Early event related fields during visually evoked pain anticipation.

PubMed

Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

2016-03-01

Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Automatic event detection in low SNR microseismic signals based on multi-scale permutation entropy and a support vector machine

NASA Astrophysics Data System (ADS)

Jia, Rui-Sheng; Sun, Hong-Mei; Peng, Yan-Jun; Liang, Yong-Quan; Lu, Xin-Ming

2017-07-01

Microseismic monitoring is an effective means for providing early warning of rock or coal dynamical disasters, and its first step is microseismic event detection, although low SNR microseismic signals often cannot effectively be detected by routine methods. To solve this problem, this paper presents permutation entropy and a support vector machine to detect low SNR microseismic events. First, an extraction method of signal features based on multi-scale permutation entropy is proposed by studying the influence of the scale factor on the signal permutation entropy. Second, the detection model of low SNR microseismic events based on the least squares support vector machine is built by performing a multi-scale permutation entropy calculation for the collected vibration signals, constructing a feature vector set of signals. Finally, a comparative analysis of the microseismic events and noise signals in the experiment proves that the different characteristics of the two can be fully expressed by using multi-scale permutation entropy. The detection model of microseismic events combined with the support vector machine, which has the features of high classification accuracy and fast real-time algorithms, can meet the requirements of online, real-time extractions of microseismic events.

Signals of New Physics in the Underlying Event

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

Harnik, Roni; /Stanford U., ITP /SLAC; Wizansky, Tommer

2010-06-11

LHC searches for new physics focus on combinations of hard physics objects. In this work we propose a qualitatively different soft signal for new physics at the LHC - the 'anomalous underlying event'. Every hard LHC event will be accompanied by a soft underlying event due to QCD and pile-up effects. Though it is often used for QCD and monte carlo studies, here we propose the incorporation of an underlying event analysis in some searches for new physics. An excess of anomalous underlying events may be a smoking-gun signal for particular new physics scenarios such as 'quirks' or 'hidden valleys'more » in which large amounts of energy may be emitted by a large multiplicity of soft particles. We discuss possible search strategies for such soft diffuse signals in the tracking system and calorimetry of the LHC experiments. We present a detailed study of the calorimetric signal in a concrete example, a simple quirk model motivated by folded supersymmetry. In these models the production and radiative decay of highly excited quirk bound states leads to an 'antenna pattern' of soft unclustered energy. Using a dedicated simulation of a toy detector and a 'CMB-like' multipole analysis we compare the signal to the expected backgrounds.« less

Characteristics of long recovery early VLF events observed by the North African AWESOME Network

NASA Astrophysics Data System (ADS)

Naitamor, S.; Cohen, M. B.; Cotts, B. R. T.; Ghalila, H.; Alabdoadaim, M. A.; Graf, K.

2013-08-01

Lightning strokes are capable of initiating disturbances in the lower ionosphere, whose recoveries persist for many minutes. These events are remotely sensed via monitoring subionospherically propagating very low frequency (VLF) transmitter signals, which are perturbed as they pass through the region above the lightning stroke. In this paper we describe the properties and characteristics of the early VLF signal perturbations, which exhibit long recovery times using subionospheric VLF transmitter data from three identical receivers located at Algiers (Algeria), Tunis (Tunisia), and Sebha (Libya). The results indicate that the observation of long recovery events depends strongly on the modal structure of the signal electromagnetic field and the distance from the disturbed region and the receiver or transmitter locations. Comparison of simultaneously collected data at the three sites indicates that the role of the causative lightning stroke properties (e.g., peak current and polarity), or that of transient luminous events may be much less important. The dominant parameter which determines the duration of the recovery time and amplitude appears to be the modal structure of the subionospheric VLF probe signal at the ionospheric disturbance, where scattering occurs, and the subsequent modal structure that propagates to the receiver location.

Event Compression Using Recursive Least Squares Signal Processing.

DTIC Science & Technology

1980-07-01

decimation of the Burstl signal with and without all-pole prefiltering to reduce aliasing . Figures 3.32a-c and 3.33a-c show the same examples but with 4/1...to reduce aliasing , w~t found that it did not improve the quality of the event compressed signals . If filtering must be performed, all-pole filtering...A-AO89 785 MASSACHUSETTS IN T OF TECH CAMBRIDGE RESEARCH LAB OF--ETC F/B 17/9 EVENT COMPRESSION USING RECURSIVE LEAST SQUARES SIGNAL PROCESSI-ETC(t

Prescription-event monitoring: developments in signal detection.

PubMed

Ferreira, Germano

2007-01-01

Prescription-event monitoring (PEM) is a non-interventional intensive method for post-marketing drug safety monitoring of newly licensed medicines. PEM studies are cohort studies where exposure is obtained from a centralised service and outcomes from simple questionnaires completed by general practitioners. Follow-up forms are sent for selected events. Because PEM captures all events and not only the suspected adverse drug reactions, PEM cohorts potentially differ in respect to the distribution of number of events per person depending on the nature of the drug under study. This variance can be related either with the condition for which the drug is prescribed (e.g. a condition causing high morbidity will have, in average, a higher number of events per person compared with a condition with lower morbidity) or with the drug effect itself. This paper describes an exploratory investigation of the distortion caused by product-related variations of the number of events to the interpretation of the proportional reporting ratio (PRR) values ("the higher the PRR, the greater the strength of the signal") computed using drug-cohort data. We studied this effect by assessing the agreement between the PRR based on events (event of interest vs all other events) and PRR based on cases (cases with the event of interest vs cases with any other events). PRR were calculated for all combinations reported to ten selected drugs against a comparator of 81 other drugs. Three of the ten drugs had a cohort with an apparent higher proportion of patients with lower number of events. The PRRs based on events were systematically higher than the PRR based on cases for the combinations reported to these three drugs. Additionally, when applying the threshold criteria for signal screening (n > or =3, PRR > or =1.5 and Chi-squared > or =4), the binary agreement was generally high but apparently lower for these three drugs. In conclusion, the distribution of events per patient in drug cohorts shall be

High gain signal averaged electrocardiogram combined with 24 hour monitoring in patients early after myocardial infarction for bedside prediction of arrhythmic events.

PubMed Central

Cripps, T; Bennett, E D; Camm, A J; Ward, D E

1988-01-01

The value of the high gain, signal averaged electrocardiogram combined with 24 hour electrocardiographic monitoring in the prediction of arrhythmic events was assessed in 159 patients in the first week after myocardial infarction. Eleven patients (7%) suffered arrhythmic events during a mean (SD) of 12 (6) months of follow up (range 2-22, median 13 months). The combination of high gain, signal averaged electrocardiography and 24 hour electrocardiographic monitoring was more accurate than either technique alone or than clinical information collected during admission in predicting these events. The combination identified a high risk group of 13 (8%) patients, with an arrhythmic event rate of 62% and a low risk group with an event rate of 2%. The combination of high gain, signal averaged electrocardiography and 24 hour electrocardiographic monitoring in the first week after myocardial infarction provides a rapid, cheap, and non-invasive bedside method for the prediction of arrhythmias. PMID:3179133

Selected control events and reporting odds ratio in signal detection methodology.

PubMed

Ooba, Nobuhiro; Kubota, Kiyoshi

2010-11-01

To know whether the reporting odds ratio (ROR) using "control events" can detect signals hidden behind striking reports on one or more particular events. We used data of 956 drug use investigations (DUIs) conducted between 1970 and 1998 in Japan and domestic spontaneous reports (SRs) between 1998 and 2008. The event terms in DUIs were converted to the preferred terms in Medical Dictionary for Regulatory Activities (MedDRA). We calculated the incidence proportion for various events and selected 20 "control events" with a relatively constant incidence proportion across DUIs and also reported regularly to the spontaneous reporting system. A "signal" was generated for the drug-event combination when the lower limit of 95% confidence interval of the ROR exceeded 1. We also compared the ROR in SRs with the RR in DUIs. The "control events" accounted for 18.2% of all reports. The ROR using "control events" may detect some hidden signals for a drug with the proportion of "control events" lower than the average. The median of the ratios of the ROR using "control events" to RR was around the unity indicating that "control events" roughly represented the exposure distribution though the range of the ratios was so diverse that the individual ROR might not be regarded as the estimate of RR. The use of the ROR with "control events" may give an adjunctive to the traditional signal detection methods to find a signal hidden behind some major events. Copyright © 2010 John Wiley & Sons, Ltd.

Vascular-mediated signalling involved in early phosphate stress response in plants.

PubMed

Zhang, Zhaoliang; Zheng, Yi; Ham, Byung-Kook; Chen, Jieyu; Yoshida, Akiko; Kochian, Leon V; Fei, Zhangjun; Lucas, William J

2016-04-04

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole-plant Pi homeostasis.

Spontaneous adverse event signaling methods: classification and use with health care treatment products.

PubMed

Clark, J A; Klincewicz, S L; Stang, P E

2001-01-01

AE signal detection and its techniques are part of the continuum of public health surveillance, borrowing from both its theory and application (171). Like public health surveillance networks, whose major goals are to identify early signs of new outbreaks, pinpoint new organisms, and monitor designated illnesses, AE signaling and surveillance systems attempt to provide early warnings of previously unsuspected product-AE pairs, hypothesize potential drug-event relations, identify populations "at risk," and facilitate case ascertainment and definition. In both examples, definitive research is often subsequently undertaken to quantify the strength of relations that may be proposed. As with any public health surveillance effort, AE surveillance provides an infrastructure for the ongoing collection of health data and its direct integration into the health regulatory policy (172), including its keystone role in risk assessment and management. However, unlike many surveillance systems, postmarketing AE systems collect case information that is often relatively incomplete and imperfect, estimate exposure based on surrogate values (e.g., sales data), and are used by both governmental and the private sector for preventive planning. These factors make AE signaling and surveillance more ambiguous, regulatory oriented, and complex than its disease counterparts (173). Despite such issues, AE signaling methods continue to evolve in extent, complexity, and acceptance (4, 131, 174). Undoubtedly, this is largely due to the widespread practical experience that has been gained with spontaneous reporting systems over the past 4 decades and the cumulative usefulness that has been demonstrated.

Response of adult mouse uterus to early disruption of estrogen receptor-alpha signaling is influenced by Krüppel-like factor 9

USDA-ARS?s Scientific Manuscript database

Inappropriate early exposure of the hormone-responsive uterus to estrogenic compounds is associated with increased risk for adult reproductive diseases including endometrial cancers. While the dysregulation of estrogen receptor-alpha (ESR1) signaling is a well-acknowledged early event in tumor initi...

Ca2+ signaling and early embryonic patterning during the blastula and gastrula periods of zebrafish and Xenopus development.

PubMed

Webb, Sarah E; Miller, Andrew L

2006-11-01

It has been proposed that Ca(2+) signaling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern forming events during early vertebrate development [L.F. Jaffe, Organization of early development by calcium patterns, BioEssays 21 (1999) 657-667; M.J. Berridge, P. Lipp, M.D. Bootman, The versatility and universality of calcium signaling, Nat. Rev. Mol. Cell Biol. 1 (2000) 11-21; S.E. Webb, A.L. Miller, Calcium signalling during embryonic development, Nat. Rev. Mol. Cell Biol. 4 (2003) 539-551]. With reference to the embryos of zebrafish (Danio rerio) and the frog, Xenopus laevis, we review the Ca(2+) signals reported during the Blastula and Gastrula Periods. This developmental window encompasses the major pattern forming events of epiboly, involution, and convergent extension, which result in the establishment of the basic germ layers and body axes [C.B. Kimmel, W.W. Ballard, S.R. Kimmel, B. Ullmann, T.F. Schilling, Stages of embryonic development of the zebrafish, Dev. Dyn. 203 (1995) 253-310]. Data will be presented to support the suggestion that propagating waves (both long and short range) of Ca(2+) release, followed by sequestration, may play a crucial role in: (1) Coordinating cell movements during these pattern forming events and (2) Contributing to the establishment of the basic embryonic axes, as well as (3) Helping to define the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen [E. Gilland, A.L. Miller, E. Karplus, R. Baker, S.E. Webb, Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation, Proc. Natl. Acad. Sci. USA 96 (1999) 157-161; J.B. Wallingford, A.J. Ewald, R.M. Harland, S.E. Fraser, Calcium signaling during convergent extension in Xenopus, Curr. Biol. 11 (2001) 652-661]. The various potential targets of these Ca(2+) transients will also be discussed, as well as how they might integrate with other known pattern forming

Operational early warning platform for extreme meteorological events

NASA Astrophysics Data System (ADS)

Mühr, Bernhard; Kunz, Michael

2015-04-01

Operational early warning platform for extreme meteorological events Most natural disasters are related to extreme weather events (e.g. typhoons); weather conditions, however, are also highly relevant for humanitarian and disaster relief operations during and after other natural disaster like earthquakes. The internet service "Wettergefahren-Frühwarnung" (WF) provides various information on extreme weather events, especially when these events are associated with a high potential for large damage. The main focus of the platform is on Central Europe, but major events are also monitored worldwide on a daily routine. WF provides high-resolution forecast maps for many weather parameters which allow detailed and reliable predictions about weather conditions during the next days in the affected areas. The WF service became operational in February 2004 and is part of the Center for Disaster Management and Risk Reduction Technology (CEDIM) since 2007. At the end of 2011, CEDIM embarked a new type of interdisciplinary disaster research termed as forensic disaster analysis (FDA) in near real time. In case of an imminent extreme weather event WF plays an important role in CEDIM's FDA group. It provides early and precise information which are always available and updated several times during a day and gives advice and assists with articles and reports on extreme events.

Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells

PubMed Central

2014-01-01

Background Branched-chain amino acids, especially leucine, are known to interact with insulin signaling pathway and glucose metabolism. However, the mechanism by which this is exerted, remain to be clearly defined. In order to examine the effect of leucine on muscle insulin signaling, a set of experiments was carried out to quantitate phosphorylation events along the insulin signaling pathway in human skeletal muscle cell cultures. Cells were exposed to insulin, leucine or both, and phosphorylation events of key insulin signaling molecules were tracked over time so as to monitor time-related responses that characterize the signaling events and could be missed by a single sampling strategy limited to pre/post stimulus events. Results Leucine is shown to increase the magnitude of insulin-dependent phosphorylation of protein kinase B (AKT) at Ser473 and glycogen synthase kinase (GSK3β) at Ser21-9. Glycogen synthesis follows the same pattern of GSK3β, with a significant increase at 100 μM leucine plus insulin stimulus. Moreover, data do not show any statistically significant increase of pGSK3β and glycogen synthesis at higher leucine concentrations. Leucine is also shown to increase the magnitude of insulin-mediated extracellularly regulated kinase (ERK) phosphorylation; however, differently from AKT and GSK3β, ERK shows a transient behavior, with an early peak response, followed by a return to the baseline condition. Conclusions These experiments demonstrate a complementary effect of leucine on insulin signaling in a human skeletal muscle cell culture, promoting insulin-activated GSK3β phosphorylation and glycogen synthesis. PMID:24646332

An Integrated Phosphoproteomics Work Flow Reveals Extensive Network Regulation in Early Lysophosphatidic Acid Signaling*

PubMed Central

Schreiber, Thiemo B.; Mäusbacher, Nina; Kéri, György; Cox, Jürgen; Daub, Henrik

2010-01-01

Lysophosphatidic acid (LPA) induces a variety of cellular signaling pathways through the activation of its cognate G protein-coupled receptors. To investigate early LPA responses and assess the contribution of epidermal growth factor (EGF) receptor transactivation in LPA signaling, we performed phosphoproteomics analyses of both total cell lysate and protein kinase-enriched fractions as complementary strategies to monitor phosphorylation changes in A498 kidney carcinoma cells. Our integrated work flow enabled the identification and quantification of more than 5,300 phosphorylation sites of which 224 were consistently regulated by LPA. In addition to induced phosphorylation events, we also obtained evidence for early dephosphorylation reactions due to rapid phosphatase regulation upon LPA treatment. Phosphorylation changes induced by direct heparin-binding EGF-like growth factor-mediated EGF receptor activation were typically weaker and only detected on a subset of LPA-regulated sites, indicating signal integration among EGF receptor transactivation and other LPA-triggered pathways. Our results reveal rapid phosphoregulation of many proteins not yet implicated in G protein-coupled receptor signaling and point to various additional mechanisms by which LPA might regulate cell survival and migration as well as gene transcription on the molecular level. Moreover, our phosphoproteomics analysis of both total lysate and kinase-enriched fractions provided highly complementary parts of the LPA-regulated signaling network and thus represents a useful and generic strategy toward comprehensive signaling studies on a system-wide level. PMID:20071362

The spatiotemporal order of signaling events unveils the logic of development signaling.

PubMed

Zhu, Hao; Owen, Markus R; Mao, Yanlan

2016-08-01

Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling. The model is available upon request. hao.zhu@ymail.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

The spatiotemporal order of signaling events unveils the logic of development signaling

PubMed Central

Zhu, Hao; Owen, Markus R.; Mao, Yanlan

2016-01-01

Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling. Availability and implementation: The model is available upon request. Contact: hao.zhu@ymail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153573

Early Warning and Early Action during the 2015-16 El Nino Event

NASA Astrophysics Data System (ADS)

Robertson, A. W.; Goddard, L. M.

2016-12-01

Strong El Niño events have a marked impact on regional climate worldwide through their influence on large-scale atmospheric circulation. As a result, seasonal climate forecasts show greater skill during El Niño events, which provide communities, governments and humanitarian agencies greater ability to plan and prepare. The scientific community has advanced considerably in the quality and content of information provided about El Niño and its impacts. As a result, society has become better aware of and engaged with this information. This talk will present some details on how we navigate the fine line between expectations and probabilistic forecasts, and how this information was used during the 2015-16 El Niño event. Examples are drawn from the health sector and food security community. Specific attention will be given to the importance of problem-focus and data availability in the appropriate tailoring of climate information for Early Warning/Early Action.

An Alternative Explanation for "Step-Like" Early VLF Event

NASA Astrophysics Data System (ADS)

Moore, R. C.

2016-12-01

A newly-deployed array of VLF receivers along the East Coast of the United States is ideally suited for detecting VLF scattering from lightning-induced disturbances to the lower ionosphere. The array was deployed in May 2016, and one VLF receiver was deployed only 20 km from the NAA transmitter (24.0 kHz) in Cutler, Maine. The phase of the NAA signal at this closest site varies significantly with time, due simply to the impedance match of the transmitter varying with time. Additionally, both the amplitude and phase exhibit periods of rapid shifts that could possibly explain at least some "step-like" VLF scattering events. Here, we distinguish between "step-like" VLF scattering events and other events in that "step-like" events are typically not closely associated with a detected causative lightning flash and also tend to exhibit little or no recovery to ambient conditions after the event onset. We present an analysis of VLF observations from the East Coast array that demonstrates interesting examples of step-like VLF events far from the transmitter that are associated with step-like events very close to the transmitter. We conclude that step-like VLF events should be treated with caution, unless definitively associated with a causative lightning flash and/or detected using observations of multiple transmitter signals.

Early Warning Signals of Ecological Transitions: Methods for Spatial Patterns

PubMed Central

Brock, William A.; Carpenter, Stephen R.; Ellison, Aaron M.; Livina, Valerie N.; Seekell, David A.; Scheffer, Marten; van Nes, Egbert H.; Dakos, Vasilis

2014-01-01

A number of ecosystems can exhibit abrupt shifts between alternative stable states. Because of their important ecological and economic consequences, recent research has focused on devising early warning signals for anticipating such abrupt ecological transitions. In particular, theoretical studies show that changes in spatial characteristics of the system could provide early warnings of approaching transitions. However, the empirical validation of these indicators lag behind their theoretical developments. Here, we summarize a range of currently available spatial early warning signals, suggest potential null models to interpret their trends, and apply them to three simulated spatial data sets of systems undergoing an abrupt transition. In addition to providing a step-by-step methodology for applying these signals to spatial data sets, we propose a statistical toolbox that may be used to help detect approaching transitions in a wide range of spatial data. We hope that our methodology together with the computer codes will stimulate the application and testing of spatial early warning signals on real spatial data. PMID:24658137

Early warning signals of regime shifts in coupled human–environment systems

PubMed Central

Bauch, Chris T.; Sigdel, Ram; Pharaon, Joe; Anand, Madhur

2016-01-01

In complex systems, a critical transition is a shift in a system’s dynamical regime from its current state to a strongly contrasting state as external conditions move beyond a tipping point. These transitions are often preceded by characteristic early warning signals such as increased system variability. However, early warning signals in complex, coupled human–environment systems (HESs) remain little studied. Here, we compare critical transitions and their early warning signals in a coupled HES model to an equivalent environment model uncoupled from the human system. We parameterize the HES model, using social and ecological data from old-growth forests in Oregon. We find that the coupled HES exhibits a richer variety of dynamics and regime shifts than the uncoupled environment system. Moreover, the early warning signals in the coupled HES can be ambiguous, heralding either an era of ecosystem conservationism or collapse of both forest ecosystems and conservationism. The presence of human feedback in the coupled HES can also mitigate the early warning signal, making it more difficult to detect the oncoming regime shift. We furthermore show how the coupled HES can be “doomed to criticality”: Strategic human interactions cause the system to remain perpetually in the vicinity of a collapse threshold, as humans become complacent when the resource seems protected but respond rapidly when it is under immediate threat. We conclude that the opportunities, benefits, and challenges of modeling regime shifts and early warning signals in coupled HESs merit further research. PMID:27815533

Social anxiety and negative early life events in university students.

PubMed

Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

2012-06-01

There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

PubMed

Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

2017-04-01

Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

Method for early detection of cooling-loss events

DOEpatents

Bermudez, Sergio A.; Hamann, Hendrik; Marianno, Fernando J.

2015-06-30

A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

Method for early detection of cooling-loss events

DOEpatents

Bermudez, Sergio A.; Hamann, Hendrik F.; Marianno, Fernando J.

2015-12-22

A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis1

PubMed Central

Chen, Yanmei; Hoehenwarter, Wolfgang

2015-01-01

Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K+ and Na+ transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. PMID:26471895

EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

EPA Science Inventory

Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

How one might miss early warning signals of critical transitions in time series data: A systematic study of two major currency pairs

PubMed Central

Ciamarra, Massimo Pica; Cheong, Siew Ann

2018-01-01

There is growing interest in the use of critical slowing down and critical fluctuations as early warning signals for critical transitions in different complex systems. However, while some studies found them effective, others found the opposite. In this paper, we investigated why this might be so, by testing three commonly used indicators: lag-1 autocorrelation, variance, and low-frequency power spectrum at anticipating critical transitions in the very-high-frequency time series data of the Australian Dollar-Japanese Yen and Swiss Franc-Japanese Yen exchange rates. Besides testing rising trends in these indicators at a strict level of confidence using the Kendall-tau test, we also required statistically significant early warning signals to be concurrent in the three indicators, which must rise to appreciable values. We then found for our data set the optimum parameters for discovering critical transitions, and showed that the set of critical transitions found is generally insensitive to variations in the parameters. Suspecting that negative results in the literature are the results of low data frequencies, we created time series with time intervals over three orders of magnitude from the raw data, and tested them for early warning signals. Early warning signals can be reliably found only if the time interval of the data is shorter than the time scale of critical transitions in our complex system of interest. Finally, we compared the set of time windows with statistically significant early warning signals with the set of time windows followed by large movements, to conclude that the early warning signals indeed provide reliable information on impending critical transitions. This reliability becomes more compelling statistically the more events we test. PMID:29538373

How one might miss early warning signals of critical transitions in time series data: A systematic study of two major currency pairs.

PubMed

Wen, Haoyu; Ciamarra, Massimo Pica; Cheong, Siew Ann

2018-01-01

There is growing interest in the use of critical slowing down and critical fluctuations as early warning signals for critical transitions in different complex systems. However, while some studies found them effective, others found the opposite. In this paper, we investigated why this might be so, by testing three commonly used indicators: lag-1 autocorrelation, variance, and low-frequency power spectrum at anticipating critical transitions in the very-high-frequency time series data of the Australian Dollar-Japanese Yen and Swiss Franc-Japanese Yen exchange rates. Besides testing rising trends in these indicators at a strict level of confidence using the Kendall-tau test, we also required statistically significant early warning signals to be concurrent in the three indicators, which must rise to appreciable values. We then found for our data set the optimum parameters for discovering critical transitions, and showed that the set of critical transitions found is generally insensitive to variations in the parameters. Suspecting that negative results in the literature are the results of low data frequencies, we created time series with time intervals over three orders of magnitude from the raw data, and tested them for early warning signals. Early warning signals can be reliably found only if the time interval of the data is shorter than the time scale of critical transitions in our complex system of interest. Finally, we compared the set of time windows with statistically significant early warning signals with the set of time windows followed by large movements, to conclude that the early warning signals indeed provide reliable information on impending critical transitions. This reliability becomes more compelling statistically the more events we test.

Regulation of early Xenopus development by ErbB signaling

PubMed Central

Nie, Shuyi; Chang, Chenbei

2008-01-01

ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2 and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements and embryonic patterning during early Xenopus development. PMID:16258939

Ephrin-B reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues.

PubMed

Dravis, Christopher; Henkemeyer, Mark

2011-07-01

We report that the disruption of bidirectional signaling between ephrin-B2 and EphB receptors impairs morphogenetic cell-cell septation and closure events during development of the embryonic midline. A novel role for reverse signaling is identified in tracheoesophageal foregut septation, as animals lacking the cytoplasmic domain of ephrin-B2 present with laryngotracheoesophageal cleft (LTEC), while both EphB2/EphB3 forward signaling and ephrin-B2 reverse signaling are shown to be required for midline fusion of the palate. In a third midline event, EphB2/EphB3 are shown to mediate ventral abdominal wall closure by acting principally as ligands to stimulate ephrin-B reverse signaling. Analysis of new ephrin-B2(6YFΔV) and ephrin-B2(ΔV) mutants that specifically ablate ephrin-B2 tyrosine phosphorylation- and/or PDZ domain-mediated signaling indicates there are at least two distinct phosphorylation-independent components of reverse signaling. These involve both PDZ domain interactions and a non-canonical SH2/PDZ-independent form of reverse signaling that may utilize associations with claudin family tetraspan molecules, as EphB2 and activated ephrin-B2 molecules are specifically co-localized with claudins in epithelia at the point of septation. Finally, the developmental phenotypes described here mirror common human midline birth defects found with the VACTERL association, suggesting a molecular link to bidirectional signaling through B-subclass Ephs and ephrins. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficient method for events detection in phonocardiographic signals

NASA Astrophysics Data System (ADS)

Martinez-Alajarin, Juan; Ruiz-Merino, Ramon

2005-06-01

The auscultation of the heart is still the first basic analysis tool used to evaluate the functional state of the heart, as well as the first indicator used to submit the patient to a cardiologist. In order to improve the diagnosis capabilities of auscultation, signal processing algorithms are currently being developed to assist the physician at primary care centers for adult and pediatric population. A basic task for the diagnosis from the phonocardiogram is to detect the events (main and additional sounds, murmurs and clicks) present in the cardiac cycle. This is usually made by applying a threshold and detecting the events that are bigger than the threshold. However, this method usually does not allow the detection of the main sounds when additional sounds and murmurs exist, or it may join several events into a unique one. In this paper we present a reliable method to detect the events present in the phonocardiogram, even in the presence of heart murmurs or additional sounds. The method detects relative maxima peaks in the amplitude envelope of the phonocardiogram, and computes a set of parameters associated with each event. Finally, a set of characteristics is extracted from each event to aid in the identification of the events. Besides, the morphology of the murmurs is also detected, which aids in the differentiation of different diseases that can occur in the same temporal localization. The algorithms have been applied to real normal heart sounds and murmurs, achieving satisfactory results.

An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull

PubMed Central

McCarthy, Neil; Sidik, Alfire; Bertrand, Julien Y.; Eberhart, Johann K.

2016-01-01

The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure. PMID:27060628

Including trait-based early warning signals helps predict population collapse

PubMed Central

Clements, Christopher F.; Ozgul, Arpat

2016-01-01

Foreseeing population collapse is an on-going target in ecology, and this has led to the development of early warning signals based on expected changes in leading indicators before a bifurcation. Such signals have been sought for in abundance time-series data on a population of interest, with varying degrees of success. Here we move beyond these established methods by including parallel time-series data of abundance and fitness-related trait dynamics. Using data from a microcosm experiment, we show that including information on the dynamics of phenotypic traits such as body size into composite early warning indices can produce more accurate inferences of whether a population is approaching a critical transition than using abundance time-series alone. By including fitness-related trait information alongside traditional abundance-based early warning signals in a single metric of risk, our generalizable approach provides a powerful new way to assess what populations may be on the verge of collapse. PMID:27009968

Signaling events during initiation of arbuscular mycorrhizal symbiosis.

PubMed

Schmitz, Alexa M; Harrison, Maria J

2014-03-01

Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal (AM) fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intracellular association with plant roots where they transfer phosphate and nitrogen to the plant in exchange for carbon. They are obligate fungi, relying on their host as their only carbon source. Much has been discovered in the last decade concerning the signaling events during initiation of the AM symbiosis, including the identification of signaling molecules generated by both partners. This signaling occurs through symbiosis-specific gene products in the host plant, which are indispensable for normal AM development. At the same time, plants have adapted complex mechanisms for avoiding infection by pathogenic fungi, including an innate immune response to general microbial molecules, such as chitin present in fungal cell walls. How it is that AM fungal colonization is maintained without eliciting a defensive response from the host is still uncertain. In this review, we present a summary of the molecular signals and their elicited responses during initiation of the AM symbiosis, including plant immune responses and their suppression. © 2014 Institute of Botany, Chinese Academy of Sciences.

An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull.

PubMed

McCarthy, Neil; Sidik, Alfire; Bertrand, Julien Y; Eberhart, Johann K

2016-07-15

The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Exploring the Potential Routine Use of Electronic Healthcare Record Data to Strengthen Early Signal Assessment in UK Medicines Regulation: Proof-of-Concept Study.

PubMed

Donegan, Katherine; Owen, Rebecca; Bird, Helena; Burch, Brian; Smith, Alex; Tregunno, Phil

2018-05-03

Electronic healthcare record (EHR) databases are used within pharmacoepidemiology studies to confirm or refute safety signals arising from spontaneous adverse event reports. However, there has been limited routine use of such data earlier in the signal management process, to help rapidly contextualise signals and strengthen preliminary assessment or to inform decisions regarding action including the need for further studies. This study explores the value of EHR used in this way within a regulatory environment via an automated analysis platform. Safety signals raised at the UK Medicines and Healthcare products Regulatory Agency (MHRA) between July 2014 and June 2015 were individually reviewed by a multi-disciplinary team. They assessed the feasibility of identifying the exposure and event of interest using primary care data from the Clinical Practice Research Datalink (CPRD) within the Commonwealth Vigilance Workbench (CVW) Longitudinal Module platform, which was designed to facilitate routine descriptive analysis of signals using EHR. Three signals, where exposure and event could be well identified, were retrospectively analysed using the platform. Of 69 unique new signals, 20 were for drugs prescribed predominately in secondary care or available without prescription, which would not be identified in primary care. A further 17 were brand, formulation, or dose-specific issues, were related to mortality, were relevant only to a subgroup of patients, or were drug interactions, and hence could not be reviewed using the platform given its limitations. Analyses of exposure and incidence of the adverse event could be produced using CPRD within the CMV Longitudinal Module for 32 (46%) signals. The case studies demonstrated that the data provided supporting evidence for confirming initial assessment of the signal and deciding upon the need for further action. CPRD can routinely provide useful early insights into clinical context when assessing a large proportion of safety

Potentiation of the early visual response to learned danger signals in adults and adolescents

PubMed Central

Howsley, Philippa; Jordan, Jeff; Johnston, Pat

2015-01-01

The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents. PMID:24652856

Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

PubMed Central

Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

2016-01-01

Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:28239613

Digital Signal Processing for the Event Horizon Telescope

NASA Astrophysics Data System (ADS)

Weintroub, Jonathan

2015-08-01

A broad international collaboration is building the Event Horizon Telescope (EHT). The aim is to test Einstein’s theory of General Relativity in one of the very few places it could break down: the strong gravity regime right at the edge of a black hole. The EHT is an earth-size VLBI array operating at the shortest radio wavelengths, that has achieved unprecedented angular resolution of a few tens of μarcseconds. For nearby super massive black holes (SMBH) this size scale is comparable to the Schwarzschild Radius, and emission in the immediate neighborhood of the event horizon can be directly observed. We give an introduction to the science behind the CASPER-enabled EHT, and outline technical developments, with emphasis on the secret sauce of high speed signal processing.

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database

PubMed Central

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung-eun; Jin, Xue-mei; Lee, Joongyub; Yang, Bo Ram

2017-01-01

Purpose To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). Materials and Methods We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. Results There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. Conclusion We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. PMID:28332362

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

PubMed

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung Eun; Jin, Xue Mei; Lee, Joongyub; Yang, Bo Ram; Park, Byung Joo

2017-05-01

To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. © Copyright: Yonsei University College of Medicine 2017

Slowing down as an early warning signal for abrupt climate change.

PubMed

Dakos, Vasilis; Scheffer, Marten; van Nes, Egbert H; Brovkin, Victor; Petoukhov, Vladimir; Held, Hermann

2008-09-23

In the Earth's history, periods of relatively stable climate have often been interrupted by sharp transitions to a contrasting state. One explanation for such events of abrupt change is that they happened when the earth system reached a critical tipping point. However, this remains hard to prove for events in the remote past, and it is even more difficult to predict if and when we might reach a tipping point for abrupt climate change in the future. Here, we analyze eight ancient abrupt climate shifts and show that they were all preceded by a characteristic slowing down of the fluctuations starting well before the actual shift. Such slowing down, measured as increased autocorrelation, can be mathematically shown to be a hallmark of tipping points. Therefore, our results imply independent empirical evidence for the idea that past abrupt shifts were associated with the passing of critical thresholds. Because the mechanism causing slowing down is fundamentally inherent to tipping points, it follows that our way to detect slowing down might be used as a universal early warning signal for upcoming catastrophic change. Because tipping points in ecosystems and other complex systems are notoriously hard to predict in other ways, this is a promising perspective.

Slowing down as an early warning signal for abrupt climate change

PubMed Central

Dakos, Vasilis; Scheffer, Marten; van Nes, Egbert H.; Brovkin, Victor; Petoukhov, Vladimir; Held, Hermann

2008-01-01

In the Earth's history, periods of relatively stable climate have often been interrupted by sharp transitions to a contrasting state. One explanation for such events of abrupt change is that they happened when the earth system reached a critical tipping point. However, this remains hard to prove for events in the remote past, and it is even more difficult to predict if and when we might reach a tipping point for abrupt climate change in the future. Here, we analyze eight ancient abrupt climate shifts and show that they were all preceded by a characteristic slowing down of the fluctuations starting well before the actual shift. Such slowing down, measured as increased autocorrelation, can be mathematically shown to be a hallmark of tipping points. Therefore, our results imply independent empirical evidence for the idea that past abrupt shifts were associated with the passing of critical thresholds. Because the mechanism causing slowing down is fundamentally inherent to tipping points, it follows that our way to detect slowing down might be used as a universal early warning signal for upcoming catastrophic change. Because tipping points in ecosystems and other complex systems are notoriously hard to predict in other ways, this is a promising perspective. PMID:18787119

Body size shifts and early warning signals precede the historic collapse of whale stocks.

PubMed

Clements, Christopher F; Blanchard, Julia L; Nash, Kirsty L; Hindell, Mark A; Ozgul, Arpat

2017-06-22

Predicting population declines is a key challenge in the face of global environmental change. Abundance-based early warning signals have been shown to precede population collapses; however, such signals are sensitive to the low reliability of abundance estimates. Here, using historical data on whales harvested during the 20th century, we demonstrate that early warning signals can be present not only in the abundance data, but also in the more reliable body size data of wild populations. We show that during the period of commercial whaling, the mean body size of caught whales declined dramatically (by up to 4 m over a 70-year period), leading to early warning signals being detectable up to 40 years before the global collapse of whale stocks. Combining abundance and body size data can reduce the length of the time series required to predict collapse, and decrease the chances of false positive early warning signals.

Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

NASA Astrophysics Data System (ADS)

Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

2017-03-01

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.

Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

PubMed Central

Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

2017-01-01

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent. PMID:28272488

Activity Dependent Signal Transduction in Skeletal Muscle

NASA Technical Reports Server (NTRS)

Hamilton, Susan L.

1999-01-01

The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.

PubMed

Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L; King, Lucy S; Thompson, Paul M; Gotlib, Ian H

2018-05-21

Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

A signal detection method for temporal variation of adverse effect with vaccine adverse event reporting system data.

PubMed

Cai, Yi; Du, Jingcheng; Huang, Jing; Ellenberg, Susan S; Hennessy, Sean; Tao, Cui; Chen, Yong

2017-07-05

To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex relationships between medications and adverse events. Since the late 1990s, efforts have been made to develop data mining tools to systematically and automatically search for safety signals in surveillance databases. Influenza vaccines present special challenges to safety surveillance because the vaccine changes every year in response to the influenza strains predicted to be prevalent that year. Therefore, it may be expected that reporting rates of adverse events following flu vaccines (number of reports for a specific vaccine-event combination/number of reports for all vaccine-event combinations) may vary substantially across reporting years. Current surveillance methods seldom consider these variations in signal detection, and reports from different years are typically collapsed together to conduct safety analyses. However, merging reports from different years ignores the potential heterogeneity of reporting rates across years and may miss important safety signals. Reports of adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse Event Reporting System (VAERS) database and formatted into a three-dimensional data array with types of vaccine, groups of adverse events and reporting time as the three dimensions. We propose a random effects model to test the heterogeneity of reporting rates for a given vaccine-event combination across reporting years. The proposed method provides a rigorous statistical procedure to detect differences of reporting rates among years. We also introduce a new visualization tool to summarize the result of the proposed method when applied to multiple vaccine-adverse event combinations. We applied the proposed method to detect safety signals of FLU3, an influenza vaccine containing three flu strains, in the VAERS database. We showed that it had high

Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA.

PubMed

Banerjee, Aditi; Basu, Malini; Blanchard, Thomas G; Chintalacharuvu, Subba R; Guang, Wei; Lillehoj, Erik P; Czinn, Steven J

2016-10-01

Murine models of Helicobacter pylori infection are used to study host-pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. The lysates of cells infected with H. pylori isolates or an isogenic cagA-deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. © 2016 John Wiley & Sons Ltd.

Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

PubMed

Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

2014-10-13

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

Ginkgo biloba Responds to Herbivory by Activating Early Signaling and Direct Defenses

PubMed Central

Atsbaha Zebelo, Simon; Foti, Maria; Fliegmann, Judith; Bossi, Simone; Maffei, Massimo E.; Bertea, Cinzia M.

2012-01-01

Background Ginkgo biloba (Ginkgoaceae) is one of the most ancient living seed plants and is regarded as a living fossil. G. biloba has a broad spectrum of resistance or tolerance to many pathogens and herbivores because of the presence of toxic leaf compounds. Little is known about early and late events occurring in G. biloba upon herbivory. The aim of this study was to assess whether herbivory by the generalist Spodoptera littoralis was able to induce early signaling and direct defense in G. biloba by evaluating early and late responses. Methodology/Principal Findings Early and late responses in mechanically wounded leaves and in leaves damaged by S. littoralis included plasma transmembrane potential (Vm) variations, time-course changes in both cytosolic calcium concentration ([Ca2+]cyt) and H2O2 production, the regulation of genes correlated to terpenoid and flavonoid biosynthesis, the induction of direct defense compounds, and the release of volatile organic compounds (VOCs). The results show that G. biloba responded to hebivory with a significant Vm depolarization which was associated to significant increases in both [Ca2+]cyt and H2O2. Several defense genes were regulated by herbivory, including those coding for ROS scavenging enzymes and the synthesis of terpenoids and flavonoids. Metabolomic analyses revealed the herbivore-induced production of several flavonoids and VOCs. Surprisingly, no significant induction by herbivory was found for two of the most characteristic G. biloba classes of bioactive compounds; ginkgolides and bilobalides. Conclusions/Significance By studying early and late responses of G. biloba to herbivory, we provided the first evidence that this “living fossil” plant responds to herbivory with the same defense mechanisms adopted by the most recent angiosperms. PMID:22448229

The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

PubMed

Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

2016-04-05

Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

A Risk Assessment System with Automatic Extraction of Event Types

NASA Astrophysics Data System (ADS)

Capet, Philippe; Delavallade, Thomas; Nakamura, Takuya; Sandor, Agnes; Tarsitano, Cedric; Voyatzi, Stavroula

In this article we describe the joint effort of experts in linguistics, information extraction and risk assessment to integrate EventSpotter, an automatic event extraction engine, into ADAC, an automated early warning system. By detecting as early as possible weak signals of emerging risks ADAC provides a dynamic synthetic picture of situations involving risk. The ADAC system calculates risk on the basis of fuzzy logic rules operated on a template graph whose leaves are event types. EventSpotter is based on a general purpose natural language dependency parser, XIP, enhanced with domain-specific lexical resources (Lexicon-Grammar). Its role is to automatically feed the leaves with input data.

The non-canonical BMP and Wnt/β-catenin signaling pathways orchestrate early tooth development

PubMed Central

Yuan, Guohua; Yang, Guobin; Zheng, Yuqian; Zhu, Xiaojing; Chen, Zhi; Zhang, Zunyi; Chen, YiPing

2015-01-01

BMP and Wnt signaling pathways play a crucial role in organogenesis, including tooth development. Despite extensive studies, the exact functions, as well as if and how these two pathways act coordinately in regulating early tooth development, remain elusive. In this study, we dissected regulatory functions of BMP and Wnt pathways in early tooth development using a transgenic noggin (Nog) overexpression model (K14Cre;pNog). It exhibits early arrested tooth development, accompanied by reduced cell proliferation and loss of odontogenic fate marker Pitx2 expression in the dental epithelium. We demonstrated that overexpression of Nog disrupted BMP non-canonical activity, which led to a dramatic reduction of cell proliferation rate but did not affect Pitx2 expression. We further identified a novel function of Nog by inhibiting Wnt/β-catenin signaling, causing loss of Pitx2 expression. Co-immunoprecipitation and TOPflash assays revealed direct binding of Nog to Wnts to functionally prevent Wnt/β-catenin signaling. In situ PLA and immunohistochemistry on Nog mutants confirmed in vivo interaction between endogenous Nog and Wnts and modulation of Wnt signaling by Nog in tooth germs. Genetic rescue experiments presented evidence that both BMP and Wnt signaling pathways contribute to cell proliferation regulation in the dental epithelium, with Wnt signaling also controlling the odontogenic fate. Reactivation of both BMP and Wnt signaling pathways, but not of only one of them, rescued tooth developmental defects in K14Cre;pNog mice, in which Wnt signaling can be substituted by transgenic activation of Pitx2. Our results reveal the orchestration of non-canonical BMP and Wnt/β-catenin signaling pathways in the regulation of early tooth development. PMID:25428587

Joint Maximum Likelihood Time Delay Estimation of Unknown Event-Related Potential Signals for EEG Sensor Signal Quality Enhancement

PubMed Central

Kim, Kyungsoo; Lim, Sung-Ho; Lee, Jaeseok; Kang, Won-Seok; Moon, Cheil; Choi, Ji-Woong

2016-01-01

Electroencephalograms (EEGs) measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI) studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR) is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP) signal that represents a brain’s response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE) schemes based on a joint maximum likelihood (ML) criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°. PMID:27322267

Analysis of low-frequency seismic signals generated during a multiple-iceberg calving event at Jakobshavn Isbræ, Greenland

USGS Publications Warehouse

Walter, Fabian; Amundson, Jason M.; O'Neel, Shad; Truffer, Martin; Fahnestock, Mark; Fricker, Helen A.

2012-01-01

We investigated seismic signals generated during a large-scale, multiple iceberg calving event that occurred at Jakobshavn Isbræ, Greenland, on 21 August 2009. The event was recorded by a high-rate time-lapse camera and five broadband seismic stations located within a few hundred kilometers of the terminus. During the event two full-glacier-thickness icebergs calved from the grounded (or nearly grounded) terminus and immediately capsized; the second iceberg to calve was two to three times smaller than the first. The individual calving and capsize events were well-correlated with the radiation of low-frequency seismic signals (<0.1 Hz) dominated by Love and Rayleigh waves. In agreement with regional records from previously published ‘glacial earthquakes’, these low-frequency seismic signals had maximum power and/or signal-to-noise ratios in the 0.05–0.1 Hz band. Similarly, full waveform inversions indicate that these signals were also generated by horizontal single forces acting at the glacier terminus. The signals therefore appear to be local manifestations of glacial earthquakes, although the magnitudes of the signals (twice-time integrated force histories) were considerably smaller than previously reported glacial earthquakes. We thus speculate that such earthquakes may be a common, if not pervasive, feature of all full-glacier-thickness calving events from grounded termini. Finally, a key result from our study is that waveform inversions performed on low-frequency, calving-generated seismic signals may have only limited ability to quantitatively estimate mass losses from calving. In particular, the choice of source time function has little impact on the inversion but dramatically changes the earthquake magnitude. Accordingly, in our analysis, it is unclear whether the smaller or larger of the two calving icebergs generated a larger seismic signal.

Performance of Earthquake Early Warning Systems during the Major Events of the 2016-2017 Central Italy Seismic Sequence.

NASA Astrophysics Data System (ADS)

Festa, G.; Picozzi, M.; Alessandro, C.; Colombelli, S.; Cattaneo, M.; Chiaraluce, L.; Elia, L.; Martino, C.; Marzorati, S.; Supino, M.; Zollo, A.

2017-12-01

Earthquake early warning systems (EEWS) are systems nowadays contributing to the seismic risk mitigation actions, both in terms of losses and societal resilience, by issuing an alert promptly after the earthquake origin and before the ground shaking impacts the targets to be protected. EEWS systems can be grouped in two main classes: network based and stand-alone systems. Network based EEWS make use of dense seismic networks surrounding the fault (e.g. Near Fault Observatory; NFO) generating the event. The rapid processing of the P-wave early portion allows for the location and magnitude estimation of the event then used to predict the shaking through ground motion prediction equations. Stand-alone systems instead analyze the early P-wave signal to predict the ground shaking carried by the late S or surface waves, through empirically calibrated scaling relationships, at the recording site itself. We compared the network-based (PRESTo, PRobabilistic and Evolutionary early warning SysTem, www.prestoews.org, Satriano et al., 2011) and the stand-alone (SAVE, on-Site-Alert-leVEl, Caruso et al., 2017) systems, by analyzing their performance during the 2016-2017 Central Italy sequence. We analyzed 9 earthquakes having magnitude 5.0 < M < 6.5 at about 200 stations located within 200 km from the epicentral area, including stations of The Altotiberina NFO (TABOO). Performances are evaluated in terms of rate of success of ground shaking intensity prediction and available lead-time, i.e. the time available for security actions. PRESTo also evaluated the accuracy of location and magnitude. Both systems well predict the ground shaking nearby the event source, with a success rate around 90% within the potential damage zone. The lead-time is significantly larger for the network based system, increasing to more than 10s at 40 km from the event epicentre. The stand-alone system better performs in the near-source region showing a positive albeit small lead-time (<3s). Far away from

DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

PubMed Central

BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

2017-01-01

The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

Differences In Early T-Cell Signaling In Cultures Grown In a Rotating Clinostat vs. Static Controls

NASA Technical Reports Server (NTRS)

Alexamder. M.; Nelman-Gonzales, M.; Penkala, J.; Sams, C.

1999-01-01

Altered gravity has previously been demonstrated to be a stress that can influence components of the immune system. Specifically, T-cell activation has been shown to be affected by changes in gravity, exhibiting a decrease in proliferative response to in vitro stimulation in microgravity. Subsequent ground based studies utilizing a rotating clinostat to model some of the effects of microgravity have been consistent with earlier flight based experiments. These ground and flight experiments have examined T-cell activation by measuring various responses including production of cytokines, DNA synthesis and the production of various cell surface activation markers. These indicators of T-cell activation were measured anywhere from 4 to 72 hours after stimulation. Prior to the work described here, the initial signaling events in T-cell activation had not been directly examined. The goal of this project was to determine how the process of early signal transduction was affected by growth in a rotating clinostat. Here we directly show a defect in signaling from TCR to MAPK in purified peripheral T-cells activated in the clinostat by OKT3/antiCD28 coated microbeads as compared to static controls.

Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy.

PubMed

Blom, Jan J; Giove, Thomas J; Favazza, Tara L; Akula, James D; Eldred, William D

2011-06-01

The nitric oxide (NO) signaling pathway is integrally involved in visual processing and changes in the NO pathway are measurable in eyes of diabetic patients. The small peptide adrenomedullin (ADM) can activate a signaling pathway to increase the enzyme activity of neuronal nitric oxide synthase (nNOS). ADM levels are elevated in eyes of diabetic patients and therefore, ADM may play a role in the pathology of diabetic retinopathy. The goal of this research was to test the effects of inhibiting the ADM/NO signaling pathway in early diabetic retinopathy. Inhibition of this pathway decreased NO production in high-glucose retinal cultures. Treating diabetic mice with the PKC β inhibitor ruboxistaurin for 5 weeks lowered ADM mRNA levels and ADM-like immunoreactivity and preserved retinal function as assessed by electroretinography. The results of this study indicate that inhibiting the ADM/NO signaling pathway prevents neuronal pathology and functional losses in early diabetic retinopathy.

Coping with Trial-to-Trial Variability of Event Related Signals: A Bayesian Inference Approach

NASA Technical Reports Server (NTRS)

Ding, Mingzhou; Chen, Youghong; Knuth, Kevin H.; Bressler, Steven L.; Schroeder, Charles E.

2005-01-01

In electro-neurophysiology, single-trial brain responses to a sensory stimulus or a motor act are commonly assumed to result from the linear superposition of a stereotypic event-related signal (e.g. the event-related potential or ERP) that is invariant across trials and some ongoing brain activity often referred to as noise. To extract the signal, one performs an ensemble average of the brain responses over many identical trials to attenuate the noise. To date, h s simple signal-plus-noise (SPN) model has been the dominant approach in cognitive neuroscience. Mounting empirical evidence has shown that the assumptions underlying this model may be overly simplistic. More realistic models have been proposed that account for the trial-to-trial variability of the event-related signal as well as the possibility of multiple differentially varying components within a given ERP waveform. The variable-signal-plus-noise (VSPN) model, which has been demonstrated to provide the foundation for separation and characterization of multiple differentially varying components, has the potential to provide a rich source of information for questions related to neural functions that complement the SPN model. Thus, being able to estimate the amplitude and latency of each ERP component on a trial-by-trial basis provides a critical link between the perceived benefits of the VSPN model and its many concrete applications. In this paper we describe a Bayesian approach to deal with this issue and the resulting strategy is referred to as the differentially Variable Component Analysis (dVCA). We compare the performance of dVCA on simulated data with Independent Component Analysis (ICA) and analyze neurobiological recordings from monkeys performing cognitive tasks.

DETECT: A MATLAB Toolbox for Event Detection and Identification in Time Series, with Applications to Artifact Detection in EEG Signals

DTIC Science & Technology

2013-04-24

DETECT: A MATLAB Toolbox for Event Detection and Identification in Time Series, with Applications to Artifact Detection in EEG Signals Vernon...datasets in the context of events, which are intervals of time where the properties of the signal change relative to a baseline signal . We have developed...As an illustration, we discuss application of the DETECT toolbox for detecting signal artifacts found in continuous multi-channel EEG recordings and

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

PubMed

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-06-07

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

PubMed Central

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-01-01

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

Persistence of carbon release events through the peak of early Eocene global warmth

NASA Astrophysics Data System (ADS)

Kirtland Turner, Sandra; Sexton, Philip F.; Charles, Christopher D.; Norris, Richard D.

2014-10-01

The Early Eocene Climatic Optimum (53-50 million years ago) was preceded by approximately six million years of progressive global warming. This warming was punctuated by a series of rapid hyperthermal warming events triggered by the release of greenhouse gases. Over these six million years, the carbon isotope record suggests that the events became more frequent but smaller in magnitude. This pattern has been suggested to reflect a thermodynamic threshold for carbon release that was more easily crossed as global temperature rose, combined with a decrease in the size of carbon reservoirs during extremely warm conditions. Here we present a continuous, 4.25-million-year-long record of the stable isotope composition of carbonate sediments from the equatorial Atlantic, spanning the peak of early Eocene global warmth. A composite of this and pre-existing records shows that the carbon isotope excursions that identify the hyperthermals exhibit continuity in magnitude and frequency throughout the approximately 10-million-year period covering the onset, peak and termination of the Early Eocene Climate Optimum. We suggest that the carbon cycle processes behind these events, excluding the largest event, the Palaeocene-Eocene Thermal Maximum (about 56 million years ago), were not exceptional. Instead, we argue that the hyperthermals may reflect orbital forcing of the carbon cycle analogous to the mechanisms proposed to operate in the cooler Oligocene and Miocene.

Early multisensory interactions affect the competition among multiple visual objects.

PubMed

Van der Burg, Erik; Talsma, Durk; Olivers, Christian N L; Hickey, Clayton; Theeuwes, Jan

2011-04-01

In dynamic cluttered environments, audition and vision may benefit from each other in determining what deserves further attention and what does not. We investigated the underlying neural mechanisms responsible for attentional guidance by audiovisual stimuli in such an environment. Event-related potentials (ERPs) were measured during visual search through dynamic displays consisting of line elements that randomly changed orientation. Search accuracy improved when a target orientation change was synchronized with an auditory signal as compared to when the auditory signal was absent or synchronized with a distractor orientation change. The ERP data show that behavioral benefits were related to an early multisensory interaction over left parieto-occipital cortex (50-60 ms post-stimulus onset), which was followed by an early positive modulation (80-100 ms) over occipital and temporal areas contralateral to the audiovisual event, an enhanced N2pc (210-250 ms), and a contralateral negative slow wave (CNSW). The early multisensory interaction was correlated with behavioral search benefits, indicating that participants with a strong multisensory interaction benefited the most from the synchronized auditory signal. We suggest that an auditory signal enhances the neural response to a synchronized visual event, which increases the chances of selection in a multiple object environment. Copyright © 2010 Elsevier Inc. All rights reserved.

Continuous event monitoring via a Bayesian predictive approach.

PubMed

Di, Jianing; Wang, Daniel; Brashear, H Robert; Dragalin, Vladimir; Krams, Michael

2016-01-01

In clinical trials, continuous monitoring of event incidence rate plays a critical role in making timely decisions affecting trial outcome. For example, continuous monitoring of adverse events protects the safety of trial participants, while continuous monitoring of efficacy events helps identify early signals of efficacy or futility. Because the endpoint of interest is often the event incidence associated with a given length of treatment duration (e.g., incidence proportion of an adverse event with 2 years of dosing), assessing the event proportion before reaching the intended treatment duration becomes challenging, especially when the event onset profile evolves over time with accumulated exposure. In particular, in the earlier part of the study, ignoring censored subjects may result in significant bias in estimating the cumulative event incidence rate. Such a problem is addressed using a predictive approach in the Bayesian framework. In the proposed approach, experts' prior knowledge about both the frequency and timing of the event occurrence is combined with observed data. More specifically, during any interim look, each event-free subject will be counted with a probability that is derived using prior knowledge. The proposed approach is particularly useful in early stage studies for signal detection based on limited information. But it can also be used as a tool for safety monitoring (e.g., data monitoring committee) during later stage trials. Application of the approach is illustrated using a case study where the incidence rate of an adverse event is continuously monitored during an Alzheimer's disease clinical trial. The performance of the proposed approach is also assessed and compared with other Bayesian and frequentist methods via simulation. Copyright © 2015 John Wiley & Sons, Ltd.

Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

EPA Science Inventory

Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

Distribution and Variability of Satellite-Derived Signals of Isolated Convection Initiation Events Over Central Eastern China

NASA Astrophysics Data System (ADS)

Huang, Yipeng; Meng, Zhiyong; Li, Jing; Li, Wanbiao; Bai, Lanqiang; Zhang, Murong; Wang, Xi

2017-11-01

This study combined measurements from the Chinese operational geostationary satellite Fengyun-2E (FY-2E) and ground-based weather radars to conduct a statistical survey of isolated convection initiation (CI) over central eastern China (CEC). The convective environment in CEC is modulated by the complex topography and monsoon climate. From May to August 2010, a total of 1,630 isolated CI signals were derived from FY-2E using a semiautomated method. The formation of these satellite-derived CI signals peaks in the early afternoon and occurs with high frequency in areas with remarkable terrain inhomogeneity (e.g., mountain, water, and mountain-water areas). The high signal frequency areas shift from northwest CEC (dry, high altitude) in early summer to southeast CEC (humid, low altitude) in midsummer along with an increasing monthly mean frequency. The satellite-derived CI signals tend to have longer lead times (the time difference between satellite-derived signal formation and radar-based CI) in the late morning and afternoon than in the early morning and night. During the early morning and night, the distinction between cloud top signatures and background terrestrial radiation becomes less apparent, resulting in delayed identification of the signals and thus short and even negative lead times. A decline in the lead time is observed from May to August, likely due to the increasing cloud growth rate and warm-rain processes. Results show increasing lead times with increasing landscape elevation, likely due to more warm-rain processes over the coastal sea and plain, along with a decreasing cloud growth rate from hill and mountain to the plateau.

Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

PubMed

Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

2018-06-16

To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P < 0.01), with fewer ophthalmic vascular events (early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P < 0.01), including peripheral retinal nonperfusion (5% vs. 2% per eye, P = 0.50), vitreous hemorrhage (9% vs. 2%, P = 0.20), subretinal hemorrhage (0% vs. 2%, P = 0.99), branch retinal vein occlusion (5% vs. 0%, P = 0.29), choroidal ischemia (14% vs. 4%, P = 0.14), and ophthalmic artery spasm/occlusion (27% vs. 0%, P < 0.01). Events did not correlate to patient age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era

Seismology-based early identification of dam-formation landquake events.

PubMed

Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

2016-01-12

Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

Using Pattern Recognition and Discriminance Analysis to Predict Critical Events in Large Signal Databases

NASA Astrophysics Data System (ADS)

Feller, Jens; Feller, Sebastian; Mauersberg, Bernhard; Mergenthaler, Wolfgang

2009-09-01

Many applications in plant management require close monitoring of equipment performance, in particular with the objective to prevent certain critical events. At each point in time, the information available to classify the criticality of the process, is represented through the historic signal database as well as the actual measurement. This paper presents an approach to detect and predict critical events, based on pattern recognition and discriminance analysis.

Flavivirus Infection Impairs Peroxisome Biogenesis and Early Antiviral Signaling

PubMed Central

You, Jaehwan; Hou, Shangmei; Malik-Soni, Natasha; Xu, Zaikun; Kumar, Anil; Rachubinski, Richard A.; Frappier, Lori

2015-01-01

ABSTRACT Flaviviruses are significant human pathogens that have an enormous impact on the global health burden. Currently, there are very few vaccines against or therapeutic treatments for flaviviruses, and our understanding of how these viruses cause disease is limited. Evidence suggests that the capsid proteins of flaviviruses play critical nonstructural roles during infection, and therefore, elucidating how these viral proteins affect cellular signaling pathways could lead to novel targets for antiviral therapy. We used affinity purification to identify host cell proteins that interact with the capsid proteins of West Nile and dengue viruses. One of the cellular proteins that formed a stable complex with flavivirus capsid proteins is the peroxisome biogenesis factor Pex19. Intriguingly, flavivirus infection resulted in a significant loss of peroxisomes, an effect that may be due in part to capsid expression. We posited that capsid protein-mediated sequestration and/or degradation of Pex19 results in loss of peroxisomes, a situation that could result in reduced early antiviral signaling. In support of this hypothesis, we observed that induction of the lambda interferon mRNA in response to a viral RNA mimic was reduced by more than 80%. Together, our findings indicate that inhibition of peroxisome biogenesis may be a novel mechanism by which flaviviruses evade the innate immune system during early stages of infection. IMPORTANCE RNA viruses infect hundreds of millions of people each year, causing significant morbidity and mortality. Chief among these pathogens are the flaviviruses, which include dengue virus and West Nile virus. Despite their medical importance, there are very few prophylactic or therapeutic treatments for these viruses. Moreover, the manner in which they subvert the innate immune response in order to establish infection in mammalian cells is not well understood. Recently, peroxisomes were reported to function in early antiviral signaling, but

Signal dependent transport of a membrane cargo from early endosomes to recycling endosomes.

PubMed

Mahmoud, Ismail S; Louber, Jade; Dower, Steve K; Verhagen, Anne M; Gleeson, Paul A

2017-08-01

Many membrane cargoes undergo endocytosis and intracellular recycling to the plasma membrane via the early endosomes and the recycling endosomes. However whether specific sorting signals are required for transport from early endosomes to recycling endosomes is not known and the current view is that transport to the recycling endosomes is by a passive default process. Here we show that the cytoplasmic tail of the neonatal Fc receptor (FcRn) contains discrete signals for endocytosis and for sorting to the recycling endosomes. The FcRn cytoplasmic tail has previously been shown to contain the unusual WISL motif for AP2/clathrin-mediated endocytosis. By analysing FcRn mutants and CD8/FcRn chimeric molecules, we have identified an extended WISL sequence (GLPAPWISL) which promotes sorting from the early endosomes to the recycling endosomes. The insertion of GLPAPWISL into the cytoplasmic tail of CD8 resulted in efficient endocytosis and trafficking to the recycling endosomes, with only low levels detected in the late endosomes. Replacement of the highly conserved GLAPAP sequence within the GLPAPWISL motif with alanine residues resulted in endocytosis of the CD8/FcRn chimera to the early endosomes which was then trafficked predominantly to the late endosomes rather than the recycling endosomes. These studies demonstrate that signals within the cytoplasmic domains of membrane cargo can mediate active transport from early to recycling endosomes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Development of minimum standards for event-based data collection loggers and performance measure definitions for signalized intersections.

DOT National Transportation Integrated Search

2017-01-01

The arterial traffic signal performance measures were not used to their fullest potential in the past. The development of traffic signal controllers with event-based, high-resolution data logging capabilities enabled the advances in derivation and vi...

Impact Constraints on Major Events in Early Mars History

NASA Technical Reports Server (NTRS)

Frey, H. V.

2004-01-01

MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

False alarms: How early warning signals falsely predict abrupt sea ice loss

NASA Astrophysics Data System (ADS)

Wagner, Till J. W.; Eisenman, Ian

2016-04-01

Uncovering universal early warning signals for critical transitions has become a coveted goal in diverse scientific disciplines, ranging from climate science to financial mathematics. There has been a flurry of recent research proposing such signals, with increasing autocorrelation and increasing variance being among the most widely discussed candidates. A number of studies have suggested that increasing autocorrelation alone may suffice to signal an impending transition, although some others have questioned this. Here we consider variance and autocorrelation in the context of sea ice loss in an idealized model of the global climate system. The model features no bifurcation, nor increased rate of retreat, as the ice disappears. Nonetheless, the autocorrelation of summer sea ice area is found to increase in a global warming scenario. The variance, by contrast, decreases. A simple physical mechanism is proposed to explain the occurrence of increasing autocorrelation but not variance when there is no approaching bifurcation. Additionally, a similar mechanism is shown to allow an increase in both indicators with no physically attainable bifurcation. This implies that relying on autocorrelation and variance as early warning signals can raise false alarms in the climate system, warning of "tipping points" that are not actually there.

The developmental disruptions of serotonin signaling may involved in autism during early brain development.

PubMed

Yang, C-J; Tan, H-P; Du, Y-J

2014-05-16

Autism is a developmental disorder defined by the presence of a triad of communication, social and stereo typical behavioral characteristics with onset before 3years of age. In spite of the fact that there are potential environmental factors for autistic behavior, the dysfunction of serotonin during early development of the brain could be playing a role in this prevalence rise. Serotonin can modulate a number of developmental events, including cell division, neuronal migration, cell differentiation and synaptogenesis. Hyperserotonemia during fetal development results in the loss of serotonin terminals through negative feedback. The increased serotonin causes a decrease of oxytocin in the paraventricular nucleus of the hypothalamus and an increase in calcitonin gene-related peptide (CGRP) in the central nucleus of the amygdale, which are associated with social interactions and vital in autism. However, hyposerotonemia may be also relevant to the development of sensory as well as motor and cognitive faculties. And the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. This review briefly summarized the developmental disruptions of serotonin signaling involved in the pathogenesis of autism during early development of the brain. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Dose and Effect Thresholds for Early Key Events in a Mode of PPARa-Mediated Action

EPA Science Inventory

ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. T...

Root phonotropism: Early signalling events following sound perception in Arabidopsis roots.

PubMed

Rodrigo-Moreno, Ana; Bazihizina, Nadia; Azzarello, Elisa; Masi, Elisa; Tran, Daniel; Bouteau, François; Baluska, Frantisek; Mancuso, Stefano

2017-11-01

Sound is a fundamental form of energy and it has been suggested that plants can make use of acoustic cues to obtain information regarding their environments and alter and fine-tune their growth and development. Despite an increasing body of evidence indicating that it can influence plant growth and physiology, many questions concerning the effect of sound waves on plant growth and the underlying signalling mechanisms remains unknown. Here we show that in Arabidopsis thaliana, exposure to sound waves (200Hz) for 2 weeks induced positive phonotropism in roots, which grew towards to sound source. We found that sound waves triggered very quickly (within  minutes) an increase in cytosolic Ca 2+ , possibly mediated by an influx through plasma membrane and a release from internal stock. Sound waves likewise elicited rapid reactive oxygen species (ROS) production and K + efflux. Taken together these results suggest that changes in ion fluxes (Ca 2+ and K + ) and an increase in superoxide production are involved in sound perception in plants, as previously established in animals. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient Volcano Deformation Event Detection over Variable Spatial Scales in Alaska

NASA Astrophysics Data System (ADS)

Li, J. D.; Rude, C. M.; Gowanlock, M.; Herring, T.; Pankratius, V.

2016-12-01

Transient deformation events driven by volcanic activity can be monitored using increasingly dense networks of continuous Global Positioning System (GPS) ground stations. The wide spatial extent of GPS networks, the large number of GPS stations, and the spatially and temporally varying scale of deformation events result in the mixing of signals from multiple sources. Typical analysis then necessitates manual identification of times and regions of volcanic activity for further study and the careful tuning of algorithmic parameters to extract possible transient events. Here we present a computer-aided discovery system that facilitates the discovery of potential transient deformation events at volcanoes by providing a framework for selecting varying spatial regions of interest and for tuning the analysis parameters. This site specification step in the framework reduces the spatial mixing of signals from different volcanic sources before applying filters to remove interfering signals originating from other geophysical processes. We analyze GPS data recorded by the Plate Boundary Observatory network and volcanic activity logs from the Alaska Volcano Observatory to search for and characterize transient inflation events in Alaska. We find 3 transient inflation events between 2008 and 2015 at the Akutan, Westdahl, and Shishaldin volcanoes in the Aleutian Islands. The inflation event detected in the first half of 2008 at Akutan is validated other studies, while the inflation events observed in early 2011 at Westdahl and in early 2013 at Shishaldin are previously unreported. Our analysis framework also incorporates modelling of the transient inflation events and enables a comparison of different magma chamber inversion models. Here, we also estimate the magma sources that best describe the deformation observed by the GPS stations at Akutan, Westdahl, and Shishaldin. We acknowledge support from NASA AIST-NNX15AG84G (PI: V. Pankratius).

Quantifying fast optical signal and event-related potential relationships during a visual oddball task.

PubMed

Proulx, Nicole; Samadani, Ali-Akbar; Chau, Tom

2018-05-16

Event-related potentials (ERPs) have previously been used to confirm the existence of the fast optical signal (FOS) but validation methods have mainly been limited to exploring the temporal correspondence of FOS peaks to those of ERPs. The purpose of this study was to systematically quantify the relationship between FOS and ERP responses to a visual oddball task in both time and frequency domains. Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) sensors were co-located over the prefrontal cortex while participants performed a visual oddball task. Fifteen participants completed 2 data collection sessions each, where they were instructed to keep a mental count of oddball images. The oddball condition produced a positive ERP at 200 ms followed by a negativity 300-500 ms after image onset in the frontal electrodes. In contrast to previous FOS studies, a FOS response was identified only in DC intensity signals and not in phase delay signals. A decrease in DC intensity was found 150-250 ms after oddball image onset with a 400-trial average in 10 of 15 participants. The latency of the positive 200 ms ERP and the FOS DC intensity decrease were significantly correlated for only 6 (out of 15) participants due to the low signal-to-noise ratio of the FOS response. Coherence values between the FOS and ERP oddball responses were found to be significant in the 3-5 Hz frequency band for 10 participants. A significant Granger causal influence of the ERP on the FOS oddball response was uncovered in the 2-6 Hz frequency band for 7 participants. Collectively, our findings suggest that, for a majority of participants, the ERP and the DC intensity signal of the FOS are spectrally coherent, specifically in narrow frequency bands previously associated with event-related oscillations in the prefrontal cortex. However, these electro-optical relationships were only found in a subset of participants. Further research on enhancing the quality of the event-related FOS

Ca2+ conduction by plant cyclic nucleotide gated channels and associated signaling components in pathogen defense signal transduction cascades.

PubMed

Ma, Wei; Berkowitz, Gerald A

2011-05-01

Ca(2+) elevation in the cytosol is an essential early event during pathogen response signaling cascades. However, the specific ion channels involved in Ca(2+) influx into plant cells, and how Ca(2+) signals are initiated and regulate downstream events during pathogen defense responses, are at present unclear. Plant cyclic nucleotide gated ion channels (CNGCs) provide a pathway for Ca(2+) conductance across the plasma membrane (PM) and facilitate cytosolic Ca(2+) elevation in response to pathogen signals. Recent studies indicate that the recognition of pathogens results in cyclic nucleotide production and the activation of CNGCs, which leads to downstream generation of pivotal signaling molecules (such as nitric oxide (NO)). Calmodulins (CaMs) and CaM-like proteins (CMLs) are also involved in this signaling, functioning as Ca(2+) sensors and mediating the synthesis of NO during the plant pathogen response signaling cascade. In this article, these and other pivotal signaling components downstream from the Ca(2+) signal, such as Ca(2+)-dependent protein kinases (CDPKs) and CaM-binding transcription activators (CAMTAs), are discussed in terms of their involvement in the pathogen response signal transduction cascade. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

Changing skewness: an early warning signal of regime shifts in ecosystems.

PubMed

Guttal, Vishwesha; Jayaprakash, Ciriyam

2008-05-01

Empirical evidence for large-scale abrupt changes in ecosystems such as lakes and vegetation of semi-arid regions is growing. Such changes, called regime shifts, can lead to degradation of ecological services. We study simple ecological models that show a catastrophic transition as a control parameter is varied and propose a novel early warning signal that exploits two ubiquitous features of ecological systems: nonlinearity and large external fluctuations. Either reduced resilience or increased external fluctuations can tip ecosystems to an alternative stable state. It is shown that changes in asymmetry in the distribution of time series data, quantified by changing skewness, is a model-independent and reliable early warning signal for both routes to regime shifts. Furthermore, using model simulations that mimic field measurements and a simple analysis of real data from abrupt climate change in the Sahara, we study the feasibility of skewness calculations using data available from routine monitoring.

A parapoxviral virion protein inhibits NF-κB signaling early in infection

PubMed Central

Khatiwada, Sushil; Delhon, Gustavo; Nagendraprabhu, Ponnuraj; Chaulagain, Sabal; Luo, Shuhong; Diel, Diego G.; Flores, Eduardo F.

2017-01-01

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Expression of ORFV073 alone was sufficient to inhibit TNFα induced activation of the NF-κB signaling in uninfected cells. Consistent with observed inhibition of IKK complex activation, ORFV073 interacted with the regulatory subunit of the IKK complex NEMO. Infection of sheep with OV-IA82Δ073 led to virus attenuation, indicating that ORFV073 is a virulence determinant in the natural host. Notably, ORFV073 represents the first poxviral virion-associated NF-κB inhibitor described, highlighting the significance of viral inhibition of NF-κB signaling very early in infection. PMID:28787456

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed Central

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

Ancestral Ca2+ Signaling Machinery in Early Animal and Fungal Evolution

PubMed Central

Cai, Xinjiang; Clapham, David E.

2012-01-01

Animals and fungi diverged from a common unicellular ancestor of Opisthokonta, yet they exhibit significant differences in their components of Ca2+ signaling pathways. Many Ca2+ signaling molecules appear to be either animal-specific or fungal-specific, which is generally believed to result from lineage-specific adaptations to distinct physiological requirements. Here, by analyzing the genomic data from several close relatives of animals and fungi, we demonstrate that many components of animal and fungal Ca2+ signaling machineries are present in the apusozoan protist Thecamonas trahens, which belongs to the putative unicellular sister group to Opisthokonta. We also identify the conserved portion of Ca2+ signaling molecules in early evolution of animals and fungi following their divergence. Furthermore, our results reveal the lineage-specific expansion of Ca2+ channels and transporters in the unicellular ancestors of animals and in basal fungi. These findings provide novel insights into the evolution and regulation of Ca2+ signaling critical for animal and fungal biology. PMID:21680871

Direct and indirect requirements of Shh/Gli signaling in early pituitary development.

PubMed

Wang, Yiwei; Martin, James F; Bai, C Brian

2010-12-15

Induction of early pituitary progenitors is achieved through combined activities of signals from adjacent embryonic tissues. Previous studies have identified a requirement for oral ectoderm derived Sonic Hedgehog (Shh) in specification and/or proliferation of early pituitary progenitors, however how different Gli genes mediate Shh signaling to control pituitary progenitor development has not yet been determined. Here we show that Gli2, which encodes a major Gli activator, is required for proliferation of specific groups of pituitary progenitors but not for initial dorsoventral patterning. We further show that the action of Gli2 occurs prior to the closure of Rathke' pouch. Lastly, we show that Shh/Gli2 signaling controls the diencephalic expression of Bone morphogenetic protein 4 (Bmp4) and Fibroblast growth factor 8 (Fgf8), two genes that are known to play critical roles in patterning and growth of Rathke's pouch. Our results therefore suggest both cell-autonomous and non-cell-autonomous requirements for Gli2 in regulation of pituitary progenitor specification, proliferation and differentiation. Copyright © 2010 Elsevier Inc. All rights reserved.

Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling

PubMed Central

Miyazaki, Mitsunori; McCarthy, John J; Fedele, Mark J; Esser, Karyn A

2011-01-01

Abstract The mammalian target of rapamycin complex 1 (mTORC1) functions as a central integrator of a wide range of signals that modulate protein metabolism and cell growth. However, the contributions of individual pathways regulating mTORC1 activity in skeletal muscle are poorly defined. The purpose of this study was to determine the regulatory mechanisms that contribute to mTORC1 activation during mechanical overload-induced skeletal muscle hypertrophy. Consistent with previous studies, mechanical overload induced progressive hypertrophy of the plantaris muscle which was associated with significant increases in total RNA content and protein metabolism. mTORC1 was activated after a single day of overload as indicated by a significant increase in S6K1 phosphorylation at T389 and T421/S424. In contrast, Akt activity, as assessed by Akt phosphorylation status (T308 and S473), phosphorylation of direct downstream targets (glycogen synthase kinase 3 β, proline-rich Akt substrate 40 kDa and tuberous sclerosis 2 (TSC2)) and a kinase assay, was not significantly increased until 2–3 days of overload. Inhibition of phosphoinositide 3-kinase (PI3K) activity by wortmannin was sufficient to block insulin-dependent signalling but did not prevent the early activation of mTORC1 in response to overload. We identified that the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent pathway was activated at day 1 after overload. In addition, a target of MEK/ERK signalling, phosphorylation of TSC2 at S664, was also increased at this early time point. These observations demonstrate that in vivo, mTORC1 activation at the early phase of mechanical overload in skeletal muscle occurs independently of PI3K/Akt signalling and provide evidence that the MEK/ERK pathway may contribute to mTORC1 activation through phosphorylation of TSC2. PMID:21300751

Early-warning signals for catastrophic soil degradation

NASA Astrophysics Data System (ADS)

Karssenberg, Derek

2010-05-01

Many earth systems have critical thresholds at which the system shifts abruptly from one state to another. Such critical transitions have been described, among others, for climate, vegetation, animal populations, and geomorphology. Predicting the timing of critical transitions before they are reached is of importance because of the large impact on nature and society associated with the transition. However, it is notably difficult to predict the timing of a transition. This is because the state variables of the system show little change before the threshold is reached. As a result, the precision of field observations is often too low to provide predictions of the timing of a transition. A possible solution is the use of spatio-temporal patterns in state variables as leading indicators of a transition. It is becoming clear that the critically slowing down of a system causes spatio-temporal autocorrelation and variance to increase before the transition. Thus, spatio-temporal patterns are important candidates for early-warning signals. In this research we will show that these early-warning signals also exist in geomorphological systems. We consider a modelled vegetation-soil system under a gradually increasing grazing pressure causing an abrupt shift towards extensive soil degradation. It is shown that changes in spatio-temporal patterns occur well ahead of this catastrophic transition. A distributed model describing the coupled processes of vegetation growth and geomorphological denudation is adapted. The model uses well-studied simple process representations for vegetation and geomorphology. A logistic growth model calculates vegetation cover as a function of grazing pressure and vegetation growth rate. Evolution of the soil thickness is modelled by soil creep and wash processes, as a function of net rain reaching the surface. The vegetation and soil system are coupled by 1) decreasing vegetation growth with decreasing soil thickness and 2) increasing soil wash with

Neighborhood Disadvantage, Stressful Life Events, and Adjustment among Mexican American Early Adolescents

ERIC Educational Resources Information Center

Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.

2010-01-01

This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…

Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

PubMed Central

Watt, Richard G.; Tsakos, Georgios

2014-01-01

Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

PubMed

Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

2017-09-01

The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

NASA Astrophysics Data System (ADS)

Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

2010-05-01

The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

Insights into the early evolution of animal calcium signaling machinery: A unicellular point of view

PubMed Central

Cai, Xinjiang; Wang, Xiangbing; Patel, Sandip; Clapham, David E.

2014-01-01

The basic principles of Ca2+ regulation emerged early in prokaryotes. Ca2+ signaling acquired more extensive and varied functions when life evolved into multicellular eukaryotes with intracellular organelles. Animals, fungi and plants display differences in the mechanisms that control cytosolic Ca2+ concentrations. The aim of this review is to examine recent findings from comparative genomics of Ca2+ signaling molecules in close unicellular relatives of animals and in common unicellular ancestors of animals and fungi. Also discussed are the evolution and origins of the sperm-specific CatSper channel complex, cation/Ca2+ exchangers and four-domain voltage-gated Ca2+ channels. Newly identified evolutionary evidence suggests that the distinct Ca2+ signaling machineries in animals, plants and fungi likely originated from an ancient Ca2+ signaling machinery prior to early eukaryotic radiation. PMID:25498309

Insights into the early evolution of animal calcium signaling machinery: a unicellular point of view.

PubMed

Cai, Xinjiang; Wang, Xiangbing; Patel, Sandip; Clapham, David E

2015-03-01

The basic principles of Ca(2+) regulation emerged early in prokaryotes. Ca(2+) signaling acquired more extensive and varied functions when life evolved into multicellular eukaryotes with intracellular organelles. Animals, fungi and plants display differences in the mechanisms that control cytosolic Ca(2+) concentrations. The aim of this review is to examine recent findings from comparative genomics of Ca(2+) signaling molecules in close unicellular relatives of animals and in common unicellular ancestors of animals and fungi. Also discussed are the evolution and origins of the sperm-specific CatSper channel complex, cation/Ca(2+) exchangers and four-domain voltage-gated Ca(2+) channels. Newly identified evolutionary evidence suggests that the distinct Ca(2+) signaling machineries in animals, plants and fungi likely originated from an ancient Ca(2+) signaling machinery prior to early eukaryotic radiation. Copyright © 2014 Elsevier Ltd. All rights reserved.

The onset of childhood amnesia in childhood: A prospective investigation of the course and determinants of forgetting of early-life events

PubMed Central

Bauer, Patricia J.; Larkina, Marina

2013-01-01

The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique events when the children were 3 years of age. Different subgroups of children were tested for recall of the events at ages 5, 6, 7, 8, and 9 years. At the later session, they were interviewed by an experimenter about the events discussed 2 to 6 years previously with their mothers (early-life events). Children ages 5, 6, and 7 remembered 60% or more of the early-life events. In contrast, children ages 8 and 9 years remembered fewer than 40% of the early-life events. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for early-life events at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the early-life events. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID:24236647

Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors

PubMed Central

Cunningham, Thomas J.; Colas, Alexandre

2016-01-01

ABSTRACT Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis. Differential expression analysis of this dataset indicated that treatment with 25 nM RA, but not 1 µM RA, provided physiologically relevant findings. The 25 nM RA dataset yielded a cohort of previously known caudal RA target genes including Fgf8 (repressed) and Sox2 (activated), plus novel early RA signaling targets with nearby conserved RA response elements. Importantly, validation of top-ranked genes in vivo using RA-deficient Raldh2−/− embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny. These findings provide evidence for early instructive and permissive roles of RA in controlling differentiation of NMPs to neural and mesodermal lineages. PMID:27793834

Liver Dysfunction and Phosphatidylinositol-3-Kinase Signalling in Early Sepsis: Experimental Studies in Rodent Models of Peritonitis

PubMed Central

Westermann, Martin; Lambeck, Sandro; Lupp, Amelie; Rudiger, Alain; Dyson, Alex; Carré, Jane E.; Kortgen, Andreas; Krafft, Christoph; Popp, Jürgen; Sponholz, Christoph; Fuhrmann, Valentin; Hilger, Ingrid; Claus, Ralf A.; Riedemann, Niels C.; Wetzker, Reinhard; Singer, Mervyn; Trauner, Michael; Bauer, Michael

2012-01-01

Background Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. Methods and Findings In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87). Conclusions Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is

Purinergic signalling in bone

PubMed Central

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

2012-01-01

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

Relation between stability and resilience determines the performance of early warning signals under different environmental drivers.

PubMed

Dai, Lei; Korolev, Kirill S; Gore, Jeff

2015-08-11

Shifting patterns of temporal fluctuations have been found to signal critical transitions in a variety of systems, from ecological communities to human physiology. However, failure of these early warning signals in some systems calls for a better understanding of their limitations. In particular, little is known about the generality of early warning signals in different deteriorating environments. In this study, we characterized how multiple environmental drivers influence the dynamics of laboratory yeast populations, which was previously shown to display alternative stable states [Dai et al., Science, 2012]. We observed that both the coefficient of variation and autocorrelation increased before population collapse in two slowly deteriorating environments, one with a rising death rate and the other one with decreasing nutrient availability. We compared the performance of early warning signals across multiple environments as "indicators for loss of resilience." We find that the varying performance is determined by how a system responds to changes in a specific driver, which can be captured by a relation between stability (recovery rate) and resilience (size of the basin of attraction). Furthermore, we demonstrate that the positive correlation between stability and resilience, as the essential assumption of indicators based on critical slowing down, can break down in this system when multiple environmental drivers are changed simultaneously. Our results suggest that the stability-resilience relation needs to be better understood for the application of early warning signals in different scenarios.

Relation between stability and resilience determines the performance of early warning signals under different environmental drivers

PubMed Central

Dai, Lei; Korolev, Kirill S.; Gore, Jeff

2015-01-01

Shifting patterns of temporal fluctuations have been found to signal critical transitions in a variety of systems, from ecological communities to human physiology. However, failure of these early warning signals in some systems calls for a better understanding of their limitations. In particular, little is known about the generality of early warning signals in different deteriorating environments. In this study, we characterized how multiple environmental drivers influence the dynamics of laboratory yeast populations, which was previously shown to display alternative stable states [Dai et al., Science, 2012]. We observed that both the coefficient of variation and autocorrelation increased before population collapse in two slowly deteriorating environments, one with a rising death rate and the other one with decreasing nutrient availability. We compared the performance of early warning signals across multiple environments as “indicators for loss of resilience.” We find that the varying performance is determined by how a system responds to changes in a specific driver, which can be captured by a relation between stability (recovery rate) and resilience (size of the basin of attraction). Furthermore, we demonstrate that the positive correlation between stability and resilience, as the essential assumption of indicators based on critical slowing down, can break down in this system when multiple environmental drivers are changed simultaneously. Our results suggest that the stability–resilience relation needs to be better understood for the application of early warning signals in different scenarios. PMID:26216946

How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

A Further Extension of the Tahiti-Darwin SOI, Early ENSO Events and Darwin Pressure.

NASA Astrophysics Data System (ADS)

Allan, Robert J.; Nicholls, Neville; Jones, Phil D.; Butterworth, Ian J.

1991-07-01

An extension of the Tahiti minus Darwin Southern Oscillation Index (SOI) from 1882 back to 1876 is reported following the recovery of early Darwin mean sea-level pressure data spanning the period 1865-81. As a result, we are able to compare, for the first time, the major 1877-78 and 1982-83 ENSO events on the basis of this commonly used index. Early Darwin and Jakarta data are also examined in terms of a measure of the Australian response to documented El Niño and/or ENSO events in 1866, 1868, 1871, 1873, 1874 and 1875.The SOI during the 1877-78 ENSO event has a similar temporal response to that in 1982-83, but the index is slightly weaker than in the recent event. Examination of documentary evidence confirms the severity of the drought conditions that affected the Australian continent during the 1877-78 ENSO, and shows that this response is in line with the wider Indo-Pacific impacts reported in the literature. Earlier El Niño phases in 1868 and 1873 are not resolved distinctly in either the Darwin or Jakarta pressure data. This appears to illustrate that El Niño event histories do not always indicate wider ENSO influences in the Indo-Pacific basin, particularly during weak to moderate phases.

Divergent β-Arrestin-dependent Signaling Events Are Dependent upon Sequences within G-protein-coupled Receptor C Termini*

PubMed Central

Pal, Kasturi; Mathur, Maneesh; Kumar, Puneet; DeFea, Kathryn

2013-01-01

β-Arrestins are multifunctional adaptor proteins that, upon recruitment to an activated G-protein-coupled receptor, can promote desensitization of G-protein signaling and receptor internalization while simultaneously eliciting an independent signal. The result of β-arrestin signaling depends upon the activating receptor. For example, activation of two Gαq-coupled receptors, protease-activated receptor-2 (PAR2) and neurokinin-1 receptor (NK1R), results in drastically different signaling events. PAR2 promotes β-arrestin-dependent membrane-sequestered extracellular signal-regulated kinase (ERK1/2) activation, cofilin activation, and cell migration, whereas NK1R promotes nuclear ERK1/2 activation and proliferation. Using bioluminescence resonance energy transfer to monitor receptor/β-arrestin interactions in real time, we observe that PAR2 has a higher apparent affinity for both β-arrestins than does NK1R, recruits them at a faster rate, and exhibits more rapid desensitization of the G-protein signal. Furthermore, recruitment of β-arrestins to PAR2 does not require prior Gαq signaling events, whereas inhibition of Gαq signaling intermediates inhibits recruitment of β-arrestins to NK1R. Using chimeric receptors in which the C terminus of PAR2 is fused to the N terminus of NK1R and vice versa and a critical Ser/Thr mutant of PAR2, we demonstrate that interactions between β-arrestins and specific phosphoresidues in the C termini of each receptor are crucial for determining the rate and magnitude of β-arrestin recruitment as well as the ultimate signaling outcome. PMID:23235155

Early warnings, weak signals and learning from healthcare disasters.

PubMed

Macrae, Carl

2014-06-01

In the wake of healthcare disasters, such as the appalling failures of care uncovered in Mid Staffordshire, inquiries and investigations often point to a litany of early warnings and weak signals that were missed, misunderstood or discounted by the professionals and organisations charged with monitoring the safety and quality of care. Some of the most urgent challenges facing those responsible for improving and regulating patient safety are therefore how to identify, interpret, integrate and act on the early warnings and weak signals of emerging risks-before those risks contribute to a disastrous failure of care. These challenges are fundamentally organisational and cultural: they relate to what information is routinely noticed, communicated and attended to within and between healthcare organisations-and, most critically, what is assumed and ignored. Analysing these organisational and cultural challenges suggests three practical ways that healthcare organisations and their regulators can improve safety and address emerging risks. First, engage in practices that actively produce and amplify fleeting signs of ignorance. Second, work to continually define and update a set of specific fears of failure. And third, routinely uncover and publicly circulate knowledge on the sources of systemic risks to patient safety and the improvements required to address them. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

PubMed

Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

2015-10-01

Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.

Atmospheric pCO2 reconstructed across five early Eocene global warming events

NASA Astrophysics Data System (ADS)

Cui, Ying; Schubert, Brian A.

2017-11-01

Multiple short-lived global warming events, known as hyperthermals, occurred during the early Eocene (56-52 Ma). Five of these events - the Paleocene-Eocene Thermal Maximum (PETM or ETM1), H1 (or ETM2), H2, I1, and I2 - are marked by a carbon isotope excursion (CIE) within both marine and terrestrial sediments. The magnitude of CIE, which is a function of the amount and isotopic composition of carbon added to the ocean-atmosphere system, varies significantly between marine versus terrestrial substrates. Here we use the increase in carbon isotope fractionation by C3 land plants in response to increased pCO2 to reconcile this difference and reconstruct a range of background pCO2 and peak pCO2 for each CIE, provided two potential carbon sources: methane hydrate destabilization and permafrost-thawing/organic matter oxidation. Although the uncertainty on each pCO2 estimate using this approach is low (e.g., median uncertainty = + 23% / - 18%), this work highlights the potential for significant systematic bias in the pCO2 estimate resulting from sampling resolution, substrate type, diagenesis, and environmental change. Careful consideration of each of these factors is required especially when applying this approach to a single marine-terrestrial CIE pair. Given these limitations, we provide an upper estimate for background early Eocene pCO2 of 463 +248/-131 ppmv (methane hydrate scenario) to 806 +127/-104 ppmv (permafrost-thawing/organic matter oxidation scenario). These results, which represent the first pCO2 proxy estimates directly tied to the Eocene hyperthermals, demonstrate that early Eocene warmth was supported by background pCO2 less than ∼3.5× preindustrial levels and that pCO2 > 1000 ppmv may have occurred only briefly, during hyperthermal events.

Dose and Effect Thresholds for Early Key Events in a Mode of ...

EPA Pesticide Factsheets

ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor-alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), and n-butyl benzyl phthalate (BBP), which vary in PPARα activity and liver tumorigenicity. Each phthalate increased expression of select PPARα target genes at 7 days, while only DEHP significantly increased liver cell proliferation labeling index (LI). Transcriptional benchmark dose (BMDT) estimates for dose-related genomic markers stratified phthalates according to hypothetical tumorigenic potencies, unlike BMDs for non-genomic endpoints (liver weights or proliferation). The 7-day BMDT values for Acot1 as a surrogate measure for PPARα activation were 29, 370, and 676 mg/kg-d for DEHP, DNOP, and BBP, respectively, distinguishing DEHP (liver tumor BMD of 35 mg/kg-d) from non-tumorigenic DNOP and BBP. Effect thresholds were generated using linear regression of DEHP effects at 7 days and 2-year tumor incidence values to anchor early response molec

Spatiotemporal transcriptome provides insights into early fruit development of tomato (Solanum lycopersicum).

PubMed

Zhang, Shuaibin; Xu, Meng; Qiu, Zhengkun; Wang, Ketao; Du, Yongchen; Gu, Lianfeng; Cui, Xia

2016-03-18

Early fruit development is crucial for crop production in tomato. After fertilization, the ovary undergoes cell division and cell expansion before maturation. Although the roles of regulatory signals such as hormone and carbohydrate during early fruit development have been studied, the spatial distribution and the sequential initiation of these regulatory signals still need to be explored. Using the tomato cultivar 'Moneymaker', we analyzed the transcriptome of the ovule and the ovary wall/pericarp dissected from four different stages of the early developing fruits by stereoscope. These datasets give us the whole picture about the spatial and temporal signal distribution in early development of ovule and pericarp. Our results indicate that the hormone signal was initiated in both ovule and pericarp after fertilization. After that, different signals were activated in ovule and pericarp due to their distinct developmental processes. Our study provides spatiotemporal regulatory landscape of gene expression with sequential information which was not studied by previous work and further strengthens the comprehension of the regulatory and metabolic events controlling early fruit development.

Signal detection of adverse events with imperfect confirmation rates in vaccine safety studies using self-controlled case series design.

PubMed

Xu, Stanley; Newcomer, Sophia; Nelson, Jennifer; Qian, Lei; McClure, David; Pan, Yi; Zeng, Chan; Glanz, Jason

2014-05-01

The Vaccine Safety Datalink project captures electronic health record data including vaccinations and medically attended adverse events on 8.8 million enrollees annually from participating managed care organizations in the United States. While the automated vaccination data are generally of high quality, a presumptive adverse event based on diagnosis codes in automated health care data may not be true (misclassification). Consequently, analyses using automated health care data can generate false positive results, where an association between the vaccine and outcome is incorrectly identified, as well as false negative findings, where a true association or signal is missed. We developed novel conditional Poisson regression models and fixed effects models that accommodate misclassification of adverse event outcome for self-controlled case series design. We conducted simulation studies to evaluate their performance in signal detection in vaccine safety hypotheses generating (screening) studies. We also reanalyzed four previously identified signals in a recent vaccine safety study using the newly proposed models. Our simulation studies demonstrated that (i) outcome misclassification resulted in both false positive and false negative signals in screening studies; (ii) the newly proposed models reduced both the rates of false positive and false negative signals. In reanalyses of four previously identified signals using the novel statistical models, the incidence rate ratio estimates and statistical significances were similar to those using conventional models and including only medical record review confirmed cases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports.

PubMed

Hoffman, Keith B; Dimbil, Mo; Tatonetti, Nicholas P; Kyle, Robert F

2016-06-01

Many serious drug adverse events (AEs) only manifest well after regulatory approval. Therefore, the development of signaling methods to use with post-approval AE databases appears vital to comprehensively assess real-world drug safety. However, with millions of potential drug-AE pairs to analyze, the issue of focus is daunting. Our objective was to develop a signaling platform that focuses on AEs with historically demonstrated regulatory interest and to analyze such AEs with a disproportional reporting method that offers broad signal detection and acceptable false-positive rates. We analyzed over 1500 US FDA regulatory actions (safety communications and drug label changes) from 2008 to 2015 to construct a list of eligible signal AEs. The FDA Adverse Event Reporting System (FAERS) was used to evaluate disproportional reporting rates, constrained by minimum case counts and confidence interval limits, of these selected AEs for 109 training drugs. This step led to 45 AEs that appeared to have a low likelihood of being added to a label by FDA, so they were removed from the signal eligible list. We measured disproportional reporting for the final group of eligible AEs on a test group of 29 drugs that were not used in either the eligible list construction or the training steps. In a group of 29 test drugs, our model reduced the number of potential drug-AE signals from 41,834 to 97 and predicted 73 % of individual drug label changes. The model also predicted at least one AE-drug pair label change in 66 % of all the label changes for the test drugs. By concentrating on AE types with already demonstrated interest to FDA, we constructed a signaling system that provided focus regarding drug-AE pairs and suitable accuracy with regard to the issuance of FDA labeling changes. We suggest that focus on historical regulatory actions may increase the utility of pharmacovigilance signaling systems.

Early Warning Signals for Abrupt Change Raise False Alarm During Sea Ice Loss

NASA Astrophysics Data System (ADS)

Wagner, T. J. W.; Eisenman, I.

2015-12-01

Uncovering universal early warning signals for critical transitions has become a coveted goal in diverse scientific disciplines, ranging from climate science to financial mathematics. There has been a flurry of recent research proposing such signals, with increasing autocorrelation and increasing variance being among the most widely discussed candidates. A number of studies have suggested that increasing autocorrelation alone may suffice to signal an impending transition, although some others have questioned this. Here, we consider variance and autocorrelation in the context of sea ice loss in an idealized model of the global climate system. The model features no bifurcation, nor increased rate of retreat, as the ice disappears. Nonetheless, the autocorrelation of summer sea ice area is found to increase with diminishing sea ice cover in a global warming scenario. The variance, by contrast, decreases. A simple physical mechanism is proposed to explain the occurrence of increasing autocorrelation but not variance in the model when there is no approaching bifurcation. Additionally, a similar mechanism is shown to allow an increase in both indicators with no physically attainable bifurcation. This implies that relying on autocorrelation and variance as early warning signals can raise false alarms in the climate system, warning of "tipping points" that are not actually there.

Mitotic wavefronts mediated by mechanical signaling in early Drosophila embryos

NASA Astrophysics Data System (ADS)

Kang, Louis; Idema, Timon; Liu, Andrea; Lubensky, Tom

2013-03-01

Mitosis in the early Drosophila embryo demonstrates spatial and temporal correlations in the form of wavefronts that travel across the embryo in each cell cycle. This coordinated phenomenon requires a signaling mechanism, which we suggest is mechanical in origin. We have constructed a theoretical model that supports nonlinear wavefront propagation in a mechanically-excitable medium. Previously, we have shown that this model captures quantitatively the wavefront speed as it varies with cell cycle number, for reasonable values of the elastic moduli and damping coefficient of the medium. Now we show that our model also captures the displacements of cell nuclei in the embryo in response to the traveling wavefront. This new result further supports that mechanical signaling may play an important role in mediating mitotic wavefronts.

Constraints on early events in Martian history as derived from the cratering record

NASA Technical Reports Server (NTRS)

Barlow, Nadine G.

1990-01-01

Constrains on early events in Martian history are derived using the planet's cratering record. Variations in the shapes of the crater size-frequency distribution curves are interpreted as indicative of the size-frequency distribution of the production populations, thus providing information about the age of the unit relative to the end of the heavy bombardment period. Results from the analysis of craters superposed on heavily cratered units across the Martian surface provide constraints on the hemispheric dichotomy and the early erosional conditions on Mars.

DETECT: a MATLAB toolbox for event detection and identification in time series, with applications to artifact detection in EEG signals.

PubMed

Lawhern, Vernon; Hairston, W David; Robbins, Kay

2013-01-01

Recent advances in sensor and recording technology have allowed scientists to acquire very large time-series datasets. Researchers often analyze these datasets in the context of events, which are intervals of time where the properties of the signal change relative to a baseline signal. We have developed DETECT, a MATLAB toolbox for detecting event time intervals in long, multi-channel time series. Our primary goal is to produce a toolbox that is simple for researchers to use, allowing them to quickly train a model on multiple classes of events, assess the accuracy of the model, and determine how closely the results agree with their own manual identification of events without requiring extensive programming knowledge or machine learning experience. As an illustration, we discuss application of the DETECT toolbox for detecting signal artifacts found in continuous multi-channel EEG recordings and show the functionality of the tools found in the toolbox. We also discuss the application of DETECT for identifying irregular heartbeat waveforms found in electrocardiogram (ECG) data as an additional illustration.

DETECT: A MATLAB Toolbox for Event Detection and Identification in Time Series, with Applications to Artifact Detection in EEG Signals

PubMed Central

Lawhern, Vernon; Hairston, W. David; Robbins, Kay

2013-01-01

Recent advances in sensor and recording technology have allowed scientists to acquire very large time-series datasets. Researchers often analyze these datasets in the context of events, which are intervals of time where the properties of the signal change relative to a baseline signal. We have developed DETECT, a MATLAB toolbox for detecting event time intervals in long, multi-channel time series. Our primary goal is to produce a toolbox that is simple for researchers to use, allowing them to quickly train a model on multiple classes of events, assess the accuracy of the model, and determine how closely the results agree with their own manual identification of events without requiring extensive programming knowledge or machine learning experience. As an illustration, we discuss application of the DETECT toolbox for detecting signal artifacts found in continuous multi-channel EEG recordings and show the functionality of the tools found in the toolbox. We also discuss the application of DETECT for identifying irregular heartbeat waveforms found in electrocardiogram (ECG) data as an additional illustration. PMID:23638169

Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

PubMed

Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

2008-12-01

This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

The early Toarcian anoxic event: what the beginning and the end of the story are?

NASA Astrophysics Data System (ADS)

Mattioli, Emanuela; Plancq, Julien; Raucsik, Béla

2010-05-01

The early Toarcian anoxic event: what the beginning and the end of the story are? E. Mattioli (1), J. Plancq (1), and B. Rauksik (2) (1) UMR 5125 PEPS, CNRS, France; Université Lyon 1, Campus de la DOUA, Bâtiment Géode, 69622 Villeurbanne Cedex, France (emanuela.mattioli@univ-lyon1.fr) (2) Department of Earth and Environmental Sciences, University of Pannonia, Veszprém, Hungary The early Toarcian anoxic event (T-OAE) and the associated biotic crisis have received much attention in the last decade. However, the events forewarning the crisis as well as its aftermath are still poorly known. The T-OAE coincides with a prominent carbon isotope negative excursion (T-CIE) that is preceded by an excursion of similar intensity at the Pliensbachian-Toarcian boundary (Hesselbo et al., 2007). The onset of T-CIE occurred some 700 kyr later than the end of the Boundary-CIE (Suan et al., 2008a). This succession of events demonstrates that the T-OAE was a complex suite of environmental perturbations. In this work, we focused on calcareous nannofossil assemblages occurring in the Peniche section (Portugal) during the Boundary-CIE with the aim to understand if calcifying plankton reacted in a similar/different way to the two CIEs. Also, two sections and one borehole located along a W-E transect, along the NW-Tethyan shelf (in the Yorkshire coast, in the E Paris Basin, and in Mecsek Basin, respectively), were investigated to assess which way calcareous nannoplankton recovered after the crisis, and if the recovery was a synchronous event. The production by nannoplankton collapsed during the T-CIE, as demonstrated by the lowest absolute abundance of nannofossils measured in Peniche and other studied sites (Mattioli et al., 2008). Besides this nannofossil abundance decrease, also the size of the incertae sedis Schizosphaerella test was drastically reduced (Suan et al., 2008b). If a similar size decrease is also recorded during the Boundary-CIE, calcareous nannofossil abundances are

Oncogenic Smad3 signaling induced by chronic inflammation is an early event in ulcerative colitis-associated carcinogenesis.

PubMed

Kawamata, Seiji; Matsuzaki, Koichi; Murata, Miki; Seki, Toshihito; Matsuoka, Katsuyoshi; Iwao, Yasushi; Hibi, Toshifumi; Okazaki, Kazuichi

2011-03-01

Both chronic inflammation and somatic mutations likely contribute to the pathogenesis of ulcerative colitis (UC)-associated dysplasia and cancer. On the other hand, both tumor suppression and oncogenesis can result from transforming growth factor (TGF)-β signaling. TGF-β type I receptor (TβRI) and Ras-associated kinases differentially phosphorylate a mediator, Smad3, to become C-terminally phosphorylated Smad3 (pSmad3C), linker phosphorylated Smad3 (pSmad3L), and both C-terminally and linker phosphorylated Smad3 (pSmad3L/C). The pSmad3C/p21(WAF1) pathway transmits a cytostatic TGF-β signal, while pSmad3L and pSmad3L/C promote cell proliferation by upregulating c-Myc oncoprotein. The purpose of this study was to clarify the alteration of Smad3 signaling during UC-associated carcinogenesis. By immunostaining and immunofluorescence, we compared pSmad3C-, pSmad3L-, and pSmad3L/C-mediated signaling in colorectal specimens representing colitis, dysplasia, or cancer from eight UC patients with signaling in normal colonic crypts. We also investigated p53 expression and mutations of p53 and K-ras genes. We further sought functional meaning of the phosphorylated Smad3-mediated signaling in vitro. As enterocytes in normal crypts migrated upward toward the lumen, cytostatic pSmad3C/p21(WAF1) tended to increase, while pSmad3L/c-Myc shown by progenitor cells gradually decreased. Colitis specimens showed prominence of pSmad3L/C/c-Myc, mediated by TGF-β and tumor necrosis factor (TNF)-α, in all enterocyte nuclei throughout entire crypts. In proportion with increases in frequency of p53 and K-ras mutations during progression from dysplasia to cancer, the oncogenic pSmad3L/c-Myc pathway came to be dominant with suppression of the pSmad3C/p21(WAF1) pathway. Oncogenic Smad3 signaling, altered by chronic inflammation and eventually somatic mutations, promotes UC-associated neoplastic progression by upregulating growth-related protein. Copyright © 2010 Crohn's & Colitis

A continued role for signaling functions in the early evolution of feathers.

PubMed

Ruxton, Graeme D; Persons Iv, W Scott; Currie, Philip J

2017-03-01

Persons and Currie (2015) argued against either flight, thermoregulation, or signaling as a functional benefit driving the earliest evolution of feathers; rather, they favored simple feathers having an initial tactile sensory function, which changed to a thermoregulatory function as density increased. Here, we explore the relative merits of early simple feathers that may have originated as tactile sensors progressing instead toward a signaling, rather than (or in addition to) a thermoregulatory function. We suggest that signaling could act in concert with a sensory function more naturally than could thermoregulation. As such, the dismissal of a possible signaling function and the presumption that an initial sensory function led directly to a thermoregulatory function (implicit in the title "bristles before down") are premature. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory.

PubMed

Sjulson, Lucas; Miesenböck, Gero

2007-02-01

Optical imaging of physiological events in real time can yield insights into biological function that would be difficult to obtain by other experimental means. However, the detection of all-or-none events, such as action potentials or vesicle fusion events, in noisy single-trial data often requires a careful balance of tradeoffs. The analysis of such experiments, as well as the design of optical reporters and instrumentation for them, is aided by an understanding of the principles of signal detection. This review illustrates these principles, using as an example action potential recording with optical voltage reporters.

[Influence of early childhood stress exposure and traumatic life events on pain perception].

PubMed

Tesarz, J; Gerhardt, A; Eich, W

2018-06-05

Adult pain perception is influenced substantially by interactions between mind, body, and social environment during early life. Early stress exposure and traumatic life events induce powerful psychophysical stress reactions that exert multiple neurofunctional processes. This has significant implications for pain perception and pain processing. As part of this review, the complex relationships between traumatic stress experiences and associated psychobiological mechanisms of chronic pain will be discussed. Based on selected studies, psychophysiological findings are presented and possible underlying mechanisms are discussed. The article concludes with a discussion of potential implications for treatment.

Early changes in physical tree characteristics during an oak decline event in the Ozark highlands

Treesearch

Martin A. Spetich

2006-01-01

An oak decline event is severely affecting up to 120 000 ha in the Ozark National Forest of Arkansas. Results of early changes in physical tree characteristics during that event are presented. In the fall and winter of 1999 and 2000, we established research plots on a site that would become a center of severe oak decline. In August 2000, standing trees > 14 cm in...

Marine ecosystem resilience during extreme deoxygenation: the Early Jurassic oceanic anoxic event.

PubMed

Caswell, Bryony A; Frid, Christopher L J

2017-01-01

Global warming during the Early Jurassic, and associated widespread ocean deoxygenation, was comparable in scale with the changes projected for the next century. This study quantifies the impact of severe global environmental change on the biological traits of marine communities that define the ecological roles and functions they deliver. We document centennial-millennial variability in the biological trait composition of Early Jurassic (Toarcian) seafloor communities and examine how this changed during the event using biological traits analysis. Environmental changes preceding the global oceanic anoxic event (OAE) produced an ecological shift leading to stressed benthic palaeocommunities with reduced resilience to the subsequent OAE. Changes in traits and ecological succession coincided with major environmental changes; and were of similar nature and magnitude to those in severely deoxygenated benthic communities today despite the very different timescales. Changes in community composition were linked to local redox conditions whereas changes in populations of opportunists were driven by primary productivity. Throughout most of the OAE substitutions by tolerant taxa conserved the trait composition and hence functioning, but periods of severe deoxygenation caused benthic defaunation that would have resulted in functional collapse. Following the OAE recovery was slow probably because the global nature of the event restricted opportunities for recruitment from outside the basin. Our findings suggest that future systems undergoing deoxygenation may initially show functional resilience, but severe global deoxygenation will impact traits and ecosystem functioning and, by limiting the species pool, will slow recovery rates.

Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

PubMed Central

Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

2016-01-01

Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

Seismic Signals Recorded During Artificial and Natural Karst Recharge Events

NASA Astrophysics Data System (ADS)

Bilek, S. L.; Luhmann, A. J.; Diniakos, R. S.; Morton, E.; Rinehart, A. J.; Alexander, E. C., Jr.; Alexander, S. C.; Larsen, M.; Green, J. A.

2016-12-01

Seismology has recently been used to explore a variety of surficial processes, including tracking landslides, glaciers, and river flow. The seismic data collected can provide useful information about these flow processes, particularly in areas where other flow-related observations are difficult to make. Underground flow through karst aquifers is an area of significant interest, where most of the flow occurs through preferential flow conduits whose locations are largely unknown. We investigate seismic signals generated by both controlled and natural recharge into a karst aquifer system located near Bear Spring, near Eyota, MN, USA. The controlled recharge experiments involved injecting a pool full of water ( 13,000 L) into a dry overflow spring, which then flowed underground until it was discharged at Bear Spring. The natural recharge fortuitously involved a large rainstorm that supplied over 2 inches of rain in a few hour period, which caused the overflow spring to start flowing and total discharge to increase from a background of 100 L/s to 300 L/s. These events were recorded by 12 seismometers (11 short period and 1 broadband with 500 Hz sampling rate) all placed within the 4500 m2 area containing the dry overflow spring and predicted underground flow path. Spectrograms for the artificial and natural recharge events show significant seismic energy over a broad frequency range (few to nearly 220 Hz) during the periods of artificial recharge, largely contained during the period of water injection. Stations closest to Bear Spring see peak seismic energy in the 20-30 Hz range during these tests, likely related to changes in the underground water flow. During the natural recharge event, we find much longer duration of seismic energy over the broad frequency range. We compare these seismic results with discharge measurements conducted during all tests at Bear Spring, as well as with rainfall measurements recorded for the natural recharge event.

MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

PubMed

Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

2011-02-15

At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

Recognizing the Palynological Signal of Heinrich Event H1

NASA Astrophysics Data System (ADS)

Delusina, I.

2017-12-01

One of the most challenging intervals for paleo-vegetation reconstruction of the post-Glacial environment is the transition that occurred at the beginning and the end of Heinrich event H1 and that stretched up to the beginning of the Younger Dryas. The main ambiguity is related to the magnitude and timing of H1 and the non-linear response of the Earth system to the Heinrich event itself in different geographical locations. We consider the H1 event as the entire transition interval since 18 to 14.5 Kya. The main problem that arises is the uncertainty in the interpretation of the pollen assemblages due to their mixed nature, particularly the presence of both "warm" and "cold" pollen. We have compared the pollen signal from the beginning to the end of the H1 event along a tropic to subpolar transect, using data from our own studies and the published literature. We find that despite regional peculiarities, most of the pollen assemblages demonstrate a similar sequence of patterns. One of the most prominent common features, seen at the beginning and the end of H1, is the appearance of saw-tooth like shapes in the variables of the pollen diagram, independent of location, vegetation composition and other factors. The most noticeable "saw-tooth" occurs after H1, between about 14 and 12 Kya, the interval that roughly corresponds to the Bølling/Allerød. The common features of a "saw-tooth" for both the beginning and the end of the H1 event, appear in this order: 1) increase in ferns, usually coinciding with or followed by an increased percentage of conifer pollen. 2) The beginning of dominance of xerophyte assemblages, again as a "saw-tooth" which lasts for about 2 Kya. 3) Each "saw-tooth", no matter where it occurs, terminates with the beginning of an increase in arboreal (or steppe) vegetation. For all of the different sites, the isotopic evidence is that this was a period of warming, but the pollen records tell a more complex story. Despite the local individualities of

MEASURING TRANSIT SIGNAL RECOVERY IN THE KEPLER PIPELINE. I. INDIVIDUAL EVENTS

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

Christiansen, Jessie L.; Clarke, Bruce D.; Burke, Christopher J.

The Kepler mission was designed to measure the frequency of Earth-size planets in the habitable zone of Sun-like stars. A crucial component for recovering the underlying planet population from a sample of detected planets is understanding the completeness of that sample-the fraction of the planets that could have been discovered in a given data set that actually were detected. Here, we outline the information required to determine the sample completeness, and describe an experiment to address a specific aspect of that question, i.e., the issue of transit signal recovery. We investigate the extent to which the Kepler pipeline preserves individualmore » transit signals by injecting simulated transits into the pixel-level data, processing the modified pixels through the pipeline, and comparing the measured transit signal-to-noise ratio (S/N) to that expected without perturbation by the pipeline. We inject simulated transit signals across the full focal plane for a set of observations for a duration of 89 days. On average, we find that the S/N of the injected signal is recovered at MS = 0.9973({+-} 0.0012) Multiplication-Sign BS - 0.0151({+-} 0.0049), where MS is the measured S/N and BS is the baseline, or expected, S/N. The 1{sigma} width of the distribution around this correlation is {+-}2.64%. This indicates an extremely high fidelity in reproducing the expected detection statistics for single transit events, and provides teams performing their own periodic transit searches the confidence that there is no systematic reduction in transit signal strength introduced by the pipeline. We discuss the pipeline processes that cause the measured S/N to deviate significantly from the baseline S/N for a small fraction of targets; these are primarily the handling of data adjacent to spacecraft re-pointings and the removal of harmonics prior to the measurement of the S/N. Finally, we outline the further work required to characterize the completeness of the Kepler pipeline.« less

Early events in copper-ion catalyzed oxidation of α-synuclein.

PubMed

Tiwari, Manish K; Leinisch, Fabian; Sahin, Cagla; Møller, Ian Max; Otzen, Daniel E; Davies, Michael J; Bjerrum, Morten J

2018-04-22

Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu 2+ /H 2 O 2 /protein and Cu 2+ /H 2 O 2 /ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu 2+ /H 2 O 2 /protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15 min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu 2+ /H 2 O 2 -mediated damage, with carbonyl formation being a minor process. With the Cu 2+ /H 2 O 2 /ascorbate system, rapid protein carbonyl formation was detected with the first 5 min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu 2+ /H 2 O 2 /ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu 2+ /H 2 O 2 -induced α-synuclein modification. Copyright © 2018. Published by Elsevier Inc.

Remote monitoring of electromagnetic signals and seismic events using smart mobile devices

NASA Astrophysics Data System (ADS)

Georgiadis, Pantelis; Cavouras, Dionisis; Sidiropoulos, Konstantinos; Ninos, Konstantinos; Nomicos, Constantine

2009-06-01

This study presents the design and development of a novel mobile wireless system to be used for monitoring seismic events and related electromagnetic signals, employing smart mobile devices like personal digital assistants (PDAs) and wireless communication technologies such as wireless local area networks (WLANs), general packet radio service (GPRS) and universal mobile telecommunications system (UMTS). The proposed system enables scientists to access critical data while being geographically independent of the sites of data sources, rendering it as a useful tool for preliminary scientific analysis.

Detection of rain events in radiological early warning networks with spectro-dosimetric systems

NASA Astrophysics Data System (ADS)

Dąbrowski, R.; Dombrowski, H.; Kessler, P.; Röttger, A.; Neumaier, S.

2017-10-01

Short-term pronounced increases of the ambient dose equivalent rate, due to rainfall are a well-known phenomenon. Increases in the same order of magnitude or even below may also be caused by a nuclear or radiological event, i.e. by artificial radiation. Hence, it is important to be able to identify natural rain events in dosimetric early warning networks and to distinguish them from radiological events. Novel spectrometric systems based on scintillators may be used to differentiate between the two scenarios, because the measured gamma spectra provide significant nuclide-specific information. This paper describes three simple, automatic methods to check whether an dot H*(10) increase is caused by a rain event or by artificial radiation. These methods were applied to measurements of three spectrometric systems based on CeBr3, LaBr3 and SrI2 scintillation crystals, investigated and tested for their practicability at a free-field reference site of PTB.

Locating seismicity on the Arctic plate boundary using multiple-event techniques and empirical signal processing

NASA Astrophysics Data System (ADS)

Gibbons, S. J.; Harris, D. B.; Dahl-Jensen, T.; Kværna, T.; Larsen, T. B.; Paulsen, B.; Voss, P. H.

2017-12-01

The oceanic boundary separating the Eurasian and North American plates between 70° and 84° north hosts large earthquakes which are well recorded teleseismically, and many more seismic events at far lower magnitudes that are well recorded only at regional distances. Existing seismic bulletins have considerable spread and bias resulting from limited station coverage and deficiencies in the velocity models applied. This is particularly acute for the lower magnitude events which may only be constrained by a small number of Pn and Sn arrivals. Over the past two decades there has been a significant improvement in the seismic network in the Arctic: a difficult region to instrument due to the harsh climate, a sparsity of accessible sites (particularly at significant distances from the sea), and the expense and difficult logistics of deploying and maintaining stations. New deployments and upgrades to stations on Greenland, Svalbard, Jan Mayen, Hopen, and Bjørnøya have resulted in a sparse but stable regional seismic network which results in events down to magnitudes below 3 generating high-quality Pn and Sn signals on multiple stations. A catalogue of several hundred events in the region since 1998 has been generated using many new phase readings on stations on both sides of the spreading ridge in addition to teleseismic P phases. A Bayesian multiple event relocation has resulted in a significant reduction in the spread of hypocentre estimates for both large and small events. Whereas single event location algorithms minimize vectors of time residuals on an event-by-event basis, the Bayesloc program finds a joint probability distribution of origins, hypocentres, and corrections to traveltime predictions for large numbers of events. The solutions obtained favour those event hypotheses resulting in time residuals which are most consistent over a given source region. The relocations have been performed with different 1-D velocity models applicable to the Arctic region and

Observation of Long Ionospheric Recoveries from Lightning-induced Electron Precipitation Events

NASA Astrophysics Data System (ADS)

Mohammadpour Salut, M.; Cohen, M.

2015-12-01

Lightning strokes induces lower ionospheric nighttime disturbances which can be detected through Very Low Frequency (VLF) remote sensing via at least two means: (1) direct heating and ionization, known as an Early event, and (2) triggered precipitation of energetic electrons from the radiation belts, known as Lightning-induced Electron Precipitation (LEP). For each, the ionospheric recover time is typically a few minutes or less. A small class of Early events have been identified as having unusually long ionospheric recoveries (10s of minutes), with the underlying mechanism still in question. Our study shows for the first time that some LEP events also demonstrate unusually long recovery. The VLF events were detected by visual inspection of the recorded data in both the North-South and East-West magnetic fields. Data from the National Lightning Detection Network (NLDN) are used to determine the location and peak current of the lightning responsible for each lightning-associated VLF perturbation. LEP or Early VLF events are determined by measuring the time delay between the causative lightning discharges and the onset of all lightning-associated perturbations. LEP events typically possess an onset delay greater than ~ 200 msec following the causative lightning discharges, while the onset of Early VLF events is time-aligned (<20 msec) with the lightning return stroke. Nonducted LEP events are distinguished from ducted events based on the location of the causative lightning relative to the precipitation region. From 15 March to 20 April and 15 October to 15 November 2011, a total of 385 LEP events observed at Indiana, Montana, Colorado and Oklahoma VLF sites, on the NAA, NLK and NML transmitter signals. 46 of these events exhibited a long recovery. It has been found that the occurrence rate of ducted long recovery LEP events is higher than nonducted. Of the 46 long recovery LEP events, 33 events were induced by ducted whistlers, and 13 events were associated with

Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

PubMed

Ohta, Ken-Ichi; Suzuki, Shingo; Warita, Katsuhiko; Kaji, Tomohiro; Kusaka, Takashi; Miki, Takanori

2017-04-01

Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood. © 2017 International Society for Neurochemistry.

Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model

NASA Astrophysics Data System (ADS)

Boulton, Chris A.; Allison, Lesley C.; Lenton, Timothy M.

2014-12-01

The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached.

Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model

PubMed Central

Boulton, Chris A.; Allison, Lesley C.; Lenton, Timothy M.

2014-01-01

The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached. PMID:25482065

Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model.

PubMed

Boulton, Chris A; Allison, Lesley C; Lenton, Timothy M

2014-12-08

The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached.

Frontrunners of T cell activation: Initial, localized Ca2+ signals mediated by NAADP and the type 1 ryanodine receptor.

PubMed

Wolf, Insa M A; Diercks, Björn-Philipp; Gattkowski, Ellen; Czarniak, Frederik; Kempski, Jan; Werner, René; Schetelig, Daniel; Mittrücker, Hans-Willi; Schumacher, Valéa; von Osten, Manuel; Lodygin, Dimitri; Flügel, Alexander; Fliegert, Ralf; Guse, Andreas H

2015-10-13

The activation of T cells is the fundamental on switch for the adaptive immune system. Ca(2+) signaling is essential for T cell activation and starts as initial, short-lived, localized Ca(2+) signals. The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) forms rapidly upon T cell activation and stimulates early Ca(2+) signaling. We developed a high-resolution imaging technique using multiple fluorescent Ca(2+) indicator dyes to characterize these early signaling events and investigate the channels involved in NAADP-dependent Ca(2+) signals. In the first seconds of activation of either primary murine T cells or human Jurkat cells with beads coated with an antibody against CD3, we detected Ca(2+) signals with diameters close to the limit of detection and that were close to the activation site at the plasma membrane. In Jurkat cells in which the ryanodine receptor (RyR) was knocked down or in primary T cells from RyR1(-/-) mice, either these early Ca(2+) signals were not detected or the number of signals was markedly reduced. Local Ca(2+) signals observed within 20 ms upon microinjection of Jurkat cells with NAADP were also sensitive to RyR knockdown. In contrast, TRPM2 (transient receptor potential channel, subtype melastatin 2), a potential NAADP target channel, was not required for the formation of initial Ca(2+) signals in primary T cells. Thus, through our high-resolution imaging method, we characterized early Ca(2+) release events in T cells and obtained evidence for the involvement of RyR and NAADP in such signals. Copyright © 2015, American Association for the Advancement of Science.

Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

PubMed Central

Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

2016-01-01

T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

Event Rate for LISA Gravitational Wave Signals from Black Hole-Massive Black Hole Coalescences

NASA Technical Reports Server (NTRS)

Bender, Peter L.

2002-01-01

Earlier work under a previous grant had been mainly on investigating the event rate for coalescences of white dwarfs or neutron stars with massive black holes (MBHs) in galactic nuclei. Under the new grant, two studies were undertaken. One was an approximate extension of the earlier study to stellar mass black holes as the lighter object, with masses in the range of roughly 3 to 20 solar mass rather than about 1 solar mass. The other was an improved estimate of the confusion noise due to galactic binaries against which the signals from BH-MBH coalescences would have to be detected. In the earlier work, the mass of the white dwarfs (WDs) and neutron stars (NSs) was assumed to be about the same as that of the evolved stars in the density cusp around the galactic center MBH. However, with the BH mass being substantially larger, the sinking down of pHs toward the center (mass segregation) became important, and was included in the model. A single representative mass of 7 solar mass was used. The other main difference involved what happened after the compact object got scattered in close enough to the MBH to start losing appreciable energy and angular momentum by gravitational radiation. For WDs or NSs, it had been found in most cases that the object would be perturbed considerably by other stars in the cusp before much energy had been lost. Thus the angular momentum would either increase enough so that gravitational radiation would be cut off, or would decrease enough so that the WD or NS would plunge into the MBH in just a few revolutions. The latter event would mean that the signal-to noise ratio would not have time to build up, and the event would not be detectable. The ratio of gradual energy loss events to plunges was found to be roughly one to a few percent, and thus substantially decreased the expected rate of detectable events.

Signal mass and Ca²⁺ kinetics in local calcium events: a modeling study.

PubMed

Baran, Irina; Ganea, Constanta; Ungureanu, Raluca; Tofolean, Ioana Teodora

2012-02-01

We use a detailed modeling formalism based on numerical simulations of local calcium release events where the blurring of the image, the presence of diffusional barriers provided by large organelles situated close to the release site, as well as the variable position of the scan line with respect to the release site are taken into consideration. We have investigated the effect of the fluorescence noise fluctuations on the accuracy in computing the signal mass from linescan recordings and obtained a quantitative description of both the signal mass and the local increase in the free Ca(2+) level as a function of the release current, the release duration and the orientation of the scan line, for three different levels of noise magnitudes. The model could provide a very good fit to a wide set of available experimental data regarding the signal mass of puffs visualized by fluorescence microscopy in the Xenopus oocyte loaded with 40 μM Oregon Green-1 in the absence of the calcium chelator EGTA. Numerical simulations also predict the amplitude and the kinetics of calcium signals evolving in the absence of the indicator, and indicate that sub-maximal activation of IP(3) receptors could produce in average levels of about 2 μM and 0.4 μM free Ca(2+) close to a release site located in the animal or in the vegetal hemisphere, respectively, whereas the maximal levels reached in more rare events could be 11 μM and 4 μM, respectively.

Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.

PubMed

Ji, Chengyuan; Chen, Gang

2016-01-01

The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.

Early intracellular signaling events induced by in vitro metreleptin administration in cardiac myocytes and uterine smooth muscle cells.

PubMed

Choi, S K; Park, S; Choi, Y; Moon, H-S

2015-08-05

Intracellular signaling pathways regulated by leptin have largely been studied in metabolically important organs such as adipose tissue and peripheral blood mononuclear cells, suggesting that leptin plays a key role in pathophysiology of insulin resistance. However, whether synthetic analog of leptin, metreleptin, has similar effects on cardiac myocytes (CM) and uterine smooth muscle cells (USMC) has not yet been studied. Hence, in order to address these questions, we extended previous observations and investigated in vitro signaling study whether metreleptin may activate key signaling pathways. We observed that metreleptin activates Jak2 and STAT3 signaling pathways in dose- and time-dependent manner in CM and USMC. Also, we found that metreleptin increases ERK1/2, JNK and/or p38 phosphorylation in CM. In vitro metreleptin administration also increased ERK1/2 and/or p38 phosphorylation in USMC. By contrast, JNK was not regulated by in vitro metreleptin administration in USMC. Moreover, metreleptin-activated all signaling pathways were blocked by pre-treatment of PD98095 (ERK inhibitor), SB203580 (p38 inhibitor) and/or SP600125 (JNK inhibitor), respectively. Finally, metreleptin increased cell size (hypertrophy) in both CM and USMC. Our data provide novel insights into the role of Jak2, STAT3, ERK1/2, JNK and/or p38 as probable mediators of the action of leptin in regulating hypertrophy in CM and USMC.

A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

PubMed

Thrower, Edwin C; Yuan, Jingzhen; Usmani, Ashar; Liu, Yannan; Jones, Courtney; Minervini, Samantha N; Alexandre, Martine; Pandol, Stephen J; Guha, Sushovan

2011-01-01

Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.

Privacy-preserving discovery of topic-based events from social sensor signals: an experimental study on Twitter.

PubMed

Nguyen, Duc T; Jung, Jai E

2014-01-01

Social network services (e.g., Twitter and Facebook) can be regarded as social sensors which can capture a number of events in the society. Particularly, in terms of time and space, various smart devices have improved the accessibility to the social network services. In this paper, we present a social software platform to detect a number of meaningful events from information diffusion patterns on such social network services. The most important feature is to process the social sensor signal for understanding social events and to support users to share relevant information along the social links. The platform has been applied to fetch and cluster tweets from Twitter into relevant categories to reveal hot topics.

High-Performance Signal Detection for Adverse Drug Events using MapReduce Paradigm.

PubMed

Fan, Kai; Sun, Xingzhi; Tao, Ying; Xu, Linhao; Wang, Chen; Mao, Xianling; Peng, Bo; Pan, Yue

2010-11-13

Post-marketing pharmacovigilance is important for public health, as many Adverse Drug Events (ADEs) are unknown when those drugs were approved for marketing. However, due to the large number of reported drugs and drug combinations, detecting ADE signals by mining these reports is becoming a challenging task in terms of computational complexity. Recently, a parallel programming model, MapReduce has been introduced by Google to support large-scale data intensive applications. In this study, we proposed a MapReduce-based algorithm, for common ADE detection approach, Proportional Reporting Ratio (PRR), and tested it in mining spontaneous ADE reports from FDA. The purpose is to investigate the possibility of using MapReduce principle to speed up biomedical data mining tasks using this pharmacovigilance case as one specific example. The results demonstrated that MapReduce programming model could improve the performance of common signal detection algorithm for pharmacovigilance in a distributed computation environment at approximately liner speedup rates.

Molecular Steps in the Immune Signaling Pathway Evoked by Plant Elicitor Peptides: Ca2+-Dependent Protein Kinases, Nitric Oxide, and Reactive Oxygen Species Are Downstream from the Early Ca2+ Signal1[OPEN

PubMed Central

Ma, Yi; Zhao, Yichen; Walker, Robin K.; Berkowitz, Gerald A.

2013-01-01

Endogenous plant elicitor peptides (Peps) can act to facilitate immune signaling and pathogen defense responses. Binding of these peptides to the Arabidopsis (Arabidopsis thaliana) plasma membrane-localized Pep receptors (PEPRs) leads to cytosolic Ca2+ elevation, an early event in a signaling cascade that activates immune responses. This immune response includes the amplification of signaling evoked by direct perception of pathogen-associated molecular patterns by plant cells under assault. Work included in this report further characterizes the Pep immune response and identifies new molecular steps in the signal transduction cascade. The PEPR coreceptor BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 contributes to generation of the Pep-activated Ca2+ signal and leads to increased defense gene expression and resistance to a virulent bacterial pathogen. Ca2+-dependent protein kinases (CPKs) decode the Ca2+ signal, also facilitating defense gene expression and enhanced resistance to the pathogen. Nitric oxide and reduced nicotinamide adenine dinucleotide phosphate oxidase-dependent reactive oxygen species generation (due to the function of Respiratory Burst Oxidase Homolog proteins D and F) are also involved downstream from the Ca2+ signal in the Pep immune defense signal transduction cascade, as is the case with BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 and CPK5, CPK6, and CPK11. These steps of the pathogen defense response are required for maximal Pep immune activation that limits growth of a virulent bacterial pathogen in the plant. We find a synergism between function of the PEPR and Flagellin Sensing2 receptors in terms of both nitric oxide and reactive oxygen species generation. Presented results are also consistent with the involvement of the secondary messenger cyclic GMP and a cyclic GMP-activated Ca2+-conducting channel in the Pep immune signaling pathway. PMID:24019427

Analysis of signal transduction in cell-free extracts and rafts of Xenopus eggs.

PubMed

Tokmakov, Alexander A; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo

2010-05-01

Intracellular signaling during egg activation/fertilization has been extensively studied using intact eggs, which can be manipulated by microinjection of different mRNAs, proteins, or chemical drugs. Furthermore, egg extracts, which retain high CSF activity (CSF-arrested extracts), were developed for studying fertilization/activation signal transduction, which have significant advantages as a model system. The addition of calcium to CSF-arrested extracts initiates a plethora of signaling events that take place during egg activation. Hence, the signaling downstream of calcium mobilization has been successfully studied in the egg extracts. Moreover, despite disruption of membrane-associated signaling compartments and ordered compartmentalization during extract preparation, CSF-arrested extracts can be successfully used to study early signaling events, which occur upstream of calcium release during egg activation/fertilization. In combination with the CSF-arrested extracts, activated egg rafts can reproduce some events of egg activation, including PLCgamma activation, IP3 production, transient calcium release, MAPK inactivation, and meiotic exit. This becomes possible due to complementation of the sperm-induced egg activation signaling machinery present in the rafts with the components of signal transduction system localized in the extracts. Herein, we describe protocols for studying molecular mechanisms of egg fertilization/activation using cell-free extracts and membrane rafts prepared from metaphase-arrested Xenopus eggs.

Event sequence detector

NASA Technical Reports Server (NTRS)

Hanna, M. F. (Inventor)

1973-01-01

An event sequence detector is described with input units, each associated with a row of bistable elements arranged in an array of rows and columns. The detector also includes a shift register which is responsive to clock pulses from any of the units to sequentially provide signals on its output lines each of which is connected to the bistable elements in a corresponding column. When the event-indicating signal is received by an input unit it provides a clock pulse to the shift register to provide the signal on one of its output lines. The input unit also enables all its bistable elements so that the particular element in the column supplied with the signal from the register is driven to an event-indicating state.

Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

PubMed

Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

2008-02-01

Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

Not Just the 8.2 event: Dynamic Early Holocene Climate in Arctic Canada

NASA Astrophysics Data System (ADS)

Axford, Y.; Briner, J. P.; Miller, G. H.; Francis, D. R.

2006-12-01

Temperature reconstructions from a lake in the eastern Canadian Arctic indicate that peak warmth in the early Holocene was interrupted by two abrupt, short-lived temperature reversals at ~9.l and ~8.5 ka. Summer temperatures at Lake CF8, Baffin Island (~500 km west of Greenland) are inferred from subfossil midge (Chironomidae) assemblages. Our results indicate that the site, like others on Baffin Island, experienced exceptionally warm summers (almost 5°C warmer than present) through much of the early Holocene, presumably in response to enhanced summer insolation. After 1000 years of very warm, stable climate, warmth was interrupted by two discrete cold reversals at ~9.1 and ~8.5 ka, during which multiple cold-stenothermous midge taxa appeared in the lake and summer temperatures dropped more than 3°C. These two clearly-defined reversals, well beyond the range of background variability, were of similar amplitude and duration, and were separated by several centuries of near-peak warmth. The only Holocene events of comparable amplitude at this site are the rapid onset of Holocene warmth, and the more gradual Neoglacial cooling after 8 ka. Abrupt cooling events over the Baffin region are consistent with model simulations of the impacts of freshwater outbursts into the Labrador Sea, such as the Lake Agassiz outburst flood that occurred ~8.4 ka. That there are two discrete events recorded at this site indicates that the "8.2 event" was not uniquely significant in this region; rather, the period between approximately ~9.2 and 8 ka was characterized by repeated climate fluctuations forced by multiple outburst floods or other mechanisms. Thus global correlations among paleoclimate records need not assume that climate perturbations during this time period necessarily correlate with the draining of Lake Agassiz or the 8.2 ka cooling in central Greenland.

Slow slip events in the early part of the earthquake cycle

NASA Astrophysics Data System (ADS)

Voss, Nicholas K.; Malservisi, Rocco; Dixon, Timothy H.; Protti, Marino

2017-08-01

In February 2014 a Mw = 7.0 slow slip event (SSE) took place beneath the Nicoya Peninsula, Costa Rica. This event occurred 17 months after the 5 September 2012, Mw = 7.6, earthquake and along the same subduction zone segment, during a period when significant postseismic deformation was ongoing. A second SSE occurred in the middle of 2015, 21 months after the 2014 SSE and 38 months after the earthquake. The recurrence interval for Nicoya SSEs was unchanged by the earthquake. However, the spatial distribution of slip for the 2014 event differed significantly from previous events, having only deep ( 40 km) slip, compared to previous events, which had both deep and shallow slip. The 2015 SSE marked a return to the combination of deep plus shallow slip of preearthquake SSEs. However, slip magnitude in 2015 was nearly twice as large (Mw = 7.2) as preearthquake SSEs. We employ Coulomb Failure Stress change modeling in order to explain these changes. Stress changes associated with the earthquake and afterslip were highest near the shallow portion of the megathrust, where preearthquake SSEs had significant slip. Lower stress change occurred on the deeper parts of the plate interface, perhaps explaining why the deep ( 40 km) region for SSEs remained unchanged. The large amount of shallow slip in the 2015 SSE may reflect lack of shallow slip in the prior SSE. These observations highlight the variability of aseismic strain release rates throughout the earthquake cycle.