Sample records for flash tgf observations

  1. A terrestrial gamma ray flash observed from an aircraft (United States)

    Smith, D. M.; Dwyer, J. R.; Hazelton, B. J.; Grefenstette, B. W.; Martinez-McKinney, G. F. M.; Zhang, Z. Y.; Lowell, A. W.; Kelley, N. A.; Splitt, M. E.; Lazarus, S. M.; Ulrich, W.; Schaal, M.; Saleh, Z. H.; Cramer, E.; Rassoul, H.; Cummer, S. A.; Lu, G.; Shao, X.-M.; Ho, C.; Hamlin, T.; Blakeslee, R. J.; Heckman, S.


    On 21 August 2009, the Airborne Detector for Energetic Lightning Emissions (ADELE), an array of six gamma-ray detectors, detected a brief burst of gamma rays while flying aboard a Gulfstream V jet near two active thunderstorm cells. The duration and spectral characteristics of the event are consistent with the terrestrial gamma ray flashes (TGFs) seen by instruments in low Earth orbit. A long-duration, complex +IC flash was taking place in the nearer cell at the same time, at a distance of ˜10 km from the plane. The sferics that are probably associated with this flash extended over 54 ms and included several ULF pulses corresponding to charge moment changes of up to 30 C km, this value being in the lower half of the range of sferics associated with TGFs seen from space. Monte Carlo simulations of gamma ray propagation in the Earth's atmosphere show that a TGF of normal intensity would, at this distance, have produced a gamma ray signal in ADELE of approximately the size and spectrum that was actually observed. We conclude that this was the first detection of a TGF from an aircraft. We show that because of the distance, ADELE's directional and spectral capabilities could not strongly constrain the source altitude of the TGF but that such constraints would be possible for TGFs detected at closer range.

  2. Observations of Positron and Neutron Emissions from Terrestrial Gamma-ray Flashes


    Bowers, Gregory Steele


    Terrestrial gamma-ray Flashes (TGFs) are intense, sub-millisecond bursts of gamma-rays routinely observed by satellites with energy spectra and timing characteristics consistent with bremsstrahlung from electron avalanches produced in thunderstorm electric fields. Since their discovery in 1994, the overwhelming majority of TGF observations have been from satellites. The goal of this work was to see how well TGFs could be observed from inst...

  3. Observations of Positron and Neutron Emissions from Terrestrial Gamma-ray Flashes (United States)

    Bowers, Gregory S.

    Terrestrial gamma-ray Flashes (TGFs) are intense, sub-millisecond bursts of gamma-rays routinely observed by satellites with energy spectra and timing characteristics consistent with bremsstrahlung from electron avalanches produced in thunderstorm electric fields. Since their discovery in 1994, the overwhelming majority of TGF observations have been from satellites. The goal of this work was to see how well TGFs could be observed from instruments on the ground or in the air, and whether there exist TGFs too dim to be seen from space, or TGF related phenomena impossible to observe from satellite. Using portable instruments consisting of scintillation radiation detectors, we report on the ground observation of a 100 ms duration neutron flash from a lightning strike to a wind turbine in Japan, and evidence of positrons associated with lightning from observations aboard an airplane inside the eyewall of Hurricane Patricia. We discuss methods for deriving TGF brightness by comparing our observations to Monte Carlo simulations. Both the neutron flash seen in Japan, and the evidence for a downward beam of positrons produced in the eyewall of Hurricane Patricia are consistent with production from TGFs with brightnesses typical of TGFs so far observed from space.

  4. The Fermi Gamma-ray Burst Monitor (GBM) Terrestrial Gamma-ray Flash (TGF) Catalog (United States)

    Briggs, M. S.; Roberts, O.; Fitzpatrick, G.; Stanbro, M.; Cramer, E.; Mailyan, B. G.; McBreen, S.; Connaughton, V.; Grove, J. E.; Chekhtman, A.; Holzworth, R.


    The revised Second Fermi GBM TGF catalog includes data on 4144 TGFs detected by the Fermi Gamma-ray Burst Monitor through 2016 July 31. The catalog includes 686 bright TGFs there were detected in orbit and 4135 TGFs that were discovered by ground analysis of GBM data (the two samples overlap). Thirty of the events may have been detected as electrons and positrons rather than gamma-rays: Terrestrial Electron Beams (TEBs). We also provide results from correlating the GBM TGFs with VLF radio detections of the World Wide Lightning Location Network (WWLLN). TGFs with WWLLN associations have their localization uncertainties improved from 800 to 10 km, making it possible to identify specific thunderstorms responsible for the TGFs and opening up new types of scientific investigations. There are 1544 TGFs with WWLLN associations; maps are provided for these and the other TGFs of the catalog. The data tables of the catalog are available for use by the scientific community at the Fermi Science Support Center, at

  5. TGF Observations From A Small, Low-Cost, Low-Mass, High-Speed Versatile Detector System. (United States)

    Sample, J. G.; Smith, D. M.; Johnson, J.; Varney, C.; Gannon, J.; Hunter, S.; Murtaugh, J.; Durtka, J.; Cunningham, B.


    The Light And Fast TGF Recorder or LAFTR is a NASA-University Student Instrumentation Project (USIP) that is designed to observe Terrestrial Gamma Flashes from a sounding balloon. LAFTR is a joint project between UC-Santa Cruz and Montana State University. LAFTR utilizes a small plastic scintillator with a fast shaped SiPM readout and a comparator based digitization similar to ADELE but with 6 energy channels. The discriminator bank is read out with a low-cost FPGA and data stored on board for recovery. LAFTR is able to time-tag gamma ray photons to 10ns at an approximate maximum rate of >5 MCounts/s. The entire systems fits well within the 6lb limit for unrestricted balloon launching and launch plans will be in advance of approaching thunderstorms. The small size of the scintillator and fast counting are ideal for unsaturated observations from near the TGF generation region which LAFTR will access via a valved latex balloon developed by the BOREALIS program at MSU. The valved balloon allows for a flight of several hours at >15km altitude. A test flight is planned for Fall 2017 followed by science observation flights throughout the next year. Although designed for single balloon flights, the low-cost nature of LAFTR potentially allows for many units to be produced allowing multi-point measurements and distributed arrays of ground and tower-based TGF observations as it affords significant student experiences throughout.

  6. Direct Observations of Different Sunspot Waves Influenced by Umbral Flashes (United States)

    Sharma, Aishawnnya; Gupta, G. R.; Tripathi, Durgesh; Kashyap, V.; Pathak, Amit


    We report the simultaneous presence of chromospheric umbral flashes and associated umbral waves, and propagating coronal disturbances, in a sunspot and related active region. We have analyzed time-distance maps obtained using the observations from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. These maps show the simultaneous occurrence of different sunspot oscillations and waves such as umbral flashes, umbral waves, and coronal waves. Analysis of the original light curves, i.e., without implementing any Fourier filtering on them, shows that the amplitudes of different sunspot waves observed at different atmospheric layers change in synchronization with the light curves obtained from the umbral flash region, thus demonstrating that these oscillations are modulated by umbral flashes. This study provides the first observational evidence of the influence of sunspot oscillations within the umbra on other sunspot waves extending up to the corona. The properties of these waves and oscillations can be utilized to study the inherent magnetic coupling among different layers of the solar atmosphere above sunspots.

  7. Plastic Scintillator Based Detector for Observations of Terrestrial Gamma-ray Flashes. (United States)

    Barghi, M. R., Sr.; Delaney, N.; Forouzani, A.; Wells, E.; Parab, A.; Smith, D.; Martinez, F.; Bowers, G. S.; Sample, J.


    We present an overview of the concept and design of the Light and Fast TGF Recorder (LAFTR), a balloon borne gamma-ray detector designed to observe Terrestrial Gamma-Ray Flashes (TGFs). Terrestrial Gamma-Ray Flashes (TGFs) are extremely bright, sub-millisecond bursts of gamma-rays observed to originate inside thunderclouds coincident with lightning. LAFTR is joint institutional project built by undergraduates at the University of California Santa Cruz and Montana State University. It consists of a detector system fed into analog front-end electronics and digital processing. The presentation focuses specifically on the UCSC components, which consists of the detector system and analog front-end electronics. Because of the extremely high count rates observed during TGFs, speed is essential for both the detector and electronics of the instrument. The detector employs a fast plastic scintillator (BC-408) read out by a SensL Silicon Photomultiplier (SiPM). BC-408 is chosen for its speed ( 4 ns decay time) and low cost and availability. Furthermore, GEANT3 simulations confirm the scintillator is sensitive to 500 counts at 7 km horizontal distance from the TGF source (for a 13 km source altitude and 26 km balloon altitude) and to 5 counts out to 20 km. The signal from the SiPM has a long exponential decay tail and is sent to a custom shaping circuit board that amplifies and shapes the signal into a semi-Gaussian pulse with a 40 ns FWHM. The signal is then input to a 6-channel discriminator board that clamps the signal and outputs a Low Voltage Differential Signal (LVDS) for processing by the digital electronics.

  8. Observations of High Peak Current 'lull' Lightning Flashes (United States)

    Zhang, Y.; Krehbiel, P. R.; Edens, H. E.; Stock, M.


    A new and peculiar type of negative cloud-to-ground (-CG) lightning flash has been found from LMA observations of storms. Called a 'lull' flash, the discharge begins with a short duration (~5-10 ms), stepped leader and high peak current return stroke, followed by a brief period of inactivity. After a few tens to a few hundreds of milliseconds, the discharge reignites in the same location as a normal -CG. VHF observations show a complete lack of activity during the lull. The flashes were first identified from LMA observations during a 2008 lightning study in West Virginia (Krehbiel, 2012 ILDC), but are seen in other normally electrified storms. They are characterized by large negative peak currents (-50 to -150 kA) in NLDN data. Here we report detailed LMA, interferometer, and fast antenna observations of lull flashes obtained at Langmuir Laboratory in 2013. A series of six lull CGs occurred over an 11 min time interval in a small storm on August 5. Analysis of the observations shows the breakdown immediately produced a stepped leader that went straight to ground. The durations from initial breakdown to the return stroke (RS) was 2-15 ms, corresponding to leader speeds of 4×105 to 3×106 m/s. Peak currents of the RSs were -32 to -188 kA. The lulls began 10-29 ms after the RSs, and lasted 40-100 ms before the discharge reignited. By contrast, the durations, speeds and peak current values of the reignited first strokes were those of normal -CGs, namely, 9 to 105 ms, -11.5kA to 55.8kA, and 0.6×105 to 6.7×105 m/s. Further analysis indicates the lull flashes occurred when the storm had substantial negative charge but little lower positive charge, allowing the initial stroke to go straight to ground at a high speed. The energetic stroke somehow quenches the discharge a short time afterward while much negative charge remains, which leads to reignition and the second part of the discharge. Exactly how and why this happens remains an open question.

  9. The TETRA-II Experiment to Observe Terrestrial Gamma Flashes at Ground Level - Preliminary Results (United States)

    Cherry, M. L.; Adams, C.; Al-Nussirat, S.; Bai, S.; Banadaki, Y.; Bitzer, P. M.; Hoffmann, J.; Khosravi, E.; Legault, M.; Orang, M.; Pleshinger, D. J.; Rodriguez, R.; Smith, D.; Trepanier, J. C.; Sunda-Meya, A.; Zimmer, N.


    An upgraded version of the TGF and Energetic Thunderstorm Rooftop Array (TETRA-II) consists of an array of BGO scintillators to detect bursts of gamma rays from thunderstorms at ground level in four separate locations: the campus of Louisiana State University in Baton Rouge, Louisiana; the campus of the University of Puerto Rico at Utuado, Puerto Rico; the Centro Nacional de Metrologia de Panama (CENAMEP) in Panama City, Panama; and the Severe Weather Institute and Radar & Lightning Laboratories in Huntsville, Alabama. The original TETRA-I array of NaI scintillators at Louisiana State University detected 37 millisecond-scale bursts of gamma rays at energies 50 keV-2 MeV associated with nearby (< 8 km) thunderstorms. TETRA-II began operation in May 2016 and now has approximately an order of magnitude greater sensitivity than TETRA-I. The ability to observe ground-level Terrestrial Gamma Flashes from close to the source allows a unique analysis of the storm cells producing these events. A brief description of the TETRA-I observations, a description of TETRA-II, and preliminary results of the first events observed by TETRA-II will be presented including frequency and time history of events, spectral information, and correlation with local radar and radio data.

  10. Simultaneous Observation of Lightning and Terrestrial Gamma-ray Flashes (United States)

    Alnussirat, S.; Christian, H. J., Jr.; Fishman, G. J.; Burchfield, J. C.


    The relative timing between TGFs and lightning optical emissions is a critical parameter that may elucidate the production mechanism(s) of TGFs. In this work, we study the correlation between optical emissions detected by the Geostationary Lightning Mapper (GLM) and TGFs triggered by the Fermi-GBM. The GLM is the only instrument that detects total lightning activities (IC and CG) continuously (day and night) over a large area of the Earth, with very high efficiency and location accuracy. The unique optical emission data from the GLM will enable us to study, for the first time, the lightning activity before and after the TGF production. From this investigation, we hope to clarify the production mechanism of TGFs and the characteristics of thundercloud cells that produce them. A description of the GLM concept and operation will be presented and as well as the preliminary results of the TGF-optical emission correlation.

  11. Analytic Perturbation Method for Estimating Ground Flash Fraction from Satellite Lightning Observations (United States)

    Koshak, William; Solakiewicz, Richard


    An analytic perturbation method is introduced for estimating the lightning ground flash fraction in a set of N lightning flashes observed by a satellite lightning mapper. The value of N is large, typically in the thousands, and the observations consist of the maximum optical group area produced by each flash. The method is tested using simulated observations that are based on Optical Transient Detector (OTD) and Lightning Imaging Sensor (LIS) data. National Lightning Detection NetworkTM (NLDN) data is used to determine the flash-type (ground or cloud) of the satellite-observed flashes, and provides the ground flash fraction truth for the simulation runs. It is found that the mean ground flash fraction retrieval errors are below 0.04 across the full range 0-1 under certain simulation conditions. In general, it is demonstrated that the retrieval errors depend on many factors (i.e., the number, N, of satellite observations, the magnitude of random and systematic measurement errors, and the number of samples used to form certain climate distributions employed in the model).

  12. An Evaluation of Lightning Flash Rate Parameterizations Based on Observations of Colorado Storms during DC3 (United States)

    Basarab, B.; Fuchs, B.; Rutledge, S. A.


    Predicting lightning activity in thunderstorms is important in order to accurately quantify the production of nitrogen oxides (NOx = NO + NO2) by lightning (LNOx). Lightning is an important global source of NOx, and since NOx is a chemical precursor to ozone, the climatological impacts of LNOx could be significant. Many cloud-resolving models rely on parameterizations to predict lightning and LNOx since the processes leading to charge separation and lightning discharge are not yet fully understood. This study evaluates predicted flash rates based on existing lightning parameterizations against flash rates observed for Colorado storms during the Deep Convective Clouds and Chemistry Experiment (DC3). Evaluating lightning parameterizations against storm observations is a useful way to possibly improve the prediction of flash rates and LNOx in models. Additionally, since convective storms that form in the eastern plains of Colorado can be different thermodynamically and electrically from storms in other regions, it is useful to test existing parameterizations against observations from these storms. We present an analysis of the dynamics, microphysics, and lightning characteristics of two case studies, severe storms that developed on 6 and 7 June 2012. This analysis includes dual-Doppler derived horizontal and vertical velocities, a hydrometeor identification based on polarimetric radar variables using the CSU-CHILL radar, and insight into the charge structure using observations from the northern Colorado Lightning Mapping Array (LMA). Flash rates were inferred from the LMA data using a flash counting algorithm. We have calculated various microphysical and dynamical parameters for these storms that have been used in empirical flash rate parameterizations. In particular, maximum vertical velocity has been used to predict flash rates in some cloud-resolving chemistry simulations. We diagnose flash rates for the 6 and 7 June storms using this parameterization and compare

  13. A Catalog of Terrestrial Gamma-Ray Flashes Observed with the Fermi- Gamma-Ray Burst Monitor: The First Sixteen Months of Operation (United States)

    Fishman, Gerald J.; Briggs, M. S.; Connaughton, V.; Bhat, P. N.


    The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) has been detecting on the average about one terrestrial gamma-ray flash every four weeks. This catalog presents the basic characteristics of observed TGFs from the beginning of the Fermi-GBM operation in 2008 July until 2009 October. The thick bismuth germanate (BGO) scintillation detectors of the GBM system have observed photon energies from TGFs at energies above 30 MeV. It is found that the TGF pulses are typically shorter than previously reported, and in several cases less than 0.2ms. Extremely high counting rates are encountered 200kcps or higher per detector during portions of some TGFs. These high rates require considerable corrections (with inherent assumptions) to the observed data in order to derive the true counting rates.

  14. Ground- and Space-based Observations of Horizontally-extensive Lightning Flashes (United States)

    Zhang, D.; Cummins, K. L.; Bitzer, P. M.


    Horizontally-extensive lightning flashes occur frequently in association with mature and late phases of multicellular thunderstorms, both in trailing stratiform regions and horizontally-extensive anvils. The spatial relationship between these flashes and the parent cloud volume is of importance for space launch operational decision making, and is of broader scientific interest. Before this question can be accurately addressed, there is a need to understand the degree to which current lightning observation systems can depict the spatial extent of these long flashes. In this ongoing work, we will intercompare the depiction of horizontally-extensive flashes using several ground-based lightning locating systems (LLSs) located at Kennedy Space Center (KSC) with space-based observations observed by the recently-launched Geostationary Lightning Mapper (GLM) onboard the GOES-16 satellite. Ground-based datasets include the KSC Lightning Mapping Array (KSCLMA), the operational narrowband digital interferometer network MERLIN, and the combined cloud-to-ground and cloud lightning dataset produced by the U.S. National Lightning Detection Network (NLDN). The KSCLMA system is a network of VHF time-of-arrival sensors that preferentially report breakdown processes, and MERLIN is a network of VHF interferometers that point to the discharges in the horizontal plane. Observations to date indicate that MERLIN and the KSCSLMA provide similar overall descriptions of the spatial and temporal extent of these flashes, while the NLDN does not provide adequate spatial mapping of these flashes. The KSC LMA system has much better location accuracy, and provides excellent 3-dimensional representation within 100 km of KSC. It also has sufficient sensitivity to provide 2-dimensional flash mapping within 250 km of KSC. The MERLIN system provides a more-detailed representation of fast leader propagation (in 2 dimensions) with 100 km of KSC. Earlier work during the CHUVA campaign in Brazil with

  15. New Observational Evidence of Flash Mixing on the White Dwarf Cooling Curve (United States)

    Brown, T. M.; Lanz, T.; Sweigart, A. V.; Cracraft, Misty; Hubeny, Ivan; Landsman, W. B.


    Blue hook stars are a class of subluminous extreme horizontal branch stars that were discovered in UV images of the massive globular clusters w Cen and NGC 2808. These stars occupy a region of the HR diagram that is unexplained by canonical stellar evolution theory. Using new theoretical evolutionary and atmospheric models, we have shown that the blue hook stars are very likely the progeny of stars that undergo extensive internal mixing during a late helium-core flash on the white dwarf cooling curve. This "flash mixing" produces hotter-than-normal EHB stars with atmospheres significantly enhanced in helium and carbon. The larger bolometric correction, combined with the decrease in hydrogen opacity, makes these stars appear sub luminous in the optical and UV. Flash mixing is more likely to occur in stars born with a high helium abundance, due to their lower mass at the main sequence turnoff. For this reason, the phenomenon is more common in those massive globular clusters that show evidence for secondary populations enhanced in helium. However, a high helium abundance does not, by itself, explain the presence of blue hook stars in massive globular clusters. Here, we present new observational evidence for flash mixing, using recent HST observations. These include UV color-magnitude diagrams of six massive globular clusters and far-UV spectroscopy of hot subdwarfs in one of these clusters (NGC 2808).

  16. Ground-Based Observations of Terrestrial Gamma Ray Flashes Associated with Downward-Directed Lightning Leaders (United States)

    Belz, J.; Abbasi, R.; Krehbiel, P. R.; LeVon, R.; Remington, J.; Rison, W.; Thomas, R. J.


    Terrestrial Gamma Flashes (TGFs) have been observed in satellite-borne gamma ray detectors for several decades, starting with the BATSE instrument on the Compton Gamma-Ray observatory in 1994. TGFs consist of bursts of upwards of 1018 primary gamma rays, with a duration of up to a few milliseconds, originating in the Earth's atmosphere. More recent observations have shown that satellite-observed TGFs are generated in upward-propagating negative leaders of intracloud lightning, suggesting that they may be sensitive to the processes responsible for the initial lightning breakdown. Here, we present the first evidence that TGFs are also produced at the beginning of negative cloud-to-ground flashes, and that they may provide a new window through which ground-based observatories may contribute to understanding the breakdown process. The Telescope Array Surface Detector (TASD) is a 700 square kilometer cosmic ray observatory, an array of 507 3m2 scintillators on a 1.2 km grid. The array is triggered and read out when at least three adjacent detectors observe activity within an 8 μs window. Following the observation of bursts of anomalous TASD triggers, lasting a few hundred microseconds and correlated with local lightning activity, a Lightning Mapping Array (LMA) and slow electric field antenna were installed at the TASD site in order to study the effect. From data obtained between 2014 and 2016, correlated observations were obtained for ten -CG flashes. In 9 out of 10 cases, bursts of up to five anomalous triggers were detected during the first ms of the flash, as negative breakdown was descending into lower positive storm charge. The triggers occurred when the LMA-detected VHF radiation sources were at altitudes between 1.5 to 4.5 km AGL. The tenth flash was initiated by an unusually energetic leader that reached the ground in 2.5 ms and produced increasingly powerful triggers down to about 500 m AGL. While the TASD is not optimized for individual gamma ray detection

  17. Ultra-Fast Flash Observatory for observation of early photons from gamma ray bursts

    DEFF Research Database (Denmark)

    Park, I. H.; Ahmad, S.; Barrillon, P.


    We describe the space project of Ultra-Fast Flash Observatory (UFFO) which will observe early optical photons from gamma-ray bursts (GRBs) with a sub-second optical response, for the first time. The UFFO will probe the early optical rise of GRBs, opening a completely new frontier in GRB and trans...... of GRB mechanisms, and potentially open up the z<10 universe to study via GRB as point source emission probes.© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only....

  18. Multipoint Space Measurements of TGF's with the TRYAD Mission (United States)

    Fuchs, J.; Briggs, M. S.; Jenke, P.


    The Terrestrial RaY Analysis and Detection (TRYAD) is a twin 6U cubesat mission designed to detect Terrestrial Gamma-ray Flashes (TGF's) from low earth orbit. Current observations of TGF's are predominantly done from single point measurements; the objective of this mission is to capture two simultaneous observations to identify a characteristic beam profile. Working models for production of TGF's suggest two main scenarios exist: one being creation in the lightening step leader which results in a wider beam profile, the other is a larger field effect in the storm resulting in a narrow beam. The TRYAD detector consists of four plastic scintillation bars that will detect flux correlated with GPS position and time. Both satellites will fly at a controlled separation of several hundred kilometers gathering data over the tropics. The data gathered from the spacecraft are matched to lightening data from the World Wide Lightning Location Network (WWLLN) to get ground and time localization along with the two point flux measurement. TRYAD will fly in 2019. We will present simulations describing TRYADs ability to discriminate between current TGF models, the TRYAD science instrument, along with its capabilities and impact for TGF science.

  19. An observational and numerical case study of a flash sea storm over the Gulf of Genoa

    Directory of Open Access Journals (Sweden)

    A. Orlandi


    Full Text Available During the night between the 8 and 9 December 2006 the seawall of the Savona harbour (Liguria Region in north west of Italy was overtopped by waves. In this work the "Savona flash sea storm" has been studied by analyzing the data recorded by meteo-marine observing stations and the data produced by high resolution meteo-marine numerical models. The data show that, due to the presence of a fast moving low pressure system, the event was characterized by a rapid transition and interaction between two different regimes of winds and related sea states.

    The results of the study suggest that the most damaging dynamics of the event could be correlated to a bi-modal structure of the wave spectrum. Based on this the authors suggest that a deeper study of the spectral structure of sea storms could lead to define new operational forecasting tools for the preventive evaluation of sea storms damaging potential.

  20. Comparison of the light flash phenomena observed in space and in laboratory experiments

    International Nuclear Information System (INIS)

    McNulty, P.J.; Pease, V.P.; Bond, V.P.


    Astronauts on Apollo and Skylab missions have reported observing a variety of visual phenomena when their eyes were closed and adapted to darkness. These observations were studied under controlled conditions during a number of sessions on board Apollo and Skylab spacecraft and the data available to date on these so-called light flashes is in the form of descriptions of the phenomena and frequency of occurrence. Similar visual phenomena have been demonstrated in a number of laboratories by exposing the eyes of human subjects to beams of neutrons, alphas, pions, and protons. More than one physical mechanism is involved in the laboratory and space phenomena. No direct comparison of the laboratory and space observations has been made by observers who have experienced both. However, the range of visual phenomena observed in the laboratory is consistent with the Apollo and Skylab observations. Measured detection efficiencies can be used to estimate the frequencies with which various phenomena would be observed if the subject was exposed to cosmic rays in space

  1. Modeling of Pulses in Terrestrial Gamma-ray Flashes (United States)

    Xu, Wei; Celestin, Sebastien; Pasko, Victor


    Terrestrial Gamma-ray Flashes (TGFs) are high-energy photon bursts originating from the Earth's atmosphere that are associated with lightning activities. After their discovery in 1994 by the Burst and Transient Source Experiment (BATSE) detector aboard the Compton Gamma-Ray Observatory [Fishman et al., Science, 264, 1313, 1994], this phenomenon has been further observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) [Smith et al., Science, 307, 1085, 2005], the Fermi Gamma-ray Space Telescope [Briggs et al., JGR, 115, A07323, 2010] and the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite [Marisaldi et al., JGR, 115, A00E13, 2010]. Photon spectra corresponding to the mechanism of relativistic runaway electron avalanches (RREAs) usually provide a very good agreement with satellite observations [Dwyer and Smith, GRL, 32, L22804, 2005]. On the other hand, Celestin and Pasko [JGR, 116, A03315, 2011] have shown theoretically that the large flux of thermal runaway electrons generated by streamers during the negative corona flash stage of stepping lightning leaders in intracloud lightning flashes could be responsible for TGFs. Recently, based on analysis of the temporal profiles of 278 TGF events observed by the Fermi Gamma-Ray Burst Monitor, Foley et al. [JGR, 119, 5931, 2014] have suggested that 67% of TGF pulses detected are asymmetric and these asymmetric pulses are consistent with the production mechanism of TGFs by relativistic feedback discharges. In the present work, we employ a Monte Carlo model to study the temporal distribution of photons at low-orbit satellite altitudes during TGF events. Using the pulse fitting method described in [Foley et al., 2014], we further investigate the characteristics of TGF pulses. We mainly focus on the effects of Compton scattering on the symmetry properties and the rise and fall times of TGF pulses.

  2. Comparison of the Effects of SMART Board Technology and Flash Card Instruction on Sight Word Recognition and Observational Learning (United States)

    Mechling, Linda C.; Gast, David L.; Thompson, Kimberly L.


    This study compared the effectiveness of SMART Board, interactive whiteboard technology and traditional flash cards in teaching reading in a small-group instructional arrangement. Three students with moderate intellectual disabilities were taught to read grocery store aisle marker words under each condition. Observational learning (students…

  3. Flash radiography

    International Nuclear Information System (INIS)

    Jamet, F.


    Flash radiography is a method for recording radiographic pictures of a non-transparent high-speed phenomenon. Such events occur in a variety of fields: Ballistics, dynamic high pressure physics, detonics, industry, and medical diagnostics. The phenomena observed by flash-radiography generally move at velocities between 100 m/s and 10000 m/s. The motion blur recorded on the picture is negligible only if the duration of the X-ray pulse (or the exposure time) falls in the range 10 -8 - 10 -7 s. With a medical or industrial radiographic device, the correct blackening of a film is obtained with a current of some milliamperes and a mean exposure time of 0.1 s. From this it is deduced that the value of the current passing through a flash X-ray tube must be approximately equal to 10 4 A. These values cannot be attained in conventional X-ray tubes with a heated cathode. The production of large currents is mainly achieved by vacuum discharges and field emission. Two applications of the technique are presented: flash radiographs of shock waves, and flash X-ray diffraction. (Auth.)

  4. [Study on TGF beta 1, TGF beta 2, TGF beta 3 expression in the chick basilar papilla following gentamicin toxicity]. (United States)

    Li, H; Wang, J


    The beta-type transforming growth factors (TGF beta s) are secreted proteins, which play an important role in regulation of cell proliferation and differentiation in the embryonic inner ear. In order to probe into the effect of TGF beta s on the hair cell regeneration, expression of TGF beta 1, TGF beta 2 and TGF beta 3 proteins were examined by using immunohistochemistry in the chicken basilar papilla during hair cell regeneration following gentamicin ototoxicity. Ten-day-old chickens received daily subcutaneous injection of gentamicin sulfate 50 mg/kg of ten consecutive days. The animals were allowed to survive 1,3,7,14,21 and 28 days before sacrifice and preparation for examination of the expression of TGF beta 1, TGF beta 2 and TGF beta 3 proteins. Immunostaining results demonstrated that TGF beta 2 and TGF beta 3 proteins were observed in the damaged region of basilar papilla. TGF beta 2 and TGF beta 3 proteins positive cells were limited to the lumenal nuclear layer within the damaged region. TGF beta 1 protein positive cell was not found in our study. These results indicated that TGF beta 2 and TGF beta 3 proteins might play a role in regulating proliferation of the supporting cells immigrated into the lumenal nuclear layer during hair cell regeneration.

  5. An observational and numerical study of a flash-flood event over south-eastern Italy

    Directory of Open Access Journals (Sweden)

    M. M. Miglietta


    Full Text Available A flash-flood episode affecting a small area in Apulia (south-eastern Italy on 22 October 2005 is documented. A rainfall amount of 160 mm was recorded in a 6 h interval in the central part of the region, producing severe damage and causing six fatalities. Synoptic maps, observations from surface stations and remote-sensing data are used here to describe the evolution of the rainfall system. The vertical profiles show features similar to those observed in other orographic heavy-rain events, such as a low-level jet, a conditionally unstable environment, and a nearly saturated warm low-level air mass. The low hills in the centre of the region play an important role in the release of the instability and the localisation of the rainfall, providing the uplift necessary to the air parcels to reach the level of free convection. Numerical simulations are performed in order to understand the mechanisms responsible for the heavy rain event. The Weather Research and Forecasting model (WRF is setup in a 2-way nesting configuration including two domains. The model is able to realistically simulate the evolution of the precipitation system and to capture fairly well the localisation, the amount and the timing of the rainfall. The simulations suggest the important synergy of low and upper-tropospheric features which act as the triggering mechanism for the development of convection. A sensitivity experiment confirms the importance of the orography for the development of convective cells.

  6. Global Properties of X-Ray Flashes and X-Ray-Rich GRBs Observed by Swift (United States)

    Sakamoto, T.; Yamazaki, R.; Cummings, J.; Krimm, H.; Parsons, A.; Hullinger, D.; Barbier, L.; Fenimore, E.; Markwardt, C.; Tueller, J.; hide


    We describe and discuss the spectral and temporal characteristics of the prompt emission and X-ray afterglow emission of X-ray flashes (XRFs) detected and observed by Swift between December 2005 and September 2006. We compare these characteristics to a sample of X-ray rich gamma-ray bursts (XRRs) and conventional classical gamma-ray bursts (C-GRBs)observed during the same period. We confirm the correlation between Epeak and fluence noted by others and find further evidence that XRFs and C-GRBs form a continuum. We also confirmed that our known redshift samples are consistent with the correlation between the peak energy (Epeak) and the isotropic radiated energy (Eiso), so called the Epeak-Eiso relation. The spectral properties of X-ray afterglows are similar to those of gamma-ray burst afterglows, but the temporal properties of the two classes are quite different. We found that the light curves of C-GRBs afterglow show a break to steeper indices (shallow-to-steep break) at much earlier times than do XRF afterglows. Moreover, the overall luminosity of X-ray afterglows of XRFs are systematically smaller by a factor of two or more compared with that of C-GRBs. These distinct differences in the X-ray afterglow between XRFs and C-GRBs are key to understanding not only a mysterious shallow-to-steep phase in the X-ray afterglow but also the unique nature of XRFs.

  7. Confining the angular distribution of terrestrial gamma ray flash emission (United States)

    Gjesteland, T.; Østgaard, N.; Collier, A. B.; Carlson, B. E.; Cohen, M. B.; Lehtinen, N. G.


    Terrestrial gamma ray flashes (TGFs) are bremsstrahlung emissions from relativistic electrons accelerated in electric fields associated with thunder storms, with photon energies up to at least 40 MeV, which sets the lowest estimate of the total potential of 40 MV. The electric field that produces TGFs will be reflected by the initial angular distribution of the TGF emission. Here we present the first constraints on the TGF emission cone based on accurately geolocated TGFs. The source lightning discharges associated with TGFs detected by RHESSI are determined from the Atmospheric Weather Electromagnetic System for Observation, Modeling, and Education (AWESOME) network and the World Wide Lightning Location Network (WWLLN). The distribution of the observation angles for 106 TGFs are compared to Monte Carlo simulations. We find that TGF emissions within a half angle >30° are consistent with the distributions of observation angle derived from the networks. In addition, 36 events occurring before 2006 are used for spectral analysis. The energy spectra are binned according to observation angle. The result is a significant softening of the TGF energy spectrum for large (>40°) observation angles, which is consistent with a TGF emission half angle (<40°). The softening is due to Compton scattering which reduces the photon energies.

  8. Optical, Infrared, and Ultraviolet Observations of the X-Ray Flash XRF 050416A (United States)

    Holland, S. T.; Boyd, P. T.; Gorosabel, J.; Hjorth, J.; Schady, P.; Thomsen, B.; Augusteijn, T.; Blustin, A. J.; Breeveld, A.; De Pasquale, M.; Fynbo, J. P. U.; Gehrels, N.; Gronwall, C.; Hunsberger, S.; Ivanushkina, M.; Landsman, W.; Laursen, P.; McGowan, K.; Mangano, V.; Markwardt, C. B.; Marshall, F.; Mason, K. O.; Moretti, A.; Page, M. J.; Poole, T.; Roming, P.; Rosen, S.; Still, M.


    We present ultraviolet, optical, and infrared photometry of the afterglow of the X-ray flash XRF 050416A taken between approximately 100 s and 36 days after the burst. We find an intrinsic spectral slope between 1930 and 22200 Å of β=-1.14+/-0.20 and a decay rate of α=-0.86+/-0.15. There is no evidence for a change in the decay rate between approximately 0.7 and 4.7 days after the burst. Our data imply that there is no spectral break between the optical and X-ray bands between 0.7 and 4.7 days after the burst and are consistent with the cooling break being redward of the Ks band (22200 Å) at 0.7 days. The combined ultraviolet/optical/infrared spectral energy distribution shows no evidence for a significant amount of extinction in the host galaxy along the line of sight to XRF 050416A. Our data suggest that the extragalactic extinction along the line of sight to the burst is only approximately AV=0.2 mag, which is significantly less than the extinction expected from the hydrogen column density inferred from X-ray observations of XRF 050416A assuming a dust-to-gas ratio similar to what is found for the Milky Way. The observed extinction, however, is consistent with the dust-to-gas ratio seen in the Small Magellanic Cloud. We suggest that XRF 050416A may have a two-component jet similar to what has been proposed for GRB 030329. If this is the case, the lack of an observed jet break between 0.7 and 42 days is an illusion due to emission from the wide jet dominating the afterglow after approximately 1.5 days.

  9. Afterglow Observations Shed New Light on the Nature of X-ray Flashes

    Energy Technology Data Exchange (ETDEWEB)

    Granot, J


    X-ray flashes (XRFs) and X-ray rich gamma-ray bursts (XRGRBs) share many observational characteristics with long duration ({approx}> 2 s) GRBs, but the reason for which the spectral energy distribution of their prompt emission peaks at lower photon energies, E{sub p}, is still a subject of debate. Although many different models have been invoked in order to explain the lower values of E{sub p}, their implications for the afterglow emission were not considered in most cases, mainly because observations of XRF afterglows have become available only recently. Here we examine the predictions of the various XRF models for the afterglow emission, and test them against the observations of XRF 030723 and XRGRB 041006, the events with the best monitored afterglow light curves in their respective class. We show that most existing XRF models are hard to reconcile with the observed afterglow light curves, which are very flat at early times. Such light curves are, however, naturally produced by a roughly uniform jet with relatively sharp edges that is viewed off-axis (i.e. from outside of the jet aperture). This type of model self consistently accommodates both the observed prompt emission and the afterglow light curves of XRGRB 041006 and XRF 030723, implying viewing angles {theta}{sub obs} from the jet axis of ({theta}{sub obs}-{theta}{sub 0}) {approx} 0.15 {theta}{sub 0} and ({theta}{sub obs}-{theta}{sub 0}) {approx} {theta}{sub 0}, respectively, where {theta}{sub 0} {approx} 3{sup o} is the half-opening angle of the jet. This suggests that GRBs, XRGRBs and XRFs are intrinsically similar relativistic jets viewed from different angles. It is then natural to identify GRBs with {gamma}({theta}{sub obs} - {theta}{sub 0}) {approx}< 1, XRGRBs with 1 {approx}< ({theta}{sub obs} - {theta}{sub 0}) {approx}< a few, and XRFs with {gamma}({theta}{sub obs} - {theta}{sub 0}) {approx}> a few, where {gamma} is the Lorentz factor of the outflow near the edge of the jet from which most of the

  10. Hot Flashes (United States)

    Hot flashes Overview Hot flashes are sudden feelings of warmth, which are usually most intense over the face, neck and chest. Your skin might redden, as if you're blushing. Hot flashes can also cause sweating, and if you ...

  11. Ultra-Fast Flash Observatory for the observation of early photons from gamma-ray bursts

    DEFF Research Database (Denmark)

    Park, I H; Brandt, Søren; Budtz-Jørgensen, Carl


    One of the least documented and understood aspects of gamma-ray bursts (GRBs) is the rise phase of the optical light curve. The Ultra-Fast Flash Observatory (UFFO) is an effort to address this question through extraordinary opportunities presented by a series of space missions including a small s...

  12. The TETRA-II Experiment to Observe Terrestrial Gamma Flashes at Ground Level - Analysis of Nearby Thunderstorm Activity and Comparison with Lightning Data (United States)

    Smith, D.; Adams, C.; Cherry, M. L.; Al-Nussirat, S.; Bai, S.; Banadaki, Y.; Bitzer, P. M.; Hoffman, J.; Khosravi, E.; Legault, M.; Orang, M.; Pleshinger, D. J.; Rodriguez, R.; Trepanier, J. C.; Sunda-Meya, A.; Zimmer, N.


    Terrestrial gamma ray flashes (TGFs) are millisecond bursts of high-energy electrons propagated within the atmosphere. An upgraded version of the TGF and Energetic Thunderstorm Rooftop Array (TETRA-II) consists of an array of BGO scintillators to detect TGFs from thunderstorms at ground-level in four locations: the campus of Louisiana State University (LSU) in Baton Rouge, Louisiana; the campus of the University of Puerto Rico at Utuado, Puerto Rico, in conjunction with the already existing Puerto Rico Lightning Detection Network (PRLDN) of radio receivers; the Centro Nacional de Metrologia de Panama (CENAMEP) in Panama City, Panama; and the Severe Weather Institute and Radar & Lightning Laboratories in Huntsville, Alabama. The original TETRA-I array of NaI scintillators at LSU detected 37 millisecond-scale bursts of gamma-rays at energies of 50 keV-2 MeV associated with nearby (< 8 km) thunderstorms. TETRA-II began operation in May 2016 and now has approximately an order of magnitude greater sensitivity to individual events than TETRA-I. The ability to observe ground-level bursts from close to the source allows an analysis of the storm cells producing these events. An analysis of storms associated with TETRA II gamma-ray events is provided using NEXRAD Level II base-reflectivity scans to determine specific storm features before, during, and after the occurrence of each event. Louisiana events appear to occur within most major thunderstorm types, in particular as the cell is transitioning into the dissipating stage of evolution.

  13. TGF Afterglows: A New Radiation Mechanism From Thunderstorms (United States)

    Rutjes, C.; Diniz, G.; Ferreira, I. S.; Ebert, U.


    Thunderstorms are known to create terrestrial gamma ray flashes (TGFs) which are microsecond-long bursts created by runaway of thermal electrons from propagating lightning leaders, as well as gamma ray glows that possibly are created by relativistic runaway electron avalanches (RREA) that can last for minutes or more and are sometimes terminated by a discharge. In this work we predict a new intermediate thunderstorm radiation mechanism, which we call TGF afterglow, as it is caused by the capture of photonuclear neutrons produced by a TGF. TGF afterglows are milliseconds to seconds long; this duration is caused by the thermalization time of the intermediate neutrons. TGF afterglows indicate that the primary TGF has produced photons in the energy range of 10-30 MeV; they are nondirectional in contrast to the primary TGF. Gurevich et al. might have reported TGF afterglows in 2011.

  14. Terrestrial gamma-ray flash production by lightning (United States)

    Carlson, Brant E.

    Terrestrial gamma-ray flashes (TGFs) are brief flashes of gamma-rays originating in the Earth's atmosphere and observed by satellites. First observed in 1994 by the Burst And Transient Source Experiment on board the Compton Gamma-Ray Observatory, TGFs consist of one or more ˜1 ms pulses of gamma-rays with a total fluence of ˜1/cm2, typically observed when the satellite is near active thunderstorms. TGFs have subsequently been observed by other satellites to have a very hard spectrum (harder than dN/d E ∝ 1/ E ) that extends from below 25 keV to above 20 MeV. When good lightning data exists, TGFs are closely associated with measurable lightning discharge. Such discharges are typically observed to occur within 300 km of the sub-satellite point and within several milliseconds of the TGF observation. The production of these intense energetic bursts of photons is the puzzle addressed herein. The presence of high-energy photons implies a source of bremsstrahlung, while bremsstrahlung implies a source of energetic electrons. As TGFs are associated with lightning, fields produced by lightning are naturally suggested to accelerate these electrons. Initial ideas about TGF production involved electric fields high above thunderstorms as suggested by upper atmospheric lightning research and the extreme energies required for lower-altitude sources. These fields, produced either quasi-statically by charges in the cloud and ionosphere or dynamically by radiation from lightning strokes, can indeed drive TGF production, but the requirements on the source lightning are too extreme and therefore not common enough to account for all existing observations. In this work, studies of satellite data, the physics of energetic electron and photon production, and consideration of lightning physics motivate a new mechanism for TGF production by lightning current pulses. This mechanism is then developed and used to make testable predictions. TGF data from satellite observations are compared

  15. Impact of agricultural management on pluvial flash floods - Case study of an extreme event observed in Austria in 2016 (United States)

    Lumassegger, Simon; Achleitner, Stefan; Kohl, Bernhard


    Central Europe was affected by extreme flash floods in summer 2016 triggered by short, high-intensity storm cells. Besides fluvial runoff, local pluvial floods appear to increase recently. In frame of the research project SAFFER-CC (sensitivity assessment of critical condition for local flash floods - evaluating the recurrence under climate change) surface runoff and pluvial flooding is assessed using a coupled hydrological/2D hydrodynamic model for the severely affected municipality of Schwertberg, Upper Austria. In this small catchment several flooding events occurred in the last years, where the most severe event occurred during summer 2016. Several areas could only be reached after the flood wave subsided with observed flood marks up to one meter. The modeled catchment is intensively cultivated with maize, sugar beets, winter wheat and soy on the hillside and hence highly vulnerable to water erosion. The average inclination is relatively steep with 15 % leading to high flow velocities of surface runoff associated with large amounts of transported sediments. To assess the influence of land use and soil conservation on flash floods, field experiments with a portable irrigation spray installation were carried out at different locations. The test plots were subjected to rainfall with constant intensity of 100 mm/h for one hour. Consecutively a super intense, one hour lasting, rainfall hydrograph was applied after 30 minutes at the same plots, ranging from 50 mm/h to 200 mm/h. Surface runoff was collected and measured in a tank and water samples were taken to determine the suspended material load. Large differences of runoff coefficients were determined depending on the agricultural management. The largest discharge was measured in a maize field, where surface runoff occurred immediately after start of irrigation. The determined runoff coefficients ranged from 0.22 for soy up to 0.65 for maize for the same soil type and inclination. The conclusion that runoff is

  16. Estimation of the Relative Severity of Floods in Small Ungauged Catchments for Preliminary Observations on Flash Flood Preparedness: A Case Study in Korea (United States)

    Kim, Eung Seok; Choi, Hyun Il


    An increase in the occurrence of sudden local flooding of great volume and short duration has caused significant danger and loss of life and property in Korea as well as many other parts of the World. Since such floods usually accompanied by rapid runoff and debris flow rise quite quickly with little or no advance warning to prevent flood damage, this study presents a new flash flood indexing methodology to promptly provide preliminary observations regarding emergency preparedness and response to flash flood disasters in small ungauged catchments. Flood runoff hydrographs are generated from a rainfall-runoff model for the annual maximum rainfall series of long-term observed data in the two selected small ungauged catchments. The relative flood severity factors quantifying characteristics of flood runoff hydrographs are standardized by the highest recorded maximum value, and then averaged to obtain the flash flood index only for flash flood events in each study catchment. It is expected that the regression equations between the proposed flash flood index and rainfall characteristics can provide the basis database of the preliminary information for forecasting the local flood severity in order to facilitate flash flood preparedness in small ungauged catchments. PMID:22690208

  17. Combining hydraulic model, hydrogeomorphological observations and chemical analyses of surface waters to improve knowledge on karst flash floods genesis

    Directory of Open Access Journals (Sweden)

    F. Raynaud


    Full Text Available During a flood event over a karst watershed, the connections between surface and ground waters appear to be complex ones. The karst may attenuate surface floods by absorbing water or contribute to the surface flood by direct contribution of karst waters in the rivers (perennial and overflowing springs and by diffuse resurgence along the hillslopes. If it is possible to monitor each known outlet of a karst system, the diffuse contribution is yet difficult to assess. Furthermore, all these connections vary over time according to several factors such as the water content of the soil and underground, the rainfall characteristics, the runoff pathways. Therefore, the contribution of each compartment is generally difficult to assess, and flood dynamics are not fully understood. To face these misunderstandings and difficulties, we analysed surface waters during six recent flood events in the Lirou watershed (a karst tributary of the Lez, in South of France. Because of the specific chemical signature of karst waters, chemical analyses can supply information about water pathways and flood dynamics. Then, we used the dilution law to combine chemical results, flow data and field observations to assess the dynamics of the karst component of the flood. To end, we discussed the surface or karst origin of the waters responsible for the apparent runoff coefficient rise during flash karst flood.

  18. Flash grundkursus

    DEFF Research Database (Denmark)

    Jensen, Henrik


    Flash er et programmeringssprog  og kan som sådant ikke noget i sig selv. Kursets mål er, at give den studerende et grundlæggende kendskab til Flash, så det kan bruges til præsentationer på skærm og til produktion af hjemmesider. På kurset arbejdes der med billede, grafik, lyd, video og interakti...

  19. Gamma Ray Signatures of Neutrons From a Terrestrial Gamma Ray Flash (United States)

    Bowers, G. S.; Smith, D. M.; Martinez-McKinney, G. F.; Kamogawa, M.; Cummer, S. A.; Dwyer, J. R.; Wang, D.; Stock, M.; Kawasaki, Z.


    Following a lightning strike to a wind turbine in Japan, we have observed a large burst of neutrons lasting 100 ms with a ground fluence of 1,000 n cm-2, thousands of times greater than the peak neutron flux associated with the largest ground level solar particle event ever observed. This is the first detection of an unequivocal signature of neutrons from a terrestrial gamma ray flash, consisting of a 2.223 MeV gamma-ray spectral line from a neutron-capture on hydrogen reaction occurring in our detector, and is shown to be consistent with the production of 1012-1013 photoneutrons from a downward terrestrial gamma ray flash (TGF) at 1.0 km, with a gamma ray brightness typical of upward TGFs observed by satellites.

  20. Standardized clinical photography: the role of flash. (United States)

    Cariello, Angelino; Viana, Giovanni André; Osaki, Midori; Pamplona, André Luis; Höfling-Lima, Ana Luisa


    Medical photographic documentation is important for professional, research, and ethical concerns. This study analyzed the possible interference that the flash could cause on evaluation of lower eyelid cosmetic results. Standardized photographs with and without flash were taken of 10 patients with dermatochalasis. The photographs were evaluated by 3 independent observers, as before (without flash) and after (with flash) an alternative esthetic treatment of the lower eyelid. The observers rated the overall cosmetic improvement of the lower eyelid photographs on a visual analog scale. The 3 surgeons believed that there was improvement in cosmetic outcome from the first (without flash) to the second (with flash) picture. The results indicate that a simple flash addition in one of 2 consecutive photographs, taken seconds apart, could influence the impression of experienced surgeons on the final outcome of oculoplastic surgeries and may constitute a bias in observer-dependent studies.

  1. Flash propagation and inferred charge structure relative to radar-observed ice alignment signatures in a small Florida mesoscale convective system (United States)

    Biggerstaff, Michael I.; Zounes, Zackery; Addison Alford, A.; Carrie, Gordon D.; Pilkey, John T.; Uman, Martin A.; Jordan, Douglas M.


    A series of vertical cross sections taken through a small mesoscale convective system observed over Florida by the dual-polarimetric SMART radar were combined with VHF radiation source locations from a lightning mapping array (LMA) to examine the lightning channel propagation paths relative to the radar-observed ice alignment signatures associated with regions of negative specific differential phase (KDP). Additionally, charge layers inferred from analysis of LMA sources were related to the ice alignment signature. It was found that intracloud flashes initiated near the upper zero-KDP boundary surrounding the negative KDP region. The zero-KDP boundary also delineated the propagation path of the lightning channel with the negative leaders following the upper boundary and positive leaders following the lower boundary. Very few LMA sources were found in the negative KDP region. We conclude that rapid dual-polarimetric radar observations can diagnose strong electric fields and may help identify surrounding regions of charge.

  2. Characteristics of cloud-to-ground lightning flashes over Sweden

    International Nuclear Information System (INIS)

    Sonnadara, Upul; Cooray, Vernon; Goetschl, Thomas


    A detailed study of the characteristics of cloud-to-ground (CG) lightning flashes over Sweden was carried out for the period 1987-2000 using data obtained from the Swedish lightning-locating network. Results are presented by analysing over half a million lightning ground flashes. The average variation of the annual mean of the total number of flashes was found to be 37%. About 12% of the CG flashes were positive flashes and their average variation about the annual mean was 26%. The average peak currents were fairly constant over the years with variations as little as 4% for negative flashes and 5% for positive flashes. The average peak current values for negative and positive flashes were -29.90 and +63.97 kA respectively. A correlation between the mean monthly flash count and percentage of positive flashes was seen. A similar relationship is seen with the mean monthly flash count and the peak currents for both polarities. In general, high flash density and high peak currents were observed in the southern part of Sweden where most of the major cities are located. Flash densities exceeding 0.4 flashes km -2 were observed for several large cities. The maximum flash rate of 32 flashes h -1 within a 10 km radius was seen in Joenkoeping (14.18 0 E, 57.78 0 N) in the province of Smaaland

  3. Simulating Terrestrial Gamma Ray Flashes due to cosmic ray shower electrons and positrons (United States)

    Connell, Paul


    The University of Valencia has developed a software simulator LEPTRACK to simulate the relativistic runaway electron avalanches, RREA, that are presumed to be the cause of Terrestrial Gamma Ray Flashes and their powerful accompanying Ionization/Excitation Flashes. We show here results of LEPTRACK simulations of RREA by the interaction of MeV energy electrons/positrons and photons in cosmic ray showers traversing plausible electric field geometries expected in storm clouds. The input beams of MeV shower products were created using the CORSIKA software package from the Karlsruhe Institute of Technology. We present images, videos and plots showing the different Ionization, Excitation and gamma-ray photon density fields produced, along with their time and spatial profile evolution, which depend critically on where the line of shower particles intercept the electric field geometry. We also show a new effect of incoming positrons in the shower, which make up a significant fraction of shower products, in particular their apparent "orbiting" within a high altitude negative induced shielding charge layer, which has been conjectured to produce a signature microwave emission, as well as a short range 511 keV annihilation line. The interesting question posed is if this conjectured positron emission can be observed and correlated with TGF orbital observations to show if a TGF originates in the macro E-fields of storm clouds or the micro E-fields of lightning leaders where this positron "orbiting" is not likely to occur.

  4. Plasma TGF beta level in rats after hemithoracic irradiation

    NARCIS (Netherlands)

    Vujaskovic, Z; Down, JD; vanWaarde, MAWH; vanAssen, AJ; Szabo, BG; Konings, AWT

    Changes in TGF-beta plasma levels were observed 18 weeks after hemithoracic irradiation in rats. This coincides with an increase in the breathing frequency, being most pronounced between 22 and 28 weeks after irradiation. The correlation suggests a potential role of the circulating TGF-beta in the

  5. TGF-beta regulation of nuclear proto-oncogenes and TGF-beta gene expression in normal human osteoblast-like cells. (United States)

    Subramaniam, M; Oursler, M J; Rasmussen, K; Riggs, B L; Spelsberg, T C


    Transforming growth factor-beta (TGF-beta) is present in high levels in bone and plays an important role in osteoblast growth and differentiation. In order to dissect the molecular mechanisms of action of TGF-beta on osteoblasts, the effects of TGF-beta on the steady state mRNA levels of c-fos, c-jun, and jun-B proto-oncogenes on normal human osteoblast-like cells (hOB) and a transformed human osteoblast cell line (MG-63) were measured. Treatment of hOBs with 2 ng/ml of TGF-beta 1 resulted in a rapid increase in c-fos mRNA levels as early as 15 min post-treatment. A maximum (10-fold) increase was observed at 30 min after TGF-beta treatment followed by a decrease to control values. Similar responses were measured whether the cells were rapidly proliferating or quiescent. TGF-beta 1 induced jun-B mRNA levels more gradually with steady increase initially observed at 30 min and a maximum induction measured at 2 h post-TGF-beta treatment. In contrast, TGF-beta treatment caused a time dependent decrease in the c-jun mRNA levels, an opposite pattern to that of jun-B mRNA. Treatment of hOBs with TGF-beta 1 in the presence of actinomycin-D abolished TGF-beta 1 induction of c-fos mRNA, suggesting that TGF-beta action is mediated via transcription. In the presence of cycloheximide, TGF-beta causes super-induction of c-fos mRNA at 30 min, indicating that the c-fos expression by TGF-beta is independent of new protein synthesis. Further, transfection of 3 kb upstream region of jun-B promoter linked to a CAT reporter gene into ROS 17/2.8 cells was sufficient to be regulated by TGF-beta 1. Interestingly, TGF-beta treatment also increased the mRNA levels of TGF-beta 1 itself at 4 h post TGF-beta treatment, with a maximum increase observed at 14 h of treatment. TGF-beta 1 treatment for 30 min were sufficient to cause a delayed increase in TGF-beta protein secretion within 24 h. These data support that TGF-beta has major effects on hOB cell proto-oncogene expression and that the

  6. DIRCM FLASH Flight Tests

    National Research Council Canada - National Science Library

    Molocher, Bernhard; Kaltenecker, Anton; Thum-Jaeger, Andrea; Regensburger, Martin; Formery, Martin


    .... FLASH operation is as follows: After handover following an alarm from the missile warning system FLASH enters autonomous passive tracking mode for tracking a missiles and sending a laser beam onto the missile...

  7. TGF-Beta and Breast Cancer Induction

    National Research Council Canada - National Science Library

    Dabovic, Branka


    .... We study the molecule TGF-beta, which blocks cell growth. TGF-beta is produced as latent complex consisting of the TGF-beta homodimer, the TGF-beta propeptide dimmer, and a second gene product, the latent TGF-beta binding protein (LTBP...

  8. Analysis of global Terrestrial Gamma Ray Flashes distribution and special focus on AGILE detections over South America (United States)

    Fabró, Ferran; Montanyà, Joan; Marisaldi, Martino; van der Velde, Oscar A.; Fuschino, Fabio


    Global distribution of the Terrestrial Gamma-ray Flashes (TGFs) detected by AGILE and RHESSI for the period from March 2009 to July 2012 has been analysed. A fourth TGF production region has been distinguished over the Pacific. It is confirmed that TGF occurrence follows the Intertropical Convergence Zone (ITCZ) seasonal migration and prefers afternoons. TGF/lightning ratio appears to be lower over America than other regions suggesting that meteorological regional differences are important for the TGF production. Diurnal cycle of TGFs peaks in the afternoon suggesting that Convective Available Potential Energy (CAPE) and convection are important for TGF production. Moreover all AGILE passages over South America in the same period have been analysed to find meteorological preferences for TGF occurrence. In each passage the analysis of Cloud Top Altitude (CTA), CAPE, number of strokes, number of storms and coverage area of clouds with temperatures below -70 °C (Cloud Top Coverage area, CTC) are computed. On average, AGILE has been exposed to 19,100 strokes between each TGF representing ∼68 h of exposure over active storms. High CAPE values, high cloud tops and high stroke occurrence suggest that meteorological conditions conducive to vigorous and electrically active storms are important for TGF production. It is shown that a high number of thunderstorms is preferable for TGF production which may be explained by a greater chance of the presence of a thunderstorm in the best development stage for TGF production. High tropopause altitude seems to be important but not primordial for TGF production.

  9. NAND flash memory technologies

    CERN Document Server

    Aritome, Seiichi


    This book discusses basic and advanced NAND flash memory technologies, including the principle of NAND flash, memory cell technologies, multi-bits cell technologies, scaling challenges of memory cell, reliability, and 3-dimensional cell as the future technology. Chapter 1 describes the background and early history of NAND flash. The basic device structures and operations are described in Chapter 2. Next, the author discusses the memory cell technologies focused on scaling in Chapter 3, and introduces the advanced operations for multi-level cells in Chapter 4. The physical limitations for scaling are examined in Chapter 5, and Chapter 6 describes the reliability of NAND flash memory. Chapter 7 examines 3-dimensional (3D) NAND flash memory cells and discusses the pros and cons in structure, process, operations, scalability, and performance. In Chapter 8, challenges of 3D NAND flash memory are dis ussed. Finally, in Chapter 9, the author summarizes and describes the prospect of technologies and market for the fu...

  10. The Power of Flash Mob Research: Conducting a Nationwide Observational Clinical Study on Capillary Refill Time in a Single Day. (United States)

    Alsma, Jelmer; van Saase, Jan L C M; Nanayakkara, Prabath W B; Schouten, W E M Ineke; Baten, Anique; Bauer, Martijn P; Holleman, Frits; Ligtenberg, Jack J M; Stassen, Patricia M; Kaasjager, Karin H A H; Haak, Harm R; Bosch, Frank H; Schuit, Stephanie C E


    Capillary refill time (CRT) is a clinical test used to evaluate the circulatory status of patients; various methods are available to assess CRT. Conventional clinical research often demands large numbers of patients, making it costly, labor-intensive, and time-consuming. We studied the interobserver agreement on CRT in a nationwide study by using a novel method of research called flash mob research (FMR). Physicians in the Netherlands were recruited by using word-of-mouth referrals, conventional media, and social media to participate in a nationwide, single-day, "nine-to-five," multicenter, cross-sectional, observational study to evaluate CRT. Patients aged ≥ 18 years presenting to the ED or who were hospitalized were eligible for inclusion. CRT was measured independently (by two investigators) at the patient's sternum and distal phalanx after application of pressure for 5 s (5s) and 15 s (15s). On October 29, 2014, a total of 458 investigators in 38 Dutch hospitals enrolled 1,734 patients. The mean CRT measured at the distal phalanx were 2.3 s (5s, SD 1.1) and 2.4 s (15s, SD 1.3). The mean CRT measured at the sternum was 2.6 s (5s, SD 1.1) and 2.7 s (15s, SD 1.1). Interobserver agreement was higher for the distal phalanx (κ value, 0.40) than for the sternum (κ value, 0.30). Interobserver agreement on CRT is, at best, moderate. CRT measured at the distal phalanx yielded higher interobserver agreement compared with sternal CRT measurements. FMR proved a valuable instrument to investigate a relatively simple clinical question in an inexpensive, quick, and reliable manner. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  11. Pro Android Flash

    CERN Document Server

    Chin, Stephen; Campesato, Oswald


    Did you know you can take your Flash skills beyond the browser, allowing you to make apps for Android, iOS and the BlackBerry Tablet OS? Build dynamic apps today starting with the easy-to-use Android smartphones and tablets. Then, take your app to other platforms without writing native code. Pro Android Flash is the definitive guide to building Flash and other rich Internet applications (RIAs) on the Android platform. It covers the most popular RIA frameworks for Android developers - Flash and Flex - and shows how to build rich, immersive user experiences on both Android smartphones and tablet

  12. Flash protection controller (United States)

    Galbraith, Lee K.


    A controller provides a high voltage to maintain an electro-optic shutter in a transparent condition until a flash of light which would be harmful to personnel is sensed by a phototransistor. The controller then shorts the shutter to ground to minimize light transmission to the user and maintains light transmission at the pre-flash level for a predetermined time to allow the flash to subside. A log converter and differential trigger circuit keep the controller from being triggered by other light flashes which are not dangerous.

  13. Flash-Type Discrimination (United States)

    Koshak, William J.


    This viewgraph presentation describes the significant progress made in the flash-type discrimination algorithm development. The contents include: 1) Highlights of Progress for GLM-R3 Flash-Type discrimination Algorithm Development; 2) Maximum Group Area (MGA) Data; 3) Retrieval Errors from Simulations; and 4) Preliminary Global-scale Retrieval.

  14. TGF-β1 factor in the cerebrovascular diseases of Alzheimer's disease. (United States)

    Zhang, X; Huang, W-J; Chen, W-W


    Transforming growth factor betas (TGF-βs) belong to three isoforms (TGF-β1, TGF-β2 and TGF-β3) members of a large pleiotropic superfamily of around 100 distinct proteins participating in the regulation of key events of development and disease, and tissue repair. In the central nervous system (CNS), all the three isoforms are produced by both glial and neuronal cells and are involved in essential tissue functions such as cell-cycle control, regulation of early development and differentiation, neuronal survival and astrocytes differentiation. Recent findings have shown abnormally increase of the levels of TGF-β1 in the brain of patients suffering Alzheimer's disease (AD), an elderly pathology reaching individuals over 65-years-old which present well-known hallmarks, including cerebrovascular deficiency, abnormal deposition of amyloid beta (Aβ), cholinergic denervation, neuroinflammation, neurofibrillary tangles and progressive loss of memory. However, related to the pathological features of AD, the brain overexpression of TGF-β1 was associated with neuroinflammation, accumulation of extracellular matrix compounds and cerebrovascular stiffness, neuronal apoptosis along with the development of vascular hypertrophy. Consistent with these observations, transgenic mice model (TGF mice) overexpressing constitutively TGF-β1 fully mimicked AD-like cerebrovascular pathology. Taken altogether, these data suggest the involvement of TGF-β1in the pathogenesis of AD, particularly in the cerebrovascular pathology which is of interest in the present review that will discuss the contribution of TGF-β1 in the cerebrovascular physiopathology of AD.

  15. The flash grab effect. (United States)

    Cavanagh, Patrick; Anstis, Stuart


    When an object moves back and forth, its trajectory appears significantly shorter than it actually is. The object appears to stop and reverse well before its actual reversal point, as if there is some averaging of location within a window of about 100 ms (Sinico et al., 2009). Surprisingly, if a bar is flashed at the physical end point of the trajectory, right on top of the object, just as it reverses direction, the flash is also shifted - grabbed by the object - and is seen at the perceived endpoint of the trajectory rather than the physical endpoint. This can shift the perceived location of the flash by as much as 2 or 3 times its physical size and by up to several degrees of visual angle. We first show that the position shift of the flash is generated by the trajectory shortening, as the same shift is seen with or without the flash. The flash itself is only grabbed if it is presented within a small spatiotemporal attraction zone around the physical end point of the trajectory. Any flash falling in that zone is pulled toward the perceived endpoint. The effect scales linearly with speed, up to a maximum, and is independent of the contrast of the moving stimulus once it is above 5%. Finally, we demonstrate that this position shift requires attention. These results reveal a new "flash grab" effect in the family of motion-induced position shifts. Although it most resembles the flash drag effect, it differs from this in the following ways: (1) it has a different temporal profile, (2) it requires attention, (3) it is about 10 times larger. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. In situ flash X-ray observation of projectile penetration processes and crater cavity growth in porous gypsum target analogous to low-density asteroids (United States)

    Yasui, Minami; Arakawa, Masahiko; Hasegawa, Sunao; Fujita, Yukihiro; Kadono, Toshihiko


    Recent studies of impact craters formed on low-density asteroids led to the proposal of a new crater formation mechanism dominated by pore collapse and compaction. Thus, it is important to study the crater formation process associated with the projectile penetration on porous cohesive targets. Laboratory impact experiments were conducted for a porous gypsum target with porosity of 50%, and flash X-rays were used to visualize the interior of the target for in situ observation of crater formation and projectile penetration. Spherical projectiles made of three different materials, stainless steel, aluminum, and nylon were impacted at 1.9-2.4 km/s (low-velocity impact) and 5.6-6.4 km/s (high-velocity impact) by using a two-stage light-gas gun. Two imaging plates were used to take two X-ray images at a different delay time from the impact moment for one shot. Two types of crater cavity shape were found on the porous gypsum target, that is, penetration holes or hemispherical cavities, depending on the projectile size and density, and the impact velocity. The drag coefficient of a projectile was determined by measuring the penetration depth changing with time, and we found that it was closely related to the crater cavity shape: it was about 0.9 for a penetration hole, while it was 2.3-3.9 for a hemispherical cavity. This large value for a hemispherical cavity could have been caused by the deformation or the disruption of the projectile. The cratering efficiency, ρtVcr(t)/mp, was found to have a power law relationship to the scaling time for crater growth, πt = vit/rp, where vi is the impact velocity, rp is the projectile radius, and t is the time after the impact, and all data for stainless steel and aluminum projectiles merged completely and could be fitted by a power-law equation of ρtVcr(t)/mp=2.69×10-1πt1.10. Furthermore, the scaled crater volume, πV = Vcr_finalρt/mp, where Vcr_final is the final crater cavity volume, ρt is the target density, and mp is the

  17. Modeling terrestrial gamma ray flashes produced by relativistic feedback discharges (United States)

    Liu, Ningyu; Dwyer, Joseph R.


    This paper reports a modeling study of terrestrial gamma ray flashes (TGFs) produced by relativistic feedback discharges. Terrestrial gamma ray flashes are intense energetic radiation originating from the Earth's atmosphere that has been observed by spacecraft. They are produced by bremsstrahlung interactions of energetic electrons, known as runaway electrons, with air atoms. An efficient physical mechanism for producing large fluxes of the runaway electrons to make the TGFs is the relativistic feedback discharge, where seed runaway electrons are generated by positrons and X-rays, products of the discharge itself. Once the relativistic feedback discharge becomes self-sustaining, an exponentially increasing number of relativistic electron avalanches propagate through the same high-field region inside the thundercloud until the electric field is partially discharged by the ionization created by the discharge. The modeling results indicate that the durations of the TGF pulses produced by the relativistic feedback discharge vary from tens of microseconds to several milliseconds, encompassing all durations of the TGFs observed so far. In addition, when a sufficiently large potential difference is available in thunderclouds, a self-propagating discharge known as the relativistic feedback streamer can be formed, which propagates like a conventional positive streamer. For the relativistic feedback streamer, the positive feedback mechanism of runaway electron production by the positrons and X-rays plays a similar role as the photoionization for the conventional positive streamer. The simulation results of the relativistic feedback streamer show that a sequence of TGF pulses with varying durations can be produced by the streamer. The relativistic streamer may initially propagate with a pulsed manner and turn into a continuous propagation mode at a later stage. Milliseconds long TGF pulses can be produced by the feedback streamer during its continuous propagation. However

  18. Floods and Flash Flooding (United States)

    Floods and flash flooding Now is the time to determine your area’s flood risk. If you are not sure whether you ... If you are in a floodplain, consider buying flood insurance. Do not drive around barricades. If your ...

  19. Coding for flash memories


    Yaakobi, Eitan


    Flash memories are, by far, the most important type of non -volatile memory in use today. They are employed widely in mobile, embedded, and mass-storage applications, and the growth in this sector continues at a staggering pace. Moreover, since flash memories do not suffer from the mechanical limitations of magnetic disk drives, solid- state drives have the potential to upstage the magnetic recording industry in the foreseeable future. The research goal of this dissertation is the discovery o...

  20. The rarity of terrestrial gamma-ray flashes (United States)

    Smith, D. M.; Dwyer, J. R.; Hazelton, B. J.; Grefenstette, B. W.; Martinez-McKinney, G. F. M.; Zhang, Z. Y.; Lowell, A. W.; Kelley, N. A.; Splitt, M. E.; Lazarus, S. M.; Ulrich, W.; Schaal, M.; Saleh, Z. H.; Cramer, E.; Rassoul, H. K.; Cummer, S. A.; Lu, G.; Blakeslee, R. J.


    We report on the first search for Terrestrial Gamma-ray Flashes (TGFs) from altitudes where they are thought to be produced. The Airborne Detector for Energetic Lightning Emissions (ADELE), an array of gamma-ray detectors, was flown near the tops of Florida thunderstorms in August/September 2009. The plane passed within 10 km horizontal distance of 1213 lightning discharges and only once detected a TGF. If these discharges had produced TGFs of the same intensity as those seen from space, every one should have been seen by ADELE. Separate and significant nondetections are established for intracloud lightning, negative cloud-to-ground lightning, and narrow bipolar events. We conclude that TGFs are not a primary triggering mechanism for lightning. We estimate the TGF-to-flash ratio to be on the order of 10-2 to 10-3 and show that TGF intensities cannot follow the well-known power-law distribution seen in earthquakes and solar flares, due to our limits on the presence of faint events.

  1. On Stellar Flash Echoes from Circular Rings (United States)

    Nemiroff, Robert; Mukherjee, Oindabi


    A flash -- or any episode of variability -- that occurs in the vicinity of a circular ring might be seen several times later, simultaneously, as echoes on the ring. Effective images of the flash are created and annihilated in pairs, with as many as four flash images visible concurrently. Videos detailing sequences of image pair creation, tandem motion, and subsequent image annihilation are shown, given simple opacity and scattering assumptions. It is proven that, surprisingly, images from a second pair creation event always annihilate with images from the first. Caustic surfaces between flash locations yielding two and four images are computed. Although such ring echos surely occur, their practical detection might be difficult as it could require dedicated observing programs involving sensitive photometry of extended objects. Potential flash sources include planetary and interstellar gas and dust rings near and around variable stars, flare stars, novae, supernovae, and GRBs. Potentially recoverable information includes size, distance, temporal history, and angular isotropy of both the ring and flash.

  2. The relation between TGF and lightning (United States)

    Ostgaard, N.; Gjesteland, T.; Hansen, R. S.; Carlson, B. E.; Collier, A.


    Based on TGF observation from space and radio emissions from lightning there seems to be growing evidence that TGFs are related to positive intracloud lightning bringing negative charges upward. On the other hand, short bursts of X-rays and gammarays observed on the ground have been associated with negative cloud to ground discharges bringing negative charges downward. X-rays are also observed in laboratory experiments during the (negative) leader formation prior to the return stroke. All these observations may indicate that X- and gamma-ray production is a natural consequence of the electrical discharge in thunderstorms and that TGFs are more common than previously believed. This is partly supported by the identification of more than twice as many TGFs in the RHESSI dataset (Gjesteland et al., 2012). An analysis of the TGF distribution as seen from space (Østgaard et al., 2012) concluded that we can not rule out the idea that all lightning discharges produce TGFs. In this paper we will present some new data relating TGFs to the lightning discharge. The observations will be discussed in the context of existing theories for X- and gamma-ray production in thunderstorms.

  3. Objective hot flashes are negatively related to verbal memory performance in midlife women. (United States)

    Maki, Pauline M; Drogos, Lauren L; Rubin, Leah H; Banuvar, Suzanne; Shulman, Lee P; Geller, Stacie E


    To test the hypothesis that hot flashes specifically relate to verbal memory performance by examining the relationship between objective hot flashes and cognitive test performance in women with moderate to severe vasomotor symptoms. In an observational study, 29 midlife women (mean age, 53 y) with moderate to severe hot flashes provided measures of objective hot flashes with an ambulatory hot flash monitor, subjective hot flashes with a diary and questionnaire, and objective measures of verbal memory and other cognitive functions with standardized neuropsychological tests. The mean number of objective hot flashes was 19.5 per day (range, 6 to 35), including 15.3 (range, 6 to 35) during waking hours and 4.2 (range, 0 to 9) during sleep. The mean sensitivity (ie, subjective detection of objectively measured hot flashes) was 60%. Regression analyses revealed that total number of objective hot flashes, sleep duration, and verbal knowledge were significant predictors of delayed verbal memory. Verbal fluency correlated positively with objective daytime hot flashes. Hot flashes did not predict performance on any of the other secondary cognitive measures (ie, attention, working memory, visual memory), although poor sleep predicted worse performance on several outcome measures. Highly symptomatic women underreport the number of objective hot flashes that they experience by 43%. Verbal memory performance relates significantly to the objective number of hot flashes women experience but not to the number of hot flashes that they report. These findings suggest that physiological factors related to hot flashes, rather than psychological factors, predict poorer verbal memory function.

  4. Enhanced detection of terrestrial gamma-ray flashes by AGILE. (United States)

    Marisaldi, M; Argan, A; Ursi, A; Gjesteland, T; Fuschino, F; Labanti, C; Galli, M; Tavani, M; Pittori, C; Verrecchia, F; D'Amico, F; Østgaard, N; Mereghetti, S; Campana, R; Cattaneo, P W; Bulgarelli, A; Colafrancesco, S; Dietrich, S; Longo, F; Gianotti, F; Giommi, P; Rappoldi, A; Trifoglio, M; Trois, A


    At the end of March 2015 the onboard software configuration of the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite was modified in order to disable the veto signal of the anticoincidence shield for the minicalorimeter instrument. The motivation for such a change was the understanding that the dead time induced by the anticoincidence prevented the detection of a large fraction of Terrestrial Gamma-Ray Flashes (TGFs). The configuration change was highly successful resulting in an increase of one order of magnitude in TGF detection rate. As expected, the largest fraction of the new events has short duration (<100 μs), and part of them has simultaneous association with lightning sferics detected by the World Wide Lightning Location Network. The new configuration provides the largest TGF detection rate surface density (TGFs/km 2 /yr) to date, opening prospects for improved correlation studies with lightning and atmospheric parameters on short spatial and temporal scales along the equatorial region.

  5. Professional Flash Lite Mobile Development

    CERN Document Server

    Anderson, J G


    Discover how to create Flash Lite mobile apps from the ground up. Adobe Flash is an ideal choice for developing rich interactive content for "Flash-enabled" mobile devices; and with this book, you'll learn how to create unique applications with Flash Lite. Through a series of code samples and extensive example applications, you'll explore the core concepts, key features, and best practices of the Flash Lite player. Coverage reveals various ways to develop Flash mobile content, create applications with a cross-platform programming framework based on the Model, View and Controller conc

  6. A control engineering approach to understanding the TGF-β paradox in cancer. (United States)

    Chung, Seung-Wook; Cooper, Carlton R; Farach-Carson, Mary C; Ogunnaike, Babatunde A


    TGF-β, a key cytokine that regulates diverse cellular processes, including proliferation and apoptosis, appears to function paradoxically as a tumour suppressor in normal cells, and as a tumour promoter in cancer cells, but the mechanisms underlying such contradictory roles remain unknown. In particular, given that this cytokine is primarily a tumour suppressor, the conundrum of the unusually high level of TGFobserved in the primary cancer tissue and blood samples of cancer patients with the worst prognosis, remains unresolved. To provide a quantitative explanation of these paradoxical observations, we present, from a control theory perspective, a mechanistic model of TGF-β-driven regulation of cell homeostasis. Analysis of the overall system model yields quantitative insight into how cell population is regulated, enabling us to propose a plausible explanation for the paradox: with the tumour suppressor role of TGF-β unchanged from normal to cancer cells, we demonstrate that the observed increased level of TGF-β is an effect of cancer cell phenotypic progression (specifically, acquired TGF-β resistance), not the cause. We are thus able to explain precisely why the clinically observed correlation between elevated TGF-β levels and poor prognosis is in fact consistent with TGF-β's original (and unchanged) role as a tumour suppressor.

  7. Positive cloud-to-ground lightning flashes in severe storms (United States)

    Rust, W. D.; Macgorman, D. R.; Arnold, R. T.


    The occurrence of cloud-to-ground flashes that effectively lower positive charge to earth (+CG flash) over flat terrain has been documented in the mature stage of severe thunderstorms. Of the 31 documented +CG flashes, most had only one return stroke. Zero-to-peak rise times for the strokes averaged 7 microsec. The +CG flashes averaged 520 ms in duration, with 25 percent lasting more than 800 ms. Many of these had field changes suggestive of continuing current. Positive flashes have been observed to emanate from several regions of severe storms: high on the back of the main storm tower, through the wall cloud, and from the downshear anvil. Visually most of these positive flashes have emanated from high in the storm, and acoustic mapping of two shows thunder sources to a height of about 15 km.

  8. Regulation of TGF-β Signal Transduction. (United States)

    Zhao, Bing; Chen, Ye-Guang


    Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.

  9. Foundation Flash Cartoon Animation

    CERN Document Server

    Jones, Tim; Rosson, Allan S


    One of Flash s most common uses is still animation for cartoons, games, advertising etc, and this book takes a fresh look at the topic, breaking it down pre-production, production, and post production, and looking at each section in detail, and covering topics such as storyboarding, character libraries and camera mechanics like no Flash book has before. The book is written by members of the Emmy award winning ANIMAX team, who have created work for clients such as Disney, AOL, Fox, WWE, ESPN, and Sesame workshop. This book is an opportunity for them to share their secrets, and is written to sui

  10. Flash x-ray

    International Nuclear Information System (INIS)

    Johnson, Q.; Pellinen, D.


    The complementary techniques of flash x-ray radiography (FXR) and flash x-ray diffraction (FXD) provide access to a unique domain in nondestructive materials testing. FXR is useful in studies of macroscopic properties during extremely short time intervals, and FXD, the newer technique, is used in studies of microscopic properties. Although these techniques are similar in many respects, there are some substantial differences. FXD generally requires low-voltage, line-radiation sources and extremely accurate timing; FXR is usually less demanding. Phenomena which can be profitably studied by FXR often can also be studied by FXD to permit a complete materials characterization

  11. In silico investigation of ADAM12 effect on TGF-β receptors trafficking

    Directory of Open Access Journals (Sweden)

    LeMeur Nolwenn


    Full Text Available Abstract Background The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-β signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-β receptors and modulates their trafficking among membranes, a crucial point in TGF-β signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-β receptors trafficking and TGF-β signaling. Findings We extracted qualitative biological observations from experimental data and defined a family of models producing a behavior compatible with the presence of ADAM12. We computationally explored the properties of this family of models which allowed us to make novel predictions. We predict that ADAM12 increases TGF-β receptors internalization rate between the cell surface and the endosomal membrane. It also appears that ADAM12 modifies TGF-β signaling shape favoring a permanent response by removing the transient component observed under physiological conditions. Conclusion In this work, confronting differential models with qualitative biological observations, we obtained predictions giving new insights into the role of ADAM12 in TGF-β signaling and hepatic fibrosis process.

  12. The rarity of terrestrial gamma-ray flashes


    Smith, D. M.; Dwyer, J. R.; Hazelton, B. J.; Grefenstette, B. W.; Martinez-McKinney, G. F. M.; Zhang, Z. Y.; Lowell, A. W.; Kelley, N. A.; Splitt, M. E.; Lazarus, S. M.; Ulrich, W.; Schaal, M.; Saleh, Z. H.; Cramer, E.; Rassoul, H. K.


    We report on the first search for Terrestrial Gamma-ray Flashes (TGFs) from altitudes where they are thought to be produced. The Airborne Detector for Energetic Lightning Emissions (ADELE), an array of gamma-ray detectors, was flown near the tops of Florida thunderstorms in August/September 2009. The plane passed within 10 km horizontal distance of 1213 lightning discharges and only once detected a TGF. If these discharges had produced TGFs of the same intensity as those seen from space, ever...

  13. Learning Flash CS4 Professional

    CERN Document Server

    Shupe, Rich


    Learning Flash CS4 Professional offers beginners and intermediate Flash developers a unique introduction to the latest version of Adobe's powerful multimedia application. This easy-to-read book is loaded with full-color examples and hands-on tasks to help you master Flash CS4's new motion editor, integrated 3D system, and character control using the new inverse kinematics bones animation system. No previous Flash experience is necessary.

  14. Jaan Toomik Flash Artis

    Index Scriptorium Estoniae


    1999. a. mai-juuni 'Flash Artis' on ajakirja Eesti korrespondendi Ando Keskküla artikkel Jaan Toomikust. Jaan Toomik on kutsutud esinema Londoni The Photographers' Gallery grupinäitusele, tema videot 'Father and Son' näidatakse Londonis avataval näitusel 'Near and Elsewhere' 11.-24. juunini

  15. Inessa Josing Flash Artis

    Index Scriptorium Estoniae


    'Flash Art'i' 1998. a. nov.-dets. numbris Rosa Martínezi artiklis suvisest Manifesta II näitusest Luxembourg'is on positiivselt mainitud ka Inessa Josingut. Illustratsiooniks toodud seitsmest fotost ühel on I. Josingu aknakujundus 'What Must I Do to be Saved?'

  16. Flash Builder and Flash Catalyst The New Workflow

    CERN Document Server

    Peeters, Steven


    The Flash Platform is changing. Flash Builder and Flash Catalyst have brought a new separation of design and coding to web development that enables a much more efficient and streamlined workflow. For designers and developers used to the close confines of Flash, this is a hugely liberating but at first alien concept. This book teaches you the new workflow for the Flash platform. It gives an overview of the technologies involved and provides you with real-world project examples and best-practice guidelines to get from design to implementation with the tools at hand. * Includes many examples* Foc

  17. The Evolution and Structure of Extreme Optical Lightning Flashes. (United States)

    Peterson, Michael; Rudlosky, Scott; Deierling, Wiebke


    This study documents the composition, morphology, and motion of extreme optical lightning flashes observed by the Lightning Imaging Sensor (LIS). The furthest separation of LIS events (groups) in any flash is 135 km (89 km), the flash with the largest footprint had an illuminated area of 10,604 km 2 , and the most dendritic flash has 234 visible branches. The longest-duration convective LIS flash lasted 28 s and is overgrouped and not physical. The longest-duration convective-to-stratiform propagating flash lasted 7.4 s, while the longest-duration entirely stratiform flash lasted 4.3 s. The longest series of nearly consecutive groups in time lasted 242 ms. The most radiant recorded LIS group (i.e., "superbolt") is 735 times more radiant than the average group. Factors that impact these optical measures of flash morphology and evolution are discussed. While it is apparent that LIS can record the horizontal development of the lightning channel in some cases, radiative transfer within the cloud limits the flash extent and level of detail measured from orbit. These analyses nonetheless suggest that lightning imagers such as LIS and Geostationary Lightning Mapper can complement ground-based lightning locating systems for studying physical lightning phenomena across large geospatial domains.

  18. Attribution of the rapid increase in flash droughts over China (United States)

    Wang, Linying; Yuan, Xing


    Recently, a rapidly developing drought that is termed as "flash drought" occurs frequently in many regions across the world and has become a hot topic. The occurrence of flash drought is often triggered by heatwave and accompanied with low soil moisture and high evapotranspiration (ET). Due to its rapid onset and unusual intensity, the impact of flash drought can be devastating in some cases. Here, we investigate the long-term trend and variability of flash droughts over China based on pentad-mean surface air temperature observations from over two thousand meteorological stations as well as soil moisture and ET estimations from multiple global reanalysis products. Flash droughts are most likely to occur over humid and semi-humid regions in China. Flash drought events averaged over China have increased by 109% from 1979 to 2010, and the increase is mainly due to a long term warming of temperature (50%), followed by the contributions from decreasing soil moisture and increasing ET. To quantify the contributions of anthropogenic and/or natural drivers for flash drought, the Community Land Model version 4.5 (CLM4.5) is being forced by multiple climate models that participated in the Coupled Model Intercomparison Project Phase 5 to provide consistent soil moisture and ET data under different forcing scenarios, and an optimal fingerprinting detection method is being used to analyze the flash drought simulations. Preliminary results indicate that anthropogenic activities have exacerbated flash drought conditions over China in recent decades.

  19. The Evolution and Structure of Extreme Optical Lightning Flashes (United States)

    Peterson, Michael; Rudlosky, Scott; Deierling, Wiebke


    This study documents the composition, morphology, and motion of extreme optical lightning flashes observed by the Lightning Imaging Sensor (LIS). The furthest separation of LIS events (groups) in any flash is 135 km (89 km), the flash with the largest footprint had an illuminated area of 10,604 km2, and the most dendritic flash has 234 visible branches. The longest-duration convective LIS flash lasted 28 s and is overgrouped and not physical. The longest-duration convective-to-stratiform propagating flash lasted 7.4 s, while the longest-duration entirely stratiform flash lasted 4.3 s. The longest series of nearly consecutive groups in time lasted 242 ms. The most radiant recorded LIS group (i.e., "superbolt") is 735 times more radiant than the average group. Factors that impact these optical measures of flash morphology and evolution are discussed. While it is apparent that LIS can record the horizontal development of the lightning channel in some cases, radiative transfer within the cloud limits the flash extent and level of detail measured from orbit. These analyses nonetheless suggest that lightning imagers such as LIS and Geostationary Lightning Mapper can complement ground-based lightning locating systems for studying physical lightning phenomena across large geospatial domains.

  20. Why Flash Type Matters: A Statistical Analysis (United States)

    Mecikalski, Retha M.; Bitzer, Phillip M.; Carey, Lawrence D.


    While the majority of research only differentiates between intracloud (IC) and cloud-to-ground (CG) flashes, there exists a third flash type, known as hybrid flashes. These flashes have extensive IC components as well as return strokes to ground but are misclassified as CG flashes in current flash type analyses due to the presence of a return stroke. In an effort to show that IC, CG, and hybrid flashes should be separately classified, the two-sample Kolmogorov-Smirnov (KS) test was applied to the flash sizes, flash initiation, and flash propagation altitudes for each of the three flash types. The KS test statistically showed that IC, CG, and hybrid flashes do not have the same parent distributions and thus should be separately classified. Separate classification of hybrid flashes will lead to improved lightning-related research, because unambiguously classified hybrid flashes occur on the same order of magnitude as CG flashes for multicellular storms.

  1. TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile); Brandan, Enrique, E-mail: [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile)


    Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.

  2. Physics Flash August 2016

    Energy Technology Data Exchange (ETDEWEB)

    Kippen, Karen Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Physics Flash is the newsletter for the Physics Division at Los Alamos National Laboratory. This newsletter is for August 2016. The following topics are covered: "Accomplishments in the Trident Laser Facility", "David Meyerhofer elected as chair-elect APS Nominating Committee", "HAWC searches for gamma rays from dark matter", "Proton Radiography Facility commissions electromagnetic magnifier", and "Cosmic ray muon computed tomography of spent nuclear fuel in dry storage casks."

  3. The lightning flash

    CERN Document Server

    Cooray, Vernon


    With contributions from today's leading lightning engineers and researchers, this updated 2nd edition of Vernon Cooray's classic text, The Lightning Flash provides the reader with an essential introduction to lightning and its impact on electrical and electronic equipment. Providing the reader with a thorough background into almost every aspect of lightning and its impact on electrical and electronic equipment, this new edition is updated throughout and features eight new chapters that bring the science up to date.

  4. Coherent imaging at FLASH

    International Nuclear Information System (INIS)

    Chapman, H N; Bajt, S; Duesterer, S; Treusch, R; Barty, A; Benner, W H; Bogan, M J; Frank, M; Hau-Riege, S P; Woods, B W; Boutet, S; Cavalleri, A; Hajdu, J; Iwan, B; Seibert, M M; Timneanu, N; Marchesini, S; Sakdinawat, A; Sokolowski-Tinten, K


    We have carried out high-resolution single-pulse coherent diffractive imaging at the FLASH free-electron laser. The intense focused FEL pulse gives a high-resolution low-noise coherent diffraction pattern of an object before that object turns into a plasma and explodes. In particular we are developing imaging of biological specimens beyond conventional radiation damage resolution limits, developing imaging of ultrafast processes, and testing methods to characterize and perform single-particle imaging.

  5. Physics Flash December 2016

    Energy Technology Data Exchange (ETDEWEB)

    Kippen, Karen Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). ADEPS Communications


    This is the December 2016 issue of Physics Flash, the newsletter of the Physics Division of Los Alamos National Laboratory (LANL). In this issue, the following topics are covered: Novel liquid helium technique to aid highly sensitive search for a neutron electrical dipole moment; Silverleaf: Prototype Red Sage experiments performed at Q-site; John L. Kline named 2016 APS Fellow; Physics students in the news; First Entropy Engine quantum random number generator hits the market; and celebrating service.

  6. The Connection Between Terrestrial Gamma-Ray Flashes and Energetic In-Cloud Lightning Pulses (United States)

    Cummer, S. A.; Lyu, F.; Briggs, M. S.; Cramer, E.; Stanbro, M.; Roberts, O.; Smith, D. M.


    Radio emissions continue to provide a unique view into the electrodynamics of terrestrial gamma ray flash (TGF) production. Here we will describe our most recent findings on the connection between energetic in-cloud pulses (EIPs) and TGFs. EIPs are a recently identified class of high peak-current lightning events that occur sometimes during the progression of lightning in-cloud negative leaders. They can be robustly detected and identified on the basis of signals from distant ground-based radio sensors. With limited statistics, previous work has shown that many, or perhaps even all, EIPs are associated with simultaneous TGFs. We have analyzed two additional years of ground-based radio and spacecraft TGF data, and report the resulting broader statistics on the EIP-TGF relationship, as well as the implications for the ability to detect a subpopulation of TGFs from ground-based radio sensors alone.

  7. Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Pooja Chandrakant Thacker

    Full Text Available Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

  8. Corrosion testing in flash tanks of kraft pulp mills

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, S.J.; Stead, N.J.


    The corrosion observed in the first flash tanks in kraft pulp mills with modified cooking practices was characterized. Coupons of carbon steel (CS), several stainless steels (SS), and Ti were exposed at two mills. At one mill, identical sets of coupons were exposed in the No. 1 and No. 2 flash tank. At the other mill, three identical sets of coupons were placed in flash tank No. 1. The results of the exposures showed that both CS and Ti suffered high rates of general corrosion, while the SS suffered varying degrees of localized attack. The ranking of the corrosion resistance in the flash tank was the same that would be expected in a reducing acid environment. Attack by organic acids was concluded to be the most likely cause of corrosion of the flash tanks.

  9. Assessment of vulnerability to extreme flash floods in design storms. (United States)

    Kim, Eung Seok; Choi, Hyun Il


    There has been an increase in the occurrence of sudden local flooding of great volume and short duration caused by heavy or excessive rainfall intensity over a small area, which presents the greatest potential danger threat to the natural environment, human life, public health and property, etc. Such flash floods have rapid runoff and debris flow that rises quickly with little or no advance warning to prevent flood damage. This study develops a flash flood index through the average of the same scale relative severity factors quantifying characteristics of hydrographs generated from a rainfall-runoff model for the long-term observed rainfall data in a small ungauged study basin, and presents regression equations between rainfall characteristics and the flash flood index. The aim of this study is to develop flash flood index-duration-frequency relation curves by combining the rainfall intensity-duration-frequency relation and the flash flood index from probability rainfall data in order to evaluate vulnerability to extreme flash floods in design storms. This study is an initial effort to quantify the flash flood severity of design storms for both existing and planned flood control facilities to cope with residual flood risks due to extreme flash floods that have ocurred frequently in recent years.

  10. Nanotopography follows force in TGF-{beta}1 stimulated epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Thoelking, Gerold; Oberleithner, Hans; Riethmuller, Christoph [Institute of Physiology II, University of Muenster (Germany); Reiss, Bjoern [Institute of Biochemistry, University of Muenster (Germany); Wegener, Joachim [Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg (Germany); Pavenstaedt, Hermann, E-mail: [Department of Medicine D, Division of General Internal Medicine and Nephrology, University Hospital Muenster (Germany)


    Inflammation and cellular fibrosis often imply an involvement of the cytokine TGF-{beta}1. TGF-{beta}1 induces epithelial-to-mesenchymal transdifferentiation (EMT), a term describing the loss of epithelium-specific function. Indicative for this process are an elongated cell shape parallel to stress fibre formation. Many signalling pathways of TGF-{beta}1 have been discovered, but mechanical aspects have not yet been investigated. In this study, atomic force microscopy (AFM) was used to analyse surface topography and mechanical properties of EMT in proximal kidney tubule epithelium (NRK52E). Elongated cells, an increase of stress fibre formation and a loss of microvillus compatible structures were observed as characteristic signs of EMT. Furthermore, AFM could identify an increase in stiffness by 71% after six days of stimulation with TGF-{beta}1. As a novel topographical phenomenon, nodular protrusions emerged at the cell-cell junctions. They occurred preferentially at sites where stress fibres cross the border. Since these nodular protrusions were sensitive to inhibitors of force generation, they can indicate intracellular tension. The results demonstrate a manifest impact of elevated tension on the cellular topography.

  11. Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis (United States)

    Madala, Satish K.; Korfhagen, Thomas R.; Schmidt, Stephanie; Davidson, Cynthia; Edukulla, Ramakrishna; Ikegami, Machiko; Violette, Shelia M.; Weinreb, Paul H.; Sheppard, Dean


    the β6 integrin attenuated histological and physiological changes in the lungs of TGF-α transgenic mice although a significant degree of fibrosis still developed. In summary, inhibition of the β6 integrin led to a modest, albeit significant, effect on pleural thickening and lung function decline observed with TGF-α-induced pulmonary fibrosis. These data support activation of the αvβ6/TGF-β pathway as a secondary effect contributing to TGF-α-induced pleural fibrosis and suggest a complex contribution of multiple mediators to the maintenance of progressive fibrosis in the lung. PMID:24508732

  12. Flash Platform Examination (United States)


    Reine (en droit du Canada), telle que représentée par le ministre de la Défense nationale, 2011 DRDC Atlantic TM 2008-291 i Abstract...concepts de l’interface utilisateur novateurs. Les applications Flash de diverses fidélités peut intégrer des fonctions de visualisation des données...diverses peuvent intégrer des fonctions de visualisation des données, d’interactivité novatrice, d’animation riche et de diverses

  13. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jing [Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang (China); Liu, Su-zhi [Department of Neurology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou 317000, Zhejiang (China); Lin, Yan; Cao, Xiao-pan [Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang (China); Liu, Jia-ming, E-mail: [School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou 325035, Zhejiang (China)


    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.

  14. Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression. (United States)

    Chen, Zhaowei; Li, Wenjing; Ning, Yan; Liu, Tong; Shao, Jingxiang; Wang, Yaojun


    The aim of the present work was to investigate the mechanism of transforming growth factor (TGF)-β1 and Sloan-Kettering Institute (Ski) in the pathogenesis of hypertrophic scars (HS). Wound healing is an inherent process, but the aberrant wound healing of skin injury may lead to HS. There has been growing evidence suggesting a role for TGF-β1 and Ski in the pathogenesis of fibrosis. The MTT assay was used to detect the cell proliferation induced by TGF-β1. The Ski gene was transduced into cells with an adenovirus, and then the function of Ski in cell proliferation and differentiation was observed. Ski mRNA levels were measured by RT-PCR. Western blotting was used to detect the protein expression of α-SMA, E-cadherin, Meox1, Meox2, Zeb1 and Zeb2. TGF-β1 can promote human skin fibroblast (HSF) cell proliferation in a time-dependent manner, but the promoting effect could be suppressed by Ski. TGF-β1 also induces the formation of the myofibroblast phenotype and the effect of TGF-β1 could be diminished by Ski. Also, Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by up-regulating the expression of Meox2. Ski diminishes the myofibroblast phenotype induced by TGF-β1 through the suppression of Zeb2 by up-regulating the expression of Meox2. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Gamma secretase inhibitor impairs epithelial-to-mesenchymal transition induced by TGF-β in ovarian tumor cell lines. (United States)

    Pazos, M C; Abramovich, D; Bechis, A; Accialini, P; Parborell, F; Tesone, M; Irusta, G


    Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β. DAPT impaired the translocation of phospho-β-catenin to the inner cell compartment observed in TGF-β-treated cells, but was not able to block the induction at protein level induced by TGF-β. Moreover, the inhibitor blocked the increased cell migration and invasiveness ability of both cell lines induced by TGF-β. Notch target genes (Hes1 and Hey1) were induced by TGF-β, decreased by DAPT treatment and remained low in the presence of both stimuli. However, DAPT alone caused no effects on most of the parameters analyzed. These results demonstrate that the γ-secretase inhibitor used in this study exerted a blockade on TGF-β-induced EMT in ovarian cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Emilie Gauthy

    Full Text Available GARP is a transmembrane protein present on stimulated human regulatory T lymphocytes (Tregs, but not on other T lymphocytes (Th cells. It presents the latent form of TGF-β1 on the Treg surface. We report here that GARP favors the cleavage of the pro-TGF-β1 precursor and increases the amount of secreted latent TGF-β1. Stimulated Tregs, which naturally express GARP, and Th cells transfected with GARP secrete a previously unknown form of latent TGF-β1 that is disulfide-linked to GARP. These GARP/TGF-β1 complexes are possibly shed from the T cell surface. Secretion of GARP/TGF-β1 complexes was not observed with transfected 293 cells and may thus be restricted to the T cell lineage. We conclude that in stimulated human Tregs, GARP not only displays latent TGF-β1 at the cell surface, but also increases its secretion by forming soluble disulfide-linked complexes. Moreover, we identified six microRNAs (miRNAs that are expressed at lower levels in Treg than in Th clones and that target a short region of the GARP 3' UTR. In transfected Th cells, the presence of this region decreased GARP levels, cleavage of pro-TGF-β1, and secretion of latent TGF-β1.

  17. Flash X-ray

    International Nuclear Information System (INIS)

    Sato, Eiichi


    Generation of quasi-monochromatic X-ray by production of weakly ionized line plasma (flash X-ray), high-speed imaging by the X-ray and high-contrast imaging by the characteristic X-ray absorption are described. The equipment for the X-ray is consisted from the high-voltage power supply and condenser, turbo molecular pump, and plasma X-ray tube. The tube has a long linear anticathode to produce the line plasma and flash X-ray at 20 kA current at maximum. X-ray spectrum is measured by the imaging plate equipped in the computed radiography system after diffracted by a LiF single crystal bender. Cu anticathode generates sharp peaks of K X-ray series. The tissue images are presented for vertebra, rabbit ear and heart, and dog heart by X-ray fluoroscopy with Ce anticathode. Generation of K-orbit characteristic X-ray with extremely low bremsstrahung is to be attempted for medical use. (N.I.)

  18. Pathogenesis of cleft palate in TGF-beta3 knockout mice. (United States)

    Taya, Y; O'Kane, S; Ferguson, M W


    We previously reported that mutation of the transforming growth factor-beta3 (TGF-beta3) gene caused cleft palate in homozygous null (-/-) mice. TGF-beta3 is normally expressed in the medial edge epithelial (MEE) cells of the palatal shelf. In the present study, we investigated the mechanisms by which TGF-beta3 deletions caused cleft palate in 129 x CF-1 mice. For organ culture, palatal shelves were dissected from embryonic day 13.5 (E13.5) mouse embryos. Palatal shelves were placed singly or in pairs on Millipore filters and cultured in DMEM/F12 medium. Shelves were placed in homologous (+/+ vs +/+, -/- vs -/-, +/- vs +/-) or heterologous (+/+ vs -/-, +/- vs -/-, +/+ vs +/-) paired combinations and examined by macroscopy and histology. Pairs of -/- and -/- shelves failed to fuse over 72 hours of culture whereas pairs of +/+ (wild-type) and +/+ or +/- (heterozygote) and +/-, as well as +/+ and -/- shelves, fused within the first 48 hour period. Histological examination of the fused +/+ and +/+ shelves showed complete disappearance of the midline epithelial seam whereas -/- and +/+ shelves still had some seam remnants. In order to investigate the ability of TGF-beta family members to rescue the fusion between -/- and -/- palatal shelves in vitro, either recombinant human (rh) TGF-beta1, porcine (p) TGF-beta2, rh TGF-beta3, rh activin, or p inhibin was added to the medium in different concentrations at specific times and for various periods during the culture. In untreated organ culture -/- palate pairs completely failed to fuse, treatment with TGF-beta3 induced complete palatal fusion, TGF-beta1 or TGF-beta2 near normal fusion, but activin and inhibin had no effect. We investigated ultrastructural features of the surface of the MEE cells using SEM to compare TGF-beta3-null embryos (E 12. 5-E 16.5) with +/+ and +/- embryos in vivo and in vitro. Up to E13.5 and after E15.5, structures resembling short rods were observed in both +/+ and -/- embryos. Just before fusion

  19. Gamma ray flashes add to mystery of upper atmosphere (United States)

    Atmospheric electricity research has come a long way since Benjamin Franklin's kite-flying days. But what researchers have been learning lately about above-thunderstorm electricity has wrought a whole new era of mysteries.For a start, last summer a Colorado meteorologist sparked interest in a terrestrial phenomenon that the community first observed more than 100 years ago: optical flashes that occur above thunderstorms—at least 30 km above Earth. Walter Lyons with the Ft. Collins-based Mission Research Corporation, demonstrated that such flashes are not anomalies, as conventional scientific wisdom had held. He filmed hundreds of flashes during a 2-week period.

  20. Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion.

    Directory of Open Access Journals (Sweden)

    Patrícia Mello Ferrão

    Full Text Available Several studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion process of mammalian host cells is described to be dependent on the activation of the host TGF-β signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be an important activator of latent TGF-β and thereby trigger TGF-β-mediated events crucial for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite lysates and purified cruzipain were able to activate latent TGF-β in vitro. This activation could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented latent TGF-β activation. We also observed that T. cruzi invasion, as well as parasite intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-β neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be completely inhibited by addition of a neutralizing anti-TGF-β antibody. Taken together, these results demonstrate that the activities of cruzipain and TGF-β in the process of cell invasion are functionally linked. Our data suggest that cruzipain inhibition is an interesting chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity, but also due to the inhibitory effect on TGF-β activation.

  1. Spatial-temporal characteristics of lightning flash size in a supercell storm (United States)

    Zhang, Zhixiao; Zheng, Dong; Zhang, Yijun; Lu, Gaopeng


    The flash sizes of a supercell storm, in New Mexico on October 5, 2004, are studied using the observations from the New Mexico Lightning Mapping Array and the Albuquerque, New Mexico, Doppler radar (KABX). First, during the temporal evolution of the supercell, the mean flash size is anti-correlated with the flash rate, following a unary power function, with a correlation coefficient of - 0.87. In addition, the mean flash size is linearly correlated with the area of reflectivity > 30 dBZ at 5 km normalized by the flash rate, with a correlation coefficient of 0.88. Second, in the horizontal, flash size increases along the direction from the region near the convection zone to the adjacent forward anvil. The region of minimum flash size usually corresponds to the region of maximum flash initiation and extent density. The horizontal correspondence between the mean flash size and the flash extent density can also be fitted by a unary power function, and the correlation coefficient is > 0.5 in 50% of the radar volume scans. Furthermore, the quality of fit is positively correlated to the convective intensity. Third, in the vertical direction, the height of the maximum flash initiation density is close to the height of maximum flash extent density, but corresponds to the height where the mean flash size is relatively small. In the discussion, the distribution of the small and dense charge regions when and where convection is vigorous in the storm, is deduced to be responsible for the relationship that flash size is temporally and spatially anti-correlated with flash rate and density, and the convective intensity.

  2. TGF-betas synthesized by RPE cells have autocrine activity on mesenchymal transformation and cell proliferation. (United States)

    Lee, S C; Kim, S H; Koh, H J; Kwon, O W


    The present study investigated the effects of transforming growth factor (TGF)-beta on retinal pigment epithelial (RPE) transformation in a simplified model and also whether or not TGF-beta exhibits similar proliferation effects on transformed RPE cells that it has on primary RPE cells. Furthermore, we examined the cell proliferation effects of RPE-conditioned medium (CM). A vertical wound measuring 2 mm in diameter was made on primary RPE monolayers. The expression of alpha-smooth muscle actin (SMA) by the cells located at the wound edges was observed using a confocal microscope under immunofluorescent staining. Cell proliferation was measured by incorporating 3H-thymidine into DNA. The presence of alpha-SMA was observed in the cells within the wound after treatment with TGF-beta2, while negative expression was observed in control cells. TGF-betas inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, but the spindle-shaped late-passaged RPE cells were not inhibited by these growth factors. The medium conditioned by RPE cells stimulated the proliferation of subconjunctival fibroblasts and inhibited the proliferation of primary RPE cells, in a manner similar to TGF-beta. These findings demonstrate that TGF-beta-stimulated RPE cells may evoke proliferative vitreoretinopathy through mesenchymal transformation and cell proliferation.

  3. TGF-β1 exerts opposing effects on grass carp leukocytes: implication in teleost immunity, receptor signaling and potential self-regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Mu Yang

    Full Text Available In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1 has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL and head kidney leukocytes (HKL. It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ and T/B cell markers [Cd4-like (Cd4l, Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5, was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5(+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes.

  4. Evaluating a flash size and energy dissipation relationship through various modeling techniques (United States)

    Salinas, V.; Brothers, M.; Bruning, E. C.; Mansell, E.


    Many studies have investigated the influence of the electrostatic and kinematic environments of thunderstorms on lightning flash size. Recent work has demonstrated a coupling of turbulent kinematic properties to flash size distribution in different regions of a storm. Additional work has also theorized a relationship of flash size and energy to the TKE spectrum. However, the physical basis for using flash size alone in these estimates remains absent. This study used the National Severe Storms Laboratory's Collaborative Model for Multiscale Atmospheric Simulation model (N-COMMAS) to simulate an observed multicellular thunderstorm to investigate the relationship between flash size and energy. Model output included the total energy dissipated for each flash, and the charge, electric potential, electric field where it propagated. These flashes were then modeled in two simplified ways. First, each flash was assumed to be convex hull volumes of charge. A 3D Poisson solver was then used on each charge volume for charge density retrieval and computation of the electric potential, using a theoretical electric field breakeven threshold and charge conservation. Second, a capacitor model was used to estimate the energy dissipated using flash area, charge, and plate spacing obtained from the COMMAS model. These two calculations of flash energy were compared to the COMMAS energy. The results suggested that flash size alone was insufficient in characterizing the energetic properties.

  5. TGF-β Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells (United States)

    Kang, Soyeong; Min, Ahrum; Im, Seock-Ah; Song, Sang-Hyun; Kim, Sang Gyun; Kim, Hyun-Ah; Kim, Hee-Jun; Oh, Do-Youn; Jong, Hyun-Soon; Kim, Tae-You; Bang, Yung-Jue


    Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor β (TGF-β) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-β can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-β-responsive and overexpress COX-2. Materials and Methods Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-β. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-β. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-β, suggesting that TGF-β–induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-β rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-β. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-β. Conclusion The results of this study show that TGF-β down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells. PMID:25544576

  6. Observation of K-shell soft X ray emission of nitrogen irradiated by XUV-free electron laser FLASH at intensities greater than 1016 W/cm2

    International Nuclear Information System (INIS)

    Galtier, E.; Rosmej, F.B.; Galtier, E.; Rosmej, F.B.; Renner, O.; Juha, L.; Chalupsky, J.; Gauthier, J.C.; White, S.; Riley, D.; Vinko, S.; Witcher, T.; Wark, J.; Nagler, B.; Lee, R.W.; Nelson, A.J.; Toleikis, S.


    In the past few years, the development of light sources of the 4. generation, namely XUV/X-ray Free Electron Lasers provides to the scientific community outstanding tools to investigate matter under extreme conditions never obtained in laboratories so far. As theory is at its infancy, the analysis of matter via the self-emission of the target is of central importance. The characterization of such dense matter is possible if photons can escape the medium. As the absorption of K-shell X-ray transitions is minimal, it plays a key role in this study. We report here the first successful observation of K-shell emission of Nitrogen at 430 eV using an XUV-Free Electron Laser to irradiate solid Boron Nitride targets under exceptional conditions: photon energy of 92 eV, pulse duration of similar to 20 fs, micro focusing leading to intensities larger than 10 16 W/cm 2 . Using a Bragg crystal of THM coupled to a CCD, we resolved K-shell line emission from different charge states. We demonstrate that the spectroscopic data allow characterization of electron heating processes when X-ray radiation is interacting with solid matter. As energy transport is non-trivial because the light source is monochromatic, these results have an important impact on the theory. (authors)

  7. Flashing coupled density wave oscillation

    International Nuclear Information System (INIS)

    Jiang Shengyao; Wu Xinxin; Zhang Youjie


    The experiment was performed on the test loop (HRTL-5), which simulates the geometry and system design of the 5 MW reactor. The phenomenon and mechanism of different kinds of two-phase flow instabilities, namely geyser instability, flashing instability and flashing coupled density wave instability are described. The especially interpreted flashing coupled density wave instability has never been studied well, it is analyzed by using a one-dimensional non-thermo equilibrium two-phase flow drift model computer code. Calculations are in good agreement with the experiment results. (5 refs.,5 figs., 1 tab.)

  8. Trisonic Gas-Dynamics Facility (TGF) (United States)

    Federal Laboratory Consortium — Description: The TGF is a two-foot square, continuous-flow, closed-circuit wind tunnel which is optimal for conducting research experiments. The facility provides a...

  9. Corrosion testing in flash tanks

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, S.J.; Stead, N.J.


    As kraft pulp mills adopt modified cooking processes, an increasing amount of corrosion of carbon steel digester systems is being encountered. Many mills have had severe corrosion in the flash tanks, in particular, the first ({number{underscore}sign}1) flash tank. The work described in this report was aimed at characterizing the corrosion. Coupons of carbon steel, several stainless steels and titanium were exposed at two mills. At mill A, identical sets of coupons were exposed in the {number{underscore}sign}1 and {number{underscore}sign}2 flash tank. At mill B, three identical sets of coupons were placed in flash tank {number{underscore}sign}1. The results of the exposures showed that both carbon steel and titanium suffered high rates of general corrosion, while the stainless steels suffered varying degrees of localized attack. The ranking of the resistance of corrosion in the flash tank was the same ranking as would be expected in a reducing acid environment. In the light of the coupon results, organic acids is concluded to be the most likely cause of corrosion of the flash tanks.

  10. Expression of the TGF-beta1 system in human testicular pathologies

    Directory of Open Access Journals (Sweden)

    Puigdomenech Elisa


    Full Text Available Abstract Background In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO and hypospermatogenesis (H are commonly found. In these pathologies, Leydig cell hyperplasia (LCH is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5, and the co-receptor endoglin in human biopsies from patients with idiopathic infertility. Methods Specific immunostaining of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5, co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-β1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR. Results Immunohistochemical studies revealed that TGF-β1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-β1 signaling, are also detected in both their phosphorylated (activated and dephosphorylated form in all samples TGF-β1, ALK-1 and endoglin gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither TGFBRII nor ALK-5 gene expression showed significant differences between pathologies. A significant correlation between ALK-1 and endoglin expression was observed. Conclusions In conclusion, the high levels of mRNA and protein expression of the TGF-β1 system in patients with LCH, particularly ALK1 and its correlation with endoglin, suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia.

  11. Inhibition of TGF-β Signaling in Tumor Cells by Small Molecule Src Family Kinase Inhibitors. (United States)

    Bartscht, Tobias; Rosien, Benjamin; Rades, Dirk; Kaufmann, Roland; Biersack, Harald; Lehnerta, Hendrik; Ungefroren, Hendrik


    In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear. In contrast, the anti-TGF-β effect of yet another Src/Abl inhibitor, bosutinib, is more variable with respect to the type of the TGF-β response and the cell type affected, and lacks a clear dose-dependency. In the light of their strong anti-activin receptor-like kinase 5 kinase effect, PP1 and PP2 should not be used when studying the role of c-Src as downstream mediators in TGF-β/activin receptor-like kinase 5 signaling. On the other hand, based upon in vitro findings, it is conceivable that part of the therapeutic effects of AZM475271 and dasatinib seen in preclinical and clinical studies with solid tumors was caused by inhibition of prometastatic TGF-β rather than Src signaling. If AZM475271 and dasatinib can indeed act as dual Src / TGF-β inhibitors in vivo, this may be beneficial for prevention of metastatic disease in more advanced tumor stages. Copyright© Bentham Science Publishers; For any queries, please email at

  12. Research of TGF-beta1 Inducing Lung Adencarcinoma PC9 Cells to Mesenchymal Cells Transition

    Directory of Open Access Journals (Sweden)

    Xiaofeng CHEN


    Full Text Available Background and objective It has been proven that epithelial-mesenchymal transition (EMT not only correlated with embryonic development but also could promote tumor invasion and metastasis. Transforming growth factor beta-1 (TGF-β1 has been identified as the main inducer of tumor EMT. The aim of this study was to investigate the effects of TGF-β1 on EMT and PI3K/AKT signaling pathway in lung adencarcinoma PC9 cells. Methods Cultured PC9 cells were treated with different concentrations of TGF-β1 for 48 h. The morphological changes were observed under phase-contrast microscopy; EMT relative marker protein changes were assessed by Western blot and immunoflurescence staining. In addition, the expression of AKT and P-AKT were also measured by Western blot. Results The data showed that TGF-β1 could induce PC9 morphological alteration from epithelial to mesenchymal and upregulate the expression of mesenchymal maker protein Fibronectin. Obviously, the expression of P-AKT was downregulated by TGF-β1 treatment for 48 h. Conclusion TGF-β1 might induce EMT of PC9 cells , accompanied by the changes of PI3K/AKT signaling pathway.

  13. Impact of rainfall spatial variability on Flash Flood Forecasting (United States)

    Douinot, Audrey; Roux, Hélène; Garambois, Pierre-André; Larnier, Kevin


    built for each studied catchment. The proposed methodology is applied on three Mediterranean catchments often submitted to flash floods. The new forecasting method as well as the Flash Flood Guidance method (uniform rainfall threshold) are tested on 25 flash floods events that had occurred on those catchments. Results show a significant impact of rainfall spatial variability. Indeed, it appears that the uniform rainfall threshold (FFG threshold) always overestimates the observed rainfall threshold. The difference between the FFG threshold and the proposed threshold ranges from 8% to 30%. The proposed methodology allows the calculation of a threshold more representative of the observed one. However, results strongly depend on the related event duration and on the catchment properties. For instance, the impact of the rainfall spatial variability seems to be correlated with the catchment size. According to these results, it seems to be interesting to introduce information on the catchment properties in the threshold calculation. Flash Flood Guidance Improvement Team, 2003. River Forecast Center (RFC) Development Management Team. Final Report. Office of Hydrologic Development (OHD), Silver Spring, Mary-land. Le Lay, M. and Saulnier, G.-M., 2007. Exploring the signature of climate and landscape spatial variabilities in flash flood events: Case of the 8-9 September 2002 Cévennes-Vivarais catastrophic event. Geophysical Research Letters, 34(L13401), doi:10.1029/2007GL029746. Roux, H., Labat, D., Garambois, P.-A., Maubourguet, M.-M., Chorda, J. and Dartus, D., 2011. A physically-based parsimonious hydrological model for flash floods in Mediterranean catchments. Nat. Hazards Earth Syst. Sci. J1 - NHESS, 11(9), 2567-2582. Zoccatelli, D., Borga, M., Zanon, F., Antonescu, B. and Stancalie, G., 2010. Which rainfall spatial information for flash flood response modelling? A numerical investigation based on data from the Carpathian range, Romania. Journal of Hydrology, 394(1-2), 148-161.


    Freeman, Ellen W.; Sammel, Mary D.; Sanders, Richard J.


    Objectives To estimate the risk of hot flashes relative to natural menopause and evaluate associations of hormone levels, behavioral and demographic variables with the risk of hot flashes following menopause. Methods Annual assessments of 255 women who were premenopausal at baseline and reached natural menopause during 16 years of follow-up. Results The prevalence of moderate/severe hot flashes increased in each premenopausal year, reaching a peak of 46% in the first two years after the final menstrual period (FMP). Hot flashes decreased slowly following menopause and did not return to premenopausal levels until 9 years after FMP. The mean duration of moderate/severe hot flashes after FMP was 4.6 (SD2.9) years (4.9, SD3.1 years for any hot flashes). One-third of women at 10 or more years following menopause continued to experience moderate/severe hot flashes. African American women (obese and non-obese) and obese white women had significantly greater risk of hot flashes compared to non-obese white women (interaction P=0.01). In multivariable analysis, increasing FSH levels before FMP (Pmenopause; more than one- third of women observed for 10 or more years following menopause had moderate/severe hot flashes. Continuation of hot flashes for more than 5 years following menopause underscores the importance of determining individual risk/benefit when selecting hormone or non-hormonal therapy for menopausal symptoms. PMID:24473530

  15. TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

    International Nuclear Information System (INIS)

    Fang, Ling; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Ma, Taotao; Liu, Xuejiao; Zhu, Qian; Zhan, Shuxiang; Li, Jun


    Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells

  16. TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Ling, E-mail: [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); The First Affiliated Hospital of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Ma, Taotao; Liu, Xuejiao; Zhu, Qian [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); Zhan, Shuxiang [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); The First Affiliated Hospital of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Li, Jun, E-mail: [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China)


    Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells

  17. Flashing light in microalgae biotechnology. (United States)

    Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David


    Flashing light can enhance photosynthesis and improve the quality and quantity of microalgal biomass, as it can increase the products of interest by magnitudes. Therefore, the integration of flashing light effect into microalgal cultivation systems should be considered. However, microalgae require a balanced mix of the light/dark cycle for higher growth rates, and respond to light intensity differently according to the pigments acquired or lost during the growth. This review highlights recently published results on flashing light effect on microalgae and its applications in biotechnology, as well as the recently developed bioreactors designed to fulfill this effect. It also discusses how this knowledge can be applied in selecting the optimal light frequencies and intensities with specific technical properties for increasing biomass production and/or the yield of the chemicals of interest by microalgae belonging to different genera. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways (United States)

    Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.


    The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

  19. Quick Guide to Flash Catalyst

    CERN Document Server

    Elmansy, Rafiq


    How do you transform user interface designs created in Photoshop or Illustrator into interactive web pages? It's easier than you think. This guide shows you how to use Adobe Flash Catalyst to create interactive UIs and website wireframes for Rich Internet Applications-without writing a single line of code. Ideal for web designers, this book introduces Flash Catalyst basics with detailed step-by-step instructions and screenshots that illustrate every part of the process. You'll learn hands-on how to turn your static design or artwork into working user interfaces that can be implemented in Fla

  20. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease. (United States)

    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas


    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Lunar Impact Flash Locations from NASA's Lunar Impact Monitoring Program (United States)

    Moser, D. E.; Suggs, R. M.; Kupferschmidt, L.; Feldman, J.


    Meteoroids are small, natural bodies traveling through space, fragments from comets, asteroids, and impact debris from planets. Unlike the Earth, which has an atmosphere that slows, ablates, and disintegrates most meteoroids before they reach the ground, the Moon has little-to-no atmosphere to prevent meteoroids from impacting the lunar surface. Upon impact, the meteoroid's kinetic energy is partitioned into crater excavation, seismic wave production, and the generation of a debris plume. A flash of light associated with the plume is detectable by instruments on Earth. Following the initial observation of a probable Taurid impact flash on the Moon in November 2005,1 the NASA Meteoroid Environment Office (MEO) began a routine monitoring program to observe the Moon for meteoroid impact flashes in early 2006, resulting in the observation of over 330 impacts to date. The main objective of the MEO is to characterize the meteoroid environment for application to spacecraft engineering and operations. The Lunar Impact Monitoring Program provides information about the meteoroid flux in near-Earth space in a size range-tens of grams to a few kilograms-difficult to measure with statistical significance by other means. A bright impact flash detected by the program in March 2013 brought into focus the importance of determining the impact flash location. Prior to this time, the location was estimated to the nearest half-degree by visually comparing the impact imagery to maps of the Moon. Better accuracy was not needed because meteoroid flux calculations did not require high-accuracy impact locations. But such a bright event was thought to have produced a fresh crater detectable from lunar orbit by the NASA spacecraft Lunar Reconnaissance Orbiter (LRO). The idea of linking the observation of an impact flash with its crater was an appealing one, as it would validate NASA photometric calculations and crater scaling laws developed from hypervelocity gun testing. This idea was

  2. Blockade of TGF-β 1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    José Luis Miguel-Carrasco


    Full Text Available NADPH oxidases constitute a major source of superoxide anion (⋅O2 - in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1.

  3. Ski inhibits TGF-β/phospho-Smad3 signaling and accelerates hypertrophic differentiation in chondrocytes. (United States)

    Kim, Kyung-Ok; Sampson, Erik R; Maynard, Robert D; O'Keefe, Regis J; Chen, Di; Drissi, Hicham; Rosier, Randy N; Hilton, Matthew J; Zuscik, Michael J


    Since transforming growing factor-β (TGF-β)/Smad signaling inhibits chondrocyte maturation, endogenous negative regulators of TGF-β signaling are likely also important regulators of the chondrocyte differentiation process. One such negative regulator, Ski, is an oncoprotein that is known to inhibit TGF-β/Smad3 signaling via its interaction with phospho-Smad3 and recruitment of histone deacetylases (HDACs) to the DNA binding complex. Based on this, we hypothesized that Ski inhibits TGF-β signaling and accelerates maturation in chondrocytes via recruitment of HDACs to transcriptional complexes containing Smads. We tested this hypothesis in chick upper sternal chondrocytes (USCs), where gain and loss of Ski expression experiments were performed. Over-expression of Ski not only reversed the inhibitory effect of TGF-β on the expression of hypertrophic marker genes such as type X collagen (colX) and osteocalcin, it induced these genes basally as well. Conversely, knockdown of Ski by RNA interference led to a reduction of colX and osteocalcin expression under basal conditions. Furthermore, Ski blocked TGF-β induction of cyclinD1 and caused a basal up-regulation of Runx2, consistent with the observed acceleration of hypertrophy. Regarding mechanism, not only does Ski associate with phospho-Smad2 and 3, but its association with phospho-Smad3 is required for recruitment of HDAC4 and 5. Implicating this recruitment of HDACs in the phenotypic effects of Ski in chondrocytes, the HDAC inhibitor SAHA reversed the up-regulation of colX and osteocalcin in Ski over-expressing cells. These results suggest that inhibition of TGF-β signaling by Ski, which involves its association with phospho-Smad3 and recruitment of HDAC4 and 5, leads to accelerated chondrocyte differentiation. Copyright © 2012 Wiley Periodicals, Inc.

  4. Didecyldimethylammonium chloride induces pulmonary fibrosis in association with TGF-β signaling in mice. (United States)

    Ohnuma-Koyama, Aya; Yoshida, Toshinori; Tajima-Horiuchi, Haruka; Takahashi, Naofumi; Yamaguchi, Satoru; Ohtsuka, Ryoichi; Takeuchi-Kashimoto, Yukiko; Kuwahara, Maki; Takeda, Makio; Nakashima, Nobuaki; Harada, Takanori


    Didecyldimethylammonium chloride (DDAC) is a representative dialkyl-quaternary ammonium compound that is used as a disinfectant against several pathogens and is also used in commercial, industrial, and residential settings. We previously investigated toxicity on air way system following single instillation of DDAC to the lungs in mice, and found that DDAC causes pulmonary injury, which is associated with altered antioxidant antimicrobial responses; the inflammatory phase is accompanied or followed by fibrotic response. The present study was conducted to monitor transforming growth factor-β (TGF-β) signaling in pulmonary fibrosis induced by DDAC. Mice were intratracheally instilled with DDAC and sacrificed 1, 3, or 7 days after treatment to measure TGF-β signaling. In order to further evaluate TGF-β signaling, we treated isolated mouse lung fibroblasts with DDAC. Fibrotic foci were observed in the lungs on day 3, and were widely extended on day 7, with evidence of increased α-smooth muscle actin-positive mesenchymal cells and upregulation of Type I procollagen mRNA. Developing fibrotic foci were likely associated with increased expression of Tgf-β1 mRNA, in addition to decreased expression of Bone morphogenetic protein-7 mRNA. In fibrotic lung samples, the expression of phosphorylated SMAD2/3 was considerably higher than that of phosphorylated SMAD1/5. In isolated lung fibroblasts, the mRNA levels of Tgf-β1 were specifically increased by DDAC treatment, which prolonged phosphorylation of SMAD2/3. These effects were abolished by treatment with SD208 - a TGF-βRI kinase inhibitor. The results suggest that DDAC induces pulmonary fibrosis in association with TGF-β signaling. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. Endogenous sulfur dioxide alleviates collagen remodeling via inhibiting TGF-β/Smad pathway in vascular smooth muscle cells. (United States)

    Huang, Yaqian; Shen, Zhizhou; Chen, Qinghua; Huang, Pan; Zhang, Heng; Du, Shuxu; Geng, Bin; Zhang, Chunyu; Li, Kun; Tang, Chaoshu; Du, Junbao; Jin, Hongfang


    The study was designed to investigate the role of endogenous sulfur dioxide (SO2) in collagen remodeling and its mechanisms in vascular smooth muscle cells (VSMCs). Overexpression of endogenous SO2 synthase aspartate aminotransferase (AAT) 1 or 2 increased SO2 levels and inhibited collagen I and III expressions induced by transforming growth factor (TGF)-β1 in VSMCs. In contrast, AAT1 or AAT2 knockdown induced a severe collagen deposition in TGF-β1-treated VSMCs. Furthermore, AAT1 or AAT2 overexpression suppressed procollagen I and III mRNA, upregulated matrix metalloproteinase (MMP)-13 expression, downregulated tissue inhibitors of MMP-1 level, and vice versa. Mechanistically, AAT1 or AAT2 overexpression inhibited phosphorylation of type I TGF-β receptor (TβRI) and Smad2/3 in TGF-β1-stimulated VSMCs. Whereas SB431542, an inhibitor of TGF-β1/Smad signaling pathway, attenuated excessive collagen deposition induced by AAT knockdown. Most importantly, ectopically expressing AAT or exogenous addition of 100 μM SO2 blocked AAT deficiency-aggravated collagen accumulation in TGF-β1-stimulatd VSMCs, while no inhibition was observed at 100 μM ethyl pyruvate. These findings indicated that endogenous SO2 alleviated collagen remodeling by controlling TGF-β1/TβRI/Smad2/3-mediated modulation of collagen synthesis and degradation.

  6. A Unified Flash Flood Database across the United States (United States)

    Gourley, Jonathan J.; Hong, Yang; Flamig, Zachary L.; Arthur, Ami; Clark, Robert; Calianno, Martin; Ruin, Isabelle; Ortel, Terry W.; Wieczorek, Michael; Kirstetter, Pierre-Emmanuel; Clark, Edward; Krajewski, Witold F.


    Despite flash flooding being one of the most deadly and costly weather-related natural hazards worldwide, individual datasets to characterize them in the United States are hampered by limited documentation and can be difficult to access. This study is the first of its kind to assemble, reprocess, describe, and disseminate a georeferenced U.S. database providing a long-term, detailed characterization of flash flooding in terms of spatiotemporal behavior and specificity of impacts. The database is composed of three primary sources: 1) the entire archive of automated discharge observations from the U.S. Geological Survey that has been reprocessed to describe individual flooding events, 2) flash-flooding reports collected by the National Weather Service from 2006 to the present, and 3) witness reports obtained directly from the public in the Severe Hazards Analysis and Verification Experiment during the summers 2008–10. Each observational data source has limitations; a major asset of the unified flash flood database is its collation of relevant information from a variety of sources that is now readily available to the community in common formats. It is anticipated that this database will be used for many diverse purposes, such as evaluating tools to predict flash flooding, characterizing seasonal and regional trends, and improving understanding of dominant flood-producing processes. We envision the initiation of this community database effort will attract and encompass future datasets.

  7. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. (United States)

    Butovsky, Oleg; Jedrychowski, Mark P; Moore, Craig S; Cialic, Ron; Lanser, Amanda J; Gabriely, Galina; Koeglsperger, Thomas; Dake, Ben; Wu, Pauline M; Doykan, Camille E; Fanek, Zain; Liu, Liping; Chen, Zhuoxun; Rothstein, Jeffrey D; Ransohoff, Richard M; Gygi, Steven P; Antel, Jack P; Weiner, Howard L


    Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia. We found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia and that microglia were absent in the CNS of TGF-β1-deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling and provide insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.

  8. Hot Flashes amd Night Sweats (PDQ) (United States)

    ... controlled with estrogen replacement therapy. Hot flashes during natural or treatment-related menopause can be controlled with estrogen replacement ... been studied in the treatment of hot flashes. Treatments that help patients cope with stress and anxiety may help manage hot flashes. Treatments ...

  9. Detection of Malicious Flash Banner Advertisements

    Directory of Open Access Journals (Sweden)

    Kirill Alekseevich Samosadnyy


    Full Text Available The paper addresses the problem of detecting malicious flash advertisements. As a result, detection method based on dynamic analysis that modify flash application and execute it in Adobe Flash player is proposed and evaluated on synthetic and real world examples.

  10. Flash CS4: The Missing Manual

    CERN Document Server

    Grover, Chris


    Unlock the power of Flash and bring gorgeous animations to life onscreen. Flash CS4: The Missing Manual includes a complete primer on animation, a guided tour of the program's tools and capabilities, lots of new illustrations, and more details on working with video. Beginners will learn to use the software in no time, and experienced Flash designers will improve their skills.

  11. Jaan Toomik ajakirjas Flash Art

    Index Scriptorium Estoniae


    Kunstiajakirja "Flash Art" maikuu numbris Ando Keskküla artikkel, mis annab ülevaate J. Toomiku loomingust ja peatub pikemalt tema olulisematel töödel. 10. juunist J. Toomiku isiknäitus Londoni fotograafide galeriis. Eksponeeritud video "Uisutaja"

  12. Ingmar Muusikuse foto Flash Artis

    Index Scriptorium Estoniae


    Flash Arti 1999. a. oktoobrinumbris virtuaalse näituse rubriigis Ando Keskküla artikkel radikaalsemast eesti kunstist ja kunstielust postsotsialistlikul ajastul. Illustratsiooniks Liina Siibi fotokompositsioonid, Ingmar Muusikuse foto Raoul Kurvitza, Ene-Liis Semperi ja Kiwa Eesti Panga performance'ist

  13. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

    International Nuclear Information System (INIS)

    Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella


    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma

  14. TGF-β1(Transforming Growth Factor-β1) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity. (United States)

    Salvarani, Nicolò; Maguy, Ange; De Simone, Stefano A; Miragoli, Michele; Jousset, Florian; Rohr, Stephan


    TGF-β 1 (transforming growth factor-β 1 ) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β 1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β 1 , applied for 24 to 48 hours at clinically relevant concentrations (≤2.5 ng/mL), causes substantial membrane depolarization concomitant with a several-fold increase of transmembrane currents. Transcriptome analysis revealed TGF-β 1 -dependent changes in 29 of 63 ion channel/pump/connexin transcripts, indicating a pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not affecting cardiomyocyte membrane potentials and cardiomyocyte-cardiomyocyte gap junctional coupling, TGF-β 1 depolarized cardiomyocytes coupled to myofibroblasts by ≈20 mV and increased gap junctional coupling between myofibroblasts and cardiomyocytes >5-fold as reflected by elevated connexin 43 and consortin transcripts. TGF-β 1 -dependent cardiomyocyte depolarization resulted from electrotonic crosstalk with myofibroblasts as demonstrated by immediate normalization of cardiomyocyte electrophysiology after targeted disruption of coupled myofibroblasts and by cessation of ectopic activity of cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic activity, block of TGF-β 1 signaling completely abolished both arrhythmogenic conditions. TGF-β 1 profoundly alters the electrophysiological phenotype of cardiac myofibroblasts. Apart from possibly contributing to the control of cell function in general, the changes proved to be pivotal for proarrhythmic myofibroblast

  15. Expression of the nos gene and firefly flashing: a test of the nitric-oxide-mediated flash control model. (United States)

    Ohtsuki, Hajime; Yokoyama, Jun; Ohba, Nobuyoshi; Ohmiya, Yoshihiro; Kawata, Masakado


    Fireflies (Coleoptera: Lampyridae) emit various types of light that differ among species and populations of the same species. Their lights are assumed to be biological properties that play important ecological and evolutionary roles. Some species in the Lampyridae emit periodic luminescence, the patterns of which are characterized by species-specific intervals. In previous work, it was predicted that the nitric oxide (NO) regulates the oxygen supply required for the bioluminescence reaction of fireflies. Here, the expression of the NO synthase (NOS) mRNA in some fireflies was examined to verify the predictive model of nitric-oxide-mediated flash control in these insects. The expression of the nos gene in the lantern organ was observed not only in nocturnal flashing species but also in diurnal non-flashing species. It was shown that the expression levels of nos were higher in the lantern of Luciola cruciata (Motschulsky) larvae, which that emits continuous light, than in other body parts, although expression in the lantern of the adults, who flash periodically, was not high. Furthermore, there was no significant difference in expression levels among adults of Luciola cruciata characterized by different flashing intervals. The data do not support the model of an NO-mediated flash control mechanism, during which oxygen becomes available for the luciferin-luciferase reaction through NO-mediated inhibition of mitochondrial respiration. It is also indicated that flash patterns do not co-vary with NOS production. However, high nos expression in the larval lantern suggests that NO may play a role in producing continuous light by functioning as a neurotransmitter signal for bioluminescence. This is an open access paper. We use the Creative Commons Attribution 3.0 license that permits unrestricted use, provided that the paper is properly attributed.

  16. TBX3, a downstream target of TGF-β1, inhibits mesangial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wensing, Lislaine A. [Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901 (Brazil); Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (Brazil); Campos, Alexandre H., E-mail: [Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901 (Brazil)


    Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-β1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-β1 regulates TBX3 gene expression in MC. This gene encodes for two main isoforms, TBX3.1 and TBX3+2α. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14{sup ARF}-Mdm2-p53 pathway, while TBX3+2α role has not been defined. We demonstrated that TBX3 overexpression abrogated MC apoptosis induced by serum deprivation. Moreover, we observed an enhancement in TBX3 protein expression both in glomerular and tubular regions in the model of 5/6 nephrectomy, temporally related to increased expression of TGF-β1, type IV collagen and fibronectin. Our results indicate that TBX3 acts as an anti-apoptotic factor in MC in vitro and may be involved in the mechanism by which TGF-β1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies. - Highlights: • TBX3 isoforms are upregulated by TGF-b1 in mesangial cells. • TBX3 isoforms have different subcellular distribution profile in mesangial cells. • TBX3 isoforms exhibit antiapoptotic action in mesangial cells. • TBX3 protein is overexpressed in a model of nephropathy (5/6 nephrectomy)

  17. Multi-Level Bitmap Indexes for Flash Memory Storage

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kesheng; Madduri, Kamesh; Canon, Shane


    Due to their low access latency, high read speed, and power-efficient operation, flash memory storage devices are rapidly emerging as an attractive alternative to traditional magnetic storage devices. However, tests show that the most efficient indexing methods are not able to take advantage of the flash memory storage devices. In this paper, we present a set of multi-level bitmap indexes that can effectively take advantage of flash storage devices. These indexing methods use coarsely binned indexes to answer queries approximately, and then use finely binned indexes to refine the answers. Our new methods read significantly lower volumes of data at the expense of an increased disk access count, thus taking full advantage of the improved read speed and low access latency of flash devices. To demonstrate the advantage of these new indexes, we measure their performance on a number of storage systems using a standard data warehousing benchmark called the Set Query Benchmark. We observe that multi-level strategies on flash drives are up to 3 times faster than traditional indexing strategies on magnetic disk drives.

  18. Lightning Channels of Cloud-to-Ground Flashes Neutralizing Multiple Charge Regions Inside Winter Thunderclouds (United States)

    Akita, Manabu; Yoshida, Satoru; Nakamura, Yoshitaka; Morimoto, Takeshi; Ushio, Tomoo; Kawasaki, Zen-Ichiro; Wang, Daohong

    Lightning Research Group of Osaka University (LRG-OU) has been developing and improving the VHF broadband digital interferometer (DITF) for thunderstorm observations. It enables us to locate the impulsive VHF radiation sources caused by lightning discharges with extremely high resolutions. As a result of the VHF observations during the 2007-2008 winter season in the Japan Sea coastal area, cloud-to-ground (CG) flashes that neutralize multiple charge regions inside thunderclouds are visualized by the VHF broadband DITF. The first flash is the positive CG flash that neutralizes multiple positive charge regions in a flash. The second flash is the bipolar lightning flash that neutralizes both positive and negative charge inside thunderclouds. In the case of bipolar lightning flashes, some tens millisecond after the return strokes, the subsequent negative breakdowns initiate from the proximities of the initiation points of the preceding negative stepped leaders. It was also found that the altitudes of negative charge regions are lower than 2km. The bipolar lightning flashes observed in this campaign neutralize positive charge after lowering the negative charge to the ground.

  19. Foundation Flash CS4 for Designers

    CERN Document Server

    Green, Tom


    In this book, you'll learn:* How to create effective animations using the new Motion Editor and animation tools * How to use the new 3D features to animate objects in 3D space * Best-practice tips and techniques from some of the top Flash practitioners on the planet * How to create captioned video and full-screen video, and deploy HD video using Flash * Techniques for using the Flash UI components as well as XML documents to create stunning,interactive presentations If you're a Flash designer looking for a solid overview of Flash CS4, this book is for you. Through the use of solid and practica

  20. uFlip: Understanding Flash IO Patterns

    DEFF Research Database (Denmark)

    Bouganim, Luc; Jonsson, Bjørn; Bonnet, Philippe


    want to establish what kind of IOs should be favored (or avoided) when designing algorithms and architectures for flash-based systems. In this paper, we focus on flash IO patterns, that capture relevant distribution of IOs in time and space, and our goal is to quantify their performance. We define u......FLIP, a benchmark for measuring the response time of flash IO patterns. We also present a benchmarking methodology which takes into account the particular characteristics of flash devices. Finally, we present the results obtained by measuring eleven flash devices, and derive a set of design hints that should drive...

  1. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Damstrup, L; Rygaard, K; Spang-Thomsen, M


    A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...... lines express TGF beta-receptors and also produce TGF beta mRNAs....

  2. From Sulfide Flash Smelting to a Novel Flash Ironmaking Technology (United States)

    Sohn, Hong Yong

    A novel flash ironmaking technology is under development at the University of Utah under the support of U.S. Department of Energy (DOE) and American Iron and Steel Institute (AISI). The history of the development from the conception of the idea to the current status will be discussed. The flash ironmaking process produces iron directly from fine iron ore concentrates without requiring cokemaking and pelletization/sintering, which will enable the technology to significantly reduce energy consumption and carbon dioxide emissions compared with blast furnace ironmaking. Unlike other gas-based ironmaking processes, this technology will not suffer from the problems of solid sticking and fusion. Current work is focused on the method of supplying the energy required to maintain the necessary temperature, as an intermediate step to determine the scalability for larger, industrial-scale pilot trials.

  3. Extreme Lightning Flash Rates as an Early Indicator of Severe Storms (United States)

    Goodman, Steven J.; Arnold, James E. (Technical Monitor)


    Extreme lightning flash rates are proving to be an early indicator of intensifying storms capable of producing tornadoes, damaging winds and hail. Most of this lightning is in the cloud, where the naked eye can not see it. Recent global observations of thunderstorms from space indicate that giant electrical storms (supercells and convective complexes) with flash rates on the order of 1 flash per second are most common over the land masses of the America sub-tropics and equatorial Congo Basin. Within the United States, the average tornado warning lead time on a national basis is about 11 min. The real-time observation of extreme flash rates and the rapid increase in the in-cloud flash rate, signalling the intensification of the storm updraft, may provide as much as a 50% increase in severe storm warning lead time.

  4. Flash release - an alternative for releasing complex mems devices

    NARCIS (Netherlands)

    Deladi, S.; Svetovoy, Vitaly; Krijnen, Gijsbertus J.M.; Elwenspoek, Michael Curt


    A novel time-saving and cost-effective release technique has been developed and is described. The physical nature of the process is explained in combination with experimental observations. The results of the flash release process are compared with those of freeze-drying and supercritical CO2

  5. Flash release an alternative for releasing complex MEMS devices

    NARCIS (Netherlands)

    Deladi, S.; Krijnen, Gijsbertus J.M.; Elwenspoek, Michael Curt


    A novel time-saving and cost-effective release technique has been developed and is described. The physical nature of the process is explained in combination with experimental observations. The results of the flash release process are compared with those of freeze-drying and supercritical CO2

  6. Spurious dispersion effects at FLASH

    International Nuclear Information System (INIS)

    Prat, Eduard


    The performance of the Free-Electron Laser (FEL) process imposes stringent demands on the transverse trajectory and size of the electron beam. Since transverse dispersion changes off-energy particle trajectories and increases the effective beam size, dispersion must be controlled. This thesis treats the concept of dispersion in linacs, and analyses the impact of dispersion on the electron beam and on the FEL process. It presents generation mechanisms for spurious dispersion, quantifying its importance for FLASH (Free-electron Laser in Hamburg) and the XFEL (European X-ray Free-Electron Laser). A method for measuring and correcting dispersion and its implementation in FLASH is described. Experiments of dispersion e ects on the transverse beam quality and on the FEL performance are presented. (orig.)

  7. Flash x-ray cinematography

    International Nuclear Information System (INIS)

    Stein, W.E.


    Experiments intended to provide an overview of the potential capabilities and limitations of flash x-ray cinematography as a diagnostic technique for a Fast Reactor Safety Test Facility are described. The results provide estimates of the x-ray pulse intensity required to obtain adequate radiographs of an array of fuel pins in a typical reactor configuration. An estimate of the upper limit on the pulse duration imposed by the reactor background radiation was also determined. X-ray cinematography has been demonstrated at a repetition rate limited only by the recording equipment on hand at the time of these measurements. These preliminary results indicate that flash x-ray cinematography of the motion of fuel in a Fast Reactor Test Facility is technically feasible

  8. Spurious dispersion effects at FLASH

    Energy Technology Data Exchange (ETDEWEB)

    Prat, Eduard


    The performance of the Free-Electron Laser (FEL) process imposes stringent demands on the transverse trajectory and size of the electron beam. Since transverse dispersion changes off-energy particle trajectories and increases the effective beam size, dispersion must be controlled. This thesis treats the concept of dispersion in linacs, and analyses the impact of dispersion on the electron beam and on the FEL process. It presents generation mechanisms for spurious dispersion, quantifying its importance for FLASH (Free-electron Laser in Hamburg) and the XFEL (European X-ray Free-Electron Laser). A method for measuring and correcting dispersion and its implementation in FLASH is described. Experiments of dispersion e ects on the transverse beam quality and on the FEL performance are presented. (orig.)

  9. Nanocrystalline magnetic materials obtained by flash annealing

    Directory of Open Access Journals (Sweden)

    Murakami R.K.


    Full Text Available The aim of the present work was to produce enhanced-remanence nanocrystalline magnetic material by crystallizing amorphous or partially amorphous Pr4.5Fe77B18.5 alloys by the flash annealing process, also known as the dc-Joule heating process, and to determine the optimal conditions for obtaining good magnetic coupling between the magnetic phases present in this material. Ribbons of Pr4.5Fe77B18.5 were produced by melt spinning and then annealed for 10-30 s at temperatures 500 - 640 °C by passing current through the sample to develop the enhanced-remanence nanocrystalline magnetic material. These materials were studied by X-ray diffraction, differential thermal analysis and magnetic measurements. Coercivity increases of up to 15% were systematically observed in relation to furnace-annealed material. Two different samples were carefully examined: (i a sample annealed at 600 °C which showed the highest coercive field Hc and remanence ratio Mr/Ms and (ii a sample annealed at 520 °C which showed phase separation in the second quadrant demagnetization curve. Our results are in agreement with other studies which show that flash annealing improves the magnetic properties of some amorphous ferromagnetic ribbons.

  10. Hot flashes and sleep in women. (United States)

    Moe, Karen E


    Sleep disturbances during menopause are often attributed to nocturnal hot flashes and 'sweats' associated with changing hormone patterns. This paper is a comprehensive critical review of the research on the relationship between sleep disturbance and hot flashes in women. Numerous studies have found a relationship between self-reported hot flashes and sleep complaints. However, hot flash studies using objective sleep assessment techniques such as polysomnography, actigraphy, or quantitative analysis of the sleep EEG are surprisingly scarce and have yielded somewhat mixed results. Much of this limited evidence suggests that hot flashes are associated with objectively identified sleep disruption in at least some women. At least some of the negative data may be due to methodological issues such as reliance upon problematic self-reports of nocturnal hot flashes and a lack of concurrent measures of hot flashes and sleep. The recent development of a reliable and non-intrusive method for objectively identifying hot flashes during the night should help address the need for substantial additional research in this area. Several areas of clinical relevance are described, including the effects of discontinuing combined hormone therapy (estrogen plus progesterone) or estrogen-only therapy, the possibility of hot flashes continuing for many years after menopause, and the link between hot flashes and depression.

  11. Effects of TGF-β1 on mineralization mediated by rat calvaria-derived osteogenic cells. (United States)

    Donato, Tatiani A G; Martinez, Elizabeth F; Arana-Chavez, Victor E


    In this study, we have analyzed the viability and cell growth, as well as, the mineralization of extracellular matrix (ECM) by alizarin red and von Kossa staining of calvaria-derived osteogenic cultures, treated with TGF-β1 alone or associated with Dex comparing with acid ascorbic (AA) + β-glicerophosphate (βGP) (positive mineralization control). The expression of the noncollagenous proteins bone sialoprotein (BSP), osteopontin (OPN) and fibronectin (FN) were evaluated by indirect immunofluorescence. In addition, the main ultrastructural morphological findings were assessed by transmission electron microscopy. Osteogenic cells were isolated of calvaria bone from newborn (2-day-old) Wistar rats were treated with TGF-β1 alone or with dexamethasone for 7, 10, and 14 days. As positive mineralization control, the cells were supplemented only with AA+ βGP. As negative control, the cells were cultured with basal medium (α-MEM + 10%FBS + 1%gentamicin). The treatment with TGF-β1, even when combined with Dex, decreased the viability and cell growth when compared with the positive control. Osteoblastic cell cultures were positive to alizarin red and von Kossa stainings after AA + βGP and Dex alone treatments. Positive immunoreaction was found for BSP, OPN and FN in all studied treatments. Otherwise, when the cell cultures were supplemented with TGF-β1 and TGF-β1 + Dex, no mineralization was observed in any of the studied periods. These present findings suggest that TGF-β1, in the studied in vitro doses, inhibits the proliferation and differentiation of osteoblastic cells by impairment of nodule formation. © 2016 Wiley Periodicals, Inc.

  12. The role of transforming growth factor-beta (TGF-beta during ovarian follicular development in sheep

    Directory of Open Access Journals (Sweden)

    Quirke Laurel D


    Full Text Available Abstract Background Recently, several members of the transforming growth factor-beta (TGF-beta superfamily have been shown to be essential for regulating the growth and differentiation of ovarian follicles and thus fertility. Methods Ovaries of neonatal and adult sheep were examined for expression of the TGF-betas 1–3 and their receptors (RI and RII by in situ hybridization using ovine cDNAs. The effects of TGF-beta 1 and 2 on proliferation and differentiation of ovine granulosa cells in vitro were also studied. Results The expression patterns of TGF-beta 1 and 2 were similar in that both mRNAs were first observed in thecal cells of type 3 (small pre-antral follicles. Expression of both mRNAs continued to be observed in the theca of larger follicles and was also present in cells within the stroma and associated with the vascular system of the ovary. There was no evidence for expression in granulosa cells or oocytes. Expression of TGF-beta 3 mRNA was limited to cells associated with the vascular system within the ovary. TGFbetaRI mRNA was observed in oocytes from the type 1 (primordial to type 5 (antral stages of follicular growth and granulosa and thecal cells expressed this mRNA at the type 3 (small pre-antral and subsequent stages of development. The TGFbetaRI signal was also observed in the ovarian stroma and vascular cells. In ovarian follicles, mRNA encoding TGFbetaRII was restricted to thecal cells of type 3 (small pre-antral and larger follicles. In addition, expression was also observed in some cells of the surface epithelium and in some stromal cells. In granulosa cells cultured for 6 days, both TGF-beta 1 and 2 decreased, in a dose dependent manner, both the amount of DNA and concentration of progesterone. Conclusion In summary, mRNA encoding both TGF-beta 1 and 2 were synthesized by ovarian theca, stroma and cells of the vascular system whereas TGF-beta 3 mRNA was synthesized by vascular cells. Luteinizing granulosa cells also

  13. Effects of electromagnetic radiation on morphology and TGF-β3 expression in mouse testicular tissue. (United States)

    Luo, Yaning; Wang, Xiaowu; Chen, Yongbin; Xu, Shenglong; Ding, Guirong; Shi, Changhong


    Exposure to electromagnetic pulses in certain doses may lead to increase in the permeability of the blood testes barrier (BTB) in mice, which in turn affects spermatogenesis, penetration and spermiation. TGF-β3 is a key molecule involved in BTB permeability via regulation of tight junction proteins, and it participates in regulating spermatogenesis, synthesis of steroids and production of the extracellular matrix in testicular tissue. Therefore, it is hypothesized that TGF-β3 plays important roles in electromagnetic pulse (EMP)-induced changes in BTB permeability. In the present study, we carried out whole-body irradiation on mice using EMP of different intensities. No obvious pathological changes or significant increase in apoptosis was detected in testicular tissues after exposure to 100 and 200 pulses of intensity 200kV/m; however, with 400 pulses we observed the degeneration and shrinkage of testicular tissues along with a significant increase in apoptotic rate. Moreover, in the 100- and 200-EMP groups, a non-significant increase in TGF-β3 mRNA and protein expression was observed, whereas in the 400-EMP group a significant increase was observed (P<0.05). These results indicate that increase in the apoptotic rate of testicular tissues and increase in TGF-β3 expression may be one of the mechanisms for EMP-induced increase in BTB permeability in mice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1 in hippocampus: effect of a TGF-β1 oligo-antisense

    Directory of Open Access Journals (Sweden)

    Lara Hernán E


    Full Text Available Abstract Background Corticosterone reduction produced by adrenalectomy (ADX induces apoptosis in dentate gyrus (DG of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor β1 (TGF-β1. Thus, we have investigated whether TGF-β1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-β1 with an antisense oligonucleotide (ASO administered intracerebrally in corticosterone depleted rats. Results It was observed an increase of apoptosis in DG, 2 and 5 days after ADX, in agreement with a reduction of corticosterone levels. However, the effect of ADX on the number of apoptotic positive cells in DG was decreased 5 days after the lesion. In CA1–CA3 regions, the effect was only observed 2 days after ADX. TGF-β1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-β1 ASO via an osmotic mini pump increased apoptosis levels in CA and DG regions 5 days after ADX as well as sham-operated control animals. No significant effect was observed following a scrambled-oligodeoxynucleotide treatment. Conclusion The changes in both the pattern and the magnitude of apoptotic-cell morphology observed 2 and 5 days after ADX suggest that, as a consequence of the reduction of corticosteroids, some trophic mechanisms restricting cell death to a particular time window are elicited. Sustained intracerebral administration of TGF-β1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-β1 plays an anti-apoptotic role in vivo in hippocampus.

  15. Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis. (United States)

    Zhou, Jia; Zhao, Yixuan; Simonenko, Vera; Xu, John J; Liu, Kai; Wang, Deling; Shi, Jingli; Zhong, Tianyi; Zhang, Lixia; Zeng, Lun; Huang, Bin; Tang, Shenggao; Lu, Alan Y; Mixson, A James; Sun, Yangbai; Lu, Patrick Y; Li, Qingfeng


    Excessive skin scars due to elective operations or trauma represent a challenging clinical problem. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing. Over expression of TGF-β1 and COX-2 play key regulatory roles of the aberrant fibrogenic responses and proinflammatory mediators. When we silenced TGF-β1 and COX-2 expression simultaneously in primary human fibroblasts, a marked increase in the apoptotic cell population occurred in contrast to those only treated with either TGF-β1 or COX-2 siRNA alone. Furthermore, using human hypertrophic scar and skin graft implant models in mice, we observed significant size reductions of the implanted tissues following intra-scar administration of TGF-β1/COX-2 specific siRNA combination packaged with Histidine Lysine Polymer (HKP). Gene expression analyses of those treated tissues revealed silencing of the target gene along with down regulations of pro-fibrotic factors such as α-SMA, hydroxyproline acid, Collagen 1 and Collagen 3. Using TUNEL assay detection, we found that the human fibroblasts in the implanted tissues treated with the TGF-β1/COX-2 siRNAs combination exhibited significant apoptotic activity. Therefore we conclude that a synergistic effect of the TGF-β1/COX-2siRNAs combination contributed to the size reductions of the hypertrophic scar implants, through activation of fibroblast apoptosis and re-balancing between scar tissue deposition and degradation.

  16. TGF-β1 serum concentrations and receptor expressions in the lens capsular of dogs with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Stephan Neumann


    Full Text Available Tissue fibrosis as complication of Diabetes mellitus is known in humans. Because TGF-β1induces fibrosis and is elevated in humans suffering from Diabetes mellitus we measured this growth factor in serum of dogs with Diabetes mellitus and compared it with healthy dogs and those with fibrotic diseases. Further we measured the expression of TGF-β1receptor on lens capsule to investigate possible association between Diabetes mellitus and cataract associated alterations. TGF-β1 was measured in serum of 12 dogs with Diabetes mellitus, 20 healthy controls and 12 dogs with fibrotic diseases. Dogs with Diabetes mellitus and fibrotic diseases have significantly increased TGF-β1 serum concentrations compared to healthy controls. Some dogs with Diabetes mellitus showed increased expression of TGF-β1 receptor in lens capsule. Based on our observations we can conclude that TGF-β1 elevation in dogs with Diabetes mellitus may induces complications of the disease and may participates on lens alteration.

  17. TGF-β1 serum concentrations and receptor expressions in the lens capsular of dogs with diabetes mellitus. (United States)

    Neumann, Stephan; Linek, Jens; Loesenbeck, Gerhard; Schüttler, Julia; Gaedke, Sonja


    Tissue fibrosis as complication of diabetes mellitus is known in humans. Because TGF-β1induces fibrosis and is elevated in humans suffering from diabetes mellitus we measured this growth factor in serum of dogs with diabetes mellitus and compared it with healthy dogs and those with fibrotic diseases. Further we measured the expression of TGF-β1receptor on lens capsule to investigate possible association between diabetes mellitus and cataract associated alterations. TGF-β1 was measured in serum of 12 dogs with diabetes mellitus, 20 healthy controls and 12 dogs with fibrotic diseases. Dogs with diabetes mellitus and fibrotic diseases have significantly increased TGF-β1 serum concentrations compared to healthy controls. Some dogs with diabetes mellitus showed increased expression of TGF-β1 receptor in lens capsule. Based on our observations we can conclude that TGF-β1 elevation in dogs with diabetes mellitus may induces complications of the disease and may participates on lens alteration.

  18. Calibration Improvements for the Hubble Space Telescope Advanced Camera for Surveys Wide Field Channel: Post-Flash and Commanding Overheads (United States)

    Miles, Nathan; Grogin, Norman; ACS Instrument Team


    The Advanced Camera for Surveys (ACS) Wide Field Channel (WFC) post-flash calibration reference file currently suffers from an improper dark subtraction resulting in a variety of image artifacts. In order to cure these artifacts, a new technique has been implemented where the total sum of the exposure time and flash duration for each image is held constant. The flash duration and exposure time are varied to produce two sets of images that are differenced to produce the new post-flash reference file. The first set all have long exposure times and short flash durations, while the second set has exactly the opposite. Next, using the newly generated post-flash reference file we derive the commanding overheads associated with any ACS/WFC post-flashed observation. Whenever ACS/WFC receives commands it takes a finite amount of time for the instrument to execute them, when commands are executed while the instrument is in ACCUM mode additional dark current builds up and is added to the exposure. This additional dark current is not accounted for in the EXPTIME header keyword and therefore is not removed during the DARKCORR processing step in CALACS. By leveraging the stability of hot-stable pixels and the new post-flash reference file, we analyze 1,273 post-flashed darks and extract the commanding overheads associated with ACS/WFC post-flashed data.

  19. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. (United States)

    Freeman, Ellen W; Sammel, Mary D; Sanders, Richard J


    This study aims to estimate the risk of hot flashes relative to natural menopause and to evaluate the associations of hormone levels, behavioral variables, and demographic variables with the risk of hot flashes after menopause. We performed annual assessment of 255 women who were premenopausal at baseline and reached natural menopause within 16 years of follow-up. The prevalence of moderate/severe hot flashes increased in each premenopausal year, reaching a peak of 46% in the first 2 years after the final menstrual period (FMP). Hot flashes decreased slowly after menopause and did not return to premenopausal levels until 9 years after the FMP. The mean (SD) duration of moderate/severe hot flashes after the FMP was 4.6 (2.9) years (for any hot flashes, 4.9 [3.1] y). One third of women at 10 years or more after menopause continued to experience moderate/severe hot flashes. African-American women (obese and nonobese) and obese white women had significantly greater risks of hot flashes compared with nonobese white women (interaction, P = 0.01). In multivariable analysis, increasing follicle-stimulating hormone levels before the FMP (P menopause; more than one third of women observed for 10 years or more after menopause have moderate/severe hot flashes. Continuation of hot flashes for more than 5 years after menopause underscores the importance of determining individual risks/benefits when selecting hormone or nonhormone therapy for menopausal symptoms.

  20. Construction and performance of large flash chambers

    International Nuclear Information System (INIS)

    Taylor, F.E.; Bogert, D.; Fisk, R.; Stutte, L.; Walker, J.K.; Wolfson, J.; Abolins, M.; Ernwein, J.; Owen, D.; Lyons, T.


    The construction and performance of 12' x 12' flash chambers used in a 340 ton neutrino detector under construction at Fermilab is described. The flash chambers supply digital information with a spatial resolution of 0.2'', and are used to finely sample the shower development of the reaction products of neutrino interactions. The flash chambers are easy and inexpensive to build and are electronically read out

  1. A Durable Flash Memory Search Tree


    Clay III, James; Wortman, Kevin


    We consider the task of optimizing the B-tree data structure, used extensively in operating systems and databases, for sustainable usage on multi-level flash memory. Empirical evidence shows that this new flash memory tree, or FM Tree, extends the operational lifespan of each block of flash memory by a factor of roughly 27 to 70 times, while still supporting logarithmic-time search tree operations.

  2. Nuclear receptor TLX inhibits TGF-β signaling in glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Erik; Zhai, Qiwei [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Zeng, Zhao-jun [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Molecular Biology Research Center, School of Life Sciences, Central South University, 110, Xiangya Road, Changsha, Hunan 410078 (China); Yoshida, Takeshi [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Funa, Keiko, E-mail: [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden)


    TLX (also called NR2E1) is an orphan nuclear receptor that maintains stemness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-β (TGF-β) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-β has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-β signaling we wanted to find out if there is any interaction between TLX and TGF-β in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-β signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-β receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-β receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-β target genes. The interaction between TLX and TGF-β may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells. - Highlights: • TLX knockdown enhances TGF-β dependent Smad signaling in glioblastoma cells • TLX knockdown increases the protein level of TGF-β receptor II. • TLX stabilizes and retains Smurf1 in the cytoplasm. • TLX enhances Smurf1-dependent ubiquitination and degradation of TGF-β receptor II.

  3. Flash CS5 The Missing Manual

    CERN Document Server

    Grover, Chris


    Once you know how to use Flash, you can create everything from simple animations to high-end desktop applications, but it's a complex tool that can be difficult to master on your own-unless you have this Missing Manual. This book will help you learn all you need to know about Flash CS5 to create animations that bring your ideas to life. Learn animation basics. Find everything you need to know to get started with FlashMaster the Flash tools. Learn the animation and effects toolset, with clear explanations and hands-on examplesUse 3D effects. Rotate and put objects in motion in three dimensions

  4. Search Engine Optimization for Flash Best Practices for Using Flash on the Web

    CERN Document Server

    Perkins, Todd


    Search Engine Optimization for Flash dispels the myth that Flash-based websites won't show up in a web search by demonstrating exactly what you can do to make your site fully searchable -- no matter how much Flash it contains. You'll learn best practices for using HTML, CSS and JavaScript, as well as SWFObject, for building sites with Flash that will stand tall in search rankings.

  5. Investigation of Current Spike Phenomena During Heavy Ion Irradiation of NAND Flash Memories (United States)

    Oldham, Timothy R.; Berg, Melanie; Friendlich, Mark; Wilcox, Ted; Seidleck, Christina; LaBel, Kenneth A.; Irom, Farokh; Buchner, Steven P.; McMorrow, Dale; Mavis, David G.; hide


    A series of heavy ion and laser irradiations were performed to investigate previously reported current spikes in flash memories. High current events were observed, however, none matches the previously reported spikes. Plausible mechanisms are discussed.

  6. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information

  7. Measurement of hot flashes by sternal skin conductance and subjective hot flash report in Puebla, Mexico. (United States)

    Sievert, Lynnette Leidy; Freedman, Robert R; Garcia, Jesus Zarain; Foster, Jennifer W; del Carmen Romano Soriano, Ma; Longcope, Christopher; Franz, Charlene


    To measure hot flashes by sternal skin conductance in an urban Mexican population and to determine variables associated with hot flash reporting and measurement. From June 1999 to August 2000, 67 perimenopausal women aged 40 to 65 years participated in interviews, anthropometric measures, and a 2-h recording of sternal skin conductance. Changes in sweating were used to demonstrate the presence/absence of a hot flash. During the test, women were asked to report if they experienced a hot flash. During the study period, 10 women reported and demonstrated every hot flash, 24 women never reported or demonstrated a hot flash, 7 demonstrated hot flashes but did not report any of them, 7 reported hot flashes but did not demonstrate any of them, and 19 showed a mixture of responses. Women who demonstrated hot flashes by sternal skin conductance were measured in a warmer room, had more years of education, consumed more eggs as a child, recalled a heavier weight at age 18, and had a lower body mass index at interview compared with women who did not demonstrate hot flashes by sternal skin conductance. Women who subjectively reported hot flashes were measured in a warmer room, were more likely to be postmenopausal, reported more frequent consumption of coffee, and spent fewer months breast-feeding their last child compared with women who did not report the experience of hot flashes during the testing period. Room temperature explained part of the variation between women who did and did not demonstrate hot flashes via sternal skin conductance, between women who did and did not report the experience of hot flashes, and between women who did and did not demonstrate concordance in objective and subjective measures. In addition to room temperature, coffee intake, months spent breast-feeding the last child, and recalled weight at age 18 were important variables predicting hot flash experience.

  8. Rh-flash acquisition card

    International Nuclear Information System (INIS)

    Bourrion, O.


    The rh-flash card main purpose is to convert and store the image of the analog data present at input into an output buffer, namely in a given timing window besides a stop signal (like a digital oscilloscope). It is conceived in VME format 1U wide with an additional connector. Novelty of this card is its ability to sample at a high frequency, due to flash coders, and this at a high repetition rate. To do that the card allows the storage of the data considered 'useful' and that is done by storing only the data exceeding a certain threshold. This can be useful for instance for viewing peaks in a spectrum, and obtaining their relative location. The goal is to stock and process the data sampled before and after the arrival of a stop signal (what entails a storage depth). A threshold is defined and any peak exceeding its level will really be stored in the output buffer which is readable through the VME bus. The peak values will be stored as well as m preceding and n subsequent values (both programmable). Obviously, if the threshold is zero the system of data processing is off and all data will be stored. The document is structured on six sections titled: 1. Description; 2. Specifications; 3. Explaining the design of channels; 4. Explaining the shared part of the design; 5. Addressing (→ user guide); 6. Software precautions. (author)

  9. Terrestrial Gamma Flashes at Ground Level - TETRA-II Instrumentation (United States)

    Pleshinger, D. J.; Adams, C.; Al-Nussirat, S.; Bai, S.; Banadaki, Y.; Bitzer, P. M.; Cherry, M. L.; Hoffmann, J.; Khosravi, E.; Legault, M.; Orang, M.; Rodriguez, R.; Smith, D.; Trepanier, J. C.; Sunda-Meya, A.; Zimmer, N.


    The TGF and Energetic Thunderstorm Rooftop Array (TETRA-II) consists of an array of BGO scintillators to detect bursts of gamma rays from thunderstorms. TETRA-II will have approximately an order of magnitude greater sensitivity for individual flashes than TETRA-I, an original array of NaI scintillators at Louisiana State University that detected 37 millisecond-scale bursts of gamma rays from 2010-2015. The BGO scintillators increase the energy range of particles detected to 10 MeV and are placed in 20 detectors boxes, each with 1180 cm3 of BGO, at 4 separate locations: the campus of Louisiana State University in Baton Rouge, Louisiana; the campus of the University of Puerto Rico at Utuado, Puerto Rico; the Centro Nacional de Metrologia de Panama (CENAMEP) in Panama City, Panama; and the Severe Weather Institute and Radar & Lightning Laboratories in Huntsville, Alabama. The data are read out with 12 microsecond resolution by National Instruments PCIe 6351 high speed data acquisition cards, with timestamps determined from a 20 MHz clock and a GPS board recording a pulse per second. Details of the array and its instrumentation, along with an overview of initial results, will be presented.

  10. Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.

  11. TGF-β Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation

    Directory of Open Access Journals (Sweden)

    Maryline Abrial


    Full Text Available The pharyngeal arch arteries (PAAs are transient embryonic blood vessels that mature into critical segments of the aortic arch and its branches. Although defects in PAA development cause life-threating congenital cardiovascular defects, the molecular mechanisms that orchestrate PAA morphogenesis remain unclear. Through small-molecule screening in zebrafish, we identified TGF-β signaling as indispensable for PAA development. Specifically, chemical inhibition of the TGF-β type I receptor ALK5 impairs PAA development because nkx2.5+ PAA progenitor cells fail to differentiate into tie1+ angioblasts. Consistent with this observation, we documented a burst of ALK5-mediated Smad3 phosphorylation within PAA progenitors that foreshadows angioblast emergence. Remarkably, premature induction of TGF-β receptor activity stimulates precocious angioblast differentiation, thereby demonstrating the sufficiency of this pathway for initiating the PAA progenitor to angioblast transition. More broadly, these data uncover TGF-β as a rare signaling pathway that is necessary and sufficient for angioblast lineage commitment.

  12. On multiphase negative flash for ideal solutions

    DEFF Research Database (Denmark)

    Yan, Wei; Stenby, Erling Halfdan


    There is a recent interest to solve multiphase negative flash problems where the phase amounts can be negative for normal positive feed composition. Solving such a negative flash problem using successive substitution needs an inner loop for phase distribution calculation at constant fugacity...

  13. FLASH Interface; a GUI for managing runtime parameters in FLASH simulations (United States)

    Walker, Christopher; Tzeferacos, Petros; Weide, Klaus; Lamb, Donald; Flocke, Norbert; Feister, Scott


    We present FLASH Interface, a novel graphical user interface (GUI) for managing runtime parameters in simulations performed with the FLASH code. FLASH Interface supports full text search of available parameters; provides descriptions of each parameter's role and function; allows for the filtering of parameters based on categories; performs input validation; and maintains all comments and non-parameter information already present in existing parameter files. The GUI can be used to edit existing parameter files or generate new ones. FLASH Interface is open source and was implemented with the Electron framework, making it available on Mac OSX, Windows, and Linux operating systems. The new interface lowers the entry barrier for new FLASH users and provides an easy-to-use tool for experienced FLASH simulators. U.S. Department of Energy (DOE), NNSA ASC/Alliances Center for Astrophysical Thermonuclear Flashes, U.S. DOE NNSA ASC through the Argonne Institute for Computing in Science, U.S. National Science Foundation.

  14. Measuring TGF-β Ligand Dynamics in Culture Medium. (United States)

    Feng, Zipei; Zi, Zhike; Liu, Xuedong


    TGF-β plays an important role in a myriad of cell activities including differentiation, proliferation, and growth arrest. These effects are influenced by the concentration of TGF-β in the surrounding milieu, which is interpreted by mammalian cells and subsequently translated into meaningful signals that guide their proliferation, survival, or death. To predict cellular responses to TGF-ß signaling based on molecular mechanisms, it is important to consider how cells respond to different ligand doses and how variations in ligand exposure impact Smad signaling dynamics and subsequent gene expression. Here we describe methods to measure TGF-β concentration in the environment and approaches to perturb cellular TGF-β exposure to gain a quantitative understanding of signaling dynamics of this pathway.

  15. TGF location, flux and fluence distribution with off-axis angle derived from FERMI data and WWLLN locations (United States)

    Connell, Paul


    The FERMI science support centre has published an online catalogue of 3356 TGFs, along with a subset of 1049 TGFs with a WWLLN temporal association. We have used these tables to create scatter plots and the angular distribution of TGF angles in the FERMI nadir FOV - originally to see what the ASIM/MXGS gamma-ray imager could expect to observe in its FOV. We have also used photon counts from the two FERMI BGO detectors to derive an estimate of TGF flux distribution and fluence with nadir angle. One interesting result is the observation of TGFs out to 50 degrees off-axis, but even more interesting is an angular flux distribution which seems to indicate that a TGF has either a very wide beam angle or that TGFs are narrow beams whose axis has a very wide angular distribution from the earth radial. Whether this indicates TGFs originate by acceleration in macro scale electric fields in storm clouds, or in the micro scale electric fields in lightning leaders, is not clear but the results do call for a more detailed analysis taking FERMI orientation into account. We have not seen any publication of this TGF off-axis angle analysis and show our results for the interest of the TGF research community.

  16. [Nikola Tesla: flashes of inspiration]. (United States)

    Villarejo-Galende, Albero; Herrero-San Martín, Alejandro


    Nikola Tesla (1856-1943) was one of the greatest inventors in history and a key player in the revolution that led to the large-scale use of electricity. He also made important contributions to such diverse fields as x-rays, remote control, radio, the theory of consciousness or electromagnetism. In his honour, the international unit of magnetic induction was named after him. Yet, his fame is scarce in comparison with that of other inventors of the time, such as Edison, with whom he had several heated arguments. He was a rather odd, reserved person who lived for his inventions, the ideas for which came to him in moments of inspiration. In his autobiography he relates these flashes with a number of neuropsychiatric manifestations, which can be seen to include migraine auras, synaesthesiae, obsessions and compulsions.

  17. Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Koni Ivanova


    Full Text Available BACKGROUND: Papillary thyroid carcinoma (PTC accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it. AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment. METHODS: For this retrospective study we investigated 69 patients immunohistochemistry with antibodies against TGF-β, TGF – β-RII, SMAD4, SMAD7, CD68+ macrophages. RESULTS: Patients with low infiltration with CD68+ cells in tumour stroma has significantly shorter survival (median of 129.267 months compared to those with high CD68+ cells infiltration (p = 0.034. From the analysis of CD68+ cells in tumour border and tumour stroma correlated with expression of TGF-β1 / SMAD proteins, we observed that the positive expression of TGF-β1 in tumour cytoplasm, significantly correlated with increased number of CD68+ cells in tumour border (X2 = 5,945; р = 0.015. CONCLUSION: TGF-β enhances motility and stimulates recruitment of monocytes, macrophages and other immune cells while directly inhibiting their anti-tumour effector functions.

  18. Abnormal Expressions of Age, RAGE, TGF- b1 and TGF- b1 Receptor in Colonic Wall Contributed to STZ-Induced Diabetic Colon Remodeling

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Gregersen, Hans


    glycation end product (AGE) and AGE receptor (RAGE) were up-regulated in the diabetic colon wall (2). However, it lacks data in relation to the association between AGE, RAGE, transforming growth factor- b1 (TGF-b1) and TGFb1 receptor expressions with colon morphological and biomechanical remodeling...... glucose level was measured. The parameters of morphometric and biomechanical properties of colonic segments were obtained from diabetic (DM) and normal (Con) rats. The expressions of AGE, RAGE, TGF- b1 and TGF- b1 receptor were detected in different layers of the colon by immunohistochemistry. In order...... to determine the expressions of AGE, RAGE, TGF- b1 and TGF- b1 receptor in association with other parameters, and to see interrelation among AGE, RAGE, TGF- b1 and TGF- b1 receptor expressions, the multiple linear regression analysis was done. Results: The expressions of AGE, RAGE, TGF-b1 and TGF- b1 receptor...

  19. Non Volatile Flash Memory Radiation Tests (United States)

    Irom, Farokh; Nguyen, Duc N.; Allen, Greg


    Commercial flash memory industry has experienced a fast growth in the recent years, because of their wide spread usage in cell phones, mp3 players and digital cameras. On the other hand, there has been increased interest in the use of high density commercial nonvolatile flash memories in space because of ever increasing data requirements and strict power requirements. Because of flash memories complex structure; they cannot be treated as just simple memories in regards to testing and analysis. It becomes quite challenging to determine how they will respond in radiation environments.

  20. Flash memory in embedded Java programs

    DEFF Research Database (Denmark)

    Korsholm, Stephan Erbs

    This paper introduces a Java execution environment with the capability for storing constant heap data in Flash, thus saving valuable RAM. The extension is motivated by the structure of three industrial applications which demonstrate the need for storing constant data in Flash on small embedded...... devices. The paper introduces the concept of host initialization of constant data to prepare a Flash image of constant data that can be kept outside the heap during runtime. The concept is implemented in an interpreter based Java execution environment....

  1. Flash memory in embedded Java programs

    DEFF Research Database (Denmark)

    Korsholm, Stephan Erbs


    This paper introduces a Java execution environment with the capability for storing constant heap data in Flash, thus saving valuable RAM. The extension is motivated by the structure of three industrial applications which demonstrate the need for storing constant data in Flash on small embedded...... devices. The paper introduces the concept of host initialization of constant data to prepare a Flash image of constant data that can be kept outside the heap during runtime. The concept is implemented in an interpreter based Java execution environment....

  2. Impact Flash Physics: Modeling and Comparisons With Experimental Results (United States)

    Rainey, E.; Stickle, A. M.; Ernst, C. M.; Schultz, P. H.; Mehta, N. L.; Brown, R. C.; Swaminathan, P. K.; Michaelis, C. H.; Erlandson, R. E.


    Hypervelocity impacts frequently generate an observable "flash" of light with two components: a short-duration spike due to emissions from vaporized material, and a long-duration peak due to thermal emissions from expanding hot debris. The intensity and duration of these peaks depend on the impact velocity, angle, and the target and projectile mass and composition. Thus remote sensing measurements of planetary impact flashes have the potential to constrain the properties of impacting meteors and improve our understanding of impact flux and cratering processes. Interpreting impact flash measurements requires a thorough understanding of how flash characteristics correlate with impact conditions. Because planetary-scale impacts cannot be replicated in the laboratory, numerical simulations are needed to provide this insight for the solar system. Computational hydrocodes can produce detailed simulations of the impact process, but they lack the radiation physics required to model the optical flash. The Johns Hopkins University Applied Physics Laboratory (APL) developed a model to calculate the optical signature from the hot debris cloud produced by an impact. While the phenomenology of the optical signature is understood, the details required to accurately model it are complicated by uncertainties in material and optical properties and the simplifications required to numerically model radiation from large-scale impacts. Comparisons with laboratory impact experiments allow us to validate our approach and to draw insight regarding processes that occur at all scales in impact events, such as melt generation. We used Sandia National Lab's CTH shock physics hydrocode along with the optical signature model developed at APL to compare with a series of laboratory experiments conducted at the NASA Ames Vertical Gun Range. The experiments used Pyrex projectiles to impact pumice powder targets with velocities ranging from 1 to 6 km/s at angles of 30 and 90 degrees with respect to

  3. Flash Extraction and Physicochemical Characterization of Oil from Elaeagnus mollis Diels Seeds. (United States)

    Kan, Lina; Wang, Lin; Ding, Qingzhen; Wu, Yanwen; Ouyang, Jie


    A flash extraction method was used to isolate Elaeagnus mollis oil (EMO). The optimal extraction parameters, sample/solvent ratio and extraction temperature, were determined to be 1:10 (g/mL) and 40°C, respectively. Especially, the extraction yield reached 49.30% when the extraction time was as short as 2 min. No obvious difference was observed in fatty acid composition, iodine value, saponification number, total phenolic content and tocopherol content between flash-extracted EMO and Soxhlet-extracted EMO, but their physicochemical values were lower than those of cold-pressed EMO. Cold-pressed EMO had higher oxidation stability, DPPH (1-diphenyl-2-picrylhydrazyl) and hydroxyl radical-scavenging activities than flash-extracted EMO and Soxlet extracted EMO. The flash extraction is demonstrated to be an alternative, efficient method for the vegetable oil production.

  4. uFLIP: Understanding the Energy Consumption of Flash Devices

    DEFF Research Database (Denmark)

    Bjørling, Matias; Bonnet, Philippe; Bouganim, Luc


    consumption (low power consumption in idle mode, average Watt consumption from the data sheets). Second, when measured at a sufficiently fine granularity, the energy consumption of a given device might complement the performance characteristics derived from its response time profile. Indeed, background work......Understanding the energy consumption of flash devices is important for two reasons. First, energy is emerging as a key metric for data management systems. It is thus important to understand how we can reason about the energy consumption of flash devices beyond their approximate aggregate...... which is not directly observable with a response time profile appears clearly when energy is used as a metric. In this paper, we discuss the results from the {uFLIP} benchmark applied to four different {SSD} devices using both response time and energy as metric....

  5. Flash Point: Evaluation, Experimentation and Estimation (United States)

    Rowley, J. R.; Freeman, D. K.; Rowley, R. L.; Oscarson, J. L.; Giles, N. F.; Wilding, W. V.


    The flash point is an important indicator of the flammability of a chemical. For safety purposes, many data compilations report the lowest value and not the most likely. This practice, combined with improper documentation and poor data storage methods, has resulted in compilations filled with fire-hazard data that are inconsistent with related properties and between members of homologous chemical series. In this study, the flash points reported in the DIPPR® 801 database and more than 1,400 other literature values were critically reviewed based on measurement method, inter-property relations, and trends in chemical series. New measurements for seven compounds illustrate the differences between experimental flash points and data commonly found in fire-hazard compilations. With a critically reviewed set of experimental data, published predictive methods for the flash point were evaluated for accuracy.

  6. Highly Sensitive Flash LADAR Camera, Phase I (United States)

    National Aeronautics and Space Administration — A highly sensitive 640 x 480-element flash LADAR camera will be developed that is capable of 100-Hz rates with better than 5-cm range precision. The design is based...

  7. MR colonography with fecal tagging: comparison between 2D turbo FLASH and 3D FLASH sequences

    International Nuclear Information System (INIS)

    Papanikolaou, Nickolas; Grammatikakis, John; Maris, Thomas; Prassopoulos, Panos; Gourtsoyiannis, Nicholas; Lauenstein, Thomas


    The objective of this study was to compare inversion recovery turbo 2D fast low-angle shot (FLASH) and 3D FLASH sequences for fecal-tagged MR colonography studies. Fifteen consecutive patients with indications for colonoscopy underwent MR colonography with fecal tagging. An inversion recovery turbo-FLASH sequence was applied and compared in terms of artifacts presence, efficiency for masking residual stool, and colonic wall conspicuity with a fat-saturated 3D FLASH sequence. Both sequences were acquired following administration of paramagnetic contrast agent. Contrast-to-noise ratio and relative contrast between colonic wall and lumen were calculated and compared for both sequences. Turbo 2D FLASH provided fewer artifacts, higher efficiency for masking the residual stool, and colonic wall conspicuity equivalent to 3D FLASH. An inversion time of 10 ms provided homogeneously low signal intensity of the colonic lumen. Contrast to noise between colonic wall and lumen was significantly higher in the 3D FLASH images, whereas differences in relative contrast were not statistically significant. An optimized inversion-recovery 2D turbo-FLASH sequence provides better fecal tagging results and should be added to the 3D FLASH sequence when designing dark-lumen MR colonography examination protocols. (orig.)

  8. Two types of flash drought over China and their connections with sub-seasonal to seasonal soil moisture drought (United States)

    Wang, L.; Yuan, X.; Xie, Z.


    Flash drought has been receiving attention recently due to its rapid development and vast damage on crops in the growing season. Accompanied with heatwave and rainfall deficit, the soil moisture decreased rapidly in a short time and may lead to the failure of root water uptake and large-scale crops wither. There are two types of flash droughts according to the causes (Mo and Lettenmaier, 2016), i.e., heat wave flash drought and rainfall deficit flash drought. Here, based on pentad-mean surface air temperature and precipitation observations from over two thousand meteorological stations as well as soil moisture and ET estimations from three global reanalysis products, the characteristics and evolution of the two types of flash droughts over China are being explored. Heat wave flash drought is more likely to occur in humid and semi-humid areas, such as southern China, while rainfall deficit flash drought is more likely to occur in northern China. Unlike the traditional drought that persists for a few months to decades, the mean durations of both types of flash droughts are very short. We use monthly mean soil moisture to calculate sub-seasonal to seasonal (S2S) soil moisture drought, and compare its characteristics and preferred conditions such as the large-scale atmospheric circulation and oceanic anomaly for both types of flash droughts. The percentages of flash drought in different periods of S2S drought are also being explored to see the potential relationship between flash drought and S2S drought over different regions.

  9. Hydrodynamic simulations of the core helium flash (United States)

    Mocák, Miroslav; Müller, Ewald; Weiss, Achim; Kifonidis, Konstantinos


    We desribe and discuss hydrodynamic simulations of the core helium flash using an initial model of a 1.25 M⊙ star with a metallicity of 0.02 near at its peak. Past research concerned with the dynamics of the core helium flash is inconclusive. Its results range from a confirmation of the standard picture, where the star remains in hydrostatic equilibrium during the flash (Deupree 1996), to a disruption or a significant mass loss of the star (Edwards 1969; Cole & Deupree 1980). However, the most recent multidimensional hydrodynamic study (Dearborn et al. 2006) suggests a quiescent behavior of the core helium flash and seems to rule out an explosive scenario. Here we present partial results of a new comprehensive study of the core helium flash, which seem to confirm this qualitative behavior and give a better insight into operation of the convection zone powered by helium burning during the flash. The hydrodynamic evolution is followed on a computational grid in spherical coordinates using our new version of the multi-dimensional hydrodynamic code HERAKLES, which is based on a direct Eulerian implementation of the piecewise parabolic method.

  10. Effect of rat ovary irradiation or OVX on the expression of COLI and TGF-β1 mRNA in the rat bone

    International Nuclear Information System (INIS)

    Gao Yanhong; Gao Jianjun; Jin Weifang; Wang Hongfu


    To observe the effects of exposure of rat ovary to radiation or OVX on the expression of TGF-β 1 and COLI in the rat bone. The mRNA levels of TGF-β 1 and COLI in rat tibiae were measured with RT-PCR after the rat ovaries were irradiated by 50 Gy of 137 Cs γ-rays or OVX. For both the radiation group and the OVX group, the COLI mRNA level in the rat bone increased, whereas the TGF-β 1 decreased. Irradiation of ovary and OVX affect the expression of COLI and TGF-β 1 mRNA in bone probably in a similar way which is related to estrogen decrease

  11. L-thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1. (United States)

    Dekkers, Bart G J; Naeimi, Saeideh; Bos, I Sophie T; Menzen, Mark H; Halayko, Andrew J; Hashjin, Goudarz Sadeghi; Meurs, Herman


    Hypothyroidism may reduce, whereas hyperthyroidism may aggravate, asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway smooth muscle (ASM) mass, may be involved. To address this hypothesis, we investigated the effects of triiodothyronine (T3) and l-thyroxine (T4) in the absence and presence of the profibrotic transforming growth factor (TGF)-β1 on human ASM cell phenotype switching. T3 (1-100 nM) and T4 (1-100 nM) did not affect basal ASM proliferation. However, when combined with TGF-β1 (2 ng/ml), T4 synergistically increased the proliferative response, whereas only a minor effect was observed for T3. In line with a switch from a contractile to a proliferative ASM phenotype, T4 reduced the TGF-β1-induced contractile protein expression by ∼50%. Cotreatment with T3 reduced TGF-β1-induced contractile protein expression by ∼25%. The synergistic increase in proliferation was almost fully inhibited by the integrin αvβ3 antagonist tetrac (100 nM), whereas no significant effects of the thyroid receptor antagonist 1-850 (3 μM) were observed. Inhibition of MEK1/2, downstream of the integrin αvβ3, also inhibited the T4- and TGF-β1-induced proliferative responses. Collectively, the results indicate that T4, and to a lesser extent T3, promotes a proliferative ASM phenotype in the presence of TGF-β1, which is predominantly mediated by the membrane-bound T4 receptor αvβ3. These results indicate that thyroid hormones may enhance ASM remodeling in asthma, which could be of relevance for hyperthyroid patients with this disease. Copyright © 2015 the American Physiological Society.

  12. A terrestrial gamma-ray flash viewed from below in the eyewall of Hurricane Patricia (United States)

    Smith, D. M.; Bowers, G. S.; Cummer, S.; Heckman, S.; Holzworth, R.


    The Airborne Detector for Energetic Lightning Emissions (ADELE) flew aboard the NOAA WP-3D Orion aircraft "Miss Piggy" on its trip through the eyewall of Hurricane Patricia on 23 October 2015 at 1732UT, just a few hours after its peak intensity and a few hours before it started weakening abruptly prior to landfall. Patricia on this day was "the strongest hurricane on record in the eastern North Pacific and North Atlantic basins" (National Hurricane Center Tropical Cyclone Report, 4 February 2016). ADELE observed a TGF while penetrating the eyewall on the inbound pass at an altitude of 2.6km. The radio sferic was observed by the Earth Networks Total Lightning Network and by Duke University VLF sensors. It was positive polarity and closely resembled sferics associated with TGFs seen from this region by the Fermi Gamma-ray Space Telescope's Gamma-ray Burst Monitor. ADELE observed a hard gamma-ray energy spectrum consistent with downward-beamed bremsstrahlung, either from the reverse-moving positrons associated with an upward relativistic runaway electron avalanche (RREA) or from the avalanche electrons in a downward RREA. The polarity of the sferic and its resemblance to ordinary TGFs, combined with the very low aircraft altitude, suggests that we have observed an upward TGF from below for the first time, and can confirm the existence of the backward positron beam predicted by TGF simulations. We will present lower limits on the TGF's intrinsic luminosity as a function of its production altitude.

  13. The role of TGF-β in polycystic ovary syndrome. (United States)

    Raja-Khan, Nazia; Urbanek, Margrit; Rodgers, Raymond J; Legro, Richard S


    Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligoanovulation and hyperandrogenism and associated with insulin resistance, type 2 diabetes, and cardiovascular risk. In recent years, genetic studies have linked PCOS to a dinucleotide marker D19S884 in the fibrillin 3 gene. Fibrillins make up the major component of microfibrils in the extracellular matrix (ECM) and interact with molecules in the ECM to regulate transforming growth factor β (TGF-β) signaling. Therefore, variations in fibrillin 3 and subsequent dysregulation of TGF-β may contribute to the pathogenesis of PCOS. Here, we review the evidence from genetic studies supporting the role of TGF-β in PCOS and describe how TGF-β dysregulation may contribute to (1) the fetal origins of PCOS, (2) reproductive abnormalities in PCOS, and (3) cardiovascular and metabolic abnormalities in PCOS.

  14. TGF-β signaling alters the pattern of liver tumorigenesis induced by Pten inactivation (United States)

    Morris, Shelli M.; Carter, Kelly T.; Baek, Ji Yeon; Koszarek, Amanda; Yeh, Matthew M.; Knoblaugh, Sue E.; Grady, William M.


    Hepatocarcinogenesis results from the accumulation of genetic and epigenetic changes in liver cells. A common mechanism through which these alterations induce liver cancer is by deregulating signaling pathways. A number of signaling pathways, including the PI3K/PTEN/AKT and transforming growth factor β (TGF-β) pathways have been implicated in normal liver development as well as in cancer formation. In this study, we assessed the effect of the TGF-β signaling pathway on liver tumors induced by Pten (phosphatase and tensin homologue) loss. Inactivation of only the TGF-β receptor type II, Tgfbr2, in the mouse liver (Tgfbr2LKO) had no overt phenotype, while inactivation of Pten alone (PtenLKO), resulted in the formation of both hepatocellular carcinomas (HCC) and cholangiocarcinomas (CC). Interestingly, deletion of both Pten and Tgfbr2 (PtenLKO;Tgfbr2LKO) in the mouse liver resulted in a dramatic shift in tumor type to predominantly CC. Assessment of the PI3K/PTEN/AKT pathway revealed increased phosphorylation of AKT and GSK-3β in both the PtenLKO and PtenLKO;Tgfbr2LKO mice, suggesting that this pathway is constitutively active regardless of the status of the TGF-β signaling pathway. However, phosphorylation of p70 S6 kinase was observed in the liver of all three phenotypes (Tgfbr2LKO, PtenLKO, PtenLKO;Tgfbr2LKO) indicating that the loss of Tgfbr2 and/or Pten leads to an increase in this signaling pathway. Analysis of markers of liver progenitor/stem cells revealed that the loss of TGF-β signaling resulted in increased expression of c-Kit and CD133. Furthermore, in addition to increased c-Kit and CD133, Scf and EpCam expression were also increased in the double knock-out mice. These results suggest that the alteration in tumor types between the PtenLKO mice and PtenLKO;Tgfbr2LKO mice is secondary to the altered regulation of stem cell features induced by the loss of TGF-β signaling. PMID:25132272

  15. Ground to Cloud Lightning Flash Currents and Electric Fields: Interaction with Aircraft and Production of Ionosphere Sprites

    Directory of Open Access Journals (Sweden)

    P. R. P. Hoole


    Full Text Available This paper presents for the first time a case for the importance of ground to cloud (upward leader lightning flash parameters for safety testing of direct aircraft-lightning interaction and protection of wind turbines, as well as the importance of radiated electric fields for indirect lightning-aircraft interaction and generation of electric discharges called sprites and halos in the ionosphere. By using an electric circuit model of the transverse magnetic waves along the return stroke channel, electric currents at ground level as well as cloud level are determined for both the cloud to ground lightning flash and the ground to cloud lightning flash. We show that when an aircraft triggers lightning, the electric currents will be much more severe in current magnitude, rate of rise of currents, and frequency spectrum than otherwise and are more severe than the parameters observed for the usual and well monitored (and measured cloud to ground (downward leader flashes. The rate of rise of currents and the frequency spectrum of the ground to cloud lightning flash are also given here. The electric fields radiated by the lightning flashes that would appear in the ionosphere are presented for both the earth flash and the ground to cloud flash.

  16. Bio-oil from Flash Pyrolysis of Agricultural Residues

    DEFF Research Database (Denmark)

    Ibrahim, Norazana

    This thesis describes the production of bio-oils from flash pyrolysis of agricultural residues, using a pyrolysis centrifugal reactor (PCR). By thermal degradation of agricultural residues in the PCR, a liquid oil, char and non-condensable gases are produced. The yield of each fraction is influen......This thesis describes the production of bio-oils from flash pyrolysis of agricultural residues, using a pyrolysis centrifugal reactor (PCR). By thermal degradation of agricultural residues in the PCR, a liquid oil, char and non-condensable gases are produced. The yield of each fraction...... lower temperatures increase the yield of char. Liquid oil, however increases with temperature up to certain point and thereafter it decreases at still higher temperature due to secondary cracking of the primary products. The presence of moisture in the feed stock may also influences the pyrolysis...... process. The influence of reaction temperature and the moisture content on the flash pyrolysis product yield has been reported in Paper I (Chapter 2). It was observed that the presence of moisture in the wheat straw with different moisture levels of 1.5 wt. %, 6.2 wt. % and 15.0 wt. % have shown...

  17. Turbulent spots and scalar flashes in pipe transition (United States)

    Adrian, Ronald; Wu, Xiaohua; Moin, Parviz


    Recent study (Wu et al., PNAS, 1509451112, 2015) demonstrated the feasibility and accuracy of direct computation of the Osborne Reynolds' pipe transition experiment without the unphysical axially periodic boundary condition. Here we use this approach to address three questions: (1) What are the dynamics of turbulent spot generation in pipe transition? (2) How is the succession of scalar flashes, as observed and sketched by Osborne Reynolds, created? (3) What happens to the succession of flashes further downstream? In this study, the inlet disturbance is of radial-mode type imposed through a narrow, three-degree numerical wedge; and the simulation Reynolds number is 6500. Numerical dye is introduced at the inlet plane locally very close to the pipe axis, similar to the needle injection by O. Reynolds. Inception of infant turbulent spots occurs when normal, forward inclined hairpin packets form near the walls from the debris of the inlet perturbations. However, the young and mature turbulent spots consist almost exclusively of reverse, backward leaning hairpin vortices. Scalar flashes appear successively downstream and persist well into the fully-developed turbulent region. Their creation mechanism is addressed. RJA gratefully acknowledges support of the National Science Foundation with NSF Award CBET-0933848.

  18. Energetic and exergetic Improvement of geothermal single flash cycle

    Directory of Open Access Journals (Sweden)

    Navid Nazari


    Full Text Available This paper presents a detailed analysis of a new method for improving energetic and exergetic efficiencies of single flash cycle. The thermodynamic process of the new method consists of extracting a fraction of hot wellhead geothermal brine for the purpose of superheating saturated steam entering the turbine. Computer programming scripts were developed and optimized based on mathematical proposed models for the different components of the systems. The operating parameters such as separator temperature, geofluid wellhead enthalpy and geothermal source temperature are varied to investigate their effects on both net power output and turbine exhaust quality of the systems. Also, full exergy assessment was performed for the new design. The results of separator temperature optimization revealed that specific net power output of the new design can be boosted up to 8% and turbine exhaust quality can be diminished up to 50% as compared to common single flash cycle. In addition, for wells with higher discharge enthalpy, superheating process improve specific net power output even up to 10%. Finally, it was observed that the overall system exergy efficiency was approximately raised 3%. Article History: Received January 5th 2016; Received in revised form June 25th 2016; Accepted July 3rd 2016; Available online How to Cite This Article: Nazari, N. and Porkhial, S. (2016. Energetic and Exergetic Improvement of Geothermal Single Flash Cycle. Int. Journal of Renewable Energy Development, 5(2,129-138. 

  19. Flash Vacuum Pyrolysis: Techniques and Reactions. (United States)

    Wentrup, Curt


    Flash vacuum pyrolysis (FVP) had its beginnings in the 1940s and 1950s, mainly through mass spectrometric detection of pyrolytically formed free radicals. In the 1960s many organic chemists started performing FVP experiments with the purpose of isolating new and interesting compounds and understanding pyrolysis processes. Meanwhile, many different types of apparatus and techniques have been developed, and it is the purpose of this review to present the most important methods as well as a survey of typical reactions and observations that can be achieved with the various techniques. This includes preparative FVP, chemical trapping reactions, matrix isolation, and low temperature spectroscopy of reactive intermediates and unstable molecules, the use of online mass, photoelectron, microwave, and millimeterwave spectroscopies, gas-phase laser pyrolysis, pulsed pyrolysis with supersonic jet expansion, very low pressure pyrolysis for kinetic investigations, solution-spray and falling-solid FVP for involatile compounds, and pyrolysis over solid supports and reagents. Moreover, the combination of FVP with matrix isolation and photochemistry is a powerful tool for investigations of reaction mechanism. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Numerical Experiments for Nuclear Flashes toward Superbursts in an Accreting Neutron Star

    Directory of Open Access Journals (Sweden)

    Masa-aki Hashimoto


    Full Text Available We show that the superburst would be originated from thermonuclear burning ignited by accumulated fuels in the deep layers compared to normal X-ray bursts. Two cases are investigated for models related to superbursts by following thermal evolution of a realistic neutron star: helium flash and carbon flash accompanied with many normal bursts. For a helium flash, the burst shows the long duration when the accretion rate is low compared with the observation. The flash could become a superburst if the burning develops to the deflagration and/or detonation. For a carbon flash accompanied with many normal bursts, after successive 2786 normal bursts during 1.81 × 109 s, the temperature reaches the deflagration temperature. This is due to the produced carbon which amount reaches to ≈0.1 in the mass fraction. The flash will develop to dynamical phenomena of the deflagration and/or detonation, which may lead to a superburst.

  1. Flashing in riser and its effect on flow stability in natural circulation system

    International Nuclear Information System (INIS)

    Wu Xinxin; Wu Shaorong; Jiang Shengyao; Zhou Lei; Tong Yunxian; Zhang Youjie; Han Bing


    The experimental investigation was performed in the full scale thermo-hydraulic simulation test loop (HRTL-5) for the 5 MW-Heating Reactor at Institute of Nuclear Energy Technology, Tsinghua University. Under different pressures the flashing in riser of natural circulation system and its effect on flow stability were studied by the method of visual observation in synchronism with data recording. The results show that the lower the system pressure, the more obvious the flashing in the riser, and the stronger the effect on flow stability in the natural circulation system. Under very low pressure even if subcooling at the exit of heated test section is relatively higher, the flashing riser will appears due to gradual energy accumulation by strong thermodynamic non-equilibrium process. Consequently, a long period flow oscillation is stimulated in the system, and the time of period can be up to 40 s. When the system pressure reaches to 1.5 MPa, the flashing in riser is vanished. Based on these experiments, the mechanism of flashing in riser and the flow instability stimulated by the flashing are basically explained

  2. The Roles of TGF-Beta and TGF-Beta Signaling Receptors in Breast Carcinogenesis. (United States)


    cell lines ( Kimchi et al., 1988;matrix formation (Massagud, 1990; Moses et al., 1990; Roberts Arteaga et al., 1988) have been shown to have low TGF3V. Since sensitivity to growth factors is dependent on the al., 1986; Shipley et al., 1986), retinoblastoma cells ( Kimchi et capacity of the...J. (1989) J. Natl. Cancer Inst. 81, 1182-1185 Kimchi , A., Wang, X-F., Weinberg, R. A., Cheifetz, S., and Massagu6, J. (1988) Wang, X. F., Lin, H. Y

  3. FPGA Flash Memory High Speed Data Acquisition (United States)

    Gonzalez, April


    The purpose of this research is to design and implement a VHDL ONFI Controller module for a Modular Instrumentation System. The goal of the Modular Instrumentation System will be to have a low power device that will store data and send the data at a low speed to a processor. The benefit of such a system will give an advantage over other purchased binary IP due to the capability of allowing NASA to re-use and modify the memory controller module. To accomplish the performance criteria of a low power system, an in house auxiliary board (Flash/ADC board), FPGA development kit, debug board, and modular instrumentation board will be jointly used for the data acquisition. The Flash/ADC board contains four, 1 MSPS, input channel signals and an Open NAND Flash memory module with an analog to digital converter. The ADC, data bits, and control line signals from the board are sent to an Microsemi/Actel FPGA development kit for VHDL programming of the flash memory WRITE, READ, READ STATUS, ERASE, and RESET operation waveforms using Libero software. The debug board will be used for verification of the analog input signal and be able to communicate via serial interface with the module instrumentation. The scope of the new controller module was to find and develop an ONFI controller with the debug board layout designed and completed for manufacture. Successful flash memory operation waveform test routines were completed, simulated, and tested to work on the FPGA board. Through connection of the Flash/ADC board with the FPGA, it was found that the device specifications were not being meet with Vdd reaching half of its voltage. Further testing showed that it was the manufactured Flash/ADC board that contained a misalignment with the ONFI memory module traces. The errors proved to be too great to fix in the time limit set for the project.

  4. The structure of the TGF-beta latency associated peptide region determines the ability of the proprotein convertase furin to cleave TGF-betas. (United States)

    Kusakabe, Makoto; Cheong, Pak-Leng; Nikfar, Reza; McLennan, Ian S; Koishi, Kyoko


    The TGF-beta family members are generated as latent pre-pro-polypeptides. The active mature peptides are cleaved from the latent forms by cellular proteases. TGF-beta 1, for instance, is predominantly processed by a substilisin-like proprotein convertase, furin. TGF-beta 2 has a consensus cleavage site for furin and therefore has been presumed to be cleaved by furin. However, TGF-beta 2 is often secreted as the latent form, which appears to be inconsistent with its postulated sensitivity to furin. We report here that both the regular (short) form of TGF-beta2 and its spliced variant with an additional exon (long form) are insensitive to furin. NIH 3T3 and CHO cells were transfected with expression vectors containing the short or long form of TGF-beta 2 or a chimeric TGF-beta consisting of the TGF-beta1 LAP region, the TGF-beta 2 cleavage site and the TGF-beta 2 mature peptide. The constructs included a c-myc epitope tag in the N-terminal region of the mature peptide. The TGF-betas produced by the transfected cells were analyzed with Western blots and immunocytochemistry. The intracellular proteins harvested from these cells were incubated with furin. Furin only inefficiently cleaved both the long and short forms of TGF-beta 2, but efficiently processed the chimeric TGF-beta. This indicates that the insensitivity of both forms of TGF-beta 2 to furin is a consequence of the tertiary structure of their LAP regions rather than their cleavage site. This differential processing of TGF-beta1 and -beta 2 may be part of the mechanism that generates isoform-specific functions of the TGF-betas.

  5. Transient Gamma-Ray Emissions Related to Thunderstorms: Coordinated RHESSI and CORONAS-F Observations (United States)

    Kudela, K.; Bučík, R.; Kuznetsov, S. N.; Lopez, L. I.; Smith, D. M.


    Transient gamma-ray emissions from the Earth's atmosphere with duration of a few milliseconds and associated with lightning discharges were discovered by the BATSE/CGRO instrument in 1994, and new features have been recently reported from the RHESSI measurements. These so-called terrestrial gamma-ray flashes (TGFs) are thought to be bremsstrahlung photons from energetic electron beams above the thunderstorms. The SOlar Neutron and Gamma rays (SONG) experiment aboard low altitude (~ 500 km) polar orbiting (~ 83°) CORONAS-F satellite, designed to detection of neutral particles from the Sun, provides 1-s measurements of hard X-rays/gamma rays in range of 30 keV to 200 MeV. The SONG consists of large effective area (≤ 314 cm2) omnidirectional scintillator well suited for detection fluxes coming from the various directions from the Earth's atmosphere. We have identified cases when the RHESSI spacecraft, observing gamma-ray flashes at an altitude of about 600 km, and CORONAS-F passed through the same regions in period April 2002 - January 2005. The simultaneous gamma-ray measurements will be reviewed and discussed. Recent analysis of the SONG data have revealed observations of the enhanced hard X-ray emissions (above 50 times the background value) above geomagnetically conjugate regions to the lightning. The issue of freshly accelerated TGF electrons from the lightning itself, contributing to the precipitated radiation-belt electrons will be discussed too.

  6. TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways.

    Directory of Open Access Journals (Sweden)

    Fátima Guerrero

    Full Text Available BACKGROUND: Transforming growth factor-β (TGF-β is a key cytokine during differentiation of mesenchymal stem cells (MSC into vascular smooth muscle cells (VSMC. High phosphate induces a phenotypic transformation of vascular smooth muscle cells (VSMC into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMC differentiation of MSC in presence or not of high phosphate. RESULTS: Our results showed that TGF-β induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22α, myocardin, and smooth muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/β-catenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-β to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-β pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition of both Wnt/β-catenin activators CHIR98014 and lithium chloride enhanced the effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase activity. CONCLUSIONS: Full VSMC differentiation induced by TGF-β may not be achieved when extracellular phosphate levels are high. Moreover, TGF-β prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/β-catenin pathway.

  7. TGF-β1 and granulocyte elastase in the evaluation of activity of inflammatory bowel disease. A pilot study

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska


    Full Text Available Introduction: The aim was to assess the usefulness of TGF-β1 and elastase in the evaluation of activity of ulcerative colitis (UC and Crohn’s disease (CD.Material and Methods: 32 patients diagnosed with UC, 31 with CD and 30 healthy volunteers were enrolled in this study. Diagnosis of the disease was confirmed by videocolonoscopy and histopathological evaluation of intestinal biopsies. Disease activity was assessed by use of the Mayo Scoring System for Assessment of Ulcerative Colitis Activity in UC patients and by CDAI in CD patients. hsCRP was determined by the immunonephelometric method, TGF-β1 and elastase plasma concentration by ELISA. The results of the study were analyzed using Statistica and R statistical language.Results: In UC a positive correlation between disease activity and platelet level, hsCRP and TGF-β1 concentration was noted. Elastase concentration in UC patients was significantly higher than in CD, but there was no correlation with the activity of the disease. In CD patients we observed a positive correlation between disease activity and leukocytes, platelet levels and elastase concentration, and a very low correlation with hsCRP and TGF-β1.Discussion: Determination of TGF-β1 can be used for evaluation of inflammatory activity in UC and it is connected with elevated concentrations of CRP and platelets. To a lower extent TGF-β1 can also be used for evaluation of inflammatory activity in CD. Examination of elastase concentration may be useful in the assessment of CD activity. Plasma elastase concentration may be helpful in UC and CD differentiation. The preliminary results of this investigation seem promising; nevertheless, more studies are necessary.

  8. Detection of an Impact Flash Candidate on the Moon with an Educational Telescope System

    Directory of Open Access Journals (Sweden)

    Eunsol Kim


    Full Text Available At the suggestion of the NASA Meteoroid Environment Office (NASA/MEO, which promotes lunar impact monitoring worldwide during NASA’s Lunar Atmosphere and Dust Environment Explorer (LADEE mission period (launched Sept. 2013, we set up a video observation system for lunar impact flashes using a 16-inch educational telescope at Chungnam National University. From Oct. 2013 through Apr. 2014, we recorded 80 hours of video observation of the unilluminated part of the crescent moon in the evening hours. We found a plausible candidate impact flash on Feb. 3, 2014 at selenographic longitude 2.1° and latitude 25.4°. The flash lasted for 0.2 s and the light curve was asymmetric with a slow decrease after a peak brightness of 8.7 ± 0.3 mag. Based on a star-like distribution of pixel brightness and asymmetric light curve, we conclude that the observed flash was due to a meteoroid impact on the lunar surface. Since unequivocal detection of an impact flash requires simultaneous observation from at least two sites, we strongly recommend that other institutes and universities in Korea set up similar inexpensive monitoring systems involving educational or amateur telescopes, and that they collaborate in the near future.

  9. Ski prevents TGF-β-induced EMT and cell invasion by repressing SMAD-dependent signaling in non-small cell lung cancer. (United States)

    Yang, Haiping; Zhan, Lei; Yang, Tianjie; Wang, Longqiang; Li, Chang; Zhao, Jun; Lei, Zhe; Li, Xiangdong; Zhang, Hong-Tao


    Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis, which confers cancer cells with increased motility and invasiveness, and EMT is characterized by loss of epithelial marker E-cadherin and gain of mesenchymal marker N-cadherin. Transforming growth factor-β (TGF-β) signaling is a crucial inducer of EMT in various types of cancer. Ski is an important negative regulator of TGF-β signaling, which interacts with SMADs to repress TGF-β signaling activity. Although there is accumulating evidence that Ski functions as a promoter or suppressor in human types of cancer, the molecular mechanisms by which Ski affects TGF-β-induced EMT and invasion in non-small cell lung cancer (NSCLC) are not largely elucidated. In the present study, we investigated the mechanistic role of Ski in NSCLC metastasis. Ski was significantly reduced in metastatic NSCLC cells or tissues when compared with non-metastatic NSCLC cells or tissues. Moreover, following TGF-β stimulation Ski-silenced A549 cells had more significant features of EMT and a higher invasive activity when compared with A549 cells overexpressing Ski. Mechanistically, Ski-silenced and overexpressed A549 cells showed an increase and a reduction in the SMAD3 phosphorylation level, respectively. This was supported by plasminogen activator inhibitor-1 (PAI-1) promoter activity obtained in Ski-silenced and overexpressed A549 cells. However, after treatment of SIS3 (inhibitor of SMAD3 phosphorylation) followed by TGF-β1 stimulation, we did not observe any effect of Ski on TGF-β-induced EMT, and invasion in Ski-silenced and overexpressed A549 cells. In conclusion, our findings suggest that Ski represses TGF-β-induced EMT and invasion by inhibiting SMAD-dependent signaling in NSCLC.

  10. Expression of podoplanin and TGF-beta in glandular odontogenic cyst and its comparison with developmental and inflammatory odontogenic cystic lesions. (United States)

    Alaeddini, Mojgan; Eshghyar, Nosratollah; Etemad-Moghadam, Shahroo


    The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions. A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05). Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs. Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Plasminogen Activator Inhibitor 1 Promotes Immunosuppression in Human Non-Small Cell Lung Cancers by Enhancing TGF-Β1 Expression in Macrophage

    Directory of Open Access Journals (Sweden)

    Chengjun Zhu


    Full Text Available Background: Plasminogen activator inhibitor-1 (PAI-1 has been regarded as a risk factor for thrombosis and atherosclerosis. Since it has been shown that PAI-1 can activate macrophages through Toll-like receptor-4, we sought to investigate the role of PAI-1 in the tumor microenvironment. Methods: The expression and distribution patterns of PAI-1 and transforming growth factor beta (TGF-β were measured in 60 non-small cell lung cancer (NSCLC tumors. A statistical correlation analysis was performed between PAI-1 and TGF-β expression and distribution in each tumor. The distribution of tumor-associated macrophages (TAMs was also measured and its correlation to PAI-1 levels was analyzed. Levels of secreted CCL-17, CCL-22, IL-6 and TGF-β were measured in cell cultures of human macrophage cell lines THP-1 and U937 treated with PAI-1. Levels of secreted PAI-1 were monitored in cell cultures of human NSCLCs cell lines 95D and A549 treated with TGF-β. Secreted proteins were measured in cell culture supernatants using ELISA. Changes in downstream signaling pathways were investigated using western blot. Results: PAI-1 and TGF-β were found to be overexpressed in human NSCLCs. PAI-1 expression was tightly correlated to TGF-β expression as well as the percentage of TAMs. PAI-1 treatment increased the expression of TAM-associated cytokines and chemokines, including CCL-17, CCL-22, and IL-6. PAI-1 treatment was also observed to enhance TGF-β expression in macrophage cell lines through an IL-6 autocrine/paracrine manner. The effects on TGF-β expression were blocked by NF-κB and STAT3 inhibition. Interestingly, TGF-β also increased levels of secreted PAI-1 in NSCLC cells through SMAD3-dependent signaling, therefore resulting in a feed-forward loop. However, this loop could be blocked by NF-κB, STAT3 and SMAD3 signaling inhibition, as well as treatment with a high concentration of TGF-β. Conclusion: PAI-1 and TGF-β promote NSCLC tumor cells and TAMs and

  12. General review of flashing jet studies. (United States)

    Polanco, Geanette; Holdø, Arne Erik; Munday, George


    The major concern on the management of superheated liquids, in industrial environments, is the large potential hazards involved in cases of any accidental release. There is a possibility that a violent phase change could take place inside the fluid released generating a flashing jet. This violent phase change might produce catastrophic consequences, such as explosions, fires or toxic exposure, in the installations and in the surroundings. The knowledge and understanding of the mechanisms involved in those releases become an important issue in the prevention of these consequences and the minimization of their impact. This work presents a comprehensive review of information about flashing processes. The review begins with a description of the single phase jet followed by a description of the two-phase flashing jet. The concepts and implications of the thermodynamic and mechanical effects on the behaviour of the jets are considered at the beginning of the review. Following the review is devoted to the classification of the different study approaches used to understand flashing processes in the past, highlighting various critical parameters on the behaviour and the hazard consequences of flashing jets. The review also contains an extensive compilation of experimental, theoretical and numerical data relating to these phenomena, which includes information on the distinct characteristics of the jet, since type of jet, velocity distribution, expansion angle and mass phase change all require individual estimation.

  13. Arctigenin represses TGF-β-induced epithelial mesenchymal transition in human lung cancer cells. (United States)

    Xu, Yanrui; Lou, Zhiyuan; Lee, Seong-Ho


    Arctigenin (ARC) is a lignan that is abundant in Asteraceae plants, which show anti-inflammatory and anti-cancer activities. The current study investigated whether ARC affects cancer progression and metastasis, focusing on EMT using invasive human non-small cell lung cancer (NSCLC) cells. No toxicity was observed in the cells treated with different doses of ARC (12-100 μM). The treatment of ARC repressed TGF-β-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-β-induced phosphorylation and transcriptional activity of smad2/3, and expression of snail. ARC also decreased expression of N-cadherin and increased expression of E-cadherin in dose-dependent and time-dependent manners. These changes were accompanied by decreased amount of phospho-smad2/3 in nucleus and nuclear translocation of smad2/3. Moreover, ARC repressed TGF-β-induced phosphorylation of ERK and transcriptional activity of β-catenin. Our data demonstrate anti-metastatic activity of ARC in lung cancer model. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. [Changes of TGF-β1 expression during orthodontic tooth movement in rats with osteoporosis]. (United States)

    Li, Ming-He; Wang, Yang; Liao, Nan-Nan; Li, Jin-Yuan; Dong, Qing


    To observe the expression and distribution of TGF-β1 in periodontal tissue under intervention of Strontium ranelate and Qianggu capsule during orthodontic tooth movement in rats, and explore the efficacy of the 2 drugs. Seventy male SD rats of 3 months old were selected in the study, and randomly divided into control group, model control group, Strontium ranelate group, Qianggu capsule group, each group had 15 animals. Retinoic acid was given by gavage to animals in the control group, Strontium ranelate group, Qianggu capsule group for 2 weeks, and bone density was detected to determine successful establishment of osteoporosis model. All rats were installed orthodontic device, and were sacrificed at 7 days, 14 days and 21 days, respectively. The tissue blocks of the first maxillary molar and adjacent alveolar bone were taken for H-E staining, immunohistochemical staining and semi-quantitative analysis was used to detect TGF-β1 expression in periodontal tissues. The data were statistically analyzed by SPSS 17.0 software package. TGF- beta 1 expression was significantly increased in Strontium ranelate group and Qianggu capsule group compared with control group (Posteoporosis rats, which is helpful to the movement of healthy teeth; the effect of Strontium ranelate is stronger than Qianggu capsule.

  15. Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections. (United States)

    Bertoli-Avella, Aida M; Gillis, Elisabeth; Morisaki, Hiroko; Verhagen, Judith M A; de Graaf, Bianca M; van de Beek, Gerarda; Gallo, Elena; Kruithof, Boudewijn P T; Venselaar, Hanka; Myers, Loretha A; Laga, Steven; Doyle, Alexander J; Oswald, Gretchen; van Cappellen, Gert W A; Yamanaka, Itaru; van der Helm, Robert M; Beverloo, Berna; de Klein, Annelies; Pardo, Luba; Lammens, Martin; Evers, Christina; Devriendt, Koenraad; Dumoulein, Michiel; Timmermans, Janneke; Bruggenwirth, Hennie T; Verheijen, Frans; Rodrigus, Inez; Baynam, Gareth; Kempers, Marlies; Saenen, Johan; Van Craenenbroeck, Emeline M; Minatoya, Kenji; Matsukawa, Ritsu; Tsukube, Takuro; Kubo, Noriaki; Hofstra, Robert; Goumans, Marie Jose; Bekkers, Jos A; Roos-Hesselink, Jolien W; van de Laar, Ingrid M B H; Dietz, Harry C; Van Laer, Lut; Morisaki, Takayuki; Wessels, Marja W; Loeys, Bart L


    Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-β signaling. This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-β signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-β signaling in association with up-regulation of the expression of TGF-β ligands. Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk. Copyright © 2015 American College of Cardiology Foundation. Published by

  16. TGF-β inhibits IL-1β-activated PAR-2 expression through multiple pathways in human primary synovial cells

    Directory of Open Access Journals (Sweden)

    Fang Sheng-Shiung


    Full Text Available Abstract To investigate the mechanism how Transforming growth factor-β(TGF-β represses Interleukin-1β (IL-1β-induced Proteinase-Activated Receptor-2 (PAR-2 expression in human primary synovial cells (hPSCs. Human chondrocytes and hPSCs isolated from cartilages and synovium of Osteoarthritis (OA patients were cultured with 10% fetal bovine serum media or serum free media before treatment with IL-1β, TGF-β1, or Connective tissue growth factor (CTGF. The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (RT-PCR and western blotting. Collagen zymography was performed to assess the activity of Matrix metalloproteinases-13 (MMP-13. It was demonstrated that IL-1β induces PAR-2 expression via p38 pathway in hPSCs. This induction can be repressed by TGF-β and was observed to persist for at least 48 hrs, suggesting that TGF-β inhibits PAR-2 expression through multiple pathways. First of all, TGF-β was able to inhibit PAR-2 activity by inhibiting IL-1β-induced p38 signal transduction and secondly the inhibition was also indirectly due to MMP-13 inactivation. Finally, TGF-β was able to induce CTGF, and in turn CTGF represses PAR-2 expression by inhibiting IL-1β-induced phospho-p38 level. TGF-β could prevent OA from progression with the anabolic ability to induce CTGF production to maintain extracellular matrix (ECM integrity and to down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue inhibitors of metalloproteinase-3 (TIMP-3 production to inhibit MMPs leading to avoid PAR-2 over-expression. Because IL-1β-induced PAR-2 expressed in hPSCs might play a significantly important role in early phase of OA, PAR-2 repression by exogenous TGF-β or other agents might be an ideal therapeutic target to prevent OA from progression.

  17. The dynamics of TGF-β in dental pulp, odontoblasts and dentin. (United States)

    Niwa, Takahiko; Yamakoshi, Yasuo; Yamazaki, Hajime; Karakida, Takeo; Chiba, Risako; Hu, Jan C-C; Nagano, Takatoshi; Yamamoto, Ryuji; Simmer, James P; Margolis, Henry C; Gomi, Kazuhiro


    Transforming growth factor-beta (TGF-β) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-β in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-β1 and TGF-β3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-β2 is high in dental pulp. TGF-β1 is a major isoform of TGF-β, and latent TGF-β1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11). Activated TGF-β1 enhances the mRNA expression levels of MMP20 and full-length dentin sialophosphoprotein (DSPP) in dental pulp cells, coinciding with the induction of odontoblast differentiation. Latent TGF-β1 synthesized in odontoblasts is primarily activated by MMP2 and MMP20 in both odontoblasts and dentin. The activity level of TGF-β1 was reduced in the dentin of MMP20 null mice, although the amount of latent TGF-β1 expression did not change between wild-type and MMP20 null mice. TGF-β1 activity was reduced with the degradation of DSPP-derived proteins that occurs with ageing. We propose that to exert its multiple biological functions, TGF-β1 is involved in a complicated dynamic interaction with matrix metalloproteinases (MMPs) and/or DSPP-derived proteins present in dental pulp, odontoblasts and dentin.

  18. A Population Synthesis Study of Terrestrial Gamma-ray Flashes (United States)

    Cramer, E. S.; Briggs, M. S.; Stanbro, M.; Dwyer, J. R.; Mailyan, B. G.; Roberts, O.


    In astrophysics, population synthesis models are tools used to determine what mix of stars could be consistent with the observations, e.g. how the intrinsic mass-to-light ratio changes by the measurement process. A similar technique could be used to understand the production of TGFs. The models used for this type of population study probe the conditions of electron acceleration inside the high electric field regions of thunderstorms, i.e. acceleration length, electric field strength, and beaming angles. In this work, we use a Monte Carlo code to generate bremsstrahlung photons from relativistic electrons that are accelerated by a large-scale RREA thunderstorm electric field. The code simulates the propagation of photons through the atmosphere at various source altitudes, where they interact with air via Compton scattering, pair production, and photoelectric absorption. We then show the differences in the hardness ratio at spacecraft altitude between these different simulations and compare them with TGF data from Fermi-GBM. Such comparisons can lead to constraints that can be applied to popular TGF beaming models, and help determine whether the population presented in this study is consistent or not with reality.

  19. A void distribution model-flashing flow

    International Nuclear Information System (INIS)

    Riznic, J.; Ishii, M.; Afgan, N.


    A new model for flashing flow based on wall nucleations is proposed here and the model predictions are compared with some experimental data. In order to calculate the bubble number density, the bubble number transport equation with a distributed source from the wall nucleation sites was used. Thus it was possible to avoid the usual assumption of a constant bubble number density. Comparisons of the model with the data shows that the model based on the nucleation site density correlation appears to be acceptable to describe the vapor generation in the flashing flow. For the limited data examined, the comparisons show rather satisfactory agreement without using a floating parameter to adjust the model. This result indicated that, at least for the experimental conditions considered here, the mechanistic predictions of the flashing phenomenon is possible on the present wall nucleation based model

  20. Mental models of flash floods and landslides. (United States)

    Wagner, Klaus


    Perceptions of flash floods and landslides were analyzed in four communities of the Bavarian Alps using the mental model approach. Thirty-eight qualitative interviews, two telephone surveys with 600 respondents, and two onsite interviews (74/95 respondents) were conducted. Mental models concerning flash floods are much better developed than those for landslides because the key physical processes for flash floods are easier for the general public to recognize and understand. Mental models are influenced by the local conditions. People who have a better knowledge about the hazards are those who use many different sources to inform themselves, express fear about natural hazards, or have previous experience with hazards. Conclusions for how to improve information for the general public are discussed.

  1. Flow ensemble prediction for flash flood warnings at ungauged basins (United States)

    Demargne, Julie; Javelle, Pierre; Organde, Didier; Caseri, Angelica; Ramos, Maria-Helena; de Saint Aubin, Céline; Jurdy, Nicolas


    for significant events of the 2010-2013 period. The evaluation showed significant improvements in terms of flash flood event detection and effective warning lead-time, compared to warnings from the current AIGA setup (without any future precipitation). Various verification metrics (e.g., Relative Mean Error, Continuous Rank Probability Skill Score) show the skill of ensemble precipitation and flow forecasts compared to single-valued persistency benchmarks. In addition to propagating the QPF uncertainty to streamflow forecasts, we discuss how to account for other sources of forecast uncertainty, including precipitation observational uncertainty (Caseri et al. 2014) and hydrologic uncertainties. Planned enhancements include ingesting other probabilistic nowcast and NWP products from Météo-France's convection-permitting AROME model, as well as developing comprehensive observational and post-event damage database to determine decision-relevant thresholds for flood magnitude and probability. Caseri, A., Javelle, P., Ramos, M.H., Leblois, E., 2014. Generating precipitation ensembles for flood alert and risk management. Journal of Flood Risk Management (submitted). Javelle, P., Demargne, J., Defrance, D., Arnaud, P., 2014. Evaluating flash flood warnings at ungauged locations using post-event surveys: a case study with the AIGA warning system. Hydrological Sciences Journal. doi: 10.1080/02626667.2014.923970

  2. Activator protein 2alpha mediates parathyroid TGF-alpha self-induction in secondary hyperparathyroidism. (United States)

    Arcidiacono, Maria Vittoria; Cozzolino, Mario; Spiegel, Noah; Tokumoto, Masanori; Yang, Jing; Lu, Yan; Sato, Tetsuhiko; Lomonte, Carlo; Basile, Carlo; Slatopolsky, Eduardo; Dusso, Adriana S


    In secondary hyperparathyroidism, enhanced expression of TGF-alpha in the parathyroid leads to its own upregulation, generating a feed-forward loop for TGF-alpha activation of its receptor, EGFR receptor (EGFR), which promotes parathyroid hyperplasia. These studies examined the role of activator protein 2alpha (AP2), an inducer of TGF-alpha gene transcription, in the upregulation of parathyroid TGF-alpha in secondary hyperparathyroidism. In rat and human secondary hyperparathyroidism, parathyroid AP2 expression strongly correlated with TGF-alpha levels and with the rate of parathyroid growth, as expected. Furthermore, the increases in rat parathyroid content of AP2 and its binding to a consensus AP2 DNA sequence preceded the increase in TGF-alpha induced by high dietary phosphate. More significant, in A431 cells, which provide a model of enhanced TGF-alpha and TGF-alpha self-induction, mutating the core AP2 site of the human TGF-alpha promoter markedly impaired promoter activity induced by endogenous or exogenous TGF-alpha. Important for therapy, in five-sixths nephrectomized rats fed high-phosphate diets, inhibition of parathyroid TGF-alpha self-induction using erlotinib, a highly specific inhibitor of TGF-alpha/EGFR-driven signals, reduced AP2 expression dosage dependently. This suggests that the increases in parathyroid AP2 occur downstream of EGFR activation by TGF-alpha and are required for TGF-alpha self-induction. Indeed, in A431 cells, erlotinib inhibition of TGF-alpha self-induction caused parallel reductions in AP2 expression and nuclear localization, as well as TGF-alpha mRNA and protein levels. In summary, increased AP2 expression and transcriptional activity at the TGF-alpha promoter determine the severity of the hyperplasia driven by parathyroid TGF-alpha self-upregulation in secondary hyperparathyroidism.

  3. Expression of transforming growth factor-beta (TGF-beta) receptors, TGF-beta 1 and TGF-beta 2 production and autocrine growth control in osteosarcoma cells

    NARCIS (Netherlands)

    Kloen, P.; Jennings, C. L.; Gebhardt, M. C.; Springfield, D. S.; Mankin, H. J.


    Transforming growth factor-beta (TGF-beta) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell-cell interactions and in growth and development. Malignant transformation has been shown to be

  4. An Analysis of Total Lightning Flash Rates Over Florida (United States)

    Mazzetti, Thomas O.; Fuelberg, Henry E.


    Although Florida is known as the "Sunshine State", it also contains the greatest lightning flash densities in the United States. Flash density has received considerable attention in the literature, but lightning flash rate has received much less attention. We use data from the Earth Networks Total Lightning Network (ENTLN) to produce a 5 year (2010-2014) set of statistics regarding total flash rates over Florida and adjacent regions. Instead of tracking individual storms, we superimpose a 0.2° × 0.2° grid over the study region and count both cloud-to-ground (CG) and in-cloud (IC) flashes over 5 min intervals. Results show that the distribution of total flash rates is highly skewed toward small values, whereas the greatest rate is 185 flashes min-1. Greatest average annual flash rates ( 3 flashes min-1) are located near Orlando. The southernmost peninsula, North Florida, and the Florida Panhandle exhibit smaller average annual flash rates ( 1.5 flashes min-1). Large flash rates > 100 flashes min-1 can occur during any season, at any time during the 24 h period, and at any location within the domain. However, they are most likely during the afternoon and early evening in East Central Florida during the spring and summer months.

  5. Age-Dependent Decrease in Serum Transforming Growth Factor (TGF-Beta 1 in Healthy Japanese Individuals; Population Study of Serum TGF-Beta 1 Level in Japanese

    Directory of Open Access Journals (Sweden)

    Yoshihiro Okamoto


    Full Text Available Transforming growth factor-beta1 (TGF-β1, a multi-functional cytokine, is involved in regulating a variety of cellular activities and the serum/plasma TGF-β1 level is altered with various diseases. However, most published reports have described adult patients, and so we investigated the clinical significance of serum TGF-β1 level in pediatric patients. The diagnostic application of the measurement of serum TGF-β1 level depends critically on the control value, however, there is no information on the control value of serum TGF-β1 for children.

  6. Murine CD4 T cells produce a new form of TGF-β as measured by a newly developed TGF-β bioassay.

    Directory of Open Access Journals (Sweden)

    Takatoku Oida


    Full Text Available It is generally assumed that T cells do not produce active TGF-β since active TGF-β as measured in supernatants by ELISA without acidification is usually not detectable. However, it is possible that active TGF-β from T cells may take a special form which is not detectable by ELISA.We constructed a TGF-β bioassay which can detect both soluble and membrane-bound forms of TGF-β from T cells. For this bioassay, 293T cells were transduced with (caga(12 Smad binding element-luciferase along with CD32 (Fc receptor and CD86. The resulting cells act as artificial antigen presenting cells in the presence of anti-CD3 and produce luciferase in response to biologically active TGF-β. We co-cultured pre-activated murine CD4(+CD25(- T cells or CD4(+CD25(+ T cells with the 293T-caga-Luc-CD32-CD86 reporter cells in the presence of anti-CD3 and IL-2. CD4(+CD25(- T cells induced higher luciferase in the reporter cells than CD4(+CD25(+ T cells. This T cell-produced TGF-β is in a soluble form since T cell culture supernatants contained the TGF-β activity. The TGF-β activity was neutralized with an anti-mouse LAP mAb or an anti-latent TGF-β/pro-TGF-β mAb, but not with anti-active TGF-β Abs. An anti-mouse LAP mAb removed virtually all acid activatable latent TGF-β from the T cell culture supernatant, but not the ability to induce TGF-β signaling in the reporter cells. The induction of TGF-β signaling by T cell culture supernatants was cell type-specific.A newly developed 293T-caga-Luc-CD32-CD86 reporter cell bioassay demonstrated that murine CD4 T cells produce an unconventional form of TGF-β which can induce TGF-β signaling. This new form of TGF-β contains LAP as a component. Our finding of a new form of T cell-produced TGF-β and the newly developed TGF-β bioassay system will provide a new avenue to investigate T cell function of the immune system.

  7. Flash Builder 4 and Flex 4 Bible

    CERN Document Server

    Gassner, David


    A complete and thorough reference for developers on the new Flex 4 platform. Create desktop applications that behave identically on Windows, Mac OS X, and Linux with Adobe's new Flash Builder 4 platform and this in-depth guide. The book's tutorials and explanations walk you step-by-step through Flash Builder's new, faster tools; the new framework for generating code; how to connect to popular application servers; upgrading from Flex 3; and much more.: Shows you how to create rich applications for the Web and desktop with the very latest version of Flex, with detailed coverage for both new and

  8. Heat Transfer in a Flash Fuser. (United States)

    Baumann, Gerald Walter

    Flash fusing is used in high speed electrophotographic computer printers to melt the thermoplastic printed image on the paper surface. This technology is not yet well understood, even though it has been used in several different machines. Consequently current fusers may be far from optimum. The aim of this research is to formulate and confirm mathematical models of the fuser. The fusing process was modelled by transient thermal conduction. The toner was assumed to fuse to the paper when its lower surface, against the paper, reached its melting point. The temperature depends on the power input to the toner from the flash tube. Hence, mathematical models were developed to describe both the electrical conduction and radiation characteristics of the flash tube. These models were coupled to the equations describing the electrical drive circuits, and the instantaneous output of the flash was computed. These results were then used in the transient heat conduction model of the toner and paper. A ballistic integrating radiometer was built to measure the total output energy of the flash tube. The electrical input power to the flash tube was measured and compared to the model. These experiments were used to support the computed power input to the toner surface. Unfused prints were exposed to a multitude of pulse shapes, pulse widths, and energies. A standard adhesion test was used to measure the degree of fusing. The temperature of the toner/paper interface was computed. The toner had significant porosity and its heat capacity varied greatly with temperature. The adsorbed water in the paper influenced the temperature profile. The experiments confirmed the melting model. The degree of fusing correlated well with computed interface temperature, and not with input energy or surface temperature. Toner porosity and flash pulse shape are potential design parameters, and they were studied in detail. Modelling results indicate that modest reductions in porosity can significantly

  9. Foundation Flash CS5 for Designers

    CERN Document Server

    Green, T


    Flash is one of the most engaging, innovative, and versatile technologies available - allowing the creation of anything from animated banners and simple cartoons to Rich Internet Applications, interactive videos, and dynamic user interfaces for web sites, kiosks, devices, or DVDs. The possibilities are endless, and now it just got better. Flash CS5 boasts a host of new features, including better support for mobile devices, a whole new animation engine enabling full manipulation of tweens and paths, custom easing, improved inverse kinematics, a revamped timeline, built-in 3D, and much more. Thi

  10. Alternative splicing of TGF-betas and their high-affinity receptors T beta RI, T beta RII and T beta RIII (betaglycan) reveal new variants in human prostatic cells. (United States)

    Konrad, Lutz; Scheiber, Jonas A; Völck-Badouin, Elke; Keilani, Marcel M; Laible, Leslie; Brandt, Heidrun; Schmidt, Ansgar; Aumüller, Gerhard; Hofmann, Rainer


    The transforming growth factors (TGF)-beta, TGF-beta1, TGF-beta2 and TGF-beta 3, and their receptors [T beta RI, T beta RII, T beta R III (betaglycan)] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants T beta RIB, T beta RIIB and TGF-beta 2B in human prostatic cells. Interestingly, a novel human receptor transcript T beta RIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant T beta RIB with four additional amino acids was identified also in human. Expression of the variant T beta RIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of T beta RIIC and TGF-beta 2B mainly in the epithelial cells with a preferential localization of TGF-beta 2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-beta ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-beta2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1) with a major participation of T beta RII. In general, expression of the splice variants was more heterogeneous in contrast to the well-known isoforms. The identification of the splice variants T beta RIB and the novel isoform T beta RIIC in man clearly contributes to the growing complexity of the TGF-beta family.

  11. Alternative splicing of TGF-betas and their high-affinity receptors TβRI, TβRII and TβRIII (betaglycan reveal new variants in human prostatic cells

    Directory of Open Access Journals (Sweden)

    Brandt Heidrun


    Full Text Available Abstract Background The transforming growth factors (TGF-β, TGF-β1, TGF-β2 and TGF-β3, and their receptors [TβRI, TβRII, TβRIII (betaglycan] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants TβRIB, TβRIIB and TGF-β2B in human prostatic cells. Results Interestingly, a novel human receptor transcript TβRIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant TβRIB with four additional amino acids was identified also in human. Expression of the variant TβRIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of TβRIIC and TGF-β2B mainly in the epithelial cells with a preferential localization of TGF-β2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-β ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-β2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1 with a major participation of TβRII. Conclusion In general, expression of the splice variants was more heterogeneous in contrast to the well-known isoforms. The identification of the splice variants TβRIB and the novel isoform TβRIIC in man clearly contributes to the growing complexity of the TGF-β family.

  12. TGF-beta and 'adaptive' Foxp3(+) regulatory T cells. (United States)

    Chen, Wanjun; Konkel, Joanne E


    In naïve T cells transforming growth factor-beta (TGF-beta) induces Foxp3, a transcription factor essential for programming and developing T regulatory cells (Treg cells). This finding reveals a physiological factor which can turn on the Foxp3 gene and establishes an experimental approach to induce antigen-specific Treg cells as a potential therapy for human diseases. While this role for TGF-beta is well confirmed, several critical questions remain largely unanswered and await further investigation. In this regard, it is imperative to understand the molecular pathways by which TGF-beta signaling initiates and regulates Foxp3 expression. It is also important to elucidate which factors and/or cytokines influence the TGF-beta-mediated conversion of naïve T cells and how to create an immunologically regulatory milieu to facilitate Treg cell generation in vivo. In this short article, we will highlight the key findings and recent progress in the field, discuss the molecular mechanisms underlying the TGF-beta-mediated induction of Foxp3, and attempt to outline the challenges ahead.

  13. Dislocation Motion and the Microphysics of Flash Heating and Weakening of Faults during Earthquakes

    Directory of Open Access Journals (Sweden)

    Elena Spagnuolo


    release due to the migration of fast-moving dislocations and the conversion of their kinetic energy into heat. From a review of the current natural and experimental observations we speculate that this mechanism tested for calcite-bearing rocks, is a general mechanism operating during flash weakening (e.g., also precursory to flash melting in the case of silicate-bearing rocks for all fault rock types undergoing fast slip acceleration due to the passage of the seismic rupture front.

  14. Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus. (United States)

    Li, Xianfeng; Miyajima, Masakazu; Jiang, Chuanlu; Arai, Hajime


    We investigated cerebrospinal fluid (CSF) samples from 21 patients with idiopathic normal pressure hydrocephalus (INPH) and 14 controls without neurological disease. The concentrations of leucine-rich alpha-2-glycoprotein (LRG), transforming growth factor (TGF)-beta1, 2, 3 and TGF-beta type II receptor (TbetaR-II) in CSF were measured using ELISA. TGF-beta1, TbetaR-II and LRG CSF levels of patients with INPH were significantly higher than controls, whereas no significant differences in TGF-beta2 levels were found between INPH patients and controls. The present study suggests that TGF-betas expressions may be modulated differently in patients with INPH. These results also indicate that the CSF level assay of TGF-beta1, TbetaR-II and LRG is useful for the diagnosis of patients with INPH, and TGF-beta1, TbetaR-II and LRG may be involved in the pathogenesis of the disease.

  15. 3D Flash LIDAR Space Laser, Phase II (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) is a small business that has developed 3D Flash LIDAR systems for space and terrestrial applications. 3D Flash LIDAR is...

  16. 3D Flash LIDAR EDL Resolution Improvement, Phase II (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) is a small business that has developed 3D Flash LIDAR systems for space and terrestrial applications. 3D Flash LIDAR is...

  17. Frequency upshift via flash ionization phenomena using semiconductor plasma

    Directory of Open Access Journals (Sweden)

    Nishida A.


    Full Text Available We have demonstrated frequency upshift in the terahertz region by flash ionization. The magnitude of upshift frequency is tuned by the laser intensity. A proof of principle experiment has been performed with a plasma creation time scale much shorter than the period of the electromagnetic wave and a plasma length longer than its wavelength. Frequency upshifted from 0.35 to 3.5 THz by irradiating a ZnSe crystal with a ultra-short laser pulse has been observed.

  18. A Hot Downflowing Model Atmosphere for Umbral Flashes and the Physical Properties of Their Dark Fibrils

    Energy Technology Data Exchange (ETDEWEB)

    Henriques, V. M. J.; Mathioudakis, M. [Astrophysics Research Centre, School of Mathematics and Physics, Queen’s University Belfast, BT7 1NN, Northern Ireland (United Kingdom); Socas-Navarro, H. [Instituto de Astrofísica de Canarias, Avda vía Láctea S/N, E-38205 La Laguna, Tenerife (Spain); Rodríguez, J. de la Cruz, E-mail: [Institute for Solar Physics, Department of Astronomy, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden)


    We perform non-LTE inversions in a large set of umbral flashes, including the dark fibrils visible within them, and in the quiescent umbra by using the inversion code NICOLE on a set of full Stokes high-resolution Ca ii λ 8542 observations of a sunspot at disk center. We find that the dark structures have Stokes profiles that are distinct from those of the quiescent and flashed regions. They are best reproduced by atmospheres that are more similar to the flashed atmosphere in terms of velocities, even if with reduced amplitudes. We also find two sets of solutions that finely fit the flashed profiles: a set that is upflowing, featuring a transition region that is deeper than in the quiescent case and preceded by a slight dip in temperature, and a second solution with a hotter atmosphere in the chromosphere but featuring downflows close to the speed of sound at such heights. Such downflows may be related, or even dependent, on the presence of coronal loops, rooted in the umbra of sunspots, as is the case in the region analyzed. Similar loops have been recently observed to have supersonic downflows in the transition region and are consistent with the earlier “sunspot plumes,” which were invariably found to display strong downflows in sunspots. Finally, we find, on average, a magnetic field reduction in the flashed areas, suggesting that the shock pressure is moving field lines in the upper layers.

  19. Venlafaxine hydrochloride for the treatment of hot flashes. (United States)

    Schober, Christina E; Ansani, Nicole T


    To review the literature evaluating venlafaxine for the treatment of hot flashes. Clinical literature accessed through MEDLINE (1966-August 2002), PubMed, Harrison's Online, and references of reviewed articles. Key terms used were venlafaxine, Effexor, hot flashes, and vasomotor symptoms. Not all patients experiencing hot flashes are candidates for traditional hormonal therapy. Nonhormonal alternatives have long been explored, but conflicting evidence of efficacy exists. Venlafaxine is an effective nonhormonal alternative for relief from uncontrolled hot flashes.

  20. Targeting TGF-β Signaling by Antisense Oligonucleotide-mediated Knockdown of TGF-β Type I Receptor

    Directory of Open Access Journals (Sweden)

    Dwi U Kemaladewi


    Full Text Available Duchenne muscular dystrophy (DMD is caused by lack of functional dystrophin and results in progressive myofiber damage and degeneration. In addition, impaired muscle regeneration and fibrosis contribute to the progressive pathology of DMD. Importantly, transforming growth factor-β (TGF-β is implicated in DMD pathology and is known to stimulate fibrosis and inhibit muscle regeneration. In this study, we present a new strategy to target TGF-β signaling cascades by specifically inhibiting the expression of TGF-β type I receptor TGFBR1 (ALK5. Antisense oligonucleotides (AONs were designed to specifically induce exon skipping of mouse ALK5 transcripts. AON-induced exon skipping of ALK5 resulted in specific downregulation of full-length receptor transcripts in vitro in different cell types, repression of TGF-β activity, and enhanced C2C12 myoblast differentiation. To determine the effect of these AONs in dystrophic muscles, we performed intramuscular injections of ALK5 AONs in mdx mice, which resulted in a decrease in expression of fibrosis-related genes and upregulation of Myog expression compared to control AON-injected muscles. In summary, our study presents a novel method to target TGF-β signaling cascades with potential beneficial effects for DMD.

  1. Mammary epithelial cell phagocytosis downstream of TGF-β3 is characterized by adherens junction reorganization. (United States)

    Fornetti, J; Flanders, K C; Henson, P M; Tan, A-C; Borges, V F; Schedin, P


    After weaning, during mammary gland involution, milk-producing mammary epithelial cells undergo apoptosis. Effective clearance of these dying cells is essential, as persistent apoptotic cells have a negative impact on gland homeostasis, future lactation and cancer susceptibility. In mice, apoptotic cells are cleared by the neighboring epithelium, yet little is known about how mammary epithelial cells become phagocytic or whether this function is conserved between species. Here we use a rat model of weaning-induced involution and involuting breast tissue from women, to demonstrate apoptotic cells within luminal epithelial cells and epithelial expression of the scavenger mannose receptor, suggesting conservation of phagocytosis by epithelial cells. In the rat, epithelial transforming growth factor-β (TGF-β) signaling is increased during involution, a pathway known to promote phagocytic capability. To test whether TGF-β enhances the phagocytic ability of mammary epithelial cells, non-transformed murine mammary epithelial EpH4 cells were cultured to achieve tight junction impermeability, such as occurs during lactation. TGF-β3 treatment promoted loss of tight junction impermeability, reorganization and cleavage of the adherens junction protein E-cadherin (E-cad), and phagocytosis. Phagocytosis correlated with junction disruption, suggesting junction reorganization is necessary for phagocytosis by epithelial cells. Supporting this hypothesis, epithelial cell E-cad reorganization and cleavage were observed in rat and human involuting mammary glands. Further, in the rat, E-cad cleavage correlated with increased γ-secretase activity and β-catenin nuclear localization. In vitro, pharmacologic inhibitors of γ-secretase or β-catenin reduced the effect of TGF-β3 on phagocytosis to near baseline levels. However, β-catenin signaling through LiCl treatment did not enhance phagocytic capacity, suggesting a model in which both reorganization of cell junctions and

  2. Decision support system for road closures in flash flood emergencies. (United States)


    Among all the natural hazards, flash flood ranks as the No. 1 weather-related killer in U.S. More : than half of the deaths in flash flood are due to drowning victims in a traffic environment. So road : closure is critical to save lives from flash fl...

  3. Flash-Aware Page Replacement Algorithm

    Directory of Open Access Journals (Sweden)

    Guangxia Xu


    Full Text Available Due to the limited main memory resource of consumer electronics equipped with NAND flash memory as storage device, an efficient page replacement algorithm called FAPRA is proposed for NAND flash memory in the light of its inherent characteristics. FAPRA introduces an efficient victim page selection scheme taking into account the benefit-to-cost ratio for evicting each victim page candidate and the combined recency and frequency value, as well as the erase count of the block to which each page belongs. Since the dirty victim page often contains clean data that exist in both the main memory and the NAND flash memory based storage device, FAPRA only writes the dirty data within the victim page back to the NAND flash memory based storage device in order to reduce the redundant write operations. We conduct a series of trace-driven simulations and experimental results show that our proposed FAPRA algorithm outperforms the state-of-the-art algorithms in terms of page hit ratio, the number of write operations, runtime, and the degree of wear leveling.

  4. Mathematical modeling of the flash converting process

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, H.Y.; Perez-Tello, M.; Riihilahti, K.M. [Utah Univ., Salt Lake City, UT (United States)


    An axisymmetric mathematical model for the Kennecott-Outokumpu flash converting process for converting solid copper matte to copper is presented. The model is an adaptation of the comprehensive mathematical model formerly developed at the University of Utah for the flash smelting of copper concentrates. The model incorporates the transport of momentum, heat, mass, and reaction kinetics between gas and particles in a particle-laden turbulent gas jet. The standard k-{epsilon} model is used to describe gas-phase turbulence in an Eulerian framework. The particle-phase is treated from a Lagrangian viewpoint which is coupled to the gas-phase via the source terms in the Eulerian gas-phase governing equations. Matte particles were represented as Cu{sub 2}S yFeS, and assumed to undergo homogeneous oxidation to Cu{sub 2}O, Fe{sub 3}O{sub 4}, and SO{sub 2}. A reaction kinetics mechanism involving both external mass transfer of oxygen gas to the particle surface and diffusion of oxygen through the porous oxide layer is proposed to estimate the particle oxidation rate Predictions of the mathematical model were compared with the experimental data collected in a bench-scale flash converting facility. Good agreement between the model predictions and the measurements was obtained. The model was used to study the effect of different gas-injection configurations on the overall fluid dynamics in a commercial size flash converting shaft. (author)

  5. TGF-β/Smad signaling in renal fibrosis

    Directory of Open Access Journals (Sweden)

    Xiao-Ming eMeng


    Full Text Available TGF-β (transforming growth factor-β is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF- signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix, and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases. Taken together, TGF-/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for chronic kidney diseases associated with renal fibrosis.

  6. ALK and TGF-Beta Resistance in Breast Cancer (United States)


    and shRNA control; o MCF10A and MDA-MB-231 cells stably expressing caALK or ALK-K210R; o Smad4-deficient MDA-MB-468, MCF10A , MDA-MB-231 and IBC3 cells...TGF--induced cell growth inhibition by gain-of-function and loss-of-function approaches. Immortalized mammary epithelial cell line MCF10A stably...expression of cell cycle regulator p15, p21 and cyclin A. We found that in MCF10A cells TGF-  treatment increased the transcription of p15, p21 and

  7. Observation of K-shell soft X ray emission of nitrogen irradiated by XUV Free Electron Laser FLASH at intensities greater than 10{sup 16} W/cm{sup 2}

    Energy Technology Data Exchange (ETDEWEB)

    Galtier, E. [Universite Pierre et Marie Curie, UPMC, Paris (France); Rosmej, F.B. [Universite Pierre et Marie Curie, UPMC, Paris (France)] [Laboratoire pour l' Utilisation des Lasers Intenses, LULI, Palaiseau (France); White, S.; Riley, D. [Queen' s University of Belfast, Belfast (United Kingdom); Vinko, S.M.; Witcher, T. [Department of Physics, Clarendon Laboratory, University of Oxford, Oxford (United Kingdom); Nagler, B. [SLAC National Accelerator Laboratory, California (United States); Nelson, A.J.; Lee, R.W. [Lawrence Livermore National Laboratory, California (United States); Chalupsky, J.; Renner, O.; Juha, L. [Academy of Sciences of the Czech Republic, Prague (Country Unknown); Toleikis, S. [Deutsches Elektronen - Synchrotron DESY, Hamburg (Germany); Gauthier, J.C. [Centre Lasers Intenses et Applications, CELIA, Bordeaux (France)


    In the past few years, the development of light sources of the fourth generation, namely XUV/X - ray Free Electron Lasers provides to the scientific community with outstanding tools to investigate matter under extreme conditions never obtained in laboratories so far. As theory is at its infancy the analysis of matter via the self - emission of the target is of central importance for this research. In order to minimize absorption to have photons which exit the dense matter, K-shell X-ray transitions play a key role. We report here about the first successful observation of K-shell emission of nitrogen using an XUV - Free Electron laser to irradiate solid BN-targets under exceptional conditions: photon energy of 92 eV, pulse duration of 15 fs, micro-focussing and intensities larger than 10{sup 16} W/cm{sup 2}. Using a Bragg crystal THM coupled to a CCD, we resolved K-shell line emission from different charge states. We demonstrate that the K-shell data allow the characterization of electron heating processes when X-ray radiation is interacting with solid matter. As energy transport is non-trivial because the light source is monochromatic, these results have important impact to theory. We also present data that show significant variation in dependence of the laser intensity, this permits quantitative characterization of the electron temperature: about 100 eV are deduced. The high electron temperatures seem to be in contradiction with the theory of pure Auger electron heating. This document is composed of an abstract followed by the slides of the presentation. (authors)

  8. Initial electric field changes of lightning flashes in two thunderstorms (United States)

    Chapman, Ryan; Marshall, Thomas; Karunarathne, Sumedhe; Stolzenburg, Maribeth


    The beginning of all 75 lightning flashes in two small thunderstorms was investigated using an array of electric field change (E-change) meters and an array of VHF sensors with the goal of determining if an initial E-change (IEC) preceded the initial breakdown (IB) pulses in each flash. IECs were found at the beginning of all 62 flashes in Storm 1 and all 13 flashes in Storm 2. Hence, it is concluded that an IEC is a fundamental part of most or all lightning initiations and that an IEC is needed prior to the first IB pulse in a flash. IEC durations averaged 0.23 ms for cloud-to-ground (CG) flashes (range 0.08-0.54 ms) and averaged 2.7 ms for normal intracloud (IC) flashes (range 0.04-9.8 ms). IEC point dipole moments averaged 26 C m for CG flashes (range 4-86 C m) and averaged -140 C m for normal IC flashes (range -8 to -650 C m). IEC current moments averaged 120 kA m for CG flashes (range 41-410 kA m) and averaged -91 kA m for normal IC flashes (range -2 to -630 kA m). E-change data support the suggestion that weak narrow bipolar event type events initiate some lightning flashes, but 41 of the 75 flashes had no detectable initiating pulse > 0.04 V m-1 range normalized to 100 km. Two flashes had two IECs; the second IEC of each flash initiated a new lightning channel that propagated in a new direction and at a higher altitude than the original development after the first IEC.

  9. TGF-β signal transduction spreading to a wider field: a broad variety of mechanisms for context-dependent effects of TGF-β. (United States)

    Ikushima, Hiroaki; Miyazono, Kohei


    Transforming growth factor (TGF)-β signaling is involved in almost all major cell behaviors under physiological and pathological conditions, and its regulatory system has therefore been vigorously investigated. The fundamental elements in TGF-β signaling are TGF-β ligands, their receptors, and intracellular Smad effectors. The TGF-β ligand induces the receptors directly to phosphorylate and activate Smad proteins, which then form transcriptional complexes to control target genes. One of the classical questions in the field of research on TGF-β signaling is how this cytokine induces multiple cell responses depending on cell type and cellular context. Possible answers to this question include cross-interaction with other signaling pathways, different repertoires of Smad-binding transcription factors, and genetic alterations, especially in cancer cells. In addition to these genetic paradigms, recent work has extended TGF-β research into new fields, including epigenetic regulation and non-coding RNAs. In this review, we first describe the basic machinery of TGF-β signaling and discuss several factors that comprise TGF-β signaling networks. We then address mechanisms by which TGF-β induces several responses in a cell-context-dependent fashion. In addition to classical frames, the interaction of TGF-β signaling with epigenetics and microRNA is discussed.

  10. The insulin response integrates increased TGF-β signaling through Akt-induced enhancement of cell surface delivery of TGF-β receptors (United States)

    Budi, Erine H.; Muthusamy, Baby Periyanayaki; Derynck, Rik


    Increased activity of transforming growth factor β (TGF-β), which binds to and stimulates cell surface receptors, contributes to cancer progression and fibrosis by driving epithelial cells toward a migratory mesenchymal phenotype and increasing the abundance of extracellular matrix proteins. The abundance of TGF-β receptors at the cell surface determines cellular responsiveness to TGF-β, which is often produced by the same cells that have the receptors, and thus serves as an autocrine signal. We found that Akt-mediated phosphorylation of AS160, a RabGAP [guanosine triphosphatase (GTPase)-activating protein] promoted the translocation of TGF-β receptors from intracellular stores to the plasma membrane of mouse embryonic fibroblasts (MEFs) and NMuMG epithelial cells. Consequently, insulin, which is commonly used to treat hyperglycemia and activates Akt signaling, increased the amount of TGF-β receptors at the cell surface, thereby enhancing TGF-β responsiveness. This insulin-induced increase in autocrine TGF-β signaling contributed to insulin-induced gene expression responses, attenuated the epithelial phenotype, and promoted the migration of NMuMG cells. Furthermore, the enhanced delivery of TGF-β receptors at the cell surface enabled insulin to increase TGF-β-induced gene responses. The enhancement of TGF-β responsiveness in response to Akt activation may help to explain the biological effects of insulin, the progression of cancers in which Akt is activated, and the increased incidence of fibroses in diabetes. PMID:26420907

  11. Cholest-4-en-3-one attenuates TGF-β responsiveness by inducing TGF-β receptors degradation in Mv1Lu cells and colorectal adenocarcinoma cells. (United States)

    Chen, Chun-Lin; Wu, Deng-Chyang; Liu, Min-Yun; Lin, Ming-Wei; Huang, Hung-Tu; Huang, Yaw-Bin; Chen, Li-Chai; Chen, Yu-Yu; Chen, Jih-Jung; Yang, Pei-Hua; Kao, Yu-Chen; Chen, Pei-Yu


    The transforming growth factor-beta (TGF-β) pathway is an important in the initiation and progression of cancer. Due to a strong association between an elevated colorectal cancer risk and increase fecal excretion of cholest-4-en-3-one, we aim to determine the effects of cholest-4-en-3-one on TGF-β signaling in the mink lung epithelial cells (Mv1Lu) and colorectal cancer cells (HT29) in vitro. The inhibitory effects of cholest-4-en-3-one on TGF-β-induced Smad signaling, cell growth inhibition, and the subcellular localization of TGF-β receptors were investigated in epithelial cells using a Western blot analysis, luciferase reporter assays, DNA synthesis assay, confocal microscopy, and subcellular fractionation. Cholest-4-en-3-one attenuated TGF-β signaling in Mv1Lu cells and HT29 cells, as judged by a TGF-β-specific reporter gene assay of plasminogen activator inhibitor-1 (PAI-1), Smad2/3 phosphorylation and nuclear translocation. We also discovered that cholest-4-en-3-one suppresses TGF-β responsiveness by increasing lipid raft and/or caveolae accumulation of TGF-β receptors and facilitating rapid degradation of TGF-β and thus suppressing TGF-β-induced signaling. Our results suggest that cholest-4-en-3-one inhibits TGF-β signaling may be due, in part to the translocation of TGF-β receptor from non-lipid raft to lipid raft microdomain in plasma membranes. Our findings also implicate that cholest-4-en-3-one may be further explored for its potential role in colorectal cancer correlate to TGF-β deficiency.

  12. Activator Protein 2α Mediates Parathyroid TGF-α Self-Induction in Secondary Hyperparathyroidism


    Arcidiacono, Maria Vittoria; Cozzolino, Mario; Spiegel, Noah; Tokumoto, Masanori; Yang, Jing; Lu, Yan; Sato, Tetsuhiko; Lomonte, Carlo; Basile, Carlo; Slatopolsky, Eduardo; Dusso, Adriana S.


    In secondary hyperparathyroidism, enhanced expression of TGF-α in the parathyroid leads to its own upregulation, generating a feed-forward loop for TGF-α activation of its receptor, EGFR receptor (EGFR), which promotes parathyroid hyperplasia. These studies examined the role of activator protein 2α (AP2), an inducer of TGF-α gene transcription, in the upregulation of parathyroid TGF-α in secondary hyperparathyroidism. In rat and human secondary hyperparathyroidism, parathyroid AP2 expression ...

  13. Wide Bandgap Semiconductor Detector Optimization for Flash X-Ray Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Roecker, Caleb Daniel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Schirato, Richard C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Charge trapping, resulting in a decreased and spatially dependent electric field, has long been a concern for wide bandgap semiconductor detectors. While significant work has been performed to characterize this degradation at varying temperatures and radiation environments, this work concentrates upon examining the event-to-event response in a flash X-ray environment. The following work investigates if charge trapping is a problem for CZT detectors, with particular emphasis on flash X-ray radiation fields at cold temperatures. Results are compared to a non-flash radiation field, using an Am-241 alpha source and similar temperature transitions. Our ability to determine if a response change occurred was hampered by the repeatability of our flash X-ray systems; a small response change was observed with the Am-241 source. Due to contrast of these results, we are in the process of revisiting the Am-241 measurements in the presence of a high radiation environment. If the response change is more pronounced in the high radiation environment, a similar test will be performed in the flash X-ray environment.

  14. A novel method to alleviate flash-line defects in coining process

    KAUST Repository

    Xu, Jiangping


    We employ a finite element framework based on a dynamic explicit algorithm to predict the flash-line defects in the coining process. The distribution of the flash-line is obtained by building a radial friction work model at the element level. The elasto-plastic behavior of porous materials undergoing large deformations is considered where the constitutive level updates are the result of a local variational minimization problem. We study the material flow at different strokes of the die across the entire coining process and observe that the change in the flow direction of the material in the rim region may contribute to the flash lines. Our proposed framework shows that a part of the rim region in which the flash-line defects appear is consistent with the reported experimental results. We also propose a novel method of redesigning the rim geometry of the workpiece to alleviate the flash-line defects which also shows good agreement with experiments. © 2012 Elsevier Inc. All rights reserved.

  15. Flash Welding Control by Use of PWM Inverter Power Supply (United States)

    Nagura, Kouki; Sato, Yukihiko; Yamamura, Naoki; Ishida, Muneaki

    The flash welding is characterized by the high quality, the high production efficiency and the large sectional area welding, and is used to weld rails and hot coils in shop welding mainly. In order to realize high accuracy and high response control of flash welding, the inverter technology has been applied to flash welding in this study. In this paper, a method of process control combined with inverter flash control and mechanical control is proposed. Experiment results of the proposed process control combined with inverter flash control and mechanical control are presented.

  16. The relativistic feedback discharge model of terrestrial gamma ray flashes (United States)

    Dwyer, Joseph R.


    As thunderclouds charge, the large-scale fields may approach the relativistic feedback threshold, above which the production of relativistic runaway electron avalanches becomes self-sustaining through the generation of backward propagating runaway positrons and backscattered X-rays. Positive intracloud (IC) lightning may force the large-scale electric fields inside thunderclouds above the relativistic feedback threshold, causing the number of runaway electrons, and the resulting X-ray and gamma ray emission, to grow exponentially, producing very large fluxes of energetic radiation. As the flux of runaway electrons increases, ionization eventually causes the electric field to discharge, bringing the field below the relativistic feedback threshold again and reducing the flux of runaway electrons. These processes are investigated with a new model that includes the production, propagation, diffusion, and avalanche multiplication of runaway electrons; the production and propagation of X-rays and gamma rays; and the production, propagation, and annihilation of runaway positrons. In this model, referred to as the relativistic feedback discharge model, the large-scale electric fields are calculated self-consistently from the charge motion of the drifting low-energy electrons and ions, produced from the ionization of air by the runaway electrons, including two- and three-body attachment and recombination. Simulation results show that when relativistic feedback is considered, bright gamma ray flashes are a natural consequence of upward +IC lightning propagating in large-scale thundercloud fields. Furthermore, these flashes have the same time structures, including both single and multiple pulses, intensities, angular distributions, current moments, and energy spectra as terrestrial gamma ray flashes, and produce large current moments that should be observable in radio waves.

  17. Occurrence of cleft-palate and alteration of Tgf-β(3) expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency. (United States)

    Maldonado, Estela; Murillo, Jorge; Barrio, Carmen; del Río, Aurora; Pérez-Miguelsanz, Juliana; López-Gordillo, Yamila; Partearroyo, Teresa; Paradas, Irene; Maestro, Carmen; Martínez-Sanz, Elena; Varela-Moreiras, Gregorio; Martínez-Álvarez, Concepción


    Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2-8 weeks' induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks' maternal FA deficiency caused complete CP in the fetuses although a 2 weeks' maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor-β(3) (TGF-β(3)) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β(3)null mutant mice, we investigated the presence of TGF-β(3) mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β(3) expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β(3) expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of TGF-β(3) to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous TGF-β(3) compensates this deficit in vitro. Copyright © 2011 S. Karger AG, Basel.

  18. Effect of captopril on radiation-induced TGF-β1 secretion in EA.Hy926 human umbilical vein endothelial cells. (United States)

    Wei, Jingni; Xu, Hui; Liu, Yinyin; Li, Baiyu; Zhou, Fuxiang


    The pathophysiological mechanism involved in the sustained endothelial secretion of cytokines that leads to fibrosis 6-16 months after radiotherapy remains unclear. Angiotensin II (Ang II) is produced by the endothelium in response to stressing stimuli, like radiation, and may induce the synthesis of TGF-β, a profibrotic cytokine. In this study we tested the hypothesis that captopril, an angiotensin-converting enzyme (ACE) inhibitor, inhibits or attenuates radiation-induced endothelial TGF-β1 secretion. The human endothelial hybrid cell line EA.HY926 was irradiated with split doses of x-rays (28 Gy delivered in 14 fractions of 2 Gy). TGF-β1 mRNA, TNF-α mRNA and TGF-β1 protein levels were evaluated by RT-PCR and western blotting each month until the fifth month post radiation. Ang II was detected using radioimmunoassays, NF-κB activity was examined using EMSA, and western blotting was used to detect the expression of Iκ-Bα. To explore the role of Ang II on radiation-induced TGF-β1 release and Iκ-Bα expression, captopril was added to cultured cells before, during, or after irradiation. Sustained strong expression of TGF-β1 was observed after conventional fractionated irradiation. TNF-α, Ang II, and NF-κB activity were also increased in EA.Hy926 cells after radiation. Captopril decreased Ang II expression, inhibited the NF-κB pathway and reduced TGF-β1 expression. These data suggest that captopril might protect the endothelium from radiation-induced injury.

  19. An Inducible TGF-β2-TGFβR Pathway Modulates the Sensitivity of HNSCC Cells to Tyrosine Kinase Inhibitors Targeting Dominant Receptor Tyrosine Kinases.

    Directory of Open Access Journals (Sweden)

    Emily K Kleczko

    Full Text Available The epidermal growth factor receptor (EGFR is overexpressed in approximately 90% of head and neck squamous cell carcinomas (HNSCC, and molecularly targeted therapy against the EGFR with the monoclonal antibody cetuximab modestly increases overall survival in head and neck cancer patients. We hypothesize that co-signaling through additional pathways limits the efficacy of cetuximab and EGFR-specific tyrosine kinase inhibitors (TKIs in the clinical treatment of HNSCC. Analysis of gene expression changes in HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs identified transforming growth factor beta 2 (TGF-β2 induction in the three cell lines tested. Measurement of TGF-β2 mRNA validated this observation and extended it to additional cell lines. Moreover, TGF-β2 mRNA was increased in primary patient HNSCC xenografts treated for 4 weeks with cetuximab, demonstrating in vivo relevance of these findings. Functional genomics analyses with shRNA libraries identified TGF-β2 and TGF-β receptors (TGFβRs as synthetic lethal genes in the context of TKI treatment. Further, direct RNAi-mediated silencing of TGF-β2 inhibited cell growth, both alone and in combination with TKIs. Also, a pharmacological TGFβRI inhibitor similarly inhibited basal growth and enhanced TKI efficacy. In summary, the studies support a TGF-β2-TGFβR pathway as a TKI-inducible growth pathway in HNSCC that limits efficacy of EGFR-specific inhibitors.

  20. Effects of Robusta coffee (Coffea canephora brewing on levels of RANKL and TGF- β1 in orthodontic tooth movement

    Directory of Open Access Journals (Sweden)

    Herniyati Herniyati


    Full Text Available Background: Orthodontic tooth movement will be followed by periodontal ligament and alveolar bone remodeling. Orthodontic mechanical force (OMF will be distributed through the teeth to periodontal ligament and alveolar bone and then will generate local pressure resulting in bone resorption and tension areas that will form new bone. Robusta coffee contains caffeine, chlorogenic acid and caffeic acid. Caffeine may increase osteoclastogenesis, and caffeic acid has antioxidant effects that may reduce oxidative stress in osteoblasts. Purpose: This study conducted to analyze the effect Robusta coffee steeping on levels of RANKL and TGF-β1 in orthodontic tooth movement. Method: 16 male rats were divided into 2 groups. Group C: rats given OMF, Group T: given OMF and coffee brew at 20 mg/ 100 g BW. OMF in rats was conducted by applying ligature wire on the molar-1 (M-1 and both incisivus of right maxilla. Subsequently, M-1 of right maxilla was moved to mesial with a Niti closed coil spring. Observations were made on days 15 and 22 by taking the GCF by putting paper point on the gingival sulcus of mesio- and disto-palatal areas of M-1 of right maxilla to determine the levels of RANKL and TGF-β1 using ELISA method. Result: The administration of coffee brew was effective to increase levels of RANKL and TGF-β1 in the compression and tension areas (p <0.05. RANKL levels in compression area were higher than in the tension area (p <0.05, while the levels of TGF-β1 in the tension area were higher than in the compression area (p <0.05. Conclusion: The administration of coffee brew was effective to increase the levels of RANKL and TGF-β, therefore it might improve alveolar bone remodeling process.

  1. DMPD: TGF-beta signaling from receptors to the nucleus. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10611754 TGF-beta signaling from receptors to the nucleus. Roberts AB. Microbes Inf...ect. 1999 Dec;1(15):1265-73. (.png) (.svg) (.html) (.csml) Show TGF-beta signaling from receptors to the nuc...leus. PubmedID 10611754 Title TGF-beta signaling from receptors to the nucleus. Authors Roberts AB. Publicat

  2. Expression of TGF-betas in the embryonic nervous system: analysis of interbalance between isoforms. (United States)

    Mecha, M; Rabadán, M A; Peña-Melián, A; Valencia, M; Mondéjar, T; Blanco, M J


    Transforming growth factor-beta (TGF-beta) is a family of growth factors with essential and multiple roles during embryonic development. In mammals, three isoforms (TGF-beta1, TGF-beta2, TGF-beta3) have been described. In the nervous system, the presence of TGF-beta1 has remained undetectable in other structures than meninges and choroids plexus, while TGF-beta2 and TGF-beta3 were considered as the neural members of the family. In the present study, we have analysed the expression pattern of the three isoforms in the neural tube, brain, and spinal cord during development in both mouse and chicken. The data reveal specific patterns for each isoform. This work also shows that both TGF-beta1 and TGF-beta3 are expressed in neural crest cells. In addition, we demonstrate the existence of interbalance between TGF-beta1 and TGF-beta3 with possible functional implications, which, together with the expression of TGF-beta1 in the CNS, represents one of the most important contributions of this work.

  3. Medium range forecasting of Hurricane Harvey flash flooding using ECMWF and social vulnerability data (United States)

    Pillosu, F. M.; Jurlina, T.; Baugh, C.; Tsonevsky, I.; Hewson, T.; Prates, F.; Pappenberger, F.; Prudhomme, C.


    During hurricane Harvey the greater east Texas area was affected by extensive flash flooding. Their localised nature meant they were too small for conventional large scale flood forecasting systems to capture. We are testing the use of two real time forecast products from the European Centre for Medium-range Weather Forecasts (ECMWF) in combination with local vulnerability information to provide flash flood forecasting tools at the medium range (up to 7 days ahead). Meteorological forecasts are the total precipitation extreme forecast index (EFI), a measure of how the ensemble forecast probability distribution differs from the model-climate distribution for the chosen location, time of year and forecast lead time; and the shift of tails (SOT) which complements the EFI by quantifying how extreme an event could potentially be. Both products give the likelihood of flash flood generating precipitation. For hurricane Harvey, 3-day EFI and SOT products for the period 26th - 29th August 2017 were used, generated from the twice daily, 18 km, 51 ensemble member ECMWF Integrated Forecast System. After regridding to 1 km resolution the forecasts were combined with vulnerable area data to produce a flash flood hazard risk area. The vulnerability data were floodplains (EU Joint Research Centre), road networks (Texas Department of Transport) and urban areas (Census Bureau geographic database), together reflecting the susceptibility to flash floods from the landscape. The flash flood hazard risk area forecasts were verified using a traditional approach against observed National Weather Service flash flood reports, a total of 153 reported flash floods have been detected in that period. Forecasts performed best for SOT = 5 (hit ratio = 65%, false alarm ratio = 44%) and EFI = 0.7 (hit ratio = 74%, false alarm ratio = 45%) at 72 h lead time. By including the vulnerable areas data, our verification results improved by 5-15%, demonstrating the value of vulnerability information within

  4. Anatomy of successive helium-shell flashes: Stationary shell burning

    International Nuclear Information System (INIS)

    Sackmann, I.


    For successive helium-shell flashes, the amounts of helium and hydrogen burned were computed over the peak flash phase, over the total flash cycle, and over the quiet, interflash phase. It was found that the frequently made assumption of stationary shell burning is violated by the helium-shell flash for the first few flashes; here, over a total flash cycle, the helium-burning shell always progresses considerably faster outward than the hydrogen-burning shell. However, after about 15 flashes, coincident with the leveling out of the peaks of the helium shell, agreement with stationary shell burning is attained, both for the 3 M/sub sun/ and 6 M/sub sun/ cases

  5. Evaluation of Fluoxtinfor Treatm Ent of Menopausal Hot Flashes

    Directory of Open Access Journals (Sweden)

    L Sakhavat


    Full Text Available Introduction: Hot flashes can be prominent problem in menopausal women. The treatment of hot flashes is hormonal thrapies but in some patients that are unable to use estrogen other treating hot flashes are required. Based on anecdotal information reqarding the efficacy of fluoxtin for treating hot flashes , the present trial was developed . Methods: This trial used a double Blinded randomized to study the effecacy of fluoxetin (20mg/day and comparing with placebo in treating hot flash in 4 week treatment. Results: 310 women began protocol thrapy. in two group: A (flouxetine and B-( placebo By the end of protocol hot flashes frequeney decreased 77.5 % with floxetin versus 13.7 % whith placebo( p=.0001The flouxetin was well tolerated . Conclusion: Flouxetin resulted well improvent in hot flashes.

  6. On the origin of X-ray Flashes

    CERN Document Server

    Dar, Arnon; Dar, Arnon; Rujula, Alvaro De


    We use the very simple and successful cannonball (CB) model of gamma ray bursts (GRBs) and their afterglows (AGs) to analyze the observational data on X-ray flashes (XRFs) and their AGs. We show that the observations support the CB-model interpretation that XRFs, like GRBs, are produced by the explosions of core-collapse supernovae (SNe) akin to SN1998bw, by jets of highly-relativistic CBs. The XRFs and GRBs are intrinsically identical objects, but the XRFs are viewed from angles (relative to the jet direction) which are typically a few times larger than the typical viewing angles of ``classical'', long-duration GRBs. XRFs of shorter duration than the ones observed so far, like short GRBs, may be produced in Type Ia SNe akin to SN1997cy.

  7. Developing a Conceptual Framwork for Modeling Deviant Cyber Flash Mob: A Socio-Computational Approach Leveraging Hypergraph Constructs

    Directory of Open Access Journals (Sweden)

    Samer Al-khateeb


    Full Text Available In a Flash Mob (FM a group of people get together in the physical world perform an unpredicted act and disperse quickly. Cyber Flash Mob (CFM is the cyber manifestation of flash mob coordinated primarily using social media. Deviant Cyber Flash Mob (or, DCFM is a special case of CFM, which is categorized as the new face of transnational crime organizations (TCOs. The DCFM phenomenon can be considered as a form of a cyber-collective action that is defined as an action aiming to improve group's conditions (such as, status or power. In this paper, we conduct a conceptual analysis of the DCFMs and model the factors that lead to success or failure with groundings in collective action and collective identity formation theories. Mathematical constructs of hypergraph are leveraged to represent the complex relations observed in the DCFM social networks. The model's efficacy is demonstrated through a test scenario.

  8. Estimating the crash reduction and vehicle dynamics effects of flashing LED stop signs : final report. (United States)


    A flashing LED stop sign is essentially a normal octagonal stop sign with light emitted diodes (LED) on the : stop signs corners. A hierarchical Bayes observational before/after study found an estimated reduction of : about 41.5% in right-angle cr...

  9. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

    Directory of Open Access Journals (Sweden)

    Xiaobao Fan

    Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

  10. Signaling by TGF-betas in tubule cultures of adult rat testis. (United States)

    Chan, Kai-Hui; Galuska, Sebastian P; Kudipudi, Pradeep Kumar; Riaz, Mohammad Assad; Loveland, Kate L; Konrad, Lutz


    Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1. In contrast, BMPs (BMP2 and BMP7) do not signal via the high-affinity type I and type II TGFβ receptors, TBR1 or TBR2. Furthermore, treatment of tubule cultures with either TGF-β1 or TGF-β2 had profound significant stimulatory effects on secretion of plasminogen activator-1 (PAI-1) through utilization of TGF-β and BMP receptors. Specific inhibitors for either TBR1 or BMP receptors yielded nearly complete inhibition of TGF-β signaling. The TBR1-TBR2 signalosome was detected with Duolink upon stimulation with either TGF-β1 or TGF-β2, predominantly in spermatogenic cells of the adult rat testis, particularly in elongated spermatids. In summary, this examination of intact rat testicular tubules demonstrated for the first time that TGF-βs signal mainly through TBR1 and TBR2 but also use BMP receptors, including for secretion of PAI-1. Whereas ALK2 participates in the TGF-β1-induced TBR1-TBR2 signalosome, ALK3 and ALK6 are involved in signaling of TGF-β2. Detection of the TBR1-TBR2 signalosome in late spermiogenic cells indicates a post-meiotic activity.

  11. TGF-β and Physiological Root Resorption of Deciduous Teeth

    Directory of Open Access Journals (Sweden)

    Emi Shimazaki


    Full Text Available The present study was performed to examine how transforming growth factor β (TGF-β in root-surrounding tissues on deciduous teeth regulates the differentiation induction into odontoclasts during physiological root resorption. We prepared root-surrounding tissues with (R or without (N physiological root resorption scraped off at three regions (R1–R3 or N1–N3 from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP activities. The TGF-β activity level was increased in N1–N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for the receptor activator of nuclear factor-κB (NF-κB ligand (RANKL-mediated osteoclast differentiation revealed that proteins from N1–N3 and R1–R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA levels of TGF-β1 in N1 and N2 were significantly increased, and corresponded with levels of osteoprotegerin (OPG. In contrast, the expression level of RANKL was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

  12. An engineered transforming growth factor β (TGF-β) monomer that functions as a dominant negative to block TGF-β signaling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Kyung; Barron, Lindsey; Hinck, Cynthia S.; Petrunak, Elyse M.; Cano, Kristin E.; Thangirala, Avinash; Iskra, Brian; Brothers, Molly; Vonberg, Machell; Leal, Belinda; Richter, Blair; Kodali, Ravindra; Taylor, Alexander B.; Du, Shoucheng; Barnes, Christopher O.; Sulea, Traian; Calero, Guillermo; Hart, P. John; Hart, Matthew J.; Demeler, Borries; Hinck, Andrew P. (Texas-HSC); (NRCC); (Pitt)


    The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-β monomers and bound TβRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-β signaling with a Ki of 20–70 nM. Investigation of the mechanism showed that the high affinity of the engineered monomer for TβRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TβRI, enabled it to bind endogenous TβRII but prevented it from binding and recruiting TβRI to form a signaling complex. Such engineered monomers provide a new avenue to probe and manipulate TGF-β signaling and may inform similar modifications of other TGF-β family members.

  13. Electrical Safety and Arc Flash Protections

    Energy Technology Data Exchange (ETDEWEB)

    R. Camp


    Over the past four years, the Electrical Safety Program at PPPL has evolved in addressing changing regulatory requirements and lessons learned from accident events, particularly in regards to arc flash hazards and implementing NFPA 70E requirements. This presentation will discuss PPPL's approaches to the areas of electrical hazards evaluation, both shock and arc flash; engineered solutions for hazards mitigation such as remote racking of medium voltage breakers, operational changes for hazards avoidance, targeted personnel training and hazard appropriate personal protective equipment. Practical solutions for nominal voltage identification and zero voltage checks for lockout/tagout will also be covered. Finally, we will review the value of a comprehensive electrical drawing program, employee attitudes expressed as a personal safety work ethic, integrated safety management, and sustained management support for continuous safety improvement.

  14. Electrical Safety and Arc Flash Protections

    International Nuclear Information System (INIS)

    Camp, R.


    Over the past four years, the Electrical Safety Program at PPPL has evolved in addressing changing regulatory requirements and lessons learned from accident events, particularly in regards to arc flash hazards and implementing NFPA 70E requirements. This presentation will discuss PPPL's approaches to the areas of electrical hazards evaluation, both shock and arc flash; engineered solutions for hazards mitigation such as remote racking of medium voltage breakers, operational changes for hazards avoidance, targeted personnel training and hazard appropriate personal protective equipment. Practical solutions for nominal voltage identification and zero voltage checks for lockout/tagout will also be covered. Finally, we will review the value of a comprehensive electrical drawing program, employee attitudes expressed as a personal safety work ethic, integrated safety management, and sustained management support for continuous safety improvement.

  15. Flash evaporation of liquid monomer particle mixture (United States)

    Affinito, John D.; Darab, John G.; Gross, Mark E.


    The present invention is a method of making a first solid composite polymer layer. The method has the steps of (a) mixing a liquid monomer with particles substantially insoluble in the liquid monomer forming a monomer particle mixture; (b) flash evaporating the particle mixture and forming a composite vapor; and (c) continuously cryocondensing said composite vapor on a cool substrate and cross-linking the cryocondensed film thereby forming the polymer layer.

  16. Mass flow determination in flashing openings


    G Polanco; A Holdø; G Munday


    The output flow characteristics in most of the industrial accidental releasesare related to a two-phase flow and their represent a potential hazard tofacilities, personnel, equipments and environment. If these releases involvesuperheated liquid then a flashing process can take place, where a liquidgasmixture due to the breaking of the metastable state can significantlyaffect the hazard zone. The calculation of the conditions for the flow after aflashing opening is very relevant in order to un...

  17. Evaluation of Flash Bainite in 4130 Steel (United States)


    and Gleeble heat affected zone tests were performed on AISI 4130 steel plate. When possible, testing was baselined against conventional quench and...Diffraction Report 34 APPENDIX F Charpy V-Notch Test Results on Flash Bainite and Q&T 4130 Plate 38 APPENDIX G Charpy V-Notch Test Results on Gleeble...provides recommendations for future testing . EXPERIMENTAL PROCEDURE Gary Cola, Sirius Protection LLC, provided 4130 steel plates to ARDEC. Both


    Directory of Open Access Journals (Sweden)

    G. Zhou


    Full Text Available A small cost-low civilian UAV (Unmanned Aerial Vehicle - UAV platform usually requests that all carried components should be light in weight, small in volume, and efficient in energy. This paper presents the advance of a pre-mature of flash LiDAR system including laser emitting system, associate with the pulsed voltage technology. A complete laser emitting system, including laser diode, conic lens, alignment, divergence angle, etc., has been designed and implemented. The laser emitting system is first simulated and tested using 3D-Tool software, and then manufactured by an industrial company. In addition, a novel power supply topology based on two coupled coils, pulse generator circuit, and a fast switch, is proposed since several 100 V in voltage, 10-100 A in current, several hundred millisecond in pulse width is needed for flash LiDAR system onboard a small low-cost civilian UAV platform, and the traditional power supply had problems in efficiency and bulk. Finally, laser emitting and the power supply are assembled and tested. The size of laser footprint is 4398.031 mm x 4398.031 mm in x and y axes, respectively, when shitting from a flight height of 300 m, which is close to the theoretic size of 4.5 m x 4.5 m. The difference of 102 mm can meet the requirement of flash LiDAR data collection at a flight height of 300 m. Future work on extensive and on-going investigation and investments for a prototype of flash LiDAR system is drawn up as well.

  19. Pressure drop in flashing flow through obstructions

    International Nuclear Information System (INIS)

    Weinle, M.E.; Johnston, B.S.


    An experiment was designed to investigate the pressure drop for flashing flow across obstructions of different geometries at various flow rates. Tests were run using two different orifices to determine if the two-phase pressure drop could be characterized by the single phase loss coefficient and the general behavior of the two-phase multiplier. For the geometries studied, it was possible to correlate the multiplier in a geometry-independent fashion

  20. Flash CS3 The Missing Manual

    CERN Document Server

    Grover, Chris


    Flash CS3, the latest version of the premier tool for creating web animations and interactive web sites, can be intimidating to learn. This entertaining reference tutorial provides a reader-friendly animation primer and a guided tour of all the program's tools and capabilities. Beginners will learn to use the software in no time, and experienced users will quickly take their skills to the next level.

  1. TGF-β Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis.

    Directory of Open Access Journals (Sweden)

    Michael R Davies

    Full Text Available Rotator cuff tears represent a large burden of muscle-tendon injuries in our aging population. While small tears can be repaired surgically with good outcomes, critical size tears are marked by muscle atrophy, fibrosis, and fatty infiltration, which can lead to failed repair, frequent re-injury, and chronic disability. Previous animal studies have indicated that Transforming Growth Factor-β (TGF-β signaling may play an important role in the development of these muscle pathologies after injury. Here, we demonstrated that inhibition of TGF-β1 signaling with the small molecule inhibitor SB431542 in a mouse model of massive rotator cuff tear results in decreased fibrosis, fatty infiltration, and muscle weight loss. These observed phenotypic changes were accompanied by decreased fibrotic, adipogenic, and atrophy-related gene expression in the injured muscle of mice treated with SB431542. We further demonstrated that treatment with SB431542 reduces the number of fibro/adipogenic progenitor (FAP cells-an important cellular origin of rotator cuff muscle fibrosis and fatty infiltration, in injured muscle by promoting apoptosis of FAPs. Together, these data indicate that the TGF-β pathway is a critical regulator of the degenerative muscle changes seen after massive rotator cuff tears. TGF-β promotes rotator cuff muscle fibrosis and fatty infiltration by preventing FAP apoptosis. TGF-β regulated FAP apoptosis may serve as an important target pathway in the future development of novel therapeutics to improve muscle outcomes following rotator cuff tear.

  2. Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling.


    Stähli, Alexandra Beatrice; Bosshardt, Dieter; Sculean, Anton; Gruber, Reinhard


    Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB43...

  3. Oil from coal by flash pyrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, I.W. (and others)


    This report summarizes the final stage of the NERDDP-funded work on coal liquefaction by flash pyrolysis. A working model pyrolyser, simulating a full-scale unit, has been operated over extended periods with Liddell and Piercefield (NSW), Acland, Millmerran and Macalister (Qld), and Loy Yang (Vic) coals. For several of the coals pyrolysed process heat was generated by combustion of some of the by-product char. Tar from Millmerran, Piercefield, Loy Yang, and Yallourn coals, produced in a separate pilot-scale pyrolyser, have been hydrogenated in continuous reactors to produce synthetic crude oils. Chars from Millmerran and Macalister sub-bituminous coals have been burned in the pilot-scale furnace with results as satisfactory as for the parent coals. The report shows that the flash pyrolysis method of making oil from coal is technically feasible, but cost studies show that in the present economic environment this method produces oil some three to four times more costly than natural oil. The report includes a summary of the overall CSIRO project of which this project formed a part, with emphasis on recent work of significance: e.g. methods of control of coke lay-down on tar hydrogenation catalysts; the combustion reactivity of pyrolysis chars; and various alternative uses of the flash pyrolysis method. Also included is an outline of related work carried out in other Australian and overseas laboratories, and a complete (to end of 1985) bibliography of all publications arising from the project.

  4. Helium shells and faint emission lines from slitless flash spectra. (United States)

    Bazin, Cyril; Koutchmy, Serge


    At the time of the two last solar total eclipses of August 1st, 2008 in Siberia and July 11th, 2010 in French Polynesia, high frame rate CCD flash spectra were obtained. These eclipses occurred in quiet Sun period and after. The slitless flash spectra show two helium shells, in the weak Paschen α 4686 Å line of the ionized helium HeII and in the neutral helium HeI line at 4713 Å. The extensions of these helium shells are typically 3 Mm. In prominences, the extension of the interface with the corona is much more extended. The observations and analysis of these lines can properly be done only in eclipse conditions, when the intensity threshold reaches the coronal level, and the parasitic scattered light is virtually zero. Under the layers of 1 Mm above the limb, many faint low FIP lines were also seen in emission. These emission lines are superposed on the continuum containing absorption lines. The solar limb can be defined using the weak continuum appearing between the emission lines at the time of the second and third contact. The variations of the singly ionized iron line, the HeI and HeII lines and the continuum intensity are analyzed. The intensity ratio of ionized to neutral helium is studied for evaluating the ionization rate in low layers up to 2 Mm and also around a prominence.

  5. Acupuncture for hot flashes in patients with prostate cancer. (United States)

    Beer, Tomasz M; Benavides, Maria; Emmons, Sandra L; Hayes, Margaret; Liu, Guohui; Garzotto, Mark; Donovan, Deirdre; Katovic, Nina; Reeder, Caron; Eilers, Kristine


    To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer. Men who had a hot flash score > 4 who were receiving androgen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks, using a predefined treatment plan. The primary endpoint was a 50% reduction in the hot flash score after 4 weeks of therapy, calculated from the patients' daily hot flash diaries. The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide, and urinary 5-hydroxyindoleacetic acid, were examined. A total of 25 men were enrolled from September 2003 to April 2007. Of these, 22 were eligible and evaluable. After 4 weeks, 9 (41%, 95% confidence interval 21%-64%) of 22 patients had had a > 50% reduction in the hot flash score. Of the 22 patients, 12 (55%, 95% confidence interval 32%-76%) met this response definition at any point during the therapy course. No patient had a significant increase in hot flash score during therapy. A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality. Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. Of the 22 patients, 41% had responded by week 4 and 55% overall in the present pilot study, providing evidence of a potentially meaningful benefit. Additional studies of acupuncture for hot flashes in this population are warranted. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. TGF-β2 and TGF-β3 from cultured β-amyloid-treated or 3xTg-AD-derived astrocytes may mediate astrocyte-neuron communication. (United States)

    Tapella, Laura; Cerruti, Matteo; Biocotino, Isabella; Stevano, Alessio; Rocchio, Francesca; Canonico, Pier Luigi; Grilli, Mariagrazia; Genazzani, Armando A; Lim, Dmitry


    Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF-β) TGF-β1, TGF-β2 and TGF-β3. TGF-β1 is the most studied isoform, while production and release of TGF-β2 and TGF-β3 by astrocytes have been poorly characterized. Here, we report that purified cultures of hippocampal astrocytes produce mainly TGF-β3 followed by TGF-β2 and TGF-β1. Furthermore, astrocytes release principally the active form of TGF-β3 over the other two. Changes in release of TGF-β were sensitive to the calcineurin (CaN) inhibitor FK506. Starvation had no effect on TGF-β1 and TGF-β3 while TGF-β2 mRNA was significantly up-regulated in a CaN-dependent manner. We further investigated production and release of astroglial TGF-β in Alzheimer's disease-related conditions. Oligomeric β-amyloid (Aβ) down-regulated TGF-β1, while up-regulating TGF-β2 and TGF-β3, in a CaN-dependent manner. In cultured hippocampal astrocytes from 3xTg-AD mice, TGF-β2 and TGF-β3, but not TGF-β1, were up-regulated, and this was CaN-independent. In hippocampal tissues from symptomatic 3xTg-AD mice, TGF-β2 was up-regulated with respect to control mice. Finally, treatment with recombinant TGF-βs showed that TGF-β2 and TGF-β3 significantly reduced PSD95 protein in cultured hippocampal neurons, and this effect was paralleled by conditioned media from Aβ-treated astrocytes or from astrocytes from 3xTg-AD mice. Taken together, our data suggest that TGF-β2 and TGF-β3 are produced by astrocytes in a CaN-dependent manner and should be investigated further in the context of astrocyte-mediated neurodegeneration. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture

    DEFF Research Database (Denmark)

    Mehlhorn, A T; Schmal, H; Kaiser, S


    of any chondrogenic growth factor or in the presence of osteogenic signals. MSCs encapsulated in alginate beads were treated with transforming growth factor (TGF)-beta 3 for 3, 6, or 14 days and then cultured in absence of TGF-beta for the remainder of the 2-week culture period. Additionally, cells were...... cultured in osteogenic medium after TGF-beta-mediated chondroinduction. Gene expression of col2a1, aggrecan, COMP, alkaline phosphatase (AP), and correlating protein synthesis was analyzed. After short-term stimulation with TGF-beta, MSCs maintained a chondrogenic phenotype. Chondrogenic gene expression...... and protein synthesis directly correlated with the extent of stimulation time and the concentration of TGF-beta. Pretreatment with TGF-beta could prevent AP mRNA expression of encapsulated MSCs. TGF- beta stimulation within the first 3 days of culture seems to be crucial for the expression of a chondrogenic...

  8. Modulation role of angelica sinensis on transforming growth factor beta 1 (TGF-β1) expression induced by radiation in the lung tissue

    International Nuclear Information System (INIS)

    Xie Conghua; Zhou Yunfeng; Peng Gang; Zhou Fuxiang; Zhang Gong; Liang Chen; Liu Hui; Chen Ji; Xia Mingtong


    . In addition, we observed a pronounced decrease of mRNA and protein production of the TGF-β 1 in the AS/XRT group as compared to the XRT group. Therefore our results indicate that Angelica Sinensis down-regulates the radiation-induced TGF-β 1 release in the lung tissue, and it is maybe one of the possible mechanisms of this drug to reduce the lung toxicity after thoracic irradiation. (authors)

  9. An early warning system for flash floods in hyper-arid Egypt (United States)

    Cools, J.; Vanderkimpen, P.; El Afandi, G.; Abdelkhalek, A.; Fockedey, S.; El Sammany, M.; Abdallah, G.; El Bihery, M.; Bauwens, W.; Huygens, M.


    An early warning system (EWS) for flash floods has been developed for part of the Sinai peninsula of Egypt, an hyper-arid area confronted with limited availability of field data, limited understanding of the response of the wadi to rainfall, and a lack of correspondence between rainfall data and observed flash flood events. This paper shows that an EWS is not a "mission impossible" when confronted with large technical and scientific uncertainties and limited data availability. Firstly, the EWS has been developed and tested based on the best available information, this being quantitative data (field measurements, simulations and remote sensing images) complemented with qualitative "expert opinion" and local stakeholders' knowledge. Secondly, a set of essential parameters has been identified to be estimated or measured under data-poor conditions. These are: (1) an inventory of past significant rainfall and flash flood events, (2) the spatial and temporal distribution of the rainfall events and (3) transmission and infiltration losses and (4) thresholds for issuing warnings. Over a period of 30 yr (1979-2010), only 20 significant rain events have been measured. Nine of these resulted in a flash flood. Five flash floods were caused by regional storms and four by local convective storms. The results for the 2010 flash flood show that 90% of the total rainfall volume was lost to infiltration and transmission losses. Finally, it is discussed that the effectiveness of an EWS is only partially determined by technological performance. A strong institutional capacity is equally important, especially skilled staff to operate and maintain the system and clear communication pathways and emergency procedures in case of an upcoming disaster.

  10. Flash Mob Science - Increasing Seismic Hazard Awareness and Preparedness in Oregon (United States)

    Hoffman, J. S.; Lownsbery, D. S.


    Living in a region of imminent threat of a magnitude-9.0 (M­­­w ≈ ­9) earthquake is a daily reality for the millions of people predicted to be directly affected by a full rupture of the Cascadia Subduction Zone (CSZ), a fault line extending for hundreds of miles off the western coast of North America. Many coastal residents and visitors will also be affected by the tsunami caused by the rupture. How can the scientific community effectively communicate with those who are unaware of the threat and unprepared to respond? We are studying the effects of a novel approach to science outreach we have called Flash Mob Science. You have probably seen examples of flash mobs staging dynamic musical and dance routines to unsuspecting audiences. Similarly, Flash Mob Science takes the challenging (and often avoided) topic of earthquake and tsunami awareness and preparedness to unsuspecting audiences. However, Flash Mob Science seeks to move beyond having an audience of observers by engaging others as participants who enact important roles in an unfolding drama. We simulate the effects of seismic and tsunami events (e.g., prolonged surface shaking, falling debris, repeated tsunami surges) and model best practices in response (e.g., "Drop, Cover, Hold On" and moving quickly to high ground). True to the general flash mob model, when the Cascadia event inevitably does occur, it will come suddenly, and everyone affected will unavoidably be involved as actors in a real-life drama of immense scale. We seek to embed the learning of basic understandings and practices for an actual Cascadia event in a very small-scale, memorable, and sometimes even humorous, dramatization. We present here the lessons we have learned in the background, planning, and implementation of Flash Mob Science. We highlight the successes, limitations, and preliminary results evaluating the effectiveness of this outreach in developing learners' understandings and preparedness in an Oregon community affected by

  11. The disintegrin and metalloproteinase ADAM12 contributes to TGF-beta signaling through interaction with the type II receptor

    DEFF Research Database (Denmark)

    Atfi, Azeddine; Dumont, Emmanuelle; Colland, Frédéric


    Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological processes through two types of Ser/Thr transmembrane receptors: the TGF-beta type I receptor and the TGF-beta type II receptor (TbetaRII). Upon ligand binding, TGF-beta type I receptor activated by TbetaRII propagat...

  12. GeckoFTL: Scalable Flash Translation Techniques For Very Large Flash Devices

    DEFF Research Database (Denmark)

    Dayan, Niv; Bonnet, Philippe; Idreos, Stratos


    thereby harming performance and device lifetime. In this paper, we identify a key component of the metadata called the Page Validity Bitmap (PVB) as the bottleneck. PVB is used by the garbage-collectors of state-of-the-art FTLs to keep track of which physical pages in the device are invalid. PVB...... Gecko. Logarithmic Gecko is similar to an LSM-tree in that it first logs updates and later reorganizes them to ensure fast and scalable access time. Relative to the baseline of storing PVB in flash, Logarithmic Gecko enables cheaper updates at the cost of slightly more expensive garbage......-collection queries. We show that this is a good trade-off because (1) updates are intrinsically more frequent than garbage-collection queries to page validity metadata, and (2) flash writes are more expensive than flash reads. We demonstrate analytically and empirically through simulation that GeckoFTL achieves a 95...

  13. A Comparative Study of Reduced Variables Based Flash and Conventional Flash

    DEFF Research Database (Denmark)

    Michelsen, Michael Locht; Yan, Wei; Stenby, Erling Halfdan

    with a smaller set of independent variables. Various versions of the reduced variables methods have been proposed since the mid 80’s. The methods were first proposed for cubic equations of state (EoS) with zero binary interaction parameters (BIPs) and later generalized to situations with non-zero BIP matrices....... Most of the studies in the last decade suggest that the reduced variables methods are much more efficient than the conventional flash method. However, Haugen and Beckner questioned the advantages of the reduced variables methods in their recent paper (SPE 141399). A fair comparison between the reduced...... variables based flash and the conventional flash is not straightforward since the former is difficult to be formulated as unconstrained minimization and involves more complicated composition derivatives. With the recent formulations by Nichita and Graciaa (2010), it is possible to code the reduced variables...

  14. Stellate Cell Activation and Imbalanced Expression of TGF-β1/TGF-β3 in Acute Autoimmune Liver Lesions Induced by ConA in Mice

    Directory of Open Access Journals (Sweden)

    Liyun Wang


    Full Text Available Objective. To study the pathogenic feature of liver injury, activation of hepatic stellate cells, and dynamic expression of TGF-β1/TGF-β3 to reveal their role in liver injury induced by ConA. Methods. Mice were randomly divided into control group and ConA treatment group. ConA (20 mg/kg was injected through vena caudalis in ConA treatment group; the controls received the same volume of saline injection. After injection for 2 h, 8 h, 24 h, and 48 h, animals were terminated. Blood, liver, and spleen were harvested. Liver function and histopathology were studied. α-SMA, vimentin, TGF-β1, and TGF-β3 were detected. Results. After ConA injection, liver damage started to increase. Expression of α-SMA, vimentin, TGF-β1, and TGF-β3 was significantly enhanced; all above indicators reached peak at 8 h; but from 24 h after ConA injection, TGF-β3 expression began to decline, while the TGF-β1/TGF-β3 ratio at 48 h was significantly lower than control. Conclusion. (1 Autoimmune liver injury induced by ConA showed time-based features, in which the most serious liver lesions happened at 8 h after ConA injection. (2 Early activation of HSC and imbalance expression of TGF-β1 and TGF-β3 existed in ConA-induced acute autoimmune liver injury, which may be associated with liver dysfunction and the mechanisms of progression to fibrosis.

  15. Induction of CTGF by TGF-β1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives

    International Nuclear Information System (INIS)

    Haydont, Valerie; Mathe, Denis; Bourgier, Celine; Abdelali, Jalil; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine


    Background and purpose: Transforming Growth Factor β1 (TGF-β1) and its downstream effector Connective Tissue Growth Factor (CTGF/CCN2), are well known fibrogenic activators and we previously showed that the Rho/ROCK pathway controls CTGF expression in intestinal smooth muscle cells isolated from patients with delayed radiation enteritis. The aim of the present work was to investigate the balance between Smad and Rho signalling pathways in the TGF-β1 CTGF induction and modulation of radiation-induced fibrogenic differentiation after addition of pravastatin, an inhibitor of Rho isoprenylation. Patients and methods: Primary human smooth muscle cells isolated from normal (N-SMC) or radiation enteritis (RE-SMC) biopsies were incubated with TGF-β1 (10 ng/ml). Induction of CTGF, as well as nucleo-cytoplasmic distribution of phospho-Smad2/3, Smad2/3 and Smad4 were analysed by Western blot and immunocytochemistry. Smad DNA binding was assessed by EMSA and Rho activation was measured by pull-down assay. Results: After TGF-β1 addition, Smads were translocated to the nucleus in both cell types. Nuclear accumulation of Smad as well as their DNA-binding activity were higher in N-SMC than in RE-SMC, whereas the opposite was observed for Rho activation, suggesting a main involvement of Rho pathway in sustained fibrogenic differentiation. This hypothesis was further supported by the antifibrotic effect observed in vitro after cell treatment with pravastatin (i.e. decreased expression of CTGF, TGF-β1 and Collagen Iα2). Conclusions: Our results suggest that TGF-β1-induced CTGF transactivation mainly depends on the Smad pathway in N-SMC, whereas in RE-SMC, Smad and Rho pathways are involved. Inhibition of Rho activity by pravastatin alters fibrogenic differentiation in vitro which opens up new therapeutic perspectives

  16. Flash memories economic principles of performance, cost and reliability optimization

    CERN Document Server

    Richter, Detlev


    The subject of this book is to introduce a model-based quantitative performance indicator methodology applicable for performance, cost and reliability optimization of non-volatile memories. The complex example of flash memories is used to introduce and apply the methodology. It has been developed by the author based on an industrial 2-bit to 4-bit per cell flash development project. For the first time, design and cost aspects of 3D integration of flash memory are treated in this book. Cell, array, performance and reliability effects of flash memories are introduced and analyzed. Key performance parameters are derived to handle the flash complexity. A performance and array memory model is developed and a set of performance indicators characterizing architecture, cost and durability is defined.   Flash memories are selected to apply the Performance Indicator Methodology to quantify design and technology innovation. A graphical representation based on trend lines is introduced to support a requirement based pr...

  17. Onset conditions for flash sintering of UO2 (United States)

    Raftery, Alicia M.; Pereira da Silva, João Gustavo; Byler, Darrin D.; Andersson, David A.; Uberuaga, Blas P.; Stanek, Christopher R.; McClellan, Kenneth J.


    In this work, flash sintering was demonstrated on stoichiometric and non-stoichiometric uranium dioxide pellets at temperatures ranging from room temperature (26 °C) up to 600 °C . The onset conditions for flash sintering were determined for three stoichiometries (UO2.00, UO2.08, and UO2.16) and analyzed against an established thermal runaway model. The presence of excess oxygen was found to enhance the flash sintering onset behavior of uranium dioxide, lowering the field required to flash and shortening the time required for a flash to occur. The results from this study highlight the effect of stoichiometry on the flash sintering behavior of uranium dioxide and will serve as the foundation for future studies on this material.

  18. Lightning flash sizes relative to storm structure and turbulence during the Kinematic Texture and Lightning Experiment (United States)

    Bruning, E. C.; Salinas, V.; Berkseth, S.; Chmielewski, V.; Brothers, M.


    Ongoing work as part of the Kinematic Texture and Lightning Experiment at Texas Tech University has quantified the lightning flash size, rate, and energy alongside the turbulent structure of thunderclouds. 2016 was the final year of observations, which fielded two high-resolution mobile Ka-band radars and mobile environmental soundings. Lightning measurements were made by a VHF Lightning Mapping Array. In order to enhance the detection of the smallest lightning discharges in the turbulent portions of the thundercloud, a rapidly-deployable mobile Lightning Mapping Array (LMA) station augmented a traditional fixed LMA. This capability of targeting particular storm complexes with LMA measurements will be described, and the improved detection capability quantified. The complete set of field measurements from 2014-16 sampled numerous individual cells and storm complexes, ranging in intensity from multicellular convection to supercells and mesoscale convective systems. Flash measurements coincident with radar observations included deep, highly turbulent convective cores and extensive anvil regions. Comparison of flash characteristics across these storm morphologies will be shown, with a focus on the dynamical organization of storms and the turbulent kinematics that drive differences in lightning flash sizes and rates.

  19. Simple flash evaporator for making thin films of compounds

    Energy Technology Data Exchange (ETDEWEB)

    Hemanadhan, M.; Bapanayya, Ch.; Agarwal, S. C. [Department of Physics, Indian Institute of Technology, Kanpur 208016 (India)


    A simple and compact arrangement for flash evaporation is described. It uses a cell phone vibrator for powder dispensing that can be incorporated into a vacuum deposition chamber without any major alterations. The performance of the flash evaporation system is checked by making thin films of the optical memory chalcogenide glass Ge{sub 2}Sb{sub 2}Te{sub 5} (GST). Energy dispersive x-ray analysis shows that the flash evaporation preserves the stoichiometry in thin films.

  20. The echo-enabled harmonic generation options for FLASH II

    International Nuclear Information System (INIS)

    Deng, Haixiao; Decking, Winfried; Faatz, Bart


    FLASH II is an upgrade to the existing free electron laser (FEL) FLASH. The echo-enabled harmonic generation (EEHG) scheme is proposed to be a potential seeding option of FLASH II. In this paper, the possibility of EEHG operation of FLASH II is investigated for the first time. With a combination of existing numerical codes, i.e. a laser-beam interaction code in an undulator (LBICU), a beam tracking code in a chicane (ELEGANT) and an universal FEL simulating code (GENESIS), the effects of beam energy chirp and coherent synchrotron radiation (CSR) on EEHG operation are studied as well. In addition, several interesting issues concerning EEHG simulation are discussed. (orig.)

  1. Flash CS5.5 The Missing Manual

    CERN Document Server

    Grover, Chris


    You can build everything from simple animations to full-fledged iOS and Android apps with Flash CS5.5, but learning this complex program can be difficult-unless you have this fully updated, bestselling guide. Learn how to create gorgeous Flash effects even if you have no programming experience. With Flash CS5.5: The Missing Manual, you'll move from the basics to power-user tools with ease. Learn animation basics. Discover how to turn simple ideas into stunning animations.Master Flash's tools. Learn the animation and effects tools with clear explanations and hands-on examples.Use 3D effects. R

  2. Analisis dan Reduksi Bahaya ARC Flash pada Sistem Kelistrikan

    Directory of Open Access Journals (Sweden)

    Firman Aji Prasongko


    Full Text Available Upaya terakhir untuk menghitung bahaya yang berhubungan dengan potensi bahaya arc flash bergantung pada proteksi arus lebih untuk menghilangkan kondisi saat diberi gangguan. Efektivitas berbagai perangkat ditentukan oleh clearing time terkait dengan gangguan arus maksimum yang ada untuk setiap lokasi sistem. Industri komersial mulai melakukan prosedur pelabelan arc flash dan mulai mengenali pencegahan arc flash sebagai bagian dari program safety, perhitungan current method memungkinkan untuk menghitung incident energy (cal/cm² terkait dengan gangguan maksimum tiga phasa. Kesalahan terbanyak adalah besaran arus kurang dari besaran arus tiga phasa maksimum. Dalam Tugas Akhir ini akan dibahas perhitungan energy dan durasi lama terjadinya arc flash pada system kelistrikan pada electrical room.

  3. ALK and TGF-Beta Resistance in Breast Cancer (United States)


    Investigate in vivo and clinical relevance of Smad4 tyrosine phosphorylation in breast cancer; 2. Determine the role of ALK- mediated Smad4 phosphorylation in...suppressing breast tumor formation . Specifically, in this proposal, we will determine whether aberrant activation of ALK causes TGF-β resistance...further characterize the impact of ALK and Smad4 tyrosine phosphorylation on Smad4 signaling and transcriptional responses. For example , we determine

  4. The Peritoneum Is Both a Source and Target of TGF-β in Women with Endometriosis (United States)

    Young, Vicky J.; Brown, Jeremy K.; Saunders, Philippa T. K.; Duncan, W. Colin; Horne, Andrew W.


    Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (Pendometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (Pendometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation. PMID:25207642

  5. Biological significance of local TGF-β activation in liver diseases

    Directory of Open Access Journals (Sweden)

    Hiromitsu eHayashi


    Full Text Available The cytokine transforming growth factor-β (TGF-β plays a pivotal role in a diverse range of cellular responses, including cell proliferation, apoptosis, differentiation, migration, adhesion, angiogenesis, stimulation of extracellular matrix (ECM synthesis, and downregulation of ECM degradation. TGF-β and its receptors are ubiquitously expressed by most cell types and tissues in vivo. In intact adult tissues and organs, TGF-β is secreted in a biologically inactive (latent form associated in a noncovalent complex with the ECM. In response to injury, local latent TGF-β complexes are converted into active TGF-β according to a tissue- and injury type-specific activation mechanism. Such a well and tightly orchestrated regulation in TGF-β activity enables an immediate, highly localized response to type-specific tissue injury. In the pathological process of liver fibrosis, TGF-β plays as a master pro-fibrogenic cytokine in promoting activation and myofibroblastic differentiation of hepatic stellate cells, a central event in liver fibrogenesis. Continuous and/or persistent TGF-β signaling induces sustained production of ECM components and of metalloproteinase synthesis. Therefore, the regulation of locally activated TGF-β levels is increasingly recognized as a therapeutic target for liver fibrogenesis. This review summarizes our present knowledge of the activation mechanisms and bioavailability of latent TGF-β in biological and pathological processes in the liver.

  6. Muzzle flash localization for the dismounted soldier (United States)

    Kennedy Scott, Will


    The ability to accurately and rapidly know the precise location of enemy fire would be a substantial capability enhancement to the dismounted soldier. Acoustic gun-shot detections systems can provide an approximate bearing but it is desired to precisely know the location (direction and range) of enemy fire; for example to know from `which window' the fire is coming from. Funded by the UK MOD (via Roke Manor Research) QinetiQ is developing an imaging solution built around an InGaAs camera. This paper presents work that QinetiQ has undertaken on the Muzzle Flash Locator system. Key technical challenges that have been overcome are explained and discussed in this paper. They include; the design of the optical sensor and processing hardware to meet low size, weight and power requirements; the algorithm approach required to maintain sensitivity whilst rejecting false alarms from sources such as close passing insects and sun glint from scene objects; and operation on the move. This work shows that such a sensor can provide sufficient sensitivity to detect muzzle flash events to militarily significant ranges and that such a system can be combined with an acoustic gunshot detection system to minimize the false alarm rate. The muzzle flash sensor developed in this work operates in real-time and has a field of view of approximately 29° (horizontal) by 12° (vertical) with a pixel resolution of 0.13°. The work has demonstrated that extension to a sensor with realistic angular rotation rate is feasible.

  7. TGF-β Signaling in Bone Remodeling and Osteosarcoma Progression

    Directory of Open Access Journals (Sweden)

    Audrey Lamora


    Full Text Available Osteosarcomas are the most prevalent malignant primary bone tumors in children. Despite intensive efforts to improve both chemotherapeutics and surgical management, 40% of all osteosarcoma patients succumb to the disease. Specifically, the clinical outcome for metastatic osteosarcoma remains poor; less than 30% of patients who present metastases will survive five years after initial diagnosis. Treating metastatic osteosarcoma thus remains a challenge. One of the main characteristics of osteosarcomas is their ability to deregulate bone remodelling. The invasion of bone tissue by tumor cells indeed affects the balance between bone resorption and bone formation. This deregulation induces the release of cytokines or growth factors initially trapped in the bone matrix, such as transforming growth factor-β (TGF-β, which in turn promote tumor progression. Over the past years, there has been considerable interest in the TGF-β pathway within the cancer research community. This review discusses the involvement of the TGF-β signalling pathway in osteosarcoma development and in their metastatic progression.

  8. Helium Extraction from LNG End Flash


    Kim, Donghoi


    Helium is an invaluable element as it is widely used in industry such as cryo-genics and welding due to its unique properties. However, helium shortage is expected in near future because of increasing demand and the anxiety of sup-ply. Consequently, helium production has attracted the attention of industry. The main source of He is natural gas and extracting it from LNG end-flash is considered as the most promising way of producing crude helium. Thus, many process suppliers have proposed proc...

  9. 3D flash lidar imager onboard UAV (United States)

    Zhou, Guoqing; Liu, Yilong; Yang, Jiazhi; Zhang, Rongting; Su, Chengjie; Shi, Yujun; Zhou, Xiang


    A new generation of flash LiDAR sensor called GLidar-I is presented in this paper. The GLidar-I has been being developed by Guilin University of Technology in cooperating with the Guilin Institute of Optical Communications. The GLidar-I consists of control and process system, transmitting system and receiving system. Each of components has been designed and implemented. The test, experiments and validation for each component have been conducted. The experimental results demonstrate that the researched and developed GLiDAR-I can effectively measure the distance about 13 m at the accuracy level about 11cm in lab.

  10. Determinants of Flash Flood Evacuation Choices and Assessment of Preferences for Flash Flood Warning Channels: The Case of Thailand


    Kannika Thampanishvong


    The Southern part of Thailand, a region with tropical climate and monsoon, has often been affected by torrential rains caused by tropical storms, depressions, and typhoons. Such heavy rain is often accompanied by flash floods – sometimes occuring so suddenly and with an enormous amount of water – that make them particularly dangerous. Hence, flash flood warnings are important to prevent flash flood hazards from becoming disasters.These warnings can give individuals the much needed information...

  11. Acquired TGF beta 1 sensitivity and TGF beta 1 expression in cell lines established from a single small cell lung cancer patient during clinical progression

    DEFF Research Database (Denmark)

    Nørgaard, P; Damstrup, L; Rygaard, K


    Three small cell lung cancer cell lines established from a single patient during longitudinal follow-up were examined for in vitro expression of TGF beta and TGF beta receptors, i.e. the components of an autocrine loop. GLC 14 was established prior to treatment, GLC 16 on relapse after chemotherapy...... was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously administrated TGF beta 1. TGF beta 1 mRNA and protein in its latent form was only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was paralleled...... II receptor gene, as examined by Southern blotting. Also, the type I receptor could not be detected by ligand binding assay in this cell line, despite expression of mRNA for this receptor. This agrees with previous findings that type I receptor cannot bind TGF beta 1 without co-expression of the type...

  12. TGF-β and Th17 cells related injuries in patients with sulfur mustard exposure. (United States)

    Panahi, Yunes; Ghanei, Mostafa; Hassani, Saeed; Sahebkar, Amirhossein


    Sulfur mustard (SM) is a vesicating agent that has been employed as a chemical warfare agent. High-dose exposure to sulfur mustard may lead to the damage of rapidly proliferating cells of bone marrow and, therefore, suppression of the immune system. This may be continued as dysfunction of the immune system, and ultimately result in secondary immune disorders. Studies have suggested a role for T cells in SM-induced lung injury. Moreover, observations from animal studies indicate a delayed-type hypersensitivity (DTH) response after skin exposure to SM, providing an understanding that SM can stimulate specific T cell-mediated immune responses. On the other hand, T helper (Th) 17 cells, which are a subset of CD4+ T cells, have recently been reported to be involved in a number of inflammatory, autoimmune, and chronic fibrotic lung diseases. Furthermore, a strong association has been established between the overproduction of profibrotic cytokines like transforming growth factor (TGF)-β and Th17 cell number. In this review, we aimed to go through the new findings about the involvement and interactions of TGF-β and Th17 in SM-related injuries. © 2017 Wiley Periodicals, Inc.

  13. Measurements in shock physics: R and D in flash radiography

    International Nuclear Information System (INIS)

    Abraham, I.; Caron, M.; Etchessahar, B.; Le Dain, L.; Negre, J.P.; Partouche-Sebban, D.; Pichoff, N.; Toury, M.


    Within the simulation program of Cea-Dam, the radiographs produced by the AIRIX facility (induction Linac for flash radiography and X-ray imaging), provide fundamental experimental data for studying the dynamic behaviour of non nuclear materials under the effects of chemical explosive detonation. In order to improve the precision on the observed phenomena (locations of materials interfaces, development of instabilities, etc.), various research and development works have been performed on the modelling of the radiographic image formation, on the optimization of the radiographic chain and on the algorithms for image processing. This article presents in particular the studies on the various technologies of X-sources, on the new configurations of radiographic chains, and on the new digital imagers. (authors)

  14. Optical emission from Al target irradiated by FLASH

    International Nuclear Information System (INIS)

    Stránský, M; Rohlena, K


    The following text touches on some peculiarities in optical emission spectroscopy results from experiments on the free-electron laser FLASH [1, 2]. Aluminum targets were irradiated with 13.5 nm ∼ 25 fs pulses at intensities of 10 13 and 10 16 W/cm 2 (20 and 1 μm foci). Surprisingly, only neutral atom lines for the case with wider focus and traces of ion lines in the tighter focus case were observed with the optical emission spectroscopy (200–600 nm range), [2]. The motivating idea behind this work is the suggestion in [1] by Zastrau that the optical spectrometer sees only emissions from a cold expanding lower-density (< 10 22 cm −3 ) plasma plume. In this contribution the notion of UV range screening is analyzed in detail.

  15. Accumulation-associated Protein Gene and TGF-beta 1 Affects the Formation of Lung Cancer-related Biological Material Staphylococcus Epidermidis Biofilm

    Directory of Open Access Journals (Sweden)

    Ying CHEN


    Full Text Available Background and objective This study was conducted to evaluate the effects of the accumulation-associated protein (Aap gene and transform growth factor-beta 1 (TGF-β1 on the biofilm formation of lung cancer-related Staphylococcus epidermidis (SE. Methods Species identification was performed to isolate SE strains from clinically implanted materials in lung cancer patients. Stable genetic aggregated proteins, which are associated with negative and positive isolates, were obtained. The biofilm-formation ability of the SE Aap gene was determined by PCR. Density gradient method was used to extract peripheral blood mononuclear cells from patients with non-small cell lung cancer. After 30 h, these cells were co-cultured with A549 at different TGF-β1 concentrations. The supernatant was then combined with SE Aap+ and SE Aap- strains and co-cultured with a medical silicone rubber. A semi-quantitative adhesion test was performed for each bacterial biofilm formation. Scanning electron microscopy was also conducted to observe the microcosmic condition of this material on the bacterial biofilm surface. Results The Aap gene was closely related to SE biofilm formation. At 10 ng/mL, 20 ng/mL, and 40 ng/mL, SE Aap+ biofilm on the medical silicone rubber surface was thicker in the TGF-β1 group than in the control group. No significant differences were found between TGF-β1 groups. For the SE Aap- strains, no evident biofilm was formed in TGF-β1 and control groups. Conclusion In plant material-related infection of lung cancer patients, SE Aap+ strain easily forms biofilm. Furthermore, TGF-β1 was conducive for the biofilm formation of SE Aap+ strains.

  16. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  17. Effect of EDTA on TGF-β1 released from the dentin matrix and its influence on dental pulp stem cell migration. (United States)

    Gonçalves, Lidiany Freitas; Fernandes, Ana Paula; Cosme-Silva, Leopoldo; Colombo, Fabio Antonio; Martins, Natália Silva; Oliveira, Thais Marchini; Araujo, Tomaz Henrique; Sakai, Vivien Thiemy


    Bioactive molecules stored in dentin, such as transforming growth factor beta1 (TGF-b1), may be involved in the signaling events related to dental tissue repair. The authors conducted an in vitro evaluation of the amount of TGF-b1 released from dentin slices after treatment with 10% ethylenediaminetetraacetic acid (EDTA), 2.5% sodium hypochlorite (NaOCl) or phosphate-buffered saline (PBS), and the effect of this growth factor on stem cell migration from human exfoliated deciduous teeth (SHED). Sixty 1-mm-thick tooth slices were prepared with or without the predentin layer, and treated with either 10% EDTA for 1 minute, 2.5% NaOCl for 5 days or kept in PBS. Tooth slice conditioned media were prepared and used for TGF-b1 ELISA and migration assays. Culture medium with different concentrations of recombinant human TGF-b1 (0.5, 1.0, 5.0 or 10.0 ng/mL) was also tested by migration assay. The data were evaluated by ANOVA and Tukey's test. Optical density values corresponding to media conditioned by tooth slices either containing or not containing the predentin layer and treated with 10% EDTA were statistically greater than the other groups and close to 1 ng/mL. Increased rates of migration toward media conditioned by tooth slices containing the predentin layer and treated with PBS, 10% EDTA or 2.5% NaOCl were observed. Recombinant human TGF-b1 also stimulated migration of SHED, irrespective of the concentration used. EDTA may be considered an effective extractant of TGF-b1 from the dentin matrix. However, it does not impact SHED migration, suggesting that other components may account for the cell migration.

  18. Analysis of thunderstorm and lightning activity associated with sprites observed during the EuroSprite campaigns

    DEFF Research Database (Denmark)

    Soula, S.; van der Velde, O.; Montanyà, J.


    -producing periods followed a maximum in the CG lightning activity and were characterized by a low CG flash rate with a high proportion of + CG flashes, typically around 50%. All sprites were associated with + CGs except one which was observed after a − CG as detected by the Météorage network. This − CG...... a subsequent CG flash (median value lightning process associated with a sprite consisted of 7 CG flashes....

  19. Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase (United States)

    Namachivayam, Kopperuncholan; Blanco, Cynthia L.; Frost, Brandy L.; Reeves, Aaron A.; Jagadeeswaran, Ramasamy; MohanKumar, Krishnan; Safarulla, Azif; Mandal, Partha; Garzon, Steven A.; Raj, J. Usha


    Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects. PMID:23558011

  20. Intra-bunch-train transverse dynamics in the superconducting accelerators FLASH and European XFEL

    Energy Technology Data Exchange (ETDEWEB)

    Hellert, Thorsten


    FLASH and the European XFEL are linear accelerator driven SASE-FELs, operating in a pulsed mode with long bunch-trains. Multi-bunch FEL operation requires longitudinal and transverse stability within the bunch-train. The purpose of this work is to investigate the intra-bunch-train transverse dynamics at FLASH and XFEL. Key relationships of superconducting RF cavity operation, their misalignments and the resulting impact on the intra-bunch-train trajectory variation are described. In this thesis a numerical model is developed and simulations for different accelerating sections at FLASH and XFEL are performed. With the current operational setup significant intra-bunch-train trajectory variation must be considered, hence approaches for their reduction are discussed. The theoretical studies are compared to experimental results at FLASH. The observed trajectory variation during multi-bunch user runs is analyzed and related to causal intra-bunch-train variations of the RF and the following impact on the multi-bunch SASSE performance. Furthermore, HOM-based cavity misalignment measurements are performed and the deduction of misalignments from multi-bunch data is considered.

  1. Case studies of selected Project "Flash" events

    Directory of Open Access Journals (Sweden)

    K. A. Nicolaides


    Full Text Available Flooding is a consequence of the prevailing meteorological situation, the intensity and duration of precipitation, geomorphology, human activities over a geographical region and other factors. Floods result in damage and destruction of infrastructure and private property and, in some cases, in fatalities. Flash floods are sudden and quite localized in extend, characterized by excessive amounts of rainfall within a short period of time and are distinguished from other floods by their degree of severity. The broader knowledge concerning flash floods is useful for the better understanding of the underlying thermodynamic and dynamic mechanisms, as well as the associated physical processes. The wider understanding of flashfloods can form part of an integrated system for short and very short forecasting of these events. In the present study, the synoptic, dynamic and thermodynamic conditions during the development of a baroclinic depression which affected the area of Cyprus on 6 November 2005 are studied. The depression was associated with extreme weather phenomena, such as thunderstorms, a water spout and high precipitation accumulations. The results indicate the importance of the dynamic parameters in the system's development and the thermodynamic analysis has shown the convective potential of the atmosphere.

  2. Flash pyrolysis fuel oil: BIO-POK

    Energy Technology Data Exchange (ETDEWEB)

    Gust, S. [Neste Oy, Porvoo (Finland)


    Flash pyrolysis oil from Ensyn Tech., Canada and Union Fenosa, Spain was combusted with simple pressure atomisation equipment commonly used with light fuel oils in intermediate size (0.1-1 MW) boilers. With a number of modifications to the combustion system, carbon monoxide (CO) and nitrous oxide (NO{sub x}) could be reduced to acceptable levels: CO < 30 ppm and NO{sub x} < 140 ppm. Particulate emissions which were initially very high (Bacharach 4-5) were reduced (Bach. 2-3) by system changes but are still higher than from light fuel oil (Bach. <1). The modifications to the combustion system were: acid resistant progressive cavity pump, higher oil preheat temperature and higher oil pressure than for light fuel oils, refractory section between burner and boiler warmed up to at least 800 deg C. In addition, it was necessary to store pyrolysis oil samples under inert conditions to prevent oxidation and to rinse nozzles with alcohol after shutdown to prevent coking. The complexity and cost of these system modifications are considered to be too great for current grades of flash pyrolysis oil to be sold as a light fuel oil replacement. Improvements to fuel quality will be necessary. The main improvements are lowering of viscosity and improving of stability

  3. Flash Infrared Thermography Contrast Data Analysis Technique (United States)

    Koshti, Ajay


    This paper provides information on an IR Contrast technique that involves extracting normalized contrast versus time evolutions from the flash thermography inspection infrared video data. The analysis calculates thermal measurement features from the contrast evolution. In addition, simulation of the contrast evolution is achieved through calibration on measured contrast evolutions from many flat-bottom holes in the subject material. The measurement features and the contrast simulation are used to evaluate flash thermography data in order to characterize delamination-like anomalies. The thermal measurement features relate to the anomaly characteristics. The contrast evolution simulation is matched to the measured contrast evolution over an anomaly to provide an assessment of the anomaly depth and width which correspond to the depth and diameter of the equivalent flat-bottom hole (EFBH) similar to that used as input to the simulation. A similar analysis, in terms of diameter and depth of an equivalent uniform gap (EUG) providing a best match with the measured contrast evolution, is also provided. An edge detection technique called the half-max is used to measure width and length of the anomaly. Results of the half-max width and the EFBH/EUG diameter are compared to evaluate the anomaly. The information provided here is geared towards explaining the IR Contrast technique. Results from a limited amount of validation data on reinforced carbon-carbon (RCC) hardware are included in this paper.

  4. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis. (United States)

    Gonzalo-Gil, Elena; Galindo-Izquierdo, María


    Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  5. RLIM interacts with Smurf2 and promotes TGF-β induced U2OS cell migration

    International Nuclear Information System (INIS)

    Huang, Yongsheng; Yang, Yang; Gao, Rui; Yang, Xianmei; Yan, Xiaohua; Wang, Chenji; Jiang, Sirui; Yu, Long


    Highlights: → RLIM directly binds to Smurf2. → RLIM enhances TGF-β responsiveness in U2OS cells. → RLIM promotes TGF-β driven migration of osteosarcoma U2OS cells. -- Abstract: TGF-β (transforming growth factor-β), a pleiotropic cytokine that regulates diverse cellular processes, has been suggested to play critical roles in cell proliferation, migration, and carcinogenesis. Here we found a novel E3 ubiquitin ligase RLIM which can directly bind to Smurf2, enhancing TGF-β responsiveness in osteosarcoma U2OS cells. We constructed a U2OS cell line stably over-expressing RLIM and demonstrated that RLIM promoted TGF-β-driven migration of U2OS cells as tested by wound healing assay. Our results indicated that RLIM is an important positive regulator in TGF-β signaling pathway and cell migration.

  6. Effect of collagen length distribution and timing for repair on the active TGF-β concentration in tendon. (United States)

    Mehdizadeh, Arash; Gardiner, Bruce S; Lavagnino, Michael; Smith, David W


    The composition of extracellular matrix (ECM) in tendon depends on the secretion profile of resident cells known as tenocytes. For tissues with a mechanical role like tendon, mechanical strain is known to play an important role in determining the secretion profile of resident cells. Previously we explored the idea of estimating average concentrations of ECM molecules as a function of tendon strain magnitude and number of loading cycles. Specifically, we developed a model of the mechanical fatigue damage of tendon collagen fibers and introduced elementary cell responses (ECRs) by which local cellular-level responses to the strain environment, combined with the fatigue damage model, were scaled up to predict tissue-level responses. Using this approach, we demonstrated that the proposed model is capable of estimating average concentrations of ECM molecules that qualitatively accord with experimental observations. In this study, we increase model realism by extending this approach to consider the implications of a non-uniform collagen fiber distribution, and the influence of time delay on repair of damaged collagen fibers. Using this approach, we focus the study on the average tenocyte secretion profile for active transforming growth factor beta (TGF-β), and discover that increasing fiber length dispersion and/or increasing repair delay leads to increasing active TGF-β concentrations, and reduced sensitivity of average concentration profile of TGF-β to tendon strain.

  7. Pentoxifylline improves liver regeneration through down-regulation of TNF-α synthesis and TGF-β1 gene expression (United States)

    Martino, Rodrigo Bronze; Coelho, Ana Maria Mendonça; Kubrusly, Márcia Saldanha; Leitão, Regina; Sampietre, Sandra Nassa; Machado, Marcel Cerqueira Cesar; Bacchella, Telesforo; D’Albuquerque, Luiz Augusto Carneiro


    AIM: To investigate the mechanism of pentoxifylline (PTX) improvement in liver regeneration. RESULTS: Rats were randomized into 4 groups: Control rats; Sham - sham-operation rats; Saline - 70% hepatectomy plus saline solution; PTX - 70% hepatectomy plus PTX. At 2 and 6 h after hepatectomy, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) serum and hepatic tissue levels were determined. Tumor growth factor (TGF)-β1 gene expression in liver tissue was evaluated 24 h after hepatectomy by quantitative reverse transcriptase polymerase chain reaction analysis. Proliferation was analyzed by mitotic index and proliferating cell nuclear antigen (PCNA) staining 48 h after hepatectomy. RESULTS: TNF-α and IL-6 serum levels increased at 2 and 6 h after hepatectomy. At 2 h after hepatectomy serum PTX was reduced but not hepatic levels of TNF-α and IL-6. A decrease in liver TGF-β1 gene expression and an increase in mitotic index and PCNA after hepatectomy were observed in the PTX treatment group in comparison to the saline group. CONCLUSION: PTX improves liver regeneration by a mechanism related to down regulation of TNF-α production and TGF-β1 gene expression. PMID:22816029

  8. Adipose-Derived Stem Cells Alleviate Radiation-Induced Muscular Fibrosis by Suppressing the Expression of TGF-β1

    Directory of Open Access Journals (Sweden)

    Wei Sun


    Full Text Available We aim to investigate the effects of adipose-derived stem cells (ASCs transplantation on irradiation-induced skeletal muscle fibrosis. Sixty-four rabbits were randomly divided into ASCs group and PBS group followed by irradiation at unilateral hip with a single dose of 80 Gy. Nonirradiated side with normal skeletal muscle served as normal control. Skeletal muscle tissues were collected from eight rabbits in each group at 1 w, 4 w, 8 w, and 26 w after irradiation. Migration of ASCs was observed in the peripheral tissues along the needle passage in the injured muscle. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than those of PBS groups at 4 w, 8 w, and 26 w after irradiation. Significant decrease was noted in the integrated optimal density of the transforming growth factor β1 (TGF-β1 in the ASCs group compared with those of PBS group at 4 w, 8 w, and 26 w after irradiation. Moreover, the expression of TGF-β1 was lower in the ASCs group compared to those of the PBS group at each time point determined by Western blot analysis. ASCs transplantation could alleviate irradiation fibrosis by suppressing the level of TGF-β1 in the irradiated skeletal muscle.

  9. Aqueous Humor Levels of TGF-β2 and TNF-α in Indonesian Eyes With Acute Primary Angle Closure. (United States)

    Artini, Widya; Gondhowiardjo, Tjahjono Darminto; Supiandi, Edi S; Tin, Aung


    To measure aqueous humor levels of TGF-β2 and TNF-α in Indonesian eyes with acute primary angle closure (APAC) and to investigate their relationship to response to treatment. A prospective observational study. On presentation, aqueous humor samples were taken from APAC eyes by paracentesis. All APAC eyes then underwent laser peripheral iridotomy (LPI). Two weeks following LPI, trabeculectomy was performed if the intraocular pressure (IOP) was still high. Alternatively, phacoemulsification was performed in cases of normal IOP. Aqueous humor samples were taken again at the time of both surgical procedures. Age-matched cataract patients were included as a control group. Cytokine samples were measured by enzyme-linked immunosorbent assay (ELISA). Forty-three Indonesian APAC subjects were recruited in this study. The mean presenting IOP was 56.4 ± 0.52 mmHg and 53% underwent trabeculectomy. Comparison of the APAC eyes to the control group showed there was a significant difference in the mean levels of TGF-β2 (2007.7 ± 827.2 pg/mL vs 466.1 ± 219.3 pg/mL, p < 0.001) and TNF-α (0.714 ± 0.33 pg/mL vs 0.228 ± 0.16 pg/mL, p < 0.001). There was no significant difference in the presented TGF-β2 and TNF-α levels between the trabeculectomy and phacoemulsification groups (p:0.391 and p:0.494). Between presentation and surgery in the trabeculectomy subgroup, both cytokine levels appeared to be significantly different (p < 0.035 and p < 0.038). This study showed the aqueous humor levels of TGF-β2 and TNF-α appeared high at presentation but decreased subsequently, with no difference detected between groups with persistently high IOP and those with normalized IOP.

  10. Induction of galectin-1 by TGF-β1 accelerates fibrosis through enhancing nuclear retention of Smad2

    Energy Technology Data Exchange (ETDEWEB)

    Jin Lim, Min; Ahn, Jiyeon [Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Youn Yi, Jae [Department of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Kim, Mi-Hyoung; Son, A-Rang; Lee, Sae-lo-oom [Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lim, Dae-Seog [Department of Applied Bioscience, CHA University (Korea, Republic of); Soo Kim, Sung [Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Ae Kang, Mi [Department of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Han, Youngsoo, E-mail: [Division of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Song, Jie-Young, E-mail: [Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)


    Fibrosis is one of the most serious side effects in cancer patients undergoing radio-/ chemo-therapy, especially of the lung, pancreas or kidney. Based on our previous finding that galectin-1 (Gal-1) was significantly increased during radiation-induced lung fibrosis in areas of pulmonary fibrosis, we herein clarified the roles and action mechanisms of Gal-1 during fibrosis. Our results revealed that treatment with TGF-β1 induced the differentiation of fibroblast cell lines (NIH3T3 and IMR-90) to myofibroblasts, as evidenced by increased expression of the fibrotic markers smooth muscle actin-alpha (α-SMA), fibronectin, and collagen (Col-1). We also observed marked and time-dependent increases in the expression level and nuclear accumulation of Gal-1. The TGF-β1-induced increases in Gal-1, α-SMA and Col-1 were decreased by inhibitors of PI3-kinase and p38 MAPK, but not ERK. Gal-1 knockdown using shRNA decreased the phosphorylation and nuclear retention of Smad2, preventing the differentiation of fibroblasts. Gal-1 interacted with Smad2 and phosphorylated Smad2, which may accelerate fibrotic processes. In addition, up-regulation of Gal-1 expression was demonstrated in a bleomycin (BLM)-induced mouse model of lung fibrosis in vivo. Together, our results indicate that Gal-1 may promote the TGF-β1-induced differentiation of fibroblasts by sustaining nuclear localization of Smad2, and could be a potential target for the treatment of pulmonary fibrotic diseases. - Highlights: • Galectin-1 (Gal-1) promotes TGF-β-induced fibroblast differentiation via activation of PI3-kinase and p38 MAPK. • Gal-1 binds to Smad2 and phosphorylated Smad2. • GAl-1 may be a new therapeutic target for attenuating lung fibrotic process.

  11. Mutations in a TGF-β Ligand, TGFB3, Cause Syndromic Aortic Aneurysms and Dissections (United States)

    Bertoli-Avella, Aida M.; Gillis, Elisabeth; Morisaki, Hiroko; Verhagen, Judith M.A.; de Graaf, Bianca M.; van de Beek, Gerarda; Gallo, Elena; Kruithof, Boudewijn P.T.; Venselaar, Hanka; Myers, Loretha A.; Laga, Steven; Doyle, Alexander J.; Oswald, Gretchen; van Cappellen, Gert W.A.; Yamanaka, Itaru; van der Helm, Robert M.; Beverloo, Berna; de Klein, Annelies; Pardo, Luba; Lammens, Martin; Evers, Christina; Devriendt, Koenraad; Dumoulein, Michiel; Timmermans, Janneke; Bruggenwirth, Hennie T.; Verheijen, Frans; Rodrigus, Inez; Baynam, Gareth; Kempers, Marlies; Saenen, Johan; Van Craenenbroeck, Emeline M.; Minatoya, Kenji; Matsukawa, Ritsu; Tsukube, Takuro; Kubo, Noriaki; Hofstra, Robert; Goumans, Marie Jose; Bekkers, Jos A.; Roos-Hesselink, Jolien W.; van de Laar, Ingrid M.B.H.; Dietz, Harry C.; Van Laer, Lut; Morisaki, Takayuki; Wessels, Marja W.; Loeys, Bart L.


    Background Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-β signaling. Objectives This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. Methods We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. Results Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-β signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-β signaling in association with up-regulation of the expression of TGF-β ligands. Conclusions Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk. PMID:25835445

  12. Down-regulation of transforming growth factor-β type II receptor (TGF-βRII protein and mRNA expression in cervical cancer

    Directory of Open Access Journals (Sweden)

    Gariglio Patricio


    Full Text Available Abstract Background Cervical carcinogenesis is a multistep process initiated by "high risk" human papillomaviruses (HR-HPV, most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β (TGF-β inhibits epithelial proliferation and altered expression of TGF-β or its receptors may be important in carcinogenesis. One cofactor candidate to initiate neoplasia in cervical cancer is the prolonged exposure to sex hormones. Interestingly, previous studies demonstrated that estrogens suppress TGF-β induced gene expression. To examine the expression of TGF-β2, TGF-βRII, p15 and c-myc we used in situ RT-PCR, real-time PCR and immunohistochemistry in transgenic mice expressing the oncogene E7 of HPV16 under control of the human Keratin-14 promoter (K14-E7 transgenic mice and nontransgenic control mice treated for 6 months with slow release pellets of 17β-estradiol. Results Estrogen-induced carcinogenesis was accompanied by an increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-E7 mice. TGF-β2 mRNA and protein levels increased in K14-E7 transgenic mice as compared with nontransgenic mice and further increased after hormone-treatment in both nontransgenic and transgenic mice. In contrast, TGF-βRII mRNA and protein levels were decreased in K14-E7 transgenic mice compared to nontransgenic mice and these levels were further decreased after hormone treatment in transgenic mice. We also observed that c-myc mRNA levels were high in K14-E7 mice irrespective of estrogen treatment and were increased in estrogen-treated nontransgenic mice. Finally we found that p15 mRNA levels were not increased in K14-E7 mice. Conclusion These results suggest that the synergy between estrogen and E7 in inducing cervical cancer may in part reflect the ability of both factors to modulate TGF-β signal transduction.

  13. Modelling of flash pyrolysis of a single wood particle.

    NARCIS (Netherlands)

    Janse, A.M.C.; Janse, A.M.C.; Westerhout, R.W.J.; Westerhout, R.W.J.; Prins, W.


    Reactors for flash pyrolysis of biomass are designed to maximize the yield of bio-oil, at the expense of the by-products gas and char. To understand which chemical and physical factors influence the yield to bio-oil, the flash pyrolysis of a cylindrical wood particle with a maximum diameter of 1000

  14. Inserting a Flash movie into a PowerPoint presentation. (United States)

    Elfarssi, Saïd


    Macromedia Flash is a multimedia authoring software that is used to create dynamic presentations for the World Wide Web. Flash allows you to mix sound, animation, and graphics into a single file that can be added to a PowerPoint presentation for dynamic effect.

  15. Microstructure of wood charcoal prepared by flash heating

    NARCIS (Netherlands)

    Kurosaki, F; Ishimaru, K; Hata, T; Bronsveld, P; Kobayashi, E; Imamura, Y


    Carbonized wood prepared by flash heating at 800 degreesC for I h shows a different microstructure and surface chemical structure than char formed after slow heating at 4 degreesC/min to 800 degreesC for I h. Flash heating produces pores that are surrounded by aggregates of carbon structures 25 to

  16. Flash radiographic technique applied to fuel injector sprays

    International Nuclear Information System (INIS)

    Vantine, H.C.


    A flash radiographic technique, using 50 ns exposure times, was used to study the pattern and density distribution of a fuel injector spray. The experimental apparatus and method are described. An 85 kVp flash x-ray generator, designed and fabricated at the Lawrence Livermore Laboratory, is utilized. Radiographic images, recorded on standard x-ray films, are digitized and computer processed

  17. Hot flashes: a review of pathophysiology and treatment modalities. (United States)

    Morrow, Phuong Khanh H; Mattair, Danielle N; Hortobagyi, Gabriel N


    Many therapies are being studied for the treatment of hot flashes for individuals with cancer, yet few studies have demonstrated safe and effective clinical benefit for those who suffer from this distressing symptom. The purpose of this paper is to assess the current options for the management of hot flashes, examining key endpoints from recent clinical trials and reviewing future directions. Hot flashes are a common stressful symptom for individuals with cancer, particularly women with a history of breast cancer and men with prostate cancer. Lifestyle modifications are proposed as the first step in the management of less severe hot flashes. Several publications have addressed nonhormonal agents as a treatment option for hot flashes. Newer antidepressant and anticonvulsant agents have been studied and show potential in treating vasomotor symptoms. Although many complementary and alternative therapies, including herbal medications and phytoestrogens, have been studied for the treatment of hot flashes, none are clinically recommended at this time. Additionally, further evidence is needed for supportive exercise such as yoga and relaxation techniques. Acupuncture may warrant further investigation in the reduction and severity of hot flashes in both men and women. Hormonal therapies, including estrogens and progestogens, are the most well-known and efficient agents in alleviating hot flashes; however, the safety of these agents is disputable.

  18. Estimate Of Positive Ground Lightning Flashes In Ibadan, Nigeria ...

    African Journals Online (AJOL)

    Positive ground lightning flashes have been monitored for a period of one year in Ibadan, Nigeria. The instrument used was lightning flash counter designed to isolate only positive lightning discharges at average radiation field change of 5.0 v/m and peak frequency response of 17.0kHz with 3dB attenuation and effective ...

  19. Comparison of colostrum TGF-β2 levels between lactating women in Japan and Nepal. (United States)

    Aihara, Yoko; Oh-oka, Kyoko; Kondo, Naoki; Sharma, Jyoti; Ishimaru, Kayoko; Hara, Mutsuko; Yamagata, Zentaro; Nakao, Atsuhito


    Maternal milk-borne transforming growth factor (TGF-β plays a potential role in the development of the mucosal immune system in infants. However, it remains unclear what factors determine TGF-β levels in breast milk. We hypothesized that microbial pressures during pregnancy might affect the expression levels of TGF-β in colostrum. This study compared TGF-β2 levels in colostrum of lactating women living in Japan and Nepal with contrasting hygiene statuses. Additionally, we identified environmental and intrinsic factors influencing TGF-β levels in colostrum. Breast milk samples and structured questionnaires were collected from 80 women living in Japan and 208 women living in Nepal. A robust regression model was used to identify factors associated with colostral TGF-β levels. Analysis using the Mann-Whitney U test showed that TGF-β levels were significantly higher in Japanese women than in Nepalese women. Japanese women who consumed animal milk daily during pregnancy and had atopic dermatitis expressed lower levels of TGF-β in colostrum, as compared to Japanese women who did not. Among Nepalese women, large family size and higher birth order were associated with lower TGF-β levels and women who gave birth to infants with low birth weight had higher expression of TGF-β levels in milk than women who gave birth to infants with normal birth weight. The results suggest that induction of TGF-β levels in colostrum depends on differences in the ethnicity of lactating women. Consumption of animal protein and parturition characteristics may affect TGF-β levels in breast milk, and may explain differences in these levels in breast milk between countries.

  20. The peritoneum is both a source and target of TGF-β in women with endometriosis.

    Directory of Open Access Journals (Sweden)

    Vicky J Young

    Full Text Available Transforming growth factor-β (TGF-β is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas from women without disease (n = 16 and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15 and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05 and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05. The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05 in expression of genes associated with tumorigenesis (MAPK8, CDC6, epithelial-mesenchymal transition (NOTCH1, angiogenesis (ID1, ID3 and neurogenesis (CREB1 in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation.

  1. TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeeyong; Kim, Mi-Ra; Kim, Hyun-Ji; An, You Sun; Yi, Jae Youn, E-mail:


    The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV. •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.

  2. A Bright Lunar Impact Flash Linked to the Virginid Meteor Complex (United States)

    Moser, D. E.; Suggs, R. M.; Suggs, R. J.


    Since early 2006, NASA's Marshall Space Flight Center (MSFC) has observed over 330 impact flashes on the Moon, produced by meteoroids striking the lunar surface. On 17 March 2013 at 03:50:54.312 UTC, the brightest flash of a 9-year routine observing campaign was observed by two 0.35 m telescopes at MSFC. The camera onboard the Lunar Reconnaissance Orbiter (LRO), a NASA spacecraft mapping the Moon from lunar orbit, discovered the fresh crater associated with this impact [1] approximately 3 km from the location predicted by a newly developed geolocation technique [2]. The meteoroid impactor responsible for this event may have been part of a stream of large particles encountered by the Earth/Moon associated with the Virginid Meteor Complex, as evidenced by a cluster of five fireballs seen in Earth's atmosphere on the same night by the NASA All Sky Fireball Network [3] and the Southern Ontario Meteor Network [4]. Crater size calculations based on assumptions derived from fireball measurements yielded an estimated crater diameter of 10-23 m rim-to-rim using the Holsapple [5] and Gault [6] models, a result consistent with the observed crater measured to be 18 m across. This is the first time a lunar impact flash has been associated with fireballs in Earth's atmosphere and an observed crater.

  3. Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling.

    Directory of Open Access Journals (Sweden)

    Alexandra Stähli

    Full Text Available Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p10-fold. Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.

  4. Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling. (United States)

    Stähli, Alexandra; Bosshardt, Dieter; Sculean, Anton; Gruber, Reinhard


    Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p10-fold). Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.

  5. Angiotensin II–dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis (United States)

    Gallo, Elena M.; Loch, David C.; Habashi, Jennifer P.; Calderon, Juan F.; Chen, Yichun; Bedja, Djahida; van Erp, Christel; Gerber, Elizabeth E.; Parker, Sarah J.; Sauls, Kimberly; Judge, Daniel P.; Cooke, Sara K.; Lindsay, Mark E.; Rouf, Rosanne; Myers, Loretha; ap Rhys, Colette M.; Kent, Kathleen C.; Norris, Russell A.; Huso, David L.; Dietz, Harry C.


    Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by a high risk for aneurysm and dissection throughout the arterial tree and phenotypically resembles Marfan syndrome. LDS is caused by heterozygous missense mutations in either TGF-β receptor gene (TGFBR1 or TGFBR2), which are predicted to result in diminished TGF-β signaling; however, aortic surgical samples from patients show evidence of paradoxically increased TGF-β signaling. We generated 2 knockin mouse strains with LDS mutations in either Tgfbr1 or Tgfbr2 and a transgenic mouse overexpressing mutant Tgfbr2. Knockin and transgenic mice, but not haploinsufficient animals, recapitulated the LDS phenotype. While heterozygous mutant cells had diminished signaling in response to exogenous TGF-β in vitro, they maintained normal levels of Smad2 phosphorylation under steady-state culture conditions, suggesting a chronic compensation. Analysis of TGF-β signaling in the aortic wall in vivo revealed progressive upregulation of Smad2 phosphorylation and TGF-β target gene output, which paralleled worsening of aneurysm pathology and coincided with upregulation of TGF-β1 ligand expression. Importantly, suppression of Smad2 phosphorylation and TGF-β1 expression correlated with the therapeutic efficacy of the angiotensin II type 1 receptor antagonist losartan. Together, these data suggest that increased TGF-β signaling contributes to postnatal aneurysm progression in LDS. PMID:24355923

  6. Flash floods in small Alpine catchments in a changing climate (United States)

    Breinl, Korbinian; Di Baldassarre, Giuliano


    Climate change is expected to increase the frequency and intensity of hazardous meteorological and hydrological events in numerous mountainous areas. The mountain environment is becoming more and more important for urbanization and the tourism-based economy. Here we show new and innovative methodologies for assessing intensity and frequency of flash floods in small Alpine catchments, in South Tyrol (Italy), under climate change. This research is done within the STEEP STREAMS project, whereby we work closely with decision makers in Italian authorities, and the final goal is to provide them with clear guidelines on how to adapt current structural solutions for mitigating hazardous events under future climate conditions. To this end, we develop a coupled framework of weather generation (i.e. extrapolation of observations and trained with climate projections), time series disaggregation and hydrological modelling using the conceptual HBV model. One of the key challenges is the transfer of comparatively coarse RCM projections to small catchments, whose sizes range from only about 10km2 to 100km2. We examine different strategies to downscale the RCM data from e.g. the EURO-CORDEX dataset using our weather generator. The selected projections represent combinations of warmer, milder, drier and wetter conditions. In general, our main focus is to develop an improved understanding of the impact of the multiple sources of uncertainty in this modelling framework, and make these uncertainties tangible. The output of this study (i.e. discharge with a return period and associated uncertainty) will allow hydraulic and sediment transport modelling of flash floods and debris flows.

  7. Investigation of multi-scale flash-weakening of rock surfaces during high speed slip (United States)

    Barbery, M. R.; Saber, O.; Chester, F. M.; Chester, J. S.


    A significant reduction in the coefficient of friction of rock can occur if sliding velocity approaches seismic rates as a consequence of weakening of microscopic sliding contacts by flash heating. Using a high-acceleration and -speed biaxial apparatus equipped with a high-speed Infra-Red (IR) camera to capture thermographs of the sliding surface, we have documented the heterogeneous distribution of temperature on flash-heated decimetric surfaces characterized by linear arrays of high-temperature, mm-size spots, and streaks. Numerical models that are informed by the character of flash heated surfaces and that consider the coupling of changes in temperature and changes in the friction of contacts, supports the hypothesis that independent mechanisms of flash weakening operate at different contact scales. Here, we report on new experiments that provide additional constraints on the life-times and rest-times of populations of millimeter-scale contacts. Rock friction experiments conducted on Westerly granite samples in a double-direct shear configuration achieve velocity steps from 1 mm/s to 900 mm/s at 100g accelerations over 2 mm of displacement with normal stresses of 22-36 MPa and 30 mm of displacement during sustained high-speed sliding. Sliding surfaces are machined to roughness similar to natural fault surfaces and that allow us to control the characteristics of millimeter-scale contact populations. Thermographs of the sliding surface show temperatures up to 200 C on millimeter-scale contacts, in agreement with 1-D heat conduction model estimates of 180 C. Preliminary comparison of thermal modeling results and experiment observations demonstrate that we can distinguish the different life-times and rest-times of contacts in thermographs and the corresponding frictional weakening behaviors. Continued work on machined surfaces that lead to different contact population characteristics will be used to test the multi-scale and multi-mechanism hypothesis for flash

  8. Spatio-temporal dimension of lightning flashes based on three-dimensional Lightning Mapping Array (United States)

    López, Jesús A.; Pineda, Nicolau; Montanyà, Joan; Velde, Oscar van der; Fabró, Ferran; Romero, David


    3D mapping system like the LMA - Lightning Mapping Array - are a leap forward in lightning observation. LMA measurements has lead to an improvement on the analysis of the fine structure of lightning, allowing to characterize the duration and maximum extension of the cloud fraction of a lightning flash. During several years of operation, the first LMA deployed in Europe has been providing a large amount of data which now allows a statistical approach to compute the full duration and horizontal extension of the in-cloud phase of a lightning flash. The "Ebro Lightning Mapping Array" (ELMA) is used in the present study. Summer and winter lighting were analyzed for seasonal periods (Dec-Feb and Jun-Aug). A simple method based on an ellipse fitting technique (EFT) has been used to characterize the spatio-temporal dimensions from a set of about 29,000 lightning flashes including both summer and winter events. Results show an average lightning flash duration of 440 ms (450 ms in winter) and a horizontal maximum length of 15.0 km (18.4 km in winter). The uncertainties for summer lightning lengths were about ± 1.2 km and ± 0.7 km for the mean and median values respectively. In case of winter lightning, the level of uncertainty reaches up to 1 km and 0.7 km of mean and median value. The results of the successful correlation of CG discharges with the EFT method, represent 6.9% and 35.5% of the total LMA flashes detected in summer and winter respectively. Additionally, the median value of lightning lengths calculated through this correlative method was approximately 17 km for both seasons. On the other hand, the highest median ratios of lightning length to CG discharges in both summer and winter were reported for positive CG discharges.

  9. The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes.

    Directory of Open Access Journals (Sweden)

    Zachary S Levine

    Full Text Available We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

  10. The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes. (United States)

    Levine, Zachary S; Hale, Scott A; Floridi, Luciano


    We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a) this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b) mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

  11. WMO World Record Lightning Extremes: Longest Reported Flash Distance and Longest Reported Flash Duration. (United States)

    Lang, Timothy J; Pédeboy, Stéphane; Rison, William; Cerveny, Randall S; Montanyà, Joan; Chauzy, Serge; MacGorman, Donald R; Holle, Ronald L; Ávila, Eldo E; Zhang, Yijun; Carbin, Gregory; Mansell, Edward R; Kuleshov, Yuriy; Peterson, Thomas C; Brunet, Manola; Driouech, Fatima; Krahenbuhl, Daniel S


    A World Meteorological Organization weather and climate extremes committee has judged that the world's longest reported distance for a single lightning flash occurred with a horizontal distance of 321 km (199.5 mi) over Oklahoma in 2007, while the world's longest reported duration for a single lightning flash is an event that lasted continuously for 7.74 seconds over southern France in 2012. In addition, the committee has unanimously recommended amendment of the AMS Glossary of Meteorology definition of lightning discharge as a "series of electrical processes taking place within 1 second" by removing the phrase "within one second" and replacing with "continuously." Validation of these new world extremes (a) demonstrates the recent and on-going dramatic augmentations and improvements to regional lightning detection and measurement networks, (b) provides reinforcement regarding the dangers of lightning, and (c) provides new information for lightning engineering concerns.

  12. Activated carbon from flash pyrolysis of eucalyptus residue

    Directory of Open Access Journals (Sweden)

    Grima-Olmedo C


    Full Text Available Forestry waste (eucalyptus sp was converted into activated carbon by initial flash pyrolysis followed carbonization and CO2 activation. These residues were obtained from a pilot plant in Spain that produces biofuel, the biochar represented 10–15% in weight. It was observed that the highest activation was achieved at a temperature of 800 °C, the specific surface increased with time but, on the contrary, high loss of matter was observed. At 600 °C, although there was an important increase of the specific surface and the volume of micropores, at this temperature it was observed that the activation time was not an influential parameter. Finally, at 400 °C it was observed that the activation process was not very significant. Assessing the average pore diameter it was found that the lowest value corresponded to the activation temperature of 600 °C, which indicated the development of microporosity. When the activation temperature increases up to 800 °C the pore diameter increased developing mesoporosity.

  13. Coherence properties of the radiation from FLASH

    International Nuclear Information System (INIS)

    Schneidmiller, E.A.; Yurkov, M.V.


    FLASH is the first free electron laser user facility operating in the vacuum ultraviolet and soft x-ray wavelength range. Many user experiments require knowledge of the spatial and temporal coherence properties of the radiation. In this paper we present an analysis of the coherence properties of the radiation for the fundamental and for the higher odd frequency harmonics. We show that temporal and spatial coherence reach maximum close to the FEL saturation but may degrade significantly in the post-saturation regime. We also find that the pointing stability of short FEL pulses is limited due to the fact that non-azimuthal FEL eigenmodes are not sufficiently suppressed. We discuss possible ways for improving the degree of transverse coherence and the pointing stability.

  14. Article coated with flash bonded superhydrophobic particles (United States)

    Simpson, John T [Clinton, TN; Blue, Craig A [Knoxville, TN; Kiggans, Jr., James O [Oak Ridge, TN


    A method of making article having a superhydrophobic surface includes: providing a solid body defining at least one surface; applying to the surface a plurality of diatomaceous earth particles and/or particles characterized by particle sizes ranging from at least 100 nm to about 10 .mu.m, the particles being further characterized by a plurality of nanopores, wherein at least some of the nanopores provide flow through porosity, the particles being further characterized by a plurality of spaced apart nanostructured features that include a contiguous, protrusive material; flash bonding the particles to the surface so that the particles are adherently bonded to the surface; and applying a hydrophobic coating layer to the surface and the particles so that the hydrophobic coating layer conforms to the nanostructured features.

  15. Optical demonstration on Honeywell FLASH program (United States)

    O'Rourke, Ken; Peterson, Eric


    Flight control system architects are increasingly integrating aircraft control and management functionality. This functional integration increases performance and cost of ownership requirements on the communication pathways. Optical signal transmission is an attractive approach to satisfying these system requirements. Investigations and demonstrations of optic signaling are needed to validate applicability of fiber based communication systems to the new system architecture performance and cost requirements. Honeywell's activities associated with the Fly-By-Light Advanced System Hardware (FLASH) program have produced a system including key optical interface elements and accomplished preliminary demonstrations needed to validate flexible, optical based aircraft control and avionic systems. The Honeywell Primary Flight Control System included Active Hand Controllers, Primary Flight Control Computers and smart actuation subsystem elements interfaced through various optical implementations and communication protocols. These successful implementations and demonstrations provide an excellent baseline for the processes, tools and materials required to make Fly-by-Light avionic systems marketable.

  16. Flash photolysis-shock tube studies

    Energy Technology Data Exchange (ETDEWEB)

    Michael, J.V. [Argonne National Laboratory, IL (United States)


    Even though this project in the past has concentrated on the measurement of thermal bimolecular reactions of atomic species with stable molecules by the flash or laser photolysis-shock tube (FP- or LP-ST) method using atomic resonance absorption spectrometry (ARAS) as the diagnostic technique, during the past year the authors have concentrated on studies of the thermal decompositions of selected chlorocarbon molecules. These studies are necessary if the degradation of chlorine containing organic molecules by incineration are to be understood at the molecular level. Clearly, destruction of these molecules will not only involve abstraction reactions, when possible, but also thermal decomposition followed by secondary reactions of the initially formed atoms and radicals. Studies on the thermal decomposition of CH{sub 3}Cl are complete, and the curve-of-growth for Cl-atom atomic resonance absorption has been determined. The new thermal decomposition studies are similar to those already reported for CH{sub 3}Cl.


    Directory of Open Access Journals (Sweden)

    Dinu Cristian


    Full Text Available The use of artificial neural networks (ANNs in modelling the hydrological processes has become a common approach in the last two decades, among side the traditional methods. In regard to the rainfall-runoff modelling, in both traditional and ANN models the use of ground rainfall measurements is prevalent, which can be challenging in areas with low rain gauging station density, especially in catchments where strong focused rainfall can generate flash-floods. The weather radar technology can prove to be a solution for such areas by providing rain estimates with good time and space resolution. This paper presents a comparison between different ANN setups using as input both ground and radar observations for modelling the rainfall-runoff process for Bahluet catchment, with focus on a flash-flood observed in the catchment.

  18. A new French flash flood warning service

    Directory of Open Access Journals (Sweden)

    de Saint-Aubin Céline


    Full Text Available The French State services in charge of flood forecasting supervise about 22,000 km among the 120,000 km of the French rivers within a warning procedure called Vigilance Crues ( Some recent dramatic flood events on small watershed not covered by Vigilance Crues highlight the need for a new warning procedure to anticipate violent flash floods that regularly affect rapid river-basins. Thus the concept emerged of an automatic warning service specifically dedicated to local crisis managers. This service will be less elaborated than Vigilance Crues, probably with false alarms and missed events sometimes, but it will deliver a first information. The generation of the warning is based on a simple rainfall-runoff hydrological model developed by Irstea on all French rivers, fed with radar-gauge rainfall grids provided by Meteo-France. Every fifteen minutes, the hydrological model estimates the discharges on the rivers eligible to the service and determine if certain thresholds corresponding to a high or very high flood are likely to be exceeded. The last step of the real-time system is to determine which municipalities are concerned with flood risk and send them an automatic warning by voice call, optionally by sms or email. A specific web interface is available for users to monitor the evolution of the flood risk on maps that are updated every 15 minutes. This new flash flood warning service will be operational early 2017 as a free service for about 8,000 French municipalities.

  19. Extracellular proteoglycans modify TGF-beta bio-availability attenuating its signaling during skeletal muscle differentiation. (United States)

    Droguett, Rebeca; Cabello-Verrugio, Claudio; Riquelme, Cecilia; Brandan, Enrique


    The onset and progression of skeletal muscle regeneration are controlled by a complex set of interactions between muscle precursor cells and their environment. Satellite cells constitute the main source of muscle precursor cells for growth and repair. After skeletal muscle injury, cell-derived signals induce their re-entry into the cell cycle and their migration into the damaged zone, where they proliferate and differentiate into mature myofibers. The surrounding extracellular matrix (ECM) together with inhibitory growth factors, such as transforming growth factor-beta (TGF-beta), also likely play an important role in growth control and muscle differentiation. Decorin, biglycan and betaglycan are proteoglycans that bind TGF-beta during skeletal muscle differentiation. In this paper, we show that the binding of TGF-beta to the receptors TGF-betaRI and-betaRII diminished in a satellite cell-derived cell line during differentiation, in spite of an increase expression of both receptors. In contrast, during the differentiation of decorin-null myoblasts (Dcn null), which lack decorin expression, the binding of TGF-beta to TGF-betaRI and -betaRII increased concomitantly with receptors levels. Both the addition and re-expression of decorin, in these myoblasts, diminished the binding of TGF-beta to its transducing receptors. Similar results were obtained when biglycan was added or over-expressed in Dcn null myoblasts. The binding of TGF-beta to TGF-betaRIII, alternatively known as betaglycan, was also augmented in Dcn null myoblasts and diminished by decorin, biglycan and betaglycan. These results suggest that decorin, biglycan and betaglycan compete for the binding of TGF-beta to its transducing receptors. Transfection studies with the TGF-beta-dependent promoter of the plasminogen activator inhibitor-1, coupled with luciferase, revealed that the addition of each proteoglycan diminished TGF-beta-dependent activity, for both TGF-beta1 and -beta2. The modulation of TGF

  20. Altered TGF-β endocytic trafficking contributes to the increased signaling in Marfan syndrome. (United States)

    Siegert, Anna-Maria; Serra-Peinado, Carla; Gutiérrez-Martínez, Enric; Rodríguez-Pascual, Fernando; Fabregat, Isabel; Egea, Gustavo


    The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of aortic aneurysms in which augmented TGF-β signaling is reported. However, the primary role of TGF-β signaling as a molecular link between the genetic mutation of fibrillin-1 and disease onset is controversial. The compartmentalization of TGF-β endocytic trafficking has been shown to determine a signaling response in which clathrin-dependent internalization leads to TGF-β signal propagation, and caveolin-1 (CAV-1) associated internalization leads to signal abrogation. We here studied the contribution of endocytic trafficking compartmentalization to increased TGF-β signaling in vascular smooth muscle cells (VSMC) from MFS patients. We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes and their increased interaction with TGF-β receptor II, as well as higher colocalization of SARA with the early endosome marker EEA1. We assessed TGF-β internalization using a biotinylated ligand (b-TGF-β), which colocalized equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls. However, in Marfan cells, colocalization of b-TGF-β with SARA and EEA1 was increased and accompanied by decreased colocalization with CAV-1 at EEA1-positive endosomes. Moreover, Marfan VSMC showed higher transcriptional levels and membrane enrichment of RAB5. Our results indicate that increased RAB5-associated SARA localization to early endosomes facilitates its TGF-β receptor binding and phosphorylation of signaling mediator SMAD2 in Marfan VSMC. This is accompanied by a reduction of TGF-β sorting into multifunctional vesicles containing cargo from both internalization pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The peritoneum is both a source and target of TGF-β in women with endometriosis. (United States)

    Young, Vicky J; Brown, Jeremy K; Saunders, Philippa T K; Duncan, W Colin; Horne, Andrew W


    Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (Pperitoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (Pendometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation.

  2. TGF-β2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. (United States)

    Maheshwari, Akhil; Kelly, David R; Nicola, Teodora; Ambalavanan, Namasivayam; Jain, Sunil K; Murphy-Ullrich, Joanne; Athar, Mohammad; Shimamura, Masako; Bhandari, Vineet; Aprahamian, Charles; Dimmitt, Reed A; Serra, Rosa; Ohls, Robin K


    Premature neonates are predisposed to necrotizing enterocolitis (NEC), an idiopathic, inflammatory bowel necrosis. We investigated whether NEC occurs in the preterm intestine due to incomplete noninflammatory differentiation of intestinal macrophages, which increases the risk of a severe mucosal inflammatory response to bacterial products. We compared inflammatory properties of human/murine fetal, neonatal, and adult intestinal macrophages. To investigate gut-specific macrophage differentiation, we next treated monocyte-derived macrophages with conditioned media from explanted human fetal and adult intestinal tissues. Transforming growth factor-β (TGF-β) expression and bioactivity were measured in fetal/adult intestine and in NEC. Finally, we used wild-type and transgenic mice to investigate the effects of deficient TGF-β signaling on NEC-like inflammatory mucosal injury. Intestinal macrophages in the human preterm intestine (fetus/premature neonate), but not in full-term neonates and adults, expressed inflammatory cytokines. Macrophage cytokine production was suppressed in the developing intestine by TGF-β, particularly the TGF-β(2) isoform. NEC was associated with decreased tissue expression of TGF-β(2) and decreased TGF-β bioactivity. In mice, disruption of TGF-β signaling worsened NEC-like inflammatory mucosal injury, whereas enteral supplementation with recombinant TGF-β(2) was protective. Intestinal macrophages progressively acquire a noninflammatory profile during gestational development. TGF-β, particularly the TGF-β(2) isoform, suppresses macrophage inflammatory responses in the developing intestine and protects against inflammatory mucosal injury. Enterally administered TGF-β(2) protected mice from experimental NEC-like injury. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro. (United States)

    Konrad, L; Keilani, M M; Laible, L; Nottelmann, U; Hofmann, R


    Massive apoptosis of pubertal male germ cells is important for the development of functional spermatogenesis in the adult testis. Although the trigger(s) for male germ cell loss at puberty remain undefined, we have hypothesized that transforming growth factor-betas (TGF-betas) play an active role. Here we demonstrate that the three mammalian TGF-beta isoforms, TGF-beta1, TGF-beta2 and TGF-beta3, induce distinct apoptosis of pubertal spermatogonia and spermatocytes in a dose-dependent manner. Induction of male germ cell death by activation of caspase-3 was most pronounced with TGF-beta2 compared to TGF-beta1 and TGF-beta3. Furthermore, we found colocalization of activated caspase-3 with apoptotic protease-activating factor-1 (Apaf-1) in apoptotic germ cells, thus indicating the importance of the intrinsic mitochondrial pathway in TGF-beta-induced apoptosis. The specificity of the TGF-beta effects was proven by addition of recombinant latency-associated peptide against TGF-beta1 (rLAP-TGF-beta1) which completely abolished TGF-beta1-induced and TGF-beta3-induced germ cell apoptosis. Although TGF-beta2-triggered germ cell death also was significantly reduced by rLAP-TGF-beta1, inhibition was not maximal. Our results suggest that the three TGF-beta isoforms induce apoptosis of pubertal male germ cells via the mitochondrial pathway in vitro and are thus likely candidates involved in the excessive first wave of apoptosis of male germ cells during puberty.

  4. Some characteristics of the digitization pulses from high pressure neon-helium flash tubes

    International Nuclear Information System (INIS)

    Chan, D.S.K.; Leung, S.K.; Ng, L.K.


    Characteristics of the digitization output pulses from high pressure neon-helium flash tubes were studied under various operation conditions using square ultra-high voltage pulses. Properties reported by previous workers were compared. Two discharge mechanisms, the Townsend avalanche discharge and the streamer discharge, were observed to occur in sequence in some events. The output waveforms for both discharge mechanisms were studied in detail. The charge induced on a detecting probe was also estimated from the measured data. (Auth.)

  5. The role of TGF-β and its crosstalk with RAC1/RAC1b signaling in breast and pancreas carcinoma. (United States)

    Melzer, Catharina; Hass, Ralf; von der Ohe, Juliane; Lehnert, Hendrik; Ungefroren, Hendrik


    This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data from our and other studies point to signaling crosstalk between TGF-β and RAC1 and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based on the exciting observation that RAC1b functions as an endogenous inhibitor of RAC1, we propose a model on how the relative abundance or activity of RAC1 and RAC1b in the tumor cells may determine their responses to TGF-β and, ultimately, the metastatic capacity of the tumor.

  6. Combining use of captopril and losartan attenuates the progress of Streptococcus pneumoniae-induced tympanosclerosis through the suppression of TGF-β1 expression. (United States)

    Yan, Wenqing; Li, Jianfeng; Chai, Renjie; Guo, Wentao; Xu, Lei; Han, Yuechen; Bai, Xiaohui; Wang, Haibo


    In this study, using an Streptococcus pneumoniae-induced tympanosclerosis (TS) model, we explored the effects of captopril and losartan in the treatment of TS and the possible mechanisms. A prospective experimental animal study. We set up the TS models in both guinea pig and wistar rat by inoculation of type-3 Streptococcus pneumoniae microorganisms and then treated the animals with the combining use of captopril and losartan. Otomicroscopy was employed to observe the development of TS. Auditory brainstem response was used to test the hearing function of animals. Hematoxylin-eosin and von Kossa staining were performed to determine the morphological changes and calcium depositions. The protein expressions of transforming growth factor β1 (TGF-β1) were assessed by western blot and immunohistochemistry staining, and the mRNA level of TGF-β1 was measured by quantitative reverse transcription- polymerase chain reaction. The combining use of captopril and losartan attenuated TS responses in terms of a decrease in the TS incidence and the ABR threshold, a reduction of hyalinization and calcification in the middle ear mucosa and the thickness of the mucosa. In addition, the TGF-β1 expression was decreased at both protein and mRNA levels. Our data indicate, for the first time, that the combining use of captopril and losartan obviously attenuates TS progress through inhibiting the overexpressing of TGF-β1.

  7. Crystallization of amorphous silicon thin-film on glass substrate preheated at 650 Degree-Sign C using Xe arc flash of 400 {mu}s

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-Hyun [Department of Mechanical and System Design Engineering, Hongik University, 72-1 Sangsoo-dong, Mapo-koo, Seoul 121-791 (Korea, Republic of); Kim, Byung-Kuk [Viatron Technologies, Suwon Industrial Complex, 972 Gosaek-dong, Kwonsun-koo, Suwon 441-813 (Korea, Republic of); Kim, Hyoung June [Department of Materials Science and Engineering, Hongik University, 72-1 Sangsoo-dong, Mapo-koo, Seoul 121-791 (Korea, Republic of); Park, Seungho, E-mail: [Department of Mechanical and System Design Engineering, Hongik University, 72-1 Sangsoo-dong, Mapo-koo, Seoul 121-791 (Korea, Republic of)


    Experimental and theoretical investigations on flash lamp annealing (FLA) of amorphous silicon (a-Si) film on glass were carried out with a view to practical applications in large-window display industries. A Xe arc flash lamp of 950 mm in length and 22 mm in bore diameter was applied with nominal input voltage of 7 kV and flash duration of 400 {mu}s. Prior to the annealing process, the specimen for FLA was preheated at 650 Degree-Sign C, which was very close to the service temperature of the glass specimen used in this study. By employing a focusing elliptic reflector, maximum light energy density of up to 8.4 J/cm{sup 2} could be attained with an active exposure width of 2 cm. Crystallization of a-Si could be achieved in solid-phase by applying a flash beam with light density of at least 5 J/cm{sup 2}, and its phase-transition characteristics that varied with energy densities could be explained by theoretically estimated temperature fields. Electron microscopy observations confirmed that solid-phase crystallization preceded melting of a-Si due to relatively long flashing (heating) duration of 400 {mu}s, which was comparable to solid-phase crystal-growth times at elevated temperatures. - Highlights: Black-Right-Pointing-Pointer Flash lamp annealing of amorphous silicon (a-Si) on glass for large-scale displays Black-Right-Pointing-Pointer Xe-arc flash lamp of 950 mm in length and 22 mm in bore diameter Black-Right-Pointing-Pointer Flash duration of 400 {mu}s at nominal input voltage of 7 kV Black-Right-Pointing-Pointer Solid-phase crystallization precedes melting of a-Si due to long flashing duration.

  8. Freeware eLearning Flash-ECG for learning electrocardiography. (United States)

    Romanov, Kalle; Kuusi, Timo


    Electrocardiographic (ECG) analysis can be taught in eLearning programmes with suitable software that permits the effective use of basic tools such as a ruler and a magnifier, required for measurements. The Flash-ECG (Research & Development Unit for Medical Education, University of Helsinki, Finland) was developed to enable teachers and students to use scanned and archived ECGs on computer screens and classroom projectors. The software requires only a standard web browser with a Flash plug-in and can be integrated with learning environments (Blackboard/WebCT, Moodle). The Flash-ECG is freeware and is available to medical teachers worldwide.

  9. Symptom clusters among MsFLASH clinical trial participants. (United States)

    Woods, Nancy Fugate; Hohensee, Chancellor; Carpenter, Janet S; Cohen, Lee; Ensrud, Kristine; Freeman, Ellen W; Guthrie, Katherine A; Joffe, Hadine; LaCroix, Andrea Z; Otte, Julie L


    Our objective was to identify symptom clusters using standardized measures completed by participants in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health clinical trial at baseline, including hot flash interference, and sleep, depressive, anxiety, and pain symptoms. Data from all women randomized to interventions and controls from Menopausal Strategies: Finding Lasting Answers to Symptoms and Health studies 1, 2, and 3 (N = 899) were included; 797 with complete data were used in the analyses. Scores from standardized measures obtained at baseline included the following: Hot Flash-Related Daily Interference Scale, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9 measure of depressed mood, Generalized Anxiety Disorder, and Brief Pain Inventory PEG scores (pain intensity [P], interference with enjoyment of life [E], and interference with daily activity [G]). Latent class analysis was used to identify symptom clusters using standardized scale scores and their established cut points. We identified five classes using the Bayesian Information Criterion and the Akaike Information Criterion. Women in classes 1 and 2 had high hot flash interference levels relative to the others, and class 1 (10.5% of total) included severe hot flash interference, severe sleep symptoms, and moderately severe pain symptoms (hot flash, sleep, pain). In class 2 (14.1%), severe hot flash interference was paired with the severe sleep symptoms, and moderate to severe depressed and anxious mood symptoms and pain (hot flash, sleep, mood, pain). In class 3 (39.6%), women reported moderately severe sleep symptoms with moderate hot flash interference, and low severity mood and pain symptoms (hot flash, sleep). Those in class 4 (7.0%) reported moderate hot flash interference with severe levels of anxiety and depressed mood symptoms, but low levels of other symptoms (hot flash, mood). Women in class 5 (28.7%) reported the lowest levels of all

  10. Hydroxysafflor Yellow A Suppresses MRC-5 Cell Activation Induced by TGF-β1 by Blocking TGF-β1 Binding to TβRII. (United States)

    Pan, Ruiyan; Zhang, Yadan; Zheng, Meng; Zang, Baoxia; Jin, Ming


    Hydroxysafflor yellow A (HSYA) is an active ingredient of Carthamus tinctorius L.. This study aimed to evaluate the effects of HSYA on transforming growth factor-β1 (TGF-β1)-induced changes in proliferation, migration, differentiation, and extracellular matrix accumulation and degradation in human fetal lung fibroblasts (MRC-5), to explore the mechanisms whereby HSYA may alleviate pulmonary fibrosis. MRC-5 cells were incubated with various doses of HSYA and/or the TGF-β receptor type I kinase inhibitor SB431542 and then stimulated with TGF-β1. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium inner salt assay. Cell migration was detected by wound-healing assay. Protein levels of α-smooth muscle actin (α-SMA), collagen I α 1 (COL1A1), and fibronectin (FN) were measured by immunofluorescence. Protein levels of matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-2, TGF-β type II receptor (TβRII), and TGF-β type I receptor were detected by western blotting. TβRII knockdown with siRNA interfered with the inhibitory effect of HSYA on α-SMA, COL1A1, and FN expression, and TGF-β1-induced Sma and Mad protein (Smad), and extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway activation. The antagonistic effect of HSYA on the binding of fluorescein isothiocyanate-TGF-β1 to MRC-5 cell cytoplasmic receptors was measured by flow cytometry. HSYA significantly suppressed TGF-β1-induced cell proliferation and migration. HSYA could antagonize the binding of FITC-TGF-β1 to MRC-5 cell cytoplasmic receptors. Also HSYA inhibited TGF-β1-activated cell expression of α-SMA, COL1A1, and FN and phosphorylation level of Smad2, Smad3, and ERK by targeting TβRII in MRC-5 cells. These findings suggest that TβRII might be the target responsible for the inhibitory effects of HSYA on TGF-β1-induced


    Directory of Open Access Journals (Sweden)

    Lukman Khairudin


    cycle of activity that consists of two cycles, where each cycle consists of planning, action, observation and reflection.This data collection instruments are observation and tests. The research results obtained I cycle that results in student learning on learning typing using Adobe Flash media learning experience an increase in the value of the average cpm on cycle 1 of 103 to 111 and 112 on CPMs CPMs cycle 2 Although still relatively good. Obtaining this value belongs to the category are capable of mastering typing practice typing speed which means that using the media learning adobe flash with cooperative learning model with computer-based learning models can meningkatakan student learning outcomes


    Directory of Open Access Journals (Sweden)

    Lukman Khairudin


    planning, action, observation and reflection.This data collection instruments are observation and tests. The research results obtained I cycle that results in student learning on learning typing using Adobe Flash media learning experience an increase in the value of the average cpm on cycle 1 of 103 to 111 and 112 on CPMs CPMs cycle 2 Although still relatively good. Obtaining this value belongs to the category are capable of mastering typing practice typing speed which means that using the media learning adobe flash with cooperative learning model with computer-based learning models can meningkatakan student learning outcomes.

  13. Maintaining the immunological balance in parasitic infections: a role for TGF-ß?

    DEFF Research Database (Denmark)

    Omer, F M; Kurtzhals, J A; Riley, E M


    Transforming growth factor beta (TGF-beta) is an important regulator of inflammation, being proinflammatory at low concentrations and anti-inflammatory at high concentrations. As such, TGF-beta might be important in maintaining the balance between control and clearance of infectious organisms...

  14. Analysis of interaction between TGF and the myogenic response in renal blood flow autoregulation

    DEFF Research Database (Denmark)

    Feldberg, R; Colding-Jørgensen, M; Holstein-Rathlou, N H


    . The contribution of TGF to smooth muscle activity is assumed to be a linear function of the glomerular capillary pressure. The results show that the myogenic response plays an important role in renal blood flow autoregulation. Without a myogenic response, mechanisms such as TGF that are localized in the distal...

  15. Synergistic induction of profibrotic PAI-1 by TGF-β and radiation depends on p53

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Jong, Edwin de; Langendijk, Johannes A.; Kampinga, Harm H.; Coppes, Robert P.


    Radiation-induced fibrosis is a severe side effect of radiotherapy. TGF-β and radiation synergistically induce expression of the profibrotic PAI-1 gene and this cooperation potentially involves p53. Here, we demonstrate that p53 is both indispensable and sufficient for the radiation effect inducing synergistic activation of PAI-1 by radiation and TGF-β.

  16. TGF-β1 and IL-10 expression in epithelial ovarian cancer cell line ...

    African Journals Online (AJOL)

    TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J Cell Biol 1991; 115: 1091-. 1105. 21. Gordinier ME, Zhang HZ, Patenia R, Levy LB, Atkinson. EN, Nash MA, Katz RL, Platsoucas CD, Freedman. RS. Quantitative analysis of transforming growth.

  17. TGF-β1 of no avail as prognostic marker in lyme disease

    Directory of Open Access Journals (Sweden)

    Julia Schumann


    Full Text Available Background. Within the present in vivo study using the wild type mouse strains C3H/HeN and FVB/N it was intended to (1 measure TGF-β1 expression in the course of lyme disease, (2 examine the potential correlation of TGF-β1 expression with the clinical outcome of a Borrelia infection (with a focus on lyme arthritis, (3 develop a diagnostic tool based on the endogenous factor TGF-β1 to predict the progressivity of lyme disease.Findings. In the course of lyme disease there was an increase in the serum content of active TGF-β1, which became significant 56 days post infection (p < 0.001. The serum concentration of total TGF-β1 in the course of infection initially decreased then rebounded and subsequently dropped again. Despite considerable individual variations in active TGF-β1 serum concentrations there were no identifiable dissimilarities in the clinical appearance of the mice. Likewise, no correlation could be seen between the serum content of active TGF-β1 and the severity of lyme arthritis of tibiotarsal joints of infected mice.Conclusions. The present study clearly shows that TGF-β1 is of no avail as prognostic marker in lyme disease. Hence, the search for an endogenous predictive factor, which can be determined in an easy and reliable manner, remains open.

  18. Mitigation of TGF-β/Smad signaling pathway-associated liver fibrosis ...

    African Journals Online (AJOL)

    The hydroxyproline content of proteins was measured as an indirect way of assessing collagen deposition. TGF-β1 levels and TGF-β/Smad signaling pathway-related genes and proteins were analyzed by quantitative polymerase chain reaction (qPCR) assay and Western blot assay. Results: After PF administration, serum ...

  19. A Mathematical Model Quantifies Proliferation and Motility Effects of TGF-β on Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shizhen Emily Wang


    Full Text Available Transforming growth factor (TGF-β is known to have properties of both a tumour suppressor and a tumour promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell–cell adhesion. Coupling mathematical modelling and experiments, we investigate the growth and motility of oncogene-expressing human mammary epithelial cells under exposure to TGF-β. We use a version of the well-known Fisher–Kolmogorov equation, and prescribe a procedure for its parametrisation. We quantify the simultaneous effects of TGF-β to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF-β treated cells in vitro, TGF-β increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells.

  20. Regulation of tumor immune surveillance and tumor immune subversion by tgf-Beta. (United States)

    Park, Hae-Young; Wakefield, Lalage M; Mamura, Mizuko


    Transforming growth factor-beta (TGF-beta) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-beta facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-beta antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-beta antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic CD8(+) T cells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-beta on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

  1. Thermal characterization of a flashing jet by planar laser-induced fluorescence (United States)

    Vetrano, M. R.; Simonini, A.; Steelant, J.; Rambaud, P.


    Flash atomization can be observed when a pressurized fluid is released in an environment at lower pressure. This phenomenon plays an important role in the security management of chemical industries where liquefied gases can be accidentally released at atmosphere. In other applications, for example in propulsion systems, it can have some potential benefits as it is known to produce a fine spray with enhanced atomization. The experimental characterization of these kinds of atomization should be performed by means of non-intrusive measurement techniques since they are very sensitive to external perturbation. In this work, the planar laser-induced fluorescence technique is used to measure the liquid phase temperature of an ethanol superheated flashing jet. The feasibility of the technique is proved, measurements are taken for different superheat conditions, and an analysis of the measurement uncertainties is presented.

  2. Expression profiling of genes regulated by TGF-beta: Differential regulation in normal and tumour cells

    Directory of Open Access Journals (Sweden)

    Takahashi Takashi


    Full Text Available Abstract Background TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Results Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. Conclusion These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.

  3. SNAIL Mediates TGF-β1-Induced Downregulation of Pentraxin 3 Expression in Human Granulosa Cells. (United States)

    Li, Hui; Chang, Hsun-Ming; Shi, Zhendan; Leung, Peter C K


    Transforming growth factor-β (TGF-β) 1 plays a critical role in regulating follicular development, and its dysregulation has been shown to be involved in the pathogenesis of ovulation dysfunction. SNAIL is a well-known transcriptional repressor that mediates TGF-β1-induced cellular functions. Pentraxin 3 (PTX3) is a key enzyme for the assembly and stabilization of the cumulus oophorus extracellular matrix, which is essential for cumulus expansion during the periovulatory stage. The purpose of the present study was to investigate the roles of TGF-β1 and SNAIL in the regulation of PTX3 expression and to examine the underlying mechanism. An established immortalized human granulosa cell (GC) line (SVOG), a GC tumor cell line (KGN), and primary human granulosa-lutein cells were used as study models. We demonstrated that TGF-β1 treatment substantially decreased the messenger RNA and protein levels of PTX3. This suppressive effect was abolished by cotreatment with the soluble TGF-β type II receptor (TβRII) or the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, SMAD2/3, or SMAD4 reversed the effects of TGF-β1-induced SNAIL upregulation and PTX3 suppression. These results indicate that TGF-β1 upregulates SNAIL and downregulates PTX3 expression via a TβRII-ALK5-mediated SMAD-dependent signaling pathway in human GCs. Additionally, TGF-β1-induced PTX3 suppression was mediated by upregulation of the SNAIL transcription factor, as knockdown of SNAIL completely reversed the suppression of PTX3 in response to TGF-β1. These findings could inform the roles of TGF-β1 and SNAIL in the regulation of follicular function and might provide therapeutic targets for the treatment of ovulation dysfunction.

  4. Association of TGF-β2 levels in breast milk with severity of breast biopsy diagnosis. (United States)

    Yang, Hannah P; Schneider, Sallie Smith; Chisholm, Christina M; Browne, Eva P; Mahmood, Sidra; Gierach, Gretchen L; Lenington, Sarah; Anderton, Douglas L; Sherman, Mark E; Arcaro, Kathleen F


    TGF-β plays a dual role in breast carcinogenesis, acting at early stages as tumor-suppressors and later as tumor-promoters. TGF-β isoforms are expressed in breast tissues and secreted in milk, suggesting that analysis of levels in milk might be informative for breast cancer risk. Accordingly, we assessed TGF-β2 levels in milk from women who had undergone a breast biopsy and related the concentrations to diagnosis. Milk donated by women who had undergone or were scheduled for a breast biopsy was shipped on ice for processing and testing. Breast cancer risk factors were obtained through a self-administered questionnaire, and biopsy diagnoses were extracted from pathology reports. TGF-β2 levels in milk, assessed as absolute levels and in relation to total protein, were analyzed in bilateral samples donated by 182 women. Linear regression was used to estimate relationships of log-transformed TGF-β2 levels and TGF-β2/ total protein ratios to biopsy category. Milk TGF-β2 levels from biopsied and non-biopsied breasts within women were highly correlated (r (2) = 0.77). Higher mean TGF-β2 milk levels (based on average of bilateral samples) were marginally associated with more severe breast pathological diagnosis, after adjusting for duration of nursing current child (adjusted p trend = 0.07). Our exploratory analysis suggests a borderline significant association between higher mean TGF-β2 levels in breast milk and more severe pathologic diagnoses. Further analysis of TGF-β signaling in milk may increase understanding of postpartum remodeling and advance efforts to analyze milk as a means of assessing risk of breast pathology.

  5. Negative control of the HGF/c-MET pathway by TGF-β: a new look at the regulation of stemness in glioblastoma. (United States)

    Papa, Eleanna; Weller, Michael; Weiss, Tobias; Ventura, Elisa; Burghardt, Isabel; Szabó, Emese


    Multiple target inhibition has gained considerable interest in combating drug resistance in glioblastoma, however, understanding the molecular mechanisms of crosstalk between signaling pathways and predicting responses of cancer cells to targeted interventions has remained challenging. Despite the significant role attributed to transforming growth factor (TGF)-β family and hepatocyte growth factor (HGF)/c-MET signaling in glioblastoma pathogenesis, their functional interactions have not been well characterized. Using genetic and pharmacological approaches to stimulate or antagonize the TGF-β pathway in human glioma-initiating cells (GIC), we observed that TGF-β exerts an inhibitory effect on c-MET phosphorylation. Inhibition of either mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway attenuated this effect. A comparison of c-MET-driven and c-MET independent GIC models revealed that TGF-β inhibits stemness in GIC at least in part via its negative regulation of c-MET activity, suggesting that stem cell (SC) maintenance may be controlled by the balance between these two oncogenic pathways. Importantly, immunohistochemical analyses of human glioblastoma and ex vivo single-cell gene expression profiling of TGF-β and HGF confirm the negative interaction between both pathways. These novel insights into the crosstalk of two major pathogenic pathways in glioblastoma may explain some of the disappointing results when targeting either pathway alone in human glioblastoma patients and inform on potential future designs on targeted pharmacological or genetic intervention.

  6. TGF-β and EGF induced HLA-I downregulation is associated with epithelial-mesenchymal transition (EMT) through upregulation of snail in prostate cancer cells. (United States)

    Chen, Xiao-Hui; Liu, Zong-Cai; Zhang, Ge; Wei, Wei; Wang, Xiao-Xiong; Wang, Hao; Ke, Hong-Peng; Zhang, Fan; Wang, Hong-Sheng; Cai, Shao-Hui; Du, Jun


    Human leukocyte antigen class I antigens (HLA-I) is essential in immune response by presenting antigenic peptides to cytotoxic T lymphocytes. Downregulation of HLA-I is observed in primary and metastatic prostate cancers, which facilitates them escape from immune surveillance, thereby promotes prostate cancer progression. In addition, elevated level of growth factors like TGF-β or EGF in microenvironment is related to the prostate cancer deterioration. Thus, we wondered whether TGF-β or EGF was involved in the regulation of HLA-I during the development of prostate cancer cells. In this study, we demonstrated that TGF-β and EGF both downregulated the expression of HLA-I, thereby attenuated the cytotoxic T cell mediated lysis of prostate cancer cells. Next, we revealed that TGF-β and EGF induced downregulation of HLA-I is associated with classical epithelial-mesenchymal transition (EMT) morphological changes and expression profiles. We further illustrated that overexpression of Snail is crucial for HLA-I downregulation and its association with EMT. At last, we discussed that NF-κB/p65 is the plausible target for Snail to induce HLA-I downregulation. Taken together, this is the first evidence to reveal that both TGF-β and EGF can induce HLA-I downregulation which is then proven to be associated with EMT in prostate cancer cells. These discoveries provide a deeper understanding of growth factors induced immune escape and introduce potential therapeutic targets for prostate cancers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Active TGF-β1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence

    NARCIS (Netherlands)

    Hawinkels, L.J.A.C.; Verspaget, H.W.; Reijden, J.J. van der; Zon, J.M. van der; Verheijen, J.H.; Hommes, D.W.; Lamers, C.B.H.W.; Sier, C.F.M.


    Transforming growth factor-β1 (TGF-β1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-β1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-β levels, showing a

  8. Some design aspects of multistage flash distillation process

    International Nuclear Information System (INIS)

    Ahmad, Mohammad.


    The purpose of this paper is to examine the effect of the design variables of multistage flash (MSF) process on the performance and/or the cost of the desalting plant, and to establish certain design trends

  9. Robust Flash 3D-FPA Sensor, Phase I (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) is a small business, which has developed a compact, eye-safe 3D Flash LIDARTM Camera (FLC) well suited for real-time...

  10. Hot Flashes and Quality of Life among Breast Cancer Patients

    National Research Council Canada - National Science Library

    Jacobs, Linda A


    This ongoing longitudinal study examines hot flashes and Quality of Life (QoL) in breast cancer (BC) patients undergoing initial treatment, and develops a taxonomy of the medical and Complementary and Alternative Medicine...

  11. Flash Cracking Reactor for Waste Plastic Processing, Phase I (United States)

    National Aeronautics and Space Administration — We propose to design, model, build, and test a novel flash cracking reactor to convert plastic waste, and potentially other unconventional hydrocarbon feedstocks,...

  12. 3D Flash LIDAR EDL Resolution Improvement, Phase I (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) is a small business, which has developed a compact, eye-safe 3D Flash LIDARTM Camera (FLC) well suited for real-time...

  13. 3D Flash LIDAR Space Laser, Phase I (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc (ASC) is a small business, which has developed a compact, eye-safe 3D Flash LIDARTM Camera (FLC) well suited for real-time...

  14. 3D Flash LIDAR real time embedded processing, Phase I (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) is a small business, which has developed a compact, eye-safe 3D Flash LIDARTM Camera (FLC) well suited for real-time...

  15. Dynamic simulation of flash drums using rigorous physical property calculations

    Directory of Open Access Journals (Sweden)

    F. M. Gonçalves


    Full Text Available The dynamics of flash drums is simulated using a formulation adequate for phase modeling with equations of state (EOS. The energy and mass balances are written as differential equations for the internal energy and the number of moles of each species. The algebraic equations of the model, solved at each time step, are those of a flash with specified internal energy, volume and mole numbers (UVN flash. A new aspect of our dynamic simulations is the use of direct iterations in phase volumes (instead of pressure for solving the algebraic equations. It was also found that an iterative procedure previously suggested in the literature for UVN flashes becomes unreliable close to phase boundaries and a new alternative is proposed. Another unusual aspect of this work is that the model expressions, including the physical properties and their analytical derivatives, were quickly implemented using computer algebra.

  16. Photosynthetic efficiency of Chlamydomonas reinhardtii in flashing light

    NARCIS (Netherlands)

    Vejrazka, C.; Janssen, M.G.J.; Streefland, M.; Wijffels, R.H.


    Efficient light to biomass conversion in photobioreactors is crucial for economically feasible microalgae production processes. It has been suggested that photosynthesis is enhanced in short light path photobioreactors by mixing-induced flashing light regimes. In this study, photosynthetic

  17. Flash 3D Rendezvous and Docking Sensor Project (United States)

    National Aeronautics and Space Administration — 3D Flash Ladar is a breakthrough technology for many emerging and existing 3D vision areas, and sensor improvements will have an impact on nearly all these fields....

  18. Abstract Specification of the UBIFS File System for Flash Memory (United States)

    Schierl, Andreas; Schellhorn, Gerhard; Haneberg, Dominik; Reif, Wolfgang

    Today we see an increasing demand for flash memory because it has certain advantages like resistance against kinetic shock. However, reliable data storage also requires a specialized file system knowing and handling the limitations of flash memory. This paper develops a formal, abstract model for the UBIFS flash file system, which has recently been included in the Linux kernel. We develop formal specifications for the core components of the file system: the inode-based file store, the flash index, its cached copy in the RAM and the journal to save the differences. Based on these data structures we give an abstract specification of the interface operations of UBIFS and prove some of the most important properties using the interactive verification system KIV.

  19. Flash 3D Rendezvous and Docking Sensor, Phase I (United States)

    National Aeronautics and Space Administration — 3D Flash Ladar is a breakthrough technology for many emerging and existing 3D vision areas, and sensor improvements will have an impact on nearly all these fields....

  20. Wedge Heat-Flux Indicators for Flash Thermography (United States)

    Koshti, Ajay M.


    Wedge indicators have been proposed for measuring thermal radiation that impinges on specimens illuminated by flash lamps for thermographic inspection. Heat fluxes measured by use of these indicators would be used, along with known thermal, radiative, and geometric properties of the specimens, to estimate peak flash temperatures on the specimen surfaces. These indicators would be inexpensive alternatives to high-speed infrared pyrometers, which would otherwise be needed for measuring peak flash surface temperatures. The wedge is made from any suitable homogenous material such as plastic. The choice of material is governed by the equation given. One side of the wedge is covered by a temperature sensitive compound that decomposes irreversibly when its temperature exceeds a rated temperature (T-rated). The uncoated side would be positioned alongside or in place of the specimen and exposed to the flash, then the wedge thickness at the boundary between the white and blackened portions measured.

  1. Space Qualified, Radiation Hardened, Dense Monolithic Flash Memory, Phase II (United States)

    National Aeronautics and Space Administration — Space Micro proposes to build a radiation hardened by design (RHBD) flash memory, using a modified version of our RH-eDRAM Memory Controller to solve all the single...

  2. Interim report on flash floods, Area 5 - Nevada Test Site

    International Nuclear Information System (INIS)

    French, R.H.


    Examination of the presently available data indicates that consideration must be given to the possibility of flash floods when siting waste management facilities in Area 5 of the Nevada Test Site. 6 figures, 7 tables

  3. The Essential Guide to 3D in Flash

    CERN Document Server

    Olsson, Ronald A


    If you are an ActionScript developer or designer and you would like to work with 3D in Flash, this book is for you. You will learn the core Flash 3D concepts, using the open source Away3D engine as a primary tool. Once you have mastered these skills, you will be able to realize the possibilities that the available Flash 3D engines, languages, and technologies have to offer you with Flash and 3D.* Describes 3D concepts in theory and their implementation using Away3D* Dives right in to show readers how to quickly create an interactive, animated 3D scene, and builds on that experience throughout

  4. Portable flash X-ray systems: applications and techniques

    International Nuclear Information System (INIS)

    Bryant, L.E.


    Three portable flash x-ray equipments are described, and applications such as jet and high explosive studies, bullet impact and lead casting experiments are given as well as techniques for triggering and protection of equipment and film

  5. Reconstructing the 2015 Flash Flood event of Salgar Colombia, The Case of a Poor Gauged Basin (United States)

    Velasquez, N.; Zapata, E.; Hoyos Ortiz, C. D.; Velez, J. I.


    Flash floods events associated with severe precipitation events are highly destructive, often resulting in significant human and economic losses. Due to their nature, flash floods trend to occur in medium to small basins located within complex high mountainous regions. In the Colombian Andean region these basins are very common, with the aggravating factor that the vulnerability is considerably high as some important human settlements are located within these basins, frequently occupating flood plains and other flash-flood prone areas. During the dawn of May 18 of 2015 two severe rainfall events generated a flash flood event in the municipality ofSalgar, La Liboriana basin, locatedin the northwestern Colombian Andes, resulting in more than 100 human casualties and significant economic losses. The present work is a reconstruction of the hydrological processes that took place before and during the Liboriana flash flood event, analyzed as a case of poorly gauged basin.The event conditions where recreated based on radar retrievals and a hydrological distributed model, linked with a proposed 1D hydraulic model and simple shallow landslide model. Results suggest that the flash flood event was caused by the occurrence of two successive severe convective events over the same basin, with an important modulation associated with soil characteristics and water storage.Despite of its simplicity, the proposed hydraulic model achieves a good representation of the flooded area during the event, with limitations due to the adopted spatial scale (12.7 meters, from ALOS PALSAR images). Observed landslides were obtained from satellite images; for this case the model simulates skillfully the landslide occurrence regions with small differences in the exact locations.To understand this case, radar data shows to be key due to specific convective cores location and rainfall intensity estimation.In mountainous regions, there exists a significant number of settlements with similar

  6. Tutorial Pengenalan Adobe Photoshop Menggunakan Adobe Flash CS3


    Mayoka, Rio


    Kajian ini bertujuan untuk membangun sebuah aplikasi yang dapat menjadi alat bantu dalam pembelajaran Adobe Photoshop, dimana terdapat beberapa materi pengenalan dasar Adobe Photoshop. Aplikasi ini suatu gagasan dengan membuat tutorial beranimasi yang interatif. Aplikasi ini dibuat dengan menggunakan Adobe Flash CS3 dan dapat dijalankan dengan Flash player. Aplikasi ini dapat membantu para penggunanya dalam memahami pengenalan Adobe Photoshop, terutama pengenalan tool pada Adob...


    Directory of Open Access Journals (Sweden)

    Rini Suswita


    in young age. The level of VEGF, TGF-β, IGF and CA 15-3 was measured before and three months after oophorectomy using the ELISA technique. Data was analyzed with non-parametric test. Of the twelve patients studied, there were increased levels of VEGF, TGF-β, IGF, and CA 15-3 before oophorectomy and there was a decrease after oophorectomy performed. Statistical analysis showed that oophorectomy significantly decreased levels of VEGF (p = 0,023, TGF-β (p = 0,02, and CA 15-3 (p = 0,002, but no significant effect on the decrease in IGF levels (p = 0,875 . Oophorectomy reduces levels of VEGF, TGF β and CA 15-3 serum significantly in the first three months of observation. Thus, it could be considered for the management of advanced breast cancer in young age.

  8. Theoretical Characterizaiton of Visual Signatures (Muzzle Flash) (United States)

    Kashinski, D. O.; Scales, A. N.; Vanderley, D. L.; Chase, G. M.; di Nallo, O. E.; Byrd, E. F. C.


    We are investigating the accuracy of theoretical models used to predict the visible, ultraviolet and infrared spectra of product materials ejected from the muzzle of currently fielded systems. Recent advances in solid propellants has made the management of muzzle signature (flash) a principle issue in weapons development across the calibers. A priori prediction of the electromagnetic spectra of formulations will allow researchers to tailor blends that yield desired signatures and determine spectrographic detection ranges. We are currently employing quantum chemistry methods at various levels of sophistication to optimize molecular geometries, compute vibrational frequencies, and determine the optical spectra of specific gas-phase molecules and radicals of interest. Electronic excitations are being computed using Time Dependent Density Functional Theory (TD-DFT). A comparison of computational results to experimental values found in the literature is used to assess the affect of basis set and functional choice on calculation accuracy. The current status of this work will be presented at the conference. Work supported by the ARL, and USMA.

  9. Flash Nanoprecipitation: Particle Structure and Stability (United States)

    Pustulka, Kevin M.; Wohl, Adam R.; Lee, Han Seung; Michel, Andrew R.; Han, Jing; Hoye, Thomas R.; McCormick, Alon V.; Panyam, Jayanth; Macosko, Christopher W.


    Flash nanoprecipitation (FNP) is a process that, through rapid mixing, stabilizes an insoluble low molecular weight compound in a nano-sized, polymer-stabilized delivery vehicle. The polymeric components are typically amphiphilic diblock copolymers (BCPs). In order to fully exploit the potential of FNP, factors affecting particle structure, size, and stability must be understood. Here we show that polymer type, hydrophobicity and crystallinity of the small molecule, and small molecule loading levels all affect particle size and stability. Of the four block copolymers (BCP) that we have studied here, poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) was most suitable for potential drug delivery applications due to its ability to give rise to stable nanoparticles, its biocompatibility, and its degradability. We found little difference in particle size when using PLGA block sizes over the range of 5 to 15kDa. The choice of hydrophobic small molecule was important, as molecules with a calculated water-octanol partition coefficient (clogP) below 6 gave rise to particles that were unstable and underwent rapid Ostwald ripening. Studies probing the internal structure of nanoparticles were also performed. Analysis of differential scanning calorimetry (DSC), cryogenic transmission electron microscopy (cryo-TEM), and 1H-NMR experiments support a three-layer core-shell-corona nanoparticle structure. PMID:24053447

  10. Mass flow determination in flashing openings

    Directory of Open Access Journals (Sweden)

    G Polanco


    Full Text Available The output flow characteristics in most of the industrial accidental releasesare related to a two-phase flow and their represent a potential hazard tofacilities, personnel, equipments and environment. If these releases involvesuperheated liquid then a flashing process can take place, where a liquidgasmixture due to the breaking of the metastable state can significantlyaffect the hazard zone. The calculation of the conditions for the flow after aflashing opening is very relevant in order to understand the mechanismspresent after the release opening. Numerical modelling represents animportant tool to approach these types of phenomena. However,the accuracy of the obtained results will depend on the realistic values ofthe flow parameters taken as input information to perform the CFD work.The model proposed here is based on the assumption of the existence ofa non reversible work in the system and the use of the thermodynamicjump formulation to model the phase change process in order to predictphase velocity and mass flow. The obtained results have a goodagreement with the experimental data available.

  11. Flash pyrolysis fuel oil: bio-pok

    Energy Technology Data Exchange (ETDEWEB)

    Gust, S. [Neste Oy, Porvoo (Finland)


    Samples of flash pyrolysis liquid produced by Union Fenosa, Spain from pine and straw and samples produced by Ensyn of Canada from mixed hardwoods were combusted with simple pressure atomization equipment commonly used with light fuel oils in intermediate size (0.1-1 MW) boilers. With a number of modifications to the combustion system, carbon monoxide (CO) and nitrous oxide (NO{sub x}) could be reduced to acceptable levels: CO < 30 ppm and NO{sub x} < 140 ppm. Particulate emissions which were initially very high (Bacharach 4-5) were reduced (Bach. 2-3) by system improvements but are still higher than from light fuel oil (Bach. <1). The modifications to the combustion system were: refractory section between burner and boiler, acid resistant progressive cavity pump, higher liquid preheat temperature and higher pressure than for light fuel oils. The main problems with pyrolysis liquids concerns their instability or reactivity. At temperatures above 100 deg C they begin to coke, their viscosity increases during storage and oxygen from air causes skin formation. This requires that special handling procedures are developed for fuel storage, delivery and combustion systems. (orig.)

  12. Production of bio-oil with flash pyrolysis; Biooeljyn tuotanto flash-pyrolyysillae ja sen poltto

    Energy Technology Data Exchange (ETDEWEB)

    Nyroenen, T. [Vapo Oy, Jyvaeskylae (Finland)


    The target of the R and D work is to study the production of bio-oils using Flash-pyrolysis technology and utilisation of the bio-oil in oil-fuelled boilers. The PDU-unit was installed at VTT Energy in Otaniemi in April 1996. The first test were carried out in June. In the whole project Vapo Oy is responsible for: acquiring the 20 kg/h PDU-device for development; follow up of the engine tests; the investment of 5 MW demonstration plant; to carry on the boiler and engine tests with Finnish bio-oils. (orig.)

  13. Some Improvements in Utilization of Flash Memory Devices (United States)

    Gender, Thomas K.; Chow, James; Ott, William E.


    Two developments improve the utilization of flash memory devices in the face of the following limitations: (1) a flash write element (page) differs in size from a flash erase element (block), (2) a block must be erased before its is rewritten, (3) lifetime of a flash memory is typically limited to about 1,000,000 erases, (4) as many as 2 percent of the blocks of a given device may fail before the expected end of its life, and (5) to ensure reliability of reading and writing, power must not be interrupted during minimum specified reading and writing times. The first development comprises interrelated software components that regulate reading, writing, and erasure operations to minimize migration of data and unevenness in wear; perform erasures during idle times; quickly make erased blocks available for writing; detect and report failed blocks; maintain the overall state of a flash memory to satisfy real-time performance requirements; and detect and initialize a new flash memory device. The second development is a combination of hardware and software that senses the failure of a main power supply and draws power from a capacitive storage circuit designed to hold enough energy to sustain operation until reading or writing is completed.

  14. Normalized Temperature Contrast Processing in Infrared Flash Thermography (United States)

    Koshti, Ajay M.


    The paper presents further development in normalized contrast processing used in flash infrared thermography method. Method of computing normalized image or pixel intensity contrast, and normalized temperature contrast are provided. Methods of converting image contrast to temperature contrast and vice versa are provided. Normalized contrast processing in flash thermography is useful in quantitative analysis of flash thermography data including flaw characterization and comparison of experimental results with simulation. Computation of normalized temperature contrast involves use of flash thermography data acquisition set-up with high reflectivity foil and high emissivity tape such that the foil, tape and test object are imaged simultaneously. Methods of assessing other quantitative parameters such as emissivity of object, afterglow heat flux, reflection temperature change and surface temperature during flash thermography are also provided. Temperature imaging and normalized temperature contrast processing provide certain advantages over normalized image contrast processing by reducing effect of reflected energy in images and measurements, therefore providing better quantitative data. Examples of incorporating afterglow heat-flux and reflection temperature evolution in flash thermography simulation are also discussed.

  15. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers.

    Directory of Open Access Journals (Sweden)

    David Gonzalez

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα, Tcf4 and α-smooth muscle actin (α-SMA levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs, which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases.

  16. Ligustrazine Inhibits Cartilage Endplate Hypertrophy via Suppression of TGF-β1

    Directory of Open Access Journals (Sweden)

    Shufen Liu


    Full Text Available CEP hypertrophy is one of the characteristics of intervertebral disc degeneration (IDD. LIG exerts a protective effect on IDD in animal model. The effect of LIG on CEP hypertrophy is further investigated in the present study. Cells were isolated from hypertrophic samples obtained from patients during vertebral fusion surgery. Cellular proliferation and the expression of type I collagen (Col I and TGF-β1 were tested. In the bipedal rats, the edges of the CEP and the sizes of noncartilaginous outgrowth, as well as the expression of osteogenic markers, Col1a, ALP, Runx2, and TGF-β1, were detected. Within two passages, the condensed hypertrophic CEP cells exhibited osteogenic capacity by bony-like nodules and ALP positive staining, along with increased expression of Col I and TGF-β1. LIG inhibited proliferation of CEP cells and downregulated the expression of Col I and TGF-β1 in vitro. Furthermore, LIG attenuated CEP hypertrophy on the lumbar spine of bipedal rats by reducing Col1a, ALP, Runx2, and TGF-β1 mRNA expression and TGF-β1 distribution in vivo. We concluded LIG exerted a preventive effect on CEP hypertrophy via suppression of TGF-β1 levels. This information could be used to develop alternative therapeutic methods to treat spinal CEP hypertrophy.

  17. Aluminum trichloride inhibits osteoblast mineralization via TGF-β1/Smad signaling pathway. (United States)

    Sun, Xudong; Cao, Zheng; Zhang, Qiuyue; Li, Miao; Han, Lulu; Li, Yanfei


    Osteoporosis is a major global public health problem. Aluminum (Al) exposure inhibits osteoblast mineralization and induces osteoporosis. However, the exact mechanism is not fully understood. The transforming growth factor β1 (TGF-β1)/Smad pathway is a major signaling cascade in regulating osteoblast mineralization. To investigate whether TGF-β1/Smad signaling pathway was involved in the Al-induced inhibition of osteoblast mineralization, osteoblasts were cultured and exposed to different concentrations of aluminum trichloride (AlCl3) (containing 0, 0.01, 0.02 and 0.04 mg/mL Al(3+)) for 24 h. We found that mineralized matrix nodules, mRNA expressions of alkaline phosphatase (ALP), type I collagen (Col I), TGF-β1, TGF-β type I receptor, TGF-β type II receptor and Smad4, protein expressions of TGF-β1 and p-Smad2/3, Smad2/3/4 trimeric complex were all decreased, whereas the mRNA expressions of Smad7 were increased in the AlCl3-treated groups compared with those in control. In conclusion, these results indicated that AlCl3 inhibited osteoblast mineralization via TGF-β1/Smad signaling pathway in rat osteoblasts. Our findings could provide novel insights into the mechanisms of action of AlCl3 in osteoporosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. (United States)

    Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L; Mears, Simon C; Askin, Frederic B; Frassica, Frank J; Chang, Weizhong; Yao, Jie; Carrino, John A; Cosgarea, Andrew; Artemov, Dmitri; Chen, Qianming; Zhao, Zhihe; Zhou, Xuedong; Riley, Lee; Sponseller, Paul; Wan, Mei; Lu, William Weijia; Cao, Xu


    Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-β1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-β1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-β1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-β activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-β type II receptor (TβRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-β1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.

  19. Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic allergic contact dermatitis. (United States)

    Tamaka, Kyoko; Seike, Masahiro; Hagiwara, Tamio; Sato, Atsushi; Ohtsu, Hiroshi


    Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (-/-) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6-trinitro-1-chlorobenzene (TNCB) on HDC (+/+) and HDC (-/-) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF-β1 in this model. Recombinant TGF-β1 or anti-TGF-β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine-regulated TGF-β on the Treg population in CACD. Recombinant TGF-β1 injection promoted the infiltration of Tregs in the skin and the production of IL-10; however, anti-TGF-β1 antibody injection suppressed the number of Tregs in the skin and the production of IL-10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF-β. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Human Aqueous Humor Levels of TGF-β2: Relationship with Axial Length

    Directory of Open Access Journals (Sweden)

    Yan Jia


    Full Text Available Purpose. To analyze the relationship between transforming growth factor-beta 2 (TGF-β2 levels in the anterior chamber aqueous humor and axial length of patients with myopia. Methods. TGF-β2 was measured with the Luminex xMAP Technology by using commercially available Milliplex xMAP Kits. Sixty-five aqueous humor samples were collected during cataract or clear lens extraction surgery and TGF-β2 levels in these specimens were analyzed. According to the axial length, the samples were divided into three groups: A (AL ≤24 mm, B (24~29 mm, and C (AL ≥ 29 mm. Results. Aqueous humor samples were analyzed from subjects with an average age of 67.0 ± 11.7 years. Mean TGF-β2 concentration of all aqueous samples was 422.2 ± 258.8 pg/mL. TGF-β2 concentration in group C (543 ± 317 pg/mL was significantly greater than that in group A (390 ± 212 pg/mL and group B (337 ± 217 pg/mL. The concentration of TGF-β2 was positively correlated with axial length (r = 0.308, P = 0.013. Conclusions. TGF-β2 is likely to be acting as a critical factor in axial elongation and development of myopia.

  1. Role of TGF-betas in normal human endometrium and endometriosis. (United States)

    Omwandho, Charles O A; Konrad, Lutz; Halis, Gülden; Oehmke, Frank; Tinneberg, Hans-Rudolf


    Endometriosis is characterized by presence of endometrial tissue outside the uterus. Prevalence is estimated at 6-10% in the general female population and many patients experience pain and/or infertility. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of viable endometriotic tissue. Mild cases are managed medically with contraceptive steroids and non-steroidal anti-inflammatory agents. Surgery provides relief to women in pain but symptoms recur in 75% of cases within 2 years. Starting with menstruation, we have categorized endometriosis into six stages, namely (1) shedding of cells, (2) cell survival, (3) escape from immune surveillance, (4) adhesion to peritoneum, (5) angiogenesis and (6) bleeding. In most of these biological processes, which resemble metastasis, transforming growth factor-beta (TGF-betas) and their high-affinity receptors are involved directly or indirectly. TGF-betas are abundantly and differentially expressed in the endometrium under hormonal control. Although they are preferentially synthesized in the stroma, glands and macrophages also secrete TGF-betas into the uterine fluid, where interaction with preimplantation embryos is suspected. Because mRNA and protein expression of all three TGF-betas is increased around menstruation, we suggest that TGF-betas might be involved in initiation of menstruation. Furthermore, because of high postmenstrual TGF-beta3 levels, we suppose that it might participate in scarless postmenstrual regeneration of endometrium. Our suggestions pave the way to novel routes of investigation into the roles of TGF-betas during menstruation and endometriosis.

  2. TGF-β1 Protection against Aβ1–42-Induced Neuroinflammation and Neurodegeneration in Rats

    Directory of Open Access Journals (Sweden)

    Wei-Xing Shen


    Full Text Available Transforming growth factor (TGF-β1, a cytokine that can be expressed in the brain, is a key regulator of the brain’s responses to injury and inflammation. Alzheimer’s disease (AD, the most common neurodegenerative disorder, involves inflammatory processes in the brain in addition to the hallmarks, amyloid-β (Aβ plaques and neurofibrillary tangles. Recently, we have shown that T-helper (Th 17 cells, a subpopulation of CD4+ T-cells with high proinflammation, also participate in the brain inflammatory process of AD. However, it is poorly known whether TGF-β1 ameliorates the lymphocyte-mediated neuroinflammation and, thereby, alleviates neurodegeneration in AD. Herein, we administered TGF-β1 via the intracerebroventricle (ICV in AD model rats, by Aβ1–42 injection in both sides of the hippocampus, to show the neuroprotection of TGF-β1. The TGF-β1 administration after the Aβ1–42 injection ameliorated cognitive deficit and neuronal loss and apoptosis, reduced amyloid precursor protein (APP expression, elevated protein phosphatase (PP2A expression, attenuated glial activation and alleviated the imbalance of the pro-inflammatory/anti-inflammatory responses of T-lymphocytes, compared to the Aβ1–42 injection alone. These findings demonstrate that TGF-β1 provides protection against AD neurodegeneration and suggest that the TGF-β1 neuroprotection is implemented by the alleviation of glial and T-cell-mediated neuroinflammation.

  3. Transforming growth factor-beta1 (TGF-beta1) and acetylcholine (ACh) alter nitric oxide (NO) and interleukin-1beta (IL-1beta) secretion in human colon adenocarcinoma cells. (United States)

    Paduch, Roman; Kandefer-Szerszeń, Martyna


    Colon adenocarcinoma is one of the most common fatal malignancies in Western countries. Progression of this cancer is dependent on tumor microenvironmental signaling molecules such as transforming growth factor-beta (TGF-beta) or acetylcholine (ACh). The present study was conducted to assess the influence of recombinant human transforming growth factor (rhTGF)-beta1 or ACh on nitric oxide (NO) and interleukin-1beta (IL-1beta) secretion by three human colon adenocarcinoma cell lines: HT29, LS180, and SW948, derived from different grade tumors (Duke's stage). The cells were cultured in 2D and 3D (spheroids) conditions. Colon carcinoma cells exhibited different sensitivities to rhTGF-beta1 or ACh dependent on the tumor grade and the culture model. ACh exhibited significant inhibitory effects towards NO, endothelial nitric oxide synthase (eNOS), and IL-1beta secretion especially by tumor cells derived form Duke's C stage of colon carcinoma. rhTGF-beta1 also decreased NO, IL-1beta, and eNOS expression, but its effect was lower than that observed after the administration of ACh. The inhibition of NO and IL-1beta production was more striking in 3D tumor spheroids than in 2D culture monolayers. Taken together, the TGF-beta1-ACh axis may regulate colon carcinoma progression and metastasis by altering NO secretion and influence inflammatory responses by modulating IL-1beta production.

  4. Insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mediate TGF-β- and myostatin-induced suppression of proliferation in porcine embryonic myogenic cell cultures

    International Nuclear Information System (INIS)

    Kamanga-Sollo, E.; Pampusch, M.S.; White, M.E.; Hathaway, M.R.; Dayton, W.R.


    We have previously shown that cultured porcine embryonic myogenic cells (PEMC) produce both insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 and secrete these proteins into their media. Exogenously added recombinant porcine (rp) IGFBP-3 and rpIGFBP-5 act via IGF-dependent and IGF-independent mechanisms to suppress proliferation of PEMC cultures. Furthermore, immunoneutralization of endogenous IGFBP-3 and IGFBP-5 in the PEMC culture medium results in increased DNA synthesis rate suggesting that endogenous IGFBP-3 and IGFBP-5 suppress PEMC proliferation. TGF-β superfamily members myostatin and TGF-β 1 have also been shown to suppress proliferation of myogenic cells, and treatment of cultured PEMC with either TGF-β 1 or myostatin significantly (P 1 and myostatin. Here, we show that immunoneutralization of IGFBP-5 also significantly (P 1 or myostatin-treated PEMC cultures restores Long-R3-IGF-I-stimulated DNA synthesis rates to 90% of the levels observed in control cultures receiving no TGF-β 1 or myostatin treatment (P 1 or myostatin-treated PEMC cultures, phosphosmad2 levels in these cultures were not affected. These findings strongly suggest that IGFBP-3 and IGFBP-5 affect processes downstream from receptor-mediated Smad phosphorylation that facilitate the ability of TGF-β and myostatin to suppress proliferation of PEMC

  5. Time-resolved dissection of early phosphoproteome and ensuing proteome changes in response to TGF

    DEFF Research Database (Denmark)

    J D'Souza, Rochelle C; Knittle, Anna M; Nagaraj, Nagarjuna


    and phosphorylation and knowledge of protein interactions and transcriptional regulation provided a comprehensive representation of the dynamic signaling events underlying TGF-β-induced changes in cell behavior. Our data suggest that in epithelial cells stimulated with TGF-β, early signaling is a mixture of both pro...... changes of cultured human keratinocytes undergoing EMT and cell cycle arrest in response to stimulation with TGF-β. We quantified significant changes in 2079 proteins and 2892 phosphorylation sites regulated by TGF-β. We identified several proteins known to be involved in TGF-β-induced cellular processes...

  6. An electro-optical timing diagnostic for pump-probe experiments at the free-electron laser in Hamburg FLASH

    International Nuclear Information System (INIS)

    Azima, Armin


    timing diagnostic was part of a series of two-color near-infrared/XUV pump-probe experiments. It was used to correct the measurement delay times of the experiments a posteriori and thus compensate for the temporal jitter of FLASH. By this means the temporal resolution of two-color pump-probe experiments at FLASH was improved by more than a factor 4 from 250 fs RMS or worse to just 60 fs RMS. A pump-probe experiment performed on a Gallium-Arsenide waver using the FLASH XUV pulse as pump pulse revealed an optical light reflectivity modulation induced by FLASH. The temporal dynamics of this process was investigated in detail due to the jitter corrections of the timing diagnostic. The improved temporal resolution lead to a high degree in the understanding and interpretation of the underlying physical processes of the observed reflectivity modulation. Meanwhile the timing diagnostic advanced to a standard diagnostic, which is regularly utilized by pump-probe experimental groups of the FLASH user facility. (orig.)

  7. An electro-optical timing diagnostic for pump-probe experiments at the free-electron laser in Hamburg FLASH

    Energy Technology Data Exchange (ETDEWEB)

    Azima, Armin


    timing diagnostic was part of a series of two-color near-infrared/XUV pump-probe experiments. It was used to correct the measurement delay times of the experiments a posteriori and thus compensate for the temporal jitter of FLASH. By this means the temporal resolution of two-color pump-probe experiments at FLASH was improved by more than a factor 4 from 250 fs RMS or worse to just 60 fs RMS. A pump-probe experiment performed on a Gallium-Arsenide waver using the FLASH XUV pulse as pump pulse revealed an optical light reflectivity modulation induced by FLASH. The temporal dynamics of this process was investigated in detail due to the jitter corrections of the timing diagnostic. The improved temporal resolution lead to a high degree in the understanding and interpretation of the underlying physical processes of the observed reflectivity modulation. Meanwhile the timing diagnostic advanced to a standard diagnostic, which is regularly utilized by pump-probe experimental groups of the FLASH user facility. (orig.)

  8. A Scalable and Highly Configurable Cache-Aware Hybrid Flash Translation Layer

    Directory of Open Access Journals (Sweden)

    Jalil Boukhobza


    Full Text Available This paper presents a cache-aware configurable hybrid flash translation layer (FTL, named CACH-FTL. It was designed based on the observation that most state-of­­-the-art flash-specific cache systems above FTLs flush groups of pages belonging to the same data block. CACH-FTL relies on this characteristic to optimize flash write operations placement, as large groups of pages are flushed to a block-mapped region, named BMR, whereas small groups are buffered into a page-mapped region, named PMR. Page group placement is based on a configurable threshold defining the limit under which it is more cost-effective to use page mapping (PMR and wait for grouping more pages before flushing to the BMR. CACH-FTL is scalable in terms of mapping table size and flexible in terms of Input/Output (I/O workload support. CACH-FTL performs very well, as the performance difference with the ideal page-mapped FTL is less than 15% in most cases and has a mean of 4% for the best CACH-FTL configurations, while using at least 78% less memory for table mapping storage on RAM.

  9. Ultra-High Speed Visualization of the Flashing Instability in Micron Size Nozzles under Vacuum Conditions

    KAUST Repository

    Alghamdi, Tariq A.


    I visualized the flash-boiling atomization of liquid jets released into a low pressure environment at frame rates of up to five million frames per second. Such a high temporal resolution allowed us to observe for the first time the bubble expansion mechanism that atomizes the jet. To visualize the dynamics in detail, I focused closely to the outflow of the nozzle using a long distance microscope objective. I documented an abrupt transition from a laminar to a fully external flashing jet by systematically reducing the ambient pressure. I performed experiments with different volatile liquids and using nozzles with different inner diameters. The inner diameters of the nozzles varied from 30 to 480 . Perfluorohexane (PFnH) was our main working fluid, but also methanol, ethanol and 1-bromopropane were tested. Surprisingly, minimum intensity profiles revealed spray angles close to ~360°, meaning drops are ejected in all directions. Also, I measured speeds of bubble expansion up to 140 m/s. That is 45 times faster than the upper bound for inertial growth speed in complete vacuum from the Rayleigh-Plesset equation. I also calculated the trajectories of the ejected droplets as well as the drop speed distribution using particle tracking. I expect that our results bring new insight into the flash-boiling atomization mechanism.

  10. "Know What to Do If You Encounter a Flash Flood": Mental Models Analysis for Improving Flash Flood Risk Communication and Public Decision Making. (United States)

    Lazrus, Heather; Morss, Rebecca E; Demuth, Julie L; Lazo, Jeffrey K; Bostrom, Ann


    Understanding how people view flash flood risks can help improve risk communication, ultimately improving outcomes. This article analyzes data from 26 mental models interviews about flash floods with members of the public in Boulder, Colorado, to understand their perspectives on flash flood risks and mitigation. The analysis includes a comparison between public and professional perspectives by referencing a companion mental models study of Boulder-area professionals. A mental models approach can help to diagnose what people already know about flash flood risks and responses, as well as any critical gaps in their knowledge that might be addressed through improved risk communication. A few public interviewees mentioned most of the key concepts discussed by professionals as important for flash flood warning decision making. However, most interviewees exhibited some incomplete understandings and misconceptions about aspects of flash flood development and exposure, effects, or mitigation that may lead to ineffective warning decisions when a flash flood threatens. These include important misunderstandings about the rapid evolution of flash floods, the speed of water in flash floods, the locations and times that pose the greatest flash flood risk in Boulder, the value of situational awareness and environmental cues, and the most appropriate responses when a flash flood threatens. The findings point to recommendations for ways to improve risk communication, over the long term and when an event threatens, to help people quickly recognize and understand threats, obtain needed information, and make informed decisions in complex, rapidly evolving extreme weather events such as flash floods. © 2015 Society for Risk Analysis.

  11. The mechanism of epithelial-mesenchymal transition induced by TGF-β1 in neuroblastoma cells. (United States)

    Shao, Jing-Bo; Gao, Zhi-Mei; Huang, Wen-Yan; Lu, Zhi-Bao


    Neuroblastoma is the second most common extracranial malignant solid tumor that occurs in childhood, and metastasis is one of the major causes of death in neuroblastoma patients. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. Therefore, this study investigated the mechanism by which transforming growth factor (TGF)-β1 induces EMT in human neuroblastoma cells. Using quantitative RT-qPCR and western blot analyses, we found that the mRNA and protein expression levels of E-cadherin were significantly decreased, whereas that of α-SMA was significantly increased after neuroblastoma cells were treated with different concentrations of TGF-β1. A scratch test and Transwell migration assay revealed that cell migration significantly and directly correlated with the concentration of TGF-β1 indicating that TGF-β1 induced EMT in neuroblastoma cells and led to their migration. Inhibiting Smad2/3 expression did not affect the expression of the key molecules involved in EMT. Further investigation found that the expression of the glioblastoma transcription factor (Gli) significantly increased in TGF-β1-stimulated neuroblastoma cells undergoing EMT, accordingly, interfering with Gli1/2 expression inhibited TGF-β1-induced EMT in neuroblastoma cells. GANT61, which is a targeted inhibitor of Gli1 and Gli2, decreased cell viability and promoted cell apoptosis. Thus, TGF-β1 induced EMT in neuroblastoma cells to increase their migration. Specifically, EMT induced by TGF-β1 in neuroblastoma cells did not depend on the Smad signaling pathway, and the transcription factor Gli participated in TGF-β1-induced EMT independent of Smad signaling.

  12. Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.; Ari, Krakowski; Luo, Kunxin; Chen, David J.; Li, Song


    Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.

  13. A neurotoxicity assessment of high flash aromatic naphtha. (United States)

    Douglas, J F; McKee, R H; Cagen, S Z; Schmitt, S L; Beatty, P W; Swanson, M S; Schreiner, C A; Ulrich, C E; Cockrell, B Y


    Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide-boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 Aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent also known as High Flash Aromatic Naphtha (HFAN). A program was initiated to assess the toxicological properties of HFAN since there may be human exposure, especially in the workplace. The current study was conducted to assess the potential for neurotoxicity in the rat. Adult male Sprague-Dawley rats of approximately 300 grams body weight, in groups of twenty, were exposed by inhalation to HFAN for 90 days at concentrations of 0, 100, 500, and 1500 ppm. During this period the animals were tested monthly for motor activity and in a functional observation battery. After three months of exposure, for 6 hours/day, 5 days/week, 10 animals/group/sex were sacrificed and selected nervous system tissue was examined histopathologically. No signs of neurotoxicity were seen in any of the evaluated parameters, nor was there evidence of pathologic changes in any of the examined tissues.

  14. Characteristics of lightning flashes generating sprites above storms

    Directory of Open Access Journals (Sweden)

    Soula Serge


    Full Text Available Sprites are Transient Luminous Events (TLEs that can extend vertically from 40 to 90 km and horizontally over several tens of km to form clusters of individual or multiple column or/and carrot-shaped luminous elements. They can even extend over more than 100 km in the form of sequential luminous emissions that are called “dancing sprites”. Their optical detection and other parameters describing the storm and the lightning activity associated allow us to understand the conditions of their production and their links with the lightning activity. Our observations confirm some characteristics of the sprites and put forward others: (i the sprites are essentially produced above the stratiform region of the Mesoscale Convective Systems after positive cloud-to-ground lightning flashes that produce large Charge Moment Change (CMC, with a shorter delay if the impulsive CMC (iCMC is larger. (ii The dancing sprites reflect the timing and the location of the successive lightning strokes that generate them. (iii The sprite elements can be shifted from the stroke location when their delay is large. (iv Bright sprites produce current signatures in ELF radiation a few milliseconds (<5 ms after the positive strokes that generate them.

  15. Technical Note: Advances in flash flood monitoring using unmanned aerial vehicles (UAVs

    Directory of Open Access Journals (Sweden)

    M. T. Perks


    Full Text Available Unmanned aerial vehicles (UAVs have the potential to capture information about the earth's surface in dangerous and previously inaccessible locations. Through image acquisition of flash flood events and subsequent object-based analysis, highly dynamic and oft-immeasurable hydraulic phenomena may be quantified at previously unattainable spatial and temporal resolutions. The potential for this approach to provide valuable information about the hydraulic conditions present during dynamic, high-energy flash floods has until now not been explored. In this paper we adopt a novel approach, utilizing the Kande–Lucas–Tomasi (KLT algorithm to track features present on the water surface which are related to the free-surface velocity. Following the successful tracking of features, a method analogous to the vector correction method has enabled accurate geometric rectification of velocity vectors. Uncertainties associated with the rectification process induced by unsteady camera movements are subsequently explored. Geo-registration errors are relatively stable and occur as a result of persistent residual distortion effects following image correction. The apparent ground movement of immobile control points between measurement intervals ranges from 0.05 to 0.13 m. The application of this approach to assess the hydraulic conditions present in the Alyth Burn, Scotland, during a 1 : 200 year flash flood resulted in the generation of an average 4.2 at a rate of 508 measurements s−1. Analysis of these vectors provides a rare insight into the complexity of channel–overbank interactions during flash floods. The uncertainty attached to the calculated velocities is relatively low, with a spatial average across the area of ±0.15 m s−1. Little difference is observed in the uncertainty attached to out-of-bank velocities (±0.15 m s−1, and within-channel velocities (±0.16 m s−1, illustrating the consistency of the approach.

  16. Comparative estimation and assessment of initial soil moisture conditions for Flash Flood warning in Saxony (United States)

    Luong, Thanh Thi; Kronenberg, Rico; Bernhofer, Christian; Janabi, Firas Al; Schütze, Niels


    Flash Floods are known as highly destructive natural hazards due to their sudden appearance and severe consequences. In Saxony/Germany flash floods occur in small and medium catchments of low mountain ranges which are typically ungauged. Besides rainfall and orography, pre-event moisture is decisive, as it determines the available natural retention in the catchment. The Flash Flood Guidance concept according to WMO and Prof. Marco Borga (University of Padua) will be adapted to incorporate pre-event moisture in real-time flood forecast within the ESF EXTRUSO project (SAB-Nr. 100270097). To arrive at pre-event moisture for the complete area of the low mountain range with flash flood potential, a widely applicable, accurate but yet simple approach is needed. Here, we use radar precipitation as input time series, detailed orographic, land-use and soil information and a lumped parameter model to estimate the overall catchment soil moisture and potential retention. When combined with rainfall forecast and its intrinsic uncertainty, the approach allows to find the point in time when precipitation exceeds the retention potential of the catchment. Then, spatially distributed and complex hydrological modeling and additional measurements can be initiated. Assuming reasonable rainfall forecasts of 24 to 48hrs, this part can start up to two days in advance of the actual event. The lumped-parameter model BROOK90 is used and tested for well observed catchments. First, physical meaningful parameters (like albedo or soil porosity) a set according to standards and second, "free" parameters (like percentage of lateral flow) were calibrated objectively by PEST (Model-Independent Parameter Estimation and Uncertainty Analysis) with the target on evapotranspiration and soil moisture which both have been measured at the study site Anchor Station Tharandt in Saxony/Germany. Finally, first results are presented for the Wernersbach catchment in Tharandt forest for main flood events in the 50

  17. Determination of the Global-Average Charge Moment of a Lightning Flash Using Schumann Resonances and the LIS/OTD Lightning Data (United States)

    Boldi, Robert; Williams, Earle; Guha, Anirban


    In this paper, we use (1) the 20 year record of Schumann resonance (SR) signals measured at West Greenwich Rhode Island, USA, (2) the 19 year Lightning Imaging Sensor (LIS)/Optical Transient Detector (OTD) lightning data, and (3) the normal mode equations for a uniform cavity model to quantify the relationship between the observed Schumann resonance modal intensity and the global-average vertical charge moment change M (C km) per lightning flash. This work, by integrating SR measurements with satellite-based optical measurements of global flash rate, accomplishes this quantification for the first time. To do this, we first fit the intensity spectra of the observed SR signals to an eight-mode, three parameter per mode, (symmetric) Lorentzian line shape model. Next, using the LIS/OTD lightning data and the normal mode equations for a uniform cavity model, we computed the expected climatological-daily-average intensity spectra. We then regressed the observed modal intensity values against the expected modal intensity values to find the best fit value of the global-average vertical charge moment change of a lightning flash (M) to be 41 C km per flash with a 99% confidence interval of ±3.9 C km per flash, independent of mode. Mode independence argues that the model adequately captured the modal intensity, the most important fit parameter herein considered. We also tested this relationship for the presence of residual modal intensity at zero lightning flashes per second and found no evidence that modal intensity is significantly different than zero at zero lightning flashes per second, setting an upper limit to the amount of nonlightning contributions to the observed modal intensity.

  18. Deficiency of thioredoxin binding protein-2 (TBP-2 enhances TGF-β signaling and promotes epithelial to mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    So Masaki

    Full Text Available Transforming growth factor beta (TGF-β has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT of various cancer cells. TGF-β-induced EMT is an important step during carcinoma progression to invasion state. Thioredoxin binding protein-2 (TBP-2, also called Txnip or VDUP1 is downregulated in various types of human cancer, and its deficiency results in the earlier onset of cancer. However, it remains unclear how TBP-2 suppresses the invasion and metastasis of cancer.In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF-β and also enhances TGF-β-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-β-responsive expression of Snail and Slug, transcriptional factors related to TGF-β-mediated induction of EMT, and promoted TGF-β-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells.Our results indicate that TBP-2 deficiency enhances TGF-β signaling and promotes TGF-β-induced EMT. The control of TGF-β-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-β signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression.

  19. Meeting report - TGF-β superfamily: signaling in development and disease. (United States)

    Zhang, Ying E; Newfeld, Stuart J


    The latest advances on the transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways were reported at the July 2013 FASEB Summer Research Conference 'The TGF-β Superfamily: Development and Disease'. The meeting was held in Steamboat Springs, Colorado, USA at 6700 feet above sea level in the Rocky Mountains. This was the seventh biannual meeting in the series. In attendance were investigators from a broad range of disciplines with a common interest in the mechanics of TGF-β and BMP signaling pathways, their normal developmental and homeostatic functions, and the diseases associated with pathway misregulation.

  20. XIAP gene expression and function is regulated by autocrine and paracrine TGF-β signaling

    Directory of Open Access Journals (Sweden)

    Van Themsche Céline


    Full Text Available Abstract Background X-linked inhibitor of apoptosis protein (XIAP is often overexpressed in cancer cells, where it plays a key role in survival and also promotes invasiveness. To date however, the extracellular signals and intracellular pathways regulating its expression and activity remain incompletely understood. We have previously showed that exposure to each of the three TGF-β (transforming growth factor beta isoforms upregulates XIAP protein content in endometrial carcinoma cells in vitro. In the present study, we have investigated the clinical relevance of TGF-β isoforms in endometrial tumours and the mechanisms through which TGF-β isoforms regulate XIAP content in uterine cancer cells. Methods TGF-β isoforms immunoreactivity in clinical samples from endometrial tumours was assessed using immunofluorescence. Two model cancer cell lines (KLE endometrial carcinoma cells and HeLa cervical cancer cells and pharmacological inhibitors were used to investigate the signalling pathways regulating XIAP expression and activity in response to autocrine and paracrine TGF-β in cancer cell. Results We have found immunoreactivity for each TGF-β isoform in clinical samples from endometrial tumours, localizing to both stromal and epithelial/cancer cells. Blockade of autocrine TGF-β signaling in KLE endometrial carcinoma cells and HeLa cervical cancer cells reduced endogenous XIAP mRNA and protein levels. In addition, each TGF-β isoform upregulated XIAP gene expression when given exogenously, in a Smad/NF-κB dependent manner. This resulted in increased polyubiquitination of PTEN (phosphatase and tensin homolog on chromosome ten, a newly identified substrate for XIAP E3 ligase activity, and in a XIAP-dependent decrease of PTEN protein levels. Although each TGF-β isoform decreased PTEN content in a XIAP- and a Smad-dependent manner, decrease of PTEN levels in response to only one isoform, TGF-β3, was blocked by PI3-K inhibitor LY294002. Conclusions

  1. TGF-?1 Regulation of Estrogen Production in Mature Rat Leydig Cells


    Liu, Man-Li; Wang, Huan; Wang, Zong-Ren; Zhang, Yu-Fen; Chen, Yan-Qiu; Zhu, Fang-Hong; Zhang, Yuan-Qiang; Ma, Jing; Li, Zhen


    BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1) is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2) synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC) between Leydig cells. METH...

  2. TGF-β1 Inhibits TLR-mediated Odontoblast Responses to Oral Bacteria


    Horst, O.V.; Tompkins, K.A.; Coats, S.R.; Braham, P.H.; Darveau, R.P.; Dale, B.A.


    TGF-β1 exerts diverse functions in tooth development and tissue repair, but its role in microbial defenses of the tooth is not well-understood. Odontoblasts extending their cellular processes into the dentin are the first cells to recognize signals from TGF-β1 and bacteria in carious dentin. This study aimed to determine the role of TGF-β1 in modulating odontoblast responses to oral bacteria. We show that these responses depend upon the expression levels of microbial recognition receptors TLR...

  3. In vivo evaluation of expression of TGF{beta}1 in the irradiated heart; Expressao da proteina TGF{beta}1 em coracao irradiado in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Affonso Junior, Renato Jose [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. Diagnostico por Imagem; Oshima, Celina Tizuko Fujiyama; Silva, Maria Regina Regis [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina. Setor de Anatomia Patologica; Kimura, Edna Teruko [Sao Paulo Univ., SP (Brazil). Inst. de Ciencias Biomedicas. Dept. de Histologia; Egami, Mizue Imoto [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Morfologia; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina. Setor de Radioterapia]. E-mail:


    The objectives of this study were to assess the latent and active TGF{beta}1 localization in the heart, to evaluate whether or not radiation induces latent TGF{beta}1 activation, and to study the distribution of collagen fibers in the irradiated heart. Thirty-two C 57 BL mice were randomly assigned in two groups: GI (non irradiated animals) and GII (irradiated animals). The mice from G II received a single whole-body radiation dose of 7 Gy, using a {sup 60}Co source at a dose rate of 0.97 Gy/min. The animals were sacrificed by cervical dislocation at 1, 14, 30 and 90 days after irradiation. The irradiated hearts showed: nuclear changes and muscle cells with decreased striations; significant increase in the collagen deposition 90 days after irradiation; latent TGF{beta}1 activation in the cardio myocytes and connective tissue cells after irradiation. Our results show the importance of TGF{beta}1 protein in the process of radiation-induced heart fibrosis and suggest that cardio myocytes and connective cells may play a role in this mechanism acting as cellular sources of active TGF{beta}1. (author)

  4. Synergistic effects of 1,25-Dihydroxyvitamin D3 and TGF-beta1 on the production of insulin-like growth factor binding protein 3 in human bone marrow stromal cell cultures

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Kassem, M


    1,25-Dihydroxyvitamin D3 (calcitriol), transforming growth factor-beta (TGF-beta), and insulin-like growth factors (IGFs) are all important bone regulatory factors known to affect proliferation and differentiation of human bone-forming cells (osteoblasts). We have previously shown that TGF-beta1...... increased IGF-I and IGF-binding protein (IGFBP)-3 production in human bone marrow stromal (hMS) osteoblast progenitors and calcitriol stimulated IGFBP-3 and IGFBP-4 production. As interaction between signaling pathways of these factors has been reported, the present study aimed at examining the concerted...... actions on components of the IGF-system. We report that co-treatment with TGF-beta1 and calcitriol resulted in a synergistic increase in IGFBP-3 production, thereby suggesting that the effects of these factors on hMS osteoblast differentiation may involve the observed increase in IGFBP-3....

  5. Potential Usefulness of Flash-Induced Superluminal Light-Echo Pairs (United States)

    Nemiroff, Robert J.; Zhong, Qi


    Astronomical flashes can create transient light-echo pair phenomena that have never yet been seen but might result in useful information, if found. Toward this end, it is first proven that all light-echo spots are intrinsically superluminal. The radial component of spot speeds toward an observer, however, may be subluminal, and spot pair creation and annihilation events will be observable, in theory, when spots cross the radial superluminal speed boundary. If found, these light-echo pairs could connect angular speeds to spatial speeds, which in turn could result in the recovery of absolute sizes, three-dimensional spatial orientations, and distances to astronomical objects. A hypothetical example is given.

  6. lncRNA H19 is involved in TGF-β1-induced epithelial to mesenchymal transition in bovine epithelial cells through PI3K/AKT Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Wei Yang


    Full Text Available Increased levels of long noncoding RNA H19 (H19 have been observed in many inflammatory and organ fibrosis diseases including ulcerative colitis, osteoarthritis, liver fibrosis, renal fibrosis and pulmonary fibrosis. However, the role of H19 in bovine mastitis and mastitis-caused fibrosis is still unclear. In our study, H19 was characterized as a novel regulator of EMT induced by transforming growth factor-β1 (TGF-β1 in bovine mammary alveolar cell-T (MAC-T cell line. We found that H19 was highly expressed in bovine mastitis tissues and inflammatory MAC-T cells induced by virulence factors of pathogens. TGF-β1 was also highly expressed in inflammatory MAC-T cells, and exogenous TGF-β1 could induce EMT, enhance extracellular matrix protein expression, and upregulate H19 expression in epithelial cells. Stable expression of H19 significantly promotes EMT progression and expression of ECM protein induced by TGF-β1 in MAC-T cells. Furthermore, by using a specific inhibitor of the PI3K/AKT pathway, we demonstrated that TGF-β1 upregulated H19 expression through PI3K/AKT pathway. All these observations imply that the lncRNA H19 modulated TGF-β1-induced epithelial to mesenchymal transition in bovine epithelial cells through PI3K/AKT signaling pathway, which suggests that mammary epithelial cells might be one source for myofibroblasts in vivo in the mammary glands under an inflammatory condition, thereby contributing to mammary gland fibrosis.

  7. Flash-flood impacts cause changes in wood anatomy of Alnus glutinosa, Fraxinus angustifolia and Quercus pyrenaica. (United States)

    Ballesteros, J A; Stoffel, M; Bollschweiler, M; Bodoque, J M; Díez-Herrero, A


    Flash floods may influence the development of trees growing on channel bars and floodplains. In this study, we analyze and quantify anatomical reactions to wounding in diffuse-porous (Alnus glutinosa L.) and ring-porous (Fraxinus angustifolia Vahl. and Quercus pyrenaica Willd.) trees in a Mediterranean environment. A total of 54 cross-sections and wedges were collected from trees that had been injured by past flash floods. From each of the samples, micro-sections were prepared at a tangential distance of 1.5 cm from the injury to determine wounding-related changes in radial width, tangential width and lumen of earlywood vessels, and fibers and parenchyma cells (FPC). In diffuse-porous A. glutinosa, the lumen area of vessels shows a significant (non-parametric test, P-value <0.05) decrease by almost 39% after wounding. For ring-porous F. angustifolia and Q. pyrenaica, significant decreases in vessel lumen area are observed as well by 59 and 42%, respectively. Radial width of vessels was generally more sensitive to the decrease than tangential width, but statistically significant values were only observed in F. angustifolia. Changes in the dimensions of earlywood FPC largely differed between species. While in ring-porous F. angustifolia and Q. pyrenaica the lumen of FPC dropped by 22 and 34% after wounding, we observed an increase in FPC lumen area in diffuse-porous A. glutinosa of approximately 35%. Our data clearly show that A. glutinosa represents a valuable species for flash-flood research in vulnerable Mediterranean environments. For this species, it will be possible in the future to gather information on past flash floods with non-destructive sampling based on increment cores. In ring-porous F. angustifolia and Q. pyrenaica, flash floods leave less drastic, yet still recognizable, signatures of flash-flood activity through significant changes in vessel lumen area. In contrast, the use of changes in FPC dimensions appears less feasible for the determination of

  8. Search for the radio occulation flash at Jupiter

    International Nuclear Information System (INIS)

    Martin, J.M.; Tyler, G.L.; Eshleman, V.R.; Wood, G.E.; Lindall, G.F.


    The 'evolute flash' a focusing effect caused by the curvature of a planet's limb, was sought in the radio data taken during the occulation of Voyager 1 by Jupiter, using a modified matched-filter technique. The expected frequency structure of the flash signal is double branched, while the intensity structure is highly localized in time. The search for the signal was carried out over a 6.4 s period. The signal parameters were varied to span the uncertainties introduced by imperfect knowledge of the orbit of the spacecraft and the shape of Jupiter. Several peaks at the 8 standard deviation level were present in the filter output. However, these peaks were separated in time by up to 3.3 s, and none could be identified as the flash. From this negative result a lower bound on the absorption along a ray with periapsis near the 4 bar level in Jupiter's atmosphere can be established at 25 dB. Employing the new Voyager results on the structure of the atmosphere of Jupiter and the mixing ratio of the absorbent ammonia, as well as the improved knowledge of flash characteristics resulting from this study, we estimate that the flash would have been detected if the distance behind the planet where the spacecraft trajectory crossed the evolute were at least 20 Jupiter radii, as compared with a value near 7 in the experiment. For focusing at this greater distance, the atmospheric pressure at the ray periapsis would be between 1.5 and 2 bar

  9. Theoretical investigation of flash vaporisation in a screw expander (United States)

    Vasuthevan, Hanushan; Brümmer, Andreas


    In the present study flash vaporisation of liquid injection in a twin screw expander for a Trilateral Flash Cycle (TFC) is examined theoretically. The TFC process comprises a pressure increase in the working fluid, followed by heating the liquid close to boiling point. The hot liquid is injected into the working chamber of a screw expander. During this process the pressure of the liquid drops below the saturation pressure, while the temperature of the liquid remains virtually constant. Hence the liquid is superheated and in a metastable state. The liquid jet seeks to achieve a stable state in thermodynamic equilibrium and is therefore partially vaporised. This effect is referred to as flash vaporisation. Accordingly, a two-phase mixture, consisting of vapour and liquid, exists in the working chamber. Thermodynamic simulations were carried out using water as the working fluid for representative screw expander geometry. The simulations presented are performed from two different aspects during the filling process of a screw expander. The first case is the vaporisation of the injected liquid in a state of thermodynamic equilibrium, whereby the two-phase mixture is treated entirely as a compressible and homogeneous gas. The second case considers flashing efficiency. It describes the quantity of flashed vapour and consists of a liquid and vapour domain. Both models are compared and analysed with respect to the operational behaviour of a screw expander.

  10. Flash photolysis of rhodopsin in the cat retina

    International Nuclear Information System (INIS)

    Ripps, H.; Mehaffey, L.; Siegel, I.M.; Ernst, W.; Kemp, C.M.


    The bleaching of rhodopsin by short-duration flashes of a xenon discharge lamp was studied in vivo in the cat retina with the aid of a rapid, spectral-scan fundus reflectometer. Difference spectra recorded over a broad range of intensities showed that the bleaching efficacy of high-intensity flashes was less than that of longer duration, steady lights delivering the same amount of energy. Both the empirical results and those derived from a theoretical analysis of flash photolysis indicate that, under the conditions of these experiments, the upper limit of the flash bleaching of rhodopsin in cat is approximately 90%. Although the fact that a full bleach could not be attained is attributable to photoreversal, i.e., the photic regeneration of rhodopsin from its light-sensitive intermediates, the 90% limit is considerably higher than the 50% (or lower) value obtained under other experimental circumstances. Thus, it appears that the duration (approximately 1 ms) and spectral composition of the flash, coupled with the kinetic parameters of the thermal and photic reactions in the cat retina, reduce the light-induced regeneration of rhodopsin to approximately 10%

  11. Venlafaxine and desvenlafaxine in the management of menopausal hot flashes

    Directory of Open Access Journals (Sweden)

    Johnson ED


    Full Text Available Vasomotor flushes are common complaints of women during and after menopause, affecting about 75 percent of this population. Estrogen therapy is the most effective treatment for hot flashes. However, there are a significant number of women who have contraindications or choose not to use estrogen due to potential risks such as breast cancer and thromboembolic disorders. These women need alternative options. The selective norepinephrine reuptake inhibitors, venlafaxine and desvenlafaxine, have shown efficacy in alleviating hot flashes.Objective: The purpose of this review is to assess the efficacy and tolerability of these two agents for treatment of hot flashes in healthy postmenopausal women.Methods: A literature search of the MEDLINE and Ovid databases from inception to June 2011 was conducted. Randomized controlled trials, published in English, with human participants were included. Studies included postmenopausal women, and trials with breast cancer only populations were excluded.Results: Venlafaxine reduced hot flashes by 37 to 61 percent and desvenlafaxine by 55 to 69 percent. Both agents were well tolerated. The most common adverse effects were headache, dry mouth, nausea, insomnia, somnolence, and dizziness.Conclusion: Based on the evidence, venlafaxine and desvenlafaxine are both viable options for reducing the frequency and severity of hot flashes.

  12. Modeling experimental plasma diagnostics in the FLASH code: proton radiography (United States)

    Flocke, Norbert; Weide, Klaus; Feister, Scott; Tzeferacos, Petros; Lamb, Donald


    Proton radiography is an important diagnostic tool for laser plasma experiments and for studying magnetized plasmas. We describe a new synthetic proton radiography diagnostic recently implemented into the FLASH code. FLASH is an open source, finite-volume Eulerian, spatially adaptive radiation hydrodynamics and magneto-hydrodynamics code that incorporates capabilities for a broad range of physical processes. Proton radiography is modeled through the use of the (relativistic) Lorentz force equation governing the motion of protons through 3D domains. Both instantaneous (one time step) and time-resolved (over many time steps) proton radiography can be simulated. The code module is also equipped with several different setup options (beam structure and detector screen placements) to reproduce a large variety of experimental proton radiography designs. FLASH's proton radiography diagnostic unit can be used either during runtime or in post-processing of simulation results. FLASH is publicly available at U.S. DOE NNSA, U.S. DOE NNSA ASC, U.S. DOE Office of Science and NSF.

  13. Immunohistochemical Evaluation of TGF-ß Isoforms in Cases with Ovarian Endometriosis and Follicular Cyst

    Directory of Open Access Journals (Sweden)

    Abdulmuttalip Şentaş


    CONCLUSION: Ovarian tissue TGF-ß1 immunoreactivity was significantly increased in endometriosis cases when compared with follicular cyst. There are needed further studies to elucidate the importance of this finding in the pathogenesis of endometriosis.

  14. The roles of TGF-beta1 gene transfer on collagen formation during Achilles tendon healing. (United States)

    Hou, Yu; Mao, ZeBing; Wei, XueLei; Lin, Lin; Chen, LianXu; Wang, HaiJun; Fu, Xin; Zhang, JiYing; Yu, ChangLong


    Collagen content and cross-linking are believed to be major determinants of tendon structural integrity and function. The current study aimed to investigate the effects of transforming growth factor (TGF)-beta1 on the collagen content and cross-linking of Achilles tendons, and on the histological and biomechanical changes occurring during Achilles tendon healing in rabbits. Bone marrow-derived mesenchymal stem cells (BMSCs) transfected with the TGF-beta1 gene were surgically implanted into experimentally injured Achilles tendons. Collagen proteins were identified by immunohistochemical staining and fiber bundle accumulation was revealed by Sirius red staining. Achilles tendons treated with TGF-beta1-transfected BMSCs showed higher concentrations of collagen I protein, more rapid matrix remodeling, and larger fiber bundles. Thus TGF-beta1 can promote mechanical strength in healing Achilles tendons by regulating collagen synthesis, cross-link formation, and matrix remodeling.

  15. Regulation of TGF-β Superfamily Signaling by SMAD Mono-Ubiquitination (United States)

    Xie, Feng; Zhang, Zhengkui; van Dam, Hans; Zhang, Long; Zhou, Fangfang


    TGF-β(transforming growth factor-β) superfamily signaling mediators are important regulators of diverse physiological and pathological events. TGF-β signals are transduced by transmembrane type I and type II serine/threonine kinase receptors and their downstream effectors, the SMAD (drosophila mothers against decapentaplegic protein) proteins. Numerous studies have already demonstrated crucial regulatory roles for modification of TGF-β pathway components by poly-ubiquitination. Recently, several studies also uncovered mono-ubiquitination of SMADs as a mechanism for SMAD activation or inactivation. Mono-ubiquitination and subsequent deubiquitination of SMAD proteins accordingly play important roles in the control of TGF-β superfamily signaling. This review highlights the major pathways regulated by SMAD mono-ubiquitination. PMID:25317929

  16. Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

    International Nuclear Information System (INIS)

    Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.


    The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

  17. Transforming growth factor (TGF)-β signalling is increased in rheumatoid synovium but TGF-β blockade does not modify experimental arthritis. (United States)

    Gonzalo-Gil, E; Criado, G; Santiago, B; Dotor, J; Pablos, J L; Galindo, M


    The aim of this study was to analyse the distribution of regulatory and inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers of active transforming growth factor (TGF)-β signalling in rheumatoid arthritis (RA) synovial tissue and to investigate the effect of TGF-β blockade in the development and progression of collagen-induced arthritis. The expression of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by immunization with chicken type-II collagen (CII). TGF-β was blocked in vivo with the specific peptide p17 starting at the time of immunization or on the day of arthritis onset. T cell population frequencies and specific responses to CII were analysed. The expression of cytokines and transcription factors was quantified in spleen and joint samples. Statistical differences between groups were compared using the Mann-Whitney U-test or one-way analysis of variance (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7 expression were detected in RA and control tissues. In RA, most lymphoid infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment with TGF-β antagonist did not affect clinical severity, joint inflammation and cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA levels of cytokines and transcription factors, specific proliferation to CII, serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins expression demonstrates active TGF-β signalling in RA synovium. However, specific TGF-β blockade does not have a significant effect in the mice model of collagen-induced arthritis. © 2013 British Society for Immunology.

  18. Induction of TGF-beta1 and TGF-beta1-dependent predominant Th17 differentiation by group A streptococcal infection. (United States)

    Wang, Beinan; Dileepan, Thamotharampillai; Briscoe, Sarah; Hyland, Kendra A; Kang, Johnthomas; Khoruts, Alexander; Cleary, P Patrick


    Recurrent group A Streptococcus (GAS) tonsillitis and associated autoimmune diseases indicate that the immune response to this organism can be ineffective and pathological. TGF-beta1 is recognized as an essential signal for generation of regulatory T cells (Tregs) and T helper (Th) 17 cells. Here, the impact of TGF-beta1 induction on the T-cell response in mouse nasal-associated lymphoid tissue (NALT) following intranasal (i.n.) infections is investigated. ELISA and TGF-beta1-luciferase reporter assays indicated that persistent infection of mouse NALT with GAS sets the stage for TGF-beta1 and IL-6 production, signals required for promotion of a Th17 immune response. As predicted, IL-17, the Th17 signature cytokine, was induced in a TGF-beta1 signaling-dependent manner in single-cell suspensions of both human tonsils and NALT. Intracellular cytokine staining and flow cytometry demonstrated that CD4(+) IL-17(+) T cells are the dominant T cells induced in NALT by i.n. infections. Moreover, naive mice acquired the potential to clear GAS by adoptive transfer of CD4(+) T cells from immunized IL-17A(+)/(+) mice but not cells from IL-17A(-)/(-) mice. These experiments link specific induction of TGF-beta1 by a bacterial infection to an in vivo Th17 immune response and show that this cellular response is sufficient for protection against GAS. The association of a Th17 response with GAS infection reveals a potential mechanism for destructive autoimmune responses in humans.

  19. Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and TGF-B1

    Energy Technology Data Exchange (ETDEWEB)

    Kurpinski, Kyle; Chu, Julia; Wang, Daojing; Li, Song


    Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was induced by TGF-{beta}1, but calponin 3 was not significantly regulated by mechanical strain or TGF-{beta}1, which was in contrast to the synergistic up-regulation of calponin 1 gene expression by cyclic strain and TGF-{beta}1. Further experiments with cycloheximide treatment suggested that the up-regulation of calponin 3 by cyclic strain was at post-transcriptional level. The results in this study suggest that both mechanical stimulation and TGF-{beta}1 signaling play unique and important roles in the regulation of MSCs at both transcriptional and post-transcriptional levels, and that a precise combination of microenvironmental cues may promote MSC differentiation.

  20. Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors. (United States)

    Li, Ning; Ren, Aihui; Wang, Xiaoshuang; Fan, Xin; Zhao, Yong; Gao, George F; Cleary, Patrick; Wang, Beinan


    Influenza infection predisposes the host to secondary bacterial pneumonia, which is a major cause of mortality during influenza epidemics. The molecular mechanisms underlying the bacterial coinfection remain elusive. Neuraminidase (NA) of influenza A virus (IAV) enhances bacterial adherence and also activates TGF-β. Because TGF-β can up-regulate host adhesion molecules such as fibronectin and integrins for bacterial binding, we hypothesized that activated TGF-β during IAV infection contributes to secondary bacterial infection by up-regulating these host adhesion molecules. Flow cytometric analyses of a human lung epithelial cell line indicated that the expression of fibronectin and α5 integrin was up-regulated after IAV infection or treatment with recombinant NA and was reversed through the inhibition of TGF-β signaling. IAV-promoted adherence of group A Streptococcus (GAS) and other coinfective pathogens that require fibronectin for binding was prevented significantly by the inhibition of TGF-β. However, IAV did not promote the adherence of Lactococcus lactis unless this bacterium expressed the fibronectin-binding protein of GAS. Mouse experiments showed that IAV infection enhanced GAS colonization in the lungs of wild-type animals but not in the lungs of mice deficient in TGF-β signaling. Taken together, these results reveal a previously unrecognized mechanism: IAV NA enhances the expression of cellular adhesins through the activation of TGF-β, leading to increased bacterial loading in the lungs. Our results suggest that TGF-β and cellular adhesins may be potential pharmaceutical targets for the prevention of coinfection.

  1. TGF-β1 regulation of estrogen production in mature rat Leydig cells.

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    Man-Li Liu

    Full Text Available BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1 is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2 synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC between Leydig cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured Leydig cells were incubated in the presence of recombinant TGF-β1 and the production of E2 as well as testosterone (T were measured by RIA. The activity of P450arom was addressed by the tritiated water release assay and the expression of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The expression of Cx43 and GJIC were investigated with immunofluorescence and fluorescence recovery after photo-bleaching (FRAP, respectively. Results from this study show that TGF-β1 down-regulates the level of E2 secretion and the activity of P450arom in a dose-dependent manner in adult Leydig cells. In addition, the expression of Cx43 and GJIC was closely related to the regulation of E2 and TGF-β1, and E2 treatment in turn restored the inhibition of TGF-β1 on GJIC. CONCLUSIONS: Our results indicate, for the first time in adult rat Leydig cells, that TGF-β1 suppresses P450arom activity, as well as the expression of the Cyp19 gene, and that depression of E2 secretion leads to down-regulation of Cx43-based GJIC between Leydig cells.

  2. Lack of association between TGF-beta-1 genotypes and microalbuminuria in essential hypertensive men. (United States)

    Dell'Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Del Prato, Stefano; Pedrinelli, Roberto


    Polymorphisms within the gene for transforming growth factor (TGF)-beta-1, a pro-fibrogenic cytokine pathophysiologically involved in hypertension and hypertensive target damage, might modulate the biological activity of the encoded protein. Through that mechanism, they might contribute to microalbuminuria, a marker of subclinical renal damage and a correlate of systemic inflammation and endothelial dysfunction in hypertension, a possibility never before tested. For this reason, we assessed the association of four TGF-beta-1 polymorphic variants (C-509T, Leu(10)-->Pro, Arg(25)-->Pro, Thr(263)-->Ile) with albuminuria in uncomplicated essential hypertensive men, using (circulating active + acid-activatable latent) TGF-beta-1 levels as an indirect index of their in vivo biological activity. Because of the close pathophysiological link of TGF-beta-1 with the renin-angiotensin system, we also tested the behaviour of the angiotensin converting enzyme (ACE) deletion/insertion (D/I) polymorphism. Albuminuria (three overnight collections), office and 24-h BP, left ventricular mass index (LVMI), BMI, renal function, glucose, lipids, plasma TGF-beta-1 (n = 162, ELISA) were measured in 222 genetically unrelated, never-treated, uncomplicated Caucasian hypertensive men. ACE D/I polymorphisms were analysed by the polymerase chain reaction technique or a 5' nuclease assay with further restriction analysis when required. Urine albumin levels or microalbuminuria (albuminuria > or =15 microg/min) did not differ by TGF-beta-1 genotypes, but both parameters were more frequent in ACE D/D homozygotes. Plasma TGF-beta-1 was similar across genetic backgrounds and was unrelated to albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously distributed across genotypes. In contrast to its link with the ACE D/I genotype, microalbuminuria was independent of TGF-beta-1 polymorphism in this group of never-treated, uncomplicated essential hypertensive men.

  3. Repeated exposure of human fibroblasts to ionizing radiation reveals an adaptive response that is not mediated by interleukin-6 or TGF

    International Nuclear Information System (INIS)

    Dieriks, Birger; De Vos, Winnok; Baatout, Sarah; Van Oostveldt, Patrick


    Exposing cells to a low dose can protect them against a subsequent higher exposure. This phenomenon is known as adaptive response and is frequently observed in a variety of cells. Even though similarities are suspected with other non-targeted effects, such as bystander effects, the exact mechanism behind adaptive response is not fully clarified. In this study human primary fibroblasts were tested for their response to ionizing radiation (IR) after administrating a low priming dose (0.1-0.5 Gy). Both the abundance of γH2AX as a marker for double-stranded breaks and the levels of cytokines, secreted in the medium, were monitored in time. Upon challenge, IR-primed cells showed modified γH2AX spot size distributions and altered repair kinetics, consistent with an adaptive response. In addition, 24 h after priming with IR, four cytokines were significantly upregulated in the medium - GM-CSF (1.33x); IL6 (4.24x); IL8 (1.33x); TGF-β (1.46x). In order to mimick the protective effect of IR priming, we primed the cells with either IL6 or TGF-β. This did not elicit an altered γH2AX response as observed in IR-primed cells, indicating that the adaptive response in these primary fibroblasts is regulated in an IL-6 and TGF-β independent manner.

  4. The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Fukada

    Full Text Available BACKGROUND: Zinc (Zn is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS. The Slc39a13 knockout (Slc39a13-KO mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP and TGF-beta signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. CONCLUSIONS/SIGNIFICANCE: Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-beta signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-beta signaling and connective tissue dysfunction.

  5. Repeated exposure of human fibroblasts to ionizing radiation reveals an adaptive response that is not mediated by interleukin-6 or TGF-{beta}

    Energy Technology Data Exchange (ETDEWEB)

    Dieriks, Birger, E-mail: [Bio-imaging and Cytometry Unit, Department of Molecular Biotechnology, Ghent University, Coupure Links 653, 9000 Gent (Belgium); De Vos, Winnok [Bio-imaging and Cytometry Unit, Department of Molecular Biotechnology, Ghent University, Coupure Links 653, 9000 Gent (Belgium); Baatout, Sarah [Bio-imaging and Cytometry Unit, Department of Molecular Biotechnology, Ghent University, Coupure Links 653, 9000 Gent (Belgium); Radiobiology Unit, Laboratory Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Center, SCK.CEN, Boeretang 200, 2400 Mol (Belgium); Van Oostveldt, Patrick, E-mail: [Bio-imaging and Cytometry Unit, Department of Molecular Biotechnology, Ghent University, Coupure Links 653, 9000 Gent (Belgium)


    Exposing cells to a low dose can protect them against a subsequent higher exposure. This phenomenon is known as adaptive response and is frequently observed in a variety of cells. Even though similarities are suspected with other non-targeted effects, such as bystander effects, the exact mechanism behind adaptive response is not fully clarified. In this study human primary fibroblasts were tested for their response to ionizing radiation (IR) after administrating a low priming dose (0.1-0.5 Gy). Both the abundance of {gamma}H2AX as a marker for double-stranded breaks and the levels of cytokines, secreted in the medium, were monitored in time. Upon challenge, IR-primed cells showed modified {gamma}H2AX spot size distributions and altered repair kinetics, consistent with an adaptive response. In addition, 24 h after priming with IR, four cytokines were significantly upregulated in the medium - GM-CSF (1.33x); IL6 (4.24x); IL8 (1.33x); TGF-{beta} (1.46x). In order to mimick the protective effect of IR priming, we primed the cells with either IL6 or TGF-{beta}. This did not elicit an altered {gamma}H2AX response as observed in IR-primed cells, indicating that the adaptive response in these primary fibroblasts is regulated in an IL-6 and TGF-{beta} independent manner.

  6. Flash Points of Secondary Alcohol and n-Alkane Mixtures. (United States)

    Esina, Zoya N; Miroshnikov, Alexander M; Korchuganova, Margarita R


    The flash point is one of the most important characteristics used to assess the ignition hazard of mixtures of flammable liquids. To determine the flash points of mixtures of secondary alcohols with n-alkanes, it is necessary to calculate the activity coefficients. In this paper, we use a model that allows us to obtain enthalpy of fusion and enthalpy of vaporization data of the pure components to calculate the liquid-solid equilibrium (LSE) and vapor-liquid equilibrium (VLE). Enthalpy of fusion and enthalpy of vaporization data of secondary alcohols in the literature are limited; thus, the prediction of these characteristics was performed using the method of thermodynamic similarity. Additionally, the empirical models provided the critical temperatures and boiling temperatures of the secondary alcohols. The modeled melting enthalpy and enthalpy of vaporization as well as the calculated LSE and VLE flash points were determined for the secondary alcohol and n-alkane mixtures.

  7. PNNL 331 Building Arc Flash Team Investigation Report

    Energy Technology Data Exchange (ETDEWEB)

    Deichman, Mark L.; Drewrey, John C.; Hodges, Hurtis; Madson, Vernon J.; Minton, Allen L.; Montgomery, Daniel M.; Olson, Marvin E.; Rojas, Pedro H.; Sanan, Sanjay K.; Sharp, Reed D.; Sparks, Bobby R.; Swearingen, Gary L.


    On Friday, April 21, 2006, a PNNL electrician was performing repair of an electrical system for the 331 Building chilled water pump (CHWP) No.2, when an electrical arc flash occurred inside a 480V combination motor starter. The electrician was taken to the on-site medical provider for evaluation and was released for return to work without restriction. The electrician was not shocked, but did receive a minor, superficial (first degree) burn on the left wrist. This report, the result of a thorough review by the 331 Building Arc Flash Assessment Team, provides an in-depth look at the steps leading up to the arc-flash and recommendations and opportunities for improvement.

  8. Architectural and Integration Options for 3D NAND Flash Memories

    Directory of Open Access Journals (Sweden)

    Rino Micheloni


    Full Text Available Nowadays, NAND Flash technology is everywhere, since it is the core of the code and data storage in mobile and embedded applications; moreover, its market share is exploding with Solid-State-Drives (SSDs, which are replacing Hard Disk Drives (HDDs in consumer and enterprise scenarios. To keep the evolutionary pace of the technology, NAND Flash must scale aggressively in terms of bit cost. When approaching ultra-scaled technologies, planar NAND is hitting a wall: both academia researchers and industry worked to cope with this issue for several decades. Then, the 3D integration approach turned out to be the definitive alternative by eventually reaching mass production. This review paper exposes several 3D NAND Flash memory technologies, along with their related integration challenges, by showing their different layouts, scaling trends and performance/reliability features.

  9. Visualization on triangle concept using Adobe Flash Professional SC6 (United States)

    Sagita, Laela; Ratih Kusumarini, Adha


    The purpose of this paper is to develop teaching aids using Adobe Flash Professional CS6 emphasize on Triangle concept. A new alternative way to deliver a basic concept in geometry with visualization is software Adobe Flash Professional CS 6. Research method is research and development with 5 phase of Ploom’s model, namely (1) preliminary, (2) design, (3) realization/ construction, (4) test, evaluation and revision, and 5) implementation. The results showed that teaching aids was valid, practice, and effective. Validity: expert judgement for material score is 3.95 and media expert judgement produce an average score of 3,2, both in the category are valid. Practically: the average of questionnaire response is 4,04 (good). Effectiveness: n-gain test value is 0,36 (medium). It concluded that developed of teaching aids using Adobe Flash CS6 on triangle can improve student achievement.

  10. Boiling water reactor stability revisited: The effects of flashing

    Energy Technology Data Exchange (ETDEWEB)

    Yadigaroglu, G. [Institute of Energy Technology, Swiss Federal Institute of Technology, ETH, ETH-Zentrum, CLT-C1, CH-8092 Zurich (Switzerland)]. E-mail:; Askari, B. [Institute of Energy Technology, Swiss Federal Institute of Technology, ETH, ETH-Zentrum, CLT-C1, CH-8092 Zurich (Switzerland)


    There are numerous investigations of two-phase flow stability with particular emphasis to BWR stability; these have become increasingly sophisticated and complete over the years. The basic features of a new development and frequency-domain code capable of considering all the channels (bundles) in a BWR, flashing of the coolant at low pressure, full coupling with 3D, two-group neutronics, etc. are described. The basic thermal-hydraulic model is used to study the effects of flashing on stability in a BWR-like channel. The behavior of the channel is highly dynamic. Contrary to what could have been intuitively guessed, the effect of flashing is stabilizing; the reasons and mechanisms leading to this are discussed.

  11. Boiling water reactor stability revisited: The effects of flashing

    International Nuclear Information System (INIS)

    Yadigaroglu, G.; Askari, B.


    There are numerous investigations of two-phase flow stability with particular emphasis to BWR stability; these have become increasingly sophisticated and complete over the years. The basic features of a new development and frequency-domain code capable of considering all the channels (bundles) in a BWR, flashing of the coolant at low pressure, full coupling with 3D, two-group neutronics, etc. are described. The basic thermal-hydraulic model is used to study the effects of flashing on stability in a BWR-like channel. The behavior of the channel is highly dynamic. Contrary to what could have been intuitively guessed, the effect of flashing is stabilizing; the reasons and mechanisms leading to this are discussed

  12. Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

    Directory of Open Access Journals (Sweden)

    Tjitske A Oenema

    Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

  13. Role of TGF-β on cardiac structural and electrical remodeling

    Directory of Open Access Journals (Sweden)

    Roberto Ramos-Mondragón


    Full Text Available Roberto Ramos-Mondragón, Carlos A Galindo, Guillermo AvilaDepartamento de Bioquímica, Cinvestav-IPN, MéxicoAbstract: The type β transforming growth factors (TGF-βs are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-β affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-β signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-β affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-β on cardiac excitation-contraction (EC coupling, action potentials, and ion channels. We also discuss the effects of TGF-β on cardiac development and disease from structural and electrophysiological points of view.Keywords: transforming growth factor, ion channel, cardiac electrophysiology

  14. Prodomain-growth factor swapping in the structure of pro-TGF-β1. (United States)

    Zhao, Bo; Xu, Shutong; Dong, Xianchi; Lu, Chafen; Springer, Timothy A


    TGF-β is synthesized as a proprotein that dimerizes in the endoplasmic reticulum. After processing in the Golgi to cleave the N-terminal prodomain from the C-terminal growth factor (GF) domain in each monomer, pro-TGF-β is secreted and stored in latent complexes. It is unclear which prodomain and GF monomer are linked before proprotein convertase cleavage and how much conformational change occurs following cleavage. We have determined a structure of pro-TGF-β1 with the proprotein convertase cleavage site mutated to mimic the structure of the TGF-β1 proprotein. Structure, mutation, and model building demonstrate that the prodomain arm domain in one monomer is linked to the GF that interacts with the arm domain in the other monomer in the dimeric structure ( i.e. the prodomain arm domain and GF domain in each monomer are swapped). Swapping has important implications for the mechanism of biosynthesis in the TGF-β family and is relevant to the mechanism for preferential formation of heterodimers over homodimers for some members of the TGF-β family. Our structure, together with two previous ones, also provides insights into which regions of the prodomain-GF complex are highly structurally conserved and which are perturbed by crystal lattice contacts. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Atypical interactions of integrin αVβ8with pro-TGF-β1. (United States)

    Wang, Jianchuan; Dong, Xianchi; Zhao, Bo; Li, Jing; Lu, Chafen; Springer, Timothy A


    Integrins α V β 6 and α V β 8 are specialized for recognizing pro-TGF-β and activating its growth factor by releasing it from the latency imposed by its surrounding prodomain. The integrin α V β 8 is atypical among integrins in lacking sites in its cytoplasmic domain for binding to actin cytoskeleton adaptors. Here, we examine α V β 8 for atypical binding to pro-TGF-β1. In contrast to α V β 6 , α V β 8 has a constitutive extended-closed conformation, and binding to pro-TGF-β1 does not stabilize the open conformation of its headpiece. Although Mn 2+ potently activates other integrins and increases affinity of α V β 6 for pro-TGF-β1 25- to 55-fold, it increases α V β 8 affinity only 2- to 3-fold. This minimal effect correlates with the inability of Mn 2+ and pro-TGF-β1 to stabilize the open conformation of the α V β 8 headpiece. Moreover, α V β 8 was inhibited by high concentrations of Mn 2+ and was stimulated and inhibited at markedly different Ca 2+ concentrations than α V β 6 These unusual characteristics are likely to be important in the still incompletely understood physiologic mechanisms that regulate α V β 8 binding to and activation of pro-TGF-β.

  16. Flash Flood Type Identification within Catchments in Beijing Mountainous Area (United States)

    Nan, W.


    Flash flood is a common type of disaster in mountainous area, Flash flood with the feature of large flow rate, strong flushing force, destructive power, has periodically caused loss to life and destruction to infrastructure in mountainous area. Beijing as China's political, economic and cultural center, the disaster prevention and control work in Beijing mountainous area has always been concerned widely. According to the transport mechanism, sediment concentration and density, the flash flood type identification within catchment can provide basis for making the hazards prevention and mitigation policy. Taking Beijing as the study area, this paper extracted parameters related to catchment morphological and topography features respectively. By using Bayes discriminant, Logistic regression and Random forest, the catchments in Beijing mountainous area were divided into water floods process, fluvial sediment transport process and debris flows process. The results found that Logistic regression analysis showed the highest accuracy, with the overall accuracy of 88.2%. Bayes discriminant and Random forest had poor prediction effects. This study confirmed the ability of morphological and topography features to identify flash flood process. The circularity ratio, elongation ratio and roughness index can be used to explain the flash flood types effectively, and the Melton ratio and elevation relief ratio also did a good job during the identification, whereas the drainage density seemed not to be an issue at this level of detail. Based on the analysis of spatial patterns of flash flood types, fluvial sediment transport process and debris flow process were the dominant hazards, while the pure water flood process was much less. The catchments dominated by fluvial sediment transport process were mainly distributed in the Yan Mountain region, where the fault belts were relatively dense. The debris flow process prone to occur in the Taihang Mountain region thanks to the abundant

  17. Expression Profiles of TGF-β and TLR Pathways in Porphyromonas gingivalis and Prevotella intermedia Challenged Osteoblasts. (United States)

    Aydin, Kubra; Ekinci, Fatma Yesim; Korachi, May


    The presence of certain oral pathogens at implant sites can hinder the osseointegration process. However, it is unclear how and by what microorganisms it happens. This study investigated whether the presence of oral pathogens of Porphyromonas gingivalis and Prevotella intermedia individually, play a role in the failure of bone formation by determining the expression profiles of Transforming Growth Factor Beta (TGF-β/Bone Morphogenic Protein (BMP) and Toll-Like Receptor (TLR) pathways in challenged osteoblasts. Cell viability of P. gingivalis and P. intermedia challenged osteoblasts were determined by WST assay. Changes in osteoblast morphology and inhibition of mineralization were observed by Scanning Electron Microscopy (SEM) and Von Kossa staining, respectively. Expression of TGF-β and TLR pathway genes on challenged cells were identified by RT profiler array. Both P. gingivalis and P. intermedia challenges resulted in reduced viability and mineralization of osteoblasts. Viability was reduced to 56.8% (P. gingivalis) and 52.75% (P. intermedia) at 1000 multiplicity. Amongst 48 genes examined, expressions of BMPER, SMAD1, IL8 and NFRKB were found to be highly upregulated by both bacterial challenges (Fold Change > 4). P. gingivalis and P. intermedia could play a role in implant failure by changing the expression profiles of genes related to bone formation and resorption.

  18. Fenomena Kerak Dalam Desalinasi Dengan Multi Stage Flash Distillation (Msf)


    Alimah, Siti


    SCALING PHENOMENA IN DESALINATION WITH MULTI STAGE FLASH DISTILLATION (MSF). Assessment of scaling phenomena in MSF desalination has been carried out. Scale is one of predominantly problem in multi stage flash (MSF) desalination installation. The main types of scale in MSF are carbonat calcium (CaC03), hydroxide magnesium (Mg(OH)2) dan sulphate calcium (CaS04). CaC03 dan Mg(OH)2 scales result from the thermal decomposition of bicarbonate ion, however sulphate calcium scale result from reactio...

  19. Inception and development of voids in flashing liquids

    International Nuclear Information System (INIS)

    Jones, O.C. Jr.


    Recent work aimed at correctly describing nonequilibrium vapor generation rates in flashing liquids in decompressing flows similar to those which might be encountered in a loss of coolant accident in a nuclear reactor is summarized. Analysis is reviewed which describes the flashing inception superheat in terms of the turbulence intensity for a given expansion rate and initial temperature, and interfacial area density and interfacial heat flux, and the volumetric vapor generation rates. Comparisons with existing data are included and further experiments being undertaken are described, including typical recent results

  20. Effect of Soybeans on Hot Flashes in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    H Mozaffari-khosravi


    Full Text Available Introduction: Hot flashes are common and discomfortable signs of menopause that present with blazing sweatiness, sense of hotness, tachycardia and agitation. Hot flashes cause disturbances in daily activity and quality of night sleep. In spite of the effect of Hormone Replacement Therapy (HRT on hot flashes, nowadays, there are diverse opinions about HRT and the reason is that it has chronic complications. In addition, the acceptance of HRT by Iranian women is very low. Study of numerous texts has shown that isofliavone present in soybean is a phytoestrogen that could be effective in control of hot flashes. The purpose of the study is to examine the changes in time periods of hot flashes in response to consumption of 74 mg Isoflavone/day present in 60 grams soybeans in menopausal women. Methods: This study was a clinical trial with before and after design that included 31 postmenopausal women. The participants were assessed with respect to daily hot flashes at baseline and after one, two and three months of intervention. Participants consumed daily 60 grams soybeans for 3 months. Blood samples were taken at the start and end of intervention for determining levels of gonadotropins and estradiol. Data was analyzed by SPSS software. Results: There was a decrease in time period of hot flashes from baseline of 5.88±2.61 to 3.45±1.82 after one month, 2.73±1.57 after two months and 2.16±1.48 after three months of consumption of soybeans (P<0.001. There was decrease in levels of FSH, LH & estradiol after 3 months, but this decrease was not significant, except in the case of estradiol. Conclusion: In line with various studies proposing the use of soybeans in the form of concentrate, drink or capsule, this study suggests that consumption of soybeans (60 gr daily as snacks may be a safe and effective method for controlling hot flashes in postmenopausal women..

  1. Color-coded intravital imaging demonstrates a transforming growth factor-β (TGF-β) antagonist selectively targets stromal cells in a human pancreatic-cancer orthotopic mouse model. (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Miyake, Kentaro; Hwang, Ho Kyoung; Kiyuna, Tasuku; DeLong, Jonathan C; Lwin, Thinzar M; Matsuyama, Ryusei; Mori, Ryutaro; Kumamoto, Takafumi; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M


    Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor-β (TGF-β) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF-β inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF-β expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). Fourteen mice were randomized into a control group (n = 7, vehicle, i.p., weekly, for 3 weeks) and a treated group (n = 7, SB431542 [TGF-β receptor type I inhibitor] 0.3 mg, i.p., weekly, for 3 weeks). Stromal cells expressing RFP and cancer cells expressing GFP were observed weekly for 3 weeks by real-time color-coded intravital imaging. The RFP fluorescence area from the stromal cells, relative to the GFP fluorescence area of the cancer cells, was significantly decreased in the TGF-β-inhibitor-treatment group compared to the control group. The present study demonstrated color-coded imaging in an orthotopic pancreatic-cancer cell-line mouse model can readily detect the selective anti-stromal-cell targeting of a TGF-β inhibitor.

  2. Flash 3D Planetary Entry, Descent and Landing Sensor Hardening Project (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) has developed a 128 x 128 frame, 3D Flash LADAR video camera which produces 3-D point clouds at 30 Hz. Flash Ladar Video...

  3. Development of a 3D Flash LADAR Video Camera for Entry, Decent and Landing, Phase I (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) has developed a 128 x 128 frame, 3D Flash LADAR video camera capable of a 30 Hz frame rate. Because Flash LADAR captures an...

  4. Development of a 3D Flash LADAR Video Camera for Entry, Decent, and Landing, Phase II (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) has developed a 128 x 128 frame, 3D Flash LADAR video camera which produces 3-D point clouds at 30 Hz. Flash LADAR captures...

  5. Development of PIN Diode Detector Arrays for 3D Flash LIDAR Space Applications, Phase I (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts, Inc. (ASC) has developed a number of 3D Flash LIDAR systems. Flash LIDAR sensors are 3D video systems that return range and intensity...

  6. Flash 3D Planetary Entry, Descent and Landing Sensor Hardening, Phase II (United States)

    National Aeronautics and Space Administration — Advanced Scientific Concepts Inc. (ASC) is a small business that has developed a number of 3D flash LADAR systems. Flash Ladar Video Cameras are 3D video cameras...

  7. Inadvertently programmed bits in Samsung 128 Mbit flash devices: a flaky investigation (United States)

    Swift, G.


    JPL's X2000 avionics design pioneers new territory by specifying a non-volatile memory (NVM) board based on flash memories. The Samsung 128Mb device chosen was found to demonstrate bit errors (mostly program disturbs) and block-erase failures that increase with cycling. Low temperature, certain pseudo- random patterns, and, probably, higher bias increase the observable bit errors. An experiment was conducted to determine the wearout dependence of the bit errors to 100k cycles at cold temperature using flight-lot devices (some pre-irradiated). The results show an exponential growth rate, a wide part-to-part variation, and some annealing behavior.

  8. A dual-mode mobile phone microscope using the onboard camera flash and ambient light. (United States)

    Orth, A; Wilson, E R; Thompson, J G; Gibson, B C


    Mobile phone microscopes are a natural platform for point-of-care imaging, but current solutions require an externally powered illumination source, thereby adding bulk and cost. We present a mobile phone microscope that uses the internal flash or sunlight as the illumination source, thereby reducing complexity whilst maintaining functionality and performance. The microscope is capable of both brightfield and darkfield imaging modes, enabling microscopic visualisation of samples ranging from plant to mammalian cells. We describe the microscope design principles, assembly process, and demonstrate its imaging capabilities through the visualisation of unlabelled cell nuclei to observing the motility of cattle sperm and zooplankton.

  9. Investigation of Supply Current Spikes in Flash Memories Using Ion-Electron Emission Microscopy (United States)

    Gerardin, S.; Bagatin, M.; Paccagnella, A.; Bisello, D.; Giubilato, P.; Mattiazzo, S.; Pantano, D.; Silvestrin, L.; Tessaro, M.; Wyss, J.; Ferlet-Cavrois, V.


    We studied the occurrence of supply current spikes and destructive events in NAND flash memories under heavy-ion exposure. In addition to broad-beam experiments, we used collimated beams and ion-electron emission microscopy to investigate the phenomena on two types of memories with different feature size. Current spikes on the supply current were observed in both devices, also with collimated beams, whereas destructive events occurred only with broad beam. We show that current spikes do not originate from charge-pump capacitors, as previously suggested, and propose that destructive events are due to the effects of temporally close heavy-ion hits on distinct areas of the tested chips.

  10. Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture. (United States)

    Riopel, L; Branchaud, C L; Goodyer, C G; Adkar, V; Lefebvre, Y


    We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

  11. TGF-β1 induces the formation of vascular-like structures in embryoid bodies derived from human embryonic stem cells. (United States)

    Wang, Yan; Qian, DE-Jian; Zhong, Wen-Yu; Lu, Jun-Hong; Guo, Xiang-Kai; Cao, Yi-Lin; Liu, Ju


    Human embryonic stem cells (ESCs) can differentiate into endothelial cells in response to stimuli from extracellular cytokines. Transforming growth factor (TGF)-β1 signaling is involved in stem cell renewal and vascular development. Previously, human ESCs were isolated from inner cell mass and a stable ESC line was developed. In the present study, the effects of extracellular TGF-β1 were investigated on human ESC-derived embryoid bodies (EB) in suspension. The structures of the EBs were analyzed with light and electron microscopy, while the cellular composition of the EBs was examined via the expression levels of specific markers. Vascular-like tubular structures and cardiomyocyte-like beating cells were observed in the EBs at day 3 and 8, respectively. The frequencies of vascular-like structures and beating cells in the TGF-β1 treated group were significantly higher compared with the control group (84.31 vs. 12.77%; Pcell types for the clinical therapy of cardiovascular diseases.

  12. Expression of Wnt-1, TGF-β and related cell–cell adhesion components following radiotherapy in salivary glands of patients with manifested radiogenic xerostomia

    International Nuclear Information System (INIS)

    Hakim, Samer George; Ribbat, Julika; Berndt, Alexander; Richter, Petra; Kosmehl, Hartwig; Benedek, Geza A.; Jacobsen, Hans Christian; Trenkle, Thomas; Sieg, Peter; Rades, Dirk


    Background: Radiation-induced xerostomia still represents a common symptom following radiotherapy of head and neck malignancies, which significantly impairs the patient’s quality of life. In this cross-sectional study, human salivary glands were investigated to assess the role of Wnt/β-catenin and TGF-β pathways in the pathogenic process of radiogenic impairment of salivary function. Methods: Irradiated human salivary glands were investigated in patients with manifested xerostomia. Alteration of Wnt-1 and cell–cell adhesion was evaluated immunohistologically as well as changes in the expression of TGF-β were assessed in salivary gland tissue. Results: We assessed two alteration patterns in which Wnt-1 expression represents one change along with up-regulation of β-catenin and E-cadherin in irradiated but viable acinar cells. Increased expression of tenascin-C was observed in sites of epithelial–mesenchymal interaction and loss of cell–cell adhesion was assessed in translocated epithelial cells in the stroma. Conclusion: Increased transdifferentiation and remodeling of acinar structures was associated with decrease of viable acinar structures. The role of Wnt and TGF signaling may provide a potential therapeutic approach to prevent radiation-induced damage to salivary glands during radiotherapy for head and neck cancer.

  13. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)


    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  14. Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: signaling by BMPs and TGF-betas. (United States)

    Flanders, K C; Kim, E S; Roberts, A B


    The eight mammalian Smad proteins mediate cellular signaling from members of the transforming growth factor-beta (TGF-beta), bone morphogenetic protein (BMP), and activin families. Smads 1, 5, and 8 transmit signals from BMPs, while Smads 2 and 3 transmit signals from TGF-betas and activin. Smad 4 is a common mediator of both pathways, while Smads 6 and 7 inhibit signaling. Signal transduction involves translocation of Smad complexes to the nucleus and subsequent gene activation. Little is known about the expression of endogenous Smad proteins during development. We identified commercially available Smad antibodies that specifically recognize a unique Smad protein and are suitable for immunohistochemistry. Here we compare the localization of Smads 1, 2, 3, 4, 5, and 6 in tissues of the 15-day gestation mouse embryo. Immunoreactive Smad proteins are seen in many tissues with differences in the localization being dependent upon the cell type. All tissues express Smad 4 and at least one each of the BMP-specific and TGF-beta-specific Smads, while expression of Smad 6 is more restricted. Differences are observed in the nuclear versus cytoplasmic localization among the Smads in different cell types or tissues, suggesting selective activation of Smads during this stage of development. Copyright 2001 Wiley-Liss, Inc.

  15. Serum TGF-beta2 and TGF-beta3 are increased and positively correlated to pain, functionality, and radiographic staging in osteoarthritis. (United States)

    Kapetanakis, Stilianos; Drygiannakis, Ioannis; Kazakos, Kostantinos; Papanas, Nikolaos; Kolios, George; Kouroumalis, Elias; Verettas, Dionysios-Alexandros


    The goal of this study was to verify or reject the hypothesis that systematic differences exist in various profibrotic or antifibrotic factors between osteoarthritic patients and controls, as well as between different stages of osteoarthritis. The study group comprised 63 patients with knee osteoarthritis and 18 controls. Transforming growth factor-beta (TGF-beta)1, -2, -3; tissue inhibitor of metalloproteinase (TIMP)-1 protein levels; and gelatinolytic activity of matrix metalloproteinase (MMP)-1, -2, -3, -9 activities were measured by enzyme-linked immunosorbent assay and gelatin zymography, respectively. Visual analog scale scores, Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Lequesne clinical osteoarthritis scales, and Kellgren-Lawrence radiographic grading were recorded for each patient.Transforming growth factor-beta2 and -3 (in contrast to TGF-beta1 and TIMP-1) serum protein levels were significantly higher in osteoarthritic patients compared to controls (210%+/-14% [P<.001] and 232%+/-7% [P<10(-7)], respectively). Additionally, TGF-beta2 and -3 were strongly positively correlated to Kellgren-Lawrence radiographic grading of the disease (P<10(-5) and P<10(-7), respectively). Moreover, TGF-beta2 correlated positively with the WOMAC scale (P=.007). However, TIMP-1 decreased as osteoarthritis progressed clinically, but remained irrelevant to radiographic staging. Furthermore, activities of MMP-2 and -9, but not MMP-1+/-3, were lower in patients with osteoarthritis. Copyright 2010, SLACK Incorporated.

  16. [Effect of Polydatin on Epithelial-Mesenchymal Transition of Human Alveolar Epithelium A549 Cells Induced by TGF-β1]. (United States)

    Yang, Jun-chao; Xu, Lu; Song, Kang; Wang, Yuan; Gao, Run-di; Chen, Rui-lin; Cao, Yu


    To explore the effect of polydatin on the growth of TGF-β₁induced humanalveolar epithelium A549 cells and the mechanism of polydatin for inhibiting the process of epithelial-mesenchymal transition (EMT). A549 cells in vitro cultured were randomly divided into five groups, i.e., the blank group, the control group, the low dose polydatin group, the middle dose polydatin group, the high dose polydatin group. Common culture fluid was added in A549 cells of the blank group. Five ng/mLTGF-β₁contained culture fluid was added in A549 cells of the control group. 50, 100, and 150 μmol/mL of polydatin plus 5 ng/mL TGF-β₁contained culture fluid was added in A549 cells of low, middle, and high dosepolydatin groups, respectively. Morphological changes were observed and recorded at different time points. The optimal concentration of polydatin was determined by MTT method. Protein and mRNA expressions of E-cad epithelial cell marker) and Vimentin (mesenchymal cell marker) were detected by Western blot and Real-time PCR. Under inverted phase contrast microscope, A549 cells turned from previous pebble shape to fusiform shape after intervened by polydatin and TGF-β1. The intercellular space was enlargedand the intercellular connection became loose. These phenomena were more obviously seen in the control group. A549 cells were more satiated in low, middle, and high dose polydatin groups than in the control group. The EMT inhibition was most obviously seen in the middle dose polydatin group at 48 h. Protein and mRNA expressions of E-cad showed an overall descending tendency after intervened by polydatin and TGF-β1 (P A549 cells time- and dose-dependently. It also played roles in inhibiting pulmonary fibrosis.

  17. Design of a controlled release system of OP-1 and TGF-β1 based in microparticles of sodium alginate and release characterization by HPLC-UV. (United States)

    Oliva-Rodríguez, Ricardo; Pérez-Urizar, José; Dibildox-Alvarado, Estela; Martínez-Saldaña, María Consolación; Avelar-González, Francisco Javier; Flores-Reyes, Héctor; Pozos-Guillén, Amaury de Jesús; Guerrero-Barrera, Alma Lilián


    A new system for sustained release of growth factors, such as osteogenic protein 1 (OP-1) and transforming growth factor β1 (TGF-β1), intended to repair and promote dental tissue regeneration in rats was designed and characterized in this work. The release system was made with microparticles of sodium alginate, produced by ionic gelling dripping technique. The release profiles of OP-1 and TGF-β1 from biopolymer matrix were determined by high-performance liquid chromatography (HPLC), and with this purpose, an HPLC-UV method was developed. About 80% of each growth factor was released in the first 24 h, reaching almost 100% in 168 h. The system was tested during the tissue repair in rat molars in comparison with calcium hydroxide and both growth factors not encapsulated. The dentin sialoprotein (DSP) was used as a repair marker. It was detected by immunohistochemistry, after 14- and 28-d post-treatment. X (2) test (p ≤ 0.001) and Fisher exact test (p ≤ 0.05) were applied for assessment of the amount of immunostaining. The treatment with encapsulated OP-1 showed an increased DSP immunostaining after 14 d and did not find any significant difference with the immunostaining observed for calcium hydroxide treatment. Treatment with TGF-β1 did not show significant difference with calcium hydroxide. Treatment with both factors OP-1 and TGF-β1 showed higher DSP immunostaining in comparison with calcium hydroxide treatment. In conclusion, the combination of both growth factors encapsulated showed more DSP immunostaining in comparison with each one separated, either encapsulated or not.

  18. TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function (United States)

    Lu, L.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)


    BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle

  19. Robust Image Denoising using a Virtual Flash Image for Monte Carlo Ray Tracing

    DEFF Research Database (Denmark)

    Moon, Bochang; Jun, Jong Yun; Lee, JongHyeob


    We propose an efficient and robust image-space denoising method for noisy images generated by Monte Carlo ray tracing methods. Our method is based on two new concepts: virtual flash images and homogeneous pixels. Inspired by recent developments in flash photography, virtual flash images emulate...

  20. TGF-β1 serum concentrations and receptor expressions in the lens capsular of dogs with diabetes mellitus


    Stephan Neumann; Jens Linek; Gerhard Loesenbeck; Julia Schüttler; Sonja Gaedke


    Tissue fibrosis as complication of diabetes mellitus is known in humans. Because TGF-?1induces fibrosis and is elevated in humans suffering from diabetes mellitus we measured this growth factor in serum of dogs with diabetes mellitus and compared it with healthy dogs and those with fibrotic diseases. Further we measured the expression of TGF-?1receptor on lens capsule to investigate possible association between diabetes mellitus and cataract associated alterations. TGF-?1 was measured in seru...