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Sample records for activity transiently contributes

  1. Transient receptor potential A1 channel contributes to activation of the muscle reflex.

    Koba, Satoshi; Hayes, Shawn G; Sinoway, Lawrence I

    2011-01-01

    This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.

  2. Quantification of metabolically active transient storage (MATS) in two reaches with contrasting transient storage and ecosystem respiration

    Alba Argerich; Roy Haggerty; Eugènia Martí; Francesc Sabater; Jay. Zarnetske

    2011-01-01

    Water transient storage zones are hotspots for metabolic activity in streams although the contribution of different types of transient storage zones to the whole�]reach metabolic activity is difficult to quantify. In this study we present a method to measure the fraction of the transient storage that is metabolically active (MATS) in two consecutive reaches...

  3. Contribution of EEG in transient neurological deficits.

    Lozeron, Pierre; Tcheumeni, Nadine Carole; Turki, Sahar; Amiel, Hélène; Meppiel, Elodie; Masmoudi, Sana; Roos, Caroline; Crassard, Isabelle; Plaisance, Patrick; Benbetka, Houria; Guichard, Jean-Pierre; Houdart, Emmanuel; Baudoin, Hélène; Kubis, Nathalie

    2018-01-01

    Identification of stroke mimics and 'chameleons' among transient neurological deficits (TND) is critical. Diagnostic workup consists of a brain imaging study, for a vascular disease or a brain tumour and EEG, for epileptiform discharges. The precise role of EEG in this diagnostic workup has, however, never been clearly delineated. However, this could be crucial in cases of atypical or incomplete presentation with consequences on disease management and treatment. We analysed the EEG patterns on 95 consecutive patients referred for an EEG within 7 days of a TND with diagnostic uncertainty. Patients were classified at the discharge or the 3-month follow-up visit as: 'ischemic origin', 'migraine aura', 'focal seizure', and 'other'. All patients had a brain imaging study. EEG characteristics were correlated to the TND symptoms, imaging study, and final diagnosis. Sixty four (67%) were of acute onset. Median symptom duration was 45 min. Thirty two % were 'ischemic', 14% 'migraine aura', 19% 'focal seizure', and 36% 'other' cause. EEGs were recorded with a median delay of 1.6 day after symptoms onset. Forty EEGs (42%) were abnormal. Focal slow waves were the most common finding (43%), also in the ischemic group (43%), whether patients had a typical presentation or not. Epileptiform discharges were found in three patients, one with focal seizure and two with migraine aura. Non-specific EEG focal slowing is commonly found in TND, and may last several days. We found no difference in EEG presentation between stroke mimics and stroke chameleons, and between other diagnoses.

  4. Transient contribution of left posterior parietal cortex to cognitive restructuring.

    Sutoh, Chihiro; Matsuzawa, Daisuke; Hirano, Yoshiyuki; Yamada, Makiko; Nagaoka, Sawako; Chakraborty, Sudesna; Ishii, Daisuke; Matsuda, Shingo; Tomizawa, Haruna; Ito, Hiroshi; Tsuji, Hiroshi; Obata, Takayuki; Shimizu, Eiji

    2015-03-17

    Cognitive restructuring is a fundamental method within cognitive behavioural therapy of changing dysfunctional beliefs into flexible beliefs and learning to react appropriately to the reality of an anxiety-causing situation. To clarify the neural mechanisms of cognitive restructuring, we designed a unique task that replicated psychotherapy during a brain scan. The brain activities of healthy male participants were analysed using functional magnetic resonance imaging. During the brain scan, participants underwent Socratic questioning aimed at cognitive restructuring regarding the necessity of handwashing after using the restroom. The behavioural result indicated that the Socratic questioning effectively decreased the participants' degree of belief (DOB) that they must wash their hands. Alterations in the DOB showed a positive correlation with activity in the left posterior parietal cortex (PPC) while the subject thought about and rated own belief. The involvement of the left PPC not only in planning and decision-making but also in conceptualization may play a pivotal role in cognitive restructuring.

  5. Japanese contributions to IAEA INTOR workshop, phase two A, part 2, chapter V: transient electromagnetics

    Kasai, Masao; Niikura, Setsuo; Ueda, Koju

    1985-07-01

    This report corresponds to Chapter V of Japanese contribution report to IAEA INTOR Workshop, Phase Two A, Part 2. Simulation results are shown for feedback control of plasma position, electromagnetic forces at disruptions, penetration of electric and magnetic fields, and benchmark tests for transient electromagnetics. Design guide lines for feedback control system and database assessments are also reported. (author)

  6. Relative contributions of transient and steady state infiltration during ephemeral streamflow

    Blasch, Kyle W.; Ferré, Ty P.A.; Hoffmann, John P.; Fleming, John B.

    2006-01-01

    Simulations of infiltration during three ephemeral streamflow events in a coarse‐grained alluvial channel overlying a less permeable basin‐fill layer were conducted to determine the relative contribution of transient infiltration at the onset of streamflow to cumulative infiltration for the event. Water content, temperature, and piezometric measurements from 2.5‐m vertical profiles within the alluvial sediments were used to constrain a variably saturated water flow and heat transport model. Simulated and measured transient infiltration rates at the onset of streamflow were about two to three orders of magnitude greater than steady state infiltration rates. The duration of simulated transient infiltration ranged from 1.8 to 20 hours, compared with steady state flow periods of 231 to 307 hours. Cumulative infiltration during the transient period represented 10 to 26% of the total cumulative infiltration, with an average contribution of approximately 18%. Cumulative infiltration error for the simulated streamflow events ranged from 9 to 25%. Cumulative infiltration error for typical streamflow events of about 8 hours in duration in is about 90%. This analysis indicates that when estimating total cumulative infiltration in coarse‐grained ephemeral stream channels, consideration of the transient infiltration at the onset of streamflow will improve predictions of the total volume of infiltration that may become groundwater recharge.

  7. Contribution of Anticipated Transients Without Scram (ATWS) to core melt at United States nuclear power plants

    Giachetti, R.T.

    1989-09-01

    This report looks at WASH-1400 and several other Probabilistic Risk Assessments (PRAs) and Probabilistic Safety Studies (PSSs) to determine the contribution of Anticipated Transients Without Scram (ATWS) events to the total core melt probability at eight nuclear power plants in the United States. After considering each plant individually, the results are compared from plant to plant to see if any generic conclusions regarding ATWS, or core melt in general, can be made. 8 refs., 34 tabs

  8. Hematopoietic stem cell development requires transient Wnt/β-catenin activity

    Ruiz-Herguido, Cristina; Guiu, Jordi; D'Altri, Teresa

    2012-01-01

    in the aorta-gonad-mesonephros (AGM) region. We show here that β-catenin is nuclear and active in few endothelial nonhematopoietic cells closely associated with the emerging hematopoietic clusters of the embryonic aorta during mouse development. Importantly, Wnt/β-catenin activity is transiently required...... of mutant cells toward the hematopoietic lineage; however, these mutant cells still contribute to the adult endothelium. Together, those findings indicate that Wnt/β-catenin activity is needed for the emergence but not the maintenance of HSCs in mouse embryos....

  9. Global thunderstorm activity estimation based on number of transients in ELF-band

    Ondraskova, Adriena; Sevcik, Sebastian

    2017-04-01

    Schumann resonances (SR) are resonant electromagnetic oscillations in extremely low frequency band (ELF, 3 Hz - 3 kHz), which arise in the Earth-ionosphere cavity due to lightning activity in planetary range. The time records in the ELF-band consist of background signals and ELF transients/Q-bursts superimposed on the background exceeding it by a factor of 5 - 10. The former are produced by the common worldwide thunderstorm activity (100 - 150 events per second), the latter origin from individual intense distant lightning discharges (100 - 120 powerful strokes per hour). A Q-burst is produced by a combination of direct and antipodal pulses and the decisive factor for its shape follows from the source-to-observer distance. Diurnal/seasonal variations of global thunderstorm activity can be deduced from spectral amplitudes of SR modes. Here we focus on diurnal/seasonal variations of the number of ELF-transients assuming that it is another way of lightning activity estimation. To search for transients, our own code was applied to the SR vertical electric component measured in October 2004 - October 2008 at the Astronomical and Geophysical Observatory of FMPI CU, Slovakia. Criteria for the identification of the burst are chosen on the basis of the transient amplitudes and their morphological features. Monthly mean daily variations in number of transients showed that African focus dominates at 14 - 16 h UT and it is more active in comparison with Asian source, which dominates at 5 - 8 h UT in dependence on winter or summer month. American source had surprisingly slight response. Meteorological observations in South America aiming to determine lightning hotspots on the Earth indicate that flash rate in this region is greatest during nocturnal 0 h - 3 h local standard time. This fact may be interpreted that Asian and South American sources contribute together in the same UT. Cumulative spectral amplitude of the first three SR modes compared with number of ELF-transients in

  10. The Zwicky Transient Facility: Overview and Commissioning Activities

    Graham, Matthew; Zwicky Transient Facility (ZTF) Project Team

    2018-01-01

    The Zwicky Transient Facility (ZTF) is the first of a new generation of LSST-scope sky surveys to be realized. It will employ a 47 square degree field-of-view camera mounted on the Samuel Oschin 48-inch Schmidt telescope at Palomar Observatory to scan more than 3750 square degrees an hour to a depth of 20.5 – 21 mag. This will lead to unprecedented discovery rates for transients – a young supernova less than 24 hours after its explosion each night as well as rarer and more exotic sources. Repeated imaging of the Northern sky (including the Galactic Plane) will produce a photometric variability catalog with nearly 300 observations each year, ideal for studies of variable stars, binaries, AGN, and asteroids. ZTF represents a significant increase in scale relative to previous surveys in terms of both data volume and data complexity. It will be the first survey to produce one million alerts a night and the first to have a trillion row data archive. We will present an overview of the survey and its challenges and describe recent commissioning activities.

  11. Transient extracellular application of gold nanostars increases hippocampal neuronal activity.

    Salinas, Kirstie; Kereselidze, Zurab; DeLuna, Frank; Peralta, Xomalin G; Santamaria, Fidel

    2014-08-20

    With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties. We synthesized star shaped gold nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse hippocampal slices while recording the action potentials from single neurons in the CA3 region. Our results show that CA3 hippocampal neurons increase their firing rate by 17% after the application of gold nanostars. The increase in excitability lasted for as much as 50 minutes after a transient 5 min application of the nanoparticles. Further analyses of the action potential shape and computational modeling suggest that nanoparticles block potassium channels responsible for the repolarization of the action potentials, thus allowing the cell to increase its firing rate. Our results show that gold nanoparticles can affect the coding properties of neurons by modifying their excitability.

  12. Transient flows of the solar wind associated with small-scale solar activity in solar minimum

    Slemzin, Vladimir; Veselovsky, Igor; Kuzin, Sergey; Gburek, Szymon; Ulyanov, Artyom; Kirichenko, Alexey; Shugay, Yulia; Goryaev, Farid

    The data obtained by the modern high sensitive EUV-XUV telescopes and photometers such as CORONAS-Photon/TESIS and SPHINX, STEREO/EUVI, PROBA2/SWAP, SDO/AIA provide good possibilities for studying small-scale solar activity (SSA), which is supposed to play an important role in heating of the corona and producing transient flows of the solar wind. During the recent unusually weak solar minimum, a large number of SSA events, such as week solar flares, small CMEs and CME-like flows were observed and recorded in the databases of flares (STEREO, SWAP, SPHINX) and CMEs (LASCO, CACTUS). On the other hand, the solar wind data obtained in this period by ACE, Wind, STEREO contain signatures of transient ICME-like structures which have shorter duration (<10h), weaker magnetic field strength (<10 nT) and lower proton temperature than usual ICMEs. To verify the assumption that ICME-like transients may be associated with the SSA events we investigated the number of weak flares of C-class and lower detected by SPHINX in 2009 and STEREO/EUVI in 2010. The flares were classified on temperature and emission measure using the diagnostic means of SPHINX and Hinode/EIS and were confronted with the parameters of the solar wind (velocity, density, ion composition and temperature, magnetic field, pitch angle distribution of the suprathermal electrons). The outflows of plasma associated with the flares were identified by their coronal signatures - CMEs (only in few cases) and dimmings. It was found that the mean parameters of the solar wind projected to the source surface for the times of the studied flares were typical for the ICME-like transients. The results support the suggestion that weak flares can be indicators of sources of transient plasma flows contributing to the slow solar wind at solar minimum, although these flows may be too weak to be considered as separate CMEs and ICMEs. The research leading to these results has received funding from the European Union’s Seventh Programme

  13. Separation of transient and oscillatory cerebral activities using over-complete rational dilation wavelet transforms

    Chaibi, S.; Lajnef, T.; Samet, M.; Kachouri, A.

    2011-01-01

    Many natural signals EEG are comprised frequency overlapping of oscillatory and transient components. In our study the intracranial EEG signals of epilepsy are composed of the superposition of oscillatory signals (HFOs: High Frequency oscillations) and a transient signals (spikes and sharp waves, etc.). The oscillatory components (HFOs) exist in the frequency band 80-500Hz. The transient components comes from nonrhythmic brain activities (spikes, sharp waves and vertex waves of varying amplitude, shape and duration) and cover a continuous wide bandwidth from low to high frequencies and resemble an HFOs events when filtered using a band pass classical filter. The classical filtering methods based on FIR filters, Wavelet transforms and the Matching Pursuit cannot separate the oscillatory from transient activities. This paper describes an approach for decomposing an iEEG signals of epilepsy into the sum of oscillatory components and a transient components based on overcomplete rational dilation wavelet transforms (overcomplete RADWT) in conjunction with morphological component analysis (MCA).

  14. Contribution to the theoretical study of transient two-phase flows

    Achard, J.L.

    1978-12-01

    The work presented in this paper has been given rise from the existence of violent boiling phenomena of the coolant that have been revealed by reactor safety studies with water and sodium. The aim as to describe in a basic mammer, one of these phenomena called ''chugging'' or ''choucage''. The experimental part of this work concerns two original works concerning the temperature measurement at the wall; a device is proposed to evaluate the contact resistance and the thermal inertia of the thermocouple; from the measurements that have been obtained, the flux the wall transfers to the flow and the temperature of the internal wall surface are deduced. A statistical method is developed for dispersed two-phase flow study, to establish: 1) a mass transfer law, 2) a law of change of the flow configuration. The proposed model contains: 1) for the dispersed phase (vapor bubbles), the basic momentum transport equations; 2) for the continuous phase (liquid), the transport equations of the classical formulation. The statistical formulation introduces the interaction phenomenon between the phases before applying the operation of the average (homogenization method); it allows to introduce the coalescence phenomena of bubbles. Finally, structures of exchange laws for transient laminar flows are proposed: transient linear momentum exchange law; possible structures of heat exchange laws [fr

  15. Increased cross-bridge recruitment contributes to transient increase in force generation beyond maximal capacity in human myocardium.

    Milani-Nejad, Nima; Chung, Jae-Hoon; Canan, Benjamin D; Fedorov, Vadim V; Whitson, Bryan A; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2018-01-01

    Cross-bridge attachment allows force generation to occur, and rate of tension redevelopment (k tr ) is a commonly used index of cross-bridge cycling rate. Tension overshoots have been observed briefly after a slack-restretch k tr maneuver in various species of animal models and humans. In this study, we set out to determine the properties of these overshoots and their possible underlying mechanism. Utilizing human cardiac trabeculae, we have found that tension overshoots are temperature-dependent and that they do not occur at resting states. In addition, we have found that myosin cross-bridge cycle is vital to these overshoots as inhibition of the cycle results in the blunting of the overshoots and the magnitude of the overshoots are dependent on the level of myofilament activation. Lastly, we show that the number of cross-bridges transiently increase during tension overshoots. These findings lead us to conclude that tension overshoots are likely due to a transient enhancement of the recruitment of myosin heads into the cross-bridge cycling, regulated by the myocardium, and with potential physiological significance in determining cardiac output. We show that isolated human myocardium is capable of transiently increasing its maximal force generation capability by increasing cross-bridge recruitment following slack-restretch maneuver. This process can potentially have important implications and significance in cardiac contraction in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Role of Active Listening and Listening Effort on Contralateral Suppression of Transient Evoked Otoacousic Emissions

    Kalaiah, Mohan Kumar; Theruvan, Nikhitha B; Kumar, Kaushlendra; Bhat, Jayashree S

    2017-01-01

    Background and Objectives The present study aimed to investigate the effect of active listening and listening effort on the contralateral suppression of transient evoked otoacoustic emissions (CSTEOAEs). Subjects and Methods Twenty eight young adults participated in the study. Transient evoked otoacoustic emissions (TEOAEs) were recorded using ?linear? clicks at 60 dB peSPL, in three contralateral noise conditions. In condition 1, TEOAEs were obtained in the presence of white noise in the con...

  17. Evidence for two distinct defects contributing to the H4 deep-level transient spectroscopy peak in electron-irradiated InP

    Darwich, R.; Massarani, B.; Kaaka, M.; Awad, F.

    2000-01-01

    Deep-level transient spectroscopy (DLTS) has been used to study the dominant deep-level H4 produced in InP by electron irradiation. The characteristics of the H4 peak in Zn-doped Inp has been studied as a function of pulse duration (t p ) before and after annealing. The results show that at least two traps contribute to the H4 peak: one is a fast trap (labeled H4 f ) and the other is a show trap (labeled H4 s ). This is show through several results concerning the activation energy, the capture cross section, the full width at half-maximum, and the peak temperature shift. It is shown that both traps are irradiation defects created in P sublattice. (authors)

  18. Concurrent Transient Activation of Wnt/β-Catenin Pathway Prevents Radiation Damage to Salivary Glands

    Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu; Boyer, Arthur; Liu, Fei

    2012-01-01

    Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/β-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/β-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/β-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/β-catenin pathway could prevent radiation-induced salivary gland dysfunction.

  19. Concurrent Transient Activation of Wnt/{beta}-Catenin Pathway Prevents Radiation Damage to Salivary Glands

    Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States); Boyer, Arthur [Department of Radiology, Scott and White Hospital, Temple, Texas (United States); Liu, Fei, E-mail: fliu@medicine.tamhsc.edu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States)

    2012-05-01

    Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/{beta}-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/{beta}-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/{beta}-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/{beta}-catenin pathway could prevent radiation-induced salivary gland dysfunction.

  20. Transient stress control of aeroengine disks based on active thermal management

    Ding, Shuiting; Wang, Ziyao; Li, Guo; Liu, Chuankai; Yang, Liu

    2016-01-01

    Highlights: • The essence of cooling in turbine system is a process of thermal management. • Active thermal management is proposed to control transient stress of disks. • The correlation between thermal load and transient stress of disks is built. • Stress level can be declined by actively adjusting the thermal load distribution. • Artificial temperature gradient can be used to counteract stress from rotating. - Abstract: The physical essence of cooling in the turbine system is a process of thermal management. In order to overcome the limits of passive thermal management based on thermal protection, the concept of active thermal management based on thermal load redistribution has been proposed. On this basis, this paper focuses on a near real aeroengine disk during a transient process and studies the stress control mechanism of active thermal management in transient conditions by a semi-analytical method. Active thermal management is conducted by imposing extra heating energy on the disk hub, which is represented by the coefficient of extra heat flow η. The results show that the transient stress level can be effectively controlled by actively adjusting the thermal load distribution. The decline ratio of the peak equivalent stress of the disk hub can be 9.0% for active thermal management load condition (η = 0.2) compared with passive condition (η = 0), even at a rotation speed of 10,000 r/min. The reason may be that the temperature distribution of the disk turns into an artificial V-shape because of the extra heating energy on the hub, and the resulting thermal stresses induced by the negative temperature gradients counteract parts of the stress from rotating.

  1. Quantitative Measurement of Physical Activity in Acute Ischemic Stroke and Transient Ischemic Attack

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2014-01-01

    BACKGROUND AND PURPOSE: The purpose of this study was to quantitatively measure and describe the amount and pattern of physical activity in patients within the first week after acute ischemic stroke and transient ischemic attack using accelerometers. METHODS: A total of 100 patients with acute is...

  2. Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle

    Calloe, Kirstine; Soltysinska, Ewa; Jespersen, Thomas

    2009-01-01

    To examine the electrophysiological and molecular properties of the transient outward current (I(to)) in canine left ventricle using a novel I(to) activator, NS5806, I(to) was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp tech...

  3. Corticospinal contribution to arm muscle activity during human walking

    Barthélemy, Dorothy; Nielsen, Jens Bo

    2010-01-01

    inhibitory interneurones, the suppression is in all likelihood caused by removal of a corticospinal contribution to the ongoing EMG activity. The data thus suggest that the motor cortex makes an active contribution, through the corticospinal tract, to the ongoing EMG activity in arm muscles during walking....

  4. Indian Contribution to IPY Outreach Activities

    Tiwari, M.; Ravindra, R.

    2007-12-01

    India is involved in a major way in both the aspects, i.e. scientific as well as outreach activities, of the International Polar Year (IPY) 2007-2008. National Centre for Antarctic & Ocean Research (NCAOR, under the Ministry of Earth Sciences, Government of India) is acting as the national coordinating agency. The launching of the Indian chapter of the IPY 2007-2008 took place at NCAOR and parallely at Jawaharlal Nehru National University (JNU), New Delhi on 1st March 2007. Two Indian scientific proposals have been endorsed by IPY, which are Project id. 70 and Project id. 129. Simultaneously, India is actively involved in the outreach activities related to IPY. NCAOR had sponsored the visit of two college students to Antarctica during the 25th Indian Antarctic Expedition (IAE). A series of lectures were delivered by one of them at more than twenty schools & colleges in the rural & suburban areas of Indian state of Maharashtra regarding the wonders of Antarctica to educate the general public and popularize polar science. NCAOR is the only Indian institute that has the capability to store and sample Antarctic ice core with special Cold Room facility that is maintained at -20°C. Students from several schools and colleges and scientists/visitors from various Indian institutes/foreign countries have visited NCAOR to get first hand experience of polar research. NCAOR has also collaborated with WWF-India (World Wide Fund for Nature) for carrying out the outreach activities to schools throughout the vast expanses of India. In this regard a calendar of event was released on 1st March 2007, which lists various competitions and activities that will be held during 2007-2008. It includes competitions such as poster & model making, stamp designing, petition writing etc. for school children. The first competition, poster making & slogan writing, was held at New Delhi on April 10, 2007 and prizes were distributed by the H'ble Minister of Science & Technology and Earth Sciences on

  5. CONNECTING FLARES AND TRANSIENT MASS-LOSS EVENTS IN MAGNETICALLY ACTIVE STARS

    Osten, Rachel A. [Space Telescope Science Institute 3700 San Martin Drive, Baltimore, MD 21218 (United States); Wolk, Scott J., E-mail: osten@stsci.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge MA 02138 (United States)

    2015-08-10

    We explore the ramification of associating the energetics of extreme magnetic reconnection events with transient mass-loss in a stellar analogy with solar eruptive events. We establish energy partitions relative to the total bolometric radiated flare energy for different observed components of stellar flares and show that there is rough agreement for these values with solar flares. We apply an equipartition between the bolometric radiated flare energy and kinetic energy in an accompanying mass ejection, seen in solar eruptive events and expected from reconnection. This allows an integrated flare rate in a particular waveband to be used to estimate the amount of associated transient mass-loss. This approach is supported by a good correspondence between observational flare signatures on high flaring rate stars and the Sun, which suggests a common physical origin. If the frequent and extreme flares that young solar-like stars and low-mass stars experience are accompanied by transient mass-loss in the form of coronal mass ejections, then the cumulative effect of this mass-loss could be large. We find that for young solar-like stars and active M dwarfs, the total mass lost due to transient magnetic eruptions could have significant impacts on disk evolution, and thus planet formation, and also exoplanet habitability.

  6. Limited recovery of soil microbial activity after transient exposure to gasoline vapors

    Modrzyński, Jakub J.; Christensen, Jan H.; Mayer, Philipp

    2016-01-01

    During gasoline spills complex mixtures of toxic volatile organic compounds (VOCs) are released to terrestrial environments. Gasoline VOCs exert baseline toxicity (narcosis) and may thus broadly affect soil biota. We assessed the functional resilience (i.e. resistance and recovery of microbial...... functions) in soil microbial communities transiently exposed to gasoline vapors by passive dosing via headspace for 40 days followed by a recovery phase of 84 days. Chemical exposure was characterized with GC-MS, whereas microbial activity was monitored as soil respiration (CO2 release) and soil bacterial...... microbial activity indicating residual soil toxicity, which could not be attributed to BTEX, but rather to mixture toxicity of more persistent gasoline constituents or degradation products. Our results indicate a limited potential for functional recovery of soil microbial communities after transient...

  7. Heavy Ion Transient Characterization of a Photobit Hardened-by-Design Active Pixel Sensor Array

    Marshall, Paul W.; Byers, Wheaton B.; Conger, Christopher; Eid, El-Sayed; Gee, George; Jones, Michael R.; Marshall, Cheryl J.; Reed, Robert; Pickel, Jim; Kniffin, Scott

    2002-01-01

    This paper presents heavy ion data on the single event transient (SET) response of a Photobit active pixel sensor (APS) four quadrant test chip with different radiation tolerant designs in a standard 0.35 micron CMOS process. The physical design techniques of enclosed geometry and P-channel guard rings are used to design the four N-type active photodiode pixels as described in a previous paper. Argon transient measurements on the 256 x 256 chip array as a function of incident angle show a significant variation in the amount of charge collected as well as the charge spreading dependent on the pixel type. The results are correlated with processing and design information provided by Photobit. In addition, there is a large degree of statistical variability between individual ion strikes. No latch-up is observed up to an LET of 106 MeV/mg/sq cm.

  8. Simulation model of a transient fault controller for an active-stall wind turbine

    Jauch, C.; Soerensen, P.; Bak Jensen, B.

    2005-01-01

    This paper describes the simulation model of a controller that enables an active-stall wind turbine to ride through transient faults. The simulated wind turbine is connected to a simple model of a power system. Certain fault scenarios are specified and the turbine shall be able to sustain operation in case of such faults. The design of the controller is described and its performance assessed by simulations. The control strategies are explained and the behaviour of the turbine discussed. (author)

  9. Contribution to the Chemistry of Plasma-Activated Water

    Julák, J.; Hujacová, A.; Scholtz, V.; Khun, J.; Holada, K.

    2018-01-01

    Plasma-activated water (PAW) was prepared by exposure to nonthermal plasma produced by a positive dc corona discharge in a transient spark regime. The activation of water was performed in atmosphere of various surrounding gases (air, nitrogen, carbon dioxide, and argon). This PAW retains its biological activity, measured on the mouse neuroblastoma cells culture, even after storage for more than one year. The highest hydrogen peroxide content was found for PAWs prepared in the atmospheres of argon or carbon dioxide, whereas the PAWs prepared in air and nitrogen exhibited lower hydrogen peroxide content. The acidity of PAWs mediated by nitric and nitrous acid formation displayed an opposite trend. It is concluded that the long-lasting biological effect of PAW is mediated by hydrogen peroxide in acid milieu only, whereas other possible active components decompose rapidly.

  10. [Contribution of blue-green pigments to hemolytic activity of Pseudomonas aeruginosa cultural fluid].

    Pyzh, A É; Nikandrov, V N

    2011-01-01

    To assess the contribution of blue-green pigments of Pseudomonas aeruginosa to hemolytic activity of its cultural fluid. MATERIALS AND METHODS. Eight hospital strains and reference strain ATCC 15442 were used. Growth dynamics of strains as well as features of accumulation of hemolytic and phospholipase activity were studied. Purified samples of pyoverdin and pyocyanin were extracted by gel-chromatography and chloroform extraction methods. Hemolytic and lecitinase activities of the samples as well as effect of active oxygen scavengers and chelating agents on these activities were studied. Dynamics of accumulation of hemolytic activity significantly differed from that of phospholipase activity when strains were grown in liquid medium. Chromatographic separation of the pigments from cultural fluid supernatants sharply reduced its hemolytic activity. Purified samples of pyoverdin and pyocyanin were capable to lyse erythrocytes and chicken egg lecitin. These characteristics of the pigments were inhibited by nitroblue tetrazolium and sensitive to chelating agents. Conclusion. Pyoverdin and pyocyanin of pathogenic strains of P. aeruginosa are capable to lyse erythrocytes and suspension of purified chicken egg lecitin, they contribute to total hemolytic activity of pathogenic strains of Pseudomonas, which is not determined only by phospholipase C produced by microorganism. Lytic activity of the pigments is blocked by nitroblue tetrazolium and susceptible to some chelating agents. Apparently, this activity is mediated by superoxide radical and determined by presence of metals with transient valence in pigments' molecules.

  11. GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge.

    Wang, Yu-Feng; Sun, Min-Yu; Hou, Qiuling; Hamilton, Kathryn A

    2013-04-01

    The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ-aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurons, and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  12. Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1 by Diacylglycerol (DAG

    Oh Seog

    2008-10-01

    Full Text Available Abstract The capsaicin receptor, known as transient receptor potential channel vanilloid subtype 1 (TRPV1, is activated by a wide range of noxious stimulants and putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by protein kinase C (PKC. However, the identity of endogenous activators for TRPV1 under physiological condition is still debated. Here, we report that diacylglycerol (DAG directly activates TRPV1 channel in a membrane-delimited manner in rat dorsal root ganglion (DRG neurons. 1-oleoyl-2-acetyl-sn-glycerol (OAG, a membrane-permeable DAG analog, elicited intracellular Ca2+ transients, cationic currents and cobalt uptake that were blocked by TRPV1-selective antagonists, but not by inhibitors of PKC and DAG lipase in rat DRG neurons or HEK 293 cells heterologously expressing TRPV1. OAG induced responses were about one fifth of capsaicin induced signals, suggesting that OAG displays partial agonism. We also found that endogenously produced DAG can activate rat TRPV1 channels. Mutagenesis of rat TRPV1 revealed that DAG-binding site is at Y511, the same site for capsaicin binding, and PtdIns(4,5P2binding site may not be critical for the activation of rat TRPV1 by DAG in heterologous system. We propose that DAG serves as an endogenous ligand for rat TRPV1, acting as an integrator of Gq/11-coupled receptors and receptor tyrosine kinases that are linked to phospholipase C.

  13. A population of highly energetic transient events in the centres of active galaxies

    Kankare, E.; Kotak, R.; Mattila, S.; Lundqvist, P.; Ward, M. J.; Fraser, M.; Lawrence, A.; Smartt, S. J.; Meikle, W. P. S.; Bruce, A.; Harmanen, J.; Hutton, S. J.; Inserra, C.; Kangas, T.; Pastorello, A.; Reynolds, T.; Romero-Cañizales, C.; Smith, K. W.; Valenti, S.; Chambers, K. C.; Hodapp, K. W.; Huber, M. E.; Kaiser, N.; Kudritzki, R.-P.; Magnier, E. A.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.

    2017-12-01

    Recent all-sky surveys have led to the discovery of new types of transients. These include stars disrupted by the central supermassive black hole, and supernovae that are 10-100 times more energetic than typical ones. However, the nature of even more energetic transients that apparently occur in the innermost regions of their host galaxies is hotly debated1-3. Here we report the discovery of the most energetic of these to date: PS1-10adi, with a total radiated energy of 2.3 × 1052 erg. The slow evolution of its light curve and persistently narrow spectral lines over ˜ 3 yr are inconsistent with known types of recurring black hole variability. The observed properties imply powering by shock interaction between expanding material and large quantities of surrounding dense matter. Plausible sources of this expanding material are a star that has been tidally disrupted by the central black hole, or a supernova. Both could satisfy the energy budget. For the former, we would be forced to invoke a new and hitherto unseen variant of a tidally disrupted star, while a supernova origin relies principally on environmental effects resulting from its nuclear location. Remarkably, we also discover that PS1-10adi is not an isolated case. We therefore surmise that this new population of transients has previously been overlooked due to incorrect association with underlying central black hole activity.

  14. HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

    Jihong Xing

    2016-07-01

    Full Text Available Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1α in regulating pro-inflammatory cytokines (PICs pathway in the rat hippocampus after cardiac arrest (CA induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR. Those PICs include interleukin-1β (IL-1β, interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α. Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1α and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1β, IL-6 and TNF-α were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1α and the time courses for HIF-1α and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1α by systemic administration of ML228, HIF-1α activator, significantly attenuated the amplified IL-6/IL-6R and TNF-α /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1β and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1β, IL-6 and TNF-α and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1α plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1α improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that

  15. Passion for leisure activity contributes to pain experiences during rehabilitation.

    Courbalay, Anne; Deroche, Thomas; Brewer, Britton

    2017-03-01

    The primary aim of this study was to determine whether the levels of obsessive passion (OP) and harmonious passion for a suspended leisure activity contribute to pain catastrophizing and pain intensity in patients undergoing the rehabilitation process. The secondary aim was to examine whether the levels of passion associated with a maintained leisure activity offset the contribution of having a leisure activity suspended to pain intensity and catastrophizing. Ninety-one outpatients from functional rehabilitation units (Mage=37, SD=13.44 years) completed measures of pain catastrophizing, pain intensity, and passion about valued leisure activities (one they were prevented from practicing and one they remained able to practice). Correlation analysis showed that the level of OP for a suspended valued leisure activity was positively associated with pain catastrophizing and pain intensity. Results showed that pain catastrophizing mediated the relationship between this level of passion and pain intensity. The levels of harmonious passion and OP for a maintained valued leisure activity did not offset the contribution of OP for a suspended leisure activity to pain-related outcomes. When prevented from practicing a valued leisure activity, only OP contributes to the prediction of pain catastrophizing and pain intensity. The contribution of pain catastrophizing provides a potential explanation for why the level of OP for a suspended leisure activity is related to pain intensity ratings. The benefits of maintaining a valued leisure activity during rehabilitation do not seem sufficient to counterbalance the maladaptive effects of being prevented from the practice of a previous/another valued leisure activity.

  16. Transient activation of mTOR following forced treadmill exercise in rats

    Elfving, Betina; Christensen, Tina; Ratner, Cecilia

    2013-01-01

    , while the induction of neurogenesis requires signaling through the VEGF receptor, Flk-1 (VEGFR-2). VEGF expression is believed to be regulated by two distinct mTOR (mammalian Target of Rapamycin)-containing multiprotein complexes mTORC1 and mTORC2, respectively. This study was initiated to investigate...... of mTOR was regulated after a single bout of exercise. In conclusion, the effect of treadmill exercise on the VEGF system is acute rather than chronic and there is a transient activation of mTOR. More studies are needed to understand whether this could be beneficial in the treatment of neuropsychiatric...

  17. Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma.

    Deering-Rice, Cassandra E; Stockmann, Chris; Romero, Erin G; Lu, Zhenyu; Shapiro, Darien; Stone, Bryan L; Fassl, Bernhard; Nkoy, Flory; Uchida, Derek A; Ward, Robert M; Veranth, John M; Reilly, Christopher A

    2016-11-25

    Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of transient receptor potential vanilloid-1 (TRPV1) would be uniquely responsive to insoluble coal fly ash compared with the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1-I315M and -T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles due to reduced translation of protein and an apparent role for Ile-585 in activation by particles. In HEK-293 cells, I585V had an inhibitory effect on wild-type TRPV1 expression, activation, and internalization/agonist-induced desensitization. In normal human bronchial epithelial cells, IL-8 secretion in response to coal fly ash treatment was reduced for cells heterozygous for TRPV1-I585V. Finally, both the I315M and I585V variants were associated with worse asthma symptom control with the effects of I315M manifesting in mild asthma and those of the I585V variant manifesting in severe, steroid-insensitive individuals. This effect may be due in part to increased transient receptor potential ankyrin-1 (TRPA1) expression by lung epithelial cells expressing the TRPV1-I585V variant. These findings suggest that specific molecular interactions control TRPV1 activation by particles, differential activation, and desensitization of TRPV1 by particles and/or other agonists, and cellular changes in the expression of TRPA1 as a result of I585V expression could contribute to variations in asthma symptom control. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Research for the energy turnaround. Phase transitions actively shape. Contributions

    Szczepanski, Petra; Wunschick, Franziska; Martin, Niklas

    2015-01-01

    The Annual Conference 2014 of the Renewable Energy Research Association was held in Berlin on 6 and 7 November 2014. This book documents the contributions of the conference on research for the energy turnaround, phase transitions actively shape. After an introduction and two contributions to the political framework, the contributions to the economic phases of the energy transition, the phase of the current turn, the phases of social energy revolution, the stages of heat turnaround (Waermewende), and the stages of the mobility turn deal with the stages of development of the energy system. Finally, the Research Association Renewable Energy is briefly presented. [de

  19. Transient expression and activity of human DNA polymerase iota in loach embryos.

    Makarova, Irina V; Kazakov, Andrey A; Makarova, Alena V; Khaidarova, Nella V; Kozikova, Larisa V; Nenasheva, Valentina V; Gening, Leonid V; Tarantul, Vyacheslav Z; Andreeva, Ludmila E

    2012-02-01

    Human DNA polymerase iota (Pol ι) is a Y-family DNA polymerase with unusual biochemical properties and not fully understood functions. Pol ι preferentially incorporates dGTP opposite template thymine. This property can be used to monitor Pol ι activity in the presence of other DNA polymerases, e.g. in cell extracts of tissues and tumors. We have now confirmed the specificity and sensitivity of the method of Pol ι activity detection in cell extracts using an animal model of loach Misgurnus fossilis embryos transiently expressing human Pol ι. The overexpression of Pol ι was shown to be accompanied by an increase in abnormalities in development and the frequency of pycnotic nuclei in fish embryos. Further analysis of fish embryos with constitutive or regulated Pol ι expression may provide insights into Pol ι functions in vertebrate animals.

  20. Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons.

    Rueckemann, Jon W; DiMauro, Audrey J; Rangel, Lara M; Han, Xue; Boyden, Edward S; Eichenbaum, Howard

    2016-02-01

    The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information. © 2015 Wiley Periodicals, Inc.

  1. Role of Active Listening and Listening Effort on Contralateral Suppression of Transient Evoked Otoacousic Emissions.

    Kalaiah, Mohan Kumar; Theruvan, Nikhitha B; Kumar, Kaushlendra; Bhat, Jayashree S

    2017-04-01

    The present study aimed to investigate the effect of active listening and listening effort on the contralateral suppression of transient evoked otoacoustic emissions (CSTEOAEs). Twenty eight young adults participated in the study. Transient evoked otoacoustic emissions (TEOAEs) were recorded using 'linear' clicks at 60 dB peSPL, in three contralateral noise conditions. In condition 1, TEOAEs were obtained in the presence of white noise in the contralateral ear. While, in condition 2, speech was embedded into white noise at +3, -3, and -9 dB signal-to-noise ratio (SNR) and delivered to the contralateral ear. The SNR was varied to investigate the effect of listening effort on the CSTEOAE. In condition 3, speech was played backwards and embedded into white noise at -3 dB SNR. The conditions 1 and 3 served as passive listening condition and the condition 2 served as active listening condition. In active listening condition, the participants categorized the words in to two groups (e.g., animal and vehicle). CSTEOAE was found to be largest in the presence of white noise, and the amount of CSTEOAE was not significantly different between active and passive listening conditions (condition 2 and 3). Listening effort had an effect on the CSTEOAE, the amount of suppression increased with listening effort, when SNR was decreased from +3 dB to -3 dB. However, when the SNR was further reduced to -9 dB, there was no further increase in the amount of CSTEOAE, instead there was a reduction in the amount of suppression. The findings of the present study show that listening effort might affect CSTEOAE.

  2. Numerical Studies of Magnetohydrodynamic Activity Resulting from Inductive Transients. Final Report

    Sovinec, Carl R.

    2005-01-01

    This report describes results from numerical studies of transients in magnetically confined plasmas. The work has been performed by University of Wisconsin graduate students James Reynolds and Giovanni Cone and by the Principal Investigator through support from contract DE-FG02-02ER54687, a Junior Faculty in Plasma Science award from the DOE Office of Science. Results from the computations have added significantly to our knowledge of magnetized plasma relaxation in the reversed-field pinch (RFP) and spheromak. In particular, they have distinguished relaxation activity expected in sustained configurations from transient effects that can persist over a significant fraction of the plasma discharge. We have also developed the numerical capability for studying electrostatic current injection in the spherical torus (ST). These configurations are being investigated as plasma confinement schemes in the international effort to achieve controlled thermonuclear fusion for environmentally benign energy production. Our numerical computations have been performed with the NIMROD code (http://nimrodteam.org) using local computing resources and massively parallel computing hardware at the National Energy Research Scientific Computing Center. Direct comparisons of simulation results for the spheromak with laboratory measurements verify the effectiveness of our numerical approach. The comparisons have been published in refereed journal articles by this group and by collaborators at Lawrence Livermore National Laboratory (see Section 4). In addition to the technical products, this grant has supported the graduate education of the two participating students for three years

  3. Simulation of corrosion product activity in pressurized water reactors under flow rate transients

    Mirza, Anwar M.; Mirza, Nasir M.; Mir, Imran

    1998-01-01

    Simulation of coolant activation due to corrosion products and impurities in a typical pressurized water reactor has been done under flow rate transients. Employing time dependent production and losses of corrosion products in the primary coolant path an approach has been developed to calculate the coolant specific activity. Results for 24 Na, 56 Mn, 59 Fe, 60 Co and 99Mo show that the specific activity in primary loop approaches equilibrium value under normal operating conditions fairly rapidly. Predominant corrosion product activity is due to Mn-56. Parametric studies at full power for various ramp decreases in flow rate show initial decline in the activity and then a gradual rise to relatively higher saturation values. The minimum value and the time taken to reach the minima are strong functions of the slope of linear decrease in flow rate. In the second part flow rate coastdown was allowed to occur at different flow half-times. The reactor scram was initiated at 90% of the normal flow rate. The results show that the specific activity decreases and the rate of decrease depends on pump half time and the reactor scram conditions

  4. Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner.

    Spahn, Viola; Fischer, Oliver; Endres-Becker, Jeannette; Schäfer, Michael; Stein, Christoph; Zöllner, Christian

    2013-04-01

    Hyperalgesia is a cardinal symptom of opioid withdrawal. The transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated ion channel expressed on sensory neurons responding to noxious heat, protons, and chemical stimuli such as capsaicin. TRPV1 can be inhibited via μ-opioid receptor (MOR)-mediated reduced activity of adenylyl cyclases (ACs) and decreased cyclic adenosine monophosphate (cAMP) levels. In contrast, opioid withdrawal following chronic activation of MOR uncovers AC superactivation and subsequent increases in cAMP and protein kinase A (PKA) activity. Here we investigated (1) whether an increase in cAMP during opioid withdrawal increases the activity of TRPV1 and (2) how opioid withdrawal modulates capsaicin-induced nocifensive behavior in rats. We applied whole-cell patch clamp, microfluorimetry, cAMP assays, radioligand binding, site-directed mutagenesis, and behavioral experiments. Opioid withdrawal significantly increased cAMP levels and capsaicin-induced TRPV1 activity in both transfected human embryonic kidney 293 cells and dissociated dorsal root ganglion (DRG) neurons. Inhibition of AC and PKA, as well as mutations of the PKA phosphorylation sites threonine 144 and serine 774, prevented the enhanced TRPV1 activity. Finally, capsaicin-induced nocifensive behavior was increased during opioid withdrawal in vivo. In summary, our results demonstrate an increased activity of TRPV1 in DRG neurons as a new mechanism contributing to opioid withdrawal-induced hyperalgesia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents.

    Stenger, Bernhard; Zehfuss, Franziska; Mückter, Harald; Schmidt, Annette; Balszuweit, Frank; Schäfer, Eva; Büch, Thomas; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

    2015-09-01

    The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in different tissues including skin, lung and neuronal tissue. Recent reports identified TRPA1 as a sensor for noxious substances, implicating a functional role in the molecular toxicology. TRPA1 is activated by various potentially harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM) is a highly reactive alkylating agent that binds to numerous biological targets. Although SM is known for almost 200 years, detailed knowledge about the pathophysiology resulting from exposure is lacking. A specific therapy is not available. In this study, we investigated whether the alkylating agent 2-chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM are able to activate TRPA1 channels. CEES induced a marked increase in the intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive toward cytotoxic effects of CEES compared with wild-type cells. At low CEES concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1-E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously, reacted with a transient calcium influx in response to CEES exposure. The CEES-dependent calcium response was diminished by AP18. In summary, our results demonstrate that alkylating agents are able to activate TRPA1. Inhibition of TRPA1 counteracted cellular toxicity and could thus represent a feasible approach to mitigate SM-induced cell damage.

  6. Forward modeling transient brightenings and microflares around an active region observed with Hi-C

    Kobelski, Adam R. [Now at National Radio Astronomy Observatory, P.O. Box 2, Green Bank, WV 24944 (United States); McKenzie, David E., E-mail: kobelski@solar.physics.montana.edu [Department of Physics, P.O. Box 173840, Montana State University, Bozeman, MT 59717-3840 (United States)

    2014-10-20

    Small-scale flare-like brightenings around active regions are among the smallest and most fundamental of energetic transient events in the corona, providing a testbed for models of heating and active region dynamics. In a previous study, we modeled a large collection of these microflares observed with Hinode/X-Ray Telescope (XRT) using EBTEL and found that they required multiple heating events, but could not distinguish between multiple heating events on a single strand, or multiple strands each experiencing a single heating event. We present here a similar study, but with extreme-ultraviolet data of Active Region 11520 from the High Resolution Coronal Imager (Hi-C) sounding rocket. Hi-C provides an order of magnitude improvement to the spatial resolution of XRT, and a cooler temperature sensitivity, which combine to provide significant improvements to our ability to detect and model microflare activity around active regions. We have found that at the spatial resolution of Hi-C (≈0.''3), the events occur much more frequently than expected (57 events detected, only 1 or 2 expected), and are most likely made from strands of the order of 100 km wide, each of which is impulsively heated with multiple heating events. These findings tend to support bursty reconnection as the cause of the energy release responsible for the brightenings.

  7. [Transient lower esophageal sphincter relaxation and the related esophageal motor activities].

    Han, Seung Hyo; Hong, Su Jin

    2012-03-01

    Transient lower esophageal sphincter (LES) relaxation (TLESR) is defined as LES relaxation without a swallow. TLESRs are observed in both of the normal individuals and the patients with gastroesophageal reflux disorder (GERD). However, TLESR is widely considered as the major mechanism of the GERD. The new equipments such as high resolution manometry and impedance pH study is helped to understand of TLESR and the related esophageal motor activities. The strong longitudinal muscle contraction was observed during development of TLESR. Most of TLESRs are terminated by TLESR related motor events such as primary peristalsis and secondary contractions. The majority of TLESRs are associated with gastroesophageal reflux. Upper esophageal sphincter (UES) contraction is mainly associated with liquid reflux during recumbent position and UES relaxation predominantly related with air reflux during upright position. The frequency of TLESR in GERD patients seems to be not different compared to normal individuals, but the refluxate of GERD patients tend to be more acidic during TLESR.

  8. Permanent Genetic Access to Transiently Active Neurons via TRAP: Targeted Recombination in Active Populations

    Guenthner, Casey J.; Miyamichi, Kazunari; Yang, Helen H.; Heller, H. Craig; Luo, Liqun

    2013-01-01

    Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed a new approach, Targeted Recombination in Active Populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreERT2 is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that expr...

  9. The relevance of the dynamic stall effect for transient fault operations of active-stall wind turbines

    Jauch, Clemens; Soerensen, Poul; Jensen, Birgitte Bak

    2005-06-15

    This article describes a methodology to quantify the influence of dynamic stall on transient fault operations of active-stall turbines. The model of the dynamic stall effect is introduced briefly. The behaviour of the dynamic stall model during a transient fault operation is described mathematically, and from this its effect quantified. Two quantities are chosen to describe the influence of the dynamic stall effect: one is active power and the other is time delay. Subsequently a transient fault scenario is simulated with and without the dynamic stall effect and the differences discussed. From this comparison, the conclusion is drawn that the dynamic stall effect has some influence on the post-fault behaviour of the wind turbine, and it is hence suggested that the dynamic stall effect is considered if an active-stall wind turbine is to be modelled realistically. (Author)

  10. Contribution to the determination of nuclear friction by studying the de-excitation of nuclei in the transient regime

    Hassani, S.

    1985-01-01

    An old idea of Kramers is to consider nuclear fission as a diffusion process in phase space corresponding to the collective variable of fission. The fission width is taken as an escape rate of the system over the barrier potential. The evolution of the distribution of this collective variable and its conjugate is governed by a Fokker-Planck equation. In a quasistationary treatment Kramers obtained a fission rate which differs from the result given by the transition state method by a friction dependent factor. The non quasistationary solution of the Fokker-Planck equation allows to obtain an escape rate that presents a transient regime: from zero it grows and reaches asymptotically the Kramers' value. This time-dependent fission width is included in a formalism that describes the deexcitation of the compound nucleus in order to calculate the neutron multiplicities in competition with fission. A sensitive friction-dependence of the multiplicities is obtained. Using this formalism and comparing the results with data of a recent experiment gives a good agreement; resolving the disagreement between data and the usual statistical model at high energy. A range of values of the friction coefficient is deduced [fr

  11. Vivo-morpholinos induced transient knockdown of physical activity related proteins.

    David P Ferguson

    Full Text Available Physical activity is associated with disease prevention and overall wellbeing. Additionally there has been evidence that physical activity level is a result of genetic influence. However, there has not been a reliable method to silence candidate genes in vivo to determine causal mechanisms of physical activity regulation. Vivo-morpholinos are a potential method to transiently silence specific genes. Thus, the aim of this study was to validate the use of Vivo-morpholinos in a mouse model for voluntary physical activity with several sub-objectives. We observed that Vivo-morpholinos achieved between 60-97% knockdown of Drd1-, Vmat2-, and Glut4-protein in skeletal muscle, the delivery moiety of Vivo-morpholinos (scramble did not influence physical activity and that a cocktail of multiple Vivo-morpholinos can be given in a single treatment to achieve protein knockdown of two different targeted proteins in skeletal muscle simultaneously. Knocking down Drd1, Vmat2, or Glut4 protein in skeletal muscle did not affect physical activity. Vivo-morpholinos injected intravenously alone did not significantly knockdown Vmat2-protein expression in the brain (p = 0.28. However, the use of a bradykinin analog to increase blood-brain-barrier permeability in conjunction with the Vivo-morpholinos significantly (p = 0.0001 decreased Vmat2-protein in the brain with a corresponding later over-expression of Vmat2 coincident with a significant (p = 0.0016 increase in physical activity. We conclude that Vivo-morpholinos can be a valuable tool in determining causal gene-phenotype relationships in whole animal models.

  12. Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons

    Correia, Patrícia A; Lottem, Eran; Banerjee, Dhruba; Machado, Ana S; Carey, Megan R; Mainen, Zachary F

    2017-01-01

    Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions. DOI: http://dx.doi.org/10.7554/eLife.20975.001 PMID:28193320

  13. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.

    Guenthner, Casey J; Miyamichi, Kazunari; Yang, Helen H; Heller, H Craig; Luo, Liqun

    2013-06-05

    Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed an approach, targeted recombination in active populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreER(T2) is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that express CreER(T2) can only undergo recombination when tamoxifen is present, allowing genetic access to neurons that are active during a time window of less than 12 hr. We show that TRAP can provide selective access to neurons activated by specific somatosensory, visual, and auditory stimuli and by experience in a novel environment. When combined with tools for labeling, tracing, recording, and manipulating neurons, TRAP offers a powerful approach for understanding how the brain processes information and generates behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Iron/argillite interactions in radioactive waste disposal context: Oxidising transient and bacterial activities influence

    Chautard, Camille; Dauzeres, Alexandre; Maillet, Anais

    2014-01-01

    disposal conditions. Indeed, the nature, the quantity of nutrients and the environmental conditions (space, temperature, water, radioactivity and pressure) are key parameters for bacterial development. Even though disposal conditions may be not favourable during a part of the thermal transient characterised by high temperature, irradiation conditions and heterogeneous water saturation, bacterial activity may resume when environmental conditions become more suitable. Moreover, argillite cracks and residual voids between the waste packages and the liner create additional space for bacterial development. Concerning the nutrient content, significant amounts of hydrogen (an energetic substrate for bacteria) produced by anoxic corrosion of metallic materials are expected, which will favour the development of hydrogenotrophic bacteria. Furthermore, it is widely accepted that micro-organisms may locally affect the corrosion processes and the corrosion rates due to their influence on the water composition, pH and redox potential of the metal/environment interface. More specifically, sulphate-reducing bacteria (SRB) may produce ferrous sulphide, a corrosive product that may lead to significant pits on steel surface. Also, under anaerobic conditions, the iron-reducing bacteria (IRB) can reduce Fe(III) from iron oxides composing passive layers, which may impact corrosion by re-exposing the metal surfaces to corrosion. Therefore, the survival of bacteria cannot be excluded and their impact on corrosion phenomena must be investigated. In this context, this paper focuses on two studies regarding iron/argillite interactions. The first one addresses these interactions under oxidising and reducing conditions, while the second one tackles bacteria effects on corrosion in conditions that may prevail in a repository. These studies are both based on laboratory and in situ experiments. Iron and carbon steel have been chosen as typical of metallic components, and the Tournemire Toarcian argillite

  15. Ontology matters: a commentary on contribution to cultural historical activity

    Martin, Jenny

    2017-10-01

    This commentary promotes discussion on the imaginary provided by Sanaz Farhangi in her article entitled, Contribution to activity: a lens for understanding students' potential and agency in physics education. The commentary is concerned with aligning ontological assumptions in research accounts of learning and development with transformative aims. A broad definition of ontology as the theory of existence is preferred. Sociocultural approaches share relational ontology as a common foundation. I agree with scholars elaborating Vygotsky's Transformative Activist Stance that a relational ontology does not imply activism. However, I argue that relational ontology provides a necessary and sufficient theoretical grounding for intentional transformation. I draw upon positioning theory to elaborate the moral aspects of language use and to illustrate that a theory of being as relational already eliminates the transcendental position. I draw on Farhangi's article to further the discussion on the necessity and sufficiency of relational ontology and associated grammars in accounting for activism.

  16. Eleven years of net network research activity - inr contributions

    Deaconu, V.; Ionita, I.; Meleg, T.; Deaconu, M.; Truta, C.; Oncioiu, G.

    2013-01-01

    The European Network on Neutron Techniques Standardization for Structural Integrity (NeT) was established in 2002, grouping institutions from industry, research and academic media. Coordinated by the European Commission.s Joint Research Centre, the main mission of this network is to develop experimental and numerical techniques and standards for the reliable characterisation of residual stresses in structural welds. Each problem is tackled by creating a dedicated Task Group which manages measurement and modelling round robin studies and undertakes a thorough analysis and interpretation of the results. Over forty institutions are active NeT partners, their specific involvement and contributions being summarised in this paper. The Institute for Nuclear Research Pitesti (INR) is one of NeT founders and its contribution is related to numerical modelling, specimen analysis, material characterisation, data analysis or SANS support. This is also emphasised throughout this paper, together with the specific NeT research topics presentation. (authors)

  17. Glycine Receptor Activation Impairs ATP-Induced Calcium Transients in Cultured Cortical Astrocytes

    Tatiana P. Morais

    2018-01-01

    Full Text Available In central nervous system, glycine receptor (GlyR is mostly expressed in the spinal cord and brainstem, but glycinergic transmission related elements have also been identified in the brain. Astrocytes are active elements at the tripartite synapse, being responsible for the maintenance of brain homeostasis and for the fine-tuning of synaptic activity. These cells communicate, spontaneously or in response to a stimulus, by elevations in their cytosolic calcium (calcium transients, Ca2+T that can be propagated to other cells. How these Ca2+T are negatively modulated is yet poorly understood. In this work, we evaluated GlyR expression and its role on calcium signaling modulation in rat brain astrocytes. We first proved that GlyR, predominantly subunits α2 and β, was expressed in brain astrocytes and its localization was confirmed in the cytoplasm and astrocytic processes by immunohistochemistry assays. Calcium imaging experiments in cultured astrocytes showed that glycine (500 μM, a GlyR agonist, caused a concentration-dependent reduction in ATP-induced Ca2+T, an effect abolished by the GlyR antagonist, strychnine (0.8 μM, as well as by nocodazole (1 μM, known to impair GlyR anchorage to the plasma membrane. This effect was mimicked by activation of GABAAR, another Cl--permeable channel. In summary, we demonstrated that GlyR activation in astrocytes mediates an inhibitory effect upon ATP induced Ca2+T, which most probably involves changes in membrane permeability to Cl- and requires GlyR anchorage at the plasma membrane. GlyR in astrocytes may thus be part of a mechanism to modulate astrocyte-to-neuron communication.

  18. Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

    Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

    2014-03-01

    The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into

  19. Activity-dependent intracellular Ca2+ transients in unmyelinated nerve fibres of the isolated adult rat vagus nerve.

    Wächtler, J; Mayer, C; Grafe, P

    1998-04-01

    Confocal laser scanning microscopy was used to follow changes in the free intracellular calcium concentration ([Ca2+]i) in nerve fibres and adjacent Schwann cells in isolated rat vagus nerves. [Ca2+]i was monitored by the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during repetitive (1-50 Hz) supramaximal electrical stimulation or by bath application of ATP. Trains of action potentials were more effective at elongated, fibre-like structures of the vagus nerves, whereas ATP-induced Ca2+ transients were found predominantly in regions of Schwann cell bodies. Activity-induced Ca2+ signals were unaffected by pharmacological manipulation of intracellular Ca2+ stores, during long-lasting application of purinergic receptor agonists, or by substitution of extracellular Na+ with Li+. However, they were abolished in the presence of Ca2+-free bathing solution or after the blocking of Ca2+ channels with Cd2+. Ca2+ transients were also observed during Ca2+ action potentials. Such "Ca2+ spikes" were elicited by electrical stimulation in the presence of a combination of tetrodotoxin and K+ channel blockers. These data suggest that voltage-dependent Ca2+ channels, activated during short trains of Na+ action potentials, produce an increase in intra-axonal [Ca2+] of rat vagus nerves. We did not find evidence for activity-dependent Ca2+ transients in the Schwann cells surrounding the unmyelinated axons.

  20. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

    Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A

    2010-01-27

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.

  1. Modeling active region transient brightenings observed with X-ray telescope as multi-stranded loops

    Kobelski, Adam R.; McKenzie, David E. [Department of Physics, P.O. Box 173840, Montana State University, Bozeman, MT 59717-3840 (United States); Donachie, Martin, E-mail: kobelski@solar.physics.montana.edu [University of Glasgow, Glasgow, G128QQ, Scotland (United Kingdom)

    2014-05-10

    Strong evidence exists that coronal loops as observed in extreme ultraviolet and soft X-rays may not be monolithic isotropic structures, but can often be more accurately modeled as bundles of independent strands. Modeling the observed active region transient brightenings (ARTBs) within this framework allows for the exploration of the energetic ramifications and characteristics of these stratified structures. Here we present a simple method of detecting and modeling ARTBs observed with the Hinode X-Ray Telescope (XRT) as groups of zero-dimensional strands, which allows us to probe parameter space to better understand the spatial and temporal dependence of strand heating in impulsively heated loops. This partially automated method can be used to analyze a large number of observations to gain a statistical insight into the parameters of coronal structures, including the number of heating events required in a given model to fit the observations. In this article, we present the methodology and demonstrate its use in detecting and modeling ARTBs in a sample data set from Hinode/XRT. These initial results show that, in general, multiple heating events are necessary to reproduce observed ARTBs, but the spatial dependence of these heating events cannot yet be established.

  2. Ambiguous hydraulic heads and 14C activities in transient regional flow.

    Schwartz, Franklin W; Sudicky, Edward A; McLaren, Robert G; Park, Young-Jin; Huber, Matthew; Apted, Mick

    2010-01-01

    A regional flow and transport model is used to explore the implications of significant variability in Pleistocene and Holocene climates on hydraulic heads and (14)C activity. Simulations involve a 39 km slice of the Death Valley Flow System through Yucca Mountain toward the Amargosa Desert. The long-time scale over which infiltration has changed (tens-of-thousands of years) is matched by the large physical extent of the flow system (many tens-of-kilometers). Estimated paleo-infiltration rates were estimated using a juniper pollen percentage that extends from the last interglacial (LIG) period (approximately 120 kyrbp) to present. Flow and (14)C transport simulations show that groundwater flow changes markedly as a function of paleoclimate. At the last glacial maximum (LGM, 21 kyrbp), the recharge to the flow system was about an order-of-magnitude higher than present, and water table was more than 100 m higher. With large basin time constants, flow is complicated because hydraulic heads at a given location reflect conditions of the past, but at another location the flow may reflect present conditions. This complexity is also manifested by processes that depend on flow, for example (14)C transport. Without a model that accounts for the historical transients in recharge for at least the last 20,000 years, there is no simple way to deconvolve the (14)C dates to explain patterns of flow.

  3. Modeling active region transient brightenings observed with X-ray telescope as multi-stranded loops

    Kobelski, Adam R.; McKenzie, David E.; Donachie, Martin

    2014-01-01

    Strong evidence exists that coronal loops as observed in extreme ultraviolet and soft X-rays may not be monolithic isotropic structures, but can often be more accurately modeled as bundles of independent strands. Modeling the observed active region transient brightenings (ARTBs) within this framework allows for the exploration of the energetic ramifications and characteristics of these stratified structures. Here we present a simple method of detecting and modeling ARTBs observed with the Hinode X-Ray Telescope (XRT) as groups of zero-dimensional strands, which allows us to probe parameter space to better understand the spatial and temporal dependence of strand heating in impulsively heated loops. This partially automated method can be used to analyze a large number of observations to gain a statistical insight into the parameters of coronal structures, including the number of heating events required in a given model to fit the observations. In this article, we present the methodology and demonstrate its use in detecting and modeling ARTBs in a sample data set from Hinode/XRT. These initial results show that, in general, multiple heating events are necessary to reproduce observed ARTBs, but the spatial dependence of these heating events cannot yet be established.

  4. Transient and sustained cortical activity elicited by connected speech of varying intelligibility

    Tiitinen Hannu

    2012-12-01

    Full Text Available Abstract Background The robustness of speech perception in the face of acoustic variation is founded on the ability of the auditory system to integrate the acoustic features of speech and to segregate them from background noise. This auditory scene analysis process is facilitated by top-down mechanisms, such as recognition memory for speech content. However, the cortical processes underlying these facilitatory mechanisms remain unclear. The present magnetoencephalography (MEG study examined how the activity of auditory cortical areas is modulated by acoustic degradation and intelligibility of connected speech. The experimental design allowed for the comparison of cortical activity patterns elicited by acoustically identical stimuli which were perceived as either intelligible or unintelligible. Results In the experiment, a set of sentences was presented to the subject in distorted, undistorted, and again in distorted form. The intervening exposure to undistorted versions of sentences rendered the initially unintelligible, distorted sentences intelligible, as evidenced by an increase from 30% to 80% in the proportion of sentences reported as intelligible. These perceptual changes were reflected in the activity of the auditory cortex, with the auditory N1m response (~100 ms being more prominent for the distorted stimuli than for the intact ones. In the time range of auditory P2m response (>200 ms, auditory cortex as well as regions anterior and posterior to this area generated a stronger response to sentences which were intelligible than unintelligible. During the sustained field (>300 ms, stronger activity was elicited by degraded stimuli in auditory cortex and by intelligible sentences in areas posterior to auditory cortex. Conclusions The current findings suggest that the auditory system comprises bottom-up and top-down processes which are reflected in transient and sustained brain activity. It appears that analysis of acoustic features occurs

  5. Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities

    Chi-Ming Lee

    2013-01-01

    Full Text Available Rutaecarpine (RUT, the major bioactive ingredient isolated from the Chinese herb Evodia rutaecarpa, possesses a wide spectrum of biological activities, including anti-inflammation and preventing cardiovascular diseases. However, its high cytotoxicity hampers pharmaceutical development. We designed and synthesized a derivative of RUT, bromo-dimethoxyrutaecarpine (Br-RUT, which showed no cytotoxicity at 20 μM. Br-RUT suppressed nitric oxide (NO production and tumor necrosis factor-α release in concentration-dependent (0~20 μM manners in lipopolysaccharide (LPS-treated RAW 264.7 macrophages; protein levels of inducible NO synthase (iNOS and cyclooxygenase-2 induced by LPS were downregulated. Br-RUT inhibited cell migration and invasion of ovarian carcinoma A2780 cells with 0~48 h of treatment. Furthermore, Br-RUT enhanced the expression of transient receptor potential vanilloid type 1 and activated endothelial NOS in human aortic endothelial cells. These results suggest that the synthetic Br-RUT possesses very low cytotoxicity but retains its activities against inflammation and vasodilation that could be beneficial for cardiovascular disease therapeutics.

  6. Cortical GABAergic excitation contributes to epileptic activities around human glioma

    Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

    2015-01-01

    Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

  7. Thrombopoietin contributes to enhanced platelet activation in cigarette smokers.

    Lupia, Enrico; Bosco, Ornella; Goffi, Alberto; Poletto, Cesare; Locatelli, Stefania; Spatola, Tiziana; Cuccurullo, Alessandra; Montrucchio, Giuseppe

    2010-05-01

    Thrombopoietin (TPO) is a humoral growth factor that primes platelet activation in response to several agonists. We recently showed that TPO enhances platelet activation in unstable angina and sepsis. Aim of this study was to investigate the role of TPO in platelet function abnormalities described in cigarette smokers. In a case-control study we enrolled 20 healthy cigarette smokers and 20 nonsmokers, and measured TPO and C-reactive protein (CRP), as well as platelet-leukocyte binding and P-selectin expression. In vitro we evaluated the priming activity of smoker or control plasma on platelet activation, and the role of TPO in this effect. We then studied the effects of acute smoking and smoking cessation on TPO levels and platelet activation indices. Chronic cigarette smokers had higher circulating TPO levels than nonsmoking controls, as well as increased platelet-leukocyte binding, P-selectin expression, and CRP levels. Serum cotinine concentrations correlated with TPO concentrations, platelet-monocyte aggregates and P-selectin expression. In addition, TPO levels significantly correlated with ex vivo platelet-monocyte aggregation and P-selectin expression. In vitro, the plasma from cigarette smokers, but not from nonsmoking controls, primed platelet-monocyte binding, which was reduced when an inhibitor of TPO was used. We also found that acute smoking slightly increased TPO levels, but did not affect platelet-leukocyte binding, whereas smoking cessation induced a significant decrease in both circulating TPO and platelet-leukocyte aggregation. Elevated TPO contributes to enhance platelet activation and platelet-monocyte cross-talk in cigarette smokers. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  8. Micromechanical modelling of heterogeneous materials in transient conditions: contributions for the study of the ageing of structural components under service

    Masson, R.

    2010-01-01

    The modelling of the mechanical behaviour of structural materials is increasingly based on microstructural parameters. Within this framework, homogenisation methods have the advantage of providing deductive methods which, starting from the properties and space distribution of each constituent, deduce the effective properties of the heterogeneous material. Nevertheless, many applications make still difficult the use of homogenisation methods. It is in particular the case of structural materials presenting elastic-viscoplastic behaviours and subjected to both non-monotone and ageing loadings. To progress on the treatment by homogenisation of these useful situations constitutes precisely the main idea of the various contributions presented in this work.For linear elasticity, new expressions for the computation of the Eshelby tensor are first of all established in order to improve the efficiency of homogenisation methods usually used. Always for linear behaviours but now viscoelastic, various approximations associated with the use of the theorem of correspondence are studied and compared. The equivalence of one of these approximations (the so-called 'collocation method') with an internal variables formulation of the effective behaviour is shown. This internal variables formulation leads to exact results in some situations and strongly simplifies the treatment of ageing linear viscoelastic behaviours. In the case of elastic-viscoplastic behaviours, is added to the previous difficulty (viscoelastic coupling) that of the treatment of nonlinear behaviour. Comparisons made between various families of estimates make it possible to determine the effects of the various approximations needed to deal with these nonlinearities. An improvement is also proposed and implemented in a particular case while the extension of this internal variable formulation to nonlinear behaviours is discussed. Finally, full-field computations of microstructures are also tackled by considering the

  9. Growing Mouse Oocytes Transiently Activate Folate Transport via Folate Receptors As They Approach Full Size.

    Meredith, Megan; MacNeil, Allison H; Trasler, Jacquetta M; Baltz, Jay M

    2016-06-01

    The folate cycle is central to cellular one-carbon metabolism, where folates are carriers of one-carbon units that are critical for synthesis of purines, thymidylate, and S-adenosylmethionine, the universal methyl donor that forms the cellular methyl pool. Although folates are well-known to be important for early embryo and fetal development, their role in oogenesis has not been clearly established. Here, folate transport proteins were detected in developing neonatal ovaries and growing oocytes by immunohistochemistry, Western blot, and immunofluorescence. The folate receptors FOLR1 and FOLR2 as well as reduced folate carrier 1 (RFC1, SLC19A1 protein) each appeared to be present in follicular cells including granulosa cells. In growing oocytes, however, only FOLR2 immunoreactivity appeared abundant. Localization of apparent FOLR2 immunofluorescence near the plasma membrane increased with oocyte growth and peaked in oocytes as they neared full size. We assessed folate transport using the model folate leucovorin (folinic acid). Unexpectedly, there was a transient burst of folate transport activity for a brief period during oocyte growth as they neared full size, while folate transport was otherwise undetectable for the rest of oogenesis and in fully grown germinal vesicle stage oocytes. This folate transport was inhibited by dynasore, an inhibitor of endocytosis, but insensitive to the anion transport inhibitor stilbene 4-acetamido-40-isothiocyanato-stilbene-2,20-disulfonic acid, consistent with folate receptor-mediated transport but not with RFC1-mediated transport. Thus, near the end of their growth, growing oocytes may take up folates that could support the final stage of oogenesis or be stored to provide the endogenous folates needed in early embryogenesis. © 2016 by the Society for the Study of Reproduction, Inc.

  10. Repetitive Transient Ischemia-Induced Cardiac Angiogenesis is Mediated by Camkii Activation

    Zhuobin Chen

    2018-05-01

    Full Text Available Background/Aims: Coronary angiogenesis is an important protective mechanism in response to myocardial ischemia in coronary artery disease. However, the underlying mechanisms remain largely unclear. Here, we investigated the role of CaMKII activation in ischemia-induced cardiac angiogenesis. Methods: Repetitive transient ischemia model was established in C57/BL6 mice by daily multiple episodes (3 times/day of short time (5 min occlusion of the left anterior descending coronary artery for 7 days. Coronary angiogenesis was detected by immunofluorescent staining. RT-qPCR and Western blot analyses were used to detect the mRNA and protein levels of CaMKII, p-CaMKII and VEGF. Primary cardiac microvascular endothelial cells (CMECs were isolated to investigate the effects of KN93 on cell proliferation and migration in hypoxic condition. Results: We found that angiogenesis was induced in the ischemic myocardium and suppressed by chronic intraperitoneal injection of CaMKII inhibitor KN93. RT-qPCR and Western blot analyses showed that myocardial ischemia induced an increased expression and autophosphorylation of CaMKII. VEGF expression was increased in the ischemia model but blunted by KN93. Moreover, KN93 suppressed the proliferation and migration of cardiac endothelial cells in hypoxic condition in which the protein expression of CaMKII, p-CaMKII and VEGF was increased. Conclusion: CaMKII is an important mediator for the ischemia-induced coronary angiogenesis, in which CaMKII-triggered VEGF expression plays a key role.

  11. Observation and Modeling of Chromospheric Evaporation in a Coronal Loop Related to Active Region Transient Brightening

    Gupta, G. R.; Sarkar, Aveek; Tripathi, Durgesh

    2018-04-01

    Using the observations recorded by the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory and the Interface Region Imaging Spectrograph (IRIS) and the Extreme-ultraviolet Imaging Spectrometer and X-Ray Telescope both on board Hinode, we present evidence of chromospheric evaporation in a coronal loop after the occurrence of two active region transient brightenings (ARTBs) at the two footpoints. The chromospheric evaporation started nearly simultaneously in all of the three hot channels of AIA 131, 94, and 335 Å and was observed to be temperature dependent, being fastest in the highest temperature channel. The whole loop became fully brightened following the ARTBs after ≈25 s in 131 Å, ≈40 s in 94 Å, and ≈6.5 minutes in 335 Å. The differential emission measurements at the two footpoints (i.e., of two ARTBs) and at the loop top suggest that the plasma attained a maximum temperature of ∼10 MK at all these locations. The spectroscopic observations from IRIS revealed the presence of redshifted emission of ∼20 km s‑1 in cooler lines like C II and Si IV during the ARTBs that was cotemporal with the evaporation flow at the footpoint of the loop. During the ARTBs, the line width of C II and Si IV increased nearly by a factor of two during the peak emission. Moreover, enhancement in the line width preceded that in the Doppler shift, which again preceded enhancement in the intensity. The observed results were qualitatively reproduced by 1D hydrodynamic simulations, where energy was deposited at both of the footpoints of a monolithic coronal loop that mimicked the ARTBs identified in the observations.

  12. Model of Transient Process Where Three-Phase Transducer Feeds Induction Motor Equivalent as a Variable Active-Inductive Load

    Nenad Marković

    2016-01-01

    Full Text Available The paper presents a new approach in the analysis of a transient state in a system where the feeding source is a transducer-IGBT inverter and load is introduced through the induction motor with its R-L parameters. Induction motors with different parameters of powers and power factors are tested. MATLAB simulation of the three-phase inverter that feeds the induction machine has replaced the missing lab equipment with which mathematical model of this system was verified. According to the selected parameters of the inverter and induction machine and through the simulation in the MATLAB program, the results are obtained in the form of diagrams that verify the model of a transient state of the induction machine operation when it operates as a motor which is presented as a variable R-L load. The transient process of the system three-phase bridge inverter whose active-inductive load is the induction machine in the conditions of the change of the load parameters is analyzed. The model of the transient process in the system formed by the inverter in PWM (Pulse Width Modulation converter and induction machine is developed in the time domain and phase coordinates.

  13. A simplified model for tritium permeation transient predictions when trapping is active

    Longhurst, G.R.

    1994-01-01

    This report describes a simplified one-dimensional tritium permeation and retention model. The model makes use of the same physical mechanisms as more sophisticated, time-transient codes such as implantation, recombination, diffusion, trapping and thermal gradient effects. It takes advantage of a number of simplifications and approximations to solve the steady-state problem and then provides interpolating functions to make estimates of intermediate states based on the steady-state solution. Comparison calculations with the verified and validated TMAP4 transient code show good agreement. ((orig.))

  14. A simplified model for tritium permeation transient predictions when trapping is active*1

    Longhurst, G. R.

    1994-09-01

    This report describes a simplified one-dimensional tritium permeation and retention model. The model makes use of the same physical mechanisms as more sophisticated, time-transient codes such as implantation, recombination, diffusion, trapping and thermal gradient effects. It takes advantage of a number of simplifications and approximations to solve the steady-state problem and then provides interpolating functions to make estimates of intermediate states based on the steady-state solution. Comparison calculations with the verified and validated TMAP4 transient code show good agreement.

  15. A simplified model for tritium permeation transient predictions when trapping is active

    Longhurst, G.R. (Fusion Safety Program, Idaho National Engineering Laboratory, P.O. Box 1625, Idaho Falls, ID 83415 (United States))

    1994-09-01

    This report describes a simplified one-dimensional tritium permeation and retention model. The model makes use of the same physical mechanisms as more sophisticated, time-transient codes such as implantation, recombination, diffusion, trapping and thermal gradient effects. It takes advantage of a number of simplifications and approximations to solve the steady-state problem and then provides interpolating functions to make estimates of intermediate states based on the steady-state solution. Comparison calculations with the verified and validated TMAP4 transient code show good agreement. ((orig.))

  16. Transient Control of Synchronous Machine Active and Reactive Power in Micro-grid Power Systems

    Weber, Luke G.

    There are two main topics associated with this dissertation. The first is to investigate phase-to-neutral fault current magnitude occurring in generators with multiple zero-sequence current sources. The second is to design, model, and tune a linear control system for operating a micro-grid in the event of a separation from the electric power system. In the former case, detailed generator, AC8B excitation system, and four-wire electric power system models are constructed. Where available, manufacturers data is used to validate the generator and exciter models. A gain-delay with frequency droop control is used to model an internal combustion engine and governor. The four wire system is connected through a transformer impedance to an infinite bus. Phase-to-neutral faults are imposed on the system, and fault magnitudes analyzed against three-phase faults to gauge their severity. In the latter case, a balanced three-phase system is assumed. The model structure from the former case - but using data for a different generator - is incorporated with a model for an energy storage device and a net load model to form a micro-grid. The primary control model for the energy storage device has a high level of detail, as does the energy storage device plant model in describing the LC filter and transformer. A gain-delay battery and inverter model is used at the front end. The net load model is intended to be the difference between renewable energy sources and load within a micro-grid system that has separated from the grid. Given the variability of both renewable generation and load, frequency and voltage stability are not guaranteed. This work is an attempt to model components of a proposed micro-grid system at the University of Wisconsin Milwaukee, and design, model, and tune a linear control system for operation in the event of a separation from the electric power system. The control module is responsible for management of frequency and active power, and voltage and reactive

  17. Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

    Mengwen Qi

    2018-02-01

    Full Text Available Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4 is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047 and GlyR (strychnine, indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC (BIM II or D-sphingosine or calcium/calmodulin-dependent protein kinase II (CaMKII (KN-62 or KN-93 antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv. injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

  18. Constraining the contribution of active galactic nuclei to reionization

    Hassan, Sultan; Davé, Romeel; Mitra, Sourav; Finlator, Kristian; Ciardi, Benedetta; Santos, Mario G.

    2018-01-01

    Recent results have suggested that active galactic nuclei (AGN) could provide enough photons to reionize the Universe. We assess the viability of this scenario using a semi-numerical framework for modelling reionization, to which we add a quasar contribution by constructing a Quasar Halo Occupancy Distribution (QHOD) based on Giallongo et al. observations. Assuming a constant QHOD, we find that an AGN-only model cannot simultaneously match observations of the optical depth τe, neutral fraction and ionizing emissivity. Such a model predicts τe too low by ∼2σ relative to Planck constraints, and reionizes the Universe at z ≲ 5. Arbitrarily increasing the AGN emissivity to match these results yields a strong mismatch with the observed ionizing emissivity at z ∼ 5. If we instead assume a redshift-independent AGN luminosity function yielding an emissivity evolution like that assumed in Madau & Haardt model, then we can match τe albeit with late reionization; however, such evolution is inconsistent with observations at z ∼ 4-6 and poorly motivated physically. These results arise because AGN are more biased towards massive haloes than typical reionizing galaxies, resulting in stronger clustering and later formation times. AGN-dominated models produce larger ionizing bubbles that are reflected in ∼×2 more 21 cm power on all scales. A model with equal part galaxies and AGN contribution is still (barely) consistent with observations, but could be distinguished using next-generation 21 cm experiments such as Hydrogen Epoch of Reionization Array and SKA-low. We conclude that, even with recent claims of more faint AGN than previously thought, AGN are highly unlikely to dominate the ionizing photon budget for reionization.

  19. Investigation of electrically-active deep levels in single-crystalline diamond by particle-induced charge transient spectroscopy

    Kada, W., E-mail: kada.wataru@gunma-u.ac.jp [Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Kambayashi, Y.; Ando, Y. [Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Onoda, S. [Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Umezawa, H.; Mokuno, Y. [National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577 (Japan); Shikata, S. [Kwansei Gakuin Univ., 2-1, Gakuen, Mita, Hyogo 669-1337 (Japan); Makino, T.; Koka, M. [Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Hanaizumi, O. [Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Kamiya, T.; Ohshima, T. [Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan)

    2016-04-01

    To investigate electrically-active deep levels in high-resistivity single-crystalline diamond, particle-induced charge transient spectroscopy (QTS) techniques were performed using 5.5 MeV alpha particles and 9 MeV carbon focused microprobes. For unintentionally-doped (UID) chemical vapor deposition (CVD) diamond, deep levels with activation energies of 0.35 eV and 0.43 eV were detected which correspond to the activation energy of boron acceptors in diamond. The results suggested that alpha particle and heavy ion induced QTS techniques are the promising candidate for in-situ investigation of deep levels in high-resistivity semiconductors.

  20. Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.

    Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B

    2013-01-08

    It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.

  1. Transient Activation of Apomixis in Sexual Neotriploids May Retain Genomically Altered States and Enhance Polyploid Establishment

    Diego Hojsgaard

    2018-02-01

    Full Text Available Polyploid genomes evolve and follow a series of dynamic transfigurations along with adaptation and speciation. The initial formation of a new polyploid individual within a diploid population usually involves a triploid bridge, a two-step mechanism of cell fusions between ubiquitous (reduced and rare (unreduced gametes. The primary fusion event creates an intermediate triploid individual with unbalanced genome sets, a situation of genomic-shock characterized by gene expression dysregulation, high dosage sensitivity, disturbed cell divisions, and physiological and reproductive attributes drastically altered. This near-sterile neotriploid must produce (even eupolyploids through secondary fusion events to restore genome steadiness, meiotic balance, and fertility required for the demographic establishment of a nascent lineage. Natural conditions locate several difficulties to polyploid establishment, including the production of highly unbalanced and rarely unreduced (euploid gametes, frequency-dependent disadvantages (minority cytotype exclusion, severe fitness loss, and ecological competition with diploid parents. Persistence and adaptation of neopolyploids depend upon genetic and phenotypic novelty coupled to joint selective forces that preserve shock-induced genomic changes (subgenome homeolog partitioning and drive meiotic (reproductive stabilization and ecological diversification. Thus, polyploid establishment through the triploid bridge is a feasible but not ubiquitous process that requires a number of low-probability events and singular circumstances. Yet, frequencies of polyploids suggest that polyploid establishment is a pervasive process. To explain this disparity, and supported in experimental evidence, I propose that situations like hybridization and ploidy-state transitions associated to genomic shock and substantial developmental alterations can transiently activate apomixis as a mechanism to halt genomic instability and cancel factors

  2. Renewed Activity from the X-Ray Transient SAXJ 1810.8-2609 with Integral

    Fiocchi, M.; Natalucci, L.; Chenevez, J.; Bazzano, A.; Tarana, A.; Ubertini, P.; Brandt, S.; Beckmann, V.; Federici, M.; Galis, R.; Hudec, R.

    2009-03-01

    We report on the results of International Gamma-Ray Astrophysics Laboratory (INTEGRAL) observations of the neutron star low-mass X-ray binary SAX J1810.8-2609 during its latest active phase in 2007 August. The current outburst is the first one since 1998 and the derived luminosity is 1.1-2.6 ×1036 erg s-1 in the 20-100 keV energy range. This low outburst luminosity and the long-term time-average accretion rate of ~5 × 10-12 M sun yr-1 suggest that SAX J1810.8-2609 is a faint soft X-ray transient. During the flux increase, spectra are consistent with a thermal Comptonization model with a temperature plasma of kT e~ 23-30 keV and an optical depth of τ~ 1.2-1.5, independent of the luminosity of the system. This is a typical low hard spectral state for which the X-ray emission is attributed to the upscattering of soft seed photons by a hot, optically thin electron plasma. During the decay, spectra have a different shape, the high energy tail being compatible with a single power law. This confirm similar behavior observed by BeppoSAX during the previous outburst, with the absence of visible cutoff in the hard X-ray spectrum. INTEGRAL/JEM-X instrument observed four X-ray bursts in Fall 2007. The first one has the highest peak flux (≈3.5 crab in 3-25 keV) giving an upper limit to the distance of the source of about 5.7 kpc, for a L Edd ≈ 3.8 × 1038 erg s-1. The observed recurrence time of ~ 1.2 days and the ratio of the total energy emitted in the persistent flux to that emitted in the bursts (α~ 73) allow us to conclude that the burst fuel was composed by mixed hydrogen and helium with X >= 0.4. INTEGRAL is an ESA project with Instruments and Science Data Center funded by ESA member states, especially the PI countries: Denmark, France, Germany, Italy, Switzerland, Spain; Czech Republic and Poland; and with the participation of Russia and USA.

  3. Physical activity energy expenditure in Dutch adolescents: contribution of active transport to school, physical education, and leisure time activities.

    Slingerland, Menno; Borghouts, Lars B; Hesselink, Matthijs K C

    2012-05-01

    Detailed knowledge about physical activity energy expenditure (PAEE) can guide the development of school interventions aimed at reducing overweight in adolescents. However, relevant components of PAEE have never been objectively quantified in this population. This study investigated the contribution of active transport to and from school, physical education (PE), and leisure time activities to total PAEE during a regular school week in adolescents. Seventy-three adolescents (mean age: 15.7 years) wore an individually calibrated combined heart rate-acceleration monitor and kept an activity diary during a regular school week. Branched equation modeling was used to calculate PAEE of the specific activity categories, and their relative contribution to total PAEE was determined. Active transport and PE contributed 30.0% and 17.4%, respectively, to school-related PAEE. Active transport to and from school contributed 15% to total PAEE. Youth with a high physical activity level (PAL) spent 4 hours less in sedentary behavior than subjects with a medium or low PAL (F = 77.415 (2.70), p activities (F = 10.583 (2.70), p Active transport and PE contribute significantly to PAEE during school hours in adolescents. To achieve an increase in total PAEE in the least active group of adolescents, promising strategies might be to reduce inactive behavior, increase participation in leisure time sports, and possibly to replace inactive for active jobs. © 2012, American School Health Association.

  4. FGOALS-s2 simulation of upper-level jet streams over East Asia: Mean state bias and synoptic-scale transient eddy activity

    Song, Fengfei; Zhou, Tianjun

    2013-05-01

    Upper-level jet streams over East Asia simulated by the LASG/IAP coupled climate system model FGOALS-s2 were assessed, and the mean state bias explained in terms of synoptic-scale transient eddy activity (STEA). The results showed that the spatial distribution of the seasonal mean jet stream was reproduced well by the model, except that following a weaker meridional temperature gradient (MTG), the intensity of the jet stream was weaker than in National Centers for Environment Prediction (NCEP)/Department of Energy Atmospheric Model Inter-comparison Project II reanalysis data (NCEP2). Based on daily mean data, the jet core number was counted to identify the geographical border between the East Asian Subtropical Jet (EASJ) and the East Asian Polar-front Jet (EAPJ). The border is located over the Tibetan Plateau according to NCEP2 data, but was not evident in FGOALS-s2 simulations. The seasonal cycles of the jet streams were found to be reasonably reproduced, except that they shifted northward relative to reanalysis data in boreal summer owing to the northward shift of negative MTGs. To identify the reasons for mean state bias, the dynamical and thermal forcings of STEA on mean flow were examined with a focus on boreal winter. The dynamical and thermal forcings were estimated by extended Eliassen-Palm flux ( E) and transient heat flux, respectively. The results showed that the failure to reproduce the tripolar-pattern of the divergence of E over the jet regions led to an unsuccessful separation of the EASJ and EAPJ, while dynamical forcing contributed less to the weaker EASJ. In contrast, the weaker transient heat flux partly explained the weaker EASJ over the ocean.

  5. Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

    Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

    2015-09-15

    Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

  6. KChIP2 regulates the cardiac Ca2+ transient and myocyte contractility by targeting ryanodine receptor activity.

    Drew M Nassal

    Full Text Available Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss. Therefore, KChIP2 was acutely silenced in isolated guinea pig myocytes, which led to significant reductions in the Ca2+ transient amplitude and prolongation of the transient duration. This change was reinforced by a decline in sarcomeric shortening. Notably, these results were unexpected when considering previous observations showing enhanced ICa,L and prolonged action potential duration following KChIP2 loss, suggesting a disruption of fundamental Ca2+ handling proteins. Evaluation of SERCA2a, phospholamban, RyR, and sodium calcium exchanger identified no change in protein expression. However, assessment of Ca2+ spark activity showed reduced spark frequency and prolonged Ca2+ decay following KChIP2 loss, suggesting an altered state of RyR activity. These changes were associated with a delocalization of the ryanodine receptor activator, presenilin, away from sarcomeric banding to more diffuse distribution, suggesting that RyR open probability are a target of KChIP2 loss mediated by a dissociation of presenilin. Typically, prolonged action potential duration and enhanced Ca2+ entry would augment cardiac contractility, but here we see KChIP2 fundamentally disrupts Ca2+ release events and compromises myocyte contraction. This novel role targeting presenilin localization and RyR activity reveals a significance for KChIP2 loss that reflects adverse remodeling observed in cardiac disease settings.

  7. 100 years after the Marsica earthquake: contribute of outreach activities

    D'Addezio, Giuliana; Giordani, Azzurra; Valle, Veronica; Riposati, Daniela

    2015-04-01

    Many outreach events have been proposed by the scientific community to celebrate the Centenary of the January 13, 1915 earthquake, that devastated the Marsica territory, located in Central Apennines. The Laboratorio Divulgazione Scientifica e Attività Museali of the Istituto Nazionale di Geofisica e Vulcanologia (INGV's Laboratory for Outreach and Museum Activities) in Rome, has realised an interactive exhibition in the Castello Piccolomini, Celano (AQ), to retrace the many aspects of the earthquake disaster, in a region such as Abruzzo affected by several destructive earthquakes during its history. The initiatives represent an ideal opportunity for the development of new programs of communication and training on seismic risk and to spread the culture of prevention. The INGV is accredited with the Servizio Civile Nazionale (National Civic Service) and volunteers are involved in the project "Science and Outreach: a comprehensive approach to the divulgation of knowledge of Earth Sciences" starting in 2014. In this contest, volunteers had the opportunity to fully contribute to the exhibition, in particular, promoting and realising two panels concerning the social and environmental consequences of the Marsica earthquake. Describing the serious consequences of the earthquake, we may raise awareness about natural hazards and about the only effective action for earthquake defense: building with anti seismic criteria. After studies and researches conducted in libraries and via web, two themes have been developped: the serious problem of orphans and the difficult reconstruction. Heavy snowfalls and the presence of wolves coming from the high and wild surrounding mountains complicated the scenario and decelerated the rescue of the affected populations. It is important to underline that the earthquake was not the only devastating event in the country in 1915; another drammatic event was, in fact, the First World War. Whole families died and the still alive infants and

  8. Optimization of an NLEO-based algorithm for automated detection of spontaneous activity transients in early preterm EEG

    Palmu, Kirsi; Vanhatalo, Sampsa; Stevenson, Nathan; Wikström, Sverre; Hellström-Westas, Lena; Palva, J Matias

    2010-01-01

    We propose here a simple algorithm for automated detection of spontaneous activity transients (SATs) in early preterm electroencephalography (EEG). The parameters of the algorithm were optimized by supervised learning using a gold standard created from visual classification data obtained from three human raters. The generalization performance of the algorithm was estimated by leave-one-out cross-validation. The mean sensitivity of the optimized algorithm was 97% (range 91–100%) and specificity 95% (76–100%). The optimized algorithm makes it possible to systematically study brain state fluctuations of preterm infants. (note)

  9. A polycystin-type transient receptor potential (Trp channel that is activated by ATP

    David Traynor

    2017-02-01

    Full Text Available ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants. We report that the DIF morphogens, cyclic-di-GMP, GABA, glutamate and adenosine all induce strong cytoplasmic calcium responses, likewise independently of TrpP. Thus, TrpP is dedicated to purinergic signalling. ATP treatment causes cell blebbing within seconds but this does not require TrpP, implicating a separate purinergic receptor. We could detect no effect of ATP on chemotaxis and TrpP mutants grow, chemotax and develop almost normally in standard conditions. No gating ligand is known for the human homologue of TrpP, polycystin-2, which causes polycystic kidney disease. Our results now show that TrpP mediates purinergic signalling in Dictyostelium and is directly or indirectly gated by ATP.

  10. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes.

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-09-14

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.

  11. Transient alterations in neurotransmitter activity in the caudate nucleus of rat brain after a high dose of ionizing radiation

    Hunt, W.A.; Dalton, T.K.; Darden, J.H.

    1979-01-01

    A single 10,000-rad dose of high-energy electrons induced an increase in dopaminergic and cholinergic activity in the caudate nucleus of the rat brain as assessed by K + -stimulated dopamine release in vitro and high-affinity choline uptake. These alterations occur during early transient incapacitation (ETI) and dissipate as the animal recovers behaviorally, in about 30 min after irradiation. Although the responses observed resemble those that result from blockade of dopamine receptors, no radiation-induced changes were found in dopamine-sensitive adenylate cyclase activity and [ 3 H]haloperidol binding, two indices of dopaminergic receptor function. The data suggest that changes in dopaminergic and cholinergic activity are associated with the development of ETI and may play a role in the behavioral decrement observed under this condition

  12. Current status of models for transient phenomena in dopant diffusion and activation

    Pichler, P.; Stiebel, D.

    2002-01-01

    Transient phenomena caused by ion-implantation processes have been studied for more than 25 years now with a continuously increasing number of research articles published in this field per year. One driving force of this research is the ongoing miniaturization of ULSI MOS and bipolar technology which uses extensively the capabilities of technology-computer-aided-design (TCAD). The other driving force which attracts also academic institutions and research institutes is the high complexity of the phenomena, involving the interaction of dopants, intrinsic point defects, extended defects and impurities like carbon as well as the interactions of mobile defects with surfaces and interfaces and their redistribution in multilayer structures. This paper outlines some recent advances towards a quantitative description of such phenomena

  13. The cartilage protein melanoma inhibitory activity contributes to inflammatory arthritis

    Yeremenko, Nataliya; Härle, Peter; Cantaert, Tineke; van Tok, Melissa; van Duivenvoorde, Leonie M.; Bosserhoff, Anja; Baeten, Dominique

    2014-01-01

    Melanoma inhibitory activity (MIA) is a small chondrocyte-specific protein with unknown function. MIA knockout mice (MIA(-/-)) have a normal phenotype with minor microarchitectural alterations of cartilage. Our previous study demonstrated that immunodominant epitopes of MIA are actively presented in

  14. Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia

    Hamid R. Sadeghnia

    2017-09-01

    Full Text Available Safranal is a monoterpene aldehyde found in saffron (Crocus sativus L. petals. It has been previously reported that safranal has a wide range of activities such as antioxidant and anti-inflammatory effects. In this study, we examined the effect of safranal on brain injuries in a transient model of focal cerebral ischemia. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min, followed by 24 h of reperfusion. Safranal in the doses of 72.5 and 145 mg/kg was administered intraperitoneally at 0, 3, and 6 h after reperfusion. Neurobehavioral deficit, infarct volume, hippocampal cell loss and markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, total sulfhydryl (SH content, and antioxidant capacity (using FRAP assay were also assessed. The focal cerebral ischemia induced a significant increase in the neurological score, infarct volume and neuronal cell loss in the ipsilateral hippocampal CA1 and CA3 subfields (p < 0.001 and also oxidative stress markers (p < 0.01. Following safranal administration, the total SH content and antioxidant capacity significantly increased, while marked decreases were observed in the neurological score, infarct volume and hippocampal cell loss, as well as TBARS level. This study concluded that safranal had protective effects on ischemic reperfusion injury in the rat model of stroke. Such effects of safranal may have been exerted mainly by suppressing the production of free radicals and increasing antioxidant activity.

  15. Activation of the Unfolded Protein Response Contributes toward the Antitumor Activity of Vorinostat

    Soumen Kahali

    2010-01-01

    Full Text Available Histone deacetylase (HDAC inhibitors represent an emerging class of anticancer agents progressing through clinical trials. Although their primary target is thought to involve acetylation of core histones, several nonhistone substrates have been identified, including heat shock protein (HSP 90, which may contribute towards their antitumor activity. Glucose-regulated protein 78 (GRP78 is a member of the HSP family of molecular chaperones and plays a central role in regulating the unfolded protein response (UPR. Emerging data suggest that GRP78 is critical in cellular adaptation and survival associated with oncogenesis and may serve as a cancer-specific therapeutic target. On the basis of shared homology with HSP family proteins, we sought to determine whether GRP78 could serve as a molecular target of the HDAC inhibitor vorinostat. Vorinostat treatment led to GRP78 acetylation, dissociation, and subsequent activation of its client protein double-stranded RNA-activated protein-like endoplasmic reticulum kinase (PERK. Investigations in a panel of cancer cell lines identified that UPR activation after vorinostat exposure is specific to certain lines. Mass spectrometry performed on immunoprecipitated GRP78 identified lysine-585 as a specific vorinostat-induced acetylation site of GRP78. Downstream activation of the UPR was confirmed, including eukaryotic initiating factor 2α phosphorylation and increase in ATF4 and C/EBP homologous protein expression. To determine the biologic relevance of UPR activation after vorinostat, RNA interference of PERK was performed, demonstrating significantly decreased sensitivity to vorinostat-induced cytotoxicity. Collectively, these findings indicate that GRP78 is a biologic target of vorinostat, and activation of the UPR through PERK phosphorylation contributes toward its antitumor activity.

  16. Adult active transport in the Netherlands: an analysis of its contribution to physical activity requirements.

    Elliot Fishman

    Full Text Available Modern, urban lifestyles have engineered physical activity out of everyday life and this presents a major threat to human health. The Netherlands is a world leader in active travel, particularly cycling, but little research has sought to quantify the cumulative amount of physical activity through everyday walking and cycling.Using data collected as part of the Dutch National Travel Survey (2010 - 2012, this paper determines the degree to which Dutch walking and cycling contributes to meeting minimum level of physical activity of 150 minutes of moderate intensity aerobic activity throughout the week. The sample includes 74,465 individuals who recorded at least some travel on the day surveyed. As physical activity benefits are cumulative, all walking and cycling trips are analysed, including those to and from public transport. These trips are then converted into an established measure of physical activity intensity, known as metabolic equivalents of tasks. Multivariate Tobit regression models were performed on a range of socio-demographic, transport resources, urban form and meteorological characteristics.The results reveal that Dutch men and women participate in 24 and 28 minutes of daily physical activity through walking and cycling, which is 41% and 55% more than the minimum recommended level. It should be noted however that some 57% of the entire sample failed to record any walking or cycling, and an investigation of this particular group serves as an important topic of future research. Active transport was positively related with age, income, bicycle ownership, urban density and air temperature. Car ownership had a strong negative relationship with physically active travel.The results of this analysis demonstrate the significance of active transport to counter the emerging issue of sedentary lifestyle disease. The Dutch experience provides other countries with a highly relevant case study in the creation of environments and cultures that

  17. Contributions for territorial management of risks associated with oil activity

    Felipe Pinto Gonçalves

    2013-06-01

    Full Text Available Whereas that the growing complexity of technical and spatial organization of the oil activity in Espírito Santo state gives new demands for land use management to the local governments, this article addresses the issue of economic and technological risks associated with such activities. Based on the evaluation of legal instruments such as the classification of land uses and the zoning, are discussed the possibilities of insertion the risks in municipal policies for land use planning

  18. Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

    Pedro L. Flores

    2017-06-01

    Full Text Available Maitotoxin (MTX is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP. Several reports indicate that MTX is an activator of non-selective cation channels (NSCC in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA approach and the two-electrode voltage-clamp technique (TEVC. The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1 protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

  19. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

    De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

    2008-06-01

    The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

  20. RENEWED ACTIVITY FROM THE X-RAY TRANSIENT SAXJ 1810.8-2609 WITH INTEGRAL

    Fiocchi, M.; Natalucci, L.; Chenevez, Jérôme

    2009-01-01

    (36) erg s(-1) in the 20-100 keV energy range. This low outburst luminosity and the long-term time-average accretion rate of similar to 5 x 10(-12) M-circle dot yr(-1) suggest that SAX J1810.8-2609 is a faint soft X-ray transient. During the flux increase, spectra are consistent with a thermal...... Comptonization model with a temperature plasma of kT(e) similar to 23-30 keV and an optical depth of tau similar to 1.2-1.5, independent of the luminosity of the system. This is a typical low hard spectral state for which the X-ray emission is attributed to the upscattering of soft seed photons by a hot......, optically thin electron plasma. During the decay, spectra have a different shape, the high energy tail being compatible with a single power law. This confirm similar behavior observed by BeppoSAX during the previous outburst, with the absence of visible cutoff in the hard X-ray spectrum. INTEGRAL...

  1. Transient Performance Improvement of Wind Turbines with Doubly Fed Induction Generators Using Active Damping Control Strategy

    Saeed Soleymani

    2016-01-01

    Full Text Available This paper Analytically investigates the effects of system and controller parameters and operating conditions on the dynamic and transient behavior of wind turbines (WTs with doubly-fed induction generators (DFIGs under voltage dips and wind speed fluctuations. Also, it deals with the design considerations regarding rotor and speed controllers. The poorly damped electrical and mechanical modes of the system are identified, and the effects of system parameters, and speed/rotor controllers on these modes are investigated by modal and sensitivity analyses. The results of theoretical studies are verified by time domain simulations. It is found that the dynamic behavior of the DFIG-based WT under voltage dips is strongly affected by the stator dynamics. Further, it is shown that the closed loop bandwidth of the rotor current control, rotor current damping, DFIG power factor and the rotor back-emf voltages have high impact on the stator modes and consequently on the DFIG dynamic behavior. Moreover, it is shown that the dynamic behavior of DFIG-based WT under wind speed fluctuation is significantly dependent on the bandwidth and damping of speed control loop.

  2. Active Interventions in Clinical Practice: Contributions of Gestalt Therapy.

    Lammert, Marilyn; Dolan, Mary M.

    1983-01-01

    Describes two dimensions of Gestalt therapy that can enhance clinical practice--orientation to the present and active-experimental style--and examines them in relation to some traditional principles of practice. Gestalt theory offers a method of discovery that is a combination of phenomenology and behaviorism. (JAC)

  3. Contribution of anthropic activities to the seawater pollution at the ...

    The high toxicity of seawater is due to the presence of lead and cadmium with concentrations exceeding 60 times the normal value (0.015 mg/l). Moreover, the deficit in D.O announces strong biological activities. This wild aggression is related to the industrial discharges in the port area. Keywords: marine pollution; heavy ...

  4. SUMOylation of the Forkhead transcription factor FOXL2 promotes its stabilization/activation through transient recruitment to PML bodies.

    Adrien Georges

    Full Text Available BACKGROUND: FOXL2 is a transcription factor essential for ovarian development and maintenance. It is mutated in the genetic condition called Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES and in cases of isolated premature ovarian failure. We and others have previously shown that FOXL2 undergoes several post-translational modifications. METHODS AND PRINCIPAL FINDINGS: Here, using cells in culture, we show that interference with FOXL2 SUMOylation leads to a robust inhibition of its transactivation ability, which correlates with a decreased stability. Interestingly, FOXL2 SUMOylation promotes its transient recruitment to subnuclear structures that we demonstrate to be PML (Promyelocytic Leukemia Nuclear Bodies. Since PML bodies are known to be sites where post-translational modifications of nuclear factors take place, we used tandem mass spectrometry to identify new post-translational modifications of FOXL2. Specifically, we detected four phosphorylated, one sulfated and three acetylated sites. CONCLUSIONS: By analogy with other transcription factors, we propose that PML Nuclear Bodies might transiently recruit FOXL2 to the vicinity of locally concentrated enzymes that could be involved in the post-translational maturation of FOXL2. FOXL2 acetylation, sulfation, phosphorylation as well as other modifications yet to be discovered might alter the transactivation capacity of FOXL2 and/or its stability, thus modulating its global intracellular activity.

  5. Pulmonary endothelial activation caused by extracellular histones contributes to neutrophil activation in acute respiratory distress syndrome.

    Zhang, Yanlin; Guan, Li; Yu, Jie; Zhao, Zanmei; Mao, Lijun; Li, Shuqiang; Zhao, Jinyuan

    2016-11-21

    During the acute respiratory distress syndrome (ARDS), neutrophils play a central role in the pathogenesis, and their activation requires interaction with the endothelium. Extracellular histones have been recognized as pivotal inflammatory mediators. This study was to investigate the role of pulmonary endothelial activation during the extracellular histone-induced inflammatory response in ARDS. ARDS was induced in male C57BL/6 mice by intravenous injection with lipopolysaccharide (LPS) or exogenous histones. Concurrent with LPS administration, anti-histone H4 antibody (anti-H4) or non-specific IgG was administered to study the role of extracellular histones. The circulating von Willebrand factor (vWF) and soluble thrombomodulin (sTM) were measured with ELISA kits at the preset time points. Myeloperoxidase (MPO) activity in lung tissue was measured with a MPO detection kit. The translocation of P-selectin and neutrophil infiltration were measured by immunohistochemical detection. For in vitro studies, histone H4 in the supernatant of mouse lung vascular endothelial cells (MLVECs) was measured by Western blot. The binding of extracellular histones with endothelial membrane was examined by confocal laser microscopy. Endothelial P-selectin translocation was measured by cell surface ELISA. Adhesion of neutrophils to MLVECs was assessed with a color video digital camera. The results showed that during LPS-induced ARDS extracellular histones caused endothelial and neutrophil activation, as seen by P-selectin translocation, release of vWF, an increase of circulating sTM, lung neutrophil infiltration and increased MPO activity. Extracellular histones directly bound and activated MLVECs in a dose-dependent manner. On the contrary, the direct stimulatory effect of exogenous histones on neutrophils was very limited, as measured by neutrophil adhesion and MPO activity. With the contribution of activated endothelium, extracellular histones could effectively activating

  6. Contributions of Glycogen to Astrocytic Energetics during Brain Activation

    Dienel, Gerald A.; Cruz, Nancy F.

    2014-01-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

  7. Contributions of glycogen to astrocytic energetics during brain activation.

    Dienel, Gerald A; Cruz, Nancy F

    2015-02-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

  8. Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and Virulence of Acinetobacter baumannii.

    Steven E Fiester

    Full Text Available Acinetobacter baumannii is an opportunistic Gram-negative pathogen that causes a wide range of infections including pneumonia, septicemia, necrotizing fasciitis and severe wound and urinary tract infections. Analysis of A. baumannii representative strains grown in Chelex 100-treated medium for hemolytic activity demonstrated that this pathogen is increasingly hemolytic to sheep, human and horse erythrocytes, which interestingly contain increasing amounts of phosphatidylcholine in their membranes. Bioinformatic, genetic and functional analyses of 19 A. baumannii isolates showed that the genomes of each strain contained two phosphatidylcholine-specific phospholipase C (PC-PLC genes, which were named plc1 and plc2. Accordingly, all of these strains were significantly hemolytic to horse erythrocytes and their culture supernatants tested positive for PC-PLC activity. Further analyses showed that the transcriptional expression of plc1 and plc2 and the production of phospholipase and thus hemolytic activity increased when bacteria were cultured under iron-chelation as compared to iron-rich conditions. Testing of the A. baumannii ATCC 19606T plc1::aph-FRT and plc2::aph isogenic insertion derivatives showed that these mutants had a significantly reduced PC-PLC activity as compared to the parental strain, while testing of plc1::ermAM/plc2::aph demonstrated that this double PC-PLC isogenic mutant expressed significantly reduced cytolytic and hemolytic activity. Interestingly, only plc1 was shown to contribute significantly to A. baumannii virulence using the Galleria mellonella infection model. Taken together, our data demonstrate that both PLC1 and PLC2, which have diverged from a common ancestor, play a concerted role in hemolytic and cytolytic activities; although PLC1 seems to play a more critical role in the virulence of A. baumannii when tested in an invertebrate model. These activities would provide access to intracellular iron stores this pathogen

  9. Estimation of transient increases in bleeding risk associated with physical activity in children with haemophilia

    Latimer Jane

    2008-06-01

    Full Text Available Abstract Background Although it is widely appreciated that vigorous physical activity can increase the risk of bleeding episodes in children with haemophilia, the magnitude of the increase in risk is not known. Accurate risk estimates could inform decisions made by children with haemophilia and their parents about participation in physical activity and aid the development of optimal prophylactic schedules. The aim of this study is to provide an accurate estimate of the risks of bleeding associated with vigorous physical activity in children with haemophilia. Methods/Design The study will be a case-crossover study nested within a prospective cohort study. Children with moderate or severe haemophilia A or B, recruited from two paediatric haematology departments in Australia, will participate in the study. The child, or the child's parent or guardian, will report bleeding episodes experienced over a 12-month period. Following a bleeding episode, the participant will be interviewed by telephone about exposures to physical activity in the case period (8 hours before the bleed and 2 control periods (an 8 hour period at the same time on the day preceding the bleed and an 8 hour period two days preceding the bleed. Conditional logistic regression will be used to estimate the risk of participating in vigorous physical activity from measures of exposure to physical activity in the case and control periods. Discussion This case-control study will provide estimates of the risk of participation in vigorous physical activity in children with haemophilia.

  10. Vinculin contributes to Cell Invasion by Regulating Contractile Activation

    Mierke, Claudia Tanja

    2008-07-01

    Vinculin is a component of the focal adhesion complex and is described as a mechano-coupling protein connecting the integrin receptor and the actin cytoskeleton. Vinculin knock-out (k.o.) cells (vin-/-) displayed increased migration on a 2-D collagen- or fibronectin-coated substrate compared to wildtype cells, but the role of vinculin in cell migration through a 3-D connective tissue is unknown. We determined the invasiveness of established tumor cell lines using a 3-D collagen invasion assay. Gene expression analysis of 4 invasive and 4 non-invasive tumor cell lines revealed that vinculin expression was significantly increased in invasive tumor cell lines. To analyze the mechanisms by which vinculin increased cell invasion in a 3-D gel, we studied mouse embryonic fibroblasts wildtype and vin-/- cells. Wildtype cells were 3-fold more invasive compared vin-/- cells. We hypothesized that the ability to generate sufficient traction forces is a prerequisite for tumor cell migration in a 3-D connective tissue matrix. Using traction microscopy, we found that wildtype exerted 3-fold higher tractions on fibronectin-coated polyacrylamide gels compared to vin-/- cells. These results show that vinculin controls two fundamental functions that lead to opposite effects on cell migration in a 2-D vs. a 3-D environment: On the one hand, vinculin stabilizes the focal adhesions (mechano-coupling function) and thereby reduces motility in 2-D. On the other hand, vinculin is also a potent activator of traction generation (mechano-regulating function) that is important for cell invasion in a 3-D environment.

  11. Transient analyzer

    Muir, M.D.

    1975-01-01

    The design and design philosophy of a high performance, extremely versatile transient analyzer is described. This sub-system was designed to be controlled through the data acquisition computer system which allows hands off operation. Thus it may be placed on the experiment side of the high voltage safety break between the experimental device and the control room. This analyzer provides control features which are extremely useful for data acquisition from PPPL diagnostics. These include dynamic sample rate changing, which may be intermixed with multiple post trigger operations with variable length blocks using normal, peak to peak or integrate modes. Included in the discussion are general remarks on the advantages of adding intelligence to transient analyzers, a detailed description of the characteristics of the PPPL transient analyzer, a description of the hardware, firmware, control language and operation of the PPPL transient analyzer, and general remarks on future trends in this type of instrumentation both at PPPL and in general

  12. Hippocampal network activity is transiently altered by induction of long-term potentiation in the dentate gyrus of freely behaving rats

    Arthur Bikbaev

    2007-12-01

    Full Text Available A role for oscillatory activity in hippocampal neuronal networks has been proposed in sensory encoding, cognitive functions and synaptic plasticity. In the hippocampus, theta (5–10 Hz and gamma (30–100 Hz oscillations may provide a mechanism for temporal encoding of information, and the basis for formation and retrieval of memory traces. Long-term potentiation (LTP of synaptic transmission, a candidate cellular model of synaptic information storage, is typically induced by high-frequency tetanisation (HFT of afferent pathways. Taking into account the role of oscillatory activity in the processing of information, dynamic changes may occur in hippocampal network activity in the period during HFT and/or soon after it. These changes in rhythmic activity may determine or, at least, contribute to successful potentiation and, in general, to formation of memory. We have found that short-term potentiation (STP and LTP as well LTPfailure are characterised with different profiles of changes in theta and gamma frequencies. Potentiation of synaptic transmission was associated with a significant increase in the relative theta power and mean amplitude of theta cycles in the period encompassing 300 seconds after HFT. Where LTP or STP, but not failure of potentiation, occurred, this facilitation of theta was accompanied by transient increases in gamma power and in the mean amplitude of gamma oscillations within a single theta cycle. Our data support that specific, correlated changes in these parameters are associated with successful synaptic potentiation. These findings suggest that changes in theta-gamma activity associated with induction of LTP may enable synaptic information storage in the hippocampus.

  13. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

    2012-01-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  14. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  15. Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold-Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction.

    Xiong, Shiqiang; Wang, Bin; Lin, Shaoyang; Zhang, Hexuan; Li, Yingsha; Wei, Xing; Cui, Yuanting; Wei, Xiao; Lu, Zongshi; Gao, Peng; Li, Li; Zhao, Zhigang; Liu, Daoyan; Zhu, Zhiming

    2017-08-02

    Environmental cold-induced hypertension is common, but how to treat cold-induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca 2+ homeostasis and the vascular function in cold-induced hypertension. Primary vascular smooth muscle cells from wild-type or Trpm8 -/- mice were cultured. In vitro, we confirmed that sarcoplasmic reticulum-resident TRPM8 participated in the regulation of cellular and mitochondrial Ca 2+ homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin II induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species-triggered Ca 2+ influx and the activation of RhoA/Rho kinase pathway. In vivo, long-term noxious cold stimulation dramatically increased vasoconstriction and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular reactive oxygen species generation, vasoconstriction, and lowered blood pressure through attenuating excessive mitochondrial reactive oxygen species mediated the activation of RhoA/Rho kinase in a TRPM8-dependent manner. These effects of menthol were further validated in angiotensin II-induced hypertensive mice. Long-term dietary menthol treatment targeting and preserving mitochondrial function may represent a nonpharmaceutical measure for environmental noxious cold-induced hypertension. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Exercise induces transient transcriptional activation of the PGC-1a gene in human skeletal muscle

    Pilegaard, Henriette; Saltin, Bengt; Neufer, P. Darrell

    2003-01-01

    Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1a (PGC-1a) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell...... culture and rodent skeletal muscle. To determine whether PGC-1a transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two......-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl...

  17. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils

    Traynor-Kaplan, A.E.; Thompson, B.L.; Harris, A.L.; Taylor, P.; Omann, G.M.; Sklar, L.A.

    1989-01-01

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation

  18. Multi-dimensional Analysis for SLB Transient in ATLAS Facility as Activity of DSP (Domestic Standard Problem)

    Bae, B. U.; Park, Y. S.; Kim, J. R.; Kang, K. H.; Choi, K. Y.; Sung, H. J.; Hwang, M. J.; Kang, D. H.; Lim, S. G.; Jun, S. S.

    2015-01-01

    Participants of DSP-03 were divided in three groups and each group has focused on the specific subject related to the enhancement of the code analysis. The group A tried to investigate scaling capability of ATLAS test data by comparing to the code analysis for a prototype, and the group C studied to investigate effect of various models in the one-dimensional codes. This paper briefly summarizes the code analysis result from the group B participants in the DSP-03 of the ATLAS test facility. The code analysis by Group B focuses highly on investigating the multi-dimensional thermal hydraulic phenomena in the ATLAS facility during the SLB transient. Even though the one-dimensional system analysis code cannot simulate the whole system of the ATLAS facility with a nodalization of the CFD (Computational Fluid Dynamics) scale, a reactor pressure vessel can be considered with multi-dimensional components to reflect the thermal mixing phenomena inside a downcomer and a core. Also, the CFD could give useful information for understanding complex phenomena in specific components such as the reactor pressure vessel. From the analysis activity of Group B in ATLAS DSP-03, participants adopted a multi-dimensional approach to the code analysis for the SLB transient in the ATLAS test facility. The main purpose of the analysis was to investigate prediction capability of multi-dimensional analysis tools for the SLB experiment result. In particular, the asymmetric cooling and thermal mixing phenomena in the reactor pressure vessel could be significantly focused for modeling the multi-dimensional components

  19. Transient ureteral obstruction prevents against kidney ischemia/reperfusion injury via hypoxia-inducible factor (HIF-2α activation.

    Shun Zhang

    Full Text Available Although the protective effect of transient ureteral obstruction (UO prior to ischemia on subsequent renal ischemia/reperfusion (I/R injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure.

  20. Hippocampal activity during transient respiratory events in the freely behaving cat

    Poe, G R; Kristensen, Morten Pilgaard; Rector, D M

    1996-01-01

    We measured dorsal hippocampal activity accompanying sighs and apnea using reflectance imaging and electrophysiologic measures in freely behaving cats. Reflected 660-nm light from a 1-mm2 area of CA1 was captured during sighs and apnea at 25 Hz through a coherent image conduit coupled to a charge...

  1. Inhibition of proteases activity in intestine needs a sustainable acidic environment rather than a transient.

    Xing, Chang; Xing, Jin-Feng; Ge, Zhi-Qiang

    2017-10-01

    α-Chymotrypsin (α-CT) and trypsin are important components of the enzymatic barrier. They could degrade the therapeutic proteins and peptides, inhibit their activity consequently, and thereby reduce their oral bioavailability. Acidic agents, as one type of indirect protease inhibitors, have shown proof of concept in clinical trials. We report here the inactivated proteases due to acid influence can be reactivated immediately by environmental pH recovery regardless of how long the inactivation last. To keep the inactivation time of proteases for 4-5 h, we designed and prepared a sustained-release tablet containing citric acid (CA) which can effectively reduce the pH below 5.0 and maintain it for 5 h in the dissolution-reaction medium. The activity of α-CT and trypsin was quantified by analyzing the residual amount of their respective substrates BTEE and TAME. More than 80% of the substrates were survived in 5.0 h of incubation, whereas the common tablet inhibited the proteases activity for only two hours in the same experimental medium. It indicates that the sustained-release tablet loaded with CA can efficiently inhibit the α-CT and trypsin activity longer than the common tablet. The results will be beneficial for designing and formulating the peroral administration of peptide and protein drugs.

  2. The Refund of Social Insurance Contributions of Disabled Persons Conducting Non-agricultural Economic Activity

    Marzena Szabłowska-Juckiewicz

    2014-01-01

    Disabled persons conducting non-agricultural economic activity may apply for the refund of social insurance contributions from the State Fund for Rehabilitation of the Disabled Persons. The exception to the general rule of financing social insurance contributions of persons conducting non-agricultural economic activity by the insured persons themselves, entirely from their own funds, constitutes one of the instruments introduced by the law-maker to enhance vocational activation of disabled pe...

  3. Transient Thermal State of an Active Braille Matrix with Incorporated Thermal Actuators by Means of Finite Element Method

    Alutei, Alexandra-Maria; Szelitzky, Emoke; Mandru, Dan

    2013-01-01

    In this article the authors present the transient thermal analysis for a developed thermal linear actuator based on wax paraffin used to drive the cells of a Braille device. A numerical investigation of transient heat transfer phenomenon during paraffin melting and solidification in an encapsulated recipient has been carried out using the ANSYS…

  4. Transient Angle Stability Analysis of Grid-Connected Converters with the First-order Active Power Loop

    Wu, Heng; Wang, Xiongfei

    2018-01-01

    . To tackle this challenge, this paper employs the phase portrait to analyze the transient stability of power converters, and it is found that the better transient stability performance can be achieved if the grid-connected converters are controlled as the first-order nonlinear system. Simulations...

  5. Transient pseudohypoaldosteronism

    Stajić Nataša

    2011-01-01

    Full Text Available Introduction. Infants with urinary tract malformations (UTM presenting with urinary tract infection (UTI are prone to develop transient type 1 pseudohypoaldosteronism (THPA1. Objective. Report on patient series with characteristics of THPA1, UTM and/or UTI and suggestions for the diagnosis and therapy. Methods. Patients underwent blood and urine electrolyte and acid-base analysis, serum aldosterosterone levels and plasma rennin activity measuring; urinalysis, urinoculture and renal ultrasound were done and medical and/or surgical therapy was instituted. Results. Hyponatraemia (120.9±5.8 mmol/L, hyperkalaemia (6.9±0.9 mmol/L, metabolic acidosis (plasma bicarbonate, 11±1.4 mmol/L, and a rise in serum creatinine levels (145±101 μmol/L were associated with inappropriately high urinary sodium (51.3±17.5 mmol/L and low potassium (14.1±5.9 mmol/L excretion. Elevated plasma aldosterone concentrations (170.4±100.5 ng/dL and the very high levels of the plasma aldosterone to potassium ratio (25.2±15.6 together with diminished urinary K/Na values (0.31±0.19 indicated tubular resistance to aldosterone. After institution of appropriate medical and/or surgical therapy, serum electrolytes, creatinine, and acid-base balance were normalized. Imaging studies showed ureteropyelic or ureterovesical junction obstruction in 3 and 2 patients, respectively, posterior urethral valves in 3, and normal UT in 1 patient. According to our knowledge, this is the first report on THPA1 in the Serbian literature. Conclusion. Male infants with hyponatraemia, hyperkalaemia and metabolic acidosis have to have their urine examined and the renal ultrasound has to be done in order to avoid both, the underdiagnosis of THPA1 and the inappropriate medication.

  6. Neuroprotective Activity of Lavender Oil on Transient Focal Cerebral Ischemia in Mice

    Qiusheng Zheng

    2012-08-01

    Full Text Available The air-dried aerial parts of Lavandula angustifolia Mill, a traditional Uygur herbal drug, is used as resuscitation-inducing therapy to treat neurodisfunctions, such as stroke. This study was designed to assess the neuroprotective effects of lavender oil against ischemia/reperfusion (IR injury in mice. Focal cerebral ischemia was induced by the intraluminal occlusion method with a nylon string. The neurodysfuntion was evaluated by neurological deficit and the infarct area was showed by 2,3,5-triphenyltetrazolium chloride (TTC staining. The histopathological changes were observed by hematoxylin and eosin staining. The levels of mitochondria-generated reactive oxygen species (ROS, malondialdehyde (MDA and carbonyl, the ratio of reduced glutathione (GSH/glutathione disulfide (GSSG, the activities of superoxide dismutase (SOD, catalase (CAT and glutathion peroxidase (GSH-Px in brain tissue were measured to estimate the oxidative stress state. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22 h of reperfusion. In comparison with the model group, treatment with lavender oil significantly decreased neurological deficit scores, infarct size, the levels of MDA, carbonyl and ROS, and attenuated neuronal damage, upregulated SOD, CAT, GSH-Px activities and GSH/GSSG ratio. These results suggested that the neuroprotective effects of lavender oil against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects.

  7. Molecular Docking Analysis of Ginger Active Compound on Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1

    Fifteen Aprila Fajrin

    2018-02-01

    Full Text Available Ginger had been reported to ameliorate painful diabetic neuropathy (PDN in an animal model. Gingerol and shogaol were active compounds of ginger that potentially act on transient receptor potential cation channel subfamily V member 1 (TRPV1, a key receptor in PDN. This study aims to predict the binding of gingerol and shogaol to TRPV1 using an in silico model. The ligands of the docking study were 3 chemical compounds of each gingerol and shogaol, i.e. 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8 gingerol and 10-gingerol. Capsaicin, a TRPV1 agonist, was used as a native ligand. The TRPV1 structure was taken from Protein Data Bank (ID 3J9J. The docking analysis was performed using Autodock Vina. The result showed that among the ginger active compounds, 6-shogaol had the strongest binding energy (-7.10 kcal/mol to TRPV1. The 6-shogaol lacked the potential hydrogen bond to Ile265 of TRPV1 protein, which capsacin had. However, it's binding energy towards TRPV1 was not significantly different compared to capsaicin. Therefore, 6-shogaol had potential to be developed as a treatment for PDN.

  8. Glycolytic metabolite methylglyoxal inhibits cold and menthol activation of the transient receptor potential melastatin type 8 channel.

    Ciobanu, A C; Selescu, T; Gasler, I; Soltuzu, L; Babes, A

    2016-03-01

    Methylglyoxal (MG) is a reactive dicarbonyl compound involved in protein modifications linked to diabetes mellitus. The plasma level of MG is elevated in diabetic patients, particularly those with painful diabetic neuropathy. Diabetic neuropathy is often associated with spontaneous pain and altered thermal perception. This study assesses effects of MG on TRPM8, an ion channel involved in innocuous cold sensing and cold allodynia and also in cold-mediated analgesia. Acute treatment with MG inhibited the activation of recombinant rat and human transient receptor potential melastatin type 8 (TRPM8) by cold and chemical agonists. A similar effect was observed when native TRPM8 was investigated in cultured rat dorsal root ganglion (DRG) neurons. DRG neurons treated with MG for 16-24 hr displayed a significant reduction in the fraction of cold- and menthol-sensitive neurons, most likely expressing TRPM8. The fraction of allyl isothiocyanate-sensitive neurons was also reduced, and the coexpression among different neuronal populations was affected. The same prolonged exposure to MG significantly reduced the expression of TRPM8 at the mRNA level. Overall, our data provide evidence for decreased activity and expression level of TRPM8 in the presence of MG, which may be linked to some of the alterations in pain and temperature sensing reported by diabetic patients. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  9. Physiological consequences of transient outward K(+) current activation during heart failure in the canine left ventricle

    Cordeiro, Jonathan M; Callø, Kirstine; Moise, N Sydney

    2012-01-01

    .7±1.4pA/pF after 5weeks, +50mV). Current decay as well as recovery of I(to) from inactivation progressively slowed with the development of heart failure. Reduction of I(to) density was paralleled by a reduction in phase 1 magnitude, epicardial action potential notch and J wave amplitude recorded from......Background: Remodeling of ion channel expression is well established in heart failure (HF). We determined the extent to which I(to) is reduced in tachypacing-induced HF and assessed the ability of an I(to) activator (NS5806) to recover this current. Method and results: Whole-cell patch clamp...

  10. IPS observations of transient interplanetary phenomena associated with solar filament activity in late august

    Watanabe, Takashi; Marubashi, Katsuhide.

    1985-01-01

    Large-scale structures of the solar wind plasma during the severe geomagnetic storm of August 27-29, 1978 are studied on the basis of IPS and spacecraft observations. Three-dimensional configuration of an interplanetary disturbance which caused the SSC of August 27, 1978 was an oblate sphere having an axial ratio of 1.7. Approximate excess mass and kinetic energy contained within the high-speed portion of the disturbance (--500 km s -1 ) were 10 16 g and 3 x 10 31 erg, respectively. An interplanetary disturbance was also observed on August 28, 1978 during the main phase of the geomagnetic storm. It is suggested that the solar-filament activity which took place near the solar disk center in August 23-25, 1978 caused these interplanetary disturbances. (author)

  11. Active region dimensionality and quantum efficiencies of InGaN LEDs from temperature dependent photoluminescence transients

    Can, Nuri; Okur, Serdal; Monavarian, Morteza; Zhang, Fan; Avrutin, Vitaliy; Morkoç, Hadis; Teke, Ali; Özgür, Ümit

    2015-03-01

    Temperature dependent recombination dynamics in c-plane InGaN light emitting diodes (LEDs) with different well thicknesses, 1.5, 2, and 3 nm, were investigated to determine the active region dimensionality and its effect on the internal quantum efficiencies. It was confirmed for all LEDs that the photoluminescence (PL) transients are governed by radiative recombination at low temperatures while nonradiative recombination dominates at room temperature. At photoexcited carrier densities of 3 - 4.5 x 1016 cm-3 , the room-temperature Shockley-Read-Hall (A) and the bimolecular (B) recombination coefficients (A, B) were deduced to be (9.2x107 s-1, 8.8x10-10 cm3s-1), (8.5x107 s-1, 6.6x10-10 cm3s-1), and (6.5x107 s-1, 1.4x10-10 cm3s-1) for the six period 1.5, 2, and 3 nm well-width LEDs, respectively. From the temperature dependence of the radiative lifetimes, τrad α Tn/2, the dimensionality n of the active region was found to decrease consistently with decreasing well width. The 3 nm wide wells exhibited ~T1.5 dependence, suggesting a three-dimensional nature, whereas the 1.5 nm wells were confirmed to be two-dimensional (~T1) and the 2 nm wells close to being two-dimensional. We demonstrate that a combination of temperature dependent PL and time-resolved PL techniques can be used to evaluate the dimensionality as well as the quantum efficiencies of the LED active regions for a better understanding of the relationship between active-region design and the efficiency limiting processes in InGaN LEDs.

  12. INTEGRAL finds renewed X-ray activity of the Neutron star X-ray transient SAX J1750.8-2900

    Sanchez-Fernandez, Celia; Chenevez, Jérôme; Kuulkers, Erik

    2015-01-01

    INTEGRAL Galactic bulge monitoring observations (ATel #438) on UT 13 September 2015 18:50-22:32 reveal renewed X-ray activity from the low-mass X-ray binary transient and Type I X-ray burster SAX J1750.8-2900 (IAU Circ. #6597). The last outburst from this source was reported in 2011 (ATels #3170,...

  13. Contribution of the mathematical modelling of knowledge to the evaluation of uncertainty margins of a LBLOCA transient (LOFT-L2-5)

    Baccou, J.; Chojnacki, E.

    2007-01-01

    This work is devoted to some recent developments in uncertainty analysis of the computer code responses used for accident management procedures in nuclear industry. The classical probabilistic approach to evaluate uncertainties is recalled. In this case, the statistical treatment of the code responses is based on the use of order statistics. It provides direct estimations of relevant statistical measures for safety studies. However, the lack of knowledge about uncertainty sources can deteriorate the decision-making. To respect the real state of knowledge, a second model, based on the Dempster-Shafer theory is introduced. It allows to mix the probabilistic approach with the possibility theory that is more appropriate when few information is available. An application of both methodologies to the uncertainty analysis of a LBLOCA transient (LOFT-L2-5) is given

  14. Activities Contributing a Great Deal to the Students' Interactive Skills in Foreign Language Classes

    Asatryan, Susanna

    2016-01-01

    While teaching speaking it is desired to provide a rich environment in class for meaningful communication to take place. With this aim, various speaking activities can contribute a great deal to students in developing their interactive skills necessary for life. These activities make students active in the learning process and at the same time…

  15. One nuclear calcium transient induced by a single burst of action potentials represents the minimum signal strength in activity-dependent transcription in hippocampal neurons.

    Yu, Yan; Oberlaender, Kristin; Bengtson, C Peter; Bading, Hilmar

    2017-07-01

    Neurons undergo dramatic changes in their gene expression profiles in response to synaptic stimulation. The coupling of neuronal excitation to gene transcription is well studied and is mediated by signaling pathways activated by cytoplasmic and nuclear calcium transients. Despite this, the minimum synaptic activity required to induce gene expression remains unknown. To address this, we used cultured hippocampal neurons and cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) that allows detection of nascent transcripts in the cell nucleus. We found that a single burst of action potentials, consisting of 24.4±5.1 action potentials during a 6.7±1.9s depolarization of 19.5±2.0mV causing a 9.3±0.9s somatic calcium transient, is sufficient to activate transcription of the immediate early gene arc (also known as Arg3.1). The total arc mRNA yield produced after a single burst-induced nuclear calcium transient was very small and, compared to unstimulated control neurons, did not lead to a significant increase in arc mRNA levels measured using quantitative reverse transcriptase PCR (qRT-PCR) of cell lysates. Significantly increased arc mRNA levels became detectable in hippocampal neurons that had undergone 5-8 consecutive burst-induced nuclear calcium transients at 0.05-0.15Hz. These results indicate that a single burst-induced nuclear calcium transient can activate gene expression and that transcription is rapidly shut off after synaptic stimulation has ceased. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Correction to: Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain.

    Nakamori, Shunsuke; Takahashi, Jun; Hyuga, Sumiko; Tanaka-Kagawa, Toshiko; Jinno, Hideto; Hyuga, Masashi; Hakamatsuka, Takashi; Odaguchi, Hiroshi; Goda, Yukihiro; Hanawa, Toshihiko; Kobayashi, Yoshinori

    2018-03-01

    The article Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain, written by Shunsuke Nakamori, Jun Takahashi, Sumiko Hyuga, Toshiko Tanaka-Kagawa, Hideto Jinno, Masashi Hyuga, Takashi Hakamatsuka, Hiroshi Odaguchi, Yukihiro Goda, Toshihiko Hanawa and Yoshinori Kobayashi, was originally published Online First without open access. After publication in volume 71, issue 1, page 105-113 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

  17. Fast calcium transients translate the distribution and conduction of neural activity in different regions of a single sensory neuron.

    Purali, Nuhan

    2017-09-01

    In the present study, cytosolic calcium concentration changes were recorded in response to various forms of excitations, using the fluorescent calcium indicator dye OG-BAPTA1 together with the current or voltage clamp methods in stretch receptor neurons of crayfish. A single action potential evoked a rise in the resting calcium level in the axon and axonal hillock, whereas an impulse train or a large saturating current injection would be required to evoke an equivalent response in the dendrite region. Under voltage clamp conditions, amplitude differences between axon and dendrite responses vanished completely. The fast activation time and the modulation of the response by extracellular calcium concentration changes indicated that the evoked calcium transients might be mediated by calcium entry into the cytosol through a voltage-gated calcium channel. The decay of the responses was slow and sensitive to extracellular sodium and calcium concentrations as well as exposure to 1-10 mM NiCl 2 and 10-500 µM lanthanum. Thus, a sodium calcium exchanger and a calcium ATPase might be responsible for calcium extrusion from the cytosol. Present results indicate that the calcium indicator OG-BAPTA1 might be an efficient but indirect way of monitoring regional membrane potential differences in a single neuron.

  18. Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.

    Wang, Shiquan; Wei, Haidong; Cai, Min; Lu, Yan; Hou, Wugang; Yang, Qianzi; Dong, Hailong; Xiong, Lize

    2014-01-01

    Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

  19. Learning from anticipated and abnormal plant transients

    Varnado, B.

    1983-01-01

    A report is given of the American Nuclear Society topical meeting on Anticipated and Abnormal Transients in Light Water Reactors held in Jackson, Wyoming in September 1983. Industry involvement in the evaluation of operating experience, human error contributions, transient management, thermal hydraulic modelling, the role of probabilistic risk assessment and the cost of transient incidents are discussed. (U.K.)

  20. Perspectives on the Contribution of Social Science to Adapted Physical Activity: Looking Forward, Looking Back

    Causgrove Dunn, Janice; Cairney, John; Zimmer, Chantelle

    2016-01-01

    In this article, we reflect on the contributions of the social sciences to the field of adapted physical activity by examining the theories and methods that have been adopted from the social science disciplines. To broaden our perspective on adapted physical activity and provide new avenues for theoretical and empirical exploration, we discuss and…

  1. Contribution of Physical Education and Active Transport to Energy Expenditure in Dutch Adolescents

    drs Menno Slingerland; dr. Lars B. Borghouts

    2010-01-01

    Introduction: It has been suggested that physical education (PE) can make a meaningful contribution to children's physical activity (PA) levels. The amount of moderate-to-vigorous physical activity (MVPA) in PE has been quantified in various manners, including heart rate monitoring and direct

  2. The Contributions of Physical Activity and Fitness to Optimal Health and Wellness

    Ohuruogu, Ben

    2016-01-01

    The paper examined the role of physical activity and fitness more especially in the area of disease prevention and control by looking at the major ways by which regular physical activity and fitness contributes to optimal health and wellness. The Surgeor General's Report (1996), stressed that physical inactivity is a national problem which…

  3. Observations of white-light flares in NOAA active region 11515: high occurrence rate and relationship with magnetic transients

    Song, Y. L.; Tian, H.; Zhang, M.; Ding, M. D.

    2018-06-01

    Aims: There are two goals in this study. One is to investigate how frequently white-light flares (WLFs) occur in a flare-productive active region (NOAA active region 11515). The other is to investigate the relationship between WLFs and magnetic transients (MTs). Methods: We used the high-cadence (45 s) full-disk continuum filtergrams and line-of-sight magnetograms taken by the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO) to identify WLFs and MTs, respectively. Images taken by the Atmospheric Imaging Assembly (AIA) on board SDO were also used to show the flare morphology in the upper atmosphere. Results: We found at least 20 WLFs out of a total of 70 flares above C class (28.6%) in NOAA active region 11515 during its passage across the solar disk (E45°-W45°). Each of these WLFs occurred in a small region, with a short duration of about 5 min. The enhancement of the white-light continuum intensity is usually small, with an average enhancement of 8.1%. The 20 WLFs we observed were found along an unusual configuration of the magnetic field that was characterized by a narrow ribbon of negative field. Furthermore, the WLFs were found to be accompanied by MTs, with radical changes in magnetic field strength (or even a sign reversal) observed during the flare. In contrast, there is no obvious signature of MTs in the 50 flares without white-light enhancements. Conclusions: Our results suggest that WLFs occur much more frequently than previously thought, with most WLFs being fairly weak enhancements. This may explain why WLFs are reported rarely. Our observations also suggest that MTs and WLFs are closely related and appear cospatial and cotemporal, when considering HMI data. A greater enhancement of WL emission is often accompanied by a greater change in the line-of-sight component of the unsigned magnetic field. Considering the close relationship between MTs and WLFs, many previously reported flares with MTs may be WLFs. The movie

  4. The Botrytis cinerea xylanase Xyn11A contributes to virulence with its necrotizing activity, not with its catalytic activity

    González Celedonio

    2010-02-01

    Full Text Available Abstract Background The Botrytis cinerea xylanase Xyn11A has been previously shown to be required for full virulence of this organism despite its poor contribution to the secreted xylanase activity and the low xylan content of B. cinerea hosts. Intriguingly, xylanases from other fungi have been shown to have the property, independent of the xylan degrading activity, to induce necrosis when applied to plant tissues, so we decided to test the hypothesis that secreted Xyn11A contributes to virulence by promoting the necrosis of the plant tissue surrounding the infection, therefore facilitating the growth of this necrotroph. Results We show here that Xyn11A has necrotizing activity on plants and that this capacity is conserved in site-directed mutants of the protein lacking the catalytic activity. Besides, Xyn11A contributes to the infection process with the necrotizing and not with the xylan hydrolyzing activity, as the catalytically-impaired Xyn11A variants were able to complement the lower virulence of the xyn11A mutant. The necrotizing activity was mapped to a 30-amino acids peptide in the protein surface, and this region was also shown to mediate binding to tobacco spheroplasts by itself. Conclusions The main contribution of the xylanase Xyn11A to the infection process of B. cinerea is to induce necrosis of the infected plant tissue. A conserved 30-amino acids region on the enzyme surface, away from the xylanase active site, is responsible for this effect and mediates binding to plant cells.

  5. Osteocalcin expressing cells from tendon sheaths in mice contribute to tendon repair by activating Hedgehog signaling

    Wang, Yi; Zhang, Xu; Huang, Huihui; Xia, Yin; Yao, YiFei; Mak, Arthur Fuk-Tat; Yung, Patrick Shu-Hang; Chan, Kai-Ming; Wang, Li; Zhang, Chenglin; Huang, Yu; Mak, Kingston King-Lun

    2017-01-01

    Both extrinsic and intrinsic tissues contribute to tendon repair, but the origin and molecular functions of extrinsic tissues in tendon repair are not fully understood. Here we show that tendon sheath cells harbor stem/progenitor cell properties and contribute to tendon repair by activating Hedgehog signaling. We found that Osteocalcin (Bglap) can be used as an adult tendon-sheath-specific marker in mice. Lineage tracing experiments show that Bglap-expressing cells in adult sheath tissues pos...

  6. Activities Contributing to Total Energy Expenditure in the United States: Results from the NHAPS Study

    Block Gladys

    2004-02-01

    Full Text Available Abstract Background Physical activity is increasingly recognized as an important factor influencing health and disease status. Total energy expenditure, both low-intensity and high-intensity, contributes to maintenance of healthy body weight. This paper presents the results of a quantitative approach to determining the activities that contribute to total energy expenditure in the United States. Methods Data from the National Human Activity Pattern Survey (NHAPS were used. In 1992–1994 the NHAPS sampled 4,185 females and 3,330 males, aged 18 years and over, weighted to be representative of the 48 contiguous United States. A detailed report of each activity performed in the previous 24 hours was obtained. A score was created for each activity, by multiplying duration and intensity for each individual and summing across individuals. This score was then used to rank each activity according to its contribution to total population energy expenditure, for the total sample and separately for each gender, race, age, region, and season. Results This analysis reveals our society to be primarily sedentary; leisure time physical activity contributed only approximately 5% of the population's total energy expenditure. Not counting sleeping, the largest contributor to energy expenditure was "Driving a car", followed by "Office work" and "Watching TV". Household activities accounted for 20.1% and 33.3% of energy expenditure for males and females respectively. Conclusion The information presented in this paper may be useful in identifying common activities that could be appropriate targets for behavioral interventions to increase physical activity.

  7. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Marcus May

    Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

  8. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  9. Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP Signaling.

    Blanchard, M.G.; Kittikulsuth, W.; Nair, A.V.; Baaij, J.H.F. de; Latta, F.; Genzen, J.R.; Kohan, D.E.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2016-01-01

    The transient receptor potential melastatin type 6 (TRPM6) epithelial Mg(2+) channels participate in transcellular Mg(2+) transport in the kidney and intestine. Previous reports suggested a hormonal cAMP-dependent regulation of Mg(2+) reabsorption in the kidney. The molecular details of this process

  10. Contributions of climate change and human activities to runoff change in seven typical catchments across China.

    Zhai, Ran; Tao, Fulu

    2017-12-15

    Climate change and human activities are two major factors affecting water resource change. It is important to understand the roles of the major factors in affecting runoff change in different basins for watershed management. Here, we investigated the trends in climate and runoff in seven typical catchments in seven basins across China from 1961 to 2014. Then we attributed the runoff change to climate change and human activities in each catchment and in three time periods (1980s, 1990s and 2000s), using the VIC model and long-term runoff observation data. During 1961-2014, temperature increased significantly, while the trends in precipitation were insignificant in most of the catchments and inconsistent among the catchments. The runoff in most of the catchments showed a decreasing trend except the Yingluoxia catchment in the northwestern China. The contributions of climate change and human activities to runoff change varied in different catchments and time periods. In the 1980s, climate change contributed more to runoff change than human activities, which was 84%, 59%, -66%, -50%, 59%, 94%, and -59% in the Nianzishan, Yingluoxia, Xiahui, Yangjiaping, Sanjiangkou, Xixian, and Changle catchment, respectively. After that, human activities had played a more essential role in runoff change. In the 1990s and 2000s, human activities contributed more to runoff change than in the 1980s. The contribution by human activities accounted for 84%, -68%, and 67% in the Yingluoxia, Xiahui, and Sanjiangkou catchment, respectively, in the 1990s; and -96%, -67%, -94%, and -142% in the Nianzishan, Yangjiaping, Xixian, and Changle catchment, respectively, in the 2000s. It is also noted that after 2000 human activities caused decrease in runoff in all catchments except the Yingluoxia. Our findings highlight that the effects of human activities, such as increase in water withdrawal, land use/cover change, operation of dams and reservoirs, should be well managed. Copyright © 2017 Elsevier

  11. Do Israeli health promoting schools contribute to students' healthy eating and physical activity habits?

    Hayek, Samah; Tessler, Riki; Bord, Shiran; Endevelt, Ronit; Satran, Carmit; Livne, Irit; Khatib, Mohammed; Harel-Fisch, Yosi; Baron-Epel, Orna

    2017-10-04

    The Israeli Health Promoting School Network (HPSN) is actively committed to enhancing a healthy lifestyle for the entire school population. This study aimed to explore the contribution of school participation in the HPSN and students' individual characteristics to healthy eating and physical activity habits among Israeli school children aged 10-12 years. A cross-sectional survey was conducted among 4166 students in grades 4-6 from 28 schools. The schools were selected from a sample of HPSN affiliated and non-HPSN schools. The contribution of individual characteristics (grade, gender and subjective self-reported health education activities at school) and school characteristics (school type, population group, deprivation score) to healthy eating and physical activity habits was analyzed using multi-level hierarchical models. Multi-level analysis indicated that student's individual characteristic was significantly associated with healthy eating and physical activity habits. The subjective self-reported health education received at school was statistically significant factor associated with students' health behaviors. The school's affiliation with the HPSN was not associated with higher healthy eating and physical activity scores after adjusting for individual factors. These findings suggest that Israeli HPSN schools do not contribute to children's health behaviors more than other schools. Therefore, health promoting activities in HPSN schools need to be improved to justify their recognition as members of the HPS network and to fulfill their mission. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Quality of Life and Leisure Activities: How Do Leisure Activities Contribute to Subjective Well-Being?

    Brajsa-Zganec, Andreja; Merkas, Marina; Sverko, Iva

    2011-01-01

    The quality of life is determined with objective factors and also with subjective perception of factors which influence human life. Leisure activities play a very important role in subjective well-being because they provide opportunities to meet life values and needs. Through participation in leisure activities people build social relationships,…

  13. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  14. Transport on prescription: How can GPs contribute to the promotion of active transport?

    Pistoll, Chance; Furler, John

    2017-10-01

    Active transport (ie walking, cycling, using public transport) can play a part in reducing non-communicable diseases (NCDs). Very little is known about how general practitioners (GPs) can contribute to promoting active transport. We explored GPs' ideas around active transport, and potential barriers and facilitators to its promotion in the clinical setting. Using a maximal variation sample, we conducted 10 semi-structured interviews with GPs in Victoria, Australia. The socioecological model informed data collection and analysis. The idea of active transport resonated with GPs. Limited awareness around active transport and safety concerns regarding commuter cycling were barriers to clinical promotion. GPs believed patients' health, cultural norms, socioeconomic position and access to supportive environments could facilitate participation. Future efforts should prioritise awareness of active transport among GPs. The perspectives of GPs would be valuable to policymakers, particularly in designing programs to mitigate inequalities around active transport access and use.

  15. Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

    Ronzoni, G.; Arco, A. Del; Mora, F.; Segovia, G.

    2016-01-01

    Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats

  16. Use of Dog Parks and the Contribution to Physical Activity for Their Owners

    Evenson, Kelly R.; Shay, Elizabeth; Williamson, Stephanie; Cohen, Deborah A.

    2016-01-01

    Purpose: This study described the use of dog parks in several diverse locations and explored the contribution dog parks made to physical activity of the dog owners. Method: The Systematic Observation of Play and Recreation in Communities (SOPARC) tool was used to count the number and characteristics of people using parks. Observations were…

  17. Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome

    Ge, Hong-You; Nie, Hongling; Madeleine, Pascal

    2009-01-01

    The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients...

  18. Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

    Johansson, S E; Andersen, X E D R; Hansen, R H

    2015-01-01

    . METHODS: Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel occlusion model, and the cerebral blood flow was measured by magnetic resonance imaging two days after reperfusion. In vitro vasoreactivity studies, immunofluorescence and quantitative PCR were performed on cerebral...... in the vascular smooth muscle cells was enhanced and correlated with decreased cerebral blood flow two days after forebrain ischaemia. Furthermore, under conditions when voltage-dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular contraction was enhanced and this enhancement...... was presumably mediated by Ca(2+) influx via upregulated transient receptor potential canonical channels 1 and 6. CONCLUSIONS: Our data demonstrates that endothelin-1-mediated influx of extracellular Ca(2+) activates transient receptor potential canonical channels 1 and 6 in cerebral vascular smooth muscle cells...

  19. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

    Yoichi Takakusagi

    Full Text Available BACKGROUND: TH-302 is a hypoxia-activated prodrug (HAP of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. METHODOLOGY/RESULTS: The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2, with minimal effect under aerobic conditions (21% O2. Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3. Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3, significantly delayed tumor growth. CONCLUSIONS/SIGNIFICANCE: Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the

  20. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

    Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; Kishimoto, Shun; Wojtkowiak, Jonathan W; DeGraff, William; Kesarwala, Aparna H; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Munasinghe, Jeeva P; Gillies, Robert J; Mitchell, James B; Hart, Charles P; Krishna, Murali C

    2014-01-01

    TH-302 is a hypoxia-activated prodrug (HAP) of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR) oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2), with minimal effect under aerobic conditions (21% O2). Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3). Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3)), significantly delayed tumor growth. Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.

  1. P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca(2+) release and SK channel activation.

    Mader, Felix; Krause, Ludwig; Tokay, Tursonjan; Hakenberg, Oliver W; Köhling, Rüdiger; Kirschstein, Timo

    2016-05-01

    Purinergic signaling plays a major role in the enteric nervous system, where it governs gut motility through a number of P2X and P2Y receptors. The aim of this study was to investigate the P2Y receptor-mediated motility in rat longitudinal ileum preparations. Ileum smooth muscle strips were prepared from rats, and fixed in an organ bath. Isometric contraction and relaxation responses of the muscle strips were measured with force transducers. Drugs were applied by adding of stock solutions to the organ bath to yield the individual final concentrations. Application of the non-hydrolyzable P2 receptor agonists α,β-Me-ATP or 2-Me-S-ADP (10, 100 μmol/L) dose-dependently elicited a transient relaxation response followed by a sustained contraction. The relaxation response was largely blocked by SK channel blockers apamin (500 nmol/L) and UCL1684 (10 μmol/L), PLC inhibitor U73122 (100 μmol/L), IP3 receptor blocker 2-APB (100 μmol/L) or sarcoendoplasmic Ca(2+) ATPase inhibitor thapsigargin (1 μmol/L), but not affected by atropine, NO synthase blocker L-NAME or tetrodotoxin. Furthermore, α,β-Me-ATP-induced relaxation was suppressed by P2Y1 receptor antagonist MRS2179 (50 μmol/L) or P2Y13 receptor antagonist MRS2211 (100 μmol/L), and was abolished by co-application of the two antagonists, whereas 2-Me-S-ADP-induced relaxation was abolished by P2Y6 receptor antagonist MRS2578 (50 μmol/L). In addition, P2Y1 receptor antagonist MRS2500 (1 μmol/L) not only abolished α,β-Me-ATP-induced relaxation, but also suppressed 2-Me-S-ADP-induced relaxation. P2Y receptor agonist-induced transient relaxation of rat ileum smooth muscle strips is mediated predominantly by P2Y1 receptor, but also by P2Y6 and P2Y13 receptors, and involves PLC, IP3, Ca(2+) release and SK channel activation, but is independent of acetylcholine and NO release.

  2. Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study

    Klausen, Thomas Kjaer; Pagani, Alberto; Minassi, Alberto

    2009-01-01

    The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-directed mutagenesis, Ca(2+) imaging, and electrophysiology....... Binding of 4alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element...

  3. Activation of Transient Receptor Potential Vanilloid 4 Impairs the Dendritic Arborization of Newborn Neurons in the Hippocampal Dentate Gyrus through the AMPK and Akt Signaling Pathways

    Yujing Tian; Mengwen Qi; Zhouqing Wang; Chunfeng Wu; Zhen Sun; Yingchun Li; Sha Sha; Yimei Du; Lei Chen; Lei Chen; Ling Chen

    2017-01-01

    Neurite growth is an important process for the adult hippocampal neurogenesis which is regulated by a specific range of the intracellular free Ca2+ concentration ([Ca2+]i). Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable channel and activation of it causes an increase in [Ca2+]i. We recently reported that TRPV4 activation promotes the proliferation of stem cells in the adult hippocampal dentate gyrus (DG). The present study aimed to examine the effect of TRPV4 activati...

  4. Transient receptor potential channel superfamily: Role in lower urinary tract function.

    Ogawa, Teruyuki; Imamura, Tetsuya; Nakazawa, Masaki; Hiragata, Shiro; Nagai, Takashi; Minagawa, Tomonori; Yokoyama, Hitoshi; Ishikawa, Masakuni; Domen, Takahisa; Ishizuka, Osamu

    2015-11-01

    Lower urinary tract symptoms associated with neurogenic bladder and overactive bladder syndrome are mediated in part by members of the transient receptor potential channel superfamily. The best studied member of this superfamily is the vanilloid receptor. Other transient receptor potential channels, such as the melastatin receptor and the ankyrin receptor, are also active in the pathogenesis of lower urinary tract dysfunction. However, the detailed mechanisms by which the transient receptor potential channels contribute to lower urinary tract symptoms are still not clear, and the therapeutic benefits of modulating transient receptor potential channel activity have not been proved in the clinical setting. In the present review, to better understand the pathophysiology and therapeutic potential for lower urinary tract symptoms, we summarize the presence and role of different members of the transient receptor potential channel superfamily in the lower urinary tract. © 2015 The Japanese Urological Association.

  5. The Contribution of Generative Leisure Activities to Cognitive Function among Sri Lankan Elderly

    Maselko, Joanna; Sebranek, Matthew; Mun, Mirna Hodzic; Perera, Bilesha; Ahs, Jill; Østbye, Truls

    2014-01-01

    OBJECTIVES Although a substantive body of research has shown a protective association between leisure activities and cognitive function, consistent evidence is lacking about which specific types of activities should be promoted. The objective of this analysis was to examine the unique contribution of generative leisure activities, defined as activities motivated by “a concern for others and a need to contribute something to the next generation” (Erikson). DESIGN Cross-sectional survey. SETTING Peri-urban and rural area in southern Sri Lanka. PARTICIPANTS Community dwelling adults aged 60+ (n=252). MEASUREMENTS Main predictors were leisure activities grouped into generative, social, or solitary. Main outcome was cognitive function assessed with Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS We found that more frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the impact of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured with the MoCA (β =0.47 (0.11 to 0.83) and the IQCODE (β = -0.81 (-1.54 to -0.09)). In this combined model, solitary activities were also independently associated with slower cognitive decline with the MoCA (β =0.40 (0.16, 0.64), but not with IQCODE (β =-0.38 (-0.88, 0.12)); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully by gender. CONCLUSION Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline among the elderly. PMID:25139145

  6. On the contribution of active galactic nuclei to the diffuse X-ray background

    Avni, Y.

    1977-01-01

    It is shown that cosmological evolution has a pronounced effect on the contributions of active galactic nuclei to the diffuse x-ray background. The dependence of such contributions on the form and amount of density evolution, on the deceleration parameter, and on the formation epoch is found. It is established, in particular, that x-ray Seyferts can account for all of the observed 2-10 keV background when the effects of evolution are considered; the required amount of evolution is intermediate between the evolution of quasars and no evolution. (author)

  7. On the contribution of active galactic nuclei to the diffuse X-ray background

    Avni, Y.

    1978-01-01

    We show that cosmological evolution has a pronounced effect on the contributions of active galactic nuclei to the diffuse x-ray background. We find the dependence of such contributions on the form and amount of density evolution, on the deceleration parameter, and on the formation epoch. We find in particular that x-ray Seyferts can account for all of the observed 2-10 keV background when the effects of evolution are considered; the required amount of evolution is intermediate between the evolution of quasars and no evolution. (orig.) [de

  8. Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway.

    Liu, Yan; Qi, Hanping; E, Mingyao; Shi, Pilong; Zhang, Qianhui; Li, Shuzhi; Wang, Ye; Cao, Yonggang; Chen, Yunping; Ba, Lina; Gao, Jingquan; Huang, Wei; Sun, Hongli

    2018-02-01

    Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca 2+ ] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-β 1 ), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-β 1 , cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-β 1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-β 1 /CDK2/cyclin E pathway in the pressure-overloaded rat hearts.

  9. Serotonin Activated Hepatic Stellate Cells Contribute to Sex Disparity in Hepatocellular CarcinomaSummary

    Qiqi Yang

    2017-05-01

    Full Text Available Background & Aims: Hepatocellular carcinoma (HCC occurs more frequently and aggressively in men than in women. Although sex hormones are believed to play a critical role in this disparity, the possible contribution of other factors largely is unknown. We aimed to investigate the role of serotonin on its contribution of sex discrepancy during HCC. Methods: By using an inducible zebrafish HCC model through hepatocyte-specific transgenic krasV12 expression, differential rates of HCC in male and female fish were characterized by both pharmaceutical and genetic interventions. The findings were validated further in human liver disease samples. Results: Accelerated HCC progression was observed in krasV12-expressing male zebrafish and male fish liver tumors were found to have higher hepatic stellate cell (HSC density and activation. Serotonin, which is essential for HSC survival and activation, similarly were found to be synthesized and accumulated more robustly in males than in females. Serotonin-activated HSCs could promote HCC carcinogenesis and concurrently increase serotonin synthesis via transforming growth factor (Tgfb1 expression, hence contributing to sex disparity in HCC. Analysis of liver disease patient samples showed similar male predominant serotonin accumulation and Tgfb1 expression. Conclusions: In both zebrafish HCC models and human liver disease samples, a predominant serotonin synthesis and accumulation in males resulted in higher HSC density and activation as well as Tgfb1 expression, thus accelerating HCC carcinogenesis in males. Keywords: Liver Cancer, TGFB1, Kras, Zebrafish

  10. The proposals on cooperation to foreign centers of science on thermophysical properties of reactor materials in a broad band of pressure and temperatures realized at normal transient and emergency operation activity of nuclear power plants

    Fortov, V.E.

    1996-01-01

    The proposals on cooperation in the area of thermophysical properties of reactor materials in a broad band of pressure and temperature realized at normal transient and emergency operation activity of nuclear power plants are discussed. 1 fig

  11. Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis.

    Souza de Lima, D; Ogusku, M M; Sadahiro, A; Pontillo, A

    2016-07-01

    Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Contribution of generative leisure activities to cognitive function in elderly Sri Lankan adults.

    Maselko, Joanna; Sebranek, Matthew; Mun, Mirna H; Perera, Bilesha; Ahs, Jill; Ostbye, Truls

    2014-09-01

    To examine the unique contribution of generative leisure activities, defined as activities motivated by a concern for others and a need to contribute something to the next generation. Cross-sectional survey. Peri-urban and rural area in southern Sri Lanka. Community-dwelling adults aged 60 and older (N = 252). The main predictors were leisure activities, grouped into generative, social, or solitary. The main outcome was cognitive function, assessed using the Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). More-frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the effect of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured using the MoCA (β = 0.47, 95% confidence interval (CI) = 0.11-0.83) and the IQCODE (β = -0.81, 95% CI = -1.54 to -0.09). In this combined model, solitary activities were also independently associated with slower cognitive decline using the MoCA (β = 0.40, 95% CI = 0.16-0.64) but not the IQCODE (β = -0.38, 95% CI = -0.88-0.12); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully according to sex. Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline in elderly adults. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  13. School children's own views, roles and contribution to choices regarding diet and activity in Spain.

    Lopez-Dicastillo, O; Grande, G; Callery, P

    2013-01-01

      Behaviours regarding food and activity are learned during childhood and continue throughout life. Children can be very important agents in making decisions concerning their own well-being and care and their perspective is essential to understanding how they and/or others make choices for them to achieve a healthy lifestyle. However, their perspectives remain under-researched. This study provides an insight into school children's own perspectives, behaviours and contribution to food and activity choices.   The paper reports on the findings from an ethnographic study with 38 Spanish children aged 5-7 years. Information was obtained through participant observations, diaries kept by children and group interviews. Data were analysed using techniques of analytical induction and constant comparison.   The children who took part in this study described choices about activities with enthusiasm. Children saw activity as a way of learning new things, mastering skills and socializing. They were willing to try and experience new activities and games. However, the activities performed depended on parents' agendas and security issues. In contrast, children reported less interest in and active involvement in food choices. They contributed to family food choices indirectly through the expression of their preferences, not wanting to eat what they disliked or tasting new foods.   Children had strong preferences and motivations, particularly about activities which could be harnessed in interventions to prevent obesity and promote healthy diet and activity. Parental involvement and commitment is also important both to encourage exercise according to children's interests and active informed food choices, including introduction to unfamiliar foods. © 2012 Blackwell Publishing Ltd.

  14. The contribution of dance to daily physical activity among adolescent girls

    Hooker Steven P

    2011-08-01

    Full Text Available Abstract Background Structured physical activity (PA programs are well positioned to promote PA among youth, however, little is known about these programs, particularly dance classes. The aims of this study were to: 1 describe PA levels of girls enrolled in dance classes, 2 determine the contribution of dance classes to total moderate-to-vigorous physical activity (MVPA, and 3 compare PA between days with a dance class (program days and days without a dance class (non-program days. Methods Participants were 149 girls (11-18 years enrolled in dance classes in 11 dance studios. Overall PA was assessed with accelerometry for 8 consecutive days, and girls reported when they attended dance classes during those days. The percent contribution of dance classes to total MVPA was calculated, and data were reduced to compare PA on program days to non-program days. Data were analyzed using mixed models, adjusting for total monitoring time. Results Girls engaged in 25.0 ± 0.9 minutes/day of MVPA. Dance classes contributed 28.7% (95% CI: 25.9%-31.6% to girls' total MVPA. Girls accumulated more MVPA on program (28.7 ± 1.4 minutes/day than non-program days (16.4 ± 1.5 minutes/day (p Conclusions Dance classes contributed a substantial proportion (29% to girls' total MVPA, and girls accumulated 70% more MVPA and 8% less sedentary behavior on program days than on non-program days. Dance classes can make an important contribution to girls' total physical activity.

  15. Transiently Active Wnt/β-Catenin Signaling Is Not Required but Must Be Silenced for Stem Cell Function during Muscle Regeneration

    Malea M. Murphy

    2014-09-01

    Full Text Available Adult muscle’s exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/β-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/β-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which β-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/β-catenin signaling that is important for muscle regeneration.

  16. Do changes in neuromuscular activation contribute to the knee extensor angle-torque relationship?

    Lanza, Marcel B; Balshaw, Thomas G; Folland, Jonathan P

    2017-08-01

    What is the central question of the study? Do changes in neuromuscular activation contribute to the knee extensor angle-torque relationship? What is the main finding and its importance? Both agonist (quadriceps) and antagonist coactivation (hamstrings) differed with knee joint angle during maximal isometric knee extensions and thus both are likely to contribute to the angle-torque relationship. Specifically, two independent measurement techniques showed quadriceps activation to be lower at more extended positions. These effects might influence the capacity for neural changes in response to training and rehabilitation at different knee joint angles. The influence of joint angle on knee extensor neuromuscular activation is unclear, owing in part to the diversity of surface electromyography (sEMG) and/or interpolated twitch technique (ITT) methods used. The aim of the study was to compare neuromuscular activation, using rigorous contemporary sEMG and ITT procedures, during isometric maximal voluntary contractions (iMVCs) of the quadriceps femoris at different knee joint angles and examine whether activation contributes to the angle-torque relationship. Sixteen healthy active men completed two familiarization sessions and two experimental sessions of isometric knee extension and knee flexion contractions. The experimental sessions included the following at each of four joint angles (25, 50, 80 and 106 deg): iMVCs (with and without superimposed evoked doublets); submaximal contractions with superimposed doublets; and evoked twitch and doublet contractions whilst voluntarily passive, and knee flexion iMVC at the same knee joint positions. The absolute quadriceps femoris EMG was normalized to the peak-to-peak amplitude of an evoked maximal M-wave, and the doublet-voluntary torque relationship was used to calculate activation with the ITT. Agonist activation, assessed with both normalized EMG and the ITT, was reduced at the more extended compared with the more flexed

  17. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

    He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Li, Xiao-Dong [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Hong, Mo-Na [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Chen, Qi-Zhi [Shanghai Institute of Hypertension, Shanghai (China); Han, Wei-Qing, E-mail: whan020@gmail.com [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Gao, Ping-Jin, E-mail: gaopingjin@sibs.ac.cn [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China)

    2016-04-29

    Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

  18. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

    He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li; Li, Xiao-Dong; Hong, Mo-Na; Chen, Qi-Zhi; Han, Wei-Qing; Gao, Ping-Jin

    2016-01-01

    Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

  19. Contributions of natural climate changes and human activities to the trend of extreme precipitation

    Gao, Lu; Huang, Jie; Chen, Xingwei; Chen, Ying; Liu, Meibing

    2018-06-01

    This study focuses on the analysis of the nonstationarity characteristics of extreme precipitation and their attributions in the southeastern coastal region of China. The maximum daily precipitation (MDP) series is extracted from observations at 79 meteorological stations in the study area during the first flood season (April-June) from 1960 to 2012. The trends of the mean (Mn) and variance (Var) of MDP are detected using the Generalized Additive Models for Location, Scale, and Shape parameters (GAMLSS) and Mann-Kendall test. The contributions of natural climate change and human activities to the Mn and Var changes of MDP are investigated using six large-scale circulation variables and emissions of four greenhouse gases based on GAMLSS and a contribution analysis method. The results demonstrate that the nonstationarity of extreme precipitation on local scales is significant. The Mn and Var of extreme precipitation increase in the north of Zhejiang, the middle of Fujian, and the south of Guangdong. In general, natural climate change contributes more to Mn from 1960 to 2012 than to Var. However, human activities cause a greater Var in the rapid socioeconomic development period (1986-2012) than in the slow socioeconomic development period (1960-1985), especially in Zhejiang and Guangdong. The community should pay more attention to the possibility of extreme precipitation events and associated disasters triggered by human activities.

  20. Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation

    Sondergaard, B C; Henriksen, K; Wulf, H

    2006-01-01

    OBJECTIVE: Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models. METHODS: Bovine articular cartilage...... explants were stimulated with oncostatin M (OSM) 10 ng/ml and tumor necrosis factor-alpha (TNF-alpha) 20 ng/ml in the presence or absence of the broad-spectrum MMP inhibitor GM6001 and the cysteine protease inhibitor, E64. Cartilage degradation was evaluated in the conditioned medium by glycosaminoglycans...... was measured from CK-deficient mice. RESULTS: OSM and TNF-alpha combined induced significant (Pcartilage degradation products measured by hydroxyproline and CTX-II compared to vehicle control. The cytokines potently induced MMP expression, assessed by zymography, and CK expression...

  1. Can exergaming contribute to improving physical activity levels and health outcomes in children?

    Daley, Amanda J

    2009-08-01

    Physical inactivity among children is a serious public health problem. It has been suggested that high levels of screen time are contributory factors that encourage sedentary lifestyles in young people. As physical inactivity and obesity levels continue to rise in young people, it has been proposed that new-generation active computer- and video-console games (otherwise known as "exergaming") may offer the opportunity to contribute to young people's energy expenditure during their free time. Although studies have produced some encouraging results regarding the energy costs involved in playing active video-console games, the energy costs of playing the authentic versions of activity-based video games are substantially larger, highlighting that active gaming is no substitute for real sports and activities. A small number of exergaming activities engage children in moderate-intensity activity, but most do not. Only 3 very small trials have considered the effects of exergaming on physical activity levels and/or other health outcomes in children. Evidence from these trials has been mixed; positive trends for improvements in some health outcomes in the intervention groups were noted in 2 trials. No adequately powered randomized, controlled trial has been published to date, and no trial has assessed the long-term impact of exergaming on children's health. We now need high-quality randomized, controlled trials to evaluate the effectiveness and sustainability of exergaming, as well as its clinical relevance; until such studies take place, we should remain cautious about its ability to positively affect children's health.

  2. The contribution of parent-child numeracy activities to young Chinese children's mathematical ability.

    Huang, Qi; Zhang, Xiao; Liu, Yingyi; Yang, Wen; Song, Zhanmei

    2017-09-01

    A growing body of recent research has shown that parent-child mathematical activities have a strong effect on children's mathematical learning. However, this research was conducted predominantly in Western societies and focused mainly on mothers' involvement in such activities. This study aimed to examine both mother-child and father-child numeracy activities in Hong Kong Chinese families and both parents' unique roles in predicting young Chinese children's mathematics ability. A sample of 104 Hong Kong Chinese children aged approximately 5 years and their mothers and fathers participated in this study. Mothers and fathers independently reported the frequency of their own numeracy activities with their children. Children were assessed individually using two measures of mathematical ability. Hierarchical regression models were used to investigate the contribution of parent-child numeracy activities to children's mathematical ability. Mothers' participation in number skill activities and fathers' participation in number game and application activities significantly predicted their children's mathematical performance even after controlling for background variables and children's language ability. This study extends previous research with a sample of Chinese kindergarten children and shows that parent-child numeracy activities are related to young children's mathematical ability. The findings highlight the important roles that mothers and fathers play in their young children's mathematical learning. © 2017 The British Psychological Society.

  3. Contribution of intestinal- and cereal-derived phytase activity on phytate degradation in young broilers.

    Morgan, N K; Walk, C L; Bedford, M R; Burton, E J

    2015-07-01

    There is little consensus as to the capability of poultry to utilize dietary phytate without supplemental phytase. Therefore, an experiment was conducted to examine the extent to which endogenous phytase of intestinal and cereal origin contributes to phytate degradation in birds aged 0 to 14 d posthatch. Ross 308 broilers (n = 720) were fed one of 4 experimental diets with differing dietary ingredient combinations and approximate total phytate levels of 10 g/kg, dietary phytase activity analyzed at 460 U/kg, dietary calcium (Ca) levels of 11 g/kg, and nonphytate-phosphorus (P) levels of 4 g/kg. Broiler performance, gizzard, duodenum, jejunum and ileum pH, Ca and P digestibility and solubility, amount of dietary phytate hydrolyzed in the gizzard, jejunum, and ileal digesta phytase activity were analyzed at d 4, 6, 8, 10, 12, and 14 posthatch. Intestinal endogenous phytase activity increased significantly (P Phytase activity and phytate hydrolysis continued to increase with age, with a greater phytase activity and associated increase in phytate hydrolysis and mineral utilization between d 10 and 12. Gizzard and jejunum Ca and P solubility and ileal Ca and P digestibility increased significantly (P phytase activity recovered in the ileum was approximately 45 U/kg. There were strong correlations between phytase activity measured in the ileum and phytate hydrolyzed in the gizzard (r = 0.905, P phytase activity is responsible for phytate-P hydrolysis in broilers. © 2015 Poultry Science Association Inc.

  4. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. The Transuranic Waste Program's integration and planning activities and the contributions of the TRU partnership

    Harms, T.C.; O'Neal, W.; Petersen, C.A.; McDonald, C.E.

    1994-02-01

    The Technical Support Division, EM-351 manages the integration and planning activities of the Transuranic Waste Program. The Transuranic Waste Program manager provides transuranic waste policy, guidance, and issue resolution to Headquarters and the Operations Offices. In addition, the program manager is responsible for developing and implementing an integrated, long-range waste management plan for the transuranic waste system. A steering committee, a core group of support contractors, and numerous interface working groups support the efforts of the program manager. This paper provides an overview of the US Department of Energy's transuranic waste integration activities and a long-range planning process that includes internal and external stakeholder participation. It discusses the contributions and benefits provided by the Transuranic Partnership, most significantly, the integration activities and the body of data collected and assembled by the Partnership

  6. Electronically active defects in the Cu2ZnSn(Se,S)4 alloys as revealed by transient photocapacitance spectroscopy

    Miller, D. Westley; Warren, Charles W.; Gunawan, Oki; Gokmen, Tayfun; Mitzi, David B.; Cohen, J. David

    2012-10-01

    Transient photocapacitance (TPC) spectra were obtained on a series of Cu2ZnSn(Se,S)4 absorber devices with varying Se:S ratios, providing bandgaps (Eg) between 1 eV and 1.5 eV. Efficiencies varied between 8.3% and 9.3% for devices with Eg ≤ 1.2 eV and were near 6.5% for devices with Eg ≥ 1.4 eV. The TPC spectra revealed a band-tail region with Urbach energies at or below 18 meV for the first group, but in the 25-30 meV range for the higher band-gap samples. A deeper defect band centered near 0.8 eV was also observed in most samples. We identified a correlation between the Urbach energies and the voltage deficit in these devices.

  7. Crack growth in first wall made of reduced activation ferritic steel by transient creep due to long pulse operation

    Honda, T.; Kudo, Y.; Hatano, T.; Kikuchi, K.; Nishimura, T.; Saito, M.

    2003-01-01

    The long pulse operation is assumed in ITER and future reactor. If the first wall has a defect, the crack may be propagated by cyclic thermal loads. In addition, flattop of more than 300 s during plasma burning is expected in ITER, so the crack propagation behavior will depend on the operation duration period. This study deals with the crack propagation behavior on F82H under high thermal load cycles. The high heat flux tests were performed under three types of duration periods to investigate creep fatigue behavior. To clarify the crack growth mechanism and the effects of transient creep, three-dimensional analyses were performed. It was concluded that the creep effect during the operation duration period enlarges stress intensity factor K in the cooling period and that consequently, the crack propagation length was increased

  8. Attending a workplace: its contribution to volume and intensity of physical activity.

    Rafferty, Daniel; Dolan, Catriona; Granat, Malcolm

    2016-12-01

    Understanding the contribution that attending a workplace has in accumulating physical activity (PA) may help inform strategies used to increase PA. This study explores the influence that attending work has on the total number of steps taken and the time spent in moderate to vigorous activity (MVPA). A global position system (GPS) was used to identify the geographical domain of the participant. An activity monitor (activPAL, PALtechnologies Ltd, Glasgow, UK) was employed to measure the number of steps taken and the cadence of those steps. Both devices were worn for seven consectutive days and 5 work days extracted post data collection. The data from the two devices were synchronised allowing domain, volume and intensity of PA to be explored. The distance from the home domain to the workplace was used to establish if there was any relationship between commute distance and number of steps accumulated and time in MVPA. Twenty-six office workers (17F; mean age 38 (range 23-65)) were recruited. The number of steps taken per day on average for the group was 11 008 (SD  ±  2999) with time spent in MVPA per day being 32.7 (SD  ±  17.1) min. The commute accounted for 32% or 3550 (SD  ±1664) of the steps taken and 68% or 22.0 (SD  ±14.1) min of MVPA. No statistically significant correlations with distance from home to the workplace for either variable were found. This work explores the contribution that attending work makes to PA, combining data from a GPS system and an objective activity monitor. The commute to works accounts for more than two-thirds of the MVPA accumulated per day. This provides meaningful in sight into the volume and intensity of individuals' activity and also its context.

  9. Contribution of Field Strength Gradients to the Net Vertical Current of Active Regions

    Vemareddy, P.

    2017-12-01

    We examined the contribution of field strength gradients for the degree of net vertical current (NVC) neutralization in active regions (ARs). We used photospheric vector magnetic field observations of AR 11158 obtained by Helioseismic and Magnetic Imager on board SDO and Hinode. The vertical component of the electric current is decomposed into twist and shear terms. The NVC exhibits systematic evolution owing to the presence of the sheared polarity inversion line between rotating and shearing magnetic regions. We found that the sign of shear current distribution is opposite in dominant pixels (60%–65%) to that of twist current distribution, and its time profile bears no systematic trend. This result indicates that the gradient of magnetic field strength contributes to an opposite signed, though smaller in magnitude, current to that contributed by the magnetic field direction in the vertical component of the current. Consequently, the net value of the shear current is negative in both polarity regions, which when added to the net twist current reduces the direct current value in the north (B z > 0) polarity, resulting in a higher degree of NVC neutralization. We conjecture that the observed opposite signs of shear and twist currents are an indication, according to Parker, that the direct volume currents of flux tubes are canceled by their return currents, which are contributed by field strength gradients. Furthermore, with the increase of spatial resolution, we found higher values of twist, shear current distributions. However, the resolution effect is more useful in resolving the field strength gradients, and therefore suggests more contribution from shear current for the degree of NVC neutralization.

  10. Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

    Xi-Tuan Ji

    Full Text Available Chemotherapy-induced neuropathic pain (CNP is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor; whereas minocycline (microglial specific inhibitor had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

  11. [The contribution of Web 2.0 technologies to the empowerment of active patients].

    Oliver-Mora, Martí; Iñiguez-Rueda, Lupicinio

    2017-03-01

    The Spanish health system has recently been marked by the emergence of more active patients who are characterized as being better informed about their disease, having a more participatory attitude, wanting to have a greater influence in making decisions about their health and asserting their rights as patients. Therefore, this article aims to report on how the introduction of Web 2.0 technologies can contribute to the empowering of more active patients. To achieve this, 14 semi-structured interviews were conducted with patients and representatives of patient associations who have used Web 2.0 technologies to interact with other patients or to communicate with health professionals. From the results obtained, we highlight the fact that Web 2.0 technologies provide greater access to health-related information, improve communication between patients and health professionals, and enable the creation of new spaces of interaction among patients. All of the facts above contribute to the formation of a more active role on the part of patients.

  12. An Evaluation Method for Activation Analysis using Pre-evaluated Contribution of Nuclides with Impurity

    Woo, Myeong Hyeon; Kim, Song Hyun; Kim, Do Hyun; Shin, Chang Ho [Hanyang University, Seoul (Korea, Republic of); Kim, Gee Suck [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    Nuclides in radiation facilities become unstable from nuclear reaction. It emits residual radiation to be stable. Some unstable nuclides remain after operation in the material. It continuously emits the radiation, which has a harmful effect to worker when they try maintenance and plant decommissioning. It is known that residual radiation from impurity occupies a large portion of the radiation dose. If impurity concentration is higher than expectation, the effects of residual radiation could be underestimated. Therefore, estimation of residual radiation is repeatedly calculated according to impurity concentration. In this study, an approach estimating the activation was proposed using pre-evaluated nuclide's contribution to reduce the calculation time and effort of worker. In this study, in order to reduce the calculation time and effort of worker, activation analysis method based on pre-evaluated nuclide contribution was proposed. This method was verified using concreate activation problem, which is located in nuclear power plant. The results show that our proposed method has good agreement with Bateman equation.

  13. Impaired activity of adherens junctions contributes to endothelial dilator dysfunction in ageing rat arteries.

    Chang, Fumin; Flavahan, Sheila; Flavahan, Nicholas A

    2017-08-01

    Ageing-induced endothelial dysfunction contributes to organ dysfunction and progression of cardiovascular disease. VE-cadherin clustering at adherens junctions promotes protective endothelial functions, including endothelium-dependent dilatation. Ageing increased internalization and degradation of VE-cadherin, resulting in impaired activity of adherens junctions. Inhibition of VE-cadherin clustering at adherens junctions (function-blocking antibody; FBA) reduced endothelial dilatation in young arteries but did not affect the already impaired dilatation in old arteries. After junctional disruption with the FBA, dilatation was similar in young and old arteries. Src tyrosine kinase activity and tyrosine phosphorylation of VE-cadherin were increased in old arteries. Src inhibition increased VE-cadherin at adherens junctions and increased endothelial dilatation in old, but not young, arteries. Src inhibition did not increase dilatation in old arteries treated with the VE-cadherin FBA. Ageing impairs the activity of adherens junctions, which contributes to endothelial dilator dysfunction. Restoring the activity of adherens junctions could be of therapeutic benefit in vascular ageing. Endothelial dilator dysfunction contributes to pathological vascular ageing. Experiments assessed whether altered activity of endothelial adherens junctions (AJs) might contribute to this dysfunction. Aortas and tail arteries were isolated from young (3-4 months) and old (22-24 months) F344 rats. VE-cadherin immunofluorescent staining at endothelial AJs and AJ width were reduced in old compared to young arteries. A 140 kDa VE-cadherin species was present on the cell surface and in TTX-insoluble fractions, consistent with junctional localization. Levels of the 140 kDa VE-cadherin were decreased, whereas levels of a TTX-soluble 115 kDa VE-cadherin species were increased in old compared to young arteries. Acetylcholine caused endothelium-dependent dilatation that was decreased in old

  14. Contribution of harbour activities to atmospheric aerosol in the Brindisi area

    Donateo, Antonio; Cesari, Daniela; Nocioni, Alessandra; Grasso, Fabio M.; Merico, Eva; Giua, Roberto; Contini, Daniele

    2013-04-01

    The port areas are economic centres and transport hubs, that bring together different transport modes (sea, road, railway transport) and also industrial activities. Ship emissions when docked and during port manoeuvring can have a substantial negative effect on local air quality. The Fagerli and Tarrason (2001) simulation results indicated that ship traffic emissions contribute to 5% and 10% of PM10 concentrations in large parts of Great Britain, Portugal and Italy; similarly to what was obtained by Dalsoren et al. (2009). At the beginning of 2012 it was started the research project CESAPO (Contribution of Emission Sources on the Air quality of the POrt-cities in Greece and Italy), funded within the framework of Interreg Italy-Greece (2007/2013), having as objective the quantification of the contribution to atmospheric particles of emission sources in two important Mediterranean port-cities, namely Patra (Greece) and Brindisi (Italy). In this work the first results of the CESAPO project will be presented giving more emphasis on the analysis of the maritime transport and the activities within the harbour of Brindisi that is characterized by several emission sources operating concurrently. In 2010 and 2011, in the port of Brindisi freight traffic and total goods movement accounted for more than 9.5 million tons, with over 520,000 passengers. To recognize the contribution of harbour activities to PM2.5 and to the total number concentration of particles with respect to other emission sources (urban traffic and industrial pollution) it has been performed an intensive observation period (IOP) of 5 months (June 1 to October 31, 2012). During the IOP the data of 10 fixed monitoring stations (of the regional network managed by ARPA Puglia) and those from two additional stations specifically installed during the project inside the harbour area. A station was used to characterize the chemical composition of PM2.5 and PAHs (in the gaseous and aerosol phases) and the other was

  15. Personalized Social Network Activity Feeds for Increased Interaction and Content Contribution

    Shlomo eBerkovsky

    2015-10-01

    Full Text Available Online social networks were originally conceived as means of sharing information and activities with friends, and their success has been one of the primary contributors of the tremendous growth of the Web. Social network activity feeds were devised as a means to aggregate recent actions of friends into a convenient list. But the volume of actions and content generated by social network users is overwhelming, such that keeping users up-to-date with friend activities is an ongoing challenge for social network providers. Personalization has been proposed as a solution to combat social network information overload and help users to identify the nuggets of relevant information in the incoming flood of network activities. In this paper, we propose and thoroughly evaluate a personalized model for predicting the relevance of the activity feed items, which informs the ranking of the feeds and facilitates personalization. Results of a live study show that the proposed feed personalization approach successfully identifies and promotes relevant feed items and boosts the uptake of the feeds. In addition, it increases the contribution of user-generated content to the social network and spurs interaction between users.

  16. Local Environmental Grassroots Activism: Contributions from Environmental Psychology, Sociology and Politics

    Mihaylov, Nikolay L.; Perkins, Douglas D.

    2015-01-01

    Local environmental grassroots activism is robust and globally ubiquitous despite the ebbs and flows of the general environmental movement. In this review we synthesize social movement, environmental politics, and environmental psychology literatures to answer the following questions: How does the environment emerge as a topic for community action and how a particular environmental discourse (preservation, conservation, public health, Deep Ecology, justice, localism and other responses to modernization and development) becomes dominant? How does a community coalesce around the environmental issue and its particular framing? What is the relationship between local and supralocal (regional, national, global) activism? We contrast “Not in My Back Yard” (NIMBY) activism and environmental liberation and discuss the significance of local knowledge and scale, nature as an issue for activism, place attachment and its disruption, and place-based power inequalities. Environmental psychology contributions to established scholarship on environmental activism are proposed: the components of place attachment are conceptualized in novel ways and a continuous dweller and activist place attachment is elaborated. PMID:25806672

  17. Local environmental grassroots activism: contributions from environmental psychology, sociology and politics.

    Mihaylov, Nikolay L; Perkins, Douglas D

    2015-03-23

    Local environmental grassroots activism is robust and globally ubiquitous despite the ebbs and flows of the general environmental movement. In this review we synthesize social movement, environmental politics, and environmental psychology literatures to answer the following questions: How does the environment emerge as a topic for community action and how a particular environmental discourse (preservation, conservation, public health, Deep Ecology, justice, localism and other responses to modernization and development) becomes dominant? How does a community coalesce around the environmental issue and its particular framing? What is the relationship between local and supralocal (regional, national, global) activism? We contrast "Not in My Back Yard" (NIMBY) activism and environmental liberation and discuss the significance of local knowledge and scale, nature as an issue for activism, place attachment and its disruption, and place-based power inequalities. Environmental psychology contributions to established scholarship on environmental activism are proposed: the components of place attachment are conceptualized in novel ways and a continuous dweller and activist place attachment is elaborated.

  18. 5-Lipoxygenase contributes to PPARγ activation in macrophages in response to apoptotic cells.

    von Knethen, Andreas; Sha, Lisa K; Kuchler, Laura; Heeg, Annika K; Fuhrmann, Dominik; Heide, Heinrich; Wittig, Ilka; Maier, Thorsten J; Steinhilber, Dieter; Brüne, Bernhard

    2013-12-01

    Macrophage polarization to an anti-inflammatory phenotype upon contact with apoptotic cells is a contributing hallmark to immune suppression during the late phase of sepsis. Although the peroxisome proliferator-activated receptor γ (PPARγ) supports this macrophage phenotype switch, it remains elusive how apoptotic cells activate PPARγ. Assuming that a molecule causing PPARγ activation in macrophages originates in the cell membrane of apoptotic cells we analyzed lipid rafts from apoptotic, necrotic, and living human Jurkat T cells which showed the presence of 5-lipoxygenase (5-LO) in lipid rafts of apoptotic cells only. Incubating macrophages with lipid rafts of apoptotic, but not necrotic or living cells, induced PPAR responsive element (PPRE)-driven mRuby reporter gene expression in RAW 264.7 macrophages stably transduced with a 4xPPRE containing vector. Experiments with lipid rafts of apoptotic murine EL4 T cells revealed similar results. To verify the involvement of 5-LO in activating PPARγ in macrophages, Jurkat T cells were incubated with the 5-LO inhibitor MK-866 prior to induction of apoptosis, which failed to induce mRuby expression. Similar results were obtained with lipid rafts of apoptotic EL4 T cells preexposed to the 5-LO inhibitors zileuton and CJ-13610. Interestingly, Jurkat T cells overexpressing 5-LO failed to activate PPARγ in macrophages, while their 5-LO overexpressing apoptotic counterparts did. Our results suggest that during apoptosis 5-LO gets associated with lipid rafts and synthesizes ligands that in turn stimulate PPARγ in macrophages. © 2013.

  19. Repeated Transient Jets from a Warped Disk in the Symbiotic Prototype Z And: A Link to the Long-lasting Active Phase

    Skopal, Augustin; Tarasova, Taya. N.; Wolf, Marek; Dubovský, Pavol A.; Kudzej, Igor

    2018-05-01

    Active phases of some symbiotic binaries survive for a long time, from years to decades. The accretion process onto a white dwarf (WD) sustaining long-lasting activity, and sometimes leading to collimated ejection, is not well understood. We present the repeated emergence of highly collimated outflows (jets) from the symbiotic prototype Z And during its 2008 and 2009–10 outbursts and suggest their link to the current long-lasting (from 2000) active phase. We monitored Z And with high-resolution spectroscopy, multicolor UBVR C—and high time resolution—photometry. The well-pronounced bipolar jets were ejected again during the 2009–10 outburst together with the simultaneous emergence of the rapid photometric variability (Δm ≈ 0.06 mag) on the timescale of hours, showing similar properties as those during the 2006 outburst. These phenomena and the measured disk–jets connection could be caused by the radiation-induced warping of the inner disk due to a significant increase of the burning WD luminosity. Ejection of transient jets by Z And around outburst maxima signals a transient accretion at rates above the upper limit of the stable hydrogen burning on the WD surface, and thus proves the nature of Z And-type outbursts. The enhanced accretion through the disk warping, supplemented by the accretion from the giant’s wind, can keep a high luminosity of the WD for a long time, until depletion of the disk. In this way, the jets provide a link to long-lasting active phases of Z And.

  20. Experimental Contribution to High Precision Characterization of Magnetic Forces in Active Magnetic Bearings

    Kjølhede, Klaus; Santos, Ilmar

    2006-01-01

    Parameter identification procedures and model validation are major steps towards intelligent machines supported by active magnetic bearings (AMB). The ability of measuring the electromagnetic bearing forces, or deriving them from measuring the magnetic flux, strongly contributes to the model...... validation and leads to novel approaches in identifying crucial rotor parameters. This is the main focus of this paper, where an intelligent AMB is being developed with the aim of aiding the accurate identification of damping and stiffness coefficients of active lubricated journal bearings. The main...... of the magnetic forces is conducted using different experimental tests: (a) by using hall sensors mounted directly on the poles (precise measurements of the magnetic flux) and by an auxiliary system, composed of strain gages and flexible beams attached to the rotor, (b) by measuring the input current and bearing...

  1. Current interruption transients calculation

    Peelo, David F

    2014-01-01

    Provides an original, detailed and practical description of current interruption transients, origins, and the circuits involved, and how they can be calculated Current Interruption Transients Calculationis a comprehensive resource for the understanding, calculation and analysis of the transient recovery voltages (TRVs) and related re-ignition or re-striking transients associated with fault current interruption and the switching of inductive and capacitive load currents in circuits. This book provides an original, detailed and practical description of current interruption transients, origins,

  2. Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia.

    Spiegel, Daniel P; Byblow, Winston D; Hess, Robert F; Thompson, Benjamin

    2013-10-01

    Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia. We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye. Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level-dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye. A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS. These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

  3. Beyond a man's world: contributions from considering gender in the study of bus drivers' work activity.

    Cunha, Liliana; Nogueira, Sónia; Lacomblez, Marianne

    2014-01-01

    Bus driving is a typically male occupation undergoing a process of feminization. Although men remain a majority, women's integration has raised some questions, namely, related to work organization or its impact on health. This paper focuses on the contributions of assuming a gender perspective in the analysis of the bus driving occupation and the conditions under which it is performed. Twenty female and 158 male bus drivers. Qualitative and quantitative approaches were combined. Ergonomic work analysis and individual interviews were used, as well as INSAT (Work and Health Questionnaire). Difficulties inherent to the work activity were highlighted, in terms of working hours and management of "peripheral tasks", with implications for the balance between professional and personal life. These difficulties were reported differently by men and women, although both made themselves clear about the impact on their career and health. Taking gender into consideration has enabled an enrichment of the questions that guide the analysis of this work activity, and contributed to a new perspective on the work performed by this occupational group as well as a new approach to study the history of the transport industry by proposing as focus of analysis issues related to "gender mobility".

  4. The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons

    Marina ePolito

    2013-11-01

    Full Text Available The NO-cGMP signaling plays an important role in the regulation of striatal function although the mechanisms of action of cGMP specifically in medium spiny neurons (MSNs remain unclear. Using genetically encoded fluorescent biosensors, including a novel Epac-based sensor (EPAC-SH150 with increased sensitivity for cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO donors in both striatonigral and striatopallidal MSNs, and this cGMP signal was controlled partially by PDE2. At the level of cAMP brief forskolin stimulations produced transient cAMP signals which differed between D1 and D2 medium spiny neurons. NO inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect that was translated and magnified downstream of cAMP, at the level of PKA. PDE2 thus appears as a critical effector of NO which modulates the post-synaptic response of MSNs to dopaminergic transmission.

  5. Geometrically nonlinear transient vibrations of actively damped anti-symmetric angle ply laminated composite shallow shell using active fibre composite (AFC) actuators

    Ashok, M. H.; Shivakumar, J.; Nandurkar, Santosh; Khadakbhavi, Vishwanath; Pujari, Sanjay

    2018-02-01

    In present work, the thin laminated composite shallow shell as smart structure with AFC material’s ACLD treatment is analyzed for geometrically nonlinear transient vibrations. The AFC material is used to make the constraining layer of the ACLD treatment. Golla-Hughes-McTavish (GHM) is used to model the constrained viscoelastic layer of the ACLD treatment in time domain. Along with a simple first-order shear deformation theory the Von Kármán type non-linear strain displacement relations are used for deriving this electromechanical coupled problem. A 3-dimensional finite element model of smart composite panels integrated with the ACLD treated patches has been modelled to reveal the performance of ACLD treated patches on improving the damping properties of slender anti-symmetric angle-ply laminated shallow shell, in controlling the transient vibrations which are geometrically nonlinear. The mathematical results explain that the ACLD treated patches considerably enhance the damping properties of anti-symmetric angle-ply panels undergoing geometrically nonlinear transient vibrations.

  6. Signal-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate without activation of phospholipase C: implications on gating of Drosophila TRPL (transient receptor potential-like) channel.

    Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

    2012-01-06

    In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P(2) in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P(2) was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P(2) is not an inhibitor of TRPL channel activation. PI(4,5)P(2) hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P(2) levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P(2) is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating.

  7. Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production.

    Deshmukh, Hitesh S; Shaver, Colleen; Case, Lisa M; Dietsch, Maggie; Wesselkamper, Scott C; Hardie, William D; Korfhagen, Thomas R; Corradi, Massimo; Nadel, Jay A; Borchers, Michael T; Leikauf, George D

    2008-04-01

    Chronic obstructive pulmonary disease (COPD), a global public health problem, is characterized by progressive difficulty in breathing, with increased mucin production, especially in the small airways. Acrolein, a constituent of cigarette smoke and an endogenous mediator of oxidative stress, increases airway mucin 5, subtypes A and C (MUC5AC) production; however, the mechanism remains unclear. In this study, increased mMUC5AC transcripts and protein were associated with increased lung matrix metalloproteinase 9 (mMMP9) transcripts, protein, and activity in acrolein-exposed mice. Increased mMUC5AC transcripts and mucin protein were diminished in gene-targeted Mmp9 mice [Mmp9((-/-))] or in mice treated with an epidermal growth factor receptor (EGFR) inhibitor, erlotinib. Acrolein also decreased mTissue inhibitor of metalloproteinase protein 3 (an MMP9 inhibitor) transcript levels. In a cell-free system, acrolein increased pro-hMMP9 cleavage and activity in concentrations (100-300 nM) found in sputum from subjects with COPD. Acrolein increased hMMP9 transcripts in human airway cells, which was inhibited by an MMP inhibitor, EGFR-neutralizing antibody, or a mitogen-activated protein kinase (MAPK) 3/2 inhibitor. Together these findings indicate that acrolein can initiate cleavage of pro-hMMP9 and EGFR/MAPK signaling that leads to additional MMP9 formation. Augmentation of hMMP9 activity, in turn, could contribute to persistent excessive mucin production.

  8. Thrombopoietin contributes to enhanced platelet activation in patients with unstable angina.

    Lupia, Enrico; Bosco, Ornella; Bergerone, Serena; Dondi, Anna Erna; Goffi, Alberto; Oliaro, Elena; Cordero, Marco; Del Sorbo, Lorenzo; Trevi, Giampaolo; Montrucchio, Giuseppe

    2006-12-05

    We sought to investigate the potential role of elevated levels of thrombopoietin (TPO) in platelet activation during unstable angina (UA). Thrombopoietin is a humoral growth factor that does not induce platelet aggregation per se, but primes platelet activation in response to several agonists. No data concerning its contribution to platelet function abnormalities described in patients with UA are available. We studied 15 patients with UA and, as controls, 15 patients with stable angina (SA) and 15 healthy subjects. We measured TPO and C-reactive protein (CRP), as well as monocyte-platelet binding and the platelet expression of P-selectin and of the TPO receptor, c-Mpl. The priming activity of patient or control plasma on platelet aggregation and monocyte-platelet binding and the role of TPO in this effect also were studied. Patients with UA showed higher circulating TPO levels, as well as increased monocyte-platelet binding, platelet P-selectin expression, and CRP levels, than those with SA and healthy control subjects. The UA patients also showed reduced platelet expression of the TPO receptor, c-Mpl. In vitro, the plasma from UA patients, but not from SA patients or healthy controls, primed platelet aggregation and monocyte-platelet binding, which were both reduced when an inhibitor of TPO was used. Thrombopoietin may enhance platelet activation in the early phases of UA, potentially participating in the pathogenesis of acute coronary syndromes.

  9. Capturing single cell genomes of active polysaccharide degraders: an unexpected contribution of Verrucomicrobia.

    Manuel Martinez-Garcia

    Full Text Available Microbial hydrolysis of polysaccharides is critical to ecosystem functioning and is of great interest in diverse biotechnological applications, such as biofuel production and bioremediation. Here we demonstrate the use of a new, efficient approach to recover genomes of active polysaccharide degraders from natural, complex microbial assemblages, using a combination of fluorescently labeled substrates, fluorescence-activated cell sorting, and single cell genomics. We employed this approach to analyze freshwater and coastal bacterioplankton for degraders of laminarin and xylan, two of the most abundant storage and structural polysaccharides in nature. Our results suggest that a few phylotypes of Verrucomicrobia make a considerable contribution to polysaccharide degradation, although they constituted only a minor fraction of the total microbial community. Genomic sequencing of five cells, representing the most predominant, polysaccharide-active Verrucomicrobia phylotype, revealed significant enrichment in genes encoding a wide spectrum of glycoside hydrolases, sulfatases, peptidases, carbohydrate lyases and esterases, confirming that these organisms were well equipped for the hydrolysis of diverse polysaccharides. Remarkably, this enrichment was on average higher than in the sequenced representatives of Bacteroidetes, which are frequently regarded as highly efficient biopolymer degraders. These findings shed light on the ecological roles of uncultured Verrucomicrobia and suggest specific taxa as promising bioprospecting targets. The employed method offers a powerful tool to rapidly identify and recover discrete genomes of active players in polysaccharide degradation, without the need for cultivation.

  10. Microglial Over-Activation by Social Defeat Stress Contributes to Anxiety- and Depressive-Like Behaviors

    Dirson J. Stein

    2017-10-01

    Full Text Available Hyper activation of the neuroimmune system is strongly related to the development of neuropsychiatric disorders. Psychosocial stress has been postulated to play an important role in triggering anxiety and major depression. In preclinical models, there is mounting evidence that social defeat stress activates microglial cells in the central nervous system. This type of stress could be one of the major factors in the development of these psychopathologies. Here, we reviewed the most recent literature on social defeat and the associated immunological reactions. We focused our attention on microglial cells and kept the effect of social defeat over microglia separate from the effect of this stressor on other immune cells and the influence of peripheral immune components in priming central immune reactions. Furthermore, we considered how social defeat stress affects microglial cells and the consequent development of anxiety- and depressive-like states in preclinical studies. We highlighted evidence for the negative impact of the over-activation of the neuroimmune system, especially by the overproduction of pro-inflammatory mediators and cytotoxins. Overproduction of these molecules may cause cellular damage and loss or decreased function of neuronal activity by excessively pruning synaptic connections that ultimately contribute to the development of anxiety- and depressive-like states.

  11. VObs.it, the Italian contribution to the international Virtual Observatory-History, activities, strategy

    Pasian, F.

    2015-06-01

    The origins of the Italian contribution to the international Virtual Observatory (VO) were mainly tied to the definition and implementation of a Data Grid using Grid standards. From there on, by means of a step-wise evolution, activities started including the implementation of VO-aware tools and facilities, or the production of services accessing data archives in ways compliant to the international VO standards. An important activity the Italian VO community has carried out is the dissemination of the VO capabilities to professionals, students and amateurs: in particular, an important and maybe unique success has been bringing to the classrooms the VO, and using it as a powerful tool to teach astronomy at all levels, from junior high school to undergraduate courses. Lately, there has been also direct involvement of the Italian community in the definition of standards and services within the framework of the International Virtual Observatory Alliance (IVOA), and participation and leadership in the IVOA Working Groups. Along this path, the national funding for these activities has been rather low, although essential to carry the activities on. There were no bursts of funding to allow a quick rise in activities leading to the fast realisation of tools and systems. Rather, the manpower involved in VObs.it has been always fairly low but steady. In the view of managing a national VO initiative with a low budget, strategic choices were made to exploit the available resources and to guarantee a constant background activity, mainly geared at providing services to the community, development in lower-priority VO areas, dissemination and support.

  12. Elevated β-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells

    Barghout, Samir H. [Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Zepeda, Nubia; Xu, Zhihua [Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Steed, Helen [Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Lee, Cheng-Han [Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Fu, YangXin, E-mail: yangxin@ualberta.ca [Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada)

    2015-12-04

    Ovarian cancer is the fifth leading cause of cancer-related mortalities in women. Epithelial ovarian cancer (EOC) represents approximately 90% of all ovarian malignancies. Most EOC patients are diagnosed at advanced stages and current chemotherapy regimens are ineffective against advanced EOC due to the development of chemoresistance. It is important to better understand the molecular mechanisms underlying acquired resistance to effectively manage this disease. In this study, we examined the expression of the Wnt/β-catenin signaling components in the paired cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) EOC cell lines. Our results showed that several negative regulators of Wnt signaling are downregulated, whereas a few Wnt ligands and known Wnt/β-catenin target genes are upregulated in A2780cp cells compared to A2780s cells, suggesting that Wnt/β-catenin signaling is more active in A2780cp cells. Further analysis revealed nuclear localization of β-catenin and higher β-catenin transcriptional activity in A2780cp cells compared to A2780s cells. Finally, we demonstrated that chemical inhibition of β-catenin transcriptional activity by its inhibitor CCT036477 sensitized A2780cp cells to carboplatin, supporting a role for β-catenin in carboplatin resistance in A2780cp cells. In conclusion, our data suggest that increased Wnt/β-catenin signaling activity contributes to carboplatin resistance in A2780cp cells. - Highlights: • Wnt ligands and target genes are upregulated in cisplatin resistant A2780cp cells. • Negative regulators of Wnt signaling are down-regulated in A2780cp cells. • β-catenin transcriptional activity is higher in A2780cp cells compared to A2780s cells. • Inhibition of β-catenin activity increases carboplatin cytotoxicity in A2780cp cells.

  13. Elevated β-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells

    Barghout, Samir H.; Zepeda, Nubia; Xu, Zhihua; Steed, Helen; Lee, Cheng-Han; Fu, YangXin

    2015-01-01

    Ovarian cancer is the fifth leading cause of cancer-related mortalities in women. Epithelial ovarian cancer (EOC) represents approximately 90% of all ovarian malignancies. Most EOC patients are diagnosed at advanced stages and current chemotherapy regimens are ineffective against advanced EOC due to the development of chemoresistance. It is important to better understand the molecular mechanisms underlying acquired resistance to effectively manage this disease. In this study, we examined the expression of the Wnt/β-catenin signaling components in the paired cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) EOC cell lines. Our results showed that several negative regulators of Wnt signaling are downregulated, whereas a few Wnt ligands and known Wnt/β-catenin target genes are upregulated in A2780cp cells compared to A2780s cells, suggesting that Wnt/β-catenin signaling is more active in A2780cp cells. Further analysis revealed nuclear localization of β-catenin and higher β-catenin transcriptional activity in A2780cp cells compared to A2780s cells. Finally, we demonstrated that chemical inhibition of β-catenin transcriptional activity by its inhibitor CCT036477 sensitized A2780cp cells to carboplatin, supporting a role for β-catenin in carboplatin resistance in A2780cp cells. In conclusion, our data suggest that increased Wnt/β-catenin signaling activity contributes to carboplatin resistance in A2780cp cells. - Highlights: • Wnt ligands and target genes are upregulated in cisplatin resistant A2780cp cells. • Negative regulators of Wnt signaling are down-regulated in A2780cp cells. • β-catenin transcriptional activity is higher in A2780cp cells compared to A2780s cells. • Inhibition of β-catenin activity increases carboplatin cytotoxicity in A2780cp cells.

  14. Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma.

    Yoo, Byoung Kwon; Santhekadur, Prasanna K; Gredler, Rachel; Chen, Dong; Emdad, Luni; Bhutia, Sujit; Pannell, Lewis; Fisher, Paul B; Sarkar, Devanand

    2011-05-01

    There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and coimmunoprecipitation followed by mass spectrometry, we identified staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Coimmunoprecipitation and colocalization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating small interfering RNA (siRNA) and micro RNA (miRNA)-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ≈74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor messenger RNAs (mRNAs) that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo, thus revealing a potential role of SND1 in hepatocarcinogenesis. We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC. Copyright © 2011 American Association for the Study of Liver Diseases.

  15. Activation of the polyol pathway may contribute to increased risk of radiocontrast agent nephrotoxicity in diabetes

    Kaplan, D.L.; Mann, P.L.; Zager, P.G.; Smith, M.A.

    1991-01-01

    The incidence of radiocontrast (RC) agent nephrotoxicity is higher in diabetic than non-diabetic patients. RC nephropathy involves both glomerular and tubular cells. The authors postulate that activation of the polyol pathway contributes to the increased susceptibility of diabetics to RC nephrotoxicity. Mesangial cells modulate GFR by altering the capillary surface area available for filtration. Toxic insult to mesangial cells can impair glomerular function. The present study was performed to determine if mesangial cells isolated from galactose fed rats, the classic model for studying the effects of polyol accumulation, demonstrate increased susceptibility to RC toxicity. A cellular model was developed to study the effects of RC agents on mesangial cells isolated from rats maintained on diets of 50% galactose (MCG) and 50% dextrin (MCD). MCG's and MCD's were plated in 96 well trays at a density of 6.25 x 10 4 cells/ml. Cells were exposed to Hypaque 90 at concentrations of 10 mM to 1 uM for 1, 2, 4 and 24 hrs. Cell viability was determined by fluorescein diacetate/propidium iodide staining. 3H-thymidine incorporation was used to determine cell proliferation rates. Hypaque 90 produced no direct cytotoxicity at any time points or concentrations tested. An increase in cell proliferation was observed 1 hr after exposure to 1 uM to 1mM Hypaque. Higher concentrations blunted cell proliferation rates. Hypaque 90 produced no direct cytotoxicity at any time points or concentrations tested. An increase in cell proliferation was observed 1 hr after exposure to 1 uM to 1mM Hypaque. Higher concentrations blunted cell proliferation. No significant effects on 3H-thymidine incorporation were observed at later time points. The effects on 3H-thymidine incorporation were more pronounced in MCG's than MCD's. Activation of the polyol pathway amplifies the proliferative response of MC to RC agents. This activation may contribute to the risk of RC nephropathy in diabetics

  16. Contribution of NADPH Oxidase to Membrane CD38 Internalization and Activation in Coronary Arterial Myocytes

    Xu, Ming; Li, Xiao-Xue; Ritter, Joseph K.; Abais, Justine M.; Zhang, Yang; Li, Pin-Lan

    2013-01-01

    The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2 ·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase signaling pathway to exert its action in these CAMs. These findings led us hypothesize that NOX1-derived O2 ·− serves in an autocrine fashion to enhance CD38 internalization, leading to redox activation of CD38-ADP-ribosylcyclase activity in mouse CAMs. To test this hypothesis, confocal microscopy, flow cytometry and a membrane protein biotinylation assay were used in the present study. We first demonstrated that CD38 internalization induced by endothelin-1 (ET-1) was inhibited by silencing of NOX1 gene, but not NOX4 gene. Correspondingly, NOX1 gene silencing abolished ET-1-induced O2 ·− production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2 ·− significantly increased CD38 internalization in CAMs. Lastly, ET-1 was found to markedly increase membrane raft clustering as shown by increased colocalization of cholera toxin-B with CD38 and NOX1. Taken together, these results provide direct evidence that Rac1-NOX1-dependent O2 ·− production mediates CD38 internalization in CAMs, which may represent an important mechanism linking receptor activation with CD38 activity in these cells. PMID:23940720

  17. EP1000 anticipated transient without scram analyses

    Saiu, G.; Frogheri, M.; Schulz, T.L.

    2001-01-01

    The present paper summarizes the main results of the Anticipated Transient Without Scram (ATWS) analysis activity, performed for the European Passive Plant Program (EPP). The behavior of the EP1000 plant following an ATWS has been analyzed by means of the RELAP5/Mod3.2 code. An ATWS is defined as an Anticipated Transient accompanied by a common mode failure in the reactor protection system, such that the control rods do not scram as required to mitigate the consequences of the transient. According to the experience gained in PWR design, the limiting ATWS events, in a PWR, have been found to be the heatup transients caused by a reduction of heat removal capability by the secondary side of the plant. For this reason, the Loss of Normal Feedwater initiating event, to which the failure of the reactor scram is associated, has been analyzed. The purpose of the study is to verify the performance requirements set for the core feedback characteristics (that is to evaluate the effect of the low boron core neutron kinetic parameters), the overpressure protection system, and boration systems to cope with the EUR Acceptance Criteria for ATWS. Another purpose of this analysis was to support development of revised PSA success criteria that would reduce the contribution of ATWS to the large release frequency (LRF). The low boron core improved the basic EP1000 response to an ATWS event. In particular, the peak pressure was significantly lower than that which would result from a standard core configuration. The improved ATWS analysis results also permitted improved ATWS PSA success criteria. For example, the reduced peak pressure allows the use of other plant features to mitigate the event, including manual initiation of feed-bleed cooling in the event of PRHR HX failure. As a result, the core melt frequency and especially the LRF are significantly reduced. (author)

  18. Analysis of Spontaneous and Nerve-Evoked Calcium Transients in Intact Extraocular Muscles in Vitro

    Feng, Cheng-Yuan; Hennig, Grant W.; Corrigan, Robert D.; Smith, Terence K.; von Bartheld, Christopher S.

    2012-01-01

    Extraocular muscles (EOMs) have unique calcium handling properties, yet little is known about the dynamics of calcium events underlying ultrafast and tonic contractions in myofibers of intact EOMs. Superior oblique EOMs of juvenile chickens were dissected with their nerve attached, maintained in oxygenated Krebs buffer, and loaded with fluo-4. Spontaneous and nerve stimulation-evoked calcium transients were recorded and, following calcium imaging, some EOMs were double-labeled with rhodamine-conjugated alpha-bungarotoxin (rhBTX) to identify EOM myofiber types. EOMs showed two main types of spontaneous calcium transients, one slow type (calcium waves with 1/2max duration of 2–12 s, velocity of 25–50 μm/s) and two fast “flash-like” types (Type 1, 30–90 ms; Type 2, 90–150 ms 1/2max duration). Single pulse nerve stimulation evoked fast calcium transients identical to the fast (Type 1) calcium transients. Calcium waves were accompanied by a local myofiber contraction that followed the calcium transient wavefront. The magnitude of calcium-wave induced myofiber contraction far exceeded those of movement induced by nerve stimulation and associated fast calcium transients. Tetrodotoxin eliminated nerve-evoked transients, but not spontaneous transients. Alpha-bungarotoxin eliminated both spontaneous and nerve-evoked fast calcium transients, but not calcium waves, and caffeine increased wave activity. Calcium waves were observed in myofibers lacking spontaneous or evoked fast transients, suggestive of multiply-innervated myofibers, and this was confirmed by double-labeling with rhBTX. We propose that the abundant spontaneous calcium transients and calcium waves with localized contractions that do not depend on innervation may contribute to intrinsic generation of tonic functions of EOMs. PMID:22579493

  19. Transient magnetoviscosity of dilute ferrofluids

    Soto-Aquino, Denisse; Rinaldi, Carlos

    2011-01-01

    The magnetic field induced change in the viscosity of a ferrofluid, commonly known as the magnetoviscous effect and parameterized through the magnetoviscosity, is one of the most interesting and practically relevant aspects of ferrofluid phenomena. Although the steady state behavior of ferrofluids under conditions of applied constant magnetic fields has received considerable attention, comparatively little attention has been given to the transient response of the magnetoviscosity to changes in the applied magnetic field or rate of shear deformation. Such transient response can provide further insight into the dynamics of ferrofluids and find practical application in the design of devices that take advantage of the magnetoviscous effect and inevitably must deal with changes in the applied magnetic field and deformation. In this contribution Brownian dynamics simulations and a simple model based on the ferrohydrodynamics equations are applied to explore the dependence of the transient magnetoviscosity for two cases: (I) a ferrofluid in a constant shear flow wherein the magnetic field is suddenly turned on, and (II) a ferrofluid in a constant magnetic field wherein the shear flow is suddenly started. Both simulations and analysis show that the transient approach to a steady state magnetoviscosity can be either monotonic or oscillatory depending on the relative magnitudes of the applied magnetic field and shear rate. - Research Highlights: →Rotational Brownian dynamics simulations were used to study the transient behavior of the magnetoviscosity of ferrofluids. →Damped and oscillatory approach to steady state magnetoviscosity was observed for step changes in shear rate and magnetic field. →A model based on the ferrohydrodynamics equations qualitatively captured the damped and oscillatory features of the transient response →The transient behavior is due to the interplay of hydrodynamic, magnetic, and Brownian torques on the suspended particles.

  20. A sodium afterdepolarization in rat superior colliculus neurons and its contribution to population activity.

    Ghitani, Nima; Bayguinov, Peter O; Basso, Michele A; Jackson, Meyer B

    2016-07-01

    The mammalian superior colliculus (SC) is a midbrain structure that integrates multimodal sensory inputs and computes commands to initiate rapid eye movements. SC neurons burst with the sudden onset of a visual stimulus, followed by persistent activity that may underlie shifts of attention and decision making. Experiments in vitro suggest that circuit reverberations play a role in the burst activity in the SC, but the origin of persistent activity is unclear. In the present study we characterized an afterdepolarization (ADP) that follows action potentials in slices of rat SC. Population responses seen with voltage-sensitive dye imaging consisted of rapid spikes followed immediately by a second distinct depolarization of lower amplitude and longer duration. Patch-clamp recordings showed qualitatively similar behavior: in nearly all neurons throughout the SC, rapid spikes were followed by an ADP. Ionic and pharmacological manipulations along with experiments with current and voltage steps indicated that the ADP of SC neurons arises from Na(+) current that either persists or resurges following Na(+) channel inactivation at the end of an action potential. Comparisons of pharmacological properties and frequency dependence revealed a clear parallel between patch-clamp recordings and voltage imaging experiments, indicating a common underlying membrane mechanism for the ADP in both single neurons and populations. The ADP can initiate repetitive spiking at intervals consistent with the frequency of persistent activity in the SC. These results indicate that SC neurons have intrinsic membrane properties that can contribute to electrical activity that underlies shifts of attention and decision making. Copyright © 2016 the American Physiological Society.

  1. INTEGRAL Galactic Bulge monitoring: transient activity from KS 1741-293, MXB 1730-335, and IGR J17498-2921

    Chenevez, J.; Brandt, S.; Kuulkers, E.; Alfonso-Garzón, J.; Beckmann, V.; Bird, T.; Courvoisier, Th.; Del Santo, M.; Domingo, A.; Ebisawa, K.; Jonker, P.; Kretschmar, P.; Markwardt, C.; Oosterbroek, T.; Paizis, A.; Pottschmidt, K.; Sánchez-Fernández, C.; Wijnands, R.

    2011-09-01

    As part of its regular monitoring of the Galactic Bulge (see ATel #438) INTEGRAL observed this region of the sky on September 13, 2011, between UTC 9:14:50 and 12:56:26. Both the JEM-X and the IBIS/ISGRI instruments detect the transient neutron star low-mass X-ray binary KS 1741-293 at the following flux levels: JEM-X: 6 ±3 mCrab (3-10 keV) and 14 ±6 mCrab (10-25 keV) ISGRI: 11 ±2 mCrab (18-40 keV) and 13 ±2 mCrab (40-100 keV) We note that the activity of this source already started two weeks ago as has been reported by Linares et al.

  2. The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo.

    Chowdhury, Golam M I; Jiang, Lihong; Rothman, Douglas L; Behar, Kevin L

    2014-07-01

    The capacity of ketone bodies to replace glucose in support of neuronal function is unresolved. Here, we determined the contributions of glucose and ketone bodies to neocortical oxidative metabolism over a large range of brain activity in rats fasted 36 hours and infused intravenously with [2,4-(13)C₂]-D-β-hydroxybutyrate (BHB). Three animal groups and conditions were studied: awake ex vivo, pentobarbital-induced isoelectricity ex vivo, and halothane-anesthetized in vivo, the latter data reanalyzed from a recent study. Rates of neuronal acetyl-CoA oxidation from ketone bodies (V(acCoA-kbN)) and pyruvate (V(pdhN)), and the glutamate-glutamine cycle (V(cyc)) were determined by metabolic modeling of (13)C label trapped in major brain amino acid pools. V(acCoA-kbN) increased gradually with increasing activity, as compared with the steeper change in tricarboxylic acid (TCA) cycle rate (V(tcaN)), supporting a decreasing percentage of neuronal ketone oxidation: ∼100% (isoelectricity), 56% (halothane anesthesia), 36% (awake) with the BHB plasma levels achieved in our experiments (6 to 13 mM). In awake animals ketone oxidation reached saturation for blood levels >17 mM, accounting for 62% of neuronal substrate oxidation, the remainder (38%) provided by glucose. We conclude that ketone bodies present at sufficient concentration to saturate metabolism provides full support of basal (housekeeping) energy needs and up to approximately half of the activity-dependent oxidative needs of neurons.

  3. Active volcanoes observed through Art: the contribution offered by the social networks

    Neri, Marco; Neri, Emilia

    2015-04-01

    Volcanoes have always fascinated people for the wild beauty of their landscapes and also for the fear that they arouse with their eruptive actions, sometimes simply spectacular, but other times terrifying and catastrophic for human activities. In the past, volcanoes were sometimes imagined as a metaphysical gateway to the otherworld; they have inspired the creation of myths and legends ever since three thousand years ago, also represented by paintings of great artistic impact. Modern technology today offers very sophisticated and readily accessed digital tools, and volcanoes continue to be frequently photographed and highly appreciated natural phenomena. Moreover, in recent years, the spread of social networks (Facebook, Twitter, YouTube, Instagram, etc.) have made the widespread dissemination of graphic contributions even easier. The result is that very active and densely inhabited volcanoes such as Etna, Vesuvius and Aeolian Islands, in Italy, have become among the most photographed subjects in the world, providing a popular science tool with formidable influence and usefulness. The beauty of these landscapes have inspired both professional artists and photographers, as well as amateurs, who compete in the social networks for the publication of the most spectacular, artistic or simply most informative images. The end result of this often frantic popular scientific activity is at least two-fold: on one hand, it provides geoscientists and science communicators a quantity of documentation that is almost impossible to acquire through the normal systems of volcano monitoring, while on the other it raises awareness and respect for the land among the civil community.

  4. The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress

    Murphy, Brian J.; Sato, Barbara G.; Dalton, Timothy P.; Laderoute, Keith R.

    2005-01-01

    Hypoxia-inducible factor-1 (HIF-1), the major transcriptional regulator of the mammalian cellular response to low oxygen (hypoxia), is embedded within a complex network of signaling pathways. We have been investigating the importance of another stress-responsive transcription factor, MTF-1, for the adaptation of cells to hypoxia. This article reports that MTF-1 plays a central role in hypoxic cells by contributing to HIF-1 activity. Loss of MTF-1 in transformed Mtf1 null mouse embryonic fibroblasts (MEFs) results in an attenuation of nuclear HIF-1α protein accumulation, HIF-1 transcriptional activity, and expression of an established HIF-1 target gene, glucose transporter-1 (Glut1). Mtf1 null (Mtf1 KO) MEFs also have constitutively higher levels of both glutathione (GSH) and the rate-limiting enzyme involved in GSH synthesis-glutamate cysteine ligase catalytic subunit-than wild type cells. The altered cellular redox state arising from increased GSH may perturb oxygen-sensing mechanisms in hypoxic Mtf1 KO cells and decrease the accumulation of HIF-1α protein. Together, these novel findings define a role for MTF-1 in the regulation of HIF-1 activity

  5. Tissue-type plasminogen activator contributes to remodeling of the rat ductus arteriosus

    Saito, Junichi; Nicho, Naoki; Zheng, Yun-Wen; Ichikawa, Yasuhiro; Ito, Satoko; Umemura, Masanari; Fujita, Takayuki; Ito, Shuichi; Taniguchi, Hideki; Asou, Toshihide; Masuda, Munetaka; Ishikawa, Yoshihiro

    2018-01-01

    Aims The ductus arteriosus (DA) closes after birth to adapt to the robust changes in hemodynamics, which require intimal thickening (IT) to occur. The smooth muscle cells of the DA have been reported to play important roles in IT formation. However, the roles of the endothelial cells (ECs) have not been fully investigated. We herein focused on tissue-type plasminogen activator (t-PA), which is a DA EC dominant gene, and investigated its contribution to IT formation in the DA. Methods and results ECs from the DA and aorta were isolated from fetal rats using fluorescence-activated cell sorting. RT-PCR showed that the t-PA mRNA expression level was 2.7-fold higher in DA ECs than in aortic ECs from full-term rat fetuses (gestational day 21). A strong immunoreaction for t-PA was detected in pre-term and full-term rat DA ECs. t-PA-mediated plasminogen-plasmin conversion activates gelatinase matrix metalloproteinases (MMPs). Gelatin zymography revealed that plasminogen supplementation significantly promoted activation of the elastolytic enzyme MMP-2 in rat DA ECs. In situ zymography demonstrated that marked gelatinase activity was observed at the site of disruption in the internal elastic laminae (IEL) in full-term rat DA. In a three-dimensional vascular model, EC-mediated plasminogen-plasmin conversion augmented the IEL disruption. In vivo administration of plasminogen to pre-term rat fetuses (gestational day 19), in which IT is poorly formed, promoted IEL disruption accompanied by gelatinase activation and enhanced IT formation in the DA. Additionally, experiments using five human DA tissues demonstrated that the t-PA expression level was 3.7-fold higher in the IT area than in the tunica media. t-PA protein expression and gelatinase activity were also detected in the IT area of the human DAs. Conclusion t-PA expressed in ECs may help to form IT of the DA via activation of MMP-2 and disruption of IEL. PMID:29304073

  6. Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance.

    Chunhu Gu

    Full Text Available Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1 is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to ischemia/reperfusion (I/R injury, and elucidate the underlying mechanisms with a focus on SIRT1. Male C57BL/6 young (4-6 mo and aged (22-24 mo mice were subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2, SIRT1 activity and protein carbonyls were assessed. Our data revealed that aged heart exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2 activity concomitant with blunted SIRT1 activity (P<0.05. Exogenous toxic aldehydes (4-HNE exposure in isolated cardiomyocyte verified that aldehyde-induced carbonyl modification on SIRT1 impaired SIRT1 activity leading to worse hypoxia/reoxygenation (H/R injury, which could all be rescued by Alda-1 (ALDH2 activator (all P<0.05. However, SIRT1 inhibitor blocked the protective effect of Alda-1 on H/R cardiomyocyte. Interestingly, myocardial I/R leads to higher carbonylation but lower activity of SIRT1 in aged hearts than that seen in young hearts (P<0.05. The application of Alda-1 significantly reduced the carbonylation on SIRT1 and markedly improved the tolerance to in vivo I/R injury in aged hearts, but failed to protect Sirt1(+/- knockout mice against myocardial I/R injury. This was verified by Alda-1 treatment improved postischemic contractile function recovery in ex vivo perfused aged but not in Sirt1(+/- hearts. Thus, aldehyde/carbonyl stress is accelerated in aging heart. These results provide a new insight that impaired cardiac SIRT1 activity by carbonyl stress plays a critical role in the increased susceptibility of aged heart to I/R injury. ALDH2 activation can restore this aging-related myocardial ischemic intolerance.

  7. THE MERGER-TRIGGERED ACTIVE GALACTIC NUCLEUS CONTRIBUTION TO THE ULTRALUMINOUS INFRARED GALAXY POPULATION

    Draper, A. R.; Ballantyne, D. R.

    2012-01-01

    It has long been thought that there is a connection between ultraluminous infrared galaxies (ULIRGs), quasars, and major mergers. Indeed, simulations show that major mergers are capable of triggering massive starbursts and quasars. However, observations by the Herschel Space Observatory suggest that, at least at high redshift, there may not always be a simple causal connection between ULIRGs and mergers. Here, we combine an evolving merger-triggered active galactic nucleus (AGN) luminosity function with a merger-triggered starburst model to calculate the maximum contribution of major mergers to the ULIRG population. We find that major mergers can account for the entire local population of ULIRGs hosting AGNs and ∼25% of the total local ULIRG luminosity density. By z ∼ 1, major mergers can no longer account for the luminosity density of ULIRGs hosting AGNs and contribute ∼<12% of the total ULIRG luminosity density. This drop is likely due to high-redshift galaxies being more gas rich and therefore able to achieve high star formation rates through secular evolution. Additionally, we find that major mergers can account for the local population of warm ULIRGs. This suggests that selecting high-redshift warm ULIRGs will allow for the identification of high-redshift merger-triggered ULIRGs. As major mergers are likely to trigger very highly obscured AGNs, a significant fraction of the high-redshift warm ULIRG population may host Compton thick AGNs.

  8. Goal clarity and financial planning activities as determinants of retirement savings contributions.

    Stawski, Robert S; Hershey, Douglas A; Jacobs-Lawson, Joy M

    2007-01-01

    Retirement counselors, financial service professionals, and retirement intervention specialists routinely emphasize the importance of developing clear goals for the future; however, few empirical studies have focused on the benefits of retirement goal setting. In the present study, the extent to which goal clarity and financial planning activities predict retirement savings practices was examined among 100 working adults. Path analysis techniques were used to test two competing models, both of which were designed to predict savings contributions. Findings provide support for the model in which retirement goal clarity is a significant predictor of planning practices, and planning, in turn, predicts savings tendencies. Two demographic variables-income and age-were also revealed to be important elements of the model, with income accounting for roughly half of the explained variance in savings contributions. The results of this study have implications for the development of age-based models of planning, as well as implications for retirement counselors and financial planners who advise workers on long-term saving strategies.

  9. Formation of hydroxyl radicals contributes to the bactericidal activity of ciprofloxacin against Pseudomonas aeruginosa biofilms.

    Jensen, Peter Ø; Briales, Alejandra; Brochmann, Rikke P; Wang, Hengzhuang; Kragh, Kasper N; Kolpen, Mette; Hempel, Casper; Bjarnsholt, Thomas; Høiby, Niels; Ciofu, Oana

    2014-04-01

    Antibiotic-tolerant, biofilm-forming Pseudomonas aeruginosa has long been recognized as a major cause of chronic lung infections of cystic fibrosis patients. The mechanisms involved in the activity of antibiotics on biofilm are not completely clear. We have investigated whether the proposed induction of cytotoxic hydroxyl radicals (OH˙) during antibiotic treatment of planktonically grown cells may contribute to action of the commonly used antibiotic ciprofloxacin on P. aeruginosa biofilms. For this purpose, WT PAO1, a catalase deficient ΔkatA and a ciprofloxacin resistant mutant of PAO1 (gyrA), were grown as biofilms in microtiter plates and treated with ciprofloxacin. Formation of OH˙ and total amount of reactive oxygen species (ROS) was measured and viability was estimated. Formation of OH˙ and total ROS in PAO1 biofilms treated with ciprofloxacin was shown but higher levels were measured in ΔkatA biofilms, and no ROS production was seen in the gyrA biofilms. Treatment with ciprofloxacin decreased the viability of PAO1 and ΔkatA biofilms but not of gyrA biofilms. Addition of thiourea, a OH˙ scavenger, decreased the OH˙ levels and killing of PAO1 biofilm. Our study shows that OH˙ is produced by P. aeruginosa biofilms treated with ciprofloxacin, which may contribute to the killing of biofilm subpopulations. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  10. Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

    Delaissé, Jean-Marie; Andersen, Thomas L; Engsig, Michael T

    2003-01-01

    The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute...... significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone...... in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations...

  11. Load rather than length sensitive feedback contributes to soleus muscle activity during human treadmill walking

    af Klint, Richard; Mazzaro, Nazarena; Nielsen, Jens Bo

    2010-01-01

    Walking requires a constant adaptation of locomotor output from sensory afferent feedback mechanisms to ensure efficient and stable gait. We investigated the nature of the sensory afferent feedback contribution to the soleus motoneuronal drive and to the corrective stretch reflex by manipulating...... on the soleus stretch reflex was measured by presenting dorsiflexion perturbations ( approximately 5 degrees, 360-400 degrees/s) in mid and late stances. Short (SLRs) and medium latency reflexes (MLRs) were quantified in a 15 ms analysis window. The MLR decreased with decreased loading (P = 0.......045), but no significant difference was observed for the SLR (P = 0.13). Similarly, the effect of the BWS was measured on the unload response, i.e., the depression in soleus activity following a plantar-flexion perturbation ( approximately 5.6 degrees, 203-247 degrees/s), quantified over a 50 ms analysis window...

  12. Women’s Socio-economic Contribution to Agriculture and Livestock Activities in Rural Areas

    Pınar AYVAZOĞLU DEMİR

    2017-07-01

    Full Text Available In this study, it was aimed to define women’s contributions to agriculture and stockbreeding in central villages of Kars province where is an important stockbreeding area with its livestock existence. The data provided from the survey conducted with 210 women chosen by simple random sampling method constituted the research material. In accordance with the data obtained from the study, it was stated that women in the area spend an average of 4.5 hours a day by stock breeding. It was determined that 37.6% women prepare feed, 40% women feed the animals, 51% women clean stables, 85.2% women make cowpat and 89.5% of them milk. As a result, it is determined that employing and promoting women who play a crucial role in agriculture and livestock activities in working status, giving instructional seminars about animal production and supporting their socio-economic status are important in terms of having qualified livestock production.

  13. Contribution of an activity checking appliance in optimizing the radioprotection in nuclear medicine

    Aubert, B.; Bodez, V.; Reboulet, G.

    1997-01-01

    To measure correctly the activity administrated to a patient with an activity-meter it is necessary to remove the syringe from the syringe-shield, to place it in the activity-meter and then after the measurement to replace it in its shield. An appliance recently issued on market called activity tester allows controlling the activity, preserving at the same time the syringe shield. From it an improvement in the protection of operator results.. Provided the performances of this appliance satisfy utilisation in clinical practice, we have analyzed its contribution in radiation protection, having in view, particularly, the application of optimization principle. Different phases in preparing a radioactive syringe up to injection require around 45 s between the end of pulling and the beginning of the injection, if one uses an activity-meter, and around 25 s if one uses an activity tester. This gain of 20 s per injection is doubled by a gain on exposition because the syringe is not removed from its shield. Considering an yearly amount of 4000 injections with 800 MBq of 99m Tc, the gain per year in effective dose can be estimated to 1.44 h.mSv and to 230 h.mSv for the dose at finger level. Taking into account the IAEA recommendation and the basic currency references used in the industrial field in optimization, 100 FR/year per 1 h.mSv saved, this appliance will be not justified if only the cost of saved dose is considered. Indeed, it costs 40 kFR, or around 4000 FR/year per 1 h.mSv saved, under the hypothesis of a service life estimated at 7 years. However, this gain in exposition must be associated to that related with a manipulations of unsealed sources, easier and shorter, hence providing fewer risks from exposition incidents and/or contamination. The global charge, taking into account a diminution of the effective dose and extremity exposition as well as the reduction of risk of incidents justifies the recommendation for such an appliance in the services of nuclear

  14. NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

    Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

    2016-01-01

    Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

  15. Towards the Development of a Second-Order Approximation in Activity Coefficient Models Based on Group Contributions

    Abildskov, Jens; Constantinou, Leonidas; Gani, Rafiqul

    1996-01-01

    A simple modification of group contribution based models for estimation of liquid phase activity coefficients is proposed. The main feature of this modification is that contributions estimated from the present first-order groups in many instances are found insufficient since the first-order groups...... correlation/prediction capabilities, distinction between isomers and ability to overcome proximity effects....

  16. Transient drainage summary report

    1996-09-01

    This report summarizes the history of transient drainage issues on the Uranium Mill Tailings Remedial Action (UMTRA) Project. It defines and describes the UMTRA Project disposal cell transient drainage process and chronicles UMTRA Project treatment of the transient drainage phenomenon. Section 4.0 includes a conceptual cross section of each UMTRA Project disposal site and summarizes design and construction information, the ground water protection strategy, and the potential for transient drainage

  17. Dynamics of an Active-Site Flap Contributes to Catalysis in a JAMM Family Metallo Deubiquitinase.

    Bueno, Amy N; Shrestha, Rashmi K; Ronau, Judith A; Babar, Aditya; Sheedlo, Michael J; Fuchs, Julian E; Paul, Lake N; Das, Chittaranjan

    2015-10-06

    The endosome-associated deubiquitinase (DUB) AMSH is a member of the JAMM family of zinc-dependent metallo isopeptidases with high selectivity for Lys63-linked polyubiquitin chains, which play a key role in endosomal-lysosomal sorting of activated cell surface receptors. The catalytic domain of the enzyme features a flexible flap near the active site that opens and closes during its catalytic cycle. Structural analysis of its homologues, AMSH-LP (AMSH-like protein) and the fission yeast counterpart, Sst2, suggests that a conserved Phe residue in the flap may be critical for substrate binding and/or catalysis. To gain insight into the contribution of this flap in substrate recognition and catalysis, we generated mutants of Sst2 and characterized them using a combination of enzyme kinetics, X-ray crystallography, molecular dynamics simulations, and isothermal titration calorimetry (ITC). Our analysis shows that the Phe residue in the flap contributes key interactions during the rate-limiting step but not to substrate binding, since mutants of Phe403 exhibit a defect only in kcat but not in KM. Moreover, ITC studies show Phe403 mutants have similar KD for ubiquitin compared to the wild-type enzyme. The X-ray structures of both Phe403Ala and the Phe403Trp, in both the free and ubiquitin bound form, reveal no appreciable structural change that might impair substrate or alter product binding. We observed that the side chain of the Trp residue is oriented identically with respect to the isopeptide moiety of the substrate as the Phe residue in the wild-type enzyme, so the loss of activity seen in this mutant cannot be explained by the absence of a group with the ability to provide van der Waals interactions that facilitate the hyrdolysis of the Lys63-linked diubiquitin. Molecular dynamics simulations indicate that the flap in the Trp mutant is quite flexible, allowing almost free rotation of the indole side chain. Therefore, it is possible that these different dynamic

  18. The design paradox: the contribution of in-house and external design activities on product market performance

    Czarnitzki, Dirk; Thorwarth, Susanne

    2009-01-01

    This paper explores the contribution of design activities on product market performance of Belgian companies. While there is mounting evidence that design can be seen as a strategic tool to successfully spur sales of new product developments at the firm level, the topic of design innovation has not been linked to the open innovation concept yet. In this paper we empirically test whether design activities conducted in-house differ in their contribution to new product sales from externally acqu...

  19. Toll-like receptor agonist augments virus-like particle-mediated protection from Ebola virus with transient immune activation.

    Karen A O Martins

    Full Text Available Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNFα, IL6, MCP1, MIP1α, KC, and MIP1β levels in the periphery and with the activation of dendritic cells (DCs, NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels.

  20. PSH Transient Simulation Modeling

    Muljadi, Eduard [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-21

    PSH Transient Simulation Modeling presentation from the WPTO FY14 - FY16 Peer Review. Transient effects are an important consideration when designing a PSH system, yet numerical techniques for hydraulic transient analysis still need improvements for adjustable-speed (AS) reversible pump-turbine applications.

  1. Modeling Transport in Fractured Porous Media with the Random-Walk Particle Method: The Transient Activity Range and the Particle-Transfer Probability

    Lehua Pan; G.S. Bodvarsson

    2001-01-01

    Multiscale features of transport processes in fractured porous media make numerical modeling a difficult task, both in conceptualization and computation. Modeling the mass transfer through the fracture-matrix interface is one of the critical issues in the simulation of transport in a fractured porous medium. Because conventional dual-continuum-based numerical methods are unable to capture the transient features of the diffusion depth into the matrix (unless they assume a passive matrix medium), such methods will overestimate the transport of tracers through the fractures, especially for the cases with large fracture spacing, resulting in artificial early breakthroughs. We have developed a new method for calculating the particle-transfer probability that can capture the transient features of diffusion depth into the matrix within the framework of the dual-continuum random-walk particle method (RWPM) by introducing a new concept of activity range of a particle within the matrix. Unlike the multiple-continuum approach, the new dual-continuum RWPM does not require using additional grid blocks to represent the matrix. It does not assume a passive matrix medium and can be applied to the cases where global water flow exists in both continua. The new method has been verified against analytical solutions for transport in the fracture-matrix systems with various fracture spacing. The calculations of the breakthrough curves of radionuclides from a potential repository to the water table in Yucca Mountain demonstrate the effectiveness of the new method for simulating 3-D, mountain-scale transport in a heterogeneous, fractured porous medium under variably saturated conditions

  2. Sodium-dependent vitamin C transporter 2 (SVCT2 expression and activity in brain capillary endothelial cells after transient ischemia in mice.

    Burkhard Gess

    Full Text Available Expression and transport activity of Sodium-dependent Vitamin C Transporter 2 (SVCT2 was shown in various tissues and organs. Vitamin C was shown to be cerebroprotective in several animal models of stroke. Data on expression, localization and transport activity of SVCT2 after cerebral ischemia, however, has been scarce so far. Thus, we studied the expression of SVCT2 after middle cerebral artery occlusion (MCAO in mice by immunohistochemistry. We found an upregulation of SVCT2 after stroke. Co-stainings with Occludin, Von-Willebrand Factor and CD34 demonstrated localization of SVCT2 in brain capillary endothelial cells in the ischemic area after stroke. Time-course analyses of SVCT2 expression by immunohistochemistry and western blots showed upregulation in the subacute phase of 2-5 days. Radioactive uptake assays using (14C-labelled ascorbic acid showed a significant increase of ascorbic acid uptake into the brain after stroke. Taken together, these results provide evidence for the expression and transport activity of SVCT2 in brain capillary endothelial cells after transient ischemia in mice. These results may lead to the development of novel neuroprotective strategies in stroke therapy.

  3. Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

    Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

    2010-09-01

    Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

  4. Contribution of hly homologs to the hemolytic activity of Prevotella intermedia.

    Suzuki, Naoko; Fukamachi, Haruka; Arimoto, Takafumi; Yamamoto, Matsuo; Igarashi, Takeshi

    2012-06-01

    Prevotella intermedia is a periodontal pathogen that requires iron for its growth. Although this organism has hemolytic activity, the precise nature of its hemolytic substances and their associated hemolytic actions are yet to be fully determined. In the present study, we identified and characterized several putative hly genes in P. intermedia ATCC25611 which appear to encode hemolysins. Six hly genes (hlyA, B, C, D, E, and hlyI) of P. intermedia were identified by comparing their nucleotide sequences to those of known hly genes of Bacteroides fragilis NCTC9343. The hlyA-E, and hlyI genes were overexpressed individually in the non-hemolytic Escherichia coli strain JW5181 and examined its contribution to the hemolytic activity on sheep blood agar plates. E. coli cells expressing the hlyA and hlyI genes exhibited hemolytic activity under anaerobic conditions. On the other hand, only E. coli cells stably expressing the hlyA gene were able to lyse the red blood cells when cultured under aerobic conditions. In addition, expression of the hlyA and hlyI genes was significantly upregulated in the presence of red blood cells. Furthermore, we found that the growth of P. intermedia was similar in an iron-limited medium supplemented with either red blood cells or heme. Taken together, our results indicate that the hlyA and hlyI genes of P. intermedia encode putative hemolysins that appear to be involved in the lysis of red blood cells, and suggest that these hemolysins might play important roles in the iron-dependent growth of this organism. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice

    Gelderblom, Mathias; Leypoldt, Frank; Lewerenz, Jan; Birkenmayer, Gabriel; Orozco, Denise; Ludewig, Peter; Thundyil, John; Arumugam, Thiruma V; Gerloff, Christian; Tolosa, Eva; Maher, Pamela; Magnus, Tim

    2012-01-01

    The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor α (TNFα) production. Fisetin also inhibited LPS-induced TNFα production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor κB activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia. PMID:22234339

  6. Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation.

    Luczak, Vincent; Blackwell, Kim T; Abel, Ted; Girault, Jean-Antoine; Gervasi, Nicolas

    2017-02-01

    In the hippocampus, cyclic-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) form a critical signaling cascade required for long-lasting synaptic plasticity, learning and memory. Plasticity and memory are known to occur following pathway-specific changes in synaptic strength that are thought to result from spatially and temporally coordinated intracellular signaling events. To better understand how cAMP and PKA dynamically operate within the structural complexity of hippocampal neurons, we used live two-photon imaging and genetically-encoded fluorescent biosensors to monitor cAMP levels or PKA activity in CA1 neurons of acute hippocampal slices. Stimulation of β-adrenergic receptors (isoproterenol) or combined activation of adenylyl cyclase (forskolin) and inhibition of phosphodiesterase (IBMX) produced cAMP transients with greater amplitude and rapid on-rates in intermediate and distal dendrites compared to somata and proximal dendrites. In contrast, isoproterenol produced greater PKA activity in somata and proximal dendrites compared to intermediate and distal dendrites, and the on-rate of PKA activity did not differ between compartments. Computational models show that our observed compartmental difference in cAMP can be reproduced by a uniform distribution of PDE4 and a variable density of adenylyl cyclase that scales with compartment size to compensate for changes in surface to volume ratios. However, reproducing our observed compartmental difference in PKA activity required enrichment of protein phosphatase in small compartments; neither reduced PKA subunits nor increased PKA substrates were sufficient. Together, our imaging and computational results show that compartment diameter interacts with rate-limiting components like adenylyl cyclase, phosphodiesterase and protein phosphatase to shape the spatial and temporal components of cAMP and PKA signaling in CA1 neurons and suggests that small neuronal compartments are most sensitive to c

  7. Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways

    Barreto, Rafael; Mandili, Giorgia; Witzmann, Frank A.; Novelli, Francesco; Zimmers, Teresa A.; Bonetto, Andrea

    2016-01-01

    Cachexia represents one of the primary complications of colorectal cancer due to its effects on depletion of muscle and fat. Evidence suggests that chemotherapeutic regimens, such as Folfiri, contribute to cachexia-related symptoms. The purpose of the present study was to investigate the cachexia signature in different conditions associated with severe muscle wasting, namely Colon-26 (C26) and Folfiri-associated cachexia. Using a quantitative LC-MS/MS approach, we identified significant changes in 386 proteins in the quadriceps muscle of Folfiri-treated mice, and 269 proteins differentially expressed in the C26 hosts (p < 0.05; −1.5 ≥ fold change ≥ +1.5). Comparative analysis isolated 240 proteins that were modulated in common, with a large majority (218) that were down-regulated in both experimental settings. Interestingly, metabolic (47.08%) and structural (21.25%) proteins were the most represented. Pathway analysis revealed mitochondrial dysfunctions in both experimental conditions, also consistent with reduced expression of mediators of mitochondrial fusion (OPA-1, mitofusin-2), fission (DRP-1) and biogenesis (Cytochrome C, PGC-1α). Alterations of oxidative phosphorylation within the TCA cycle, fatty acid metabolism, and Ca2+ signaling were also detected. Overall, the proteomic signature in the presence of both chemotherapy and cancer suggests the activation of mechanisms associated with movement disorders, necrosis, muscle cell death, muscle weakness and muscle damage. Conversely, this is consistent with the inhibition of pathways that regulate nucleotide and fatty acid metabolism, synthesis of ATP, muscle and heart function, as well as ROS scavenging. Interestingly, strong up-regulation of pro-inflammatory acute-phase proteins and a more coordinated modulation of mitochondrial and lipidic metabolisms were observed in the muscle of the C26 hosts that were different from the Folfiri-treated animals. In conclusion, our results suggest that both cancer

  8. Simulation Model of a Transient

    Jauch, Clemens; Sørensen, Poul; Bak-Jensen, Birgitte

    2005-01-01

    This paper describes the simulation model of a controller that enables an active-stall wind turbine to ride through transient faults. The simulated wind turbine is connected to a simple model of a power system. Certain fault scenarios are specified and the turbine shall be able to sustain operati...

  9. Contribution of sensory feedback to plantar flexor muscle activation during push-off in adults with cerebral palsy.

    Frisk, Rasmus F; Jensen, Peter; Kirk, Henrik; Bouyer, Laurent J; Lorentzen, Jakob; Nielsen, Jens B

    2017-12-01

    Exaggerated sensory activity has been assumed to contribute to functional impairment following lesion of the central motor pathway. However, recent studies have suggested that sensory contribution to muscle activity during gait is reduced in stroke patients and children with cerebral palsy (CP). We investigated whether this also occurs in CP adults and whether daily treadmill training is accompanied by alterations in sensory contribution to muscle activity. Seventeen adults with CP and 12 uninjured individuals participated. The participants walked on a treadmill while a robotized ankle-foot orthosis applied unload perturbations at the ankle, thereby removing sensory feedback naturally activated during push-off. Reduction of electromyographic (EMG) activity in the soleus muscle caused by unloads was compared and related to kinematics and ankle joint stiffness measurements. Similar measures were obtained after 6 wk of gait training. We found that sensory contribution to soleus EMG activation was reduced in CP adults compared with uninjured adults. The lowest contribution of sensory feedback was found in participants with lowest maximal gait speed. This was related to increased ankle plantar flexor stiffness. Six weeks of gait training did not alter the contribution of sensory feedback. We conclude that exaggerated sensory activity is unlikely to contribute to impaired gait in CP adults, because sensory contribution to muscle activity during gait was reduced compared with in uninjured individuals. Increased passive stiffness around the ankle joint is likely to diminish sensory feedback during gait so that a larger part of plantar flexor muscle activity must be generated by descending motor commands. NEW & NOTEWORTHY Findings suggest that adults with cerebral palsy have less contribution of sensory feedback to ongoing soleus muscle activation during push-off than uninjured individuals. Increased passive stiffness around the ankle joint is likely to diminish sensory

  10. Factors Contributing to Pelvis Instability in Female Adolescent Athletes During Unilateral Repeated Partial Squat Activity

    Scarborough, Donna Moxley; Linderman, Shannon; Berkson, Eric M.; Oh, Luke S.

    2017-01-01

    Objectives: Unilateral partial squat tasks are often used to assess athletes’ lower extremity (LE) neuromuscular control. Single squat biomechanics such as lateral drop of the non-stance limb’s pelvis have been linked to knee injury risk. Yet, there are limited studies on the factors contributing to pelvic instability during the unilateral partial squat such as anatomical alignment of the knee and hip strength. The purpose of this study was 1) to assess the influence of leg dominance on pelvic drop among female athletes during the repeated unilateral partial squat activity and 2) to investigate the contributions that lower limb kinematics and hip strength have on pelvis drop. Methods: 42 female athletes (27= softball pitchers, 15=gymnasts, avg age=16.48 ± 2.54 years) underwent lower limb assessment. The quadriceps angle (Q angle) and the average of 3 trials for hip abduction and extension strength (handheld dynamometer measurements) were used for analyses. 3D biomechanical analysis of the repeated unilateral partial squat activity followed using a 20 motion capture camera system which created a 15 segment model of each subject. The subject stood on one leg at the lateral edge of a 17.78 cm box with hands placed on the hips and squatted so that the free hanging contralateral limb came as close to the ground without contact for 5 continuous repetitions. One trial for each limb was performed. Peak pelvic drop and ankle, knee and hip angles and torques (normalized by weight) at this time point were calculated using Visual 3D (C-Motion) biomechanical software. Paired T-test, Spearman correlations and multiple regression model statistical analyses were performed. Results: Peak pelvic drop during the unilateral partial squat did not differ significantly on the basis of limb dominance (p=0.831, Dom: -3.40 ± 5.10° , ND: -3.46 ± 4.44°). Peak pelvic drop displayed a Spearman correlation with the functional measure of hip abduction/adduction (ABD/ADD) angle (rs= 0

  11. The European contribution to the development and validation activities for the design of IFMIF lithium facility

    Miccichè, Gioacchino, E-mail: gioacchino.micciche@enea.it [EURATOM-ENEA, CR Brasimone I-40035 Camugnano, BO (Italy); Aiello, Antonio; Bernardi, Davide; Favuzza, Paolo; Agostini, Pietro [EURATOM-ENEA, CR Brasimone I-40035 Camugnano, BO (Italy); Frisoni, Manuela [EURATOM-ENEA, CR Bologna I-40129, BO Italy (Italy); Pinna, Tonio; Porfiri, MariaTeresa [EURATOM-ENEA, CR Frascati I-0044 Frascati, Roma (Italy); Tincani, Amelia [EURATOM-ENEA, CR Brasimone I-40035 Camugnano, BO (Italy); Di Maio, PieroAlessandro [University of Palermo, I-90128 Palermo (Italy); Knaepen, Bernard [Université libre de Bruxelles, I-1050 Bruxelles (Belgium)

    2013-10-15

    Highlights: • Engineering design of the target assembly. • Erosion, corrosion phenomena promoted by the lithium are studied. • Purification system implemented in the LiFus6 loop. • Study of the remote handling maintenance for the IFMIF TA. -- Abstract: The International Fusion Materials Irradiation Facility (IFMIF) is an accelerator-driven intense neutron source where candidate materials for fusion reactors will be tested and validated. The high energy neutron flux is produced by means of two deuteron beams (total current of 250 mA, energy of 40 MeV) that strikes a liquid lithium target circulating in a lithium loop of IFMIF plant. The European (EU) contribution to the development of the lithium facility comprises five procurement packages, as follow: (1) participation to the experimental activities of the EVEDA lithium test loop in Oarai (Japan); (2) study aimed at evaluating the corrosion and erosion phenomena, promoted by lithium, for structural fusion reference materials like AISI 316L and Eurofer; (3) design and validation of the lithium purification method with the aim to provide input data for the design of the purification system of IFIMF lithium loop; (4) design and validation of the remote handling (RH) procedures for the refurbishment/replacement of the EU concept of IFMIF target assembly including the design of the remote handling tools; (5) the engineering design of the European target assembly for IFMIF and the safety and RAMI analyses for the entire IFMIF lithium facility. The paper gives an overview of the status of the activities and of the main outcomes achieved so far.

  12. The European contribution to the development and validation activities for the design of IFMIF lithium facility

    Miccichè, Gioacchino; Aiello, Antonio; Bernardi, Davide; Favuzza, Paolo; Agostini, Pietro; Frisoni, Manuela; Pinna, Tonio; Porfiri, MariaTeresa; Tincani, Amelia; Di Maio, PieroAlessandro; Knaepen, Bernard

    2013-01-01

    Highlights: • Engineering design of the target assembly. • Erosion, corrosion phenomena promoted by the lithium are studied. • Purification system implemented in the LiFus6 loop. • Study of the remote handling maintenance for the IFMIF TA. -- Abstract: The International Fusion Materials Irradiation Facility (IFMIF) is an accelerator-driven intense neutron source where candidate materials for fusion reactors will be tested and validated. The high energy neutron flux is produced by means of two deuteron beams (total current of 250 mA, energy of 40 MeV) that strikes a liquid lithium target circulating in a lithium loop of IFMIF plant. The European (EU) contribution to the development of the lithium facility comprises five procurement packages, as follow: (1) participation to the experimental activities of the EVEDA lithium test loop in Oarai (Japan); (2) study aimed at evaluating the corrosion and erosion phenomena, promoted by lithium, for structural fusion reference materials like AISI 316L and Eurofer; (3) design and validation of the lithium purification method with the aim to provide input data for the design of the purification system of IFIMF lithium loop; (4) design and validation of the remote handling (RH) procedures for the refurbishment/replacement of the EU concept of IFMIF target assembly including the design of the remote handling tools; (5) the engineering design of the European target assembly for IFMIF and the safety and RAMI analyses for the entire IFMIF lithium facility. The paper gives an overview of the status of the activities and of the main outcomes achieved so far

  13. Cognitive aspects of human motor activity: Contribution of right hemisphere and cerebellum

    Sedov A. S.

    2017-09-01

    Full Text Available Background. Concepts of movement and action are not completely synonymous, but what distinguishes one from the other? Movement may be defined as stimulus- driven motor acts, while action implies realization of a specific motor goal, essential for cognitively driven behavior. Although recent clinical and neuroimaging studies have revealed some areas of the brain that mediate cognitive aspects of human motor behavior, the identification of the basic neural circuit underlying the interaction between cognitive and motor functions remains a challenge for neurophysiology and psychology. Objective. In the current study, we used functional magnetic resonance imaging (fMRI to investigate elementary cognitive aspects of human motor behavior. Design. Twenty healthy right-handed volunteers were asked to perform stimulus-driven and goal-directed movements by clenching the right hand into a fist (7 times. The cognitive component lay in anticipation of simple stimuli signals. In order to disentangle the purely motor component of stimulus-driven movements, we used the event-related (ER paradigm. FMRI was performed on a 3 Tesla Siemens Magnetom Verio MR-scanner with 32-channel head coil. Results. We have shown differences in the localization of brain activity depending on the involvement of cognitive functions. These differences testify to the role of the cerebellum and the right hemisphere in motor cognition. In particular, our results suggest that right associative cortical areas, together with the right posterolateral cerebellum (Crus I and lobule VI and basal ganglia, de ne cognitive control of motor activity, promoting a shift from a stimulus-driven to a goal-directed mode. Conclusion. These results, along with recent data from research on cerebro-cerebellar circuitry, redefine the scope of tasks for exploring the contribution of the cerebellum to diverse aspects of human motor behavior and cognition.

  14. Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair.

    Oslund, Karen L; Hyde, Dallas M; Putney, Leialoha F; Alfaro, Mario F; Walby, William F; Tyler, Nancy K; Schelegle, Edward S

    2008-09-01

    We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-2'-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stress-positive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

  15. [From surveillance to work-related accident prevention: the contribution of the ergonomics of the activity].

    Vilela, Rodolfo Andrade de Gouveia; Almeida, Ildeberto Muniz de; Mendes, Renata Wey Berti

    2012-10-01

    Work-related accidents are complex phenomena determined by the work organization process, the dimensions of which are usually invisible to surveillance agents. The scope of this paper was a case study based on documentary evidence to analyze and compare the success of an intervention conducted at a meat processing and packaging factory, by focusing on checking health and safety norms in 1997, and incorporating ergonomic concepts in 2008. In 1997, surveillance actions focused primarily on visible risk factors. Despite fulfilling sanitation requirements, the company still had an annual accident rate of 26% in 2008, which motivated the search for a new approach. In 2008, it was seen that accidents were caused by a vicious cycle involving intense work, technical inadequacy, absenteeism and high turnover (84%) that led the company to recruit inexperienced workers. This scenario was aggravated by authoritarian management practices. The ergonomics of the activity contributed to the understanding of organizational causes -thus superseding the normative aspects of traditional surveillance - which revealed the importance of ensuring that surveillance actions for prevention are more effective.

  16. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

    Hanlon, Lauren A.; Huh, Jimmy W.

    2016-01-01

    Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

  17. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

    John Meshki

    Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

  18. Explaining educational differences in leisure-time physical activity in Europe: the contribution of work-related factors

    Mäkinen, T. E.; Sippola, R.; Borodulin, K.; Rahkonen, O.; Kunst, A.; Klumbiene, J.; Regidor, E.; Ekholm, O.; Mackenbach, J.; Prättälä, R.

    2012-01-01

    Although educational differences in leisure-time physical activity (LTPA) exist across Europe, the independent effect of educational level on leisure-time physical activity has rarely been explored. This study examines the relative contribution of occupational class, employment status, and

  19. What contributes to action plan enactment? Examining characteristics of physical activity plans.

    Fleig, Lena; Gardner, Benjamin; Keller, Jan; Lippke, Sonia; Pomp, Sarah; Wiedemann, Amelie U

    2017-11-01

    Individuals with chronic conditions can benefit from formulating action plans to engage in regular physical activity. However, the content and the successful translation of plans into action, so-called plan enactment, are rarely adequately evaluated. The aim of this study was to describe the content of user-specified plans and to examine whether participants were more likely to enact their plans if these plans were highly specific, viable, and instrumental. The study presents secondary analyses from a larger behavioural intervention in cardiac and orthopaedic rehabilitation. The content of 619 action plans from 229 participants was evaluated by two independent raters (i.e., qualitative analyses and ratings of specificity) and by participants themselves (i.e., instrumentality and viability). Plan enactment was also measured via self-reports. Multilevel analyses examined the relationship between these plan characteristics and subsequent plan enactment, and between plan enactment and aggregated physical activity. Participants preferred to plan leisure-time physical activities anchored around time-based cues. Specificity of occasion cues (i.e., when to act) and highly instrumental plans were positively associated with plan enactment. Interestingly, individuals who planned less specific behavioural responses (i.e., what to do) were more likely to enact their plans. Plan enactment was positively associated with aggregated behaviour. Interventions should not only emphasize the importance of planning, but also the benefits of formulating specific contextual cues. Planning of the behavioural response seems to require less precision. Allowing for some flexibility in executing the anticipated target behaviour seems to aid successful plan enactment. Statement of Contribution What is already known on this subject? Action planning interventions are efficacious in promoting health behaviour. Characteristics of plan content (i.e., specificity) matter for unconditional behaviour

  20. Two different avian cold-sensitive sensory neurons: Transient receptor potential melastatin 8 (TRPM8)-dependent and -independent activation mechanisms.

    Yamamoto, A; Takahashi, K; Saito, S; Tominaga, M; Ohta, T

    2016-12-01

    Sensing the ambient temperature is an important function for survival in animals. Some TRP channels play important roles as detectors of temperature and irritating chemicals. There are functional differences of TRP channels among species. TRPM8 in mammals is activated by cooling compounds and cold temperature, but less information is available on the functional role of TRPM8 in avian species. Here we investigated the pharmacological properties and thermal sensitivities of chicken TRPM8 (cTRPM8) and cold-sensitive mechanisms in avian sensory neurons. In heterologously expressed cTRPM8, menthol and its derivative, WS-12 elicited [Ca 2+ ] i increases, but icilin did not. In chicken sensory neurons, icilin increased [Ca 2+ ] i, in a TRPA1-dependent manner. Icilin selectively stimulated heterologously expressed chicken TRPA1 (cTRPA1). Similar to mammalian orthologue, cTRPM8 was activated by cold. Both heterologous and endogenous expressed cTRPM8 were sensitive to mammalian TRPM8 antagonists. There are two types of cold-sensitive cells regarding menthol sensitivity in chicken sensory neurons. The temperature threshold of menthol-insensitive neurons was significantly lower than that of menthol-sensitive ones. The population of menthol-insensitive neurons was large in chicken but almost little in mammals. The cold-induced [Ca 2+ ] i increases were not abolished by the external Ca 2+ removal or by blockades of PLC-IP 3 pathways and ryanodine channels. The cold stimulation failed to evoke [Ca 2+ ] i increases after intracellular Ca 2+ store-depletion. These results indicate that cTRPM8 acts as a cold-sensor similar to mammals. It is noteworthy that TRPM8-independent cold-sensitive neurons are abundant in chicken sensory neurons. Our results suggest that most of the cold-induced [Ca 2+ ] i increases are mediated via Ca 2+ release from intracellular stores and that these mechanisms may be specific to avian species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Transient behaviour of an adsorption refrigerator. Experimental study of the alcohol/activated carbon system; Comportement transitoire d`une machine frigorifique a absorption. Etude experimentale du systeme alcool / charbon actif

    Luo, L. [Centre National de la Recherche Scientifique (CNRS), 54 - Nancy (France). Lab. des sciences du genie chimique; Feidt, M. [Nancy-1 Univ., 54 - Vandoeuvre-les-Nancy (France)

    1997-03-01

    The objective of this article is to present an experimental study of an adsorption refrigerator, accounting for the transient phenomena in each component of the machine, in particular in the adsorber. The couples adsorbate/adsorbent investigated (activated carbon/methanol or ethanol) have been chosen on the basis of an earlier comparative study. We have performed a full series of experiments to investigate the transient evolution of temperatures, pressures and the cycled mass, in a discontinuous cycle, and along the components of the refrigerating machine. The influence of various parameters is studies by varying one at a time: adsorbate/ adsorbent couple, alcohol load in adsorber, alcohol flowrate, heating power, initial desorption temperature. All these experimental observation are discussed and compared to transient models developed in a separate article. (authors) 12 refs.

  2. Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: implications for mood disorders.

    Stan, Ana D; Schirda, Claudiu V; Bertocci, Michele A; Bebko, Genna M; Kronhaus, Dina M; Aslam, Haris A; LaBarbara, Eduard J; Tanase, Costin; Lockovich, Jeanette C; Pollock, Myrna H; Stiffler, Richelle S; Phillips, Mary L

    2014-09-30

    The dorsomedial prefrontal cortex (MdPFC) and anterior cingulate cortices (ACC) play a critical role in implicit emotion regulation; however the understanding of the specific neurotransmitters that mediate such role is lacking. In this study, we examined relationships between MdPFC concentrations of two neurotransmitters, glutamate and γ-amino butyric acid (GABA), and BOLD activity in ACC during performance of an implicit facial emotion-processing task. Twenty healthy volunteers, aged 20-35 years, were scanned while performing an implicit facial emotion-processing task, whereby presented facial expressions changed from neutral to one of the four emotions: happy, anger, fear, or sad. Glutamate concentrations were measured before and after the emotion-processing task in right MdPFC using magnetic resonance spectroscopy (MRS). GABA concentrations were measured in bilateral MdPFC after the emotion-processing task. Multiple regression models were run to determine the relative contribution of glutamate and GABA concentration, age, and gender to BOLD signal in ACC to each of the four emotions. Multiple regression analyses revealed a significant negative correlation between MdPFC GABA concentration and BOLD signal in subgenual ACC (psad versus shape contrast. For the anger versus shape contrast, there was a significant negative correlation between age and BOLD signal in pregenual ACC (p<0.05, corrected) and a positive correlation between MdPFC glutamate concentration (pre-task) and BOLD signal in pregenual ACC (p<0.05, corrected). Our findings are the first to provide insight into relationships between MdPFC neurotransmitter concentrations and ACC BOLD signal, and could further understanding of molecular mechanisms underlying emotion processing in healthy and mood-disordered individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. On the contribution of active galactic nuclei to the high-redshift metagalactic ionizing background

    D'Aloisio, Anson; Upton Sanderbeck, Phoebe R.; McQuinn, Matthew; Trac, Hy; Shapiro, Paul R.

    2017-07-01

    Motivated by the claimed detection of a large population of faint active galactic nuclei (AGNs) at high redshift, recent studies have proposed models in which AGNs contribute significantly to the z > 4 H I ionizing background. In some models, AGNs are even the chief sources of reionization. If proved true, these models would make necessary a complete revision to the standard view that galaxies dominated the high-redshift ionizing background. It has been suggested that AGN-dominated models can better account for two recent observations that appear to be in conflict with the standard view: (1) large opacity variations in the z ˜ 5.5 H I Ly α forest, and (2) slow evolution in the mean opacity of the He II Ly α forest. Large spatial fluctuations in the ionizing background from the brightness and rarity of AGNs may account for the former, while the earlier onset of He II reionization in these models may account for the latter. Here we show that models in which AGN emissions source ≳50 per cent of the ionizing background generally provide a better fit to the observed H I Ly α forest opacity variations compared to standard galaxy-dominated models. However, we argue that these AGN-dominated models are in tension with constraints on the thermal history of the intergalactic medium (IGM). Under standard assumptions about the spectra of AGNs, we show that the earlier onset of He II reionization heats up the IGM well above recent temperature measurements. We further argue that the slower evolution of the mean opacity of the He II Ly α forest relative to simulations may reflect deficiencies in current simulations rather than favour AGN-dominated models as has been suggested.

  4. Contribution of individual and environmental factors to physical activity level among Spanish adults.

    José Antonio Serrano-Sanchez

    Full Text Available BACKGROUND: Lack of physical activity (PA is a major risk for chronic disease and obesity. The main aims of the present study were to identify individual and environmental factors independently associated with PA and examine the relative contribution of these factors to PA level in Spanish adults. METHODOLOGY/PRINCIPAL FINDINGS: A population-based cross-sectional sample of 3,000 adults (18-75 years old from Gran Canaria (Spain was selected using a multistage stratified random sampling method. The participants were interviewed at home using a validated questionnaire to assess PA as well as individual and environmental factors. The data were analyzed using bivariate and multivariate logistic regression. One demographic variable (education, two cognitive (self-efficacy and perceived barriers, and one social environmental (organized format were independently associated with PA in both genders. Odds ratios ranged between 1.76-2.07 in men and 1.35-2.50 in women (both p<0.05. Individual and environmental factors explained about one-third of the variance in PA level. CONCLUSIONS/SIGNIFICANCE: Self-efficacy and perceived barriers were the most significant factors to meet an adequate level of PA. The risk of insufficient PA was twofold greater in men with primary or lesser studies and who are employed. In women, living in rural environments increased the risk of insufficient PA. The promotion of organized PA may be an efficient way to increase the level of PA in the general population. Improvement in the access to sport facilities and places for PA is a prerequisite that may be insufficient and should be combined with strategies to improve self-efficacy and overcome perceived barriers in adulthood.

  5. Resuscitation of the rare biosphere contributes to pulses of ecosystem activity

    Zach eAanderud

    2015-01-01

    Full Text Available Dormancy is a life history trait that may have important implications for linking microbial communities to the functioning of natural and managed ecosystems. Rapid changes in environmental cues may resuscitate dormant bacteria and create pulses of ecosystem activity. In this study, we used heavy-water (H218O stable isotope probing (SIP to identify fast-growing bacteria that were associated with pulses of trace gases (CO2, CH4, and N2O from different ecosystems (agricultural site, grassland, deciduous forest, and coniferous forest following a soil-rewetting event. Irrespective of ecosystem type, a large fraction (69 - 74% of the bacteria that responded to rewetting were below detection limits in the dry soils. Based on the recovery of sequences, in just a few days, hundreds of rare taxa increased in abundance and in some cases became dominant members of the rewetted communities, especially bacteria belonging to the Sphingomonadaceae, Comamonadaceae, and Oxalobacteraceae. Resuscitation led to dynamic shifts in the rank abundance of taxa that caused previously rare bacteria to comprise nearly 60% of the sequences that were recovered in rewetted communities. This rapid turnover of the bacterial community corresponded with a 5 20 fold increase in the net production of CO2 and up to a 150% reduction in the net production of CH4 from rewetted soils. Results from our study demonstrate that the rare biosphere may account for a large and dynamic fraction of a community that is important for the maintenance of bacterial biodiversity. Moreover, our findings suggest that the resuscitation of rare taxa from seed banks contribute to ecosystem functioning.

  6. Partial discharge transients: The field theoretical approach

    McAllister, Iain Wilson; Crichton, George C

    1998-01-01

    Up until the mid-1980s the theory of partial discharge transients was essentially static. This situation had arisen because of the fixation with the concept of void capacitance and the use of circuit theory to address what is in essence a field problem. Pedersen rejected this approach and instead...... began to apply field theory to the problem of partial discharge transients. In the present paper, the contributions of Pedersen using the field theoretical approach will be reviewed and discussed....

  7. Problematic issues of accounting reflection and accounting recognition of contributions while carrying out joint activities without forming a legal entity

    Куришко, Лілія Анатоліївна

    2015-01-01

    The methodic of accounting reflection of the business transactions related to contributions into the joint activities without forming a legal entity has been studied; the types of contributions defined legally and the possibility of their reflection in accounting have been elucidated; the author’s understanding of the essence of contributions’ types has been formed as well as the approach towards their identification in accounting has been offered

  8. Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic.

    Indranil Mukhopadhyay

    Full Text Available Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1 is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca(+2 influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1.

  9. Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

    Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2018-04-27

    Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential

  10. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

    Ke, Ruian; Lewin, Sharon R; Elliott, Julian H; Perelson, Alan S

    2015-10-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  11. A CLOSER VIEW OF THE RADIO-FIR CORRELATION: DISENTANGLING THE CONTRIBUTIONS OF STAR FORMATION AND ACTIVE GALACTIC NUCLEUS ACTIVITY

    Moric, I.; Smolcic, V.; Riechers, D. A.; Scoville, N.; Kimball, A.; Ivezic, Z.

    2010-01-01

    We extend the Unified Radio Catalog, a catalog of sources detected by various (NVSS, FIRST, WENSS, GB6) radio surveys, and SDSS, to IR wavelengths by matching it to the IRAS Point and Faint Source catalogs. By fitting each NVSS-selected galaxy's NUV-NIR spectral energy distribution (SED) with stellar population synthesis models we add to the catalog star formation rates (SFRs), stellar masses, and attenuations. We further add information about optical emission-line properties for NVSS-selected galaxies with available SDSS spectroscopy. Using an NVSS 20 cm (F 1.4 G Hz ∼> 2.5 mJy) selected sample, matched to the SDSS spectroscopic ('main' galaxy and quasar) catalogs and IRAS data (0.04 < z ∼< 0.2) we perform an in-depth analysis of the radio-FIR correlation for various types of galaxies, separated into (1) quasars, (2) star-forming, (3) composite, (4) Seyfert, (5) LINER, and (6) absorption line galaxies using the standard optical spectroscopic diagnostic tools. We utilize SED-based SFRs to independently quantify the source of radio and FIR emission in our galaxies. Our results show that Seyfert galaxies have FIR/radio ratios lower than, but still within the scatter of, the canonical value due to an additional (likely active galactic nucleus (AGN)) contribution to their radio continuum emission. Furthermore, IR-detected absorption and LINER galaxies are on average strongly dominated by AGN activity in both their FIR and radio emission; however their average FIR/radio ratio is consistent with that expected for star-forming galaxies. In summary, we find that most AGN-containing galaxies in our NVSS-IRAS-SDSS sample have FIR/radio flux ratios indistinguishable from those of the star-forming galaxies that define the radio-FIR correlation. Thus, attempts to separate AGNs from star-forming galaxies by their FIR/radio flux ratios alone can separate only a small fraction of the AGNs, such as the radio-loud quasars.

  12. TRANSIENT ELECTRONICS CATEGORIZATION

    2017-08-24

    AFRL-RY-WP-TR-2017-0169 TRANSIENT ELECTRONICS CATEGORIZATION Dr. Burhan Bayraktaroglu Devices for Sensing Branch Aerospace Components & Subsystems...SUBTITLE TRANSIENT ELECTRONICS CATEGORIZATION 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER N/A 6. AUTHOR(S) Dr. Burhan...88ABW-2017-3747, Clearance Date 31 July 2017. Paper contains color. 14. ABSTRACT Transient electronics is an emerging technology area that lacks proper

  13. Activation of Transient Receptor Potential Vanilloid 4 Impairs the Dendritic Arborization of Newborn Neurons in the Hippocampal Dentate Gyrus through the AMPK and Akt Signaling Pathways

    Yujing Tian

    2017-06-01

    Full Text Available Neurite growth is an important process for the adult hippocampal neurogenesis which is regulated by a specific range of the intracellular free Ca2+ concentration ([Ca2+]i. Transient receptor potential vanilloid 4 (TRPV4 is a calcium-permeable channel and activation of it causes an increase in [Ca2+]i. We recently reported that TRPV4 activation promotes the proliferation of stem cells in the adult hippocampal dentate gyrus (DG. The present study aimed to examine the effect of TRPV4 activation on the dendrite morphology of newborn neurons in the adult hippocampal DG. Here, we report that intracerebroventricular injection of the TRPV4 agonist GSK1016790A for 5 days (GSK1016790A-injected mice reduced the number of doublecortin immunopositive (DCX+ cells and DCX+ fibers in the hippocampal DG, showing the impaired dendritic arborization of newborn neurons. The phosphorylated AMP-activated protein kinase (p-AMPK protein level increased from 30 min to 2 h, and then decreased from 1 to 5 days after GSK1016790A injection. The phosphorylated protein kinase B (p-Akt protein level decreased from 30 min to 5 days after GSK1016790A injection; this decrease was markedly attenuated by the AMPK antagonist compound C (CC, but not by the AMPK agonist AICAR. Moreover, the phosphorylated mammalian target of rapamycin (mTOR and p70 ribosomal S6 kinase (p70S6k protein levels were decreased by GSK1016790A; these changes were sensitive to 740 Y-P and CC. The phosphorylation of glycogen synthase kinase 3β (GSK3β at Y216 was increased by GSK1016790A, and this change was accompanied by increased phosphorylation of microtubule-associated protein 2 (MAP2 and collapsin response mediator protein-2 (CRMP-2. These changes were markedly blocked by 740 Y-P and CC. Finally, GSK1016790A-induced decrease of DCX+ cells and DCX+ fibers was markedly attenuated by 740 Y-P and CC, but was unaffected by AICAR. We conclude that TRPV4 activation impairs the dendritic arborization of newborn

  14. The contribution of human agricultural activities to increasing evapotranspiration is significantly greater than climate change effect over Heihe agricultural region.

    Zou, Minzhong; Niu, Jun; Kang, Shaozhong; Li, Xiaolin; Lu, Hongna

    2017-08-18

    Evapotranspiration (ET) is a major component linking the water, energy, and carbon cycles. Understanding changes in ET and the relative contribution rates of human activity and of climate change at the basin scale is important for sound water resources management. In this study, changes in ET in the Heihe agricultural region in northwest China during 1984-2014 were examined using remotely-sensed ET data with the Soil and Water Assessment Tool (SWAT). Correlation analysis identified the dominant factors that influence change in ET per unit area and those that influence change in total ET. Factor analysis identified the relative contribution rates of the dominant factors in each case. The results show that human activity, which includes factors for agronomy and irrigation, and climate change, including factors for precipitation and relative humidity, both contribute to increases in ET per unit area at rates of 60.93% and 28.01%, respectively. Human activity, including the same factors, and climate change, including factors for relative humidity and wind speed, contribute to increases in total ET at rates of 53.86% and 35.68%, respectively. Overall, in the Heihe agricultural region, the contribution of human agricultural activities to increased ET was significantly greater than that of climate change.

  15. In-duct removal of mercury from coal-fired power plant flue gas by activated carbon: assessment of entrained flow versus wall surface contributions

    Scala, F.; Chirone, R.; Lancia, A. [CNR, Naples (Italy). Institute for Research on Combustion

    2008-12-15

    In-duct mercury capture efficiency by activated carbon from coal-combustion flue gas was investigated. To this end, elemental mercury capture experiments were conducted at 100 C in a purposely designed 65-mm ID labscale pyrex apparatus operated as an entrained flow reactor. Gas residence times were varied between 0.7 and 2.0 s. Commercial-powdered activated carbon was continuously injected in the reactor and both mercury concentration and carbon elutriation rate were followed at the outlet. Transient mercury concentration profiles at the outlet showed that steady-state conditions were reached in a time interval of 15-20 min, much longer than the gas residence time in the reactor. Results indicate that the influence of the walls is non-negligible in determining the residence time of fine carbon particles in the adsorption zone, because of surface deposition and/or the establishment of a fluid-dynamic boundary layer near the walls. Total mercury capture efficiencies of 20-50% were obtained with carbon injection rates in the range 0.07-0.25 g/min. However, only a fraction of this capture was attributable to free-flowing carbon particles, a significant contribution coming from activated carbon staying near the reactor walls. Entrained bed experiments at lab-scale conditions are probably not properly representative of full-scale conditions, where the influence of wall interactions is lower. Moreover, previously reported entrained flow lab-scale mercury capture data should be reconsidered by taking into account the influence of particle-wall interactions.

  16. Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

    Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

    2017-02-01

    Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs.

    Mian-Er Cong

    Full Text Available Pre-exposure prophylaxis (PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10. PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005. SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043 but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.

  18. Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

    Xianhua Zhang

    2017-07-01

    Full Text Available Previously, we only apply a traditional Chinese medicine (TCM Danshen-Chuanxiong-Honghua (DCH for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO. We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS, we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg and FA (100 mg/kg improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.

  19. Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin

    Takahito Miyake

    2017-11-01

    Full Text Available Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1 is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD, which causes sensitization of TRPA1 to reactive oxygen species (ROS. Furthermore, PHD inhibition endows cold-insensitive human TRPA1 (hTRPA1 with ROS-dependent cold sensitivity. Since cysteine oxidation and proline hydroxylation regulate its activity, their association with oxaliplatin-induced TRPA1 activation and acquirement of cold sensitivity were investigated in the present study. A high concentration of oxaliplatin (1 mM induced outward-rectifier whole-cell currents and increased the intracellular Ca2+ concentration in hTRPA1-expressing HEK293 cells, but did not increase the probability of hTRPA1 channel opening in the inside-out configuration. Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala-expressing cells showed similar whole-cell currents and Ca2+ influx. By contrast, a lower concentration of oxaliplatin (100 μM did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower

  20. Assessment of odor activity value coefficient and odor contribution based on binary interaction effects in waste disposal plant

    Wu, Chuandong; Liu, Jiemin; Yan, Luchun; Chen, Haiying; Shao, Huiqi; Meng, Tian

    2015-02-01

    Odor activity value (OAV) has been widely used for the assessment of odor pollution from various sources. However, little attention has been paid to the extreme OAV variation and potential inaccuracies of odor contribution assessment caused by odor interaction effects. The objective of this study is to assess the odor interaction effect for precise assessment of odor contribution. In this paper, samples were collected from a food waste disposal plant, and analyzed by instrumental and olfactory method to conclude odorants' occurrence and OAV. Then odor activity value coefficient (γ) was first proposed to evaluate the type and the level of binary interaction effects based on determination of OAV variation. By multiplying OAV and γ, odor activity factor (OAF) was used to reflect the real OAV. Correlation between the sum of OAF and odor concentration reached 80.0 ± 5.7%, which was 10 times higher than the sum of OAV used before. Results showed that hydrogen sulfide contributed most (annual average 66.4 ± 15.8%) to odor pollution in the waste disposal plant. However, as odor intensity of samples in summer rising, odor contribution of trimethylamine increased to 48.3 ± 3.7% by the strong synergistic interaction effect, while odor contribution of phenol decreased to 0.1 ± 0.02% for the increasing antagonistic interaction effect.

  1. Personal and environmental factors contributing to participation in romantic relationships and sexual activity of young adults with cerebral palsy.

    Wiegerink, Diana J H G; Stam, Henk J; Ketelaar, Marjolijn; Cohen-Kettenis, Peggy T; Roebroeck, Marij E

    2012-01-01

    To study determinants of romantic relationships and sexual activity of young adults with cerebral palsy (CP), focusing on personal and environmental factors. A cohort study was performed with 74 young adults (46 men; 28 women) aged 20-25 years (SD 1.4) with CP (49% unilateral CP, 76% GMFCS level I, 85% MACS level I). All participants were of normal intelligence. Romantic relationships, sexual activity (outcome measures), personal and environmental factors (associated factors) were assessed. Associations were analyzed using logistic regression analyses. More females than males with CP were in a current romantic relationship. Self-esteem, sexual esteem and feelings of competence regarding self-efficacy contributed positively to having current romantic relationships. A negative parenting style contributed negatively. Age and gross motor functioning explained 20% of the variance in experience with intercourse. In addition, sexual esteem and taking initiative contributed significantly to intercourse experience. For young adults with CP personal factors (20-35% explained variances) seem to contribute more than environmental factors (9-12% explained variances) to current romantic relationships and sexual experiences. We advice parents and professionals to focus on self-efficacy, self-esteem and sexual self-esteem in development of young adults with CP. [ • The severity of gross motor functioning contributed somewhat to sexual activities, but not to romantic relationships.• High self-efficacy, self-esteem and sexual self-esteem can facilitate involvement in romantic and sexual relationships for young adults with CP.

  2. Transient analysis for Laguna Verde nuclear power plant

    Ramos Pablos, J.C. et.al.

    1991-01-01

    Relationship between transients analysis and safety of Laguna Verde nuclear power plant is described a general panorama of safety thermal limits of a nuclear station, as well as transients classification and events simulation codes are exposed. Activities of a group of transients analysis of electrical research institute are also mentioned (Author)

  3. Spectroscopic classification of transients

    Stritzinger, M. D.; Fraser, M.; Hummelmose, N. N.

    2017-01-01

    We report the spectroscopic classification of several transients based on observations taken with the Nordic Optical Telescope (NOT) equipped with ALFOSC, over the nights 23-25 August 2017.......We report the spectroscopic classification of several transients based on observations taken with the Nordic Optical Telescope (NOT) equipped with ALFOSC, over the nights 23-25 August 2017....

  4. Review of research institute library activity through the contributed papers. The case of the Japan Atomic Energy Research Institute Library

    Ikeda, Kiyoshi; Habara, Tadashi; Ishikawa, Masashi; Itabashi, Keizo; Yonezawa, Minoru

    2007-03-01

    The Japan Atomic Energy Research Institute (JAERI) Library had contributed 312 papers through the library activities in half-century. We made the bibliography of these papers as well as categorized them into general', 'library functions', 'management and promotion of research results' and 'international exchange of information' and explained them under the four categories. A subject index, an author index of these papers and chronology of JAERI library activities were also compiled for reference. (author)

  5. Contribution of Arginine 13 to the Catalytic Activity of Human Class Pi Glutathione Transferase P1-1

    Kong, Ji Na; Jo, Dong Hyeon; Do, Hyun Dong; Lee, Jin Ju; Kong, Kwang Hoon

    2010-01-01

    Arg13 is a conserved active-site residue in all known Pi class glutathione S-transferases (GSTs) and in most Alpha class GSTs. To evaluate its contribution to substrate binding and catalysis of this residue, three mutants (R13A, R13K, and R13L) were expressed in Escherichia coli and purified by GSH affinity chromatography. The substitutions of Arg13 significantly affected GSH-conjugation activity, while scarcely affecting glutathione peroxidase or steroid isomerase activities. Mutation of Arg13 into Ala largely reduced the GSH-conjugation activity by approximately 85 - 95%, whereas substitutions by Lys and Leu barely affected activity. These results suggest that, in the GSH-conjugation activity of hGST P1-1, the contribution of Arg13 toward catalytic activity is highly dependent on substrate specificities and the size of the side chain at position 13. From the kinetic parameters, introduction of larger side chains at position 13 results in stronger affinity (Leu > Lys, Arg > Ala) towards GSH. The substitutions of Arg13 with alanine and leucine significantly affected k cat , whereas substitution with Lys was similar to that of the wild type, indicating the significance of a positively charged residue at position 13. From the plots of log (k cat /K m CDNB ) against pH, the pK a values of the thiol group of GSH bound in R13A, R13K, and R13L were estimated to be 1.8, 1.4, and 1.8 pK units higher than the pK a value of the wildtype enzyme, demonstrating the contribution of the Arg13 guanidinium group to the electrostatic field in the active site. From these results, we suggest that contribution of Arg13 in substrate binding is highly dependent on the nature of the electrophilic substrates, while in the catalytic mechanism, it stabilizes the GSH thiolate through hydrogen bonding

  6. Explaining educational differences in leisure-time physical activity in Europe: the contribution of work-related factors

    Mäkinen, T E; Sippola, R; Borodulin, K

    2011-01-01

    Although educational differences in leisure-time physical activity (LTPA) exist across Europe, the independent effect of educational level on leisure-time physical activity has rarely been explored. This study examines the relative contribution of occupational class, employment status...... and employment status had only a modest effect on educational differences in LTPA in most of the examined countries, suggesting that education remains an important predictor of LTPA....

  7. Different contributions of HtrA protease and chaperone activities to Campylobacter jejuni stress tolerance and physiology

    Bæk, Kristoffer Torbjørn; Vegge, Christina Skovgaard; Skórko-Glonek, Joanna

    2011-01-01

    activity is sufficient for growth at high temperature or oxidative stress, whereas the HtrA protease activity is only essential at conditions close to the growth limit for C. jejuni. However, the protease activity was required to prevent induction of the cytoplasmic heat-shock response even at optimal......The microaerophilic bacterium Campylobacter jejuni is the most common cause of bacterial food-borne infections in the developed world. Tolerance to environmental stress relies on proteases and chaperones in the cell envelope such as HtrA and SurA. HtrA displays both chaperone and protease activity......, but little is known about how each of these activities contributes to stress tolerance in bacteria. In vitro experiments showed temperature dependent protease and chaperone activities of C. jejuni HtrA. A C. jejuni mutant lacking only the protease activity of HtrA was used to show that the HtrA chaperone...

  8. Analysis of the Contribution Rate of Climate Change and Anthropogenic Activity to Runoff Variation in Nenjiang Basin, China

    Liqin Dong

    2017-12-01

    Full Text Available The Pettitt abrupt change test method based on ArcGIS was used to undertake change-point analysis on climatic (precipitation and potential evapotranspiration; 39 meteorological stations and runoff data (27 hydrological stations from 1954–2015 in the Nenjiang basin. The hydrological sensitivity analysis method was also used to calculate the influential component of climate change upstream, mid-stream, and downstream of the Nenjiang basin, as well as the effect of anthropogenic activities on runoff. Our results show that the upstream area has the highest contribution rate of climate change, followed by the mid-stream area; the downstream area has the lowest contribution rate. Studying climate change contribution rates in various sites in the Nenjiang basin, in addition to anthropogenic activities affecting runoff, can provide the foundation for the protection and utilization of basin water resources, as well as the conservation and restoration of wetlands.

  9. Contribution of the autolysin AtlA to the bactericidal activity of amoxicillin against Enterococcus faecalis JH2-2.

    Bravetti, Anne-Lise; Mesnage, Stéphane; Lefort, Agnès; Chau, Françoise; Eckert, Catherine; Garry, Louis; Arthur, Michel; Fantin, Bruno

    2009-04-01

    The bactericidal activity of amoxicillin was investigated against Enterococcus faecalis JH2-2 and against an isogenic mutant deficient in the production of the N-acetylglucosaminidase AtlA. Comparison of the two strains indicated that this autolysin contributes to killing by amoxicillin both in vitro and in a rabbit model of experimental endocarditis.

  10. The Contribution of Executive Functions to Participation in School Activities of Children with High Functioning Autism Spectrum Disorder

    Zingerevich, Chaya; Patricia D., LaVesser

    2009-01-01

    This study describes the contribution of executive functions to participation in school activities of children diagnosed with ASD ages 6-9 years while controlling for sensory processing. Twenty-four children, ages 73-112 months (S.D. = 11.4), diagnosed with high functioning ASD were assessed with the Wisconsin Card Sorting Test. Their teachers…

  11. Cerebrospinal fluid (CSF) transient responses induced by hypercapnia

    Fisher, M.J.

    1984-01-01

    CSF transient responses to CO 2 inhalation were measured before and after facilitated perfusate flow through subarachnoid spaces of anesthetized cats during ventriculocisternal perfusion with artificial CSF containing 14 C-dextran. Convective mixing of perfusate in subarachnoid spaces was augmented while infusion constant, either by impeding cisternal efflux of perfusate by raising the cisternal outflow cannula (high CSF pressure), or by preventing CSF outflow by clamping the cisternal outflow cannula (stopflow; S-F). CSF transients were also measured before and after systemic administration of phenoxybenzamine (PBZ) in order to evaluate the contribution of sympatho-adrenergic activity to craniospinal CSF redistribution and mixing. Results from high CSF pressure and S-F experiments indicate that unequilibrated CSF contributes significantly to the reduced tracer concentration in CSF volume (Vd) since SCF effluent tracer concentration (Cd) was decreased after subarachnoid facilitated flow. Further, results from S-F studies indicate that at least 50% of Cd is due to craniospinal fluid redistribution, a process which, along with CSF outflow transients, was unaffected by PBZ. Conversely, PBZ administration decreased steady state SCF formation and absorption through alpha-mediated cerebrovascular responses and/or through beta-adrenoceptor inhibition of metabolism of CSF secretory epithelium

  12. Contribution of Organized and Nonorganized Activity to Children's Motor Skills and Fitness

    Hardy, Louise L.; O'Hara, Blythe J.; Rogers, Kris; St George, Alexis; Bauman, Adrian

    2014-01-01

    Background: To examine the associations between children's organized physical activity (OPA), nonorganized physical activity (NOPA), and health-related outcomes (fundamental movement skill [FMS] fitness). Methods: Cross-sectional survey of children aged 10-16?years (N?=?4273). Organized physical activity and NOPA were assessed by self-report,…

  13. Contributing Factors on Malaysia Preschool Teachers' Belief, Attitude and Competence in Using Play Activities

    Jantan, Hafsah Binti; Bin Hamdan, Abdul Rahim; Yahya, Fauziah Hj; Saleh, Halimatussadiah Binti; Ong, Mohd Hanafi Bin Azman

    2015-01-01

    This study focused on preschool teachers' belief, attitude, knowledge and competence in using play in Malaysia. Its purpose is to find out indicators significantly contribute to belief, attitude, knowledge and competence in play of preschool teachers in Malaysia. The method used was factor analysis in order to confirm indicators in each variable…

  14. 11 CFR 100.94 - Uncompensated Internet activity by individuals that is not a contribution.

    2010-01-01

    ..., acting independently or in coordination with any candidate, authorized committee, or political party... of another person's Web site; and any other form of communication distributed over the Internet. (c... definition of contribution: (1) Any payment for a public communication (as defined in 11 CFR 100.26) other...

  15. Transient elevation of element contents as a result of neuronal death in mutant-mice cerebellum studied by neutron activation analysis

    Kranda, K.; Kucera, J.; Baeurle, J.

    2006-01-01

    Accumulation of some metals, in particular iron or manganese, has long been considered to trigger or accentuate neurodegenerative processes in humans. The two most frequently cited examples are Parkinson's and Alzheimer diseases, where excitotoxic processes lead to neuronal death. However, these neuropathies are somewhat unsuitable for investigating the time course of the metal accumulation because the applied analytical methods such as neutron activation analysis (NAA) are invasive. Hence, only one measurement can be made after the patient's death. Animal models of Parkinson's type neurodegeneration, such as mice mutants, are more suitable as a larger number of animals can be investigated at various postnatal ages. In this study we used one type of mice mutants weaver, where primary neurodegeneration is principally confined to the cerebellum and centred in time around the postnatal age of six days. Elemental composition of brain segments with dry mass as low as 0.5 mg, which were isolated from weaver and wild type (normal) mice were investigated using a combination of INAA and RNAA. Elevated concentration of the following elements Fe, Zn, Cu, K, Na, Rb, and Br that were observed in the weaver's cerebella closely followed the time course of neurodegeneration documented for this type of mutant. The transient elevation of these elements never preceded the onset of neurodegeneration but closely mirrored its time course reaching its peak on the sixth day. The concentration of these elements in the weaver's cerebella declined afterwards to converge on the elemental time course observed in the wild type mice. In conclusion, metal and other elemental elevation observed in the cerebella of these mutants are an expression of neurodegenerative processes rather than its precondition. (author)

  16. Effects of transient global ischaemia on freezing behaviour and activity in a context-dependent fear conditioning task--implications for memory investigations.

    Henrich-Noack, Petra; Krautwald, Karla; Reymann, Klaus G; Wetzel, Wolfram

    2011-07-15

    Transient global ischaemia induces cell death in the CA1 layer of the hippocampus. To evaluate the functional consequences, we performed context-dependent fear conditioning. Ischaemia was induced by 2-vessel-occlusion (2VO) in gerbils. On day 6 post ischaemia or sham procedures (in control group) gerbils were placed in a test chamber and after 3 min adaption time exposed to foot-shocks (training session). On the next day the animals were placed in the same test chamber without foot-shocks (test session). As a parameter for memory performance we used the standard method of measuring the total freezing time via a cumulative time-sampling procedure during the test session. We found a significant longer total freezing time in control animals than in ischaemic animals. In addition, however, we applied a more detailed analysis of (i) quantifying the number of freezing bouts, (ii) the average duration of single freezing bouts, (iii) the activity pattern during the training and test situation and (iv) we differentially evaluated all the single time segments of the experiment. These analyses revealed that although maintenance of freezing (duration of freezing bout) was significantly lower in ischaemic animals compared to controls, the initiation of freezing (number of freezing bouts) was not significantly different between the two groups during the test session. The activity scores of ischaemic and non-ischaemic gerbils were similar during the adaption time of the training session. The foot-shock, however, induced a significantly different pattern of behaviour in the ischaemic animals, which was selectively reproduced during the test session. In conclusion, ischaemic gerbils reacted to a fearsome thread with a behavioural pattern different from unlesioned animals and they revealed this specific foot-shock induced behaviour again during the test session. This indicated that CA1 hippocampal death did not interrupt memory performance but changed expression of fear. Therefore

  17. Climatic feedbacks between stationary and transient eddies

    Branscome, L.E.

    1994-01-01

    Stationary eddies make a significant contribution to poleward heat transport during Northern Hemisphere winter, equaling the transport by transient eddies. On the other hand, stationary eddy transport during the summer is negligible. The effect of topography on time-mean stationary waves and low-frequency variability has been widely studied. In contrast, little attention has been given to the climatic feedbacks associated with stationary eddies. Furthermore, the relationship between stationary and transient eddies in the context of global and regional climate is not well understood. The response of the climate system to anthropogenic forcing is likely to have some dependence on stationary wave transport and its interaction with transient eddies. Some early GCM simulations and observational analyses indicate a strong feedback between the meridional heat fluxes of stationary and transient eddies

  18. Transient virulence of emerging pathogens.

    Bolker, Benjamin M; Nanda, Arjun; Shah, Dharmini

    2010-05-06

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

  19. Factors Contributing to Pelvis Instability in Female Adolescent Athletes During Unilateral Repeated Partial Squat Activity

    Scarborough, Donna Moxley; Linderman, Shannon; Berkson, Eric M.; Oh, Luke S.

    2017-01-01

    Objectives: Unilateral partial squat tasks are often used to assess athletes? lower extremity (LE) neuromuscular control. Single squat biomechanics such as lateral drop of the non-stance limb?s pelvis have been linked to knee injury risk. Yet, there are limited studies on the factors contributing to pelvic instability during the unilateral partial squat such as anatomical alignment of the knee and hip strength. The purpose of this study was 1) to assess the influence of leg dominance on pelvi...

  20. Business success in Serbian hotels viewed through influence of business activities which contribute to the creation of value

    Ognjanović Jasmina

    2016-01-01

    Full Text Available Analysis of business activities and defining future business plans are based on an analysis of appropriate business performance - financial and non-financial. Value of business performance reflects success of the company. The way of organizing business activities of the company, cooperation among employees, level of capacity utilization, innovation affect on the business performance. This paper analyzes the business activities which contribute to the creation of value (human resource management, marketing activities aimed at the efficient utilization of hotel capacities and activities of innovation and business performance - financial (return on assets, return on equity, employee productivity and non-financial (quality of hotel service, motivation of employees. The main objective of the research is to examine the interrelationship between business activities that contribute to creating value and business performance of the hotel. Results of the regression analyzes leads to the conclusion that the analyzed business activities affect on employee productivity and affect on non-financial performance - the quality of hotel services and motivation of employees.

  1. Summary of transient analysis

    Saha, P.

    1984-01-01

    This chapter reviews the papers on the pressurized water reactor (PWR) and boiling water reactor (BWR) transient analyses given at the American Nuclear Society Topical Meeting on Anticipated and Abnormal Plant Transients in Light Water Reactors. Most of the papers were based on the systems calculations performed using the TRAC-PWR, RELAP5 and RETRAN codes. The status of the nuclear industry in the code applications area is discussed. It is concluded that even though comprehensive computer codes are available for plant transient analysis, there is still a need to exercise engineering judgment, simpler tools and even hand calculations to supplement these codes

  2. The Contribution of Parent-Child Numeracy Activities to Young Chinese Children's Mathematical Ability

    Huang, Qi; Zhang, Xiao; Liu, Yingyi; Yang, Wen; Song, Zhanmei

    2017-01-01

    Background: A growing body of recent research has shown that parent-child mathematical activities have a strong effect on children's mathematical learning. However, this research was conducted predominantly in Western societies and focused mainly on mothers' involvement in such activities. Aims: This study aimed to examine both mother-child and…

  3. Emotion at Work: A Contribution to Third-Generation Cultural-Historical Activity Theory

    Roth, Wolff-Michael

    2007-01-01

    Second-generation cultural-historical activity theory, which drew its inspiration from Leont'ev's work, constituted an advance over Vygotsky's first-generation theory by explicitly articulating the dialectical relation between individual and collective. As part of an effort to develop third-generation-historical activity theory, I propose in this…

  4. The contributions of leisure and active recreation to health and well ...

    Many people today are physically active as part of their recreation or leisure. Therefore, the purpose of this paper was to present an overview of literature that has explored the relationships that leisure and active recreation have to health and well-being. Research, both qualitative and quantitative, has been conducted in the ...

  5. GABAergic contributions to gating, timing, and phase precession of hippocampal neuronal activity during theta oscillations.

    Cutsuridis, Vassilis; Hasselmo, Michael

    2012-07-01

    Successful spatial exploration requires gating, storage, and retrieval of spatial memories in the correct order. The hippocampus is known to play an important role in the temporal organization of spatial information. Temporally ordered spatial memories are encoded and retrieved by the firing rate and phase of hippocampal pyramidal cells and inhibitory interneurons with respect to ongoing network theta oscillations paced by intra- and extrahippocampal areas. Much is known about the anatomical, physiological, and molecular characteristics as well as the connectivity and synaptic properties of various cell types in the hippocampal microcircuits, but how these detailed properties of individual neurons give rise to temporal organization of spatial memories remains unclear. We present a model of the hippocampal CA1 microcircuit based on observed biophysical properties of pyramidal cells and six types of inhibitory interneurons: axo-axonic, basket, bistratistified, neurogliaform, ivy, and oriens lacunosum-moleculare cells. The model simulates a virtual rat running on a linear track. Excitatory transient inputs come from the entorhinal cortex (EC) and the CA3 Schaffer collaterals and impinge on both the pyramidal cells and inhibitory interneurons, whereas inhibitory inputs from the medial septum impinge only on the inhibitory interneurons. Dopamine operates as a gate-keeper modulating the spatial memory flow to the PC distal dendrites in a frequency-dependent manner. A mechanism for spike-timing-dependent plasticity in distal and proximal PC dendrites consisting of three calcium detectors, which responds to the instantaneous calcium level and its time course in the dendrite, is used to model the plasticity effects. The model simulates the timing of firing of different hippocampal cell types relative to theta oscillations, and proposes functional roles for the different classes of the hippocampal and septal inhibitory interneurons in the correct ordering of spatial memories

  6. Contribution to the investigation of the p53 in vivo and in vitro trans-activation activity

    Meiller, A.

    2004-03-01

    Among the body's defence mechanisms, the programmed cellular death or apoptosis is an important safeguard way which allows the body to get rid of the injured cells before they acquire steady genetic modifications leading to an anarchistic multiplication. As p53 tumor suppressor gene plays a predominant role within this process, this research report first presents the p53 protein, its structure, its activities as a transcription factor, its modifications and the implications on its functional activities, its biological activities, and describes the p53 intracellular rate regulation and the use of this protein in radiology, particularly in 'in vivo' investigations on irradiated mice. It also presents the p53 family. Then, the author reports experimental investigations on possible other genes which could be trans-activated by p53. A gene is identified as a new target gene. She also demonstrates a new p53 activation path induced by another member of the p53 family, the p73 alpha protein

  7. Active citizenship for urban green infrastructure: fostering the diversity and dynamics of citizen contributions through mosaic governance : System dynamics and sustainability

    Buijs, Arjen E; Mattijssen, Thomas JM; Van der Jagt, Alexander PN; Ambrose-Oji, Bianca; Andersson, Erik; Elands, Birgit HM; Steen Møller, Maja

    2016-01-01

    Active citizens may contribute to the environmental, social, and institutional resilience of cities. This review discusses how citizen initiatives protect biodiversity hotspots, contribute to social cohesion, institutional innovation, and diversity in urban green space management. Challenges related

  8. PWR systems transient analysis

    Kennedy, M.F.; Peeler, G.B.; Abramson, P.B.

    1985-01-01

    Analysis of transients in pressurized water reactor (PWR) systems involves the assessment of the response of the total plant, including primary and secondary coolant systems, steam piping and turbine (possibly including the complete feedwater train), and various control and safety systems. Transient analysis is performed as part of the plant safety analysis to insure the adequacy of the reactor design and operating procedures and to verify the applicable plant emergency guidelines. Event sequences which must be examined are developed by considering possible failures or maloperations of plant components. These vary in severity (and calculational difficulty) from a series of normal operational transients, such as minor load changes, reactor trips, valve and pump malfunctions, up to the double-ended guillotine rupture of a primary reactor coolant system pipe known as a Large Break Loss of Coolant Accident (LBLOCA). The focus of this paper is the analysis of all those transients and accidents except loss of coolant accidents

  9. Transients: The regulator's view

    Sheron, B.W.; Speis, T.P.

    1984-01-01

    This chapter attempts to clarify the basis for the regulator's concerns for transient events. Transients are defined as both anticipated operational occurrences and postulated accidents. Recent operational experience, supplemented by improved probabilistic risk analysis methods, has demonstrated that non-LOCA transient events can be significant contributors to overall risk. Topics considered include lessons learned from events and issues, the regulations governing plant transients, multiple failures, different failure frequencies, operator errors, and public pressure. It is concluded that the formation of Owners Groups and Regulatory Response Groups within the owners groups are positive signs of the industry's concern for safety and responsible dealing with the issues affecting both the US NRC and the industry

  10. The Contribution of Home, Neighbourhood and School Environmental Factors in Explaining Physical Activity among Adolescents

    Haerens, L.; Deforche, B.; Cardon, G.; Bourdeaudhuij, I.D.; Craeynest, M.; Maes, L.

    2010-01-01

    The present study aimed at investigating the influence of home, neighbourhood and school environmental factors on adolescents' engagement in self-reported extracurricular physical activity and leisure time sports and on MVPA objectively measured by accelerometers. Environmental factors were assessed using questionnaires. Gender specific hierarchical regression analyses were conducted, with demographic variables entered in the first block, and environmental, psychosocial factors and interactions terms entered in the second block. Participation in extracurricular activities at school was positively related to the number of organized activities and the provision of supervision. Perceived accessibility of neighborhood facilities was not related to engagement in leisure time sports, whereas the availability of sedentary and physical activity equipment was. Findings were generally supportive of ecological theories stating that behaviors are influenced by personal and environmental factors that are constantly interacting.

  11. Macrophages activate iNOS signaling in adventitial fibroblasts and contribute to adventitia fibrosis.

    Zhang, Guannan; Li, Xiaodong; Sheng, Chengyu; Chen, Xiaohui; Chen, Yu; Zhu, Dingliang; Gao, Pingjin

    2016-12-30

    A large amount of NO is generated through the inducible nitric oxide synthase (iNOS) pathway from the vascular adventitia in various vascular diseases. However, it is currently not fully understood how the iNOS signaling pathway is activated. In the present study, this question was addressed in the context of adventitial cellular interactions. A rat model of acute hypertension in the contralateral carotid arteries was established through transverse aortic constriction (TAC) surgery. In this model, activated macrophages were found surrounded by a large quantity of iNOS-expressing adventitial fibroblasts (AFs), suggesting a possible causal relationship between macrophages and iNOS activation of the neighboring AFs. In an in vitro model, a macrophage-like cell line RAW 264.7 was first activated by LPS treatment. The supernatant was then harvested and applied to treat primary rat AFs. iNOS in AFs was activated robustly by the supernatant treatment but not by LPS itself. Treating AFs with interleukin-1β (IL-1β) also activated iNOS signaling, suggesting that the IL-1β pathway might be a possible mediator. As a consequence of the iNOS activation, total protein nitration and S-nitrosylation significantly increased in those AFs. Additionally, increased deposition of type I and type III collagens was observed in both in vitro and in vivo models. The collagen deposition was partially restored by an iNOS inhibitor, 1400 W. These findings highlight the importance of iNOS signaling during vascular inflammation, and advance our understanding of its activation through a cellular interaction perspective. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    Kasim, Vivi; Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia; Yang, Li; Miyagishi, Makoto; Wu, Shourong

    2014-01-01

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73

  13. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    Kasim, Vivi, E-mail: vivikasim78@gmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Yang, Li [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Miyagishi, Makoto [Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566 (Japan); Wu, Shourong, E-mail: shourongwu@hotmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2014-07-04

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.

  14. Transient multivariable sensor evaluation

    Vilim, Richard B.; Heifetz, Alexander

    2017-02-21

    A method and system for performing transient multivariable sensor evaluation. The method and system includes a computer system for identifying a model form, providing training measurement data, generating a basis vector, monitoring system data from sensor, loading the system data in a non-transient memory, performing an estimation to provide desired data and comparing the system data to the desired data and outputting an alarm for a defective sensor.

  15. Developmental changes in fact and source recall: Contributions from executive function and brain electrical activity

    Vinaya Rajan

    2015-04-01

    Full Text Available Source memory involves recollecting the contextual details surrounding a memory episode. When source information is bound together, it makes a memory episodic in nature. Unfortunately, very little is known about the factors that contribute to its formation in early development. This study examined the development of source memory in middle childhood. Measures of executive function were examined as potential sources of variation in fact and source recall. Continuous electroencephalogram (EEG measures were collected during baseline and fact and source retrieval in order to examine memory-related changes in EEG power. Six and 8-year-old children were taught 10 novel facts from two different sources and recall for fact and source information was later tested. Older children were better on fact recall, but both ages were comparable on source recall. However, source recall performance was poor at both ages, suggesting that this ability continues to develop beyond middle childhood. Regression analyses revealed that executive function uniquely predicted variance in source recall performance. Task-related increases in theta power were observed at frontal, temporal and parietal electrode sites during fact and source retrieval. This investigation contributes to our understanding of age-related differences in source memory processing in middle childhood.

  16. Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

    Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

    2017-06-15

    Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Contribution of organized and nonorganized activity to children's motor skills and fitness.

    Hardy, Louise L; O'Hara, Blythe J; Rogers, Kris; St George, Alexis; Bauman, Adrian

    2014-11-01

    To examine the associations between children's organized physical activity (OPA), nonorganized physical activity (NOPA), and health-related outcomes (fundamental movement skill [FMS] fitness). Cross-sectional survey of children aged 10-16 years (N = 4273). Organized physical activity and NOPA were assessed by self-report, FMS by process-orientated criteria, and fitness by 20-m shuttle run test. Boys spent 97.5 minutes and girls 86.6 minutes in daily physical activity with the majority spent in OPA (boys, 56.3%; girls 60.5%). Organized physical activity increased with grade, whereas NOPA decreased. Organized physical activity and NOPA were associated with fitness, and OPA was consistently associated with FMS competency. Boys' fitness was associated with OPA and NOPA (adjusted odds ratio [AOR] 1.42, 95% confidence interval [CI]: 1.04, 1.94; AOR 1.26, 95% CI: 1.03, 1.54, respectively), FMS competency (side gallop leap, kick) with OPA and catch, and over-arm throw with both OPA and NOPA. Girls' fitness (AOR 2.62, 95% CI: 1.88, 3.66) and FMS competency were consistently associated with OPA. Both OPA and NOPA are important contributors to children's physical activity; however, for girls, OPA was more strongly associated with fitness and FMS competency. Our findings support the importance of providing children with opportunities to engage in daily OPA. School physical education programs are an ideal delivery vehicle for OPA and need to be central to education policy. © 2014, American School Health Association.

  18. Transient Exciplex Formation Electron Transfer Mechanism

    Michael G. Kuzmin; Irina V. Soboleva; Elena V. Dolotova

    2011-01-01

    Transient exciplex formation mechanism of excited-state electron transfer reactions is analyzed in terms of experimental data on thermodynamics and kinetics of exciplex formation and decay. Experimental profiles of free energy, enthalpy, and entropy for transient exciplex formation and decay are considered for several electron transfer reactions in various solvents. Strong electronic coupling in contact pairs of reactants causes substantial decrease of activation energy relative to that for c...

  19. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes

    Csermely, P.; Szamel, M.; Resch, K.; Somogyi, J.

    1988-01-01

    In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested. In the present report, the authors demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes,and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn 2+ , while Fe 2+ and Mn 2+ are only partially counteractive. The results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca 2+ , phorbol ester, or antigen

  20. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes

    Csermely, P.; Szamel, M.; Resch, K.; Somogyi, J.

    1988-05-15

    In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested. In the present report, the authors demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes,and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn/sup 2 +/, while Fe/sup 2 +/ and Mn/sup 2 +/ are only partially counteractive. The results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca/sup 2 +/, phorbol ester, or antigen.

  1. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

    Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D'Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G; Ricci, Giovanni; Cunha, Cristina; Romani, Luigina

    2012-01-01

    The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. PMID:22543832

  2. A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events.

    McCarty, Mark F

    2004-01-01

    Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard. Copyright 2004 Elsevier Ltd.

  3. IRPA's contribution to E and T activities for radiation protection professionals

    Gallego, E.; Hefner, A.

    2009-01-01

    The International Radiation Protection Association (IRPA) promotes excellence in the practice of radiation protection through national and regional Associate Societies for radiation protection professionals. IRPA has recently prepared and E and T Plan structured around three main lines: the cooperation with international and regional organizations dealing with E and T in Radiation Protection; the internal stimulation of E and T by organizing discussion forums during IRPA Congresses; and the stimulation and support to the organization of E and T activities either by IRPA or by its Associate Societies. The main innovations are in the possibility of undertaking common activities by two or more Associate Societies; the promotion of E and T networks sharing language or regional proximity; and the emergence of activities to attract young generations to the profession. (authors)

  4. Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin.

    Engels, Christina; Schwab, Clarissa; Zhang, Jianbo; Stevens, Marc J A; Bieri, Corinne; Ebert, Marc-Olivier; McNeill, Kristopher; Sturla, Shana J; Lacroix, Christophe

    2016-11-07

    Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.

  5. How Sport and Physical Activity Education Could Contribute to Human Survival

    Earle F. Zeigler

    2014-10-01

    Full Text Available Sport and related physical activity education are not being employed in the best possible ways in the developed world because the decision-makers in society don’t truly understand the situation. Illogically, people of all ages in the developed world are not getting sufficient physical activity, whereas those in the undeveloped world are getting too much! In addition, the author questions the vast overemphasis on highly competitive sport at the various levels including the Olympic Games. Further, the situation for the majority of “special-needs” people is poor including those who are exploited by sport competition overemphasis. Six different types of selected competencies are recommended for all children and youth within the educational-system experience. Finally, the author asks five specific questions that should be considered as we seek to improve the overall situation. Keywords: sport and physical activity education, memes, the Olympic Games

  6. Physical activity and body mass index: the contribution of age and workplace characteristics.

    Nelson, Candace C; Wagner, Gregory R; Caban-Martinez, Alberto J; Buxton, Orfeu M; Kenwood, Christopher T; Sabbath, Erika L; Hashimoto, Dean M; Hopcia, Karen; Allen, Jennifer; Sorensen, Glorian

    2014-03-01

    The workplace is an important domain for adults, and many effective interventions targeting physical activity and weight reduction have been implemented in the workplace. However, the U.S. workforce is aging, and few studies have examined the relationship of BMI, physical activity, and age as they relate to workplace characteristics. This paper reports on the distribution of physical activity and BMI by age in a population of hospital-based healthcare workers and investigates the relationships among workplace characteristics, physical activity, and BMI. Data from a survey of patient care workers in two large academic hospitals in the Boston area were collected in late 2009 and analyzed in early 2013. In multivariate models, workers reporting greater decision latitude (OR=1.02, 95% CI=1.01, 1.03) and job flexibility (OR=1.05, 95% CI=1.01, 1.10) reported greater physical activity. Overweight and obesity increased with age (pworkplace characteristics. Sleep deficiency (OR=1.56, 95% CI=1.15, 2.12) and workplace harassment (OR=1.62, 95% CI=1.20, 2.18) were also associated with obesity. These findings underscore the persistent impact of the work environment for workers of all ages. Based on these results, programs or policies aimed at improving the work environment, especially decision latitude, job flexibility, and workplace harassment should be included in the design of worksite-based health promotion interventions targeting physical activity or obesity. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Giardia lamblia: identification of molecules that contribute to direct mast cell activation.

    Muñoz-Cruz, Samira; Gomez-García, Argelia; Matadamas-Martínez, Félix; Alvarado-Torres, Juan A; Meza-Cervantez, Patricia; Arriaga-Pizano, Lourdes; Yépez-Mulia, Lilián

    2018-06-02

    Mast cells play a central role in the early clearance of the intestinal parasite Giardia lamblia. In a previous study, we reported that G. lamblia live trophozoites or trophozoite-derived total soluble extract induced direct activation (IgE-independent) of mast cells and release of IL-6 and TNF-α. To identify the Giardia molecules and the mast cell receptors involved in this activation, trophozoite-derived total soluble proteins separated into three fractions (F1-F3) were evaluated for its ability to activate mast cells in vitro. F2 activated mast cells in a greater extent than F1 and F3. Furthermore, F2 induced the release of IL-6 and TNF-α by mast cells. TLR2 and TLR4 expression increased slightly after mast cell stimulation with either F2 or total soluble extract; however, these receptors were not involved in F2 or total soluble extract-induced proinflammatory cytokine production. Proteins present in F2 as unique and high-intensity bands identified by liquid chromatography coupled with tandem mass spectrometry, include molecules with important biological activities such as enolase and arginine deiminase (ADI). Recombinant ADI and enolase were tested for their ability to activate mast cells, but only ADI induced a significant release of IL-6 and TNF-α. ADI product, citrulline but not ammonium, also induced mast cell release of TNF-α. Interestingly, recombinant ADI still stimulated the secretion of TNF-α by mast cells in a arginine-free medium, although in a lower extend that in the presence of arginine, indicating that either ADI itself can stimulate mast cells or through its metabolic product, citrulline.

  8. Calibration of activation detectors in a monoenergetic neutron beam. Contribution to criticality dosimetry

    Massoutie, Martine.

    1981-05-01

    Activation detectors have been calibrated for critical dosimetry applications. Measurements are made using a monoenergetic neutron flux. 14 MeV neutrons obtained par (D-T) reaction are produced by 150 kV accelerator. Neutron flux determined by different methods leads us to obtain an accuracy better than 6%. The present dosimetric system (Activation Neutron Spectrometer - SNAC) gives few informations in the (10 keV - 2 MeV) energetic range. The system has been improved and modified so that SNAC detectors must be read out by gamma spectrometer [fr

  9. Contribution of neutron activation analysis and radioanalytical techniques to trace element speciation in environmental analysis

    Gallorini, M.; Orvini, E.; Sabbioni, E.; Pietra, R.

    1984-01-01

    The feasibility of the NAA in contributing to trace element speciation in environmental and biological samples is shown by a few selected applications. They are: (i) the determination of different species of vanadium, arsenic and selenium in freshwater. The pre-irradiation treatments in which the different chemical species are selectively isolated are critically evaluated. Problems arising from possible contaminations or losses and from blanks are discussed; (ii) the use of NAA in metallobiochemical speciation once biochemical methods of cellular fractionation for the isolation of metallobiocomplexes are developed. Examples concern the biochemical speciation of vanadium in human blood and the development of a method for speciation of inorganic and organic arsenic compounds in biological samples. The use of radioanalytical techniques in developing the separation procedures of different trace metal chemical and biochemical species is also briefly discussed. 24 references, 5 figures, 4 tables

  10. HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.

    Reszka-Blanco, Natalia J; Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

    2015-08-01

    Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are rapidly activated during HIV-1 infection and are implicated in reducing the early viral load, as well as contributing to HIV-1-induced pathogenesis. However, most cell-free HIV-1 isolates are inefficient in activating human pDCs, and the mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly defined. In this study, we report that two genetically similar HIV-1 variants (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to produce alpha interferon (IFN-α). The highly pathogenic R3A efficiently activated pDCs to induce robust IFN-α production, while the less pathogenic R3B did not. The viral determinant for efficient pDC activation was mapped to the V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity. Furthermore, we showed that the Nef protein was also required for the activation of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated that Nef domains involved in CD4 downregulation were necessary for R3A to activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs, which contributes to pathogenesis. Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-α production, while most HIV-1 isolates are inefficient in activating pDCs. We have discovered that R3A-induced pDC activation depends on

  11. Mechanisms of transient radiation-induced creep

    Pyatiletov, Yu.S.

    1981-01-01

    Radiation-induced creep at the transient stage is investigated for metals. The situation, when several possible creep mechanisms operate simultaneously is studied. Among them revealed are those which give the main contribution and determine thereby the creep behaviour. The time dependence of creep rate and its relation to the smelling rate is obtained. The results satisfactorily agree with the available experimental data [ru

  12. Contributing to a Vibrant Countryside? The Impact of Side Activities on Rural Development

    Markantoni, Marianna; Koster, Sierdjan; Strijker, Dirk; Woolvin, Mike

    This paper focuses on the side activities of non-farmers in rural areas in the Netherlands and more specifically on their impact on rural development. Empirical evidence from 36 Dutch municipalities on three key aspects was examined: economy, social and physical environment. The findings indicate

  13. Living in old age: contributions to active aging in rural areas

    Maria Conceição Antunes

    2016-11-01

    Full Text Available The intervention here described resulted from a research / intervention work developed with the elderly who attended an adult education workshop, which purpose was to promote active aging by means of sociocultural animation. It involved a group of 22 participants aged between 67 and 92 years. The authors developed a participatory action-research, applying the interpretive-hermeneutic paradigm and resorting to sociocultural animation techniques - methodologies that usually foster motivation and participation on the target population. Based on the interests, needs and potential of the participants seven workshops were developed: Manual and Decorative Arts; Preventive Health; Gardening; Cooking; Musical Expression; Gymnastics; and Religious Activities. Various types of activities (physical, cognitive, recreational, social, emotional and spiritual were fostered, which allowed the development of the elderly’s functional abilities (e.g. mobility, memory, creativity, critical reflection; the fostering of interactional and interpersonal processes, valuing the traditions and fomenting spirituality. The intervention had positive results as the final evaluation revealed: the participants highlighted the benefits of the project, in particular, the levels of physical and psychological well-being, the augment of the quality of their relationships with others and the acquisition of new apprenticeships. This project reiterated the importance of social and cultural activities regarding the elderly’s learning processes, welfare and quality of life.

  14. Does Lesson Study contribute to activating and cognitively demanding teaching behavior? A single case study

    de Vries, Siebrich; Roorda, Gerrit

    2015-01-01

    Activating and cognitively demanding teaching behavior is problematic for many teachers in Dutch secondary education, in particular for the less experienced advanced beginners. In the context of a Professional Learning Community (PLC) for both less and more experienced teachers of mathematics,

  15. Transparency about multidimensional activities and performance: What can U-map and U-multirank contribute?

    Westerheijden, Donald F.; Rosa, Maria Joao; Amaral, Alberto

    2014-01-01

    Two new, user-driven and web-based transparency tools for higher education are presented: U-Map, a classification of higher education institutions according to their actual activities, and U-Multirank, a multidimensional ranking of higher education institutions’ and study fields’ performances. The

  16. Physical Activity Patterns in Portuguese Adolescents: The Contribution of Extracurricular Sports

    Silva, Pedro; Sousa, Michael; Aires, Luisa; Seabra, Andre; Ribeiro, Jose; Welk, Gregory; Mota, Jorge

    2010-01-01

    In Portugal, two sports systems exist, one through schools and the other in community clubs. The purpose was to determine the impact of extra-curricular sports (EC sports) on boys' and girls' moderate to vigorous physical activity (MVPA). 208 adolescents (79 boys and 129 girls), between 12 and 18 years old, wore an accelerometer over seven days.…

  17. Difference, Adapted Physical Activity and Human Development: Potential Contribution of Capabilities Approach

    Silva, Carla Filomena; Howe, P. David

    2012-01-01

    This paper is a call to Adapted Physical Activity (APA) professionals to increase the reflexive nature of their practice. Drawing upon Foucault's concept of governmentality (1977) APA action may work against its own publicized goals of empowerment and self-determination. To highlight these inconsistencies, we will draw upon historical and social…

  18. Rapid limb-specific modulation of vestibular contributions to ankle muscle activity during locomotion

    Forbes, Patrick A.; Vlutters, Mark; Dakin, Christopher J.; van der Kooij, Herman; Blouin, Jean Sébastien; Schouten, Alfred C.

    2017-01-01

    Key points: -The vestibular influence on human walking is phase-dependent and modulated across both limbs with changes in locomotor velocity and cadence. -Using a split-belt treadmill, we show that vestibular influence on locomotor activity is modulated independently in each limb. -The independent

  19. Rapid limb-specific modulation of vestibular contributions to ankle muscle activity during locomotion

    Forbes, P.A.; Vlutters, M; Dakin, CJ; van der Kooij, H.; Blouin, JS; Schouten, A.C.

    2017-01-01

    During walking, the vestibular influence on locomotor activity is phase-dependent and modulated in both limbs with changes in velocity. It is unclear, however, whether this bilateral modulation is due to a coordinated mechanism between both limbs or instead through limb-specific processes that

  20. Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid

    Jae Gwang Park

    2016-06-01

    Full Text Available Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO and prostaglandin (PG E2 from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF-κB and activator protein (AP-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1 and spleen tyrosine kinase (Syk. Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.

  1. How socio-economic status contributes to participation in leisure-time physical activity

    The aim of this cross-sectional study was to identify individual, social, and environmental contributors (mediators) to individual- and area-level differences in leisure-time physical activity across socio-economic groups. A two-stage stratified sampling design was used to recruit 20– to 65-year-old...

  2. Contribution of activation products to occupational exposure following treatment using high-energy photons in radiotherapy

    Petrovic, N.; Krestic-Vesovic, J.; Stojanovic, D.; Ciraj-Bjelac, O.; Lazarevic, D.; Kovacevic, M.

    2011-01-01

    When high-energy photon beams are used for irradiation in radiotherapy, neutrons that are the result of photonuclear reactions create activation products that affect the occupational dose of radiotherapy staff. For the assessment of activation products in situ gamma spectroscopy was performed parallel to dose-rate measurements following irradiation, by using a high-energy photon beam from a linear accelerator Elekta Precise (Elekta, Stockholm (Sweden)) used in radiotherapy. The major identified activation products were the following radioisotopes: 2 '8Al, 24 Na, 56 Mn, 5 4 M n, 187 W, 64 Cu and 62 Cu. Based on the typical workload and dose-rate measurement, the assessed additional annual occupational dose ranged from 1.7 to 0.25 mSv. As the measured dose rate arising from the activation products rapidly decreases as a function of time, the assessed additional dose is negligible after 10 min following irradiation. To keep the occupational dose as low as reasonably achievable, it is recommended to delay entrance to the therapy room at least 2-4 min, when high-energy photons are used. This would reduce the effective dose by 30 %. (authors)

  3. Contribution of galloylation and polymerization to the antioxidant activity of polyphenols in fish lipid systems.

    Iglesias, Jacobo; Pazos, Manuel; Lois, Salomé; Medina, Isabel

    2010-06-23

    Polyphenolic fractions extracted from pine (Pinus pinaster) bark, grape (Vitis vinifera) pomace, and witch hazel (Hamamelis virginiana) bark were selected for investigating the influence of the number of phenolic units, polymerization, and the content of esterified galloyl residues (galloylation) on their efficacy for inhibiting lipid oxidation in fish lipid enriched foodstuffs. Experiments carried out with nongalloylated pine bark fractions with different polymerization degrees demonstrated that the number of catechin residues per molecule modulates their reducing and chelating properties in solution. In real food systems such as bulk fish oil and fish oil-in-water emulsions, the efficacy against lipid oxidation was highly dependent on the physical location of the antioxidant at the oxidative sensitive sites. The lowest polymerized fractions were the most efficient in bulk fish oil samples, whereas proanthocyanidins with an intermediate polymerization degree showed the highest activity in fish oil-in-water emulsions. Galloylation did not influence the antioxidant effectiveness of proanthocyanidins in bulk fish oils. The presence of galloyl groups favored the antioxidant activity of the polyphenols in emulsions, although results indicated that a high degree of galloylation did not improve significantly the activity found with medium galloylated proanthocyanidins. The results obtained in this research provide useful information about the relationship between structure and antioxidant activity in order to design antioxidant additives with application in fish oil-enriched functional foods.

  4. Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus.

    Benjamin Mielich-Süss

    2017-11-01

    Full Text Available Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM, a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen.

  5. Glomalin in a mediterranean ecosystem affected by mining activities and its contribution to heavy metals sequestration

    Cornejo, P.; Meier, F.; Borie, G.; Borie, F.

    2009-07-01

    Glomalin-related soil protein (GRSP), a glycoprotein produced by arbuscular mycorrhizal fungi (AMF) and usually presents in high amounts in soil, may stabilize heavy metals such as Cu an Zn in soils affected by mining activities, as large areas of central Chile. (Author)

  6. Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid.

    Park, Jae Gwang; Son, Young-Jin; Kim, Mi-Yeon; Cho, Jae Youl

    2016-06-22

    Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS)-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO) and prostaglandin (PG) E₂ from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF)-κB and activator protein (AP)-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1) and spleen tyrosine kinase (Syk). Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.

  7. Microbial electrolysis contribution to anaerobic digestion of waste activated sludge, leading to accelerated methane production

    Liu, Wenzong; Cai, Weiwei; Guo, Zechong

    2016-01-01

    Methane production rate (MPR) in waste activated sludge (WAS) digestion processes is typically limitedby the initial steps of complex organic matter degradation, leading to a limited MPR due to sludgefermentation speed of solid particles. In this study, a novel microbial electrolysis AD reactor (ME...

  8. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

    McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

    2014-07-10

    Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the

  9. Anisotropic Covalency Contributions to Superexchange Pathways in Type One Copper Active Sites

    2015-01-01

    Type one (T1) Cu sites deliver electrons to catalytic Cu active sites: the mononuclear type two (T2) Cu site in nitrite reductases (NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs). The T1 Cu and the remote catalytic sites are connected via a Cys-His intramolecular electron-transfer (ET) bridge, which contains two potential ET pathways: P1 through the protein backbone and P2 through the H-bond between the Cys and the His. The high covalency of the T1 Cu–S(Cys) bond is shown here to activate the T1 Cu site for hole superexchange via occupied valence orbitals of the bridge. This covalency-activated electronic coupling (HDA) facilitates long-range ET through both pathways. These pathways can be selectively activated depending on the geometric and electronic structure of the T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys) bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type) T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs to NiRs, the second-sphere environment changes the conformation of the Cys-His pathway, which selectively activates HDA for superexchange by blue π sites for efficient turnover in catalysis. These studies show that a given protein bridge, here Cys-His, provides different superexchange pathways and electronic couplings depending on the anisotropic covalencies of the donor and acceptor metal sites. PMID:25310460

  10. Investigation of practical use situation and performance for electric transient analysis programs in the U.S. nuclear power plants

    Shimada, Yoshio

    2010-01-01

    The purposes of the present study are firstly to investigate the status of practical use of electric transient analysis programs used in U.S. nuclear power plants, which has been extracted as good examples from the information analysis of overseas troubles, and secondly to select a program to be recommended for use in implementing electric transient analysis in domestic nuclear power plants. In addition, to promote its practical use, a selected electric transient analysis program was tested by simulating the transient response during a load sequence test of an emergency diesel generator (EDG) in a domestic representative nuclear plant to evaluate its simulation accuracy by comparing its result with the measured plant data. The results obtained are as follows: (1) In U.S. nuclear power plants, simulations using electric transient analysis programs, such as ETAP, EMPT, etc., are widely performed, which contributed to improve the plant safety. (2) A selected transient analysis program EMTP was verified in its accuracy in terms of transient response of active power, current, voltage and frequency of the EDG during the load sequence test in a domestic representative nuclear power plant. (author)

  11. Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.

    Fan, Jing; Stemkowski, Patrick L; Gandini, Maria A; Black, Stefanie A; Zhang, Zizhen; Souza, Ivana A; Chen, Lina; Zamponi, Gerald W

    2016-01-01

    Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here, we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrP(C) profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 μM). HCN channel activity appeared to be functionally regulated by PrP(C). The amplitude of voltage sag, a characteristic of activating HCN channel current (I h), was decreased in null mice. Moreover, I h peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

  12. Proximity does not contribute to activity enhancement in the glucose oxidase-horseradish peroxidase cascade

    Zhang, Yifei; Tsitkov, Stanislav; Hess, Henry

    2016-12-01

    A proximity effect has been invoked to explain the enhanced activity of enzyme cascades on DNA scaffolds. Using the cascade reaction carried out by glucose oxidase and horseradish peroxidase as a model system, here we study the kinetics of the cascade reaction when the enzymes are free in solution, when they are conjugated to each other and when a competing enzyme is present. No proximity effect is found, which is in agreement with models predicting that the rapidly diffusing hydrogen peroxide intermediate is well mixed. We suggest that the reason for the activity enhancement of enzymes localized by DNA scaffolds is that the pH near the surface of the negatively charged DNA nanostructures is lower than that in the bulk solution, creating a more optimal pH environment for the anchored enzymes. Our findings challenge the notion of a proximity effect and provide new insights into the role of DNA scaffolds.

  13. [Cancer Disease Trajectory and the Contribution of Artistic Outreach Activity to Palliative Care].

    Oshiro, Hisako; Oshiro, Tatsuo; Tanimizu, Masahito

    2018-03-01

    The purpose of this article is to show some unintentional aspects of palliative supports offered by the community. The activities of the Opera Ehime, an amateur opera group, play an important role in palliative and grief care. This community is also committed to providing supportive care for home hospice cancer patients through an outreach music program that offers patients connection with others and reduces isolation. Assessment by the coordinator includes determiningthe patients' preferences and the relevance of music throughout their lives. Then, the coordinator predicts the cancer trajectory and invites patients to participate in the home hospice concert at any stage of their illness. These activities are an effective form of supportingcancer care for patients to promote wellness and improve physical and emotional well-being, as well as quality of life.

  14. The effects of changing solar activity on climate: contributions from palaeoclimatological studies

    Engels Stefan

    2012-07-01

    Full Text Available Natural climate change currently acts in concert with human-induced changes in the climate system. To disentangle the natural variability in the climate system and the human-induced effects on the global climate, a critical analysis of climate change in the past may offer a better understanding of the processes that drive the global climate system. In this review paper, we present palaeoclimatological evidence for the past influence of solar variability on Earth’s climate, highlighting the effects of solar forcing on a range of timescales. On a decadal timescale, instrumental measurements as well as historical records show the effects of the 11-year Schwabe cycle on climate. The variation in total solar irradiance that is associated with a Schwabe cycle is only ~1 W m−2 between a solar minimum and a maximum, but winter and spring temperatures on the Northern Hemisphere show a response even to this small-scale variability. There is a large body of evidence from palaeoclimatic reconstructions that shows the influence of solar activity on a centennial to millennial timescale. We highlight a period of low solar activity starting at 2800 years before present when Europe experienced a shift to colder and wetter climate conditions. The spatial pattern of climate change that can be recognized in the palaeoclimatological data is in line with the suggested pattern of climate change as simulated by climate models. Millennial-scale climate oscillations can be recognized in sediment records from the Atlantic Ocean as well as in records of lake-level fluctuations in southeastern France. These oscillations coincide with variation in 14C production as recognized in the atmospheric 14C record (which is a proxy-record for solar activity, suggesting that Earth’s climate is sensitive to changes in solar activity on a millennial timescale as well.

  15. E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and Contributes to Its Turnover.

    Saha, Siddhartha S; Caviness, Gary; Yi, Guanghui; Raymond, Ernest L; Mbow, M Lamine; Kao, C Cheng

    2018-01-01

    Signaling by the interleukin-36 receptor (IL-36R) is linked to inflammatory diseases such as psoriasis. However, the regulation of IL-36R signaling is poorly understood. Activation of IL-36R signaling in cultured cells results in an increased polyubiquitination of the receptor subunit, IL-1Rrp2. Treatment with deubiquitinases shows that the receptor subunit of IL-36R, IL-1Rrp2, is primarily polyubiquitinated at the K63 position, which is associated with endocytic trafficking and signal transduction. A minor amount of ubiquitination is at the K48 position that is associated with protein degradation. A focused siRNA screen identified RNF125, an E3 ubiquitin ligase, to ubiquitinate IL-1Rrp2 upon activation of IL-36R signaling while not affecting the activated IL-1 receptor. Knockdown of RNF125 decreases signal transduction by the IL-36R. Overexpression of RNF125 in HEK293T cells activates IL-36R signaling and increases the ubiquitination of IL-1Rrp2 and its subsequent turnover. RNF125 can coimmunoprecipitate with the IL-36R, and it traffics with IL-1Rrp2 from the cell surface to lysosomes. Mutations of Lys568 and Lys569 in the C-terminal tail of IL-1Rrp2 decrease ubiquitination by RNF125 and increase the steady-state levels of IL-1Rrp2. These results demonstrate that RNF125 has multiple regulatory roles in the signaling, trafficking, and turnover of the IL-36R. © 2017 S. Karger AG, Basel.

  16. Activation of NMDA receptor by elevated homocysteine in chronic liver disease contributes to encephalopathy.

    Choudhury, Sabanum; Borah, Anupom

    2015-07-01

    Liver diseases lead to a complex syndrome characterized by neurological, neuro-psychiatric and motor complications, called hepatic encephalopathy, which is prevalent in patients and animal models of acute, sub-chronic and chronic liver failure. Although alterations in GABAergic, glutamatergic, cholinergic and serotonergic neuronal functions have been implicated in HE, the molecular mechanisms that lead to HE in chronic liver disease (CLD) is least illustrated. Due to hepatocellular failure, levels of ammonia and homocysteine (Hcy), in addition to others, are found to increase in the brain as well as plasma. Hcy, a non-protein forming amino acid and an excitotoxin, activates ionotropic glutamate (n-methyl-d-aspartate; NMDA) receptors, and thereby leads to influx of Ca(2+) into neurons, which in turn activates several pathways that trigger oxidative stress, inflammation and apoptosis, collectively called excitotoxicity. Elevated levels of Hcy in the plasma and brain, a condition called Hyperhomocysteinemia (HHcy), and the resultant NMDA receptor-mediated excitotoxicity has been implicated in several diseases, including Parkinson's disease and Alzheimer's disease. Although, hyperammonemia has been shown to cause excitotoxicity, the role of HHcy in the development of behavioral and neurochemical alterations that occur in HE has not been illustrated yet. It is hypothesized that CLD-induced HHcy plays a major role in the development of HE through activation of NMDA receptors. It is further hypothesized that HHcy synergizes with hyperammonemia to activate NMDA receptor in the brain, and thereby cause oxidative stress, inflammation and apoptosis, and neuronal loss that leads to HE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

    Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

    1999-01-01

    We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

  18. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W.

    1991-01-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions

  19. Short Communication. Resin tapping activity as a contribution to the management of maritime pine forest

    Palma, A.; Pereira, J.M.; Soares, P.

    2016-07-01

    Aim of the study: In this work potential resin yield in a region of high forest ability where maritime pine is the main species was estimated in order to understand the viability of promoting resin exploitation. Area of study: This study was conducted in Castro Da ire County in central region of Portugal. Material and methods: To quantify the resin yield of trees tapped for the first time two plots were installed in a maritime pine stand with average tree age 65 years. Before the beginning of the resin tapping, dendrometric tree variables were measured. Also, in a neighbouring stand, 25 trees were selected to check the relation between tree dbh and resin yield. Gum resin from every tree was weighted during the season. Estimates of potential resin yield in Castro Daire County were made based on data from National Forest Inventory plots, resin tapping legislation and resin yield values obtained in the field. Two scenarios were considered: high and low resin yield. To understand the intentions of forest owners towards restarting resin tapping activity 16 maritime pine forest owners were interviewed. Main results: The results point out a high yield potential capacity for gum resin production in the County: values between 2,025 and 5,873 tons were obtained. Research highlights: Results may highlight the important socio-economical role of the resin tapping activity and can be used to support national forest policies to the resin sector and give forest owners motivation to reactivate resin tapping activity. (Author)

  20. Possible Contribution of PTSD to Altered Cortisol Activity in Young Adult Obese African-American Women.

    Taylor, Teletia R; Van Kirk, Kendra; Tapscott, Denia; Bernard, Monet; Llano, Juliana; Mellman, Thomas A

    2015-06-01

    African-Americans have been found to experience increased rates of post-traumatic stress disorder (PTSD), obesity, and flatter diurnal cortisol slopes compared to other demographic groups. Further exploration, however, is needed to understand how PTSD impacts diurnal cortisol activity in obese African-American women. The purpose of the current study is to examine the relationship between salivary cortisol levels and PTSD in a sample of obese young adult African-American women and to examine how depression and insomnia influence the relationship. Thirty-four young adult African-American women (mean age = 24.0 years; mean BMI = 37.4 kg/m(2), 6/34 of the sample had a score of 40 or above on the PTSD Checklist (PCL) representing clinically significant PTSD) filled out questionnaires assessing PTSD, lifetime exposure to traumatic events, insomnia severity, and depression. A home-based assessment of salivary cortisol was provided upon awakening at 30 min and 1, 3, 6, and 12 h. There was a significant interaction between PTSD status and diurnal cortisol activity (p cortisol levels at awakening (p cortisol was attenuated by co-varying for depression and insomnia (p > 0.05). PTSD, influenced by depression and insomnia symptoms, has an impact on diurnal cortisol activity in obese young adult African-American women.

  1. Phosphorylation and nuclear accumulation are distinct events contributing to the activation of p53

    O'Hagan, Heather M.; Ljungman, Mats

    2004-01-01

    It has been recently shown that ionizing radiation (IR) and the mRNA synthesis inhibitor 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) act in synergy to induce p53-mediated transactivation of reporter plasmids in human cells [Oncogene 19 (2000) 3829]. We have extended these studies and show that ionizing radiation and DRB also act in synergy to induce ATM-mediated phosphorylation of the ser15 site of p53 and enhance the expression of endogenous p21 protein. Examination of the localization of p53 revealed that while DRB did not induce phosphorylation of the ser15 site of p53 but efficiently accumulated p53 in the nucleus, ionizing radiation induced phosphorylation of the ser15 site of p53 without prolonged nuclear accumulation. Importantly, the combination of DRB and IR resulted in a strong accumulation of phosphorylated p53 in the nucleus that was more persistent then p53 accumulation after IR alone. Furthermore, the nuclear export inhibitor leptomycin B showed a similar synergy with IR as did DRB regarding ser15 phosphorylation of p53 and p21 induction. These results suggest that the synergistic activation of the p53 response by the combination treatment is due to the activation of two distinct pathways where DRB causes the prolonged nuclear accumulation of p53 while ionizing radiation activates p53 by ATM-mediated phosphorylation

  2. Contribution to the relation between volume activity of soil and indoor radon

    Mojzes, A.

    1999-01-01

    There were carried out some repeated manual measurements of volume activity of radon-222 (VAR) in both soil air of subsoil and also indoor air of buildings in two different areas in Bratislava. All measurements were done with a portable scintillation detector based on exchangeable Lucas cells. The measurements were repeated in different day and year intervals. There were repeated 259 measurements of volume activity of radon-222 in soil air with the average valuer 11.95 kBq/m 3 and the standard deviation 1.53 kBq/m 3 in the subsoil of the one-story house and 597 measurements of VAR in soil air of the subsoil of the second study building with the average 9.44 kBq/m 3 and the standard deviation 3.08 kBq/m 3 . Presented results of measurement of radon-222 volume activity in both soil and indoor air demonstrate that also in case of low radon concentrations in soil air of geological basement the level of radon in indoor air could be considerably high. It depends mainly on used technology of laying building foundations, on the distance from subsoil and on regime of ventilation. In case of older buildings the ventilation is very effective way to reduce the presence of radon in indoor air. (author)

  3. Activation of AMPK by Buddleja officinalis Maxim. Flower Extract Contributes to Protecting Hepatocytes from Oxidative Stress.

    Jung, Ji Yun; Lee, Chul Won; Park, Sang Mi; Jegal, Kyung Hwan; Kim, Jae Kwang; Park, Chung A; Cho, Il Je; Jung, Dae Hwa; An, Won G; Ku, Sae Kwang; Zhao, Rongjie; Kim, Sang Chan

    2017-01-01

    The Buddleja officinalis Maxim. flower is used in traditional Chinese and Korean medicine to treat inflammation, vascular diseases, headache, and stroke, as well as enhance liver function. This research investigated the effects of B. officinalis Maxim. flower extract (BFE) on hepatotoxicity. The cytoprotective effects and mechanism of BFE against severe mitochondrial dysfunction and H 2 O 2 production in hepatotoxicity induced by coadministration of arachidonic acid (AA) and iron were observed in the HepG2 cell line. In addition, we performed blood biochemical, histopathological, and histomorphometric analyses of mice with carbon tetrachloride- (CCl 4 -) induced acute liver damage. BFE inhibited the AA + iron-mediated hepatotoxicity of HepG2 cells. Moreover, it inhibited mitochondrial dysfunction, H 2 O 2 production, and glutathione depletion mediated by AA + iron in the same cells. Meanwhile, the cytoprotective effects of BFE against oxidative stress were associated with the activation of AMP-activated protein kinase (AMPK). In particular, based on the histopathological observations, BFE (30 and 100 mg/kg) showed clear hepatoprotective effects against CCl 4 -induced acute hepatic damage. Furthermore, it inhibited 4-hydroxynonenal and nitrotyrosine immunoreactivity in hepatocytes. These results provide evidence that BFE has beneficial hepatoprotective effects against hepatic damage via the activation of AMPK pathway. Accordingly, BFE may have therapeutic potential for diverse liver disorders.

  4. Academic research as human activity: Occupational Therapy contributions for consumer participation

    Tatiana Dimov

    2016-07-01

    Full Text Available The involvement of consumers in research is a recent trend in the world. Involving consumers in researches on health services, therapeutic approaches, effectiveness of support groups, mutual help groups, and even on medication is crucial for obtaining academic results that are representative of the group of consumers, and influence public policies that are effective and functional for consumers. This paper presents an analysis of how consumers can get involved in a research and what can be the role of an occupational therapist in such activity. When governed by the principles of autonomy, empowerment, and recovery, researches with consumer participation promote the principles of equality and recognition, allowing inclusion in the research process, and promoting the recognition of consumer knowledge. As an activity, research can be a motivator, mobilizing wills and desires. It can also be a possibility of leaving stagnation and making decisions. The occupational therapist can help this process. Occupational therapy focus on activities that are significant to the life of individuals. Participation in research becomes a focus for the therapeutic process to the extent that it presents itself as a demand for the client.

  5. Active and Healthy Ageing as a Wicked Problem: The Contribution of a Multidisciplinary Research University.

    Riva, Giuseppe; Graffigna, Guendalina; Baitieri, Maddalena; Amato, Alessandra; Bonanomi, Maria Grazia; Valentini, Paolo; Castelli, Guido

    2014-01-01

    The quest for an active and healthy ageing can be considered a "wicked problem." It is a social and cultural problem, which is difficult to solve because of incomplete, changing, and contradictory requirements. These problems are tough to manage because of their social complexity. They are a group of linked problems embedded in the structure of the communities in which they occur. First, they require the knowledge of the social and cultural context in which they occur. They can be solved only by understanding of what people do and why they do it. Second, they require a multidisciplinary approach. Wicked problems can have different solutions, so it is critical to capture the full range of possibilities and interpretations. Thus, we suggest that Università Cattolica del Sacro Cuore (UCSC) is well suited for accepting and managing this challenge because of its applied research orientation, multidisciplinary approach, and integrated vision. After presenting the research activity of UCSC, we describe a possible "systems thinking" strategy to consider the complexity and interdependence of active ageing and healthy living.

  6. Activation of AMPK by Buddleja officinalis Maxim. Flower Extract Contributes to Protecting Hepatocytes from Oxidative Stress

    Ji Yun Jung

    2017-01-01

    Full Text Available The Buddleja officinalis Maxim. flower is used in traditional Chinese and Korean medicine to treat inflammation, vascular diseases, headache, and stroke, as well as enhance liver function. This research investigated the effects of B. officinalis Maxim. flower extract (BFE on hepatotoxicity. The cytoprotective effects and mechanism of BFE against severe mitochondrial dysfunction and H2O2 production in hepatotoxicity induced by coadministration of arachidonic acid (AA and iron were observed in the HepG2 cell line. In addition, we performed blood biochemical, histopathological, and histomorphometric analyses of mice with carbon tetrachloride- (CCl4- induced acute liver damage. BFE inhibited the AA + iron-mediated hepatotoxicity of HepG2 cells. Moreover, it inhibited mitochondrial dysfunction, H2O2 production, and glutathione depletion mediated by AA + iron in the same cells. Meanwhile, the cytoprotective effects of BFE against oxidative stress were associated with the activation of AMP-activated protein kinase (AMPK. In particular, based on the histopathological observations, BFE (30 and 100 mg/kg showed clear hepatoprotective effects against CCl4-induced acute hepatic damage. Furthermore, it inhibited 4-hydroxynonenal and nitrotyrosine immunoreactivity in hepatocytes. These results provide evidence that BFE has beneficial hepatoprotective effects against hepatic damage via the activation of AMPK pathway. Accordingly, BFE may have therapeutic potential for diverse liver disorders.

  7. Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

    Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

    2014-12-01

    Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. Copyright © 2014 the American Physiological Society.

  8. Cortical computations via transient attractors.

    Oliver L C Rourke

    Full Text Available The ability of sensory networks to transiently store information on the scale of seconds can confer many advantages in processing time-varying stimuli. How a network could store information on such intermediate time scales, between typical neurophysiological time scales and those of long-term memory, is typically attributed to persistent neural activity. An alternative mechanism which might allow for such information storage is through temporary modifications to the neural connectivity which decay on the same second-long time scale as the underlying memories. Earlier work that has explored this method has done so by emphasizing one attractor from a limited, pre-defined set. Here, we describe an alternative, a Transient Attractor network, which can learn any pattern presented to it, store several simultaneously, and robustly recall them on demand using targeted probes in a manner reminiscent of Hopfield networks. We hypothesize that such functionality could be usefully embedded within sensory cortex, and allow for a flexibly-gated short-term memory, as well as conferring the ability of the network to perform automatic de-noising, and separation of input signals into distinct perceptual objects. We demonstrate that the stored information can be refreshed to extend storage time, is not sensitive to noise in the system, and can be turned on or off by simple neuromodulation. The diverse capabilities of transient attractors, as well as their resemblance to many features observed in sensory cortex, suggest the possibility that their actions might underlie neural processing in many sensory areas.

  9. Cortical computations via transient attractors.

    Rourke, Oliver L C; Butts, Daniel A

    2017-01-01

    The ability of sensory networks to transiently store information on the scale of seconds can confer many advantages in processing time-varying stimuli. How a network could store information on such intermediate time scales, between typical neurophysiological time scales and those of long-term memory, is typically attributed to persistent neural activity. An alternative mechanism which might allow for such information storage is through temporary modifications to the neural connectivity which decay on the same second-long time scale as the underlying memories. Earlier work that has explored this method has done so by emphasizing one attractor from a limited, pre-defined set. Here, we describe an alternative, a Transient Attractor network, which can learn any pattern presented to it, store several simultaneously, and robustly recall them on demand using targeted probes in a manner reminiscent of Hopfield networks. We hypothesize that such functionality could be usefully embedded within sensory cortex, and allow for a flexibly-gated short-term memory, as well as conferring the ability of the network to perform automatic de-noising, and separation of input signals into distinct perceptual objects. We demonstrate that the stored information can be refreshed to extend storage time, is not sensitive to noise in the system, and can be turned on or off by simple neuromodulation. The diverse capabilities of transient attractors, as well as their resemblance to many features observed in sensory cortex, suggest the possibility that their actions might underlie neural processing in many sensory areas.

  10. How implicitly activated and explicitly acquired knowledge contribute to the effectiveness of retrieval cues.

    Nelson, Douglas L; Fisher, Serena L; Akirmak, Umit

    2007-12-01

    The extralist cued recall task simulates everyday reminding because a memory is encoded on the fly and retrieved later by an unexpected cue. Target words are studied individually, and recall is cued by associatively related words having preexisting forward links to them. In Experiments 1 and 2, forward cue-to-target and backward target-to-cue strengths were varied over an extended range in order to determine how these two sources of strength are related and which source has a greater effect. Forward and backward strengths had additive effects on recall, with forward strength having a consistently larger effect. The PIER2 model accurately predicted these findings, but a plausible generation-recognition version of the model, called PIER.GR, could not. In Experiment 3, forward and backward strengths, level of processing, and study time were varied in order to determine how preexisting lexical knowledge is related to knowledge acquired during the study episode. The main finding indicates that preexisting knowledge and episodic knowledge have additive effects on extralist cued recall. PIER2 can explain these findings because it assumes that these sources of strength contribute independently to recall, whereas the eSAM model cannot explain the findings because it assumes that the sources of strength are multiplicatively related.

  11. Active liquid/liquid interfaces: contributions of non linear optics and tensiometry

    Gassin, P.M.

    2013-01-01

    Liquid-liquid extraction processes are widely used in the industrial fields of selective separation. Despite its numerous applications, the microscopic mechanisms which occur during a liquid-liquid extraction processes are really unknown specially at the liquid/liquid interface. Thus, this work deals on the understanding of the phenomena which drive the mass transfer across a liquid/liquid interface. Two experimental techniques were used in this work: dynamic interfacial tension measurement and non-linear optical experiments. Along with the use of this experimental approach, a numerical model describing the mass transfer dynamic has been developed. This model works under the assumption that both diffusion and a chemical step describing adsorption and desorption processes contribute to the global transfer kinetics. Model systems of surfactant molecules, chromophore molecules and complexing molecule were investigated at liquid/liquid and air/liquid interface. Interfacial phenomena like adsorption, surface aggregation and ion complexing were studied. Finally, the methodology developed in this work was applied to studied an extractant molecule with potential industrial application. (author) [fr

  12. Gamma rays from active regions in the galaxy: the possible contribution of stellar winds

    Cesarsky, C.J.; Montmerle, Thierry.

    1982-08-01

    Massive stars release a considerable amount of mechanical energy in the form of strong stellar winds. A fraction of this energy may be transferred to relativistic cosmic rays by diffusive shock acceleration at the wind boundary, and/or in the expanding, turbulent wind itself. Massive stars are most frequently found in OB associations, surrounded by H II regions lying at the edge of dense molecular clouds. The interaction of the freshly accelerated particles with matter gives rise to #betta#-ray emission. In this paper, we first briefly review the current knowledge on the energetics of strong stellar winds from O and Wolf-Rayet stars, as well as from T Tauri stars. Taking into account the finite lifetime of these stars, we then proceed to show that stellar winds dominate the energetics of OB associations during the first 4 to 6 million years, after which supernovae take over. In the solar neighborhood, the star formation rate is constant, and a steady-state situation prevails, in which the supernova contribution is found to be dominant. A small, but meaningful fraction of the CO S-B #betta#-ray sources may be fueled by WR and O stellar winds in OB associations, while the power released by T Tauri stars alone is perhaps insufficient to account for the #betta#-ray emission of nearby dark clouds. Finally, we discuss some controversial aspects of the physics of particle acceleration by stellar winds

  13. Institutional opening: contribution to the public acceptance of the nuclear activities

    Martin, Hugo R.

    2003-01-01

    Activities that the National Atomic Energy Commission (CNEA) has carried out during a half century in Cordoba city show a long misunderstanding and confrontations with the provincial and municipal authorities, and with the neighbors and environmentalist antinuclear organizations. Most of the information that the people have received about the risks and benefits of the activities has generally been produced by the media. The media have always started the pressures on the political leadership and the government officials, to get measures on activities that are perceived as excessively dangerous. However the experience indicates that the demands for the protection of the health or the environment and sometimes the claiming for the closing of the facilities have been directly related with what people really know about the activities in the site. All that they know, comes from listening the radio and television or reading the newspapers. The common denominator that one observes in the conflicts of the past, is the high degree of ignorance on the part of the citizenship on the activities that are carried out in the place. This is valid for the neighbors of the place, for the competent authorities and even for the Cordoba's scientific and technical qualified community. From the analysis it also arises that the conflicts were originated by the absence of preventive actions to assist them properly (or to neutralize them in premature form) as well as for fair reasons related with unacceptable risks for the society. Finally the facts have demonstrated that the incompatibility among the reasoning of the technicians supporting their positions in rational arguments and the fundamentalism of the environmentalist's methodology using incomplete and emotional arguments, makes impossible a sustainable agreement for the development of the activities of the CNEA in Cordoba city. The origin of the conflicts are essentially two: the existence in the site of the residues of the minerals

  14. Cell wall-anchored nuclease of Streptococcus sanguinis contributes to escape from neutrophil extracellular trap-mediated bacteriocidal activity.

    Chisato Morita

    Full Text Available Streptococcus sanguinis, a member of the commensal mitis group of streptococci, is a primary colonizer of the tooth surface, and has been implicated in infectious complications including bacteremia and infective endocarditis. During disease progression, S. sanguinis may utilize various cell surface molecules to evade the host immune system to survive in blood. In the present study, we discovered a novel cell surface nuclease with a cell-wall anchor domain, termed SWAN (streptococcal wall-anchored nuclease, and investigated its contribution to bacterial resistance against the bacteriocidal activity of neutrophil extracellular traps (NETs. Recombinant SWAN protein (rSWAN digested multiple forms of DNA including NET DNA and human RNA, which required both Mg(2+ and Ca(2+ for optimum activity. Furthermore, DNase activity of S. sanguinis was detected around growing colonies on agar plates containing DNA. In-frame deletion of the swan gene mostly reduced that activity. These findings indicated that SWAN is a major nuclease displayed on the surface, which was further confirmed by immuno-detection of SWAN in the cell wall fraction. The sensitivity of S. sanguinis to NET killing was reduced by swan gene deletion. Moreover, heterologous expression of the swan gene rendered a Lactococcus lactis strain more resistant to NET killing. Our results suggest that the SWAN nuclease on the bacterial surface contributes to survival in the potential situation of S. sanguinis encountering NETs during the course of disease progression.

  15. Cell wall-anchored nuclease of Streptococcus sanguinis contributes to escape from neutrophil extracellular trap-mediated bacteriocidal activity.

    Morita, Chisato; Sumioka, Ryuichi; Nakata, Masanobu; Okahashi, Nobuo; Wada, Satoshi; Yamashiro, Takashi; Hayashi, Mikako; Hamada, Shigeyuki; Sumitomo, Tomoko; Kawabata, Shigetada

    2014-01-01

    Streptococcus sanguinis, a member of the commensal mitis group of streptococci, is a primary colonizer of the tooth surface, and has been implicated in infectious complications including bacteremia and infective endocarditis. During disease progression, S. sanguinis may utilize various cell surface molecules to evade the host immune system to survive in blood. In the present study, we discovered a novel cell surface nuclease with a cell-wall anchor domain, termed SWAN (streptococcal wall-anchored nuclease), and investigated its contribution to bacterial resistance against the bacteriocidal activity of neutrophil extracellular traps (NETs). Recombinant SWAN protein (rSWAN) digested multiple forms of DNA including NET DNA and human RNA, which required both Mg(2+) and Ca(2+) for optimum activity. Furthermore, DNase activity of S. sanguinis was detected around growing colonies on agar plates containing DNA. In-frame deletion of the swan gene mostly reduced that activity. These findings indicated that SWAN is a major nuclease displayed on the surface, which was further confirmed by immuno-detection of SWAN in the cell wall fraction. The sensitivity of S. sanguinis to NET killing was reduced by swan gene deletion. Moreover, heterologous expression of the swan gene rendered a Lactococcus lactis strain more resistant to NET killing. Our results suggest that the SWAN nuclease on the bacterial surface contributes to survival in the potential situation of S. sanguinis encountering NETs during the course of disease progression.

  16. INTEGRAL Galactic Bulge monitoring: transient activity from KS 1741-293, MXB 1730-335, and IGR J17498-2921

    Chenevez, Jérôme; Brandt, Søren; Kuulkers, E.

    2011-01-01

    sigma upper limit of 10 mCrab (40-100 keV) A series of 15 type II bursts is detected when the source was inside the JEM-X field of view, with an average burst recurrence time of about four minutes. The new transient source IGR J17498-2921 (see, e.g., ATels #3551, #3556, #3558, #3568, #3606) is only...

  17. Ethanol activation of protein kinase A regulates GABA-A receptor subunit expression in the cerebral cortex and contributes to ethanol-induced hypnosis

    Sandeep eKumar

    2012-04-01

    Full Text Available Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking and synaptic excitability. Both protein kinase C (PKC and A (PKA are involved in regulation of γ-aminobutyric acid type A (GABA-A receptors through phosphorylation. However, the role of PKA in regulating GABA-A receptors following acute ethanol exposure is not known. The present study investigated the role of PKA in ethanol effects on GABA-A receptor α1 subunit expression in the P2 synaptosomal fraction of the rat cerebral cortex. Additionally, GABA-related behaviors were also examined. Rats were administered ethanol (2.0 – 3.5 g/kg or saline and PKC, PKA and GABA-A receptor α1 subunit levels were measured by Western blot analysis. Ethanol (3.5 g/kg transiently increased GABA-A receptor α1 subunit expression and PKA RIIβ subunit expression at similar time points whereas PKA RIIα was increased at later time points. In contrast, PKC isoform expression remained unchanged. Notably, the moderate ethanol dose (2.0g/kg had no effect on GABA-A α1 subunit levels although PKA RIIα and RIIβ were increased at 10 and 60 minutes, when PKC isozymes are also known to be elevated. To determine if PKA activation was responsible for the ethanol-induced elevation of GABA-A α1 subunits, the PKA antagonist H89 was administered to rats prior to ethanol exposure. H89 administration prevented ethanol-induced increases in GABA-A receptor α1 subunit expression. Moreover, increasing PKA activity intracerebroventricularly with Sp-cAMP prior to a hypnotic dose of ethanol increased ethanol-induced loss of righting reflex duration. This effect appears to be mediated in part by GABA-A receptors as increasing PKA activity also increased the duration of muscimol-induced loss of righting reflex. Overall these data suggest that PKA mediates ethanol-induced GABA-A receptor expression and contributes to ethanol behavioral effects involving GABA-A receptors.

  18. Transient flow combustion

    Tacina, R. R.

    1984-01-01

    Non-steady combustion problems can result from engine sources such as accelerations, decelerations, nozzle adjustments, augmentor ignition, and air perturbations into and out of the compressor. Also non-steady combustion can be generated internally from combustion instability or self-induced oscillations. A premixed-prevaporized combustor would be particularly sensitive to flow transients because of its susceptability to flashback-autoignition and blowout. An experimental program, the Transient Flow Combustion Study is in progress to study the effects of air and fuel flow transients on a premixed-prevaporized combustor. Preliminary tests performed at an inlet air temperature of 600 K, a reference velocity of 30 m/s, and a pressure of 700 kPa. The airflow was reduced to 1/3 of its original value in a 40 ms ramp before flashback occurred. Ramping the airflow up has shown that blowout is more sensitive than flashback to flow transients. Blowout occurred with a 25 percent increase in airflow (at a constant fuel-air ratio) in a 20 ms ramp. Combustion resonance was found at some conditions and may be important in determining the effects of flow transients.

  19. Short Communication. Resin tapping activity as a contribution to the management of maritime pine forest

    Amélia Palma

    2016-07-01

    Full Text Available Aim of the study: In this work potential resin yield in a region of high forest ability where maritime pine is the main species was estimated in order to understand the viability of promoting resin exploitation. Area of study: This study was conducted in Castro Daire County in central region of Portugal. Material and methods: To quantify the resin yield of trees tapped for the first time two plots were installed in a maritime pine stand with average tree age 65 years. Before the beginning of the resin tapping, dendrometric tree variables were measured. Also, in a neighbouring stand, 25 trees were selected to check the relation between tree dbh and resin yield. Gum resin from every tree was weighted during the season. Estimates of potential resin yield in Castro Daire County were made based on data from National Forest Inventory plots, resin tapping legislation and resin yield values obtained in the field. Two scenarios were considered: high and low resin yield. To understand the intentions of forest owners towards restarting resin tapping activity 16 maritime pine forest owners were interviewed. Main results: The results point out a high yield potential capacity for gum resin production in the County: values between 2,025 and 5,873 tons were obtained. Research highlights: Results may highlight the important socio-economical role of the resin tapping activity and can be used to support national forest policies to the resin sector and give forest owners motivation to reactivate resin tapping activity. Keywords: non-wood forest product; resin yield potential; forest owner.

  20. Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome.

    Rong Li

    Full Text Available Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1 control group; (2 SA (stable angina group; and (3 ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day and high-statin (atorvastatin, 20 mg/kg/day group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

  1. Assessment of Activity Concentration of Ilmenite and its Contribution to Environment

    Syed Asraf Fahlawi Wafa Syed Mohd Ghazi; Ismail Sulaiman; Mohd Rodzi Ali; Rahimah Abdul Rahim; Noraisyah Yusof; Juliana Mahamad Napiah

    2014-01-01

    Ferum Titanium Oxide (FeTiO 3 ) is the Natural Occurring Radioactive Material (NORM). This mineral contains radionuclides from uranium decay series like Radium-226 ( 226 Ra) and from thorium decay series nuclide like Radium-228 ( 228 Ra) and also from Potassium-40 ( 40 K). This radionuclide in large quantities will increase the radiation exposure risk to mankind and environment. In-situ measurement using scintillation survey meter show that external dose rate at 1 and 0.05 meter from soil surface was 97.0 ± 23.3 and 117 ± 26 nSv/ hour. This figure nearly the same with the average dose rate for Malaysia but higher than world average (UNSCEAR 2000). Monitoring of U and Th concentration from the air show that the result was below detection limit of < 0.0001 Bq/ m 3 . It show that's no radionuclide transfer or migrate to environment. Activity concentration of natural radionuclide of 40 K, 226 Ra, 232 Th and 238 U from the soil was 573 ± 184 Bqkg -1 , 30.6 ± 10.2 Bqkg -1 , 18.8 ± 6.4 Bqkg -1 , and 64.0 ± 34.3 Bqkg -1 . For ilmenite, the activity concentration was 39.0 ± 10.0 Bqkg -1 , 28.0 ± 6.7 Bqkg -1 , 84.0 ± 6.9 Bqkg -1 dan 50.0 ± 7.4 Bqkg -1 for the same natural radionuclide. Effective dose for the public show that the value of 0.17 mSv/ year was lower than the world average effective dose from the natural radioactivity. Radium equivalent for ilmenite and soil was 173 ± 77 and 42.7 ± 0.4 respectively. External Hazard Index is 0.47 ± 0.21 dan 0.36 ± 0.12 for ilmenite and soil. The external radiation hazard index is less than 1, which means it is safe for human to carry out their activities in the area. The estimated cancer risk value was 4.25 x 10 -4 . The probability of increase of cancer risk from the industry is a minor fraction of ICRP values. Event though the result show that the activity from the industry was insignificant to increase the radiation exposure, but all the safety precautions must be follow as per standards and the legislation

  2. Side Chain and Flexibility Contributions to the Raman Optical Activity Spectra of a Model Cyclic Hexapeptide

    Hudecová, J.; Kapitán, Josef; Baumruk, V.; Hammer, R. P.; Keiderling, T. A.; Bouř, Petr

    2010-01-01

    Roč. 114, č. 28 (2010), s. 7642-7651 ISSN 1089-5639 R&D Projects: GA ČR GA203/06/0420; GA ČR GA202/07/0732; GA AV ČR IAA400550702 Grant - others:GA UK(CZ) 126310 Institutional research plan: CEZ:AV0Z40550506 Keywords : Raman optical activity * ab initio * side chain * flexibility * peptide Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.732, year: 2010

  3. Potential antioxidant Bauhinia Leaves and Bark kalbreyeri Harms: Contribution of your Flavonoids in this activity

    Ortiz, Heidy F; Sanchez, Wilmer F; Mendez A John; Murillo P, Elizabeth

    2009-01-01

    In this study the antioxidant and antitrosative capacity of the extracts and isolated flavonoids from the leaves and bark of Bauhinia kalbreyeri Harms (Cow Hoof. Fabaceae) was examinated. The extracts showed high antioxidant and antinitrosative functionality, while the flavonoids ability to capture metals and inhibit the NO. Significative differences were found among the extracts, and into those and the flavonoids fractions (p < 0.05). The antioxidant activity of the plant seems to be based in the whole phenolic derivatives. The results obtained indicate that the antioxidant potential of B. kalbreyeri is comparable with the Butylated Hydroxytoluene and the ascorbic acid used as antioxidants by the food and pharmaceutical industry.

  4. The ciliate, Troglodytella abrassarti, contributes to polysaccharide hydrolytic activities in the chimpanzee colon

    Profousová, Ilona; Mihaliková, K.; Laho, T.; Váradyová, Z.; Petrželková, Klára Judita; Modrý, David; Kišidayová, S.

    2011-01-01

    Roč. 56, č. 4 (2011), s. 339-343 ISSN 0015-5632 R&D Projects: GA ČR GA524/06/0264; GA ČR GA206/09/0927 Grant - others:VFU(CZ) 245/2009/FVL Institutional research plan: CEZ:AV0Z60930519; CEZ:AV0Z60220518 Keywords : different protozoal populations * low-fiber diets * Eudiplodinium maggii * fibrolytic activity * degrading enzymes Subject RIV: EG - Zoology Impact factor: 0.677, year: 2011

  5. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  6. International conference on lessons learned from the decommissioning of nuclear facilities and the safe termination of nuclear activities. Contributed papers

    2006-12-01

    The International Atomic Energy Agency (IAEA), in cooperation with the European Commission (EC), Nuclear Energy Agency to the Organisation for Economic Co-operation and Development (OECD/NEA), and the World Nuclear Association (WNA), organized an International Conference on Lessons Learned from the Decommissioning of Nuclear Facilities and the Safe Termination of Nuclear Activities from 11 to 15 December 2006 in Athens, Greece. This Book of Contributed Papers contains technical papers and posters contributed by experts from operating organisations, regulatory bodies, technical support organisations, and other institutions on issues falling within the scope of the Conference. The following main topics were covered: Evolution of national and international policies and criteria for the safe and efficient decommissioning of nuclear facilities and safe termination of nuclear activities; Review of lessons learned from ongoing or completed activities associated with decommissioning; Improvement of safety and efficiency through the use of new and innovative technologies; Practical aspects in the management of material, waste and sites resulting from decommissioning, including the management of waste in the absence of repositories and waste acceptance requirements; Procedures for demonstrating compliance with clearance criteria; Experience from radiological assessments associated with decommissioning; Involvement of the local communities and the impact that decommissioning activities has on them. The presented papers and posters were reviewed and accepted following the guidelines established by the Conference Programme Committee for consideration at the Conference. The material compiled in this Book of Contributed Papers has not undergone rigorous editing by the editorial staff of the IAEA. However, certain modifications were made: a unified format was adopted for all papers; and minor corrections were made in the text where required. Each paper and poster has been indexed

  7. International conference on lessons learned from the decommissioning of nuclear facilities and the safe termination of nuclear activities. Contributed papers

    NONE

    2006-12-15

    The International Atomic Energy Agency (IAEA), in cooperation with the European Commission (EC), Nuclear Energy Agency to the Organisation for Economic Co-operation and Development (OECD/NEA), and the World Nuclear Association (WNA), organized an International Conference on Lessons Learned from the Decommissioning of Nuclear Facilities and the Safe Termination of Nuclear Activities from 11 to 15 December 2006 in Athens, Greece. This Book of Contributed Papers contains technical papers and posters contributed by experts from operating organisations, regulatory bodies, technical support organisations, and other institutions on issues falling within the scope of the Conference. The following main topics were covered: Evolution of national and international policies and criteria for the safe and efficient decommissioning of nuclear facilities and safe termination of nuclear activities; Review of lessons learned from ongoing or completed activities associated with decommissioning; Improvement of safety and efficiency through the use of new and innovative technologies; Practical aspects in the management of material, waste and sites resulting from decommissioning, including the management of waste in the absence of repositories and waste acceptance requirements; Procedures for demonstrating compliance with clearance criteria; Experience from radiological assessments associated with decommissioning; Involvement of the local communities and the impact that decommissioning activities has on them. The presented papers and posters were reviewed and accepted following the guidelines established by the Conference Programme Committee for consideration at the Conference. The material compiled in this Book of Contributed Papers has not undergone rigorous editing by the editorial staff of the IAEA. However, certain modifications were made: a unified format was adopted for all papers; and minor corrections were made in the text where required. Each paper and poster has been indexed

  8. Enhanced electrochemomechanical activity of polyaniline films towards high pH region: contribution of Donnan effect

    Takashima, Wataru; Nakashima, Megumi; Pandey, Shyam S.; Kaneto, Keiichi

    2004-01-01

    Enhancement of electrochemomechanical deformation (ECMD) and expansion of ECMD activity towards high pH have been simultaneously achieved in the electrolytes equilibrated with HCl and NaCl solutions for polyaniline (PANI) film. The maximum deformation has been reached to 6.7% in the mixture of 3 M HCl and 3 M NaCl equilibrated at pH 3 at ambient temperature. By comparing the fact that the ECMD magnitude is 3.2% in 1 M HCl equilibrated at pH 0.5, the simple judicious selection of electrolyte condition leads to the enhancement of ECMD magnitude by around two times. The concentration dependence on both electrical conductivity and absorption spectra elucidates the increase of protonation ratio as a function of electrolyte concentration. The results indicate that the high concentration retains both the electrochemical and ECMD activities in PANI film towards high pH region, which is the enhanced functionality of PANI supported by Donnan effect

  9. Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis.

    Yanagawa, Masato; Uchida, Kazushige; Ando, Yugo; Tomiyama, Takashi; Yamaguchi, Takashi; Ikeura, Tsukasa; Fukui, Toshiro; Nishio, Akiyoshi; Uemura, Yoshiko; Miyara, Takayuki; Okamoto, Hiroyuki; Satoi, Souhei; Okazaki, Kazuichi

    2018-03-01

    Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP. By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells. Additionally, we obtained peripheral blood samples from 27 healthy subjects, 40 patients with type 1 AIP, 8 patients with alcoholic chronic pancreatitis, 10 patients with bronchial asthma, and 10 patients with atopic dermatitis, and analyzed activation of basophils by stimulating them with ligands of TLR1-9. We also compared TLR expression in basophils from the tissue and blood samples. Basophils were detected in pancreatic tissues from 10 of 13 patients with type 1 AIP. Flow cytometric analysis revealed that the ratios of basophils activated by TLR4 stimulation in type 1 AIP (9.875 ± 1.148%) and atopic dermatitis (11.768 ± 1.899%) were significantly higher than those in healthy subjects (5.051 ± 0.730%; P pathophysiology of type 1 AIP.

  10. Translational Science: How experimental research has contributed to the understanding of spontaneous Physical Activity and Energy Homeostasis

    Izabelle D Benfato

    2017-05-01

    Full Text Available Abstract Spontaneous physical activity (SPA consists of all daily living activities other than volitional exercise (e.g. sports and fitness-related activities. SPA is an important component of energy expenditure and may protect from overweight and obesity. Little is known about the biological regulation of SPA, but animal researchhas contributedsignificantly to expand our knowledge in this field. Studies in rodents have shown that SPA is influenced by nutrients and volitional exercise. High-fat diet seems to decrease SPA, which contributes to weigh gain. Volitional exercisemayalso reduce SPA, helping to explain the commonly reported low efficiency of exercise to cause weight loss, and highlighting the need to finda volume/intensity of exercise to maximize total daily energy expenditure. Animal studieshave also allowed for the identification of some brain areas and chemical mediatorsinvolved in SPA regulation. These discoveries could enable the development of new therapeutics aiming to enhance SPA.

  11. Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

    Miguel Angel Burguillos

    2015-03-01

    Full Text Available Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4 in microglia’s inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3 released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.

  12. Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock.

    Whitt, Joshua P; McNally, Beth A; Meredith, Andrea L

    2018-02-05

    Large conductance K + (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca 2+ (Ca 2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca 2+ channels (VGCCs) and channels mediating Ca 2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca 2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca 2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca 2+ i are reduced. Here, to determine whether diurnal regulation of Ca 2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca 2+ channels (LTCCs) are the primary daytime Ca 2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)-mediated Ca 2+ i release. The N- and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca 2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. © 2018 Whitt et al.

  13. Contributions to the prompt neutron activation analysis of industrially used coals and zinc roasting products

    Dammermann, H.

    1982-01-01

    The construction of an irradiation plant for calibration measurement by means of prompt neutron activation analysis is described. A 5.84 μg and 16.3 μg Cf-252 source serve as neutron sources. Tests have shown an inner centred arrangement to offer the best solution for sources of this strength. The use of the PNAA method for determining sulphur, iron and chloride content in brown coal was tested and calibration curves drawn. The sulphur content of the coal briquettes tested was found to be 0.27% S, the iron content amounting to 0.21% Fe and chloride to 0.06%. These values correlate closely with values obtained from wet chemical industrial analysis. (WI)

  14. The Contribution of Innovation Strategy Development and Implementation in Active Facilitation of Pharmaceutical Front End Innovation

    Aagaard, Annabeth

    2012-01-01

    Front end innovation (FEI) represents the first building blocks of product development, but is often regarded as a weak link in innovation literature. Various theorists emphasize that a firm’s innovation can benefit substantially by improving the front end of innovation process (Reinertsen, 1999,......-oriented longitudinal case study of a Danish pharmaceutical company. The findings and key learnings from the study are presented as propositions of how innovation strategies can be applied to actively facilitate FEI and with measurable results.......Front end innovation (FEI) represents the first building blocks of product development, but is often regarded as a weak link in innovation literature. Various theorists emphasize that a firm’s innovation can benefit substantially by improving the front end of innovation process (Reinertsen, 1999...

  15. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that—against general belief—neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress. PMID:24569689

  16. Contribution to the dosimetry of tritium in the presence of inactive or active gases

    Soudain, G.

    1966-01-01

    Tritium is a dangerous gas for man and the maximum admissible doses in the atmosphere are sufficiently low for the dosage to be fairly difficult. We have developed an apparatus for measuring selectively the contamination of air by this gas when it is alone or when it is associated with other gaseous contaminants. The differential apparatus using two ionization chambers makes it possible to eliminate a parasitic γ radiation field. In a few particular cases, the presence of the radio-active gas has been studied. From the practical point of view, the use of these chambers made of stainless steel makes for easier use since the problems connected with wall adsorption have been satisfactorily resolved. The method can be applied without restriction and very easily to the dosage of traces tritium in air or in the form of tritiated water or tritiated steam in the atmosphere. (author) [fr

  17. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia.

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-06-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

  18. Sexuality and intimacy among people living with serious mental illnesses: Factors contributing to sexual activity.

    Bonfils, Kelsey A; Firmin, Ruth L; Salyers, Michelle P; Wright, Eric R

    2015-09-01

    Limited research has focused on sexuality for those diagnosed with a severe mental illness. We aimed to extend existing work by exploring relationships between mastery (perception of control of one's life and future), sexual self-esteem (perceptions of one's capacity to engage in healthy sexual behavior), sexual attitudes (permissive ideas about sexuality), and perceived importance of relationships/sexuality and number of sexual partners. A secondary analysis of survey data from adult participants living with a severe mental illness (N = 401) in the Indiana Mental Health Services and HIV-Risk Study (Perry & Wright, 2006) was conducted. Analysis of covariance (controlling for marital status) compared those with 0 partners, 1 partner, or multiple partners over the past 3 months on the dependent variables of mastery, sexual self-esteem, sexual attitudes, and perceived importance. Participants with more permissive attitudes, greater perceived importance, and higher mastery were more likely to be sexually active with multiple partners. Self-esteem did not differentiate groups. Given the key role of sexual satisfaction in quality of life and the high rates of sexual risk behavior in this population, it is important that clinicians systematically assess mastery, perceived importance, and attitudes about sexuality when working with consumers diagnosed with a severe mental illness. Individually tailoring existing interventions on the basis of consumers' levels of mastery, related to self-efficacy for implementing changes in life, could improve long-term outcomes for these programs. Future research should examine other constructs that may account for more variance in sexual activity, such as perceptions of risk, intentions for sexual safety, or romantic relationship functioning. (c) 2015 APA, all rights reserved).

  19. Evaluation of the inflammatory activity in chronic osteomyelitis. Contribution of the scintigraphy with polyclonal antibodies

    Sapienza, Marcelo Tatit

    1996-01-01

    Active chronic osteomyelitis or complicating osteomyelitis (superimposed on diseases that changes the normal bone structure fractures, post-surgery, prosthesis) can be difficult to diagnose by anatomic radiological imaging modalities, like plain radiograph and CT. These diseases frequently cause also increased bone remodeling, leading to nonspecific uptake of Tc-99m-bone scan agents and gallium-67. New radiopharmaceuticals with greater inflammation/infection avidity and specificity are being developed, including the nonspecific polyclonal immunoglobulin (IgG) labeled with technetium-99. Tc-99m-IgG may be available as a ready to use kit, with no reported side effects, low patient absorbed radiation dose and low cost. The mechanism of IgG uptake at the inflammation site has not been fully elucidated yet. Specific (receptor linking, physico-chemical immunoglobulin properties) and nonspecific mechanisms (enhanced vascular permeability and macromolecular exudate) has been suggested. IgG scintigraphy results are affected by the isotope, labeling procedure adopted and characteristics of the inflammatory focus. Nineteen patients with suspected osteomyelitis (active chronic osteomyelitis or violated bone osteomyelitis) were studied by Tc-99m-IgG scintigraphy (directly labeled polyclonal immunoglobulin, Sandoglobuilina - Sandoz). All patients also underwent standard three-phase bone scintigraphy using methylene diphosphonate (Tc-99m-MDP), gallium-67 scintigraphy and plain radiographs. Infection was found in 8 sites. Sensitivity and specificity for Tc-99m-MDP, gallium-67 and Tc 99m-IgG scintigraphy were, respectively, 88 and 36%, 75 and 73%,88 and 82%. All patients with false positive IgG scintigraphies had previous surgery. Other current scintigraphic procedures used in the diagnosis of osteomyelitis are also reviewed. (author)

  20. Phenolic Profiles and Contribution of Individual Compounds to Antioxidant Activity of Apple Powders.

    Raudone, Lina; Raudonis, Raimondas; Liaudanskas, Mindaugas; Viskelis, Jonas; Pukalskas, Audrius; Janulis, Valdimaras

    2016-05-01

    Apples (Malus domestica L.) are the most common source of phenolic compounds in northern European diet. Besides pectins, dietary fibers, vitamins, and oligosaccharides they contain phenolic compounds of different classes. Apple powders are convenient functional forms retaining significant amounts of phenolic antioxidants. In this study reducing and radical scavenging profiles of freeze-dried powders of "Aldas,ˮ "Auksis,ˮ "Connel Red,ˮ "Ligol,ˮ "Lodel,ˮ and "Rajkaˮ were determined and phenolic constituents were identified using ultra high-performance liquid chromatography coupled to quadrupole and time-of-flight mass spectrometers. A negative ionization mode was applied and seventeen compounds: phenolic acids (coumaroylquinic, chlorogenic), flavonoids (quercetin derivatives), and procyanidin derivatives (B1, B2, and C1) were identified in all tested apple samples. Total values of Trolox equivalents varied from 7.72 ± 0.32 up to 20.02 ± 0.52 and from 11.10 ± 0.57 up to 21.42 ± 0.75 μmol/g of dry weight of apple powder in FRAP (ferric reducing antioxidant power) and ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) postcolumn assays, respectively. The greatest Trolox equivalent values were determined for apples of "Aldasˮ cultivar. Chlorogenic acid and procyanidin C1 were the most significant contributors to total reducing and radical scavenging activity in all apple cultivars tested, therefore they could be considered as markers of antioxidant activity. © 2016 Institute of Food Technologists®

  1. Transient hardened power FETs

    Dawes, W.R. Jr.; Fischer, T.A.; Huang, C.C.C.; Meyer, W.J.; Smith, C.S.; Blanchard, R.A.; Fortier, T.J.

    1986-01-01

    N-channel power FETs offer significant advantages in power conditioning circuits. Similiarily to all MOS technologies, power FET devices are vulnerable to ionizing radiation, and are particularily susceptible to burn-out in high dose rate irradiations (>1E10 rads(Si)/sec.), which precludes their use in many military environments. This paper will summarize the physical mechanisms responsible for burn-out, and discuss various fabrication techniques designed to improve the transient hardness of power FETs. Power FET devices were fabricated with several of these techniques, and data will be presented which demonstrates that transient hardness levels in excess of 1E12 rads(Si)/sec. are easily achievable

  2. Transients in the Vivitron

    Cooke, C.M.; Frick, G.; Roumie, M.

    1993-01-01

    Electrical measurements are presented for the construction of a model for the study of transients in the Vivitron. Observation of the transmission of electrical pulses in the porticos clearly shows transmission-line behaviour. Measurements of the vector impedance of the outer porticos show the same transmission-line properties, but also gives a description of the modification from a pure transmission line due to the circular electrodes. The results of this investigation should allow the construction of a computer model which predicts the evolution of the transients in the case of a spark in the Vivitron. (orig.)

  3. Platelet activating factor-induced ceramide micro-domains drive endothelial NOS activation and contribute to barrier dysfunction.

    Sanda Predescu

    Full Text Available The spatial and functional relationship between platelet activating factor-receptor (PAF-R and nitric oxide synthase (eNOS in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles.

  4. Fatty acid, carotenoid and tocopherol compositions of 20 Canadian lentil cultivars and synergistic contribution to antioxidant activities.

    Zhang, Bing; Deng, Zeyuan; Tang, Yao; Chen, Peter; Liu, Ronghua; Ramdath, D Dan; Liu, Qiang; Hernandez, Marta; Tsao, Rong

    2014-10-15

    Understanding the profile of lipophilic phytochemicals in lentils is necessary to better understand the health benefits of lentils. The fatty acid, carotenoid and tocopherol compositions and antioxidant activities of the lipophilic extracts of 20 lentil cultivars (10 red and 10 green) were therefore examined. Lentils contained 1.52-2.95% lipids, of which 77.5-81.7% were unsaturated essential fatty acids. Total tocopherols ranged from 37 to 64μg/g DW, predominantly γ-tocopherol (96-98% of the tocopherol content), followed by δ- and α-tocopherol. trans-Lutein was the primary and major carotenoid (64-78%) followed by trans-zeaxanthin (5-13%). Carotenoids and tocopherols showed weak correlation with 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity (r=0.4893 and 0.3259, respectively), but good correlation when combined (r=0.6688), suggesting they may act synergistically. Carotenoids were found to contribute the most to the strong antioxidant activity measured by photochemiluminescence (PCL) assay. Results from this study contribute to the development of lentil cultivars and related functional foods with increased health benefits. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  5. Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

    Daniel eBoulton

    2016-05-01

    Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

  6. p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.

    Dana Austin

    Full Text Available Rift Valley fever virus (RVFV is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.

  7. External locus of control contributes to racial disparities in memory and reasoning training gains in ACTIVE

    Zahodne, Laura B.; Meyer, Oanh L.; Choi, Eunhee; Thomas, Michael L.; Willis, Sherry L.; Marsiske, Michael; Gross, Alden L.; Rebok, George W.; Parisi, Jeanine M.

    2015-01-01

    Racial disparities in cognitive outcomes may be partly explained by differences in locus of control. African Americans report more external locus of control than non-Hispanic Whites, and external locus of control is associated with poorer health and cognition. The aims of this study were to compare cognitive training gains between African American and non-Hispanic White participants in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study and determine whether racial differences in training gains are mediated by locus of control. The sample comprised 2,062 (26% African American) adults aged 65 and older who participated in memory, reasoning, or speed training. Latent growth curve models evaluated predictors of 10-year cognitive trajectories separately by training group. Multiple group modeling examined associations between training gains and locus of control across racial groups. Compared to non-Hispanic Whites, African Americans evidenced less improvement in memory and reasoning performance after training. These effects were partially mediated by locus of control, controlling for age, sex, education, health, depression, testing site, and initial cognitive ability. African Americans reported more external locus of control, which was associated with smaller training gains. External locus of control also had a stronger negative association with reasoning training gain for African Americans than for Whites. No racial difference in training gain was identified for speed training. Future intervention research with African Americans should test whether explicitly targeting external locus of control leads to greater cognitive improvement following cognitive training. PMID:26237116

  8. External locus of control contributes to racial disparities in memory and reasoning training gains in ACTIVE.

    Zahodne, Laura B; Meyer, Oanh L; Choi, Eunhee; Thomas, Michael L; Willis, Sherry L; Marsiske, Michael; Gross, Alden L; Rebok, George W; Parisi, Jeanine M

    2015-09-01

    Racial disparities in cognitive outcomes may be partly explained by differences in locus of control. African Americans report more external locus of control than non-Hispanic Whites, and external locus of control is associated with poorer health and cognition. The aims of this study were to compare cognitive training gains between African American and non-Hispanic White participants in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study and determine whether racial differences in training gains are mediated by locus of control. The sample comprised 2,062 (26% African American) adults aged 65 and older who participated in memory, reasoning, or speed training. Latent growth curve models evaluated predictors of 10-year cognitive trajectories separately by training group. Multiple group modeling examined associations between training gains and locus of control across racial groups. Compared to non-Hispanic Whites, African Americans evidenced less improvement in memory and reasoning performance after training. These effects were partially mediated by locus of control, controlling for age, sex, education, health, depression, testing site, and initial cognitive ability. African Americans reported more external locus of control, which was associated with smaller training gains. External locus of control also had a stronger negative association with reasoning training gain for African Americans than for Whites. No racial difference in training gain was identified for speed training. Future intervention research with African Americans should test whether explicitly targeting external locus of control leads to greater cognitive improvement following cognitive training. (c) 2015 APA, all rights reserved).

  9. Contribution of the active control to the measurement of fluid-elastic coupling strengths

    Legendre, S.

    1999-01-01

    A precise dimensioning of the tubes inside a steam generator requires a better knowledge of the fluid-elastic coupling phenomena. The direct method for the determination of fluid-elastic coupling coefficients allows to explore only a reduced range of flow velocities and is unsuitable for the low velocities and for velocities close to the critical instability velocity. The active damping control method has been validated both with air and water and offers the possibility to extend the range of flow velocities using an artificial supply of damping: 50% of increase in single-phase flow conditions with measurements performed beyond the critical instability velocity, a doubling of the explored range of velocities in two-phase flow conditions. For a 25% two-phase flow, a stabilization of the damping of the coupled fluid-structure system is observed beyond the critical instability velocity. Finally, the calculation of fluid-elastic dimensionless coefficients has permitted to show the influence of the reduced velocity on the fluid-elastic coupling in two-phase flow conditions. (J.S.)

  10. Inactivation of Candida glabrata by a humid DC argon discharge afterglow: dominant contributions of short-lived aqueous active species

    Xiong, Qing; Liu, Hongbin; Xu, Le; Wang, Xia; Zhu, Qunlin; Lu, Weiping; Chen, Qiang; Zeng, Xue; Yi, Ping

    2017-01-01

    Plasma medicine applications are currently attracting significant interest all over the world. Bactericidal treatments of Candida glabrata cultured in saline suspension are performed in this study by a room-temperature reactive afterglow of a DC-driven argon discharge. Water vapor was added to the discharge to study the inactivation contributions of reactive hydrolytic species including OH and H 2 O 2 transporting along the gas flow to the treated solutions. The inactivation results indicate that the dominant roles in the bactericidal treatments are played by the short-lived aqueous active species, but not the stable species like H 2 O 2aq (aq indicates an aqueous species). Further analysis shows that the ·OH aq radicals play an important role in the inactivation process. The ·OH aq radicals in the suspension are mostly produced from the direct dissolution of the OH species in the reactive afterglow. With the increase of added water vapor content, the ·OH aq production increases and enhances the inactivation efficiency of C. glabrata . Furthermore, it is found that the ambient air diffusion shows essential effects on the bactericidal activity of the remote humid argon discharge. Higher bactericidal effects can be obtained in open-space treatments compared to in a controlled Ar + H 2 O gas atmosphere. Key active air-byproduct species are believed to be generated in the suspension during the treatments and contributing to the inactivation process. Based on chemical analysis, the peroxynitrous acid ONOOH aq is considered as the key antimicrobial air-byproduct species. These results indicate the important dependence of plasma biomedical effects on the processing environment, which finally relates to the critical contributions of the key reactive species formed therein. (paper)

  11. Inactivation of Candida glabrata by a humid DC argon discharge afterglow: dominant contributions of short-lived aqueous active species

    Xiong, Qing; Liu, Hongbin; Lu, Weiping; Chen, Qiang; Xu, Le; Wang, Xia; Zhu, Qunlin; Zeng, Xue; Yi, Ping

    2017-05-01

    Plasma medicine applications are currently attracting significant interest all over the world. Bactericidal treatments of Candida glabrata cultured in saline suspension are performed in this study by a room-temperature reactive afterglow of a DC-driven argon discharge. Water vapor was added to the discharge to study the inactivation contributions of reactive hydrolytic species including OH and H2O2 transporting along the gas flow to the treated solutions. The inactivation results indicate that the dominant roles in the bactericidal treatments are played by the short-lived aqueous active species, but not the stable species like H2O2aq (aq indicates an aqueous species). Further analysis shows that the ·OHaq radicals play an important role in the inactivation process. The ·OHaq radicals in the suspension are mostly produced from the direct dissolution of the OH species in the reactive afterglow. With the increase of added water vapor content, the ·OHaq production increases and enhances the inactivation efficiency of C. glabrata. Furthermore, it is found that the ambient air diffusion shows essential effects on the bactericidal activity of the remote humid argon discharge. Higher bactericidal effects can be obtained in open-space treatments compared to in a controlled Ar + H2O gas atmosphere. Key active air-byproduct species are believed to be generated in the suspension during the treatments and contributing to the inactivation process. Based on chemical analysis, the peroxynitrous acid ONOOHaq is considered as the key antimicrobial air-byproduct species. These results indicate the important dependence of plasma biomedical effects on the processing environment, which finally relates to the critical contributions of the key reactive species formed therein.

  12. Reward and behavioral factors contributing to the tonic activity of monkey pedunculopontine tegmental nucleus neurons during saccade tasks

    Ken-ichi Okada

    2016-11-01

    Full Text Available The pedunculopontine tegmental nucleus (PPTg in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target, then made saccades to the peripheral saccade target, and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity

  13. Reward and Behavioral Factors Contributing to the Tonic Activity of Monkey Pedunculopontine Tegmental Nucleus Neurons during Saccade Tasks.

    Okada, Ken-Ichi; Kobayashi, Yasushi

    2016-01-01

    The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined the activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target (FT), then made saccades to the peripheral saccade target and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity continued

  14. Cell cycle progression, but not genotoxic activity, mainly contributes to citrinin-induced renal carcinogenesis

    Kuroda, Ken; Ishii, Yuji; Takasu, Shinji; Kijima, Aki; Matsushita, Kohei; Watanabe, Maiko; Takahashi, Haruo; Sugita-Konishi, Yoshiko; Sakai, Hiroki; Yanai, Tokuma; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    Citrinin (CTN) is a food-contaminating mycotoxin that efficiently induces renal tumors in rats. However, the modes of carcinogenic action are still unknown, preventing assessment of the risks of CTN in humans. In the present study, the proliferative effects of CTN and its causal factors were investigated in the kidneys of gpt delta rats. In addition, three in vivo genotoxicity assays (reporter gene mutation using gpt delta rats and comet and micronucleus assays using F344 rats) were performed to clarify whether CTN was genotoxic in vivo. CTN was administrated at 20 and 40 mg/kg/day, the higher dose being the maximal tolerated dose and a nearly carcinogenic dose. In the kidney cortex of gpt delta rats, significant increases in the labeling indices of proliferating cell nuclear antigen (PCNA)-positive cells were observed at all doses of CTN. Increases in the mRNA expression levels of Ccna2, Ccnb1, Ccne1, and its transcription factor E2f1 were also detected, suggesting induction of cell cycle progression at all tested doses of CTN. However, histopathological changes were found only in rats treated with the higher dose of CTN, which was consistent with increases in the mRNA expression levels of mitogenic factors associated with tissue damage/regeneration, such as Hgf and Lcn2, at the same dose. Thus, the proliferative effects of CTN may result not only from compensatory reactions, but also from direct mitogenic action. Western blot analysis showed that ERK phosphorylation was increased at all doses, implying that cell cycle progression may be mediated by activation of the ERK pathway. On the other hand, in vivo genotoxicity analyses were negative, implying that CTN did not have the potential for inducing DNA damage, gene mutations, or chromosomal aberrations. The overall data clearly demonstrated the molecular events underlying CTN-induced cell cycle progression, which could be helpful to understand CTN-induced renal carcinogenesis

  15. Adrenergic and cholinergic activity contributes to the cardiovascular effects of lionfish (Pterois volitans) venom.

    Church, Jarrod E; Hodgson, Wayne C

    2002-06-01

    The aim of the present study was to further investigate the cardiovascular activity of Pterois volitans crude venom. Venom (0.6-18 microg protein/ml) produced dose- and endothelium-dependent relaxation in porcine coronary arteries that was potentiated by atropine (10nM), but significantly attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NOLA; 0.1mM), by prior exposure of the tissue to stonefish antivenom (SFAV, 3 units/ml, 10 min), or by removal of extracellular Ca(2+). In rat paced left atria, venom (10 microg protein/ml) produced a decrease, followed by an increase, in contractile force. Atropine (0.5 microM) abolished the decrease in force and potentiated the increase. Propranolol (5 microM) did not affect the decrease in force but significantly attenuated the increase. In spontaneously beating right atria, venom (10 microg protein/ml) produced an increase in rate that was significantly attenuated by propranolol (5 microM). Prior incubation with SFAV (0.3 units/microg protein, 10 min) abolished both the inotropic and chronotropic responses to venom. In the anaesthetised rat, venom (100 micro protein/kg, i.v.) produced a pressor response, followed by a sustained depressor response. Atropine (1mg/kg, i.v.) potentiated the pressor response. The further addition of prazosin (50 microg/kg, i.v.) restored the original response to venom. Prior administration of SFAV (100 units/kg, i.v., 10 min) significantly attenuated the in vivo response to venom. It is concluded that P. volitans venom produces its cardiovascular effects primarily by acting on muscarinic cholinergic receptors and adrenoceptors. As SFAV neutralised many of the effects of P. volitans venom, we suggest that the two venoms share a similar component(s). Copright 2002 Elsevier Science Ltd.

  16. Daily physical activity and its contribution to the health-related quality of life of ambulatory individuals with chronic stroke

    Rand, Debbie; Eng, Janice J; Tang, Pei-Fang; Hung, Chihya; Jeng, Jiann-Shing

    2010-01-01

    Abstract Background Participation in daily physical activity (PA) post-stroke has not previously been investigated as a possible explanatory variable of health-related quality of life (HRQL). The aims were 1) to determine the contribution of daily PA to the HRQL of individuals with chronic stroke and 2) to assess the relationship between the functional ability of these individuals to the amount of daily PA. Methods The amount of daily PA of forty adults with chronic stroke (mean age 66.5 ± 9....

  17. Contribution of Psychosocial Factors to Physical Activity in Women of Color in the Saving Lives Staying Active (SALSA) Study.

    Mama, Scherezade K; McNeill, Lorna H; Soltero, Erica G; Orlando Edwards, Raul; Lee, Rebecca E

    2017-07-01

    Culturally appropriate, innovative strategies to increase physical activity (PA) in women of color are needed. This study examined whether participation in SALSA, an 8-week randomized, crossover pilot study to promote PA, led to improved psychosocial outcomes and whether these changes were associated with changes in PA over time. Women of color (N = 50) completed Internet-based questionnaires on PA, exercise self-efficacy, motivational readiness, stress, and social support at three time points. Women reported high socioeconomic status, decreases in exercise self-efficacy, and increases in motivational readiness for exercise and a number of stressful events (p motivational readiness for exercise varied by group (p = .043). Changes in psychosocial factors were associated with increases in PA. Latin dance improved motivational readiness for PA. Future studies are needed to determine whether Latin dance improves other psychological measures and quality of life in women of color in an effort to increase PA and reduce health disparities.

  18. CYP24A1 exacerbated activity during diabetes contributes to kidney tubular apoptosis via caspase-3 increased expression and activation.

    Alexandre Tourigny

    Full Text Available Decreases in circulating 25,hydroxyl-vitamin D3 (25 OH D3 and 1,25,dihydroxyl-vitamin D3 (1,25 (OH2 D3 have been extensively documented in patients with type 2 diabetes. Nevertheless, the molecular reasons behind this drop, and whether it is a cause or an effect of disease progression is still poorly understood. With the skin and the liver, the kidney is one of the most important sites for vitamin D metabolism. Previous studies have also shown that CYP24A1 (an enzyme implicated in vitamin D metabolism, might play an important role in furthering the progression of kidney lesions during diabetic nephropathy. In this study we show a link between CYP24A1 increase and senescence followed by apoptosis induction in the renal proximal tubules of diabetic kidneys. We show that CYP24A1 expression was increased during diabetic nephropathy progression. This increase derived from protein kinase C activation and increased H(2O(2 cellular production. CYP24A1 increase had a major impact on cellular phenotype, by pushing cells into senescence, and later into apoptosis. Our data suggest that control of CYP24A1 increase during diabetes has a beneficial effect on senescence induction and caspase-3 increased expression. We concluded that diabetes induces an increase in CYP24A1 expression, destabilizing vitamin D metabolism in the renal proximal tubules, leading to cellular instability and apoptosis, and thereby accelerating tubular injury progression during diabetic nephropathy.

  19. Generation of Platelet Microparticles after Cryopreservation of Apheresis Platelet Concentrates Contributes to Hemostatic Activity

    İbrahim Eker

    2017-03-01

    Full Text Available Objective: In the last decade, substantial evidence has accumulated about the use of cryopreserved platelet concentrates, especially in trauma. However, little reference has been made in these studies to the morphological and functional changes of platelets. Recently platelets have been shown to be activated by cryopreservation processes and to undergo procoagulant membrane changes resulting in the generation of platelet-derived microparticles (PMPs, platelet degranulation, and release of platelet-derived growth factors (PDGFs. We assessed the viabilities and the PMP and PDGF levels of cryopreserved platelets, and their relation with thrombin generation. Materials and Methods: Apheresis platelet concentrates (APCs from 20 donors were stored for 1 day and cryopreserved with 6% dimethyl sulfoxide. Cryopreserved APCs were kept at -80 °C for 1 day. Thawed APCs (100 mL were diluted with 20 mL of autologous plasma and specimens were analyzed for viabilities and PMPs by flow cytometry, for thrombin generation by calibrated automated thrombogram, and for PDGFs by enzyme-linked immunosorbent assay testing. Results: The mean PMP and PDGF levels in freeze-thawed APCs were significantly higher (2763±399.4/μL vs. 319.9±80.5/μL, p<0.001 and 550.9±73.6 pg/mL vs. 96.5±49 pg/mL, p<0.001, respectively, but the viability rates were significantly lower (68.2±13.7% vs. 94±7.5%, p<0.001 than those of fresh APCs. The mean endogenous thrombin potential (ETP of freeze-thawed APCs was significantly higher than that of the fresh APCs (3406.1±430.4 nM.min vs. 2757.6±485.7 nM.min, p<0.001. Moreover, there was a significant positive poor correlation between ETP levels and PMP levels (r=0.192, p=0.014. Conclusion: Our results showed that, after cryopreservation, while levels of PMPs were increasing, significantly higher and earlier thrombin formation was occurring in the samples analyzed despite the significant decrease in viability. Considering the damage caused

  20. Transient Heat Conduction

    Rode, Carsten

    1998-01-01

    Analytical theory of transient heat conduction.Fourier's law. General heat conducation equation. Thermal diffusivity. Biot and Fourier numbers. Lumped analysis and time constant. Semi-infinite body: fixed surface temperature, convective heat transfer at the surface, or constant surface heat flux...

  1. Transient cavitation in pipelines

    Kranenburg, C.

    1974-01-01

    The aim of the present study is to set up a one-dimensional mathematical model, which describes the transient flow in pipelines, taking into account the influence of cavitation and free gas. The flow will be conceived of as a three-phase flow of the liquid, its vapour and non-condensible gas. The

  2. Transient cognitive dynamics, metastability, and decision making.

    Mikhail I Rabinovich

    2008-05-01

    Full Text Available The idea that cognitive activity can be understood using nonlinear dynamics has been intensively discussed at length for the last 15 years. One of the popular points of view is that metastable states play a key role in the execution of cognitive functions. Experimental and modeling studies suggest that most of these functions are the result of transient activity of large-scale brain networks in the presence of noise. Such transients may consist of a sequential switching between different metastable cognitive states. The main problem faced when using dynamical theory to describe transient cognitive processes is the fundamental contradiction between reproducibility and flexibility of transient behavior. In this paper, we propose a theoretical description of transient cognitive dynamics based on the interaction of functionally dependent metastable cognitive states. The mathematical image of such transient activity is a stable heteroclinic channel, i.e., a set of trajectories in the vicinity of a heteroclinic skeleton that consists of saddles and unstable separatrices that connect their surroundings. We suggest a basic mathematical model, a strongly dissipative dynamical system, and formulate the conditions for the robustness and reproducibility of cognitive transients that satisfy the competing requirements for stability and flexibility. Based on this approach, we describe here an effective solution for the problem of sequential decision making, represented as a fixed time game: a player takes sequential actions in a changing noisy environment so as to maximize a cumulative reward. As we predict and verify in computer simulations, noise plays an important role in optimizing the gain.

  3. Investigation of electrically active defects in InGaAs quantum wire intermediate-band solar cells using deep-level transient spectroscopy (DLTS) technique

    Al Saqri, Noor alhuda; Felix, Jorlandio F.; Aziz, Mohsin; Kunets, Vasyl P.; Jameel, Dler Adil; Taylor, David; Henini, M.; Abd El-sadek, Mahmmoud S.; Furrow, Colin; Ware, Morgan E.; Benamara, Mourad; Mortazavi, Mansour; Salamo, Gregory

    2016-01-01

    InGaAs quantum wire (QWr) intermediate-band solar cell based nanostructures grown by molecular beam epitaxy are studied. The electrical and interface properties of these solar cell devices, as determined by current–voltage (I–V) and capacitance–voltage (C-V) techniques, were found to change with temperature over a wide range of 20–340 K. The electron and hole traps present in these devices have been investigated using deep-level transient spectroscopy (DLTS). The DLTS results showed that the ...

  4. Compressive Transient Imaging

    Sun, Qilin

    2017-04-01

    High resolution transient/3D imaging technology is of high interest in both scientific research and commercial application. Nowadays, all of the transient imaging methods suffer from low resolution or time consuming mechanical scanning. We proposed a new method based on TCSPC and Compressive Sensing to achieve a high resolution transient imaging with a several seconds capturing process. Picosecond laser sends a serious of equal interval pulse while synchronized SPAD camera\\'s detecting gate window has a precise phase delay at each cycle. After capturing enough points, we are able to make up a whole signal. By inserting a DMD device into the system, we are able to modulate all the frames of data using binary random patterns to reconstruct a super resolution transient/3D image later. Because the low fill factor of SPAD sensor will make a compressive sensing scenario ill-conditioned, We designed and fabricated a diffractive microlens array. We proposed a new CS reconstruction algorithm which is able to denoise at the same time for the measurements suffering from Poisson noise. Instead of a single SPAD senor, we chose a SPAD array because it can drastically reduce the requirement for the number of measurements and its reconstruction time. Further more, it not easy to reconstruct a high resolution image with only one single sensor while for an array, it just needs to reconstruct small patches and a few measurements. In this thesis, we evaluated the reconstruction methods using both clean measurements and the version corrupted by Poisson noise. The results show how the integration over the layers influence the image quality and our algorithm works well while the measurements suffer from non-trival Poisson noise. It\\'s a breakthrough in the areas of both transient imaging and compressive sensing.

  5. Educational inequalities in general and mental health: differential contribution of physical activity, smoking, alcohol consumption and diet.

    Kurtze, Nanna; Eikemo, Terje A; Kamphuis, Carlijn B M

    2013-04-01

    Behavioural, material and psychosocial risk factors may explain educational inequalities in general health. To what extent these risk factors have similar or different contributions to educational inequalities in mental health is unknown. Data were derived from the Norwegian Survey of Level of Living from 2005, comprising 5791 respondents aged ≥ 25 years. The study objectives were addressed by means of a series of logistic regression analyses in which we examined: (i) educational inequalities in self-reported general and mental health; (ii) the associations between behavioural, material and psychosocial risk factors and general and mental health, controlled for sex, age and education; and (iii) the contribution of risk factors to the observed health gradients. The lower educated were more likely to be in poor health [odds ratio (OR): 3.46 (95% confidence interval, CI: 2.84-4.21)] and to be in poor mental health [OR: 1.41 (95% CI: 1.12-1.78)] than the highest educated. The joint contribution of behavioural, material and psychosocial risk factors explained all the variations of mental health inequalities, whereas these were able to explain ~40% of the inequalities in general health. Both behavioural and material risk factors contributed substantially to the explanation of general and mental health inequalities, whereas the psychosocial risk factor (i.e. having close persons to communicate with) only seemed to make a larger difference for the explanation of mental health inequalities. Policies and interventions to reduce health inequalities should have a broad focus. Combined strategies should be applied to improve physical activity, decrease smoking and improve material and psychosocial conditions among lower educated groups, to achieve the true potential of reducing inequalities in both general and mental health.

  6. Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation.

    Jeffrey L Bose

    Full Text Available The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM and a glucosaminidase (GL. Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable to the parental strain, but showed clumping phenotypes and lysis profiles that were distinct from the parental strain and each other, suggesting distinct roles in cell wall metabolism. Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development. Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm. The results of this study provide insight into the relative contributions of AM and GL in S. aureus and demonstrate the contribution of Atl-mediated lysis in biofilm development.

  7. Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation.

    Bose, Jeffrey L; Lehman, McKenzie K; Fey, Paul D; Bayles, Kenneth W

    2012-01-01

    The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM) and a glucosaminidase (GL). Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable to the parental strain, but showed clumping phenotypes and lysis profiles that were distinct from the parental strain and each other, suggesting distinct roles in cell wall metabolism. Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development. Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm. The results of this study provide insight into the relative contributions of AM and GL in S. aureus and demonstrate the contribution of Atl-mediated lysis in biofilm development.

  8. Understanding the contribution of biofilm in an integrated fixed-film-activated sludge system (IFAS) designed for nitrogen removal.

    Moretti, P; Choubert, J M; Canler, J P; Petrimaux, O; Buffiere, P; Lessard, P

    2015-01-01

    The objective of this study is to improve knowledge on the integrated fixed-film-activated sludge (IFAS) system designed for nitrogen removal. Biofilm growth and its contribution to nitrification were monitored under various operating conditions in a semi-industrial pilot-scale plant. Nitrification rates were observed in biofilms developed on free-floating media and in activated sludge operated under a low sludge retention time (4 days) and at an ammonia loading rate of 45-70 gNH4-N/kgMLVSS/d. Operational conditions, i.e. oxygen concentration, redox potential, suspended solids concentration, ammonium and nitrates, were monitored continuously in the reactors. High removal efficiencies were observed for carbon and ammonium at high-loading rate. The contribution of biofilm to nitrification was determined as 40-70% of total NOx-N production under the operating conditions tested. Optimal conditions to optimize process compacity were determined. The tested configuration responds especially well to winter and summer nitrification conditions. These results help provide a deeper understanding of how autotrophic biomass evolves through environmental and operational conditions in IFAS systems.

  9. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes.

    Csermely, P; Szamel, M; Resch, K; Somogyi, J

    1988-05-15

    In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested (Parker, P.J., Coussens, L., Totty, N., Rhee, L., Young, S., Chen, E., Stabel, S., Waterfield, M.D., and Ullrich, A. (1986) Science 233, 853-859). In the present report, we demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes, and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn2+, while Fe2+ and Mn2+ are only partially counteractive. Our results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca2+, phorbol ester, or antigen.

  10. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  11. N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel

    Hynková, Anna; Maršáková, Lenka; Vašková, Jana; Vlachová, Viktorie

    2016-01-01

    Roč. 6, Jun 27 (2016), s. 28700 ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA15-15839S Institutional support: RVO:67985823 Keywords : ankyrin receptor subtype 1 * transient receptor potential * gating * ankyrin repeat * whole-cell electrophysiology * N-terminus * mutagenesis Subject RIV: FH - Neurology Impact factor: 4.259, year: 2016

  12. Daily physical activity and its contribution to the health-related quality of life of ambulatory individuals with chronic stroke.

    Rand, Debbie; Eng, Janice J; Tang, Pei-Fang; Hung, Chihya; Jeng, Jiann-Shing

    2010-08-03

    Participation in daily physical activity (PA) post-stroke has not previously been investigated as a possible explanatory variable of health-related quality of life (HRQL). The aims were 1) to determine the contribution of daily PA to the HRQL of individuals with chronic stroke and 2) to assess the relationship between the functional ability of these individuals to the amount of daily PA. The amount of daily PA of forty adults with chronic stroke (mean age 66.5 +/- 9.6 years) was monitored using two measures. Accelerometers (Actical) were worn on the hip for three consecutive days in conjunction with a self-report questionnaire [the PA Scale for Individuals with Physical Disabilities (PASIPD)]. The daily physical activity was measured as the mean total accelerometer activity counts/day and the PASIPD scores as the metabolic equivalent (MET) hr/day. HRQL was assessed by the Physical and Mental composite scores of the Medical Outcomes Study Short-Form 36 (SF-36) in addition to the functional ability of the participants. Correlation and regression analyses were performed. After controlling for the severity of the motor impairment, the amount of daily PA, as assessed by the PASIPD and accelerometers, was found to independently contribute to 10-12% of the variance of the Physical Composite Score of the SF-36. No significant relationship was found between PA and the Mental Composite Score of the SF-36.The functional ability of the participants was found to be correlated to the amount of daily PA (r = 0.33 - 0.67, p < 0.01). The results suggest that daily PA is associated with better HRQL (as assessed by the Physical composite score of the SF-36) for people living with stroke. Daily PA should be encouraged to potentially increase HRQL. Accelerometers in conjunction with a self-report questionnaire may provide important measures of PA which can be monitored and modified, and potentially influence HRQL.

  13. Daily physical activity and its contribution to the health-related quality of life of ambulatory individuals with chronic stroke

    Rand Debbie

    2010-08-01

    Full Text Available Abstract Background Participation in daily physical activity (PA post-stroke has not previously been investigated as a possible explanatory variable of health-related quality of life (HRQL. The aims were 1 to determine the contribution of daily PA to the HRQL of individuals with chronic stroke and 2 to assess the relationship between the functional ability of these individuals to the amount of daily PA. Methods The amount of daily PA of forty adults with chronic stroke (mean age 66.5 ± 9.6 years was monitored using two measures. Accelerometers (Actical were worn on the hip for three consecutive days in conjunction with a self-report questionnaire [the PA Scale for Individuals with Physical Disabilities (PASIPD]. The daily physical activity was measured as the mean total accelerometer activity counts/day and the PASIPD scores as the metabolic equivalent (MET hr/day. HRQL was assessed by the Physical and Mental composite scores of the Medical Outcomes Study Short-Form 36 (SF-36 in addition to the functional ability of the participants. Correlation and regression analyses were performed. Results After controlling for the severity of the motor impairment, the amount of daily PA, as assessed by the PASIPD and accelerometers, was found to independently contribute to 10-12% of the variance of the Physical Composite Score of the SF-36. No significant relationship was found between PA and the Mental Composite Score of the SF-36.The functional ability of the participants was found to be correlated to the amount of daily PA (r = 0.33 - 0.67, p Conclusion The results suggest that daily PA is associated with better HRQL (as assessed by the Physical composite score of the SF-36 for people living with stroke. Daily PA should be encouraged to potentially increase HRQL. Accelerometers in conjunction with a self-report questionnaire may provide important measures of PA which can be monitored and modified, and potentially influence HRQL.

  14. Time scales of transient enhanced diffusion: Free and clustered interstitials

    Cowern, N. E. B.; Huizing, H. G. A.; Stolk, P. A.; Visser, C. C. G.; de Kruif, R. C. M.; Kyllesbech Larsen, K.; Privitera, V.; Nanver, L. K.; Crans, W.

    1996-12-01

    Transient enhanced diffusion (TED) and electrical activation after nonamorphizing Si implantations into lightly B-doped Si multilayers shows two distinct timescales, each related to a different class of interstitial defect. At 700°C, ultrafast TED occurs within the first 15 s with a B diffusivity enhancement of > 2 × 10 5. Immobile clustered B is present at low concentration levels after the ultrafast transient and persists for an extended period (˜ 10 2-10 3 s). The later phase of TED exhibits a near-constant diffusivity enhancement of ≈ 1 × 10 4, consistent with interstitial injection controlled by dissolving {113} interstitial clusters. The relative contributions of the ultrafast and regular TED regimes to the final diffusive broadening of the B profile depends on the proportion of interstitials that escape capture by {113} clusters growing within the implant damage region upon annealing. Our results explain the ultrafast TED recently observed after medium-dose B implantation. In that case there are enough B atoms to trap a large proportion of interstitials in SiB clusters, and the remaining interstitials contribute to TED without passing through an intermediate {113} defect stage. The data on the ultrafast TED pulse allows us to extract lower limits for the diffusivities of the Si interstitial ( DI > 2 × 10 -10 cm 2s -1) and the B interstitial(cy) defect ( DBi > 2 × 10 -13 cm 2s -1) at 700°C.

  15. Transient osteoporosis of hip

    Mahesh M Choudhary

    2015-01-01

    Full Text Available We report a case of transient osteoporosis of the hip (TOH in a 50-year-old man including the clinical presentation, diagnostic studies, management, and clinical progress. TOH is a rare self-limiting condition that typically affects middle-aged men or, less frequently, women in the third trimester of pregnancy. Affected individuals present clinically with acute hip pain, limping gait, and limited ranges of hip motion. TOH may begin spontaneously or after a minor trauma. Radiographs are typically unremarkable but magnetic resonance (MR imaging studies yield findings consistent with bone marrow edema. TOH is referred to as regional migratory osteoporosis (RMO if it travels to other joints or the contralateral hip. TOH often resembles osteonecrosis but the two conditions must be differentiated due to different prognoses and management approaches. The term TOH is often used interchangeably and synonymously with transient bone marrow edema (TBME.

  16. Stability of Ignition Transients

    V.E. Zarko

    1991-01-01

    The problem of ignition stability arises in the case of the action of intense external heat stimuli when, resulting from the cut-off of solid substance heating, momentary ignition is followed by extinction. Physical pattern of solid propellant ignition is considered and ignition criteria available in the literature are discussed. It is shown that the above mentioned problem amounts to transient burning at a given arbitrary temperature distribution in the condensed phase. A brief survey...

  17. Transient FDTD simulation validation

    Jauregui Tellería, Ricardo; Riu Costa, Pere Joan; Silva Martínez, Fernando

    2010-01-01

    In computational electromagnetic simulations, most validation methods have been developed until now to be used in the frequency domain. However, the EMC analysis of the systems in the frequency domain many times is not enough to evaluate the immunity of current communication devices. Based on several studies, in this paper we propose an alternative method of validation of the transients in time domain allowing a rapid and objective quantification of the simulations results.

  18. MHD aspects of coronal transients

    Anzer, U.

    1979-10-01

    If one defines coronal transients as events which occur in the solar corona on rapid time scales (< approx. several hours) then one would have to include a large variety of solar phenomena: flares, sprays, erupting prominences, X-ray transients, white light transients, etc. Here we shall focus our attention on the latter two phenomena. (orig.) 891 WL/orig. 892 RDG

  19. Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells

    Lola Boutin

    2018-04-01

    Full Text Available Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg, such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277 molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset.

  20. C/EBPβ contributes to transcriptional activation of long non-coding RNA NEAT1 during APL cell differentiation.

    Wang, Yewei; Fu, Lei; Sun, Ailian; Tang, Doudou; Xu, Yunxiao; Li, Zheyuan; Chen, Mingjie; Zhang, Guangsen

    2018-05-05

    Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPβ bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPβ binding sites both around -54 bp and -1453 bp upstream of the transcription start site. Moreover, the expression of C/EBPβ was increased after ATRA treatment, and the binding of C/EBPβ in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBPβ significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBPβ directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBPβ impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBPβ contributes to ATRA-induced activation of NEAT1 during APL cell differentiation. Our results enrich our knowledge on the regulation of lncRNAs and the regulatory role of C/EBPβ in APL cell differentiation. Copyright © 2017. Published by Elsevier Inc.

  1. The contribution of pharmaceutically active compounds from healthcare facilities to a receiving sewage treatment plant in Canada.

    Kleywegt, Sonya; Pileggi, Vince; Lam, Yuet Ming; Elises, Alan; Puddicomb, Aaron; Purba, Gurminder; Di Caro, Joanne; Fletcher, Tim

    2016-04-01

    Concentrations and percent loadings of pharmaceutically active compounds (PhACs) and other emerging contaminants released from healthcare facilities (2 hospitals and a long-term care facility) to a sewage treatment plant (STP) in a large urban sewershed were evaluated. An additional hospital outside the sewershed was also monitored. Fourteen of the 24 steroids/hormones and 88 of the 117 PhACs and emerging contaminants were detected at least once. Commonly used substances, including cotinine, caffeine and its metabolite 1,7-dimethylxanthine, ibuprofen and naproxen (analgesics), venlafaxine (antidepressant), and N,N-diethyl-meta-toluamide (insect repellant), were detected in all samples at all sites. Concentrations detected in the large specialty hospital outside the sewershed were similar to those within the sewershed. Cytotoxic drugs (tamoxifen and cyclophosphamide) and x-ray contrast media (iopamidol and diatrizoic acid) were infrequently detected in hospital effluents. Analysis for antibiotics indicated that azithromycin, clarithromycin, ciprofloxacin, erythromycin, ofloxacin, and sulfamethoxazole were consistently detected in hospital wastewaters, as was triclosan (antibacterial agent). Fifteen compounds individually contributed greater than 1% to the total PhAC and emerging contaminant load to the STP from the 2 hospitals in the sewershed, and 9 compounds in the STP effluent exceeded ecotoxicological criteria. The present survey demonstrates that point source discharges from healthcare facilities in this sewershed make a small contribution to the overall PhAC and emerging contaminant loading compared with the total concentrations entering the receiving STP. © 2015 SETAC.

  2. Contributions to accelerating atmospheric CO2 growth from economic activity, carbon intensity, and efficiency of natural sinks

    Canadella, J.G.; Raupacha, M.R.; Le Quere, C.; Buitenhuis, E.T.; Gillett, N.P.; Field, C.B.; Ciais, P.; Conway, T.J.; Houghton, R.A.; Marland, G.

    2007-01-01

    The growth rate of atmospheric carbon dioxide (CO2), the largest human contributor to human-induced climate change, is increasing rapidly. Three processes contribute to this rapid increase. Two of these processes concern emissions. Recent growth of the world economy combined with an increase in its carbon intensity have led to rapid growth in fossil fuel CO2 emissions since 2000: comparing the 1990s with 2000-2006, the emissions growth rate increased from 1.3% to 3.3%/y. The third process is indicated by increasing evidence (P 0.89) for a long-term (50-year) increase in the airborne fraction (AF) of CO2 emissions, implying a decline in the efficiency of CO2 sinks on land and oceans in absorbing anthropogenic emissions. Since 2000, the contributions of these three factors to the increase in the atmospheric CO2 growth rate have been ∼65 ± 16% from increasing global economic activity, 17 ± 6% from the increasing carbon intensity of the global economy, and 18 ± 15% from the increase in AF. An increasing AF is consistent with results of climate-carbon cycle models, but the magnitude of the observed signal appears larger than that estimated by models. All of these changes characterize a carbon cycle that is generating stronger-than-expected and sooner-than-expected climate forcing. airborne fraction anthropogenic carbon emissions carbon-climate feedback terrestrial and ocean carbon emissions vulnerabilities of the carbon cycle

  3. Transcriptomic effects-based monitoring for endocrine active chemicals: Assessing relative contribution of treated wastewater to downstream pollution

    Martinovic-Weigelt, Dalma; Mehinto, Alvine C.; Ankley, Gerald T.; Denslow, Nancy D.; Barber, Larry B.; Lee, Kathy E.; King, Ryan J.; Schoenfuss, Heiko L.; Schroeder, Anthony L.; Villeneuve, Daniel L.

    2014-01-01

    The present study investigated whether a combination of targeted analytical chemistry information with unsupervised, data-rich biological methodology (i.e., transcriptomics) could be utilized to evaluate relative contributions of wastewater treatment plant (WWTP) effluents to biological effects. The effects of WWTP effluents on fish exposed to ambient, receiving waters were studied at three locations with distinct WWTP and watershed characteristics. At each location, 4 d exposures of male fathead minnows to the WWTP effluent and upstream and downstream ambient waters were conducted. Transcriptomic analyses were performed on livers using 15 000 feature microarrays, followed by a canonical pathway and gene set enrichment analyses. Enrichment of gene sets indicative of teleost brain–pituitary–gonadal–hepatic (BPGH) axis function indicated that WWTPs serve as an important source of endocrine active chemicals (EACs) that affect the BPGH axis (e.g., cholesterol and steroid metabolism were altered). The results indicated that transcriptomics may even pinpoint pertinent adverse outcomes (i.e., liver vacuolization) and groups of chemicals that preselected chemical analytes may miss. Transcriptomic Effects-Based monitoring was capable of distinguishing sites, and it reflected chemical pollution gradients, thus holding promise for assessment of relative contributions of point sources to pollution and the efficacy of pollution remediation.

  4. Contributions of microbial activity and ash deposition to post-fire nitrogen availability in a pine savanna

    Ficken, Cari D.; Wright, Justin P.

    2017-01-01

    Many ecosystems experience drastic changes to soil nutrient availability associated with fire, but the magnitude and duration of these changes are highly variable among vegetation and fire types. In pyrogenic pine savannas across the southeastern United States, pulses of soil inorganic nitrogen (N) occur in tandem with ecosystem-scale nutrient losses from prescribed burns. Despite the importance of this management tool for restoring and maintaining fire-dependent plant communities, the contributions of different mechanisms underlying fire-associated changes to soil N availability remain unclear. Pulses of N availability following fire have been hypothesized to occur through (1) changes to microbial cycling rates and (2) direct ash deposition. Here, we document fire-associated changes to N availability across the growing season in a longleaf pine savanna in North Carolina. To differentiate between possible mechanisms driving soil N pulses, we measured net microbial cycling rates and changes to soil δ15N before and after a burn. Our findings refute both proposed mechanisms: we found no evidence for changes in microbial activity, and limited evidence that ash deposition could account for the increase in ammonium availability to more than 5-25 times background levels. Consequently, we propose a third mechanism to explain post-fire patterns of soil N availability, namely that (3) changes to plant sink strength may contribute to ephemeral increases in soil N availability, and encourage future studies to explicitly test this mechanism.

  5. The contribution of indigenous knowledge to disaster risk reduction activities in Zimbabwe: A big call to practitioners

    Ernest Dube

    2018-03-01

    Full Text Available This article examined the contribution of indigenous knowledge to disaster risk reduction activities in Zimbabwe. The current discourse underrates the use of indigenous knowledge of communities by practitioners when dealing with disasters’, as the knowledge is often viewed as outdated and primitive. This study, which was conducted in 2016, sought to examine this problem through analysing the potential contribution of indigenous knowledge as a useful disaster risk reduction intervention. Tsholotsho district in Matabeleland, North province of Zimbabwe, which frequently experiences perennial devastating floods, was used as a case study. Interviews and researcher observations were used to gather data from 40 research participants. The findings were that communities understand weather patterns and could predict imminent flooding after studying trees and clouds, and the behaviours of certain animal species. Local communities also use available local resources to put structural measures in place as part of disaster risk reduction interventions. Despite this important potential, the study found that the indigenous knowledge of disaster risk reduction of the communities is often shunned by practitioners. The practitioners claim that indigenous knowledge lacks documentation, it is not found in all generational classes, it is contextualised to particular communities and the knowledge cannot be scientifically validated. The study concluded that both local communities and disaster risk reduction practitioners can benefit from the indigenous knowledge of communities. This research has the potential to benefit communities, policymakers and disaster risk reduction practitioners.

  6. Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

    Hatch, R J; Jennings, E A; Ivanusic, J J

    2013-08-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

  7. Four RNA families with functional transient structures.

    Zhu, Jing Yun A; Meyer, Irmtraud M

    2015-01-01

    Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5' flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5' UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All

  8. Transient trimethylaminuria related to menstruation

    Shimizu, Makiko; Cashman, John R; Yamazaki, Hiroshi

    2007-01-01

    Background Trimethylaminuria, or fish odor syndrome, includes a transient or mild malodor caused by an excessive amount of malodorous trimethylamine as a result of body secretions. Herein, we describe data to support the proposal that menses can be an additional factor causing transient trimethylaminuria in self-reported subjects suffering from malodor and even in healthy women harboring functionally active flavin-containing monooxygenase 3 (FMO3). Methods FMO3 metabolic capacity (conversion of trimethylamine to trimethylamine N-oxide) was defined as the urinary ratio of trimethylamine N-oxide to total trimethylamine. Results Self-reported Case (A) that was homozygous for inactive Arg500stop FMO3, showed decreased metabolic capacity of FMO3 (i.e., ~10% the unaffected metabolic capacity) during 120 days of observation. For Case (B) that was homozygous for common [Glu158Lys; Glu308Gly] FMO3 polymorphisms, metabolic capacity of FMO3 was almost ~90%, except for a few days surrounding menstruation showing 90%) metabolic capacity, however, on days around menstruation the FMO3 metabolic capacity was decreased to ~60–70%. Conclusion Together, these results indicate that abnormal FMO3 capacity is caused by menstruation particularly in the presence, in homozygous form, of mild genetic variants such as [Glu158Lys; Glu308Gly] that cause a reduced FMO3 function. PMID:17257434

  9. Targeting physical activity and nutrition interventions towards mothers with young children: a review on components that contribute to attendance and effectiveness

    Hartman, Marieke A.; Hosper, Karen; Stronks, Karien

    2011-01-01

    To gain insight into intervention components targeted specifically to mothers of young children that may contribute to attendance and effectiveness on physical activity and healthy eating. Systematic literature searches were performed using MEDLINE, Embase and cited references. Articles were

  10. The Relevance of the Dynamic Stall Effect for Transient

    Jauch, Clemens; Sørensen, Poul; Bak-Jensen, Birgitte

    2005-01-01

    This article describes a methodology to quantify the influence of dynamic stall on transient fault operations of active-stall turbines. The model of the dynamic stall effect is introduced briefly. The behaviour of the dynamic stall model during a transient fault operation is described mathematica...

  11. Transient Exciplex Formation Electron Transfer Mechanism

    Michael G. Kuzmin

    2011-01-01

    Full Text Available Transient exciplex formation mechanism of excited-state electron transfer reactions is analyzed in terms of experimental data on thermodynamics and kinetics of exciplex formation and decay. Experimental profiles of free energy, enthalpy, and entropy for transient exciplex formation and decay are considered for several electron transfer reactions in various solvents. Strong electronic coupling in contact pairs of reactants causes substantial decrease of activation energy relative to that for conventional long-range ET mechanism, especially for endergonic reactions, and provides the possibility for medium reorganization concatenated to gradual charge shift in contrast to conventional preliminary medium and reactants reorganization. Experimental criteria for transient exciplex formation (concatenated mechanism of excited-state electron transfer are considered. Available experimental data show that this mechanism dominates for endergonic ET reactions and provides a natural explanation for a lot of known paradoxes of ET reactions.

  12. Na+K+-ATPase activity and K+ channels differently contribute to vascular relaxation in male and female rats.

    Fernanda Moura Vargas Dias

    Full Text Available Gender associated differences in vascular reactivity regulation might contribute to the low incidence of cardiovascular disease in women. Cardiovascular protection is suggested to depend on female sex hormones' effects on endothelial function and vascular tone regulation. We tested the hypothesis that potassium (K+ channels and Na+K+-ATPase may be involved in the gender-based vascular reactivity differences. Aortic rings from female and male rats were used to examine the involvement of K+ channels and Na+K+-ATPase in vascular reactivity. Acetylcholine (ACh-induced relaxation was analyzed in the presence of L-NAME (100 µM and the following K+ channels blockers: tetraethylammonium (TEA, 2 mM, 4-aminopyridine (4-AP, 5 mM, iberiotoxin (IbTX, 30 nM, apamin (0.5 µM and charybdotoxin (ChTX, 0.1 µM. The ACh-induced relaxation sensitivity was greater in the female group. After incubation with 4-AP the ACh-dependent relaxation was reduced in both groups. However, the dAUC was greater in males, suggesting that the voltage-dependent K+ channel (Kv participates more in males. Inhibition of the three types of Ca2+-activated K+ channels induced a greater reduction in Rmax in females than in males. The functional activity of the Na+K+-ATPase was evaluated by KCl-induced relaxation after L-NAME and OUA incubation. OUA reduced K+-induced relaxation in female and male groups, however, it was greater in males, suggesting a greater Na+K+-ATPase functional activity. L-NAME reduced K+-induced relaxation only in the female group, suggesting that nitric oxide (NO participates more in their functional Na+K+-ATPase activity. These results suggest that the K+ channels involved in the gender-based vascular relaxation differences are the large conductance Ca2+-activated K+ channels (BKCa in females and Kv in males and in the K+-induced relaxation and the Na+K+-ATPase vascular functional activity is greater in males.

  13. CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

    Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

    2014-08-01

    Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Ultrafast triggered transient energy storage by atomic layer deposition into porous silicon for integrated transient electronics

    Douglas, Anna; Muralidharan, Nitin; Carter, Rachel; Share, Keith; Pint, Cary L.

    2016-03-01

    Here we demonstrate the first on-chip silicon-integrated rechargeable transient power source based on atomic layer deposition (ALD) coating of vanadium oxide (VOx) into porous silicon. A stable specific capacitance above 20 F g-1 is achieved until the device is triggered with alkaline solutions. Due to the rational design of the active VOx coating enabled by ALD, transience occurs through a rapid disabling step that occurs within seconds, followed by full dissolution of all active materials within 30 minutes of the initial trigger. This work demonstrates how engineered materials for energy storage can provide a basis for next-generation transient systems and highlights porous silicon as a versatile scaffold to integrate transient energy storage into transient electronics.Here we demonstrate the first on-chip silicon-integrated rechargeable transient power source based on atomic layer deposition (ALD) coating of vanadium oxide (VOx) into porous silicon. A stable specific capacitance above 20 F g-1 is achieved until the device is triggered with alkaline solutions. Due to the rational design of the active VOx coating enabled by ALD, transience occurs through a rapid disabling step that occurs within seconds, followed by full dissolution of all active materials within 30 minutes of the initial trigger. This work demonstrates how engineered materials for energy storage can provide a basis for next-generation transient systems and highlights porous silicon as a versatile scaffold to integrate transient energy storage into transient electronics. Electronic supplementary information (ESI) available: (i) Experimental details for ALD and material fabrication, ellipsometry film thickness, preparation of gel electrolyte and separator, details for electrochemical measurements, HRTEM image of VOx coated porous silicon, Raman spectroscopy for VOx as-deposited as well as annealed in air for 1 hour at 450 °C, SEM and transient behavior dissolution tests of uniformly coated VOx on

  15. Magnetic transients in flares

    Zirin, H.; Tanaka, K.

    1981-01-01

    We present data on magnetic transients (mgtr's) observed in flares on 1980 July 1 and 5 with Big Bear videomagnetograph (VMG). The 1980 July 1 event was a white light flare in which a strong bipolar mgtr was observed, and a definite change in the sunspots occurred at the time of the flare. In the 1980 July 5 flare, a mgtr was observed in only one polarity, and, although no sunspot changes occurred simultaneous with the flare, major spot changes occurred in a period of hours

  16. Familial Transient Global Amnesia

    R.Rhys Davies

    2012-12-01

    Full Text Available Following an episode of typical transient global amnesia (TGA, a female patient reported similar clinical attacks in 2 maternal aunts. Prior reports of familial TGA are few, and no previous account of affected relatives more distant than siblings or parents was discovered in a literature survey. The aetiology of familial TGA is unknown. A pathophysiological mechanism akin to that in migraine attacks, comorbidity reported in a number of the examples of familial TGA, is one possibility. The study of familial TGA cases might facilitate the understanding of TGA aetiology.

  17. Transient activation of Wnt/β-catenin signaling reporter in fibrotic scar formation after compression spinal cord injury in adult mice.

    Yamagami, Takashi; Pleasure, David E; Lam, Kit S; Zhou, Chengji J

    2018-02-19

    After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/β-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury. Using various representative cell lineage markers, we demonstrate that, these transiently TOPgal positive cells are a group of Fibronectin(+);GFAP(-) fibroblast-like cells in the core scar region. Some of them are proliferative. These results indicate that Wnt/β-catenin signaling may play a key role in fibrotic scar formation after traumatic spinal cord injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

    Jihong Xing

    2016-11-01

    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

  19. ROS-mediated inhibition of S-nitrosoglutathione reductase contributes to the activation of anti-oxidative mechanisms

    Izabella Kovacs

    2016-11-01

    Full Text Available Nitric oxide (NO has emerged as a signaling molecule in plants being involved in diverse physiological processes like germination, root growth, stomata closing and response to biotic and abiotic stress. S-nitrosoglutathione (GSNO as a biological NO donor has a very important function in NO signaling since it can transfer its NO moiety to other proteins (trans-nitrosylation. Such trans-nitrosylation reactions are equilibrium reactions and depend on GSNO level. The breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR. In this way, this enzyme controls S-nitrosothiol levels and regulates NO signaling. Here we report that Arabidopsis thaliana GSNOR activity is reversibly inhibited by H2O2 in-vitro and by paraquat-induced oxidative stress in-vivo. Light scattering analyses of reduced and oxidized recombinant GSNOR demonstrated that GSNOR proteins form dimers under both reducing and oxidizing conditions. Moreover, mass spectrometric analyses revealed that H2O2-treatment increased the amount of oxidative modifications on Zn2+-coordinating Cys47 and Cys177. Inhibition of GSNOR results in enhanced levels of S-nitrosothiols followed by accumulation of glutathione. Moreover, transcript levels of redox-regulated genes and activities of glutathione-dependent enzymes are increased in gsnor-ko plants, which may contribute to the enhanced resistance against oxidative stress. In sum, our results demonstrate that ROS-dependent inhibition of GSNOR is playing an important role in activation of anti-oxidative mechanisms to damping oxidative damage and imply a direct crosstalk between ROS- and NO-signaling.

  20. Concentration activities of natural radionuclides in three fish species in Brazilian coast and their contributions to the absorbed doses

    Pereira, Wagner de S.; Py Junior, Delcy de A.; Kelecom, Alphonse

    2009-01-01

    Activity concentrations of U-238, Ra-226, Pb-210, Th-232 e Ra-228 were analysed in three fish species at the Brasilian Coast. The fish 'Cubera snapper' (Lutjanus cyanopterus, Cuvier, 1828), in the region of Ceara and 'Whitemouth croaker' (Micropogonias furnieri, Desmarest, 1823) and 'Lebranche mullet' (Mugil liza, Valenciennes, 1836) in the region of Rio de Janeiro. These concentrations were transformed in absorbed dose rate using a dose conversion factor in unit of gray per year (μGy y -1 ), per becquerel per kilogram (Bq kg -1 ). Only the absorbed dose due to intake of radionuclides was examined, and the contributions due to radionuclides present in water and sediment were disregarded. The radionuclides were considered to be uniformly distributed in the fish body. The limit of the dose rate used, proposed by the Department of Energy of the USA, is equal to 3.65 10 03 mGy y -1 . The average dose rate due to the studied radionuclides is equal to 6.09 10 00 μGy y -1 , a value minor than 0.1% than the limits indicated by DOE, and quite similar to that found in the literature for 'benthic' fish. The most important radionuclides were the alpha emitters Ra-226 having 61 % of absorbed dose rate. U-238 and Th-232, each contributes with approximately 20 % of the absorbed dose rate. These three radionuclides are responsible for almost 100% of the dose rate received by the studied organisms. The beta emitters Ra-228 and Pb-210 account for approximately 1 % of the absorbed dose rate. (author)

  1. Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine

    Baker, Salah A.; Drumm, Bernard T.; Saur, Dieter; Hennig, Grant W.; Ward, Sean M.

    2016-01-01

    Key points Interstitial cells of Cajal at the level of the deep muscular plexus (ICC‐DMP) in the small intestine generate spontaneous Ca2+ transients that consist of localized Ca2+ events and limited propagating Ca2+ waves.Ca2+ transients in ICC‐DMP display variable characteristics: from discrete, highly localized Ca2+ transients to regionalized Ca2+ waves with variable rates of occurrence, amplitude, duration and spatial spread.Ca2+ transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells.Ca2+ transients in ICC‐DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s).Functional intracellular Ca2+ stores are essential for spontaneous Ca2+ transients, and the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump is necessary for maintenance of spontaneity.Ca2+ release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3Rs). Release from these channels is interdependent.ICC express transcripts of multiple RyRs and InsP3Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Abstract Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC‐DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC‐DMP are mediated by activation of Ca2+‐activated Cl− channels; thus, Ca2+ signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca2+ transients in ICC‐DMP within intact jejunal muscles expressing a genetically encoded Ca2+ indicator (GCaMP3) selectively in ICC. ICC‐DMP displayed spontaneous Ca2+ transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca2+ transients was highly variable, and it was

  2. Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine.

    Baker, Salah A; Drumm, Bernard T; Saur, Dieter; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

    2016-06-15

    Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it

  3. Measurand transient signal suppressor

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    A transient signal suppressor for use in a controls system which is adapted to respond to a change in a physical parameter whenever it crosses a predetermined threshold value in a selected direction of increasing or decreasing values with respect to the threshold value and is sustained for a selected discrete time interval is presented. The suppressor includes a sensor transducer for sensing the physical parameter and generating an electrical input signal whenever the sensed physical parameter crosses the threshold level in the selected direction. A manually operated switch is provided for adapting the suppressor to produce an output drive signal whenever the physical parameter crosses the threshold value in the selected direction of increasing or decreasing values. A time delay circuit is selectively adjustable for suppressing the transducer input signal for a preselected one of a plurality of available discrete suppression time and producing an output signal only if the input signal is sustained for a time greater than the selected suppression time. An electronic gate is coupled to receive the transducer input signal and the timer output signal and produce an output drive signal for energizing a control relay whenever the transducer input is a non-transient signal which is sustained beyond the selected time interval.

  4. Transient regional osteoporosis

    F. Trotta

    2011-09-01

    Full Text Available Transient osteoporosis of the hip and regional migratory osteoporosis are uncommon and probably underdiagnosed bone diseases characterized by pain and functional limitation mainly affecting weight-bearing joints of the lower limbs. These conditions are usually self-limiting and symptoms tend to abate within a few months without sequelae. Routine laboratory investigations are unremarkable. Middle aged men and women during the last months of pregnancy or in the immediate post-partum period are principally affected. Osteopenia with preservation of articular space and transitory edema of the bone marrow provided by magnetic resonance imaging are common to these two conditions, so they are also known by the term regional transitory osteoporosis. The appearance of bone marrow edema is not specific to regional transitory osteoporosis but can be observed in several diseases, i.e. trauma, reflex sympathetic dystrophy, avascular osteonecrosis, infections, tumors from which it must be differentiated. The etiology of this condition is unknown. Pathogenesis is still debated in particular the relationship with reflex sympathetic dystrophy, with which regional transitory osteoporosis is often identified. The purpose of the present review is to remark on the relationship between transient osteoporosis of the hip and regional migratory osteoporosis with particular attention to the bone marrow edema pattern and relative differential diagnosis.

  5. Contribution to the dosimetry of tritium in the presence of inactive or active gases; Contribution a la dosimetrie du tritium en presence de gaz inactifs ou actifs

    Soudain, G [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1966-07-01

    Tritium is a dangerous gas for man and the maximum admissible doses in the atmosphere are sufficiently low for the dosage to be fairly difficult. We have developed an apparatus for measuring selectively the contamination of air by this gas when it is alone or when it is associated with other gaseous contaminants. The differential apparatus using two ionization chambers makes it possible to eliminate a parasitic {gamma} radiation field. In a few particular cases, the presence of the radio-active gas has been studied. From the practical point of view, the use of these chambers made of stainless steel makes for easier use since the problems connected with wall adsorption have been satisfactorily resolved. The method can be applied without restriction and very easily to the dosage of traces tritium in air or in the form of tritiated water or tritiated steam in the atmosphere. (author) [French] Le tritium est un gaz dangereux pour l'homme et les concentrations maximales admissibles dans l'atmosphere sont suffisamment basses pour que le dosage soit delicat. Nous avons etudie et realise un appareil qui permet de mesurer selectivement la contamination de l'air par ce gaz lorsqu'il est seul ou lorsqu'il est associe a d'autres agents gazeux contaminants. Le montage differentiel a deux chambres d'ionisation permet d'eliminer un champ de rayonnement {beta} parasite. Dans certains cas particuliers, la presence du gaz radioactif a ete etudiee. Sur le plan pratique, l'utilisation des chambres en acier inoxydable facilite les applications car les problemes d'adsorption aux parois ont ete bien resolus. La methode peut s'appliquer sans restriction et tres pratiquement au dosage des traces de tritium dans l'air ou encore sous forme d'eau tritiee ou de vapeur d'eau tritiee dans l'atmosphere. (auteur)

  6. Mechanical modelling of transient- to- failure SFR fuel cladding

    Feria, F.; Herranz, L. E.

    2014-07-01

    The response of Sodium Fast Reactor (SFR) fuel rods to transient accident conditions is an important safety concern. During transients the cladding strain caused by the stress due to pellet cladding mechanical interaction (PCMI) can lead to failure. Due to the fact that SFR fuel rods are commonly clad with strengthened material made of stainless steel (SS), cladding is usually treated as an elastic-perfectly-plastic material. However, viscoplastic behaviour can contribute to mechanical strain at high temperature (> 1000 K). (Author)

  7. A gas turbine diagnostic approach with transient measurements.

    Li, Y. G.

    2003-01-01

    Most gas turbine performance analysis based diagnostic methods use the information from steady state measurements. Unfortunately, steady state measurement may not be obtained easily in some situations, and some types of gas turbine fault contribute little to performance deviation at steady state operating conditions but significantly during transient processes. Therefore, gas turbine diagnostics with transient measurement is superior to that with steady state measurement. In this paper, an ac...

  8. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    David Britton

    Full Text Available LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application.Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12, were labelled with tandem mass tags (TMT 8-plex, separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset.Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1, but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites, 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold in different cases highlighting their predictive power.Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  9. Contribution of social isolation, restraint, and hindlimb unloading to changes in hemodynamic parameters and motion activity in rats.

    Darya Tsvirkun

    Full Text Available The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint, and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.

  10. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Britton, David; Zen, Yoh; Quaglia, Alberto; Selzer, Stefan; Mitra, Vikram; Löβner, Christopher; Jung, Stephan; Böhm, Gitte; Schmid, Peter; Prefot, Petra; Hoehle, Claudia; Koncarevic, Sasa; Gee, Julia; Nicholson, Robert; Ward, Malcolm; Castellano, Leandro; Stebbing, Justin; Zucht, Hans Dieter; Sarker, Debashis; Heaton, Nigel; Pike, Ian

    2014-01-01

    LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset. Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  11. Computational investigation of the flow field contribution to improve electricity generation in granular activated carbon-assisted microbial fuel cells

    Zhao, Lei; Li, Jian; Battaglia, Francine; He, Zhen

    2016-11-01

    Microbial fuel cells (MFCs) offer an alternative approach to treat wastewater with less energy input and direct electricity generation. To optimize MFC anodic performance, adding granular activated carbon (GAC) has been proved to be an effective way, most likely due to the enlarged electrode surface for biomass attachment and improved mixing of the flow field. The impact of a flow field on the current enhancement within a porous anode medium (e.g., GAC) has not been well understood before, and thus is investigated in this study by using mathematical modeling of the multi-order Butler-Volmer equation with computational fluid dynamics (CFD) techniques. By comparing three different CFD cases (without GAC, with GAC as a nonreactive porous medium, and with GAC as a reactive porous medium), it is demonstrated that adding GAC contributes to a uniform flow field and a total current enhancement of 17%, a factor that cannot be neglected in MFC design. However, in an actual MFC operation, this percentage could be even higher because of the microbial competition and energy loss issues within a porous medium. The results of the present study are expected to help with formulating strategies to optimize MFC with a better flow pattern design.

  12. Flavan hetero-dimers in the Cymbopogon citratus infusion tannin fraction and their contribution to the antioxidant activity.

    Costa, Gustavo; González-Manzano, Susana; González-Paramás, Ana; Figueiredo, Isabel Vitória; Santos-Buelga, Celestino; Batista, Maria Teresa

    2015-03-01

    Cymbopogon citratus (lemongrass) leaf infusion, a commonly used ingredient in Asian, African and Latin American cuisines, is also used in traditional medicine for the treatment of several pathological conditions; however, little is known about their bioactive compounds. Recent studies revealed the crucial role of the phenolic compounds namely flavonoids and tannins on the infusion bioactivity. Flavonoids have already been characterized; however the tannin fraction of lemongrass infusion is still uncharted. The aim of the present work is to characterize this fraction, and to evaluate its contribution to the antioxidant potential of this plant. Chemical characterization was achieved by HPLC-DAD-ESI/tandem MS and the antioxidant activity was evaluated using DPPH, ABTS and FRAP assays. Hetero-dimeric flavan structures have been described for the first time in lemongrass consisting of apigeniflavan or luteoliflavan units linked to a flavanone, either naringenin or eriodictyol, which may occur as aglycone or glycosylated forms. The antioxidant capacity of the fraction containing these compounds was significantly higher than the infusion, indicating its potential as a source of natural antioxidants.

  13. Ergonomic analysis of work activity for the purpose of developing training programs: the contribution of ergonomics to vocational didactics.

    Ouellet, Sylvie

    2012-01-01

    Questions related to job skills and the teaching situations that best promote skill development are investigated by specialists in various fields, notably among them, ergonomists. This paper presents the findings of an ergonomic intervention study whose aim was to develop a meat-deboning training program by taking into account both the training content to be constructed and the working conditions that might facilitate or hinder skill development. One-on-one interviews and group discussions, on-the-job and videotape playback observations, as well as self-confrontation interviews were carried out. Activity analysis revealed major variability in work methods. The reasoning behind the experienced workers' actions and the experiential job knowledge they had developed were brought to light and served to develop the training content. The determining factors in the choice of work methods were identified, allowing adjustments to be made to the working conditions that might hinder skill development. The ergonomic process that implied taking working conditions into account in our study may make a significant contribution to vocational didactics, which is based on the cognitive analysis of work for the purpose of improving the effectiveness of job-skills training.

  14. Activation of calcitonin gene-related peptide receptor during ozone inhalation contributes to airway epithelial injury and repair.

    Oslund, Karen L; Hyde, Dallas M; Putney, Leialoha F; Alfaro, Mario F; Walby, William F; Tyler, Nancy K; Schelegle, Edward S

    2009-10-01

    The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP(8-37)) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5'-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP(8-37) had significantly reduced epithelial injury in terminal bronchioles and reduced epithelial proliferation in proximal airways and terminal bronchioles. Bronchoalveolar lavage and sections of terminal bronchioles showed no significant difference in the number of neutrophils emigrating into airways in CGRP(8-37)-treated rats. The airway epithelial cell line, HBE-1, showed no difference in the number of oxidant stress positive cells during exposure to hydrogen peroxide and a range of CGRP(8-37) doses, demonstrating no antioxidant effect of CGRP(8-37). We conclude that activation of CGRP receptors during ozone inhalation contributes to airway epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

  15. The joy of transient chaos

    Tél, Tamás [Institute for Theoretical Physics, Eötvös University, and MTA-ELTE Theoretical Physics Research Group, Pázmány P. s. 1/A, Budapest H-1117 (Hungary)

    2015-09-15

    We intend to show that transient chaos is a very appealing, but still not widely appreciated, subfield of nonlinear dynamics. Besides flashing its basic properties and giving a brief overview of the many applications, a few recent transient-chaos-related subjects are introduced in some detail. These include the dynamics of decision making, dispersion, and sedimentation of volcanic ash, doubly transient chaos of undriven autonomous mechanical systems, and a dynamical systems approach to energy absorption or explosion.

  16. Transient osteoporosis of the hip

    McWalter, Patricia; Hassan Ahmed

    2007-01-01

    Transient osteoporosis of the hip is an uncommon cause of hip pain, mostly affecting healthy middle-aged men and also women in the third trimester of pregnancy. We present a case of transient osteoporosis of the hip in a 33-year-old non-pregnant female patient. This case highlights the importance of considering a diagnosis of transient osteoporosis of the hip in patients who present with hip pain. (author)

  17. The ZTF Bright Transient Survey

    Fremling, C.; Sharma, Y.; Kulkarni, S. R.; Miller, A. A.; Taggart, K.; Perley, D. A.; Gooba, A.

    2018-06-01

    As a supplement to the Zwicky Transient Facility (ZTF; ATel #11266) public alerts (ATel #11685) we plan to report (following ATel #11615) bright probable supernovae identified in the raw alert stream from the ZTF Northern Sky Survey ("Celestial Cinematography"; see Bellm & Kulkarni, 2017, Nature Astronomy 1, 71) to the Transient Name Server (https://wis-tns.weizmann.ac.il) on a daily basis; the ZTF Bright Transient Survey (BTS; see Kulkarni et al., 2018; arXiv:1710.04223).

  18. The joy of transient chaos.

    Tél, Tamás

    2015-09-01

    We intend to show that transient chaos is a very appealing, but still not widely appreciated, subfield of nonlinear dynamics. Besides flashing its basic properties and giving a brief overview of the many applications, a few recent transient-chaos-related subjects are introduced in some detail. These include the dynamics of decision making, dispersion, and sedimentation of volcanic ash, doubly transient chaos of undriven autonomous mechanical systems, and a dynamical systems approach to energy absorption or explosion.

  19. Transient Infrared Emission Spectroscopy

    Jones, Roger W.; McClelland, John F.

    1989-12-01

    Transient Infrared Emission Spectroscopy (TIRES) is a new technique that reduces the occurrence of self-absorption in optically thick solid samples so that analytically useful emission spectra may be observed. Conventional emission spectroscopy, in which the sample is held at an elevated, uniform temperature, is practical only for optically thin samples. In thick samples the emission from deep layers of the material is partially absorbed by overlying layers.1 This self-absorption results in emission spectra from most optically thick samples that closely resemble black-body spectra. The characteristic discrete emission bands are severely truncated and altered in shape. TIRES bypasses this difficulty by using a laser to heat only an optically thin surface layer. The increased temperature of the layer is transient since the layer will rapidly cool and thicken by thermal diffusion; hence the emission collection must be correlated with the laser heating. TIRES may be done with both pulsed and cw lasers.2,3 When a pulsed laser is used, the spectrometer sampling must be synchronized with the laser pulsing so that only emission during and immediately after each laser pulse is observed.3 If a cw laser is used, the sample must move rapidly through the beam. The hot, transient layer is then in the beam track on the sample at and immediately behind the beam position, so the spectrometer field of view must be limited to this region near the beam position.2 How much self-absorption the observed emission suffers depends on how thick the heated layer has grown by thermal diffusion when the spectrometer samples the emission. Use of a pulsed laser synchronized with the spectrometer sampling readily permits reduction of the time available for heat diffusion to about 100 acs .3 When a cw laser is used, the heat-diffusion time is controlled by how small the spectrometer field of view is and by how rapidly the sample moves past within this field. Both a very small field of view and a

  20. Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease.

    Nagata, Keiko; Kumata, Keisuke; Nakayama, Yuji; Satoh, Yukio; Sugihara, Hirotsugu; Hara, Sayuri; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Hayashi, Kazuhiko

    2017-04-01

    Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity. We showed that the EBV reactivation induces the production of every isotype of Ig and suggested that the Ig production was catalyzed by AID through LMP1 and NF-κB. The results that the amount of IgM was significantly larger compared with IgG suggested the polyclonal B cell activation due to LMP1. We proposed the pathway of EBV reactivation induced Ig production; B cells newly infected with EBV are activated by polyclonal B cell activation and produce Igs through plasma cell differentiation induced by EBV reactivation. LMP1-induced AID enabled B cells to undergo class-switch recombination to produce every isotype of Ig. According to this mechanism, EBV rescues autoreactive B cells to produce autoantibodies, which contribute to the development and exacerbation of autoimmune diseases.

  1. Direct Quantification of Ice Nucleation Active Bacteria in Aerosols and Precipitation: Their Potential Contribution as Ice Nuclei

    Hill, T. C.; DeMott, P. J.; Garcia, E.; Moffett, B. F.; Prenni, A. J.; Kreidenweis, S. M.; Franc, G. D.

    2013-12-01

    Ice nucleation active (INA) bacteria are a potentially prodigious source of highly active (≥-12°C) atmospheric ice nuclei, especially from agricultural land. However, we know little about the conditions that promote their release (eg, daily or seasonal cycles, precipitation, harvesting or post-harvest decay of litter) or their typical contribution to the pool of boundary layer ice nucleating particles (INP). To initiate these investigations we developed a quantitative Polymerase Chain Reaction (qPCR) test of the ina gene, the gene that codes for the ice nucleating protein, to directly count INA bacteria in environmental samples. The qPCR test amplifies most forms of the gene and is highly sensitive, able to detect perhaps a single gene copy (ie, a single bacterium) in DNA extracted from precipitation. Direct measurement of the INA bacteria is essential because environmental populations will be a mixture of living, viable-but-not culturable, moribund and dead cells, all of which may retain ice nucleating proteins. Using the qPCR test on leaf washings of plants from three farms in Wyoming, Colorado and Nebraska we found INA bacteria to be abundant on crops, especially on cereals. Mid-summer populations on wheat and barley were ~108/g fresh weigh of foliage. Broadleaf crops, such as corn, alfalfa, sugar beet and potato supported 105-107/g. Unexpectedly, however, in the absence of a significant physical disturbance, such as harvesting, we were unable to detect the ina gene in aerosols sampled above the crops. Likewise, in fresh snow samples taken over two winters, ina genes from a range of INA bacteria were detected in about half the samples but at abundances that equated to INA bacterial numbers that accounted for only a minor proportion of INP active at -10°C. By contrast, in a hail sample from a summer thunderstorm we found 0.3 INA bacteria per INP at -10°C and ~0.5 per hail stone. Although the role of the INA bacteria as warm-temperature INP in these samples

  2. Anticipated transients without scram

    Lellouche, G.S.

    1980-01-01

    This article discusses in various degrees of depth the publications WASH-1270, WASH-1400, and NUREG-0460, and has as its purpose a description of the technical work done by Electric Power Research Institute (EPRI) personnel and its contractors on the subject of anticipated transients without scram (ATWS). It demonstrates the close relation between the probability of scram failure derived from historical scram data and that derived from the use of component data in a model of a system (the so-called synthesis method), such as was done in WASH-1400. The inherent conservatism of these models is demonstrated by showing that they predict significantly more events than have in fact occurred and that such models still predict scram failure probabilities low enough to make ATWS an insignificant contributor to accident risk

  3. Transient fuel melting

    Roche, L.; Schmitz, F.

    1982-10-01

    The observation of micrographic documents from fuel after a CABRI test leads to postulate a specific mode of transient fuel melting during a rapid nuclear power excursion. When reaching the melt threshold, the bands which are characteristic for the solid state are broken statistically over a macroscopic region. The time of maintaining the fuel at the critical enthalpy level between solid and liquid is too short to lead to a phase separation. A significant life-time (approximately 1 second) of this intermediate ''unsolide'' state would have consequences on the variation of physical properties linked to the phase transition solid/liquid: viscosity, specific volume and (for the irradiated fuel) fission gas release [fr

  4. Transient osteoporosis of pregnancy.

    Maliha, George; Morgan, Jordan; Vrahas, Mark

    2012-08-01

    Transient osteoporosis of pregnancy (TOP) is a rare yet perhaps under-reported condition that has affected otherwise healthy pregnancies throughout the world. The condition presents suddenly in the third trimester of a usually uneventful pregnancy and progressively immobilizes the mother. Radiographic studies detect drastic loss of bone mass, elevated rates of turnover in the bone, and oedema in the affected portion. Weakness of the bone can lead to fractures during delivery and other complications for the mother. Then, within weeks of labour, symptoms and radiological findings resolve. Aetiology is currently unknown, although neural, vascular, haematological, endocrine, nutrient-deficiency, and other etiologies have been proposed. Several treatments have also been explored, including simple bed rest, steroids, bisphosphonates, calcitonin, induced termination of pregnancy, and surgical intervention. The orthopedist plays an essential role in monitoring the condition (and potential complications) as well as ensuring satisfactory outcomes for both the mother and newborn. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. X-Ray Observations of the Black Hole Transient 4U 1630-47 during 2 Years of X-Ray Activity

    Tomsick, John A.; Corbel, Stéphane; Goldwurm, Andrea; Kaaret, Philip

    2005-09-01

    The black hole candidate (BHC) X-ray transient 4U 1630-47 continuously produced strong X-ray emission for more than 2 years during its 2002-2004 outburst, which is one of the brightest and longest outbursts ever seen from this source. We use more than 300 observations made with the Rossi X-Ray Timing Explorer (RXTE) to study the source throughout the outburst, along with hard X-ray images from the International Gamma-Ray Astrophysics Laboratory (INTEGRAL), which are critical for interpreting the RXTE data in this crowded field. The source exhibits extreme behaviors, which can be interpreted as an indication that the system luminosity approaches the Eddington limit. For 15 observations, fitting the spectral continuum with a disk-blackbody plus power-law model results in measured inner disk temperatures between 2.7 and 3.8 keV, and such temperatures are only rivaled by the brightest BHC systems, such as GRS 1915+105 and XTE J1550-564. If the high temperatures are caused by the dominance of electron scattering opacity in the inner regions of the accretion