell lineage tracers into single identified adult myogenic cells (muscle or noncontractile muscle-derived electrocytes) revealed no fragmentation or cellularization proximal to the amputation plane. In contrast, ultrastructural and immunolabeling studies verified the presence of myogenic stem cells that express the satellite cell marker Pax7 in mature muscle fibers and electrocytes of S. macrurus. These data provide the first example of Pax-7 positive muscle stem cells localized within a non-contractile electrogenic tissue. Moreover, upon amputation, Pax-7 positive cells underwent a robust replication and were detected exclusively in regions that give rise to myogenic cells and dorsal spinal cord components revealing a regeneration process in S. macrurus that is dependent on the activation of myogenic stem cells for the renewal of both skeletal muscle and the muscle-derived electric organ. These data are consistent with the emergent concept in vertebrate regeneration that different tissues provide a distinct progenitor cell population to the regeneration blastema, and these progenitor cells subsequently restore the original tissue. PMID:22685526

Lessons from (triggered) tremor

USGS Publications Warehouse

Gomberg, Joan

2010-01-01

I test a “clock-advance” model that implies triggered tremor is ambient tremor that occurs at a sped-up rate as a result of loading from passing seismic waves. This proposed model predicts that triggering probability is proportional to the product of the ambient tremor rate and a function describing the efficacy of the triggering wave to initiate a tremor event. Using data mostly from Cascadia, I have compared qualitatively a suite of teleseismic waves that did and did not trigger tremor with ambient tremor rates. Many of the observations are consistent with the model if the efficacy of the triggering wave depends on wave amplitude. One triggered tremor observation clearly violates the clock-advance model. The model prediction that larger triggering waves result in larger triggered tremor signals also appears inconsistent with the measurements. I conclude that the tremor source process is a more complex system than that described by the clock-advance model predictions tested. Results of this and previous studies also demonstrate that (1) conditions suitable for tremor generation exist in many tectonic environments, but, within each, only occur at particular spots whose locations change with time; (2) any fluid flow must be restricted to less than a meter; (3) the degree to which delayed failure and secondary triggering occurs is likely insignificant; and 4) both shear and dilatational deformations may trigger tremor. Triggered and ambient tremor rates correlate more strongly with stress than stressing rate, suggesting tremor sources result from time-dependent weakening processes rather than simple Coulomb failure.

Studying Triggers for Interest and Engagement Using Observational Methods

ERIC Educational Resources Information Center

Renninger, K. Ann; Bachrach, Jessica E.

2015-01-01

In this article, we discuss the contribution of observational methods to understanding the processes involved in triggering interest and establishing engagement. We begin by reviewing the literatures on interest and engagement, noting their similarities, differences, and the utility to each of better understanding the triggering process. We then…

Widespread Triggering of Earthquakes in the Central US by the 2011 M9.0 Tohoku-Oki Earthquake

NASA Astrophysics Data System (ADS)

Rubinstein, J. L.; Savage, H. M.

2011-12-01

The strong shaking of the 2011 M9.0 off-Tohoku earthquake triggered tectonic tremor and earthquakes in many locations around the world. We analyze broadband records from the USARRAY to identify triggered seismicity in more than 10 different locations in the Central United States. We identify triggered events in many states including: Kansas, Nebraska, Arkansas, Minnesota, and Iowa. The locally triggered earthquakes are obscured in broadband records by the Tohoku-Oki mainshock but can be revealed with high-pass filtering. With the exception of one location (central Arkansas), the triggered seismicity occurred in regions that are seismically quiet. The coincidence of this seismicity with the Tohoku-Oki event suggests that these earthquakes were triggered. The triggered seismicity in Arkansas occurred in a region where there has been an active swarm of seismicity since August 2010. There are two lines of evidence to indicate that the seismicity in Arkansas is triggered instead of part of the swarm: (1) we observe two earthquakes that initiate coincident with the arrival of shear wave and Love wave; (2) the seismicity rate increased dramatically following the Tohoku-Oki mainshock. Our observations of widespread earthquake triggering in regions thought to be seismically quiet remind us that earthquakes can occur in most any location. Studying additional teleseismic events has the potential to reveal regions with a propensity for earthquake triggering.

NAD+ depletion or PAR polymer formation: which plays the role of executioner in ischaemic cell death?

PubMed

Siegel, C; McCullough, L D

2011-09-01

Multiple cell death pathways are activated in cerebral ischaemia. Much of the initial injury, especially in the core of the infarct where cerebral blood flow is severely reduced, is necrotic and secondary to severe energy failure. However, there is considerable evidence that delayed cell death continues for several days, primarily in the penumbral region. As reperfusion therapies grow in number and effectiveness, restoration of blood flow early after injury may lead to a shift towards apoptosis. It is important to elucidate what are the key mediators of apoptotic cell death after stroke, as inhibition of apoptosis may have therapeutic implications. There are two well described pathways that lead to apoptotic cell death; the caspase pathway and the more recently described caspase-independent pathway triggered by poly-ADP-ribose polymers (PARP) activation. Caspase-induced cell death is initiated by release of mitochondrial cytochrome c, formation of the cytosolic apoptosome, and activation of endonucleases leading to a multitude of small randomly cleaved DNA fragments. In contrast caspase-independent cell death is secondary to activation of apoptosis inducing factor (AIF). Mitochondrial AIF translocates to the nucleus, where it induces peripheral chromatin condensation, as well as characteristic high-molecular-weight (50 kbp) DNA fragmentation. Although caspase-independent cell death has been recognized for some time and is known to contribute to ischaemic injury, the upstream triggering events leading to activation of this pathway remain unclear. The two major theories are that ischaemia leads to nicotinamide adenine dinucleotide (NAD+) depletion and subsequent energy failure, or alternatively that cell death is directly triggered by a pro-apoptotic factor produced by activation of the DNA repair enzyme PARP. PARP activation is robust in the ischaemic brain producing variable lengths of poly-ADP-ribose (PAR) polymers as byproducts of PARP activation. PAR polymers may be directly toxic by triggering mitochondrial AIF release independently of NAD+ depletion. Recently, sex differences have been discovered that illustrate the importance of understanding these molecular pathways, especially as new therapeutics targeting apoptotic cell death are developed. Cell death in females proceeds primarily via caspase activation whereas caspase-independent mechanisms triggered by the activation of PARP predominate in the male brain. This review summarizes the current literature in an attempt to clarify the roles of NAD+ and PAR polymers in caspase-independent cell death, and discuss sex specific cell death to provide an example of the possible importance of these downstream mediators. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

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.

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.

Neural circuit mechanisms of short-term memory

NASA Astrophysics Data System (ADS)

Goldman, Mark

Memory over time scales of seconds to tens of seconds is thought to be maintained by neural activity that is triggered by a memorized stimulus and persists long after the stimulus is turned off. This presents a challenge to current models of memory-storing mechanisms, because the typical time scales associated with cellular and synaptic dynamics are two orders of magnitude smaller than this. While such long time scales can easily be achieved by bistable processes that toggle like a flip-flop between a baseline and elevated-activity state, many neuronal systems have been observed experimentally to be capable of maintaining a continuum of stable states. For example, in neural integrator networks involved in the accumulation of evidence for decision making and in motor control, individual neurons have been recorded whose activity reflects the mathematical integral of their inputs; in the absence of input, these neurons sustain activity at a level proportional to the running total of their inputs. This represents an analog form of memory whose dynamics can be conceptualized through an energy landscape with a continuum of lowest-energy states. Such continuous attractor landscapes are structurally non-robust, in seeming violation of the relative robustness of biological memory systems. In this talk, I will present and compare different biologically motivated circuit motifs for the accumulation and storage of signals in short-term memory. Challenges to generating robust memory maintenance will be highlighted and potential mechanisms for ameliorating the sensitivity of memory networks to perturbations will be discussed. Funding for this work was provided by NIH R01 MH065034, NSF IIS-1208218, Simons Foundation 324260, and a UC Davis Ophthalmology Research to Prevent Blindness Grant.

Prediction of Human Performance Using Electroencephalography under Different Indoor Room Temperatures

PubMed Central

Zhang, Tinghe; Mao, Zijing; Xu, Xiaojing; Zhang, Lin; Pack, Daniel J.; Dong, Bing; Huang, Yufei

2018-01-01

Varying indoor environmental conditions is known to affect office worker’s performance; wherein past research studies have reported the effects of unfavorable indoor temperature and air quality causing sick building syndrome (SBS) among office workers. Thus, investigating factors that can predict performance in changing indoor environments have become a highly important research topic bearing significant impact in our society. While past research studies have attempted to determine predictors for performance, they do not provide satisfactory prediction ability. Therefore, in this preliminary study, we attempt to predict performance during office-work tasks triggered by different indoor room temperatures (22.2 °C and 30 °C) from human brain signals recorded using electroencephalography (EEG). Seven participants were recruited, from whom EEG, skin temperature, heart rate and thermal survey questionnaires were collected. Regression analyses were carried out to investigate the effectiveness of using EEG power spectral densities (PSD) as predictors of performance. Our results indicate EEG PSDs as predictors provide the highest R2 (> 0.70), that is 17 times higher than using other physiological signals as predictors and is more robust. Finally, the paper provides insight on the selected predictors based on brain activity patterns for low- and high-performance levels under different indoor-temperatures. PMID:29690601

Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease.

PubMed

Christensen, Ditte Z; Bayer, Thomas A; Wirths, Oliver

2010-07-01

Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model. Expression of the APP transgene was found in ChAT-positive neurons of motor nuclei accompanied by robust intracellular Abeta accumulation, whereas no APP expressing neurons and thus no intracellular Abeta accumulation were found in neither the forebrain or pons complexes, nor in the caudate putamen. This expression pattern was used as a model system to study the effect of intra- and extracellular Abeta accumulation on neuron loss in the cholinergic system. Stereological quantification revealed a loss of ChAT-positive neurons in APP/PS1KI mice only in the motor nuclei Mo5 and 7N accumulating intracellular Abeta. This study supports the hypothesis of intracellular Abeta accumulation as an early pathological alteration contributing to cell death in AD. Copyright 2008 Elsevier Inc. All rights reserved.

Prediction of Human Performance Using Electroencephalography under Different Indoor Room Temperatures.

PubMed

Nayak, Tapsya; Zhang, Tinghe; Mao, Zijing; Xu, Xiaojing; Zhang, Lin; Pack, Daniel J; Dong, Bing; Huang, Yufei

2018-04-23

Varying indoor environmental conditions is known to affect office worker’s performance; wherein past research studies have reported the effects of unfavorable indoor temperature and air quality causing sick building syndrome (SBS) among office workers. Thus, investigating factors that can predict performance in changing indoor environments have become a highly important research topic bearing significant impact in our society. While past research studies have attempted to determine predictors for performance, they do not provide satisfactory prediction ability. Therefore, in this preliminary study, we attempt to predict performance during office-work tasks triggered by different indoor room temperatures (22.2 °C and 30 °C) from human brain signals recorded using electroencephalography (EEG). Seven participants were recruited, from whom EEG, skin temperature, heart rate and thermal survey questionnaires were collected. Regression analyses were carried out to investigate the effectiveness of using EEG power spectral densities (PSD) as predictors of performance. Our results indicate EEG PSDs as predictors provide the highest R ² (> 0.70), that is 17 times higher than using other physiological signals as predictors and is more robust. Finally, the paper provides insight on the selected predictors based on brain activity patterns for low- and high-performance levels under different indoor-temperatures.

Simulating Shock Triggered Star Formation with AstroBEAR2.0

NASA Astrophysics Data System (ADS)

Li, Shule; Frank, Adam; Blackman, Eric

2013-07-01

Star formation can be triggered by the compression from shocks running over stable clouds. Triggered star formation is a favored explanation for the traces of SLRI's in our solar system. Previous research has shown that when parameters such as shock speed are within a certain range, the gravitational collapse of otherwise stable, dense cloud cores is possible. However, these studies usually focus on the precursors of star formation, and the conditions for the triggering. We use AstroBEAR2.0 code to simulate the collapse and subsequent evolution of a stable Bonnor-Ebert cloud by an incoming shock. Through our simulations, we show that interesting physics happens when the newly formed star interacts with the cloud residue and the post-shock flow. We identify these interactions as controlled by the initial conditions of the triggering and study the flow pattern as well as the evolution of important physics quantities such as accretion rate and angular momentum.

Analysis of a potential trigger of an acute illness.

PubMed

Becker, Niels G; Salim, Agus; Kelman, Christopher W

2006-01-01

Sometimes certain short-term risk exposures are postulated to act as a trigger for the onset of a specific acute illness. When the incidence of the illness is low it is desirable to investigate this possible association using only data on cases detected during a specific observation period. Here we propose an analysis for such a study based on a model expressed in terms of the probability that the exposure triggers the illness and a random delay from a triggered illness until its diagnosis. Both the natural hazard rate for the illness and the probability that the exposure triggers the illness are assumed to be small and possibly dependent on age and covariates such as sex and duration or severity of the exposure. The method of analysis is illustrated with a study of the association between long flights and hospitalization for venous thromboembolism.

Triggering of longitudinal combustion instabilities in solid rocket motors: Nonlinear combustion response

NASA Technical Reports Server (NTRS)

Wicker, J. M.; Greene, W. D.; Kim, S. I.; Yang, V.

1995-01-01

Pulsed oscillations in solid rocket motors are investigated with emphasis on nonlinear combustion response. The study employs a wave equation governing the unsteady motions in a two-phase flow, and a solution technique based on spatial- and time-averaging. A wide class of combustion response functions is studied to second-order in fluctuation amplitude to determine if, when, and how triggered instabilities arise. Conditions for triggering are derived from analysis of limit cycles, and regions of triggering are found in parametric space. Based on the behavior of model dynamical systems, introduction of linear cross-coupling and quadratic self-coupling among the acoustic modes appears to be the manner in which 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.

Electrochemical latent redox ratiometric probes for real-time tracking and quantification of endogenous hydrogen sulfide production in living cells.

PubMed

Manibalan, Kesavan; Mani, Veerappan; Chang, Pu-Chieh; Huang, Chih-Hung; Huang, Sheng-Tung; Marchlewicz, Kasper; Neethirajan, Suresh

2017-10-15

Hydrogen sulfide (H 2 S) was discovered as a third gasotransmitter in biological systems and recent years have seen a growing interest to understand its physiological and pathological functions. However, one major limiting factor is the lack of robust sensors to quantitatively track its production in real-time. We described a facile electrochemical assay based on latent redox probe approach for highly specific and sensitive quantification in living cells. Two chemical probes, Azido Benzyl ferrocene carbamate (ABFC) and N-alkyl Azido Benzyl ferrocene carbamate (NABFC) composed of azide trigger group were designed. H 2 S molecules specifically triggered the release of reporters from probes and the current response was monitored using graphene oxide film modified electrode as transducer. The detection limits are 0.32µM (ABFC) and 0.076µM (NABFC) which are comparable to those of current sensitive methods. The probes are successful in the determination of H 2 S spiked in whole human blood, fetal bovine serum, and E. coli. The continuous monitoring and quantification of endogenous H 2 S production in E. coli were successfully accomplished. This work lays first step stone towards real-time electrochemical quantification of endogenous H 2 S in living cells, thus hold great promise in the analytical aspects of H 2 S. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

PubMed

An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-04-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

Improving Robot Motor Learning with Negatively Valenced Reinforcement Signals

PubMed Central

Navarro-Guerrero, Nicolás; Lowe, Robert J.; Wermter, Stefan

2017-01-01

Both nociception and punishment signals have been used in robotics. However, the potential for using these negatively valenced types of reinforcement learning signals for robot learning has not been exploited in detail yet. Nociceptive signals are primarily used as triggers of preprogrammed action sequences. Punishment signals are typically disembodied, i.e., with no or little relation to the agent-intrinsic limitations, and they are often used to impose behavioral constraints. Here, we provide an alternative approach for nociceptive signals as drivers of learning rather than simple triggers of preprogrammed behavior. Explicitly, we use nociception to expand the state space while we use punishment as a negative reinforcement learning signal. We compare the performance—in terms of task error, the amount of perceived nociception, and length of learned action sequences—of different neural networks imbued with punishment-based reinforcement signals for inverse kinematic learning. We contrast the performance of a version of the neural network that receives nociceptive inputs to that without such a process. Furthermore, we provide evidence that nociception can improve learning—making the algorithm more robust against network initializations—as well as behavioral performance by reducing the task error, perceived nociception, and length of learned action sequences. Moreover, we provide evidence that punishment, at least as typically used within reinforcement learning applications, may be detrimental in all relevant metrics. PMID:28420976

Consideration of reference points for the management of renewable resources under an adaptive management paradigm

USGS Publications Warehouse

Irwin, Brian J.; Conroy, Michael J.

2013-01-01

The success of natural resource management depends on monitoring, assessment and enforcement. In support of these efforts, reference points (RPs) are often viewed as critical values of management-relevant indicators. This paper considers RPs from the standpoint of objective-driven decision making in dynamic resource systems, guided by principles of structured decision making (SDM) and adaptive resource management (AM). During the development of natural resource policy, RPs have been variously treated as either ‘targets’ or ‘triggers’. Under a SDM/AM paradigm, target RPs correspond approximately to value-based objectives, which may in turn be either of fundamental interest to stakeholders or intermediaries to other central objectives. By contrast, trigger RPs correspond to decision rules that are presumed to lead to desirable outcomes (such as the programme targets). Casting RPs as triggers or targets within a SDM framework is helpful towards clarifying why (or whether) a particular metric is appropriate. Further, the benefits of a SDM/AM process include elucidation of underlying untested assumptions that may reveal alternative metrics for use as RPs. Likewise, a structured decision-analytic framework may also reveal that failure to achieve management goals is not because the metrics are wrong, but because the decision-making process in which they are embedded is insufficiently robust to uncertainty, is not efficiently directed at producing a resource objective, or is incapable of adaptation to new knowledge.

Staphylococcus aureus Extracellular Adherence Protein Triggers TNFα Release, Promoting Attachment to Endothelial Cells via Protein A

PubMed Central

Edwards, Andrew M.; Bowden, Maria Gabriela; Brown, Eric L.; Laabei, Maisem; Massey, Ruth C.

2012-01-01

Staphylococcus aureus is a leading cause of bacteraemia, which frequently results in complications such as infective endocarditis, osteomyelitis and exit from the bloodstream to cause metastatic abscesses. Interaction with endothelial cells is critical to these complications and several bacterial proteins have been shown to be involved. The S. aureus extracellular adhesion protein (Eap) has many functions, it binds several host glyco-proteins and has both pro- and anti-inflammatory activity. Unfortunately its role in vivo has not been robustly tested to date, due to difficulties in complementing its activity in mutant strains. We previously found Eap to have pro-inflammatory activity, and here show that purified native Eap triggered TNFα release in whole human blood in a dose-dependent manner. This level of TNFα increased adhesion of S. aureus to endothelial cells 4-fold via a mechanism involving protein A on the bacterial surface and gC1qR/p33 on the endothelial cell surface. The contribution this and other Eap activities play in disease severity during bacteraemia was tested by constructing an isogenic set of strains in which the eap gene was inactivated and complemented by inserting an intact copy elsewhere on the bacterial chromosome. Using a murine bacteraemia model we found that Eap expressing strains cause a more severe infection, demonstrating its role in invasive disease. PMID:22905199

How Robust Is Your Project? From Local Failures to Global Catastrophes: A Complex Networks Approach to Project Systemic Risk.

PubMed

Ellinas, Christos; Allan, Neil; Durugbo, Christopher; Johansson, Anders

2015-01-01

Current societal requirements necessitate the effective delivery of complex projects that can do more while using less. Yet, recent large-scale project failures suggest that our ability to successfully deliver them is still at its infancy. Such failures can be seen to arise through various failure mechanisms; this work focuses on one such mechanism. Specifically, it examines the likelihood of a project sustaining a large-scale catastrophe, as triggered by single task failure and delivered via a cascading process. To do so, an analytical model was developed and tested on an empirical dataset by the means of numerical simulation. This paper makes three main contributions. First, it provides a methodology to identify the tasks most capable of impacting a project. In doing so, it is noted that a significant number of tasks induce no cascades, while a handful are capable of triggering surprisingly large ones. Secondly, it illustrates that crude task characteristics cannot aid in identifying them, highlighting the complexity of the underlying process and the utility of this approach. Thirdly, it draws parallels with systems encountered within the natural sciences by noting the emergence of self-organised criticality, commonly found within natural systems. These findings strengthen the need to account for structural intricacies of a project's underlying task precedence structure as they can provide the conditions upon which large-scale catastrophes materialise.

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…

GnRHa to trigger final oocyte maturation: a time to reconsider.

PubMed

Humaidan, P; Papanikolaou, E G; Tarlatzis, B C

2009-10-01

Recently GnRH antagonist protocols for the prevention of a premature LH surge were introduced, allowing final oocyte maturation to be triggered with a single bolus of a GnRH agonist (GnRHa). GnRHa is as effective as hCG for the induction of ovulation, and apart from the LH surge a FSH surge is also induced. Until recently, prospective randomized studies reported a poor clinical outcome when GnRHa was used to trigger final oocyte maturation in IVF/ICSI antagonist protocols, presumably due to a luteal phase deficiency, despite standard luteal phase supplementation with progesterone and estradiol. As GnRHa triggering of final oocyte maturation could possess advantages over hCG triggering in terms of a reduced if not eliminated risk of ovarian hyperstimulation syndrome (OHSS) and the retrieval of more mature oocytes, the challenge has been to rescue the luteal phase. In the literature now several studies report a luteal phase rescue with a reproductive outcome comparable to that of hCG induced final oocyte maturation. Although more research is needed, GnRHa triggering is now a valid alternative with potential benefits.

An Intercompany Perspective on Biopharmaceutical Drug Product Robustness Studies.

PubMed

Morar-Mitrica, Sorina; Adams, Monica L; Crotts, George; Wurth, Christine; Ihnat, Peter M; Tabish, Tanvir; Antochshuk, Valentyn; DiLuzio, Willow; Dix, Daniel B; Fernandez, Jason E; Gupta, Kapil; Fleming, Michael S; He, Bing; Kranz, James K; Liu, Dingjiang; Narasimhan, Chakravarthy; Routhier, Eric; Taylor, Katherine D; Truong, Nobel; Stokes, Elaine S E

2018-02-01

The Biophorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Point Share group conducted an intercompany collaboration exercise, which included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration revealed several key common themes: (1) overall DP robustness is defined by both the formulation and the manufacturing process robustness; (2) robustness integrates the principles of quality by design (QbD); (3) DP robustness is an important factor in setting critical quality attribute control strategies and commercial specifications; (4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics, to develop the DP design space; (5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product and process knowledge. The BPDG-Formulation Point Share discusses identified industry challenges with regard to biopharmaceutical DP robustness and presents some recommendations for best practices. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Public health importance of triggers of myocardial infarction: a comparative risk assessment.

PubMed

Nawrot, Tim S; Perez, Laura; Künzli, Nino; Munters, Elke; Nemery, Benoit

2011-02-26

Acute myocardial infarction is triggered by various factors, such as physical exertion, stressful events, heavy meals, or increases in air pollution. However, the importance and relevance of each trigger are uncertain. We compared triggers of myocardial infarction at an individual and population level. We searched PubMed and the Web of Science citation databases to identify studies of triggers of non-fatal myocardial infarction to calculate population attributable fractions (PAF). When feasible, we did a meta-regression analysis for studies of the same trigger. Of the epidemiologic studies reviewed, 36 provided sufficient details to be considered. In the studied populations, the exposure prevalence for triggers in the relevant control time window ranged from 0.04% for cocaine use to 100% for air pollution. The reported odds ratios (OR) ranged from 1.05 to 23.7. Ranking triggers from the highest to the lowest OR resulted in the following order: use of cocaine, heavy meal, smoking of marijuana, negative emotions, physical exertion, positive emotions, anger, sexual activity, traffic exposure, respiratory infections, coffee consumption, air pollution (based on a difference of 30 μg/m3 in particulate matter with a diameter <10 μm [PM10]). Taking into account the OR and the prevalences of exposure, the highest PAF was estimated for traffic exposure (7.4%), followed by physical exertion (6.2%), alcohol (5.0%), coffee (5.0%), a difference of 30 μg/m3 in PM10 (4.8%), negative emotions (3.9%), anger (3.1%), heavy meal (2.7%), positive emotions (2.4%), sexual activity (2.2%), cocaine use (0.9%), marijuana smoking (0.8%) and respiratory infections (0.6%). Interpretation In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of myocardial infarction, it is of similar magnitude (PAF 5-7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance. The research on air pollution and health at Hasselt University is supported by a grant from the Flemish Scientific Fund (FWO, Krediet aan navorsers/G.0873.11), tUL-impulse financing, and bijzonder onderzoeksfonds (BOF) and at the Katholieke Universiteit Leuven by the sustainable development programme of BELSPO (Belgian Science Policy).

Remote Triggering of Microseismicity in Antarctica

NASA Astrophysics Data System (ADS)

Ji, M.; Li, C.; Peng, Z.; Walter, J. I.

2017-12-01

It is well known that large distant earthquakes can trigger microearthquakes/tectonic tremors during or immediately following their surface waves. Globally, triggered seismicity is mostly found in active plate boundary regions. Recent studies have shown that icequakes in Antartica can also be triggered by teleseismic events. However, it is still not clear how widespread this phenomenon is and whether there are any connections between large earthquakes and subsequent glacial movements. In this study, we conduct a systematic search for remotely triggered activity in Antarctica following recent large earthquakes, including the 2004 Mw9.1 Sumatra, 2011 Mw9.1 Tohoku, 2012 Mw8.6 Indian Ocean and 2014-2015 Chile earthquakes. We download seismic data recorded at the POLENET (YT) and the Argentina Antarctica Network (AI) from the Incorporated Research Institutions for Seismology (IRIS) Data Management Center (DMC). We apply a 2-8 Hz band-pass-filter to the continuous waveforms and visually identify local events during and immediately after the large amplitude surface waves. Spectrograms are computed as additional tools to identify triggered seismicity and are further confirmed by comparing the signals before and after the distant mainshocks. So far we have identified possible triggered seismicity in both networks' area following the 2010 Chile and 2011 Tohoku earthquakes. Our next step is to apply a waveform matching method to automatically detect possible triggered seismicity and check through all the available networks in Antarctica for the last decades, which should help to better understand the potential interaction between large earthquakes and icequakes in this region.

Cascading hazards: Understanding triggering relations between wet tropical cyclones, landslides, and earthquakes

NASA Astrophysics Data System (ADS)

Wdowinski, S.; Peng, Z.; Ferrier, K.; Lin, C. H.; Hsu, Y. J.; Shyu, J. B. H.

2017-12-01

Earthquakes, landslides, and tropical cyclones are extreme hazards that pose significant threats to human life and property. Some of the couplings between these hazards are well known. For example, sudden, widespread landsliding can be triggered by large earthquakes and by extreme rainfall events like tropical cyclones. Recent studies have also shown that earthquakes can be triggered by erosional unloading over 100-year timescales. In a NASA supported project, titled "Cascading hazards: Understanding triggering relations between wet tropical cyclones, landslides, and earthquake", we study triggering relations between these hazard types. The project focuses on such triggering relations in Taiwan, which is subjected to very wet tropical storms, landslides, and earthquakes. One example for such triggering relations is the 2009 Morakot typhoon, which was the wettest recorded typhoon in Taiwan (2850 mm of rain in 100 hours). The typhoon caused widespread flooding and triggered more than 20,000 landslides, including the devastating Hsiaolin landslide. Six months later, the same area was hit by the 2010 M=6.4 Jiashian earthquake near Kaohsiung city, which added to the infrastructure damage induced by the typhoon and the landslides. Preliminary analysis of temporal relations between main-shock earthquakes and the six wettest typhoons in Taiwan's past 50 years reveals similar temporal relations between M≥5 events and wet typhoons. Future work in the project will include remote sensing analysis of landsliding, seismic and geodetic monitoring of landslides, detection of microseismicity and tremor activities, and mechanical modeling of crustal stress changes due to surface unloading.

Note: Novel trigger pulse feed method for mega-volt gas switch.

PubMed

Yin, Jiahui; Sun, Fengju; Jiang, Xiaofeng; Wang, Zhiguo; Liang, Tianxue; Jiang, Hongyu; Qiu, Aici

2017-07-01

It is difficult to feed the trigger pulse into an electrically triggered mega-volt switch, and the present note presents a novel trigger pulse feed method. The trigger pulse is introduced via a damping resistor, which is mounted between the inner and outer cylindrical electrodes of the pulse transmission line. The mega-volt pulse is damped because the voltage is resistively divided by the resistor and trigger cable arrangement. Both the complex breakdown processes of the switch and its insulation issues are experimentally studied. The function and the beneficial effects of the damping resistor, installed together with an additional inductor, are discussed. Finally, the parameters of these two damping components are set to 500 Ω and 2 μH values for which the switch has been demonstrated to work successfully at over 2.3 MV.

AMP-Conjugated Quantum Dots: Low Immunotoxicity Both In Vitro and In Vivo

NASA Astrophysics Data System (ADS)

Dai, Tongcheng; Li, Na; Liu, Lu; Liu, Qin; Zhang, Yuanxing

2015-11-01

Quantum dots (QDs) are engineered nanoparticles that possess special optical and electronic properties and have shown great promise for future biomedical applications. In this work, adenosine 5'-monophosphate (AMP), a small biocompatible molecular, was conjugated to organic QDs to produce hydrophilic AMP-QDs. Using macrophage J774A.1 as the cell model, AMP-QDs exhibited both prior imaging property and low toxicity, and more importantly, triggered limited innate immune responses in macrophage, indicating low immunotoxicity in vitro. Using BALB/c mice as the animal model, AMP-QDs were found to be detained in immune organs but did not evoke robust inflammation responses or obvious histopathological abnormalities, which reveals low immunotoxicity in vivo. This work suggests that AMP is an excellent surface ligand with low immunotoxicity, and potentially used in surface modification for more extensive nanoparticles.

Clinical-Grade Manufacturing of Therapeutic Human Mesenchymal Stem/Stromal Cells in Microcarrier-Based Culture Systems.

PubMed

Fernandes-Platzgummer, Ana; Carmelo, Joana G; da Silva, Cláudia Lobato; Cabral, Joaquim M S

2016-01-01

The therapeutic potential of mesenchymal stem/stromal cells (MSC) has triggered the need for high cell doses in a vast number of clinical applications. This demand requires the development of good manufacturing practices (GMP)-compliant ex vivo expansion protocols that should be effective to deliver a robust and reproducible supply of clinical-grade cells in a safe and cost-effective manner. Controlled stirred-tank bioreactor systems under xenogeneic (xeno)-free culture conditions offer ideal settings to develop and optimize cell manufacturing to meet the standards and needs of human MSC for cellular therapies. Herein we describe two microcarrier-based stirred culture systems using spinner flasks and controlled stirred-tank bioreactors under xeno-free conditions for the efficient ex vivo expansion of human bone marrow and adipose tissue-derived MSC.

A robust and stable PLC based control system for 40kJ/25kV EMM system

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

Sharma, Vijay; Saroj, P.C.; Kulkarni, M.R.

2014-07-01

This paper describes the PLC based control system developed for a 40kJ/25kV Electro-magnetic machining (EMM) system. In EMM system large capacitor banks is charged with high voltage to store large energy and the banks is made to discharge into a coil within few milli-seconds using a triggered spark gaps. During discharge of the capacitor large surges and transients are generated in the system. The control system monitors/controls and interlocks all the units of the system for proper operation. The control system is the only subsystem which is electrically connected to all the low and high voltage subsystems. Care should bemore » taken at the signal interfacing with the control system to protect the control system. (author)« less

The Regulatory Capacity of Bivalent Genes—A Theoretical Approach

PubMed Central

Thalheim, Torsten; Herberg, Maria; Loeffler, Markus; Galle, Joerg

2017-01-01

Bivalent genes are frequently associated with developmental and lineage specification processes. Resolving their bivalency enables fast changes in their expression, which potentially can trigger cell fate decisions. Here, we provide a theoretical model of bivalency that allows for predictions on the occurrence, stability and regulatory capacity of this prominent modification state. We suggest that bivalency enables balanced gene expression heterogeneity that constitutes a prerequisite of robust lineage priming in somatic stem cells. Moreover, we demonstrate that interactions between the histone and DNA methylation machineries together with the proliferation activity control the stability of the bivalent state and can turn it into an unmodified state. We suggest that deregulation of these interactions underlies cell transformation processes as associated with acute myeloid leukemia (AML) and provide a model of AML blast formation following deregulation of the Ten-eleven Translocation (TET) pathway. PMID:28513551

Jet-like correlations with direct-photon and neutral-pion triggers at √{sNN} = 200 GeV

NASA Astrophysics Data System (ADS)

Adamczyk, L.; Adkins, J. K.; Agakishiev, G.; Aggarwal, M. M.; Ahammed, Z.; Alekseev, I.; Anderson, D. M.; Aparin, A.; Arkhipkin, D.; Aschenauer, E. C.; Ashraf, M. U.; Attri, A.; Averichev, G. S.; Bai, X.; Bairathi, V.; Bellwied, R.; Bhasin, A.; Bhati, A. K.; Bhattarai, P.; Bielcik, J.; Bielcikova, J.; Bland, L. C.; Bordyuzhin, I. G.; Bouchet, J.; Brandenburg, J. D.; Brandin, A. V.; Bunzarov, I.; Butterworth, J.; Caines, H.; Calderón de la Barca Sánchez, M.; Campbell, J. M.; Cebra, D.; Chakaberia, I.; Chaloupka, P.; Chang, Z.; Chatterjee, A.; Chattopadhyay, S.; Chen, X.; Chen, J. H.; Cheng, J.; Cherney, M.; Christie, W.; Contin, G.; Crawford, H. J.; Das, S.; De Silva, L. C.; Debbe, R. R.; Dedovich, T. G.; Deng, J.; Derevschikov, A. A.; di Ruzza, B.; Didenko, L.; Dilks, C.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Du, C. M.; Dunkelberger, L. E.; Dunlop, J. C.; Efimov, L. G.; Engelage, J.; Eppley, G.; Esha, R.; Evdokimov, O.; Eyser, O.; Fatemi, R.; Fazio, S.; Federic, P.; Fedorisin, J.; Feng, Z.; Filip, P.; Fisyak, Y.; Flores, C. E.; Fulek, L.; Gagliardi, C. A.; Garand, D.; Geurts, F.; Gibson, A.; Girard, M.; Greiner, L.; Grosnick, D.; Gunarathne, D. S.; Guo, Y.; Gupta, S.; Gupta, A.; Guryn, W.; Hamad, A. I.; Hamed, A.; Haque, R.; Harris, J. W.; He, L.; Heppelmann, S.; Heppelmann, S.; Hirsch, A.; Hoffmann, G. W.; Horvat, S.; Huang, T.; Huang, B.; Huang, X.; Huang, H. Z.; Huck, P.; Humanic, T. J.; Igo, G.; Jacobs, W. W.; Jang, H.; Jentsch, A.; Jia, J.; Jiang, K.; Judd, E. G.; Kabana, S.; Kalinkin, D.; Kang, K.; Kauder, K.; Ke, H. W.; Keane, D.; Kechechyan, A.; Khan, Z. H.; Kikoła, D. P.; Kisel, I.; Kisiel, A.; Kochenda, L.; Koetke, D. D.; Kosarzewski, L. K.; Kraishan, A. F.; Kravtsov, P.; Krueger, K.; Kumar, L.; Lamont, M. A. C.; Landgraf, J. M.; Landry, K. D.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, J. H.; Li, X.; Li, Y.; Li, C.; Li, W.; Li, X.; Lin, T.; Lisa, M. A.; Liu, F.; Liu, Y.; Ljubicic, T.; Llope, W. J.; Lomnitz, M.; Longacre, R. S.; Luo, X.; Luo, S.; Ma, G. L.; Ma, L.; Ma, Y. G.; Ma, R.; Magdy, N.; Majka, R.; Manion, A.; Margetis, S.; Markert, C.; Matis, H. S.; McDonald, D.; McKinzie, S.; Meehan, K.; Mei, J. C.; Miller, Z. W.; Minaev, N. G.; Mioduszewski, S.; Mishra, D.; Mohanty, B.; Mondal, M. M.; Morozov, D. A.; Mustafa, M. K.; Nandi, B. K.; Nasim, Md.; Nayak, T. K.; Nigmatkulov, G.; Niida, T.; Nogach, L. V.; Noh, S. Y.; Novak, J.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Oh, K.; Okorokov, V. A.; Olvitt, D.; Page, B. S.; Pak, R.; Pan, Y. X.; Pandit, Y.; Panebratsev, Y.; Pawlik, B.; Pei, H.; Perkins, C.; Pile, P.; Pluta, J.; Poniatowska, K.; Porter, J.; Posik, M.; Poskanzer, A. M.; Pruthi, N. K.; Przybycien, M.; Putschke, J.; Qiu, H.; Quintero, A.; Ramachandran, S.; Ray, R. L.; Reed, R.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Ruan, L.; Rusnak, J.; Rusnakova, O.; Sahoo, N. R.; Sahu, P. K.; Sakrejda, I.; Salur, S.; Sandweiss, J.; Sarkar, A.; Schambach, J.; Scharenberg, R. P.; Schmah, A. M.; Schmidke, W. B.; Schmitz, N.; Seger, J.; Seyboth, P.; Shah, N.; Shahaliev, E.; Shanmuganathan, P. V.; Shao, M.; Sharma, A.; Sharma, B.; Sharma, M. K.; Shen, W. Q.; Shi, Z.; Shi, S. S.; Shou, Q. Y.; Sichtermann, E. P.; Sikora, R.; Simko, M.; Singha, S.; Skoby, M. J.; Smirnov, D.; Smirnov, N.; Solyst, W.; Song, L.; Sorensen, P.; Spinka, H. M.; Srivastava, B.; Stanislaus, T. D. S.; Stepanov, M.; Stock, R.; Strikhanov, M.; Stringfellow, B.; Sumbera, M.; Summa, B.; Sun, Y.; Sun, Z.; Sun, X. M.; Surrow, B.; Svirida, D. N.; Tang, Z.; Tang, A. H.; Tarnowsky, T.; Tawfik, A.; Thäder, J.; Thomas, J. H.; Timmins, A. R.; Tlusty, D.; Todoroki, T.; Tokarev, M.; Trentalange, S.; Tribble, R. E.; Tribedy, P.; Tripathy, S. K.; Tsai, O. D.; Ullrich, T.; Underwood, D. G.; Upsal, I.; Van Buren, G.; van Nieuwenhuizen, G.; Vandenbroucke, M.; Varma, R.; Vasiliev, A. N.; Vertesi, R.; Videbæk, F.; Vokal, S.; Voloshin, S. A.; Vossen, A.; Wang, H.; Wang, F.; Wang, Y.; Wang, J. S.; Wang, G.; Wang, Y.; Webb, J. C.; Webb, G.; Wen, L.; Westfall, G. D.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, Y.; Xiao, Z. G.; Xie, W.; Xie, G.; Xin, K.; Xu, N.; Xu, Q. H.; Xu, Z.; Xu, J.; Xu, H.; Xu, Y. F.; Yang, S.; Yang, Y.; Yang, C.; Yang, Y.; Yang, Y.; Yang, Q.; Ye, Z.; Ye, Z.; Yi, L.; Yip, K.; Yoo, I.-K.; Yu, N.; Zbroszczyk, H.; Zha, W.; Zhang, Z.; Zhang, J. B.; Zhang, S.; Zhang, S.; Zhang, X. P.; Zhang, Y.; Zhang, J.; Zhang, J.; Zhao, J.; Zhong, C.; Zhou, L.; Zhu, X.; Zoulkarneeva, Y.; Zyzak, M.; STAR Collaboration

2016-09-01

Azimuthal correlations of charged hadrons with direct-photon (γdir) and neutral-pion (π0) trigger particles are analyzed in central Au+Au and minimum-bias p + p collisions at √{sNN} = 200 GeV in the STAR experiment. The charged-hadron per-trigger yields at mid-rapidity from central Au+Au collisions are compared with p + p collisions to quantify the suppression in Au+Au collisions. The suppression of the away-side associated-particle yields per γdir trigger is independent of the transverse momentum of the trigger particle (pTtrig), whereas the suppression is smaller at low transverse momentum of the associated charged hadrons (pTassoc). Within uncertainty, similar levels of suppression are observed for γdir and π0 triggers as a function of zT (≡ pTassoc/pTtrig). The results are compared with energy-loss-inspired theoretical model predictions. Our studies support previous conclusions that the lost energy reappears predominantly at low transverse momentum, regardless of the trigger energy.

Cryptochrome and Phytochrome Cooperatively but Independently Reduce Active Gibberellin Content in Rice Seedlings under Light Irradiation

PubMed Central

Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

2012-01-01

In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4–OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants. PMID:22764280

Cryptochrome and phytochrome cooperatively but independently reduce active gibberellin content in rice seedlings under light irradiation.

PubMed

Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

2012-09-01

In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4-OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants.

A hypothesis for delayed dynamic earthquake triggering

USGS Publications Warehouse

Parsons, T.

2005-01-01

It's uncertain whether more near-field earthquakes are triggered by static or dynamic stress changes. This ratio matters because static earthquake interactions are increasingly incorporated into probabilistic forecasts. Recent studies were unable to demonstrate all predictions from the static-stress-change hypothesis, particularly seismicity rate reductions. However, current dynamic stress change hypotheses do not explain delayed earthquake triggering and Omori's law. Here I show numerically that if seismic waves can alter some frictional contacts in neighboring fault zones, then dynamic triggering might cause delayed triggering and an Omori-law response. The hypothesis depends on faults following a rate/state friction law, and on seismic waves changing the mean critical slip distance (Dc) at nucleation zones.

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

PubMed Central

Spadavecchia, Jolanda; Movia, Dania; Moore, Caroline; Maguire, Ciaran Manus; Moustaoui, Hanane; Casale, Sandra; Volkov, Yuri; Prina-Mello, Adriele

2016-01-01

The main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG)-gold nanoparticles (AuNPs) and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]). In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50) and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene 1 (hERG1) channel aberrantly expressed on the membrane of pancreatic cancer cells. Targeted PEG-AuNPs were translocated into the lysosomes and were associated to an increased lysosomal function in PANC-1 cells. Additionally, doxorubicin release into an aqueous environment was almost negligible after 7 days, suggesting that drug release from PEG-AuNPs was triggered by enzymatic activity. Although preliminary, data gathered from this study have considerable potential in the application of safe-by-design nano-enabled drug-delivery systems (ie, nanomedicines) for the treatment of pancreatic cancer, a disease with a poor prognosis and one of the main current burdens of today’s health care bill of industrialized countries. PMID:27013874

Natural experimentation is a challenging method for identifying headache triggers.

PubMed

Houle, Timothy T; Turner, Dana P

2013-04-01

In this study, we set out to determine whether individual headache sufferers can learn about the potency of their headache triggers (causes) using only natural experimentation. Headache patients naturally use the covariation of the presence-absence of triggers with headache attacks to assess the potency of triggers. The validity of this natural experimentation has never been investigated. A companion study has proposed 3 assumptions that are important for assigning causal status to triggers. This manuscript examines one of these assumptions, constancy in trigger presentation, using real-world conditions. The similarity of day-to-day weather conditions over 4 years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in 9 regularly cycling headache sufferers, was examined using several available time series. An arbitrary threshold of 90% similarity using Gower's index identified similar days for comparison. The day-to-day variability in just these 3 headache triggers is substantial enough that finding 2 naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine vs not drinking wine) will only infrequently occur. Fluctuations in weather patterns resulted in a median of 2.3 days each year that were similar (range 0-27.4). Considering fluctuations in stress patterns and ovarian hormones, only 1.5 days/month (95% confidence interval 1.2-2.9) and 2.0 days/month (95% confidence interval 1.9-2.2), respectively, met our threshold for similarity. Although assessing the personal causes of headache is an age-old endeavor, the great many candidate triggers exhibit variability that may prevent sound conclusions without assistance from formal experimentation or statistical balancing. © 2013 American Headache Society.

Natural experimentation is a challenging method for identifying headache triggers

PubMed Central

Houle, Timothy T.; Turner, Dana P.

2015-01-01

Objective In this study we set out to determine whether individual headache sufferers can learn about the potency of their headache triggers (causes) using only natural experimentation. Background Headache patients naturally use the covariation of the presence-absence of triggers with headache attacks to assess the potency of triggers. The validity of this natural experimentation has never been investigated. A companion study has proposed three assumptions that are important for assigning causal status to triggers. This manuscript examines one of these assumptions, constancy in trigger presentation, using real-world conditions. Methods The similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine regularly cycling headache sufferers were examined using several available time-series. An arbitrary threshold of 90% similarity using Gower's index identified similar days for comparison. Results The day-to-day variability in just these three headache triggers is substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (e.g., drinking wine versus not drinking wine) will only infrequently occur. Fluctuations in weather patterns resulted in a median of 2.3 days each year that were similar (range: 0 to 27.4). Considering fluctuations in stress patterns and ovarian hormones, only 1.5 days/month (95%CI: 1.2 to 2.9) and 2.0 days/month (95%CI: 1.9 to 2.2), respectively, met our threshold for similarity.. Conclusion Although assessing the personal causes of headache is an age-old endeavor, the great many candidate triggers exhibit variability that may prevent sound conclusions without assistance from formal experimentation or statistical balancing. PMID:23534852

GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

PubMed

Humaidan, P; Kol, S; Papanikolaou, E G

2011-01-01

GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering. This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors' knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate. In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: -0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: -0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: -0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02-0.40)]. GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering.

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.

Comparison of shoulder strength in males with and without myofascial trigger points in the upper trapezius.

PubMed

Kim, H A; Hwang, U J; Jung, S H; Ahn, S H; Kim, J H; Kwon, O Y

2017-11-01

This study was conducted in order to compare the strength of scapular elevator and shoulder abductor with and without restricted scapular elevation between male subjects with and without myofascial trigger points in the upper trapezius. In total, 15 male subjects with myofascial trigger points, and 15age- and weight-matched male subjects without myofascial trigger points in the upper trapezius. Each subject was measured in the strength of maximum isometric scapular elevation and shoulder abduction with and without restricted scapular elevation. Maximum isometric contractions were measured using the Smart KEMA strength measurement system. Independent t-tests were used to compare shoulder strength values between the myofascial trigger points and non- myofascial trigger points groups. The results showed that shoulder abductor strength in the group with myofascial trigger points (5.64kgf) was significantly lower than in the group without myofascial trigger points (11.96kgf) when scapular elevation was restricted (p<0.05). However, there was no significant difference in the strength of the scapular elevator or shoulder abductor between groups (p>0.05). These findings suggest that decreased strength in the shoulder abductor with restricted scapular elevation should be considered in evaluating and treating individuals with myofascial trigger points of the upper trapezius. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ambient Tremor, But No Triggered Tremor at the Northern Costa Rica Subduction Zone

NASA Astrophysics Data System (ADS)

Swiecki, Z.; Schwartz, S. Y.

2010-12-01

Non-volcanic tremor (NVT) has been found to be triggered during the passage of surface waves from various teleseismic events in locations around the world including Cascadia, Southwest Japan, Taiwan, and California. In this study we examine the northern Costa Rica subduction zone for evidence of triggered tremor. The Nicoya Peninsula segment of the northern Costa Rica margin experiences both slow-slip and tremor and is thus a prime candidate for triggered tremor observations. Eleven teleseismic events with magnitudes (Mw) greater than 8 occurring between 2006 and 2010 were examined using data from both broadband and short period sensors deployed on the Nicoya Peninsula, Costa Rica. Waveforms from several large regional events were also considered. The largest teleseismic and regional events (27 February 2010 Chile, Mw 8.8 and 28 May 2009 Honduras, Mw 7.3) induced peak ground velocities (PGV) at the NIcoya stations of ~2 and 6 mm/s, respectively; larger than PGVs in other locations that have triggered tremor. Many of the earthquakes examined occurred during small episodes of background ambient tremor. In spite of this, no triggered tremor was observed during the passage of seismic waves from any event. This is significant because other studies have demonstrated that NVT is not triggered everywhere by all events above some threshold magnitude, indicating that unique conditions are required for its occurrence. The lack of triggered tremor at the Costa Rica margin can help to better quantify the requisite conditions and triggering mechanisms. An inherent difference between the Costa Rica margin and the other subduction zones where triggered tremor exists is its erosional rather than accretionary nature. Its relatively low sediment supply likely results in a drier, lower pore fluid pressure, stronger and less compliant thrust interface that is less receptive to triggering tremor from external stresses generated by teleseismic or strong local earthquakes. Another important factor is Costa Rica’s relatively cool subduction zone structure where temperatures required for the fluid generating basalt/ecloginte reaction are not reached until far below tremor producing depths.

Impact of adaptation currents on synchronization of coupled exponential integrate-and-fire neurons.

PubMed

Ladenbauer, Josef; Augustin, Moritz; Shiau, LieJune; Obermayer, Klaus

2012-01-01

The ability of spiking neurons to synchronize their activity in a network depends on the response behavior of these neurons as quantified by the phase response curve (PRC) and on coupling properties. The PRC characterizes the effects of transient inputs on spike timing and can be measured experimentally. Here we use the adaptive exponential integrate-and-fire (aEIF) neuron model to determine how subthreshold and spike-triggered slow adaptation currents shape the PRC. Based on that, we predict how synchrony and phase locked states of coupled neurons change in presence of synaptic delays and unequal coupling strengths. We find that increased subthreshold adaptation currents cause a transition of the PRC from only phase advances to phase advances and delays in response to excitatory perturbations. Increased spike-triggered adaptation currents on the other hand predominantly skew the PRC to the right. Both adaptation induced changes of the PRC are modulated by spike frequency, being more prominent at lower frequencies. Applying phase reduction theory, we show that subthreshold adaptation stabilizes synchrony for pairs of coupled excitatory neurons, while spike-triggered adaptation causes locking with a small phase difference, as long as synaptic heterogeneities are negligible. For inhibitory pairs synchrony is stable and robust against conduction delays, and adaptation can mediate bistability of in-phase and anti-phase locking. We further demonstrate that stable synchrony and bistable in/anti-phase locking of pairs carry over to synchronization and clustering of larger networks. The effects of adaptation in aEIF neurons on PRCs and network dynamics qualitatively reflect those of biophysical adaptation currents in detailed Hodgkin-Huxley-based neurons, which underscores the utility of the aEIF model for investigating the dynamical behavior of networks. Our results suggest neuronal spike frequency adaptation as a mechanism synchronizing low frequency oscillations in local excitatory networks, but indicate that inhibition rather than excitation generates coherent rhythms at higher frequencies.

Impact of Adaptation Currents on Synchronization of Coupled Exponential Integrate-and-Fire Neurons

PubMed Central

Ladenbauer, Josef; Augustin, Moritz; Shiau, LieJune; Obermayer, Klaus

2012-01-01

The ability of spiking neurons to synchronize their activity in a network depends on the response behavior of these neurons as quantified by the phase response curve (PRC) and on coupling properties. The PRC characterizes the effects of transient inputs on spike timing and can be measured experimentally. Here we use the adaptive exponential integrate-and-fire (aEIF) neuron model to determine how subthreshold and spike-triggered slow adaptation currents shape the PRC. Based on that, we predict how synchrony and phase locked states of coupled neurons change in presence of synaptic delays and unequal coupling strengths. We find that increased subthreshold adaptation currents cause a transition of the PRC from only phase advances to phase advances and delays in response to excitatory perturbations. Increased spike-triggered adaptation currents on the other hand predominantly skew the PRC to the right. Both adaptation induced changes of the PRC are modulated by spike frequency, being more prominent at lower frequencies. Applying phase reduction theory, we show that subthreshold adaptation stabilizes synchrony for pairs of coupled excitatory neurons, while spike-triggered adaptation causes locking with a small phase difference, as long as synaptic heterogeneities are negligible. For inhibitory pairs synchrony is stable and robust against conduction delays, and adaptation can mediate bistability of in-phase and anti-phase locking. We further demonstrate that stable synchrony and bistable in/anti-phase locking of pairs carry over to synchronization and clustering of larger networks. The effects of adaptation in aEIF neurons on PRCs and network dynamics qualitatively reflect those of biophysical adaptation currents in detailed Hodgkin-Huxley-based neurons, which underscores the utility of the aEIF model for investigating the dynamical behavior of networks. Our results suggest neuronal spike frequency adaptation as a mechanism synchronizing low frequency oscillations in local excitatory networks, but indicate that inhibition rather than excitation generates coherent rhythms at higher frequencies. PMID:22511861

What started your labor? Responses from mothers in the third pregnancy, infection, and nutrition study.

PubMed

Bovbjerg, Marit L; Evenson, Kelly R; Bradley, Chyrise; Thorp, John M

2014-01-01

Many behaviors and substances have been purported to induce labor. Using data from the Third Pregnancy, Infection, and Nutrition cohort, we focus on 663 women who experienced spontaneous labor. Of the women who reported a specific labor trigger, 32% reported physical activity (usually walking), 24% a clinician-mediated trigger, 19% a natural phenomenon, 14% some other physical trigger (including sexual activity), 12% reported ingesting something, 12% an emotional trigger, and 7% maternal illness. With the exceptions of walking and sexual intercourse, few women reported any one specific trigger, although various foods/substances were listed in the "ingesting something" category. Discussion of potential risks associated with "old wives' tale" ways to induce labor may be warranted as women approach term.

Derivation of data-driven triggers for palliative care consultation in critically ill patients.

PubMed

Hua, May S; Ma, Xiaoyue; Li, Guohua; Wunsch, Hannah

2018-04-30

To examine the ability of existing triggers for intensive care unit (ICU) palliative care consultation to predict 6-month mortality, and derive new triggers for consultation based on risk factors for 6-month mortality. Retrospective cohort study of NY state residents who received intensive care, 2008-2013. We examined sensitivity and specificity of existing triggers for predicting 6-month mortality and used logistic regression to generate patient subgroups at high-risk for 6-month mortality as potential novel triggers for ICU palliative care consultation. Of 1,019,849 patients, 195,847 (19.2%) died within 6 months of admission. Existing triggers were specific but not sensitive for predicting 6-month mortality, (sensitivity 0.3%-11.1%, specificity 96.5-99.9% for individual triggers). Using logistic regression, patient subgroups with the highest predicted probability of 6-month mortality were older patients admitted with sepsis (age 70-79 probability 49.7%, [49.5-50.0]) or cancer (non-metastatic cancer, age 70-79 probability 51.5%, [51.1-51.9]; metastatic cancer, age 70-79 probability 60.3%, [59.9-60.6]). Sensitivity and specificity of novel triggers ranged from 0.05% to 9.2% and 98.6% to 99.9%, respectively. Existing triggers for palliative care consultation are specific, but insensitive for 6-month mortality. Using a data-driven approach to derive novel triggers may identify subgroups of patients at high-risk of 6-month mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: I. Robust Linear Optimization and Robust Mixed Integer Linear Optimization

PubMed Central

Li, Zukui; Ding, Ran; Floudas, Christodoulos A.

2011-01-01

Robust counterpart optimization techniques for linear optimization and mixed integer linear optimization problems are studied in this paper. Different uncertainty sets, including those studied in literature (i.e., interval set; combined interval and ellipsoidal set; combined interval and polyhedral set) and new ones (i.e., adjustable box; pure ellipsoidal; pure polyhedral; combined interval, ellipsoidal, and polyhedral set) are studied in this work and their geometric relationship is discussed. For uncertainty in the left hand side, right hand side, and objective function of the optimization problems, robust counterpart optimization formulations induced by those different uncertainty sets are derived. Numerical studies are performed to compare the solutions of the robust counterpart optimization models and applications in refinery production planning and batch process scheduling problem are presented. PMID:21935263

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.

Using adaptive processes and adverse outcome pathways to develop meaningful, robust, and actionable environmental monitoring programs.

PubMed

Arciszewski, Tim J; Munkittrick, Kelly R; Scrimgeour, Garry J; Dubé, Monique G; Wrona, Fred J; Hazewinkel, Rod R

2017-09-01

The primary goals of environmental monitoring are to indicate whether unexpected changes related to development are occurring in the physical, chemical, and biological attributes of ecosystems and to inform meaningful management intervention. Although achieving these objectives is conceptually simple, varying scientific and social challenges often result in their breakdown. Conceptualizing, designing, and operating programs that better delineate monitoring, management, and risk assessment processes supported by hypothesis-driven approaches, strong inference, and adverse outcome pathways can overcome many of the challenges. Generally, a robust monitoring program is characterized by hypothesis-driven questions associated with potential adverse outcomes and feedback loops informed by data. Specifically, key and basic features are predictions of future observations (triggers) and mechanisms to respond to success or failure of those predictions (tiers). The adaptive processes accelerate or decelerate the effort to highlight and overcome ignorance while preventing the potentially unnecessary escalation of unguided monitoring and management. The deployment of the mutually reinforcing components can allow for more meaningful and actionable monitoring programs that better associate activities with consequences. Integr Environ Assess Manag 2017;13:877-891. © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Slowing down of North Pacific climate variability and its implications for abrupt ecosystem change.

PubMed

Boulton, Chris A; Lenton, Timothy M

2015-09-15

Marine ecosystems are sensitive to stochastic environmental variability, with higher-amplitude, lower-frequency--i.e., "redder"--variability posing a greater threat of triggering large ecosystem changes. Here we show that fluctuations in the Pacific Decadal Oscillation (PDO) index have slowed down markedly over the observational record (1900-present), as indicated by a robust increase in autocorrelation. This "reddening" of the spectrum of climate variability is also found in regionally averaged North Pacific sea surface temperatures (SSTs), and can be at least partly explained by observed deepening of the ocean mixed layer. The progressive reddening of North Pacific climate variability has important implications for marine ecosystems. Ecosystem variables that respond linearly to climate forcing will have become prone to much larger variations over the observational record, whereas ecosystem variables that respond nonlinearly to climate forcing will have become prone to more frequent "regime shifts." Thus, slowing down of North Pacific climate variability can help explain the large magnitude and potentially the quick succession of well-known abrupt changes in North Pacific ecosystems in 1977 and 1989. When looking ahead, despite model limitations in simulating mixed layer depth (MLD) in the North Pacific, global warming is robustly expected to decrease MLD. This could potentially reverse the observed trend of slowing down of North Pacific climate variability and its effects on marine ecosystems.

Bioinspired production of magnetic laccase-biotitania particles for the removal of endocrine disrupting chemicals.

PubMed

Ardao, Inés; Magnin, Delphine; Agathos, Spiros N

2015-10-01

Microbial laccases are powerful enzymes capable of degrading lignin and other recalcitrant compounds including endocrine disrupting chemicals (EDCs). Efficient EDC removal on an industrial scale requires robust, stable, easy to handle and cost-effective immobilized biocatalysts. In this direction, magnetic biocatalysts are attractive due to their easy separation through an external magnetic field. Recently, a bioinspired immobilization technique that mimics the natural biomineralization reactions in diatoms has emerged as a fast and versatile tool for generating robust, cheap, and highly stable (nano) biocatalysts. In this work, bioinspired formation of a biotitania matrix is triggered on the surface of magnetic particles in the presence of laccase in order to produce laccase-biotitania (lac-bioTiO2 ) biocatalysts suitable for environmental applications using a novel, fast and versatile enzyme entrapment technique. Highly active lac-bioTiO2 particles have been produced and the effect of different parameters (enzyme loading, titania precursor concentration, pH, duration of the biotitania formation, and laccase adsorption steps) on the apparent activity yield of these biocatalysts were evaluated, the concentration of the titania precursor being the most influential. The lac-bioTiO2 particles were able to catalyze the removal of bisphenol A, 17α-ethinylestradiol and diclofenac in a mixture of six model EDCs and retained 90% of activity after five reaction cycles and 60% after 10 cycles. © 2015 Wiley Periodicals, Inc.

Developing a Taxonomy of Dark Triad Triggers at Work – A Grounded Theory Study Protocol

PubMed Central

Nübold, Annika; Bader, Josef; Bozin, Nera; Depala, Romil; Eidast, Helena; Johannessen, Elisabeth A.; Prinz, Gerhard

2017-01-01

In past years, research and corporate scandals have evidenced the destructive effects of the dark triad at work, consisting of narcissism (extreme self-centeredness), psychopathy (lack of empathy and remorse) and Machiavellianism (a sense of duplicity and manipulativeness). The dark triad dimensions have typically been conceptualized as stable personality traits, ignoring the accumulating evidence that momentary personality expressions – personality states – may change due to the characteristics of the situation. The present research protocol describes a qualitative study that aims to identify triggers of dark triad states at work by following a grounded theory approach using semi-structured interviews. By building a comprehensive categorization of dark triad triggers at work scholars may study these triggers in a parsimonious and structured way and organizations may derive more effective interventions to buffer or prevent the detrimental effects of dark personality at work. PMID:28326048

Jet-like correlations with direct-photon and neutral-pion triggers at s N N = 200  GeV

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

Adamczyk, L.; Adkins, J. K.; Agakishiev, G.

2016-07-22

Azimuthal correlations of charged hadrons with direct-photon (γ dir) and neutral-pion (π 0) trigger particles are analyzed in central Au+Au and minimum-bias p+p collisions atmore » $$\\sqrt{s}$$$_{NN}$$ =200 GeV in the STAR experiment. The charged-hadron per-trigger yields at mid-rapidity from central Au+Au collisions are compared with p+p collisions to quantify the suppression in Au+Au collisions. The suppression of the away-side associated-particle yields per γ dir trigger is independent of the transverse momentum of the trigger particle ( P$$trig\\atop{T}$$, whereas the suppression is smaller at low transverse momentum of the associated charged hadrons ( P$$assoc\\atop{T}$$). Within uncertainty, similar levels of suppression are observed for γ dir and π 0 triggers as a function of z T ($$\\equiv$$ P$$assoc\\atop{T}$$/$ P$$trig\\atop{T}$$). The results are compared with energy-loss-inspired theoretical model predictions. In conclusion, our studies support previous conclusions that the lost energy reappears predominantly at low transverse momentum, regardless of the trigger energy.« less

The NA62 trigger system

NASA Astrophysics Data System (ADS)

Krivda, M.; NA62 Collaboration

2013-08-01

The main aim of the NA62 experiment (NA62 Technical Design Report, [1]) is to study ultra-rare Kaon decays. In order to select rare events over the overwhelming background, central systems with high-performance, high bandwidth, flexibility and configurability are necessary, that minimize dead time while maximizing data collection reliability. The NA62 experiment consists of 12 sub-detector systems and several trigger and control systems, for a total channel count of less than 100,000. The GigaTracKer (GTK) has the largest number of channels (54,000), and the Liquid Krypton (LKr) calorimeter shares with it the largest raw data rate (19 GB/s). The NA62 trigger system works with 3 trigger levels. The first trigger level is based on a hardware central trigger unit, so-called L0 Trigger Processor (L0TP), and Local Trigger Units (LTU), which are all located in the experimental cavern. Other two trigger levels are based on software, and done with a computer farm located on surface. The L0TP receives information from triggering sub-detectors asynchronously via Ethernet; it processes the information, and then transmits a final trigger decision synchronously to each sub-detector through the Trigger and Timing Control (TTC) system. The interface between L0TP and the TTC system, which is used for trigger and clock distribution, is provided by the Local Trigger Unit board (LTU). The LTU can work in two modes: global and stand-alone. In the global mode, the LTU provides an interface between L0TP and TTC system. In the stand-alone mode, the LTU can fully emulate L0TP and so provides an independent way for each sub-detector for testing or calibration purposes. In addition to the emulation functionality, a further functionality is implemented that allows to synchronize the clock of the LTU with the L0TP and the TTC system. For testing and debugging purposes, a Snap Shot Memory (SSM) interface is implemented, that can work both in an input or an output mode. The trigger rates will be permanently monitored by reading counters at regular intervals. This paper describes the overall NA62 trigger system focusing on the setup for the dry and technical runs in 2012.

Photon-triggered nanowire transistors

NASA Astrophysics Data System (ADS)

Kim, Jungkil; Lee, Hoo-Cheol; Kim, Kyoung-Ho; Hwang, Min-Soo; Park, Jin-Sung; Lee, Jung Min; So, Jae-Pil; Choi, Jae-Hyuck; Kwon, Soon-Hong; Barrelet, Carl J.; Park, Hong-Gyu

2017-10-01

Photon-triggered electronic circuits have been a long-standing goal of photonics. Recent demonstrations include either all-optical transistors in which photons control other photons or phototransistors with the gate response tuned or enhanced by photons. However, only a few studies report on devices in which electronic currents are optically switched and amplified without an electrical gate. Here we show photon-triggered nanowire (NW) transistors, photon-triggered NW logic gates and a single NW photodetection system. NWs are synthesized with long crystalline silicon (CSi) segments connected by short porous silicon (PSi) segments. In a fabricated device, the electrical contacts on both ends of the NW are connected to a single PSi segment in the middle. Exposing the PSi segment to light triggers a current in the NW with a high on/off ratio of >8 × 106. A device that contains two PSi segments along the NW can be triggered using two independent optical input signals. Using localized pump lasers, we demonstrate photon-triggered logic gates including AND, OR and NAND gates. A photon-triggered NW transistor of diameter 25 nm with a single 100 nm PSi segment requires less than 300 pW of power. Furthermore, we take advantage of the high photosensitivity and fabricate a submicrometre-resolution photodetection system. Photon-triggered transistors offer a new venue towards multifunctional device applications such as programmable logic elements and ultrasensitive photodetectors.

Photon-triggered nanowire transistors.

PubMed

Kim, Jungkil; Lee, Hoo-Cheol; Kim, Kyoung-Ho; Hwang, Min-Soo; Park, Jin-Sung; Lee, Jung Min; So, Jae-Pil; Choi, Jae-Hyuck; Kwon, Soon-Hong; Barrelet, Carl J; Park, Hong-Gyu

2017-10-01

Photon-triggered electronic circuits have been a long-standing goal of photonics. Recent demonstrations include either all-optical transistors in which photons control other photons or phototransistors with the gate response tuned or enhanced by photons. However, only a few studies report on devices in which electronic currents are optically switched and amplified without an electrical gate. Here we show photon-triggered nanowire (NW) transistors, photon-triggered NW logic gates and a single NW photodetection system. NWs are synthesized with long crystalline silicon (CSi) segments connected by short porous silicon (PSi) segments. In a fabricated device, the electrical contacts on both ends of the NW are connected to a single PSi segment in the middle. Exposing the PSi segment to light triggers a current in the NW with a high on/off ratio of >8 × 10 6 . A device that contains two PSi segments along the NW can be triggered using two independent optical input signals. Using localized pump lasers, we demonstrate photon-triggered logic gates including AND, OR and NAND gates. A photon-triggered NW transistor of diameter 25 nm with a single 100 nm PSi segment requires less than 300 pW of power. Furthermore, we take advantage of the high photosensitivity and fabricate a submicrometre-resolution photodetection system. Photon-triggered transistors offer a new venue towards multifunctional device applications such as programmable logic elements and ultrasensitive photodetectors.

Development of a novel scintillation-trigger detector for the MTV experiment using aluminum-metallized film tapes

NASA Astrophysics Data System (ADS)

Tanaka, S.; Ozaki, S.; Sakamoto, Y.; Tanuma, R.; Yoshida, T.; Murata, J.

2014-07-01

A new type of a trigger-scintillation counter array designed for the MTV experiment at TRIUMF-ISAC has been developed, which uses aluminum-metallized film tape for wrapping to achieve the required assembling precision of ±0.5 mm. The MTV experiment uses a cylindrical drift chamber (CDC) as the main electron-tracking detector. The barrel-type trigger counter is placed inside the CDC to generate a trigger signal using 1 mm thick, 300 mm long thin plastic scintillation counters. Detection efficiency and light attenuation compared with conventional wrapping materials are studied.

Skier triggering of backcountry avalanches with skilled route selection

NASA Astrophysics Data System (ADS)

Sinickas, Alexandra; Haegeli, Pascal; Jamieson, Bruce

2015-04-01

Jamieson (2009) provided numerical estimates for the baseline probabilities of triggering an avalanche by a backcountry skier making fresh tracks without skilled route selection as a function of the North American avalanche danger scale (i.e., hazard levels Low, Moderate, Considerable, High and Extreme). Using the results of an expert survey, he showed that triggering probabilities while skiing directly up, down or across a trigger zone without skilled route selection increase roughly by a factor of 10 with each step of the North American avalanche danger scale (i.e. hazard level). The objective of the present study is to examine the effect of skilled route selection on the relationship between triggering probability and hazard level. To assess the effect of skilled route selection on triggering probability by hazard level, we analysed avalanche hazard assessments as well as reports of skiing activity and triggering of avalanches from 11 Canadian helicopter and snowcat operations during two winters (2012-13 and 2013-14). These reports were submitted to the daily information exchange among Canadian avalanche safety operations, and reflect professional decision-making and route selection practices of guides leading groups of skiers. We selected all skier-controlled or accidentally triggered avalanches with a destructive size greater than size 1 according to the Canadian avalanche size classification, triggered by any member of a guided group (guide or guest). These operations forecast the avalanche hazard daily for each of three elevation bands: alpine, treeline and below treeline. In contrast to the 2009 study, an exposure was defined as a group skiing within any one of the three elevation bands, and consequently within a hazard rating, for the day (~4,300 ratings over two winters). For example, a group that skied below treeline (rated Moderate) and treeline (rated Considerable) in one day, would receive one count for exposure to Moderate hazard, and one count for exposure to Considerable hazard. While the absolute values for triggering probability cannot be compared to the 2009 study because of different definitions of exposure, our preliminary results suggest that with skilled route selection the triggering probability is similar all hazard levels, except for extreme for which there are few exposures. This means that the guiding teams of backcountry skiing operations effectively control the hazard from triggering avalanches with skilled route selection. Groups were exposed relatively evenly to Low hazard (1275 times or 29% of total exposure), Moderate hazard (1450 times or 33 %) and Considerable hazard (1215 times or 28 %). At higher levels, the exposure reduced to roughly 380 times (9 % of total exposure) to High hazard, and only 13 times (0.3 %) to Extreme hazard. We assess the sensitivity of the results to some of our key assumptions.

Adverse Drug Event Detection in Pediatric Oncology and Hematology Patients: Using Medication Triggers to Identify Patient Harm in a Specialized Pediatric Patient Population

PubMed Central

Call, Rosemary J.; Burlison, Jonathan D.; Robertson, Jennifer J.; Scott, Jeffrey R.; Baker, Donald K.; Rossi, Michael G.; Howard, Scott C.; Hoffman, James M.

2014-01-01

Objective To investigate the use of a trigger tool for adverse drug event (ADE) detection in a pediatric hospital specializing in oncology, hematology, and other catastrophic diseases. Study design A medication-based trigger tool package analyzed electronic health records from February 2009 to February 2013. Chart review determined whether an ADE precipitated the trigger. Severity was assigned to ADEs, and preventability was assessed. Preventable ADEs were compared with the hospital’s electronic voluntary event reporting system to identify whether these ADEs had been previously identified. The positive predictive values (PPVs) of the entire trigger tool and individual triggers were calculated to assess their accuracy to detect ADEs. Results Trigger occurrences (n=706) were detected in 390 patients from six medication triggers, 33 of which were ADEs (overall PPV = 16%). Hyaluronidase had the highest PPV (60%). Most ADEs were category E harm (temporary harm) per the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index. One event was category H harm (intervention to sustain life). Naloxone was associated with the most grade 4 ADEs per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Twenty-one (64%) ADEs were preventable; 3 of which were submitted via the voluntary reporting system. Conclusion Most of the medication-based triggers yielded low PPVs. Refining the triggers based on patients’ characteristics and medication usage patterns could increase the PPVs and make them more useful for quality improvement. To efficiently detect ADEs, triggers must be revised to reflect specialized pediatric patient populations such as hematology and oncology patients. PMID:24768254

[Performance and optimisation of a trigger tool for the detection of adverse events in hospitalised adult patients].

PubMed

Guzmán Ruiz, Óscar; Pérez Lázaro, Juan José; Ruiz López, Pedro

To characterise the performance of the triggers used in the detection of adverse events (AE) of hospitalised adult patients and to define a simplified panel of triggers to facilitate the detection of AE. Cross-sectional study of charts of patients from a service of internal medicine to detect EA through systematic review of the charts and identification of triggers (clinical event often related to AE), determining if there was AE as the context in which it appeared the trigger. Once the EA was detected, we proceeded to the characterization of the triggers that detected it. Logistic regression was applied to select the triggers with greater AE detection capability. A total of 291 charts were reviewed, with a total of 562 triggers in 103 patients, of which 163 were involved in detecting an AE. The triggers that detected the most AE were "A.1. Pressure ulcer" (9.82%), "B.5. Laxative or enema" (8.59%), "A.8. Agitation" (8.59%), "A.9. Over-sedation" (7.98%), "A.7. Haemorrhage" (6.75%) and "B.4. Antipsychotic" (6.75%). A simplified model was obtained using logistic regression, and included the variable "Number of drugs" and the triggers "Over-sedation", "Urinary catheterisation", "Readmission in 30 days", "Laxative or enema" and "Abrupt medication stop". This model showed a probability of 81% to correctly classify charts with EA or without EA (p <0.001; 95% confidence interval: 0.763-0.871). A high number of triggers were associated with AE. The summary model is capable of detecting a large amount of AE, with a minimum of elements. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

RELATIVISTIC MHD SIMULATIONS OF COLLISION-INDUCED MAGNETIC DISSIPATION IN POYNTING-FLUX-DOMINATED JETS/OUTFLOWS

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

Deng, Wei; Zhang, Bing; Li, Hui

We perform 3D relativistic ideal magnetohydrodynamics (MHD) simulations to study the collisions between high-σ (Poynting-flux-dominated (PFD)) blobs which contain both poloidal and toroidal magnetic field components. This is meant to mimic the interactions inside a highly variable PFD jet. We discover a significant electromagnetic field (EMF) energy dissipation with an Alfvénic rate with the efficiency around 35%. Detailed analyses show that this dissipation is mostly facilitated by the collision-induced magnetic reconnection. Additional resolution and parameter studies show a robust result that the relative EMF energy dissipation efficiency is nearly independent of the numerical resolution or most physical parameters in themore » relevant parameter range. The reconnection outflows in our simulation can potentially form the multi-orientation relativistic mini jets as needed for several analytical models. We also find a linear relationship between the σ values before and after the major EMF energy dissipation process. Our results give support to the proposed astrophysical models that invoke significant magnetic energy dissipation in PFD jets, such as the internal collision-induced magnetic reconnection and turbulence model for gamma-ray bursts, and reconnection triggered mini jets model for active galactic nuclei. The simulation movies are shown in http://www.physics.unlv.edu/∼deng/simulation1.html.« less

High-Precision In Situ 87Sr/86Sr Analyses through Microsampling on Solid Samples: Applications to Earth and Life Sciences

PubMed Central

Di Salvo, Sara; Casalini, Martina; Marchionni, Sara; Adani, Teresa; Ulivi, Maurizio; Tommasini, Simone; Avanzinelli, Riccardo; Mazza, Paul P. A.; Francalanci, Lorella

2018-01-01

An analytical protocol for high-precision, in situ microscale isotopic investigations is presented here, which combines the use of a high-performing mechanical microsampling device and high-precision TIMS measurements on micro-Sr samples, allowing for excellent results both in accuracy and precision. The present paper is a detailed methodological description of the whole analytical procedure from sampling to elemental purification and Sr-isotope measurements. The method offers the potential to attain isotope data at the microscale on a wide range of solid materials with the use of minimally invasive sampling. In addition, we present three significant case studies for geological and life sciences, as examples of the various applications of microscale 87Sr/86Sr isotope ratios, concerning (i) the pre-eruptive mechanisms triggering recent eruptions at Nisyros volcano (Greece), (ii) the dynamics involved with the initial magma ascent during Eyjafjallajökull volcano's (Iceland) 2010 eruption, which are usually related to the precursory signals of the eruption, and (iii) the environmental context of a MIS 3 cave bear, Ursus spelaeus. The studied cases show the robustness of the methods, which can be also be applied in other areas, such as cultural heritage, archaeology, petrology, and forensic sciences. PMID:29850369

Live and let die--Arabidopsis nonhost resistance to powdery mildews.

PubMed

Lipka, Ulrike; Fuchs, Rene; Kuhns, Christine; Petutschnig, Elena; Lipka, Volker

2010-01-01

The term "nonhost resistance" (NHR) describes the phenomenon that an entire plant species is resistant to all genetic variants of a non-adapted pathogen species. In nature, NHR represents the most robust form of plant immunity and is therefore of scientific as well as economic importance. Due to its highly complex nature, NHR has previously not been studied in detail. Recently, the establishment of model interaction systems utilizing Arabidopsis and non-adapted powdery mildews allowed the identification of several key components and conceptual conclusions. It is now generally accepted that NHR of Arabidopsis to powdery mildews comprises two distinct layers of defence: pre-invasion entry control at the cell periphery and post-invasion resistance based on cell death execution. The timely production and localised discharge of toxic compounds at sites of fungal attack appear to be pivotal for entry control. This process requires proteins involved in secretion and trans-membrane transport, synthesis and activation of indolic glucosinolates as well as gene regulation and post-translational protein modification. Post-invasion defence relies on lipase-like proteins and salicylic acid signalling. To what extent pathogen-associated molecular pattern- or effector-triggered immunity contribute to NHR remains to be investigated and is likely to depend on the model system studied. Copyright 2009 Elsevier GmbH. All rights reserved.

Design of polymer motifs for nucleic acid recognition and assembly stabilization

NASA Astrophysics Data System (ADS)

Zhou, Zhun

This dissertation describes the synthesis and assembly of bio-functional polymers and the applications of these polymers to drug encapsulation, delivery, and multivalent biomimetic macromolecular recognition between synthetic polymer and nucleic acids. The main content is divided into three parts: (1) polyacidic domains as strongly stabilizing design elements for aqueous phase polyacrylate diblock assembly; (2) small molecule/polymer recognition triggered macromolecular assembly and drug encapsulation; (3) trizaine derivatized polymer as a novel class of "bifacial polymer nucleic acid" (bPoNA) and applications of bPoNA to nanoparticle loading of DNA/RNA, silencing delivery as well as control of aptamer function. Through the studies in part (1) and part (2), it was demonstrated that well-designed polymer motifs are not only able to enhance assemblies driven by non-specific hydrophobic effect, but are also able to direct assemblies based on specific recognitions. In part (3) of this dissertation, this concept was further extended by the design of polyacrylate polymers that are capable of discrete and robust hybridization with nucleic acids. This surprising finding demonstrated both fundamental and practical applications. Overall, these studies provided insights into the rational design elements for improving the bio-functions of synthetic polymers, and significantly expanded the scope of biological applications in which polymers synthesized via controlled radical polymerization may play a role.

Applying threshold concepts to conservation management of dryland ecosystems: Case studies on the Colorado Plateau

USGS Publications Warehouse

Bowker, Matthew A.; Miller, Mark E.; Garman, Steven L.; Belote, Travis; Guntenspergen, Glenn R.

2014-01-01

Ecosystems may occupy functionally distinct alternative states, some of which are more or less desirable from a management standpoint. Transitions from state to state are usually associated with a particular trigger or sequence of triggers, such as the addition or subtraction of a disturbance. Transitions are often not linear, rather it is common to see an abrupt transition come about even though the trigger increases only incrementally; these are examples of threshold behaviors. An ideal monitoring program, such as the National Park Service’s Inventory and Monitoring Program, would quantify triggers, and be able to inform managers when measurements of a trigger are approaching a threshold so that management action can avoid an unwanted state transition. Unfortunately, both triggers and the threshold points at which state transitions occur are generally only partially known. Using case studies, we advance a general procedure to help identify triggers and estimate where threshold dynamics may occur. Our procedure is as follows: (1) Operationally define the ecosystem type being considered; we suggest that the ecological site concept of the Natural Resource Conservation Service is a useful system, (2) Using all available a priori knowledge to develop a state-and-transition model (STM), which defines possible ecosystem states, plausible transitions among them and likely triggers, (3) Validate the STM by verifying the existence of its states to the greatest degree possible, (4) Use the STM model to identify transitions and triggers likely to be detectable by a monitoring program, and estimate to the greatest degree possible the value of a measurable indicator of a trigger at the point that a state transition is imminent (tipping point), and values that may indicate when management intervention should be considered (assessment points). We illustrate two different methods for attaining these goals using a data-rich case study in Canyonlands National Park, and a data-poor case study in Wupatki National Monument. In the data-rich case, STMs are validated and revised, and tipping and assessment points are estimated using statistical analysis of data. In the data-poor case, we develop an iterative expert opinion survey approach to validate the degree of confidence in an STM, revise the model, identify lack of confidence in specific model components, and create reasonable first approximations of tipping and assessment points, which can later be refined when more data are available. Our goal should be to develop the best set of models possible given the level of information available to support decisions, which is often not much. The approach presented here offers a flexible means of achieving this goal, and determining specific research areas in need of study.

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans.

PubMed

Ting, S Y; Ishola, O A; Ahmed, M A; Tabana, Y M; Dahham, S; Agha, M T; Musa, S F; Muhammed, R; Than, L T L; Sandai, D

2017-03-01

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Recognising triggers for soft-sediment deformation: Current understanding and future directions

NASA Astrophysics Data System (ADS)

Owen, Geraint; Moretti, Massimo; Alfaro, Pedro

2011-04-01

Most of the 16 papers in this special issue were presented at a session entitled "The recognition of trigger mechanisms for soft-sediment deformation" at the 27th IAS Meeting of Sedimentology in Alghero, Sardinia, Italy, which took place from 20th-23rd September 2009. They describe soft-sediment deformation structures that range widely in morphology, age, depositional environment and tectonic setting. In their interpretations, the authors have been asked to focus on identifying the agent that triggered deformation. Our aims in this introductory overview are to: (1) review the definition and scope of soft-sediment deformation; (2) clarify the significance and role of the trigger; (3) set the contributions in context and summarise their findings; and (4) discuss strategies for reliably identifying triggers and make recommendations for future study of this widespread and significant category of sedimentary structures. We recommend a three-stage approach to trigger recognition, combining the assessment of facies, potential triggers, and available criteria. This focus on the trigger for deformation distinguishes this collection of papers on soft-sediment deformation from other important collections, notably those edited by Jones and Preston (1987), Maltman (1994), Maltman et al. (2000), Shiki et al. (2000), Ettensohn et al. (2002b), Van Rensbergen et al. (2003) and Storti and Vannucchi (2007).

Self-adaptive robot training of stroke survivors for continuous tracking movements.

PubMed

Vergaro, Elena; Casadio, Maura; Squeri, Valentina; Giannoni, Psiche; Morasso, Pietro; Sanguineti, Vittorio

2010-03-15

Although robot therapy is progressively becoming an accepted method of treatment for stroke survivors, few studies have investigated how to adapt the robot/subject interaction forces in an automatic way. The paper is a feasibility study of a novel self-adaptive robot controller to be applied with continuous tracking movements. The haptic robot Braccio di Ferro is used, in relation with a tracking task. The proposed control architecture is based on three main modules: 1) a force field generator that combines a non linear attractive field and a viscous field; 2) a performance evaluation module; 3) an adaptive controller. The first module operates in a continuous time fashion; the other two modules operate in an intermittent way and are triggered at the end of the current block of trials. The controller progressively decreases the gain of the force field, within a session, but operates in a non monotonic way between sessions: it remembers the minimum gain achieved in a session and propagates it to the next one, which starts with a block whose gain is greater than the previous one. The initial assistance gains are chosen according to a minimal assistance strategy. The scheme can also be applied with closed eyes in order to enhance the role of proprioception in learning and control. The preliminary results with a small group of patients (10 chronic hemiplegic subjects) show that the scheme is robust and promotes a statistically significant improvement in performance indicators as well as a recalibration of the visual and proprioceptive channels. The results confirm that the minimally assistive, self-adaptive strategy is well tolerated by severely impaired subjects and is beneficial also for less severe patients. The experiments provide detailed information about the stability and robustness of the adaptive controller of robot assistance that could be quite relevant for the design of future large scale controlled clinical trials. Moreover, the study suggests that including continuous movement in the repertoire of training is acceptable also by rather severely impaired subjects and confirms the stabilizing effect of alternating vision/no vision trials already found in previous studies.

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

Xie, Xueqian; Greuter, Marcel J. W.; Groen, Jaap M.

Purpose: Coronary artery calcium score, traditionally based on electrocardiography (ECG)-triggered computed tomography (CT), predicts cardiovascular risk. However, nontriggered CT is extensively utilized. The study-purpose is to evaluate the in vitro agreement in coronary calcium score between nontriggered thoracic CT and ECG-triggered cardiac CT.Methods: Three artificial coronary arteries containing calcifications of different densities (high, medium, and low), and sizes (large, medium, and small), were studied in a moving cardiac phantom. Two 64-detector CT systems were used. The phantom moved at 0–90 mm/s in nontriggered low-dose CT as index test, and at 0–30 mm/s in ECG-triggered CT as reference. Differences in calciummore » scores between nontriggered and ECG-triggered CT were analyzed by t-test and 95% confidence interval. The sensitivity to detect calcification was calculated as the percentage of positive calcium scores.Results: Overall, calcium scores in nontriggered CT were not significantly different to those in ECG-triggered CT (p > 0.05). Calcium scores in nontriggered CT were within the 95% confidence interval of calcium scores in ECG-triggered CT, except predominantly at higher velocities (≥50 mm/s) for the high-density and large-size calcifications. The sensitivity for a nonzero calcium score was 100% for large calcifications, but 46%± 11% for small calcifications in nontriggered CT.Conclusions: When performing multiple measurements, good agreement in positive calcium scores is found between nontriggered thoracic and ECG-triggered cardiac CT. Agreement decreases with increasing coronary velocity. From this phantom study, it can be concluded that a high calcium score can be detected by nontriggered CT, and thus, that nontriggered CT likely can identify individuals at high risk of cardiovascular disease. On the other hand, a zero calcium score in nontriggered CT does not reliably exclude coronary calcification.« less

Observing earthquakes triggered in the near field by dynamic deformations

USGS Publications Warehouse

Gomberg, J.; Bodin, P.; Reasenberg, P.A.

2003-01-01

We examine the hypothesis that dynamic deformations associated with seismic waves trigger earthquakes in many tectonic environments. Our analysis focuses on seismicity at close range (within the aftershock zone), complementing published studies of long-range triggering. Our results suggest that dynamic triggering is not confined to remote distances or to geothermal and volcanic regions. Long unilaterally propagating ruptures may focus radiated dynamic deformations in the propagation direction. Therefore, we expect seismicity triggered dynamically by a directive rupture to occur asymmetrically, with a majority of triggered earthquakes in the direction of rupture propagation. Bilaterally propagating ruptures also may be directive, and we propose simple criteria for assessing their directivity. We compare the inferred rupture direction and observed seismicity rate change following 15 earthquakes (M 5.7 to M 8.1) that occured in California and Idaho in the United States, the Gulf of Aqaba, Syria, Guatemala, China, New Guinea, Turkey, Japan, Mexico, and Antarctica. Nine of these mainshocks had clearly directive, unilateral ruptures. Of these nine, seven apparently induced an asymmetric increase in seismicity rate that correlates with the rupture direction. The two exceptions include an earthquake preceded by a comparable-magnitude event on a conjugate fault and another for which data limitations prohibited conclusive results. Similar (but weaker) correlations were found for the bilaterally rupturing earthquakes we studied. Although the static stress change also may trigger seismicity, it and the seismicity it triggers are expected to be similarly asymmetric only if the final slip is skewed toward the rupture terminus. For several of the directive earthquakes, we suggest that the seismicity rate change correlates better with the dynamic stress field than the static stress change.

Complex Non-volcanic Tremor in Guerrero Mexico Triggered by the 2010 Mw 8.8 Chilean Earthquake

NASA Astrophysics Data System (ADS)

Zigone, D.; Campillo, M.; Husker, A. L.; Kostoglodov, V.; Payero, J. S.; Frank, W.; Shapiro, N. M.; Voisin, C.; Cougoulat, G.; Cotte, N.

2010-12-01

In this study we analyze the tremors triggered in Guerrero region (Mexico) by the 2010 magnitude 8.8 Chilean Earthquake using mini-seismic array data from the French-Mexican G-GAP project and broadband data from the Servicio Sismologico Nacional of Mexico. The strong dynamic shaking by the earthquake produced the first observed triggered non-volcanic tremors (NVT) in Mexico so far with at least 3 different types of tremors at different time scales. There was a slow slip event (SSE) occurring at the time of the earthquake, which may have increased the probability of tremor triggering in the region. The first type of observed triggered tremors occurred during the S waves, Love waves and Rayleigh waves as already reported in other subductions zones and continental faults (Miyazawa and Mori, 2005, 2006; Rubinstein et al., 2007; Gomberg et al., 2008; Peng et al, 2009…). The greatest amount of energy and duration accompanies the long-period Rayleigh waves, with smaller bursts during the S and Love waves. For this particular tremor we observed the dispersion of Rayleigh waves in the envelopes of triggered tremors, which indicates a very strong modulation of the source by the passing surface wave. An unexpected short-term tremor occurred approximately one hour later of the arrival of the surface waves on the coastal stations. The NVT has only been previously observed at distances > 100 km inland. It also has a shorter frequency range (3-6 Hz) than other NVT (1-10 Hz) observed in the region. Finally, we observed a significant increase of so-called ambient tremor activity with higher intensity than all triggered NVT during the days after the earthquake. This study adds new types of tremors to the lexicon of triggered NVT observed in the world.

The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles.

PubMed

Huang, Chen-Yu; Shieh, Miawh-Lirng; Li, Hsin-Yang

2016-07-01

To assess the pregnancy outcome and ovarian hyperstimulation syndrome (OHSS) incidence in high responders receiving gonadotropin-releasing hormone agonist (GnRHa) trigger plus individualized support of low-dose human chorionic gonadotropin (hCG). Such support includes 500-1000 IU hCG given at trigger and, if serum estradiol (E2) dropped to below 800 pg/mL before the 6(th) day after oocyte retrieval, an additional rescue dose of 300 IU hCG. This was a retrospective study of potential high responders aged from 28 years to 40 years at a tertiary fertility center in Taiwan. By means of chart review, we assessed the pregnancy outcome and OHSS incidence in high responders receiving GnRHa trigger plus individualized low-dose hCG support. The main outcomes were measured by ongoing pregnancy rate and OHSS incidence (SPSS), in which statistical significance was determined by Chi-square test. Moderate to severe OHSS did not develop in any patient receiving GnRHa trigger plus individualized low-dose hCG support. In fact, a satisfactory ongoing pregnancy rate (46.9%) was noted in patients receiving GnRHa trigger plus individualized low-dose hCG support. Our study suggested that GnRHa trigger combined with individualized low-dose hCG support appears to be a safe approach with a satisfactory pregnancy outcome. Copyright © 2016. Published by Elsevier Taiwan LLC.

EMIC triggered chorus emissions in Cluster data

NASA Astrophysics Data System (ADS)

Grison, B.; SantolíK, O.; Cornilleau-Wehrlin, N.; Masson, A.; Engebretson, M. J.; Pickett, J. S.; Omura, Y.; Robert, P.; Nomura, R.

2013-03-01

Electromagnetic ion cyclotron (EMIC) triggered chorus emissions have recently been a subject of several experimental, theoretical and simulation case studies, noting their similarities with whistler-mode chorus. We perform a survey of 8 years of Cluster data in order to increase the database of EMIC triggered emissions. The results of this is that EMIC triggered emissions have been unambiguously observed for only three different days. These three events are studied in detail. All cases have been observed at the plasmapause between 22 and 24 magnetic local time (MLT) and between - 15° and 15° magnetic latitude (λm). Triggered emissions are also observed for the first time below the local He+ gyrofrequency (fHe+). The number of events is too low to produce statistical results, nevertheless we point out a variety of common properties of those waves. The rising tones have a high level of coherence and the waves propagate away from the equatorial region. The propagation angle and degree of polarization are related to the distance from the equator, whereas the slope and the frequency extent vary from one event to the other. From the various spacecraft separations, we determine that the triggering process is a localized phenomenon in space and time. However, we are unable to determine the occurrence rates of these waves. Small frequency extent rising tones are more common than large ones. The newly reported EMIC triggered events are generally observed during periods of large AE index values and in time periods close to solar maximum.

Triggers in advanced neurological conditions: prediction and management of the terminal phase.

PubMed

Hussain, Jamilla; Adams, Debi; Allgar, Victoria; Campbell, Colin

2014-03-01

The challenge to provide a palliative care service for individuals with advanced neurological conditions is compounded by variability in disease trajectories and symptom profiles. The National End of Life Care Programme (2010) recommended seven 'triggers' for a palliative approach to care for patients with advanced neurological conditions. To establish the frequency of triggers in the palliative phase, and if they could be reduced to fewer components. Management of the terminal phase also was evaluated. Retrospective study of 62 consecutive patients under the care of a specialist palliative neurology service, who had died. Principle component analysis (PCA) was performed to establish the interrelationship between triggers. Frequency of triggers increased as each patient approached death. PCA found that four symptom components explained 76.8% of the variance. These represented: rapid physical decline; significant complex symptoms, including pain; infection in combination with cognitive impairment; and risk of aspiration. Median follow-up under the palliative care service was 336 days. In 56.5% of patients, the cause of death was pneumonia. The terminal phase was recognised in 72.6%. The duration of the terminal phase was 8.8 days on average, and the Liverpool Care of the dying Pathway was commenced in 33.9%. All carers were offered bereavement support. Referral criteria based on the triggers can facilitate appropriate and timely patient access to palliative care. The components deduced through PCA have face validity; however larger studies prospectively validating the triggers are required. Closer scrutiny of the terminal phase is necessary to optimise management.

Low Current Surface Flashover for Initiation of Electric Propulsion Devices

NASA Astrophysics Data System (ADS)

Dary, Omar G.

There has been a recent increase in interest in miniaturization of propulsion systems for satellites. These systems are needed to propel micro- and nano-satellites, where platforms are much smaller than conventional satellites and require smaller levels of thrust. Micro-propulsion systems for these satellites are in their infancy and they must manage with smaller power systems and smaller propellant volumes. Electric propulsion systems operating on various types of electric discharges are typically used for these needs. One of the central components of such electrical micropropulsion systems are ignitor subsystems, which are required for creation the breakdown and initiation of the main discharge. Ignitors have to provide reliable ignition for entire lifetime of the micropropulsion system. Electric breakdown in vacuum usually require high voltage potentials of hundreds of kilovolts per mm to induce breakdown. The breakdown voltage can be significantly decreased (down to several kVs per mm) if dielectric surface flashover is utilized. However, classical dielectric surface flashover operates at large electric current (100s of Amperes) and associated with overheating and damage of the electrodes/dielectric assembly after several flashover events. The central idea of this work was to eliminate the damage to the flashover electrode assembly by limiting the flashover currents to low values in milliampere range (Low Current Surface Flashover -LCSF) and utilize LCSF system as an ignition source for the main discharge on the micropropulsion system. The main objective of this research was to create a robust LCSF ignition system, capable producing a large number of surface flashover triggering events without significant damage to the LCSF electrode assembly. The thesis aims to characterize the plasma plume created at LCSF, study electrodes ablation and identify conditions required for robust triggering of main discharge utilized on micro-propulsion system. Conditioning of a new LCSF assembly (flashover current was limited to <100 mA in all experiments) was measured and breakdown voltages in the range of 8kV to 12kV were observed for the fully conditioned assembly. No damage to the LCSF electrode assembly was observed after about 104 LCSF events. The LCSF assembly created sufficient amount of seed plasma in order to bridge a vacuum gap between the high-current electrodes and to reliably ignite high-current arcs (10A-12A arc were used in this work). Ignition of the high-current arc was observed at three different cases of LCSF with limiting currents 100 mA, 33 mA and 20 mA respectively. Plasma parameter measurements were conducted with variety of Langmuir probes inside the LCSF plume. Ion currents created by the LCSF were primarily expelled directly perpendicular from the insulator surface. The plasma expansion for the LCSF assembly was measured to be 2 x 106-6 x 106 cm/s. Plasma density was measured to range 10 10-1011 cm-3. The plasma density was maximal near the LCSF assembly and quickly reduced radially. Temporal decay of the plasma was observed on a time scale of about 5 micros after the LCSF event. The results of this work are significant for creation of ignitor for micropropulsion systems. LCSF system offers reliable triggering for numerous ignition pulses for entire lifetime of the micropropulsion system and reduces complexity and volume of the system by excluding moving parts and the need for an external gas tanks.

Tunable Gas Sensing Gels by Cooperative Assembly

PubMed Central

Hussain, Abid; Semeano, Ana T. S.; Palma, Susana I. C. J.; Pina, Ana S.; Almeida, José; Medrado, Bárbara F.; Pádua, Ana C. C. S.; Carvalho, Ana L.; Dionísio, Madalena; Li, Rosamaria W. C.; Gamboa, Hugo; Ulijn, Rein V.; Gruber, Jonas; Roque, Ana C. A.

2017-01-01

The cooperative assembly of biopolymers and small molecules can yield functional materials with precisely tunable properties. Here, the fabrication, characterization, and use of multicomponent hybrid gels as selective gas sensors are reported. The gels are composed of liquid crystal droplets self-assembled in the presence of ionic liquids, which further coassemble with biopolymers to form stable matrices. Each individual component can be varied and acts cooperatively to tune gels’ structure and function. The unique molecular environment in hybrid gels is explored for supramolecular recognition of volatile compounds. Gels with distinct compositions are used as optical and electrical gas sensors, yielding a combinatorial response conceptually mimicking olfactory biological systems, and tested to distinguish volatile organic compounds and to quantify ethanol in automotive fuel. The gel response is rapid, reversible, and reproducible. These robust, versatile, modular, pliant electro-optical soft materials possess new possibilities in sensing triggered by chemical and physical stimuli. PMID:28747856

Structural Health Monitoring: Leveraging Pain in the Human Body

NASA Astrophysics Data System (ADS)

Nayak, Subhadarshi

2012-07-01

Tissue damage, or the perception thereof, is managed through pain experience. The neurobiological process of pain triggers most effective defense mechanisms for our safety. Structural health monitoring (SHM) is also a very similar function, albeit in engineering systems. SHM technology can leverage many aspects of pain mechanisms to progress in several critical areas. Discrimination between features from the undamaged and damaged structures can follow the threshold gate mechanism of the pain perception. Furthermore, the sensing mechanisms can be adaptive to changes by adjusting the threshold as does the pain perception. A distributed sensor network, often advanced by SHM, can be made fault-tolerant and robust by following the perception way of self-organization and redundancy. Data handling in real life is a huge challenge for large-scale SHM. As sensory data of pain is first cleaned, the threshold is then processed through experiential information gathering and use.

CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors

PubMed Central

Cutforth, Tyler; DeMille, Mellissa MC; Agalliu, Ilir; Agalliu, Dritan

2016-01-01

Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham’s chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met for the requisite neurovascular pathology and behavioral deficits found in SC/PANDAS. PMID:27110222

The Ion Channel TRPA1 Is Required for Chronic Itch

PubMed Central

Wilson, Sarah R.; Nelson, Aislyn M.; Batia, Lyn; Morita, Takeshi; Estandian, Daniel; Owens, David M.; Lumpkin, Ellen A.; Bautista, Diana M.

2013-01-01

Chronic itch is a debilitating condition that affects one in 10 people. Little is known about the molecules that mediate chronic itch in primary sensory neurons and skin. We demonstrate that the ion channel TRPA1 is required for chronic itch. Using a mouse model of chronic itch, we show that scratching evoked by impaired skin barrier is abolished in TRPA1-deficient animals. This model recapitulates many of the pathophysiological hallmarks of chronic itch that are observed in prevalent human diseases such as atopic dermatitis and psoriasis, including robust scratching, extensive epidermal hyperplasia, and dramatic changes in gene expression in sensory neurons and skin. Remarkably, TRPA1 is required for both transduction of chronic itch signals to the CNS and for the dramatic skin changes triggered by dry-skin-evoked itch and scratching. These data suggest that TRPA1 regulates both itch transduction and pathophysiological changes in the skin that promote chronic itch. PMID:23719797

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

PubMed

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S; Jain, Shalini; Lowell, Bradford B; Krashes, Michael J; Wess, Jürgen

2016-01-08

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

Theta–gamma coordination between anterior cingulate and prefrontal cortex indexes correct attention shifts

PubMed Central

Voloh, Benjamin; Valiante, Taufik A.; Everling, Stefan; Womelsdorf, Thilo

2015-01-01

Anterior cingulate and lateral prefrontal cortex (ACC/PFC) are believed to coordinate activity to flexibly prioritize the processing of goal-relevant over irrelevant information. This between-area coordination may be realized by common low-frequency excitability changes synchronizing segregated high-frequency activations. We tested this coordination hypothesis by recording in macaque ACC/PFC during the covert utilization of attention cues. We found robust increases of 5–10 Hz (theta) to 35–55 Hz (gamma) phase–amplitude correlation between ACC and PFC during successful attention shifts but not before errors. Cortical sites providing theta phases (i) showed a prominent cue-induced phase reset, (ii) were more likely in ACC than PFC, and (iii) hosted neurons with burst firing events that synchronized to distant gamma activity. These findings suggest that interareal theta–gamma correlations could follow mechanistically from a cue-triggered reactivation of rule memory that synchronizes theta across ACC/PFC. PMID:26100868

High-Intensity Radiated Field Fault-Injection Experiment for a Fault-Tolerant Distributed Communication System

NASA Technical Reports Server (NTRS)

Yates, Amy M.; Torres-Pomales, Wilfredo; Malekpour, Mahyar R.; Gonzalez, Oscar R.; Gray, W. Steven

2010-01-01

Safety-critical distributed flight control systems require robustness in the presence of faults. In general, these systems consist of a number of input/output (I/O) and computation nodes interacting through a fault-tolerant data communication system. The communication system transfers sensor data and control commands and can handle most faults under typical operating conditions. However, the performance of the closed-loop system can be adversely affected as a result of operating in harsh environments. In particular, High-Intensity Radiated Field (HIRF) environments have the potential to cause random fault manifestations in individual avionic components and to generate simultaneous system-wide communication faults that overwhelm existing fault management mechanisms. This paper presents the design of an experiment conducted at the NASA Langley Research Center's HIRF Laboratory to statistically characterize the faults that a HIRF environment can trigger on a single node of a distributed flight control system.

From disorganized capitalism to transnational fine tuning? Recent trends in wage development, industrial relations, and 'work' as a sociological category.

PubMed

Hasse, Raimund; Leiulfsrud, Håkon

2002-03-01

The disorganization thesis concentrates upon globalization and market dynamics, which are believed to trigger the breakdown of any kind of institutional structures. The diversity of capitalism approach, by contrast, places much emphasis on the persistence of distinct paths of national economies. Referring to comparative data from the OECD and other sources it is shown that some variables indicate a robustness of national styles of capitalism. Others hint at resemblance: e.g. there is a striking synchronization of the overall and sectoral wage development, there is a significant decrease in industrial disputes, and the class composition tends to become more similar. A move beyond the disorganization thesis and diversity of capitalism approach is suggested. Special attention should be paid to the profound impacts of transnational institutions and knowledge carriers in the form of experts and guidelines.

Aggregation of trypsin and trypsin inhibitor by Al cation.

PubMed

Chanphai, P; Kreplak, L; Tajmir-Riahi, H A

2017-04-01

Al cation may trigger protein structural changes such as aggregation and fibrillation, causing neurodegenerative diseases. We report the effect of Al cation on the solution structures of trypsin (try) and trypsin inhibitor (tryi), using thermodynamic analysis, UV-Visible, Fourier transform infrared (FTIR) spectroscopic methods and atomic force microscopy (AFM). Thermodynamic parameters showed Al-protein bindings occur via H-bonding and van der Waals contacts for trypsin and trypsin inhibitor. AFM showed that Al cations are able to force trypsin into larger or more robust aggregates than trypsin inhibitor, with trypsin 5±1 SE (n=52) proteins per aggregate and for trypsin inhibitor 8.3±0.7 SE (n=118). Thioflavin T test showed no major protein fibrillation in the presence of Al cation. Al complexation induced more alterations of trypsin inhibitor conformation than trypsin. Copyright © 2017 Elsevier B.V. All rights reserved.

Modeling the effect of boost timing in murine irradiated sporozoite prime-boost vaccines

PubMed Central

Zhang, Min; Herrero, Miguel A.; Acosta, Francisco J.; Tsuji, Moriya

2018-01-01

Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T cell-mediated protection against pre-erythrocytic stages of malaria. Empirical evidence suggests that successive inoculations often improve the efficacy of this type of vaccines. An initial dose (prime) triggers a specific cellular response, and subsequent inoculations (boost) amplify this response to create a robust CD8+ T cell memory. In this work we propose a model to analyze the effect of T cell dynamics on the performance of prime-boost vaccines. This model suggests that boost doses and timings should be selected according to the T cell response elicited by priming. Specifically, boosting during late stages of clonal contraction would maximize T cell memory production for vaccines using lower doses of irradiated sporozoites. In contrast, single-dose inoculations would be indicated for higher vaccine doses. Experimental data have been obtained that support theoretical predictions of the model. PMID:29329308

HGCAL: a High-Granularity Calorimeter for the endcaps of CMS at HL-LHC

NASA Astrophysics Data System (ADS)

Magnan, A.-M.

2017-01-01

Calorimetry at the High Luminosity LHC (HL-LHC) faces two enormous challenges, particularly in the forward direction: radiation tolerance and unprecedented in-time event pileup. To meet these challenges, the CMS experiment has decided to construct a High Granularity Calorimeter (HGCAL), featuring a previously unrealized transverse and longitudinal segmentation, for both electromagnetic and hadronic compartments. This will facilitate particle-flow-type calorimetry, where the fine structure of showers can be measured and used to enhance particle identification, energy resolution and pileup rejection. The majority of the HGCAL will be based on robust and cost-effective hexagonal silicon sensors with simeq 1 cm2 or 0.5 cm2 hexagonal cell size, with the final five interaction lengths of the hadronic compartment being based on highly segmented plastic scintillator with on-scintillator SiPM readout. We present an overview of the HGCAL project, including the motivation, engineering design, readout/trigger concept and simulated performance.

Development and performance of electronic acute kidney injury triggers to identify pediatric patients at risk for nephrotoxic medication-associated harm.

PubMed

Kirkendall, E S; Spires, W L; Mottes, T A; Schaffzin, J K; Barclay, C; Goldstein, S L

2014-01-01

Nephrotoxic medication-associated acute kidney injury (NTMx-AKI) is a costly clinical phenomenon and more common than previously recognized. Prior efforts to use technology to identify AKI have focused on detection after renal injury has occurred. Describe an approach and provide a technical framework for the creation of risk-stratifying AKI triggers and the development of an application to manage the AKI trigger data. Report the performance characteristics of those triggers and the refinement process and on the challenges of implementation. Initial manual trigger screening guided design of an automated electronic trigger report. A web-based application was designed to alleviate inefficiency and serve as a user interface and central workspace for the project. Performance of the NTMx exposure trigger reports from September 2011 to September 2013 were evaluated using sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). Automated reports were created to replace manual screening for NTMx-AKI. The initial performance of the NTMx exposure triggers for SN, SP, PPV, and NPV all were ≥0.78, and increased over the study, with all four measures reaching ≥0.95 consistently. A web-based application was implemented that simplifies data entry and couriering from the reports, expedites results viewing, and interfaces with an automated data visualization tool. Sociotechnical challenges were logged and reported. We have built a risk-stratifying system based on electronic triggers that detects patients at-risk for NTMx-AKI before injury occurs. The performance of the NTMx-exposed reports has neared 100% through iterative optimization. The complexity of the trigger logic and clinical workflows surrounding NTMx-AKI led to a challenging implementation, but one that has been successful from technical, clinical, and quality improvement standpoints. This report summarizes the construction of a trigger-based application, the performance of the triggers, and the challenges uncovered during the design, build, and implementation of the system.

Infrequent triggering of tremor along the San Jacinto Fault near Anza, California

USGS Publications Warehouse

Wang, Tien-Huei; Cochran, Elizabeth S.; Agnew, Duncan Carr; Oglesby, David D.

2013-01-01

We examine the conditions necessary to trigger tremor along the San Jacinto fault (SJF) near Anza, California, where previous studies suggest triggered tremor occurs, but observations are sparse. We investigate the stress required to trigger tremor using continuous broadband seismograms from 11 stations located near Anza, California. We examine 44 Mw≥7.4 teleseismic events between 2001 and 2011; these events occur at a wide range of back azimuths and hypocentral distances. In addition, we included one smaller‐magnitude, regional event, the 2009 Mw 6.5 Gulf of California earthquake, because it induced extremely high strains at Anza. We find the only episode of triggered tremor occurred during the 3 November 2002 Mw 7.8 Denali earthquake. The tremor episode lasted 300 s, was composed of 12 tremor bursts, and was located along SJF at the northwestern edge of the Anza gap at approximately 13 km depth. The tremor episode started at the Love‐wave arrival, when surface‐wave particle motions are primarily in the transverse direction. We find that the Denali earthquake induced the second highest stress (~35  kPa) among the 44 teleseismic events and 1 regional event. The dominant period of the Denali surface wave was 22.8 s, at the lower end of the range observed for all events (20–40 s), similar to periods shown to trigger tremor in other locations. The surface waves from the 2009 Mw 6.5 Gulf of California earthquake had the highest observed strain, yet a much shorter dominant period of 10 s and did not trigger tremor. This result suggests that not only the amplitude of the induced strain, but also the period of the incoming surface wave, may control triggering of tremors 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 San Andreas fault.

Triggers, risk factors and clinico-pathological features of urticaria in dogs - a prospective observational study of 24 cases.

PubMed

Rostaher, Ana; Hofer-Inteeworn, Natalie; Kümmerle-Fraune, Claudia; Fischer, Nina Maria; Favrot, Claude

2017-02-01

Urticaria and anaphylaxis are frequently encountered in veterinary practice, but little is known about the causes and relative frequencies of these reactions. This study was designed to improve current knowledge on the triggers, risk factors and clinico-pathological features of urticaria. Twenty four dogs with signs of urticaria with or without anaphylaxis. The study included dogs with cutaneous immediate-type hypersensitivity reactions. The cases were grouped by clinical severity into either an urticaria or an anaphylaxis group. All treatments and diagnostic tests (haematology, biochemical profile, allergy investigation) were recorded. A causality algorithm for urticaria and anaphylaxis (ALUA) was designed to determine the probability of the identified triggers and cofactors. Disease incidence, breed, age and gender predispositions were evaluated statistically. Sixteen of 24 urticaria cases were associated with anaphylaxis whilst 8 of 24 were confined to the skin. The annual hospital incidence was 0.12%. Females seemed to be over-represented (2.4:1) and most of the dog breeds were pure breed (22 of 24), with Rhodesian ridgeback, boxer, beagle, Jack Russell terrier, French bulldog and Vizslas over-represented. In addition to skin lesions, the most frequently and severely affected organ systems were the gastrointestinal and cardiovascular systems. The predominant blood abnormalities were elevated lipase and alanine aminotransferase values. Insects, food and drugs were the most commonly identified triggers. To the best of our knowledge, this is the first study describing the trigger factors and clinico-pathological features of dogs with urticaria in veterinary medicine. Insects, food and drugs were the most frequently detected triggers. © 2016 ESVD and ACVD.

VISA is an adapter protein required for virus-triggered IFN-beta signaling.

PubMed

Xu, Liang-Guo; Wang, Yan-Yi; Han, Ke-Jun; Li, Lian-Yun; Zhai, Zhonghe; Shu, Hong-Bing

2005-09-16

Viral infection or stimulation of TLR3 triggers signaling cascades, leading to activation of the transcription factors IRF-3 and NF-kappaB, which collaborate to induce transcription of type I interferon (IFN) genes. In this study, we identified a protein termed VISA (for virus-induced signaling adaptor) as a critical component in the IFN-beta signaling pathways. VISA recruits IRF-3 to the cytoplasmic viral dsRNA sensor RIG-I. Depletion of VISA inhibits virus-triggered and RIG-I-mediated activation of IRF-3, NF-kappaB, and the IFN-beta promoter, suggesting that VISA plays a central role in virus-triggered TLR3-independent IFN-beta signaling. Our data also indicate that VISA interacts with TRIF and TRAF6 and mediates bifurcation of the TLR3-triggered NF-kappaB and IRF-3 activation pathways. These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling.

Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A Systematic Review and Meta-analysis.

PubMed

Ding, Nan; Liu, Xingchen; Jian, Qiliang; Liang, Zhongzhen; Wang, Fang

2017-11-01

Increasing evidence indicates that a dual trigger (a gonadotrophin-releasing hormone agonist [GnRH-a] with a human chorionic gonadotrophin [hCG] trigger) is the best choice for final oocyte maturation in the GnRH antagonist (GnRH-ant) cycle. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of a GnRH-a combined with a standard hCG trigger in comparison with hCG alone for final oocyte maturation in the GnRH-ant cycle for in vitro fertilization. Complete electronic databases, including PubMed, Embase, The Cochrane Library, and Web of Science, were searched for relevant randomized controlled trials (RCT). The search was not restricted by language or publication time. Two reviewers selected trials and assessed trial quality independently by using the Cochrane Handbook 5.1.0. Four eligible RCT studies involving 527 women were included. The results of this meta-analysis indicated that the dual trigger group had a significantly higher pregnancy rate (relative risk [RR], 1.55; 95% confidence interval [CI], 1.17-2.06) than the hCG-only trigger group. No significant differences were found in the number of oocytes retrieved (weighted mean difference [WMD], 0.47; 95% CI, -0.42 to 1.37), number of mature oocytes retrieved (WMD, 0.41; 95% CI, -0.48 to 1.30), number of fertilized oocytes (WMD, 0.47; 95% CI, -0.32 to 1.26), number of good-quality embryos (WMD, 0.17; 95% CI, -0.29 to 0.64), or implantation rate (RR, 1.17; 95% CI, 0.69-2.00) between the two groups. GnRH-a and hCG as dual trigger was equivalent to hCG in triggering oocyte maturation and may be beneficial in improving reproductive outcomes. Further intensive randomized-controlled studies should be conducted to investigate the efficacy of the dual trigger. Copyright © 2017 Elsevier B.V. All rights reserved.

Children with migraine: Provocation of headache via pressure to myofascial trigger points in the trapezius muscle? - A prospective controlled observational study.

PubMed

Landgraf, M N; Biebl, J T; Langhagen, T; Hannibal, I; Eggert, T; Vill, K; Gerstl, L; Albers, L; von Kries, R; Straube, A; Heinen, F

2018-02-01

The objective was to evaluate a supposed clinical interdependency of myofascial trigger points and migraine in children. Such interdependency would support an interaction of spinal and trigeminal afferences in the trigemino-cervical complex as a contributing factor in migraine. Children ≤18 years with the confirmed diagnosis of migraine were prospectively investigated. Comprehensive data on medical history, clinical neurological and psychological status were gathered. Trigger points in the trapezius muscle were identified by palpation and the threshold of pressure pain at these points was measured. Manual pressure was applied to the trigger points, and the occurrence and duration of induced headache were recorded. At a second consultation (4 weeks after the first), manual pressure with the detected pressure threshold was applied to non-trigger points within the same trapezius muscle (control). Headache and related parameters were again recorded and compared to the results of the first consultation. A total of 13 girls and 13 boys with migraine and a median age of 14.5 (Range 6.3-17.8) years took part in the study. Manual pressure to trigger points in the trapezius muscle led to lasting headache after termination of the manual pressure in 13 patients while no patient experienced headache when manual pressure was applied to non-trigger points at the control visit (p < 0.001). Headache was induced significantly more often in children ≥12 years and those with internalizing behavioural disorder. We found an association between trapezius muscle myofascial trigger points and migraine, which might underline the concept of the trigemino-cervical complex, especially in adolescents. In children with migraine headache can often be induced by pressure to myofascial trigger points, but not by pressure to non-trigger points in the trapezius muscle. This supports the hypothesis of a trigemino-cervical-complex in the pathophysiology of migraine, which might have implications for innovative therapies in children with migraine. © 2017 European Pain Federation - EFIC®.

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.

Airport metal detector activation is rare after posterior spinal fusion in children with scoliosis.

PubMed

Fabricant, Peter D; Robles, Alex; Blanco, John S

2013-12-01

Since the September 11, 2001 terrorist attacks on the World Trade Center in New York City, travel security has become an ever-increasing priority in the United States. Frequent parent and patient inquiry and recent literature reports have generated interest in the impact of heightened security measures on patients with orthopaedic implants, and have indicated increasing rates of metal detector triggering. There are no reports to date, however, evaluating children and adolescents who have undergone posterior spinal fusion for scoliosis, so responses to patient and parent inquiries are not data-driven. The purpose of this study is to determine the frequency of airport metal detector triggering by patients who have had posterior-only spinal fusion and to characterise any potential predictors of metal detector activation. A cross-sectional study was performed by interviewing 90 patients who underwent posterior-only spinal fusion for a diagnosis of juvenile or adolescent idiopathic scoliosis and have travelled by air in the past year. Demographic, clinical and surgical instrumentation data were collected and evaluated, along with patients' reports of airport metal detector triggering and subsequent screening procedures. Five patients with stainless steel instrumentation (5.6 % of the cohort) triggered an airport walkthrough metal detector, and an additional five patients who did not trigger an airport detector triggered a handheld detector at a different venue. All patients who triggered an airport metal detector had stainless steel instrumentation implanted prior to 2008, and no patient with titanium instrumentation triggered any detector in any venue. All trigger events required subsequent screening procedures, even when an implant card was presented. In this cohort of children and adolescents with posterior spinal instrumentation, airport walkthrough metal detector triggering was a rare event. Therefore, we advise patients and families with planned posterior scoliosis fusions using titanium instrumentation that airport detection risk is essentially non-existent, and only rare for those with planned stainless steel instrumentation. We no longer issue implant cards postoperatively, as these did not prevent further screening procedures in this cohort. Prognostic level 2. cross-sectional.

Automatic Classification of Extensive Aftershock Sequences Using Empirical Matched Field Processing

NASA Astrophysics Data System (ADS)

Gibbons, Steven J.; Harris, David B.; Kværna, Tormod; Dodge, Douglas A.

2013-04-01

The aftershock sequences that follow large earthquakes create considerable problems for data centers attempting to produce comprehensive event bulletins in near real-time. The greatly increased number of events which require processing can overwhelm analyst resources and reduce the capacity for analyzing events of monitoring interest. This exacerbates a potentially reduced detection capability at key stations, due the noise generated by the sequence, and a deterioration in the quality of the fully automatic preliminary event bulletins caused by the difficulty in associating the vast numbers of closely spaced arrivals over the network. Considerable success has been enjoyed by waveform correlation methods for the automatic identification of groups of events belonging to the same geographical source region, facilitating the more time-efficient analysis of event ensembles as opposed to individual events. There are, however, formidable challenges associated with the automation of correlation procedures. The signal generated by a very large earthquake seldom correlates well enough with the signals generated by far smaller aftershocks for a correlation detector to produce statistically significant triggers at the correct times. Correlation between events within clusters of aftershocks is significantly better, although the issues of when and how to initiate new pattern detectors are still being investigated. Empirical Matched Field Processing (EMFP) is a highly promising method for detecting event waveforms suitable as templates for correlation detectors. EMFP is a quasi-frequency-domain technique that calibrates the spatial structure of a wavefront crossing a seismic array in a collection of narrow frequency bands. The amplitude and phase weights that result are applied in a frequency-domain beamforming operation that compensates for scattering and refraction effects not properly modeled by plane-wave beams. It has been demonstrated to outperform waveform correlation as a classifier of ripple-fired mining blasts since the narrowband procedure is insensitive to differences in the source-time functions. For sequences in which the spectral content and time-histories of the signals from the main shock and aftershocks vary greatly, the spatial structure calibrated by EMFP is an invariant that permits reliable detection of events in the specific source region. Examples from the 2005 Kashmir and 2011 Van earthquakes demonstrate how EMFP templates from the main events detect arrivals from the aftershock sequences with high sensitivity and exceptionally low false alarm rates. Classical waveform correlation detectors are demonstrated to fail for these examples. Even arrivals with SNR below unity can produce significant EMFP triggers as the spatial pattern of the incoming wavefront is identified, leading to robust detections at a greater number of stations and potentially more reliable automatic bulletins. False EMFP triggers are readily screened by scanning a space of phase shifts relative to the imposed template. EMFP has the potential to produce a rapid and robust overview of the evolving aftershock sequence such that correlation and subspace detectors can be applied semi-autonomously, with well-chosen parameter specifications, to identify and classify clusters of very closely spaced aftershocks.

Application of in vivo measurements for the management of cyanobacteria breakthrough into drinking water treatment plants.

PubMed

Zamyadi, Arash; Dorner, Sarah; Ndong, Mouhamed; Ellis, Donald; Bolduc, Anouka; Bastien, Christian; Prévost, Michèle

2014-02-01

The increasing presence of potentially toxic cyanobacterial blooms in drinking water sources and within drinking water treatment plants (DWTPs) has been reported worldwide. The objectives of this study are to validate the application of in vivo probes for the detection and management of cyanobacteria breakthrough inside DWTPs, and to verify the possibility of treatment adjustment based on intensive real-time monitoring. In vivo phycocyanin YSI probes were used to monitor the fate of cyanobacteria in raw water, clarified water, filtered water, and chlorinated water in a full scale DWTP. Simultaneous samples were also taken for microscopic enumeration. The in vivo probe was successfully used to detect the incoming densities of high cyanobacterial cell number into the clarification process and their breakthrough into the filtered water. In vivo probes were used to trace the increase in floating cells over the clarifier, a robust sign of malfunction of the coagulation-sedimentation process. Pre-emptive treatment adjustments, based on in vivo probe monitoring, resulted in successful removal of cyanobacterial cells. The field results on validation of the probes with cyanobacterial bloom samples showed that the probe responses are highly linear and can be used to trigger alerts to take action.

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.

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

Covalently crosslinked diels-alder polymer networks.

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

Bowman, Christopher; Adzima, Brian J.; Anderson, Benjamin John

2011-09-01

This project examines the utility of cycloaddition reactions for the synthesis of polymer networks. Cycloaddition reactions are desirable because they produce no unwanted side reactions or small molecules, allowing for the formation of high molecular weight species and glassy crosslinked networks. Both the Diels-Alder reaction and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) were studied. Accomplishments include externally triggered healing of a thermoreversible covalent network via self-limited hysteresis heating, the creation of Diels-Alder based photoresists, and the successful photochemical catalysis of CuAAC as an alternative to the use of ascorbic acid for the generation of Cu(I) in click reactions. An analysis ofmore » the results reveals that these new methods offer the promise of efficiently creating robust, high molecular weight species and delicate three dimensional structures that incorporate chemical functionality in the patterned material. This work was performed under a Strategic Partnerships LDRD during FY10 and FY11 as part of a Sandia National Laboratories/University of Colorado-Boulder Excellence in Science and Engineering Fellowship awarded to Brian J. Adzima, a graduate student at UC-Boulder. Benjamin J. Anderson (Org. 1833) was the Sandia National Laboratories point-of-contact for this fellowship.« less

Readout architecture based on the use of Silicon PhotoMultiplier (SiPM, or MMPC)

NASA Astrophysics Data System (ADS)

Marteau, J.; Carlus, B.; Gardien, S.; Girerd, C.; Ianigro, J.-C.; Montorio, J.-L.; Gibert, D.; Nicollin, F.

2012-04-01

The DIAPHANE project is pluri-disciplinary collaboration between particle physicists and geophysicists to perform the tomography of large geological structure mainly devoted to the study of active volcanoes. The detector used for this tomography, hereafter referred to as telescope, uses a standard, robust, cost-effective and well-known technology based on solid plastic scintillator readout by photomultiplier(s). The first generation of those telescopes, presently running in the Mont-Terri underground laboratory (St-Ursanne, Switzerland) and on the active volcano of La Soufrière (Guadeloupe, Lesser Antilles, France), uses Hamamatsu H8804-200mod photomultipliers. We present an upgrade of the readout architecture based on the use of Silicon PhotoMultiplier (SiPM, or MMPC) which allows to simplify the optical connections w.r.t. the present design and to benefit from the high photo-dectection efficiency of the SiPM. To ensure an effective increase in the muon detection efficiency one has to optimize the first trigger level and find the best compromise between photostatistics and the tails of the dark noise contributions. Several readout architectures, based or not on dedicated ASICs, are discussed and compared in this article.

Tsunami evacuation buildings and evacuation planning in Banda Aceh, Indonesia.

PubMed

Yuzal, Hendri; Kim, Karl; Pant, Pradip; Yamashita, Eric

Indonesia, a country of more than 17,000 islands, is exposed to many hazards. A magnitude 9.1 earthquake struck off the coast of Sumatra, Indonesia, on December 26, 2004. It triggered a series of tsunami waves that spread across the Indian Ocean causing damage in 11 countries. Banda Aceh, the capital city of Aceh Province, was among the most damaged. More than 31,000 people were killed. At the time, there were no early warning systems nor evacuation buildings that could provide safe refuge for residents. Since then, four tsunami evacuation buildings (TEBs) have been constructed in the Meuraxa subdistrict of Banda Aceh. Based on analysis of evacuation routes and travel times, the capacity of existing TEBs is examined. Existing TEBs would not be able to shelter all of the at-risk population. In this study, additional buildings and locations for TEBs are proposed and residents are assigned to the closest TEBs. While TEBs may be part of a larger system of tsunami mitigation efforts, other strategies and approaches need to be considered. In addition to TEBs, robust detection, warning and alert systems, land use planning, training, exercises, and other preparedness strategies are essential to tsunami risk reduction.

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.

Potential for a hazardous geospheric response to projected future climate changes.

PubMed

McGuire, B

2010-05-28

Periods of exceptional climate change in Earth history are associated with a dynamic response from the geosphere, involving enhanced levels of potentially hazardous geological and geomorphological activity. The response is expressed through the adjustment, modulation or triggering of a broad range of surface and crustal phenomena, including volcanic and seismic activity, submarine and subaerial landslides, tsunamis and landslide 'splash' waves, glacial outburst and rock-dam failure floods, debris flows and gas-hydrate destabilization. In relation to anthropogenic climate change, modelling studies and projection of current trends point towards increased risk in relation to a spectrum of geological and geomorphological hazards in a warmer world, while observations suggest that the ongoing rise in global average temperatures may already be eliciting a hazardous response from the geosphere. Here, the potential influences of anthropogenic warming are reviewed in relation to an array of geological and geomorphological hazards across a range of environmental settings. A programme of focused research is advocated in order to: (i) understand better those mechanisms by which contemporary climate change may drive hazardous geological and geomorphological activity; (ii) delineate those parts of the world that are most susceptible; and (iii) provide a more robust appreciation of potential impacts for society and infrastructure.

RGO/AuNR/HA-5FU nanocomposite with multi-stage release behavior and efficient antitumor activity for synergistic therapy.

PubMed

Yang, Ying; Wang, Yunlong; Zhu, Manzhou; Chen, Yan; Xiao, Yazhong; Shen, Yuhua; Xie, Anjian

2017-05-02

A reduced graphene oxide (RGO)/gold nanorod (AuNR)/hydroxyapatite (HA) nanocomposite was designed and successfully synthesized for the first time. An anticancer drug, 5-fluorouracil (5FU), was chosen as a model drug to be loaded in RGO/AuNR/HA. The fabricated RGO/AuNR/HA-5FU showed robust, selective targeting and penetrating efficiency against HeLa cells due to the good compatibility and nontoxicity of HA, and showed excellent synergetic antitumor effects through combined chemotherapy (CT) by 5FU and photothermal therapy (PTT) by both RGO and AuNRs under near-infrared (NIR) laser irradiation. More importantly, this synergistic dual therapy based on RGO/AuNR/HA can also minimize side effects in normal cells and exhibits greater antitumor activity because of a multi-stage drug release ability triggered by the pH sensitivity of HA in the first stage and the combined photothermal conversion capabilities of RGO and AuNRs by means of the NIR laser irradiation in the second stage. This study suggests that the novel RGO/AuNR/HA multi-stage drug delivery system may represent a promising potential application of multifunctional composite materials in the biomedical field.

IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector

PubMed Central

Hopewell, Emily L.; Bronk, Crystina C.; Massengill, Michael; Engelman, Robert W.; Beg, Amer A.

2012-01-01

Microbial adjuvants in vaccines activate key transcription factors, including NF-κB and interferon response factors (IRFs). However, the individual role of these transcription factor pathways in promoting adaptive immunity by adjuvants is not clear. It is widely believed that induction of a strong inflammatory response potentiates an adaptive immune response. In this study, we sought to determine whether activation of the pro-inflammatory inhibitor of κB kinase β (IKKβ) canonical NF-κB pathway promoted vaccine-induced immune responses. An adenovirus expressing constitutively-activated IKKβ (AdIKK) induced robust DC maturation and high expression of key cytokines compared to a control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary infection, increased leukocyte entry into draining LNs, and enhanced early antibody and T-cell responses. Notably, AdIKK did not influence the overall magnitude of the adaptive immune response. These results indicate that induction of inflammation by IKKβ/NF-κB in this setting impacts the kinetics but not the magnitude of adaptive immune responses. These findings therefore help define the individual role of a key pathway induced by vaccine adjuvants in promoting adaptive immunity. PMID:22161279

Earthquake Declustering via a Nearest-Neighbor Approach in Space-Time-Magnitude Domain

NASA Astrophysics Data System (ADS)

Zaliapin, I. V.; Ben-Zion, Y.

2016-12-01

We propose a new method for earthquake declustering based on nearest-neighbor analysis of earthquakes in space-time-magnitude domain. The nearest-neighbor approach was recently applied to a variety of seismological problems that validate the general utility of the technique and reveal the existence of several different robust types of earthquake clusters. Notably, it was demonstrated that clustering associated with the largest earthquakes is statistically different from that of small-to-medium events. In particular, the characteristic bimodality of the nearest-neighbor distances that helps separating clustered and background events is often violated after the largest earthquakes in their vicinity, which is dominated by triggered events. This prevents using a simple threshold between the two modes of the nearest-neighbor distance distribution for declustering. The current study resolves this problem hence extending the nearest-neighbor approach to the problem of earthquake declustering. The proposed technique is applied to seismicity of different areas in California (San Jacinto, Coso, Salton Sea, Parkfield, Ventura, Mojave, etc.), as well as to the global seismicity, to demonstrate its stability and efficiency in treating various clustering types. The results are compared with those of alternative declustering methods.

GENERAL EARTHQUAKE-OBSERVATION SYSTEM (GEOS).

USGS Publications Warehouse

Borcherdt, R.D.; Fletcher, Joe B.; Jensen, E.G.; Maxwell, G.L.; VanSchaack, J.R.; Warrick, R.E.; Cranswick, E.; Johnston, M.J.S.; McClearn, R.

1985-01-01

Microprocessor technology has permitted the development of a General Earthquake-Observation System (GEOS) useful for most seismic applications. Central-processing-unit control via robust software of system functions that are isolated on hardware modules permits field adaptability of the system to a wide variety of active and passive seismic experiments and straightforward modification for incorporation of improvements in technology. Various laboratory tests and numerous deployments of a set of the systems in the field have confirmed design goals, including: wide linear dynamic range (16 bit/96 dB); broad bandwidth (36 hr to 600 Hz; greater than 36 hr available); selectable sensor-type (accelerometer, seismometer, dilatometer); selectable channels (1 to 6); selectable record mode (continuous, preset, trigger); large data capacity (1. 4 to 60 Mbytes); selectable time standard (WWVB, master, manual); automatic self-calibration; simple field operation; full capability to adapt system in the field to a wide variety of experiments; low power; portability; and modest costs. System design goals for a microcomputer-controlled system with modular software and hardware components as implemented on the GEOS are presented. The systems have been deployed for 15 experiments, including: studies of near-source strong motion; high-frequency microearthquakes; crustal structure; down-hole wave propagation; teleseismicity; and earth-tidal strains.

Persistent Cold Air Outbreaks over North America Under Climate Warming

NASA Astrophysics Data System (ADS)

Gao, Y.; Leung, L. R.; Lu, J.

2014-12-01

This study evaluates the change of cold air outbreaks (CAO) over North America using Coupled Model Intercomparison Project Phase 5 (CMIP5) multi-model ensemble of global climate simulations as well as regional high resolution climate simulations. In future, while robust decrease of CAO duration dominates in most of the North America, the decrease over northwestern U.S. was found to have much smaller magnitude than the surrounding regions. We found statistically significant increase of the sea level pressure over gulf of Alaska, leading to the advection of cold air to northwestern U.S.. By shifting the probability distribution of present temperature towards future warmer conditions, we identified the changes in large scale circulation contribute to about 50% of the enhanced sea level pressure. Using the high resolution regional climate model results, we found that increases of existing snowpack could potentially trigger the increase of CAO in the near future over the southwestern U.S. and Rocky Mountain through surface albedo effects. By the end of this century, the top 5 most extreme historical CAO events may still occur and wind chill warning will continue to have societal impacts over North America in particular over northwestern United States.

Left Posterior Orbitofrontal Cortex Is Associated With Odor-Induced Autobiographical Memory: An fMRI Study.

PubMed

Watanabe, Keiko; Masaoka, Yuri; Kawamura, Mitsuru; Yoshida, Masaki; Koiwa, Nobuyoshi; Yoshikawa, Akira; Kubota, Satomi; Ida, Masahiro; Ono, Kenjiro; Izumizaki, Masahiko

2018-01-01

Autobiographical odor memory (AM-odor) accompanied by a sense of realism of a specific memory elicits strong emotions. AM-odor differs from memory triggered by other sensory modalities, possibly because olfaction involves a unique sensory process. Here, we examined the orbitofrontal cortex (OFC), using functional magnetic resonance imaging (fMRI) to determine which OFC subregions are related to AM-odor. Both AM-odor and a control odor successively increased subjective ratings of comfortableness and pleasantness. Importantly, AM-odor also increased arousal levels and the vividness of memories, and was associated with a deep and slow breathing pattern. fMRI analysis indicated robust activation in the left posterior OFC (L-POFC). Connectivity between the POFC and whole brain regions was estimated using psychophysiological interaction analysis (PPI). We detected several trends in connectivity between L-POFC and bilateral precuneus, bilateral rostral dorsal anterior cingulate cortex (rdACC), and left parahippocampus, which will be useful for targeting our hypotheses for future investigations. The slow breathing observed in AM-odor was correlated with rdACC activation. Odor associated with emotionally significant autobiographical memories was accompanied by slow and deep breathing, possibly involving rdACC processing.

The Space-Time Variation of Global Crop Yields, Detecting Simultaneous Outliers and Identifying the Teleconnections with Climatic Patterns

NASA Astrophysics Data System (ADS)

Najafi, E.; Devineni, N.; Pal, I.; Khanbilvardi, R.

2017-12-01

An understanding of the climate factors that influence the space-time variability of crop yields is important for food security purposes and can help us predict global food availability. In this study, we address how the crop yield trends of countries globally were related to each other during the last several decades and the main climatic variables that triggered high/low crop yields simultaneously across the world. Robust Principal Component Analysis (rPCA) is used to identify the primary modes of variation in wheat, maize, sorghum, rice, soybeans, and barley yields. Relations between these modes of variability and important climatic variables, especially anomalous sea surface temperature (SSTa), are examined from 1964 to 2010. rPCA is also used to identify simultaneous outliers in each year, i.e. systematic high/low crop yields across the globe. The results demonstrated spatiotemporal patterns of these crop yields and the climate-related events that caused them as well as the connection of outliers with weather extremes. We find that among climatic variables, SST has had the most impact on creating simultaneous crop yields variability and yield outliers in many countries. An understanding of this phenomenon can benefit global crop trade networks.

Designing monitoring programs for chemicals of emerging concern in potable reuse--what to include and what not to include?

PubMed

Drewes, J E; Anderson, P; Denslow, N; Olivieri, A; Schlenk, D; Snyder, S A; Maruya, K A

2013-01-01

This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than '1' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound.

The long pollen tube journey and in vitro pollen germination of Phalaenopsis orchids.

PubMed

Chen, Jhun-Chen; Fang, Su-Chiung

2016-06-01

Pollen biology in P. aphrodite. Orchids have a distinct reproductive program. Pollination triggers ovule development and differentiation within flowers, and fertilization occurs days to months after pollination. It is unclear how pollen tubes travel through the developing ovaries during ovule development and when pollen tubes arrive at the mature embryo sac to achieve fertilization. Here, we report a robust staining protocol to image and record the timing of pollen germination, progressive growth of pollen tubes in ovaries, and arrival of pollen tubes at embryo sacs in Phalaenopsis aphrodite. The pollen germinated and pollen tubes entered the ovary 3 days after pollination. Pollen tubes continued to grow and filled the entire cavity of the ovary as the ovary elongated and ovules developed. Pollen tubes were found to enter the matured embryo sacs at approximately 60-65 days after pollination in an acropetal manner. Moreover, these temporal changes in developmental events such as growth of pollen tubes and fertilization were associated with expression of molecular markers. In addition, we developed an in vitro pollen germination protocol, which is valuable to enable studies on pollen tube guidance and tip growth regulation in Phalaenopsis orchids and possibly in other orchid species.

Supraspinal Control of Urine Storage and Micturition in Men—An fMRI Study

PubMed Central

Michels, Lars; Blok, Bertil F.M.; Gregorini, Flavia; Kurz, Michael; Schurch, Brigitte; Kessler, Thomas M.; Kollias, Spyros; Mehnert, Ulrich

2015-01-01

Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showed less robust activation during initiation of micturition, with activity in the forebrain and brainstem particularly lacking. Our findings suggest that micturition is controlled by a specific supraspinal network which is essential for the voluntary initiation of micturition. Once this network triggers the bulbospinal micturition reflex via brainstem centers, micturition continues automatically without further supraspinal input. Unsuccessful micturition is characterized by a failure to activate the periaqueductal gray and pons during initiation. PMID:24969474

Engineering design of the PLX- α coaxial gun

NASA Astrophysics Data System (ADS)

Cruz, E.; Brockington, S.; Case, A.; Luna, M.; Witherspoon, F. D.; Thio, Y. C. Francis; PLX-α Team

2017-10-01

We describe the engineering and technical improvements, as well as provide a detailed overview of the design choices, of the latest PLX- α coaxial gun designed for the 60-gun scaling study of spherically imploding plasma liners as a standoff driver for plasma-jet-driven magneto-inertial fusion. Each coaxial gun incorporates a fast, dense gas injection and triggering system, a compact low-weight pfn with integral sparkgap switching, and a contoured gap designed to suppress the blow-by instability. The evolution of the latest Alpha gun is presented with emphasis on its upgraded performance. Changes include a faster more robust gas valve, better-quality ceramic insulator material and enhancements to overall design layout. These changes result in a gun with increased repeatability, reduced potential failure modes, improved fault tolerance and better than expected efficiency. A custom 600- μF, 5-kV pfn and a set of six inline sparkgap switches operated in parallel are mounted directly to the back of the gun, and are designed to reduce inductance, cost, and complexity, maximize efficiency and system reliability, and ensure symmetric current flow. This work supported by the ARPA-E ALPHA Program under contract DE-AR0000566 and Strong Atomics, LLC.

Spatio-temporal correlations in models of collective motion ruled by different dynamical laws.

PubMed

Cavagna, Andrea; Conti, Daniele; Giardina, Irene; Grigera, Tomas S; Melillo, Stefania; Viale, Massimiliano

2016-11-15

Information transfer is an essential factor in determining the robustness of biological systems with distributed control. The most direct way to study the mechanisms ruling information transfer is to experimentally observe the propagation across the system of a signal triggered by some perturbation. However, this method may be inefficient for experiments in the field, as the possibilities to perturb the system are limited and empirical observations must rely on natural events. An alternative approach is to use spatio-temporal correlations to probe the information transfer mechanism directly from the spontaneous fluctuations of the system, without the need to have an actual propagating signal on record. Here we test this method on models of collective behaviour in their deeply ordered phase by using ground truth data provided by numerical simulations in three dimensions. We compare two models characterized by very different dynamical equations and information transfer mechanisms: the classic Vicsek model, describing an overdamped noninertial dynamics and the inertial spin model, characterized by an underdamped inertial dynamics. By using dynamic finite-size scaling, we show that spatio-temporal correlations are able to distinguish unambiguously the diffusive information transfer mechanism of the Vicsek model from the linear mechanism of the inertial spin model.

TRIM29 Negatively Regulates the Type I IFN Production in Response to RNA Virus.

PubMed

Xing, Junji; Zhang, Ao; Minze, Laurie J; Li, Xian Chang; Zhang, Zhiqiang

2018-05-16

The innate immunity is critically important in protection against virus infections, and in the case of RNA viral infections, the signaling mechanisms that initiate robust protective innate immunity without triggering autoimmune inflammation remain incompletely defined. In this study, we found the E3 ligase TRIM29 was specifically expressed in poly I:C-stimulated human myeloid dendritic cells. The induced TRIM29 played a negative role in type I IFN production in response to poly I:C or dsRNA virus reovirus infection. Importantly, the challenge of wild-type mice with reovirus led to lethal infection. In contrast, deletion of TRIM29 protected the mice from this developing lethality. Additionally, TRIM29 -/- mice have lower titers of reovirus in the heart, intestine, spleen, liver, and brain because of elevated production of type I IFN. Mechanistically, TRIM29 was shown to interact with MAVS and subsequently induce its K11-linked ubiquitination and degradation. Taken together, TRIM29 regulates negatively the host innate immune response to RNA virus, which could be employed by RNA viruses for viral pathogenesis. Copyright © 2018 by The American Association of Immunologists, Inc.

An effector Peptide family required for Drosophila toll-mediated immunity.

PubMed

Clemmons, Alexa W; Lindsay, Scott A; Wasserman, Steven A

2015-04-01

In Drosophila melanogaster, recognition of an invading pathogen activates the Toll or Imd signaling pathway, triggering robust upregulation of innate immune effectors. Although the mechanisms of pathogen recognition and signaling are now well understood, the functions of the immune-induced transcriptome and proteome remain much less well characterized. Through bioinformatic analysis of effector gene sequences, we have defined a family of twelve genes - the Bomanins (Boms) - that are specifically induced by Toll and that encode small, secreted peptides of unknown biochemical activity. Using targeted genome engineering, we have deleted ten of the twelve Bom genes. Remarkably, inactivating these ten genes decreases survival upon microbial infection to the same extent, and with the same specificity, as does eliminating Toll pathway function. Toll signaling, however, appears unaffected. Assaying bacterial load post-infection in wild-type and mutant flies, we provide evidence that the Boms are required for resistance to, rather than tolerance of, infection. In addition, by generating and assaying a deletion of a smaller subset of the Bom genes, we find that there is overlap in Bom activity toward particular pathogens. Together, these studies deepen our understanding of Toll-mediated immunity and provide a new in vivo model for exploration of the innate immune effector repertoire.

Selective functionalization of carbon nanotube tips allowing fabrication of new classes of nanoscale sensing and manipulation tools

NASA Technical Reports Server (NTRS)

Wade, Lawrence A. (Inventor); Shapiro, Ian R. (Inventor); Bittner, Jr., Vern Garrett (Inventor); Collier, Charles Patrick (Inventor); Esplandiu, Maria J. (Inventor); Giapis, Konstantinos P. (Inventor)

2009-01-01

Embodiments in accordance with the present invention relate to techniques for the growth and attachment of single wall carbon nanotubes (SWNT), facilitating their use as robust and well-characterized tools for AFM imaging and other applications. In accordance with one embodiment, SWNTs attached to an AFM tip can function as a structural scaffold for nanoscale device fabrication on a scanning probe. Such a probe can trigger, with nanometer precision, specific biochemical reactions or conformational changes in biological systems. The consequences of such triggering can be observed in real time by single-molecule fluorescence, electrical, and/or AFM sensing. Specific embodiments in accordance with the present invention utilize sensing and manipulation of individual molecules with carbon nanotubes, coupled with single-molecule fluorescence imaging, to allow observation of spectroscopic signals in response to mechanically induced molecular changes. Biological macromolecules such as proteins or DNA can be attached to nanotubes to create highly specific single-molecule probes for investigations of intermolecular dynamics, for assembling hybrid biological and nanoscale materials, or for developing molecular electronics. In one example, electrical wiring of single redox enzymes to carbon nanotube scanning probes allows observation and electrochemical control over single enzymatic reactions by monitoring fluorescence from a redox-active cofactor or the formation of fluorescent products. Enzymes ''nanowired'' to the tips of carbon nanotubes in accordance with embodiments of the present invention, may enable extremely sensitive probing of biological stimulus-response with high spatial resolution, including product-induced signal transduction.

Swift-BAT: The First Year of Gamma-Ray Burst Detections

NASA Technical Reports Server (NTRS)

Krimm, Hans A.

2006-01-01

The Burst Alert Telescope (BAT) on the Swift has been detecting gamma-ray bursts (GRBs) since Dec. 17,2004 and automated burst alerts have been distributed since Feb. 14,2005. Since commissioning the BAT has triggered on more than 100 GRBs, nearly all of which have been followed up by the narrow-field instruments on Swift through automatic repointing, and by ground and other satellite telescopes after rapid notification. Within seconds of a trigger the BAT produces and relays to the ground a position good to three arc minutes and a four channel light curve. A full ten minutes of event data follows on subsequent ground station passes. The burst archive has allowed us to determine ensemble burst parameters such as fluence, peak flux and duration. An overview of the properties of BAT bursts and BAT'S performance as a burst monitor will be presented in this talk. BAT is a coded aperture imaging system with a wide (approx.2 sr) field of view consisting of a large coded mask located 1 m above a 5200 cm2 array of 32.768 CdZnTe detectors. All electronics and other hardware systems on the BAT have been operating well since commissioning and there is no sign of any degradation on orbit. The flight and ground software have proven similarly robust and allow the real time localization of all bursts and the rapid derivation of burst light curves, spectra and spectral fits on the ground.

The therapeutic value of laughter in medicine.

PubMed

Mora-Ripoll, Ramon

2010-01-01

The aim of this review is to identify, critically evaluate, and summarize the laughter literature across a number of fields related to medicine and health care to assess to what extent laughter health-related benefits are currently supported by empirical evidence. A comprehensive laughter literature search was performed. A thorough search of the gray literature was also undertaken. A list of inclusion and exclusion criteria was identified. It was necessary to distinguish between humor and laughter to assess health-related outcomes elicited by laughter only. Thematic analysis was applied to summarize laughter health-related outcomes, relationships, and general robustness. Laughter has shown physiological, psychological, social, spiritual, and quality-of-life benefits. Adverse effects are very limited, and laughter is practically lacking in contraindications. Therapeutic efficacy of laughter is mainly derived from spontaneous laughter (triggered by external stimuli or positive emotions) and self-induced laughter (triggered by oneself at will), both occurring with or without humor. The brain is not able to distinguish between these types; therefore, it is assumed that similar benefits may be achieved with one or the other. Although there is not enough data to demonstrate that laughter is an all-around healing agent, this review concludes that there exists sufficient evidence to suggest that laughter has some positive, quantifiable effects on certain aspects of health. In this era of evidence-based medicine, it would be appropriate for laughter to be used as a complementary/alternative medicine in the prevention and treatment of illnesses, although further well-designed research is warranted.

Open Source Tools for Seismicity Analysis

NASA Astrophysics Data System (ADS)

Powers, P.

2010-12-01

The spatio-temporal analysis of seismicity plays an important role in earthquake forecasting and is integral to research on earthquake interactions and triggering. For instance, the third version of the Uniform California Earthquake Rupture Forecast (UCERF), currently under development, will use Epidemic Type Aftershock Sequences (ETAS) as a model for earthquake triggering. UCERF will be a "living" model and therefore requires robust, tested, and well-documented ETAS algorithms to ensure transparency and reproducibility. Likewise, as earthquake aftershock sequences unfold, real-time access to high quality hypocenter data makes it possible to monitor the temporal variability of statistical properties such as the parameters of the Omori Law and the Gutenberg Richter b-value. Such statistical properties are valuable as they provide a measure of how much a particular sequence deviates from expected behavior and can be used when assigning probabilities of aftershock occurrence. To address these demands and provide public access to standard methods employed in statistical seismology, we present well-documented, open-source JavaScript and Java software libraries for the on- and off-line analysis of seismicity. The Javascript classes facilitate web-based asynchronous access to earthquake catalog data and provide a framework for in-browser display, analysis, and manipulation of catalog statistics; implementations of this framework will be made available on the USGS Earthquake Hazards website. The Java classes, in addition to providing tools for seismicity analysis, provide tools for modeling seismicity and generating synthetic catalogs. These tools are extensible and will be released as part of the open-source OpenSHA Commons library.

A novel trigger for pseudospark switch with high repetition rate, low jitter, and compact structure

NASA Astrophysics Data System (ADS)

Yan, Jiaqi; Shen, Saikang; Wang, Yanan; Zhang, Siyu; Cheng, Le; Ding, Weidong

2018-06-01

This paper presents the design and development of a trigger with a high repetition rate, low jitter, and compact structure for the pseudospark switch (PSS), which includes an improved Marx generator based on avalanche transistors and a corona-plasma trigger unit. The generator adopted a novel 3 × 12-stage Marx circuit based on avalanche transistors in which the failure rate of transistors in the first and second stages was significantly reduced by connecting the parallel capacitors compared to the previous similar generator. The reason for the improved performance was also discussed. The main parameters of output pulses were an amplitude of -7 kV, rise time of 6 ns, jitter of 0.2 ns, and repetition rate of 2 kHz. The corona-plasma trigger unit adopted BaTiO3 ceramics with high ɛr as the dielectric and was arranged in the hollow cathode of the PSS. The experiments of triggering a PSS prototype were conducted. The influence of anode voltage and pressure on the trigger delay and jitter was studied, and the minimum trigger jitter achieved <1 ns. This trigger worked for 107 shots at the repetition rate of 2 kHz continuously without obvious performance degradation and any failure of the generator. The main advantage of this trigger is the simultaneous combination of the high repetition rate, low jitter, long lifetime, and great simplicity in a compact structure.

Dynamic Earthquake Triggering on Seismogenic Faults in Oklahoma

NASA Astrophysics Data System (ADS)

Qin, Y.; Chen, X.; Peng, Z.; Aiken, C.

2016-12-01

Regions with high pore pressure are generally more susceptible to dynamic triggering from transient stress change caused by surface wave of distant earthquakes. The stress threshold from triggering studies can help understand the stress state of seismogenic faults. The recent dramatic seismicity increase in central US provides a rich database for assessing dynamic triggering phenomena. We begin our study by conducting a systematic analysis of dynamic triggering for the continental U.S using ANSS catalog (with magnitude of completeness Mc=3) from 49 global mainshocks (Ms>6.5, depth<100km, estimated dynamic stress>1kPa). We calculate β value for each 1° by 1° bins in 30 days before and 10 days after the mainshock. To identify regions that experience triggering from a distant mainshock, we generate a stacked map using β≥2 - which represents significant seismicity rate increase. As expected, the geothermal and volcanic fields in California show clear response to distant earthquakes. We also note areas in Oklahoma and north Texas show enhanced triggering, where wastewater-injection induced seismicity are occurring. Next we focus on Oklahoma and use a local catalog from Oklahoma Geological Survey with lower completeness threshold Mc to calculate the beta map in 0.2° by 0.2° bins for each selected mainshock to obtain finer spatial resolutions of the triggering behavior. For those grids with β larger than 2.0, we use waveforms from nearby stations to search for triggered events. The April 2015 M7.8 Nepal earthquake causes a statistically significant increase of local seismicity (β=3.5) in the Woodward area (west Oklahoma) during an on-going earthquake sequence. By visually examining the surface wave from the nearest station, we identify 3 larger local events, and 10 additional smaller events with weaker but discernable amplitude. Preliminary analysis shows that the triggering is related to Rayleigh wave, which would cause dilatational or shear stress changes along the strike direction of Woodward fault, given the azimuth between Nepal and Oklahoma. Our next step is to apply matched-filter technique to generate a complete catalog for an extended period of time, in order to better understand dynamic triggering and spatio-temporal evolution of this sequence - one of the largest sequences in western Oklahoma.

Direct Comparison of Respiration-Correlated Four-Dimensional Magnetic Resonance Imaging Reconstructed Using Concurrent Internal Navigator and External Bellows.

PubMed

Li, Guang; Wei, Jie; Olek, Devin; Kadbi, Mo; Tyagi, Neelam; Zakian, Kristen; Mechalakos, James; Deasy, Joseph O; Hunt, Margie

2017-03-01

To compare the image quality of amplitude-binned 4-dimensional magnetic resonance imaging (4DMRI) reconstructed using 2 concurrent respiratory (navigator and bellows) waveforms. A prospective, respiratory-correlated 4DMRI scanning program was used to acquire T2-weighted single-breath 4DMRI images with internal navigator and external bellows. After a 10-second training waveform of a surrogate signal, 2-dimensional MRI acquisition was triggered at a level (bin) and anatomic location (slice) until the bin-slice table was completed for 4DMRI reconstruction. The bellows signal was always collected, even when the navigator trigger was used, to retrospectively reconstruct a bellows-rebinned 4DMRI. Ten volunteers participated in this institutional review board-approved 4DMRI study. Four scans were acquired for each subject, including coronal and sagittal scans triggered by either navigator or bellows, and 6 4DMRI images (navigator-triggered, bellows-rebinned, and bellows-triggered) were reconstructed. The simultaneously acquired waveforms and resulting 4DMRI quality were compared using signal correlation, bin/phase shift, and binning motion artifacts. The consecutive bellows-triggered 4DMRI scan was used for indirect comparison. Correlation coefficients between the navigator and bellows signals were found to be patient-specific and inhalation-/exhalation-dependent, ranging from 0.1 to 0.9 because of breathing irregularities (>50% scans) and commonly observed bin/phase shifts (-1.1 ± 0.6 bin) in both 1-dimensional waveforms and diaphragm motion extracted from 4D images. Navigator-triggered 4DMRI contained many fewer binning motion artifacts at the diaphragm than did the bellows-rebinned and bellows-triggered 4DMRI scans. Coronal scans were faster than sagittal scans because of the fewer slices and higher achievable acceleration factors. Navigator-triggered 4DMRI contains substantially fewer binning motion artifacts than bellows-rebinned and bellows-triggered 4DMRI, primarily owing to the deviation of the external from the internal surrogate. The present study compared 2 concurrent surrogates during the same 4DMRI scan and their resulting 4DMRI quality. The navigator-triggered 4DMRI scanning protocol should be preferred to the bellows-based, especially for coronal scans, for clinical respiratory motion simulation. Copyright © 2016 Elsevier Inc. All rights reserved.