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Sample records for prominently potent ability

  1. Solar prominences

    CERN Document Server

    Engvold, Oddbjørn

    2015-01-01

    This volume presents the latest research results on solar prominences, including new developments on e.g. chirality, fine structure, magnetism, diagnostic tools and relevant solar plasma physics. In 1875 solar prominences, as seen out of the solar limb, were described by P.A. Secchi in his book Le Soleil as "gigantic pink or peach-flower coloured flames". The development of spectroscopy, coronagraphy and polarimetry brought tremendous observational advances in the twentieth century. The authors present and discuss exciting new challenges (resulting from observations made by space and ground-based telescopes in the 1990s and the first decade of the 21st century) concerning the diagnostics of prominences, their formation, their life time and their eruption along with their impact in the heliosphere (including the Earth). The book starts with a general introduction of the prominence “object” with some historical background on observations and instrumentation. In the next chapter, the various forms of promine...

  2. Formation and support of prominence

    International Nuclear Information System (INIS)

    Forbes, T.G.

    1986-01-01

    A short introduction is given to the concepts discussed by the group on the formation and support of prominences. Only quiescent and long-lived active region prominences were considered, since transient prominence phenomena, such as sprays, surges, H alpha flare-loops, and coronal rain, are dynamically distinct from long-lived, prominences. Stable prominences (which are often referred to as filaments when seen against the disk) can be subdivided into three categories, namely active region prominences, quiescent prominences and polar crown prominences. The third category is closely related to the second since a quiescent prominence will eventually evolve into a polar crown prominence if it lasts long enough. The distinction between the first and second categories is not sharp either since intermediates exist here as well (Martin, 1973)

  3. Apparent Solar Tornado-Like Prominences

    Science.gov (United States)

    Panasenco, Olga; Martin, Sara F.; Velli, Marco

    2014-02-01

    Recent high-resolution observations from the Solar Dynamics Observatory (SDO) have reawakened interest in the old and fascinating phenomenon of solar tornado-like prominences. This class of prominences was first introduced by Pettit ( Astrophys. J. 76, 9, 1932), who studied them over many years. Observations of tornado prominences similar to the ones seen by SDO had already been documented by Secchi ( Le Soleil, 1877). High-resolution and high-cadence multiwavelength data obtained by SDO reveal that the tornado-like appearance of these prominences is mainly an illusion due to projection effects. We discuss two different cases where prominences on the limb might appear to have a tornado-like behavior. One case of apparent vortical motions in prominence spines and barbs arises from the (mostly) 2D counterstreaming plasma motion along the prominence spine and barbs together with oscillations along individual threads. The other case of apparent rotational motion is observed in a prominence cavity and results from the 3D plasma motion along the writhed magnetic fields inside and along the prominence cavity as seen projected on the limb. Thus, the "tornado" impression results either from counterstreaming and oscillations or from the projection on the plane of the sky of plasma motion along magnetic-field lines, rather than from a true vortical motion around an (apparent) vertical or horizontal axis. We discuss the link between tornado-like prominences, filament barbs, and photospheric vortices at their base.

  4. Re-interpreting Prominences Classified as Tornadoes

    Science.gov (United States)

    Martin, Sara F.; Venkataramanasastry, Aparna

    2015-04-01

    Some papers in the recent literature identify tornado prominences with barbs of quiescent prominences while papers in the much older historic literature include a second category of tornado prominence that does not correspond to a barb of a quiescent prominence. The latter are described as prominence mass rotating around a nearly vertical axis prior to its eruption and the rotation was verified by spectral measurements. From H alpha Doppler-shifted mass motions recorded at Helio Research or the Dutch Open Telescope, we illustrate how the apparent tornado-like motions, identified with barbs, are illusions in our mind’s eye resulting from poorly resolved counterstreaming threads of mass in the barbs of quiescent prominences. In contrast, we confirm the second category of rotational motion in prominences shortly before and during eruption. In addition, we identify this second category as part of the late phase of a phenomenon called the roll effect in erupting prominences. In these cases, the eruption begins with the sideways rolling of the top of a prominence. As the eruption proceeds the rolling motion propagates down one leg or both legs of the prominence depending on whether the eruption is asymmetric or symmetric respectively. As an asymmetric eruption continues, the longer lasting leg becomes nearly vertical and its rotational motion also continues. If only this phase of the eruption was observed, as in some historic cases, it was called a tornado prominence. However, when we now observe entire eruptions in time-lapse sequences, the similarity to terrestrial tornadoes is lost. We conclude that neither prominence barbs, that give the illusion of rotation, nor the cases of true rotational motion, in the legs of erupting prominences, are usefully described as tornado prominences when the complete prominence structure or complete erupting event is observed.

  5. Prominence mass supply and the cavity

    Energy Technology Data Exchange (ETDEWEB)

    Schmit, Donald J.; Innes, D. [Max Planck Institute for Solar System Research, D-37191 Katlenburg-Lindau (Germany); Gibson, S. [High Altitude Observatory, National Center for Atmospheric Research, Boulder, CO 80307 (United States); Luna, M. [Instituto de Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain); Karpen, J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2013-12-20

    A prevalent but untested paradigm is often used to describe the prominence-cavity system: the cavity is under-dense because it is evacuated by supplying mass to the condensed prominence. The thermal non-equilibrium (TNE) model of prominence formation offers a theoretical framework to predict the thermodynamic evolution of the prominence and the surrounding corona. We examine the evidence for a prominence-cavity connection by comparing the TNE model with diagnostics of dynamic extreme ultraviolet (EUV) emission surrounding the prominence, specifically prominence horns. Horns are correlated extensions of prominence plasma and coronal plasma which appear to connect the prominence and cavity. The TNE model predicts that large-scale brightenings will occur in the Solar Dynamics Observatory Atmospheric Imaging Assembly 171 Å bandpass near the prominence that are associated with the cooling phase of condensation formation. In our simulations, variations in the magnitude of footpoint heating lead to variations in the duration, spatial scale, and temporal offset between emission enhancements in the other EUV bandpasses. While these predictions match well a subset of the horn observations, the range of variations in the observed structures is not captured by the model. We discuss the implications of our one-dimensional loop simulations for the three-dimensional time-averaged equilibrium in the prominence and the cavity. Evidence suggests that horns are likely caused by condensing prominence plasma, but the larger question of whether this process produces a density-depleted cavity requires a more tightly constrained model of heating and better knowledge of the associated magnetic structure.

  6. Prominence Mass Supply and the Cavity

    Science.gov (United States)

    Schmit, Donald J.; Gibson, S.; Luna, M.; Karpen, J.; Innes, D.

    2013-01-01

    A prevalent but untested paradigm is often used to describe the prominence-cavity system; the cavity is under-dense because it it evacuated by supplying mass to the condensed prominence. The thermal non-equilibrium (TNE) model of prominence formation offers a theoretical framework to predict the thermodynamic evolutin of the prominence and the surrounding corona. We examine the evidence for a prominence-cavity connection by comparing the TNE model and diagnostics of dynamic extreme ultraviolet (EUV) emission surrounding the prominence, specifically prominence horns. Horns are correlated extensions of prminence plasma and coronal plasma which appear to connect the prominence and cavity. The TNE model predicts that large-scale brightenings will occur in the Solar Dynamics Observatory Atmospheric Imaging Assembly 171 A badpass near he prominence that are associated with the cooling phase of condensation formation. In our simulations, variations in the magnitude of footpoint heating lead to variations in the duration, spatial scale, and temporal offset between emission enhancements in the other EUV bandpasses. While these predictions match well a subset of the horn observations, the range of variations in the observed structures is not captured by the model. We discuss the implications of one-dimensional loop simulations for the three-dimensional time-averaged equilibrium in the prominence and the cavity. Evidence suggests that horns are likely caused by condensing prominence plasma, but the larger question of whether this process produces a density-depleted cavity requires a more tightly constrained model of heating and better knowledge of the associated magnetic structure.

  7. A three-dimensional model for solar prominences

    International Nuclear Information System (INIS)

    Demoulin, P.; Priest, E.R.; Anzer, U.

    1989-01-01

    Prominences have been modelled largely as one-or two-dimensional structures, and yet observations show them to possess important variations in the third dimension along the prominence axis with great arches with feet reaching down towards the solar surface. As an initial attempt to understand this structure we consider a three-dimensional linear force-free field model for the global magnetic field around a quiescent prominence. It consists of a fundamental together with a harmonic that is periodic along the prominence. At the solar surface there is a series of flux concentrations spaced out periodically on both sides of the prominence. Between a pair of oppositely directed flux concentration, the magnetic field in the prominence is stronger and tends to be less highly sheared than elsewhere. This modulation of the field strength and shear angle along the prominence decreases with height and almost disappears above 10 Mm. Prominence fields that increase with height occur when the shear is large and the length-scale for field variations perpendicular to the prominence exceeds that along it. The variation of the prominence height along the prominence is calculated and it is suggested that feet occur where the prominence sags down to low heights. For prominences of Normal polarity this tends to occur near supergranule centres where the transverse field is least, whereas for those of Inverse polarity it usually takes place near the chromospheric network where the transverse field is greatest. The effect of concentrating the base flux by including extra harmonics is also included. For Normal polarity prominences it tends to make the foot wider, and for Inverse polarity configurations, it usually creates deeper and narrower feet

  8. QUIESCENT PROMINENCES IN THE ERA OF ALMA: SIMULATED OBSERVATIONS USING THE 3D WHOLE-PROMINENCE FINE STRUCTURE MODEL

    Energy Technology Data Exchange (ETDEWEB)

    Gunár, Stanislav; Heinzel, Petr [Astronomical Institute, The Czech Academy of Sciences, 25165 Ondřejov (Czech Republic); Mackay, Duncan H. [School of Mathematics and Statistics, University of St Andrews, North Haugh, St Andrews KY16 9SS (United Kingdom); Anzer, Ulrich [Max-Planck-Institut für Astrophysik, Karl-Schwarzschild-Str. 1, D-85740 Garching bei München (Germany)

    2016-12-20

    We use the detailed 3D whole-prominence fine structure model to produce the first simulated high-resolution ALMA observations of a modeled quiescent solar prominence. The maps of synthetic brightness temperature and optical thickness shown in the present paper are produced using a visualization method for synthesis of the submillimeter/millimeter radio continua. We have obtained the simulated observations of both the prominence at the limb and the filament on the disk at wavelengths covering a broad range that encompasses the full potential of ALMA. We demonstrate here extent to which the small-scale and large-scale prominence and filament structures will be visible in the ALMA observations spanning both the optically thin and thick regimes. We analyze the relationship between the brightness and kinetic temperature of the prominence plasma. We also illustrate the opportunities ALMA will provide for studying the thermal structure of the prominence plasma from the cores of the cool prominence fine structure to the prominence–corona transition region. In addition, we show that detailed 3D modeling of entire prominences with their numerous fine structures will be important for the correct interpretation of future ALMA observations of prominences.

  9. Solar Features - Prominences and Filaments

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Prominences and filaments are two manifestations of the same phenomenon. Both prominences and filaments are features formed above the chromosphere by cool dense...

  10. New perspectives on solar prominences

    Science.gov (United States)

    Schmieder, B.; Aulanier, G.

    2012-06-01

    Recent observations of prominences obtained with high spatial and temporal resolution instruments, on board satellites (Hinode, SDO) as well as on the ground (SST) have provided very intriguing movies and open a new area for understanding the nature of prominences. The main topics are still debate: formation, dynamics, and characteristics of the plasma in the core and in the transition zone between the prominence and corona. We will review briefly the recent advances made in these topics, observationally as well as theoretically.

  11. TANGLED MAGNETIC FIELDS IN SOLAR PROMINENCES

    International Nuclear Information System (INIS)

    Van Ballegooijen, A. A.; Cranmer, S. R.

    2010-01-01

    Solar prominences are an important tool for studying the structure and evolution of the coronal magnetic field. Here we consider so-called hedgerow prominences, which consist of thin vertical threads. We explore the possibility that such prominences are supported by tangled magnetic fields. A variety of different approaches are used. First, the dynamics of plasma within a tangled field is considered. We find that the contorted shape of the flux tubes significantly reduces the flow velocity compared to the supersonic free fall that would occur in a straight vertical tube. Second, linear force-free models of tangled fields are developed, and the elastic response of such fields to gravitational forces is considered. We demonstrate that the prominence plasma can be supported by the magnetic pressure of a tangled field that pervades not only the observed dense threads but also their local surroundings. Tangled fields with field strengths of about 10 G are able to support prominence threads with observed hydrogen density of the order of 10 11 cm -3 . Finally, we suggest that the observed vertical threads are the result of Rayleigh-Taylor instability. Simulations of the density distribution within a prominence thread indicate that the peak density is much larger than the average density. We conclude that tangled fields provide a viable mechanism for magnetic support of hedgerow prominences.

  12. Magnetohydrodynamic (MHD) simulation of solar prominence formation

    International Nuclear Information System (INIS)

    Bao, J.

    1987-01-01

    Formation of Kippenhahn-Schluter type solar prominences by chromospheric mass injection is studied via numerical simulation. The numerical model is based on a two-dimensional, time-dependent magnetohydrodynamic (MHD) theory. In addition, an analysis of gravitational thermal MHD instabilities related to condensation is performed by using the small-perturbation method. The conclusions are: (1) Both quiescent and active-region prominences can be formed by chromospheric mass injection, provided certain optimum conditions are satisfied. (2) Quiescent prominences cannot be formed without condensation, though enough mass is supplied from chromosphere. The mass of a quiescent prominence is composed of both the mass injected from the chromosphere and the mass condensed from the corona. On the other hand, condensation is not important to active region prominence formation. (3) In addition to channeling and supporting effects, the magnetic field plays another important role, i.e. containing the prominence material. (4) In the model cases, prominences are supported by the Lorentz force, the gas-pressure gradient and the mass-injection momentum. (5) Due to gravity, more MHD condensation instability modes appear in addition to the basic condensation mode

  13. Nonlinear MHD Waves in a Prominence Foot

    Science.gov (United States)

    Ofman, L.; Knizhnik, K.; Kucera, T.; Schmieder, B.

    2015-11-01

    We study nonlinear waves in a prominence foot using a 2.5D MHD model motivated by recent high-resolution observations with Hinode/Solar Optical Telescope in Ca ii emission of a prominence on 2012 October 10 showing highly dynamic small-scale motions in the prominence material. Observations of Hα intensities and of Doppler shifts show similar propagating fluctuations. However, the optically thick nature of the emission lines inhibits a unique quantitative interpretation in terms of density. Nevertheless, we find evidence of nonlinear wave activity in the prominence foot by examining the relative magnitude of the fluctuation intensity (δI/I ˜ δn/n). The waves are evident as significant density fluctuations that vary with height and apparently travel upward from the chromosphere into the prominence material with quasi-periodic fluctuations with a typical period in the range of 5-11 minutes and wavelengths <2000 km. Recent Doppler shift observations show the transverse displacement of the propagating waves. The magnetic field was measured with the THEMIS instrument and was found to be 5-14 G. For the typical prominence density the corresponding fast magnetosonic speed is ˜20 km s-1, in qualitative agreement with the propagation speed of the detected waves. The 2.5D MHD numerical model is constrained with the typical parameters of the prominence waves seen in observations. Our numerical results reproduce the nonlinear fast magnetosonic waves and provide strong support for the presence of these waves in the prominence foot. We also explore gravitational MHD oscillations of the heavy prominence foot material supported by dipped magnetic field structure.

  14. NONLINEAR MHD WAVES IN A PROMINENCE FOOT

    Energy Technology Data Exchange (ETDEWEB)

    Ofman, L. [Catholic University of America, Washington, DC 20064 (United States); Knizhnik, K.; Kucera, T. [NASA Goddard Space Flight Center, Code 671, Greenbelt, MD 20771 (United States); Schmieder, B. [LESIA, Observatoire de Paris, PSL Research University, CNRS, Sorbonne Universités, UPMC Univ. Paris 06, Univ. Paris-Diderot, Sorbonne Paris Cit, 5 place Jules Janssen, F-92195 Meudon (France)

    2015-11-10

    We study nonlinear waves in a prominence foot using a 2.5D MHD model motivated by recent high-resolution observations with Hinode/Solar Optical Telescope in Ca ii emission of a prominence on 2012 October 10 showing highly dynamic small-scale motions in the prominence material. Observations of Hα intensities and of Doppler shifts show similar propagating fluctuations. However, the optically thick nature of the emission lines inhibits a unique quantitative interpretation in terms of density. Nevertheless, we find evidence of nonlinear wave activity in the prominence foot by examining the relative magnitude of the fluctuation intensity (δI/I ∼ δn/n). The waves are evident as significant density fluctuations that vary with height and apparently travel upward from the chromosphere into the prominence material with quasi-periodic fluctuations with a typical period in the range of 5–11 minutes and wavelengths <2000 km. Recent Doppler shift observations show the transverse displacement of the propagating waves. The magnetic field was measured with the THEMIS instrument and was found to be 5–14 G. For the typical prominence density the corresponding fast magnetosonic speed is ∼20 km s{sup −1}, in qualitative agreement with the propagation speed of the detected waves. The 2.5D MHD numerical model is constrained with the typical parameters of the prominence waves seen in observations. Our numerical results reproduce the nonlinear fast magnetosonic waves and provide strong support for the presence of these waves in the prominence foot. We also explore gravitational MHD oscillations of the heavy prominence foot material supported by dipped magnetic field structure.

  15. Two Categories of Apparent Tornado-like Prominences

    Science.gov (United States)

    Martin, Sara F.; Venkataramanasastry, Aparna

    2014-06-01

    Two categories of solar prominences have been described in the literature as having a pattern of mass motions and/or a shape similar to terrestrial tornados. We first identify the two categories associated with prominences in the historic literature and then show that counterparts do exist for both in recent literature but one has not been called a tornado prominence. One category described as being similar to tornados is associated with the barbs of quiescent filaments but barbs appear to have rotational motion only under special conditions. H alpha Doppler observations from Helio Research confirm that this category is an illusion in our mind’s eye resulting from counterstreaming in the large barbs of quiescent filaments. The second category is a special case of rotational motion occurring during the early stages of some erupting prominences, in recent years called the roll effect in erupting prominences. In these cases, the eruption begins with the sideways rolling of the top of a prominence. As the eruption proceeds the rolling motion propagates down one leg or both legs of an erupting prominence depending on whether the eruption is asymmetric or symmetric respectively. As an asymmetric eruption proceeds, the longer lasting leg becomes nearly vertical and has true rotational motion. If only this phase of the eruption was observed, as in the historic cases, it was called a tornado prominence and spectra recorded in these cases provide proof of the rotational motion. When one observes an entire eruption which exhibits the rolling motion, as accomplished at Helio Research, the similarity to a tornado is lost because the event as a whole has quite a different nature and the analogy to a terrestrial tornado not longer appears suitable or helpful in understanding the observed and deduced physical processes. Our conclusion is that there are no solar prominences with motions that are usefully described as tornado or tornado-like events aside from the fun of observing

  16. Signs of helicity in solar prominences and related features

    Science.gov (United States)

    Martin, S.

    This review illustrates several ways to identify the chirality (handedness) of solar prominences (filaments) from their structure and the structure of their surrounding magnetic fields in the chromosphere and corona. For prominences, these structural elements include the axial magnetic field direction, orientation of barbs, and direction of the prominence fine structure. The surrounding structures include the pattern of fibrils beneath the prominences and the pattern of coronal loops above the prominences. These ways of identifying chirality are then interpreted in terms of the formal definitions of helicity to yield a consistent set of one-to-one helicity relationships for all features. The helicity of some prominences can also be independently determined during their eruption by their fine structure, apparent crossings in the line-of-sight of different parts of the same prominence, and by large- scale twist of the prominence structure. Unlike observations of prominences (filaments) observed prior to eruption, in some cases evidence of both signs of helicity are found within the same erupting prominence. This indicates the continued application of forces on the prominences during the eruption process or the possible introduction of force(s) not present during earlier stages of their evolution.

  17. Automated image based prominent nucleoli detection.

    Science.gov (United States)

    Yap, Choon K; Kalaw, Emarene M; Singh, Malay; Chong, Kian T; Giron, Danilo M; Huang, Chao-Hui; Cheng, Li; Law, Yan N; Lee, Hwee Kuan

    2015-01-01

    Nucleolar changes in cancer cells are one of the cytologic features important to the tumor pathologist in cancer assessments of tissue biopsies. However, inter-observer variability and the manual approach to this work hamper the accuracy of the assessment by pathologists. In this paper, we propose a computational method for prominent nucleoli pattern detection. Thirty-five hematoxylin and eosin stained images were acquired from prostate cancer, breast cancer, renal clear cell cancer and renal papillary cell cancer tissues. Prostate cancer images were used for the development of a computer-based automated prominent nucleoli pattern detector built on a cascade farm. An ensemble of approximately 1000 cascades was constructed by permuting different combinations of classifiers such as support vector machines, eXclusive component analysis, boosting, and logistic regression. The output of cascades was then combined using the RankBoost algorithm. The output of our prominent nucleoli pattern detector is a ranked set of detected image patches of patterns of prominent nucleoli. The mean number of detected prominent nucleoli patterns in the top 100 ranked detected objects was 58 in the prostate cancer dataset, 68 in the breast cancer dataset, 86 in the renal clear cell cancer dataset, and 76 in the renal papillary cell cancer dataset. The proposed cascade farm performs twice as good as the use of a single cascade proposed in the seminal paper by Viola and Jones. For comparison, a naive algorithm that randomly chooses a pixel as a nucleoli pattern would detect five correct patterns in the first 100 ranked objects. Detection of sparse nucleoli patterns in a large background of highly variable tissue patterns is a difficult challenge our method has overcome. This study developed an accurate prominent nucleoli pattern detector with the potential to be used in the clinical settings.

  18. Automated image based prominent nucleoli detection

    Directory of Open Access Journals (Sweden)

    Choon K Yap

    2015-01-01

    Full Text Available Introduction: Nucleolar changes in cancer cells are one of the cytologic features important to the tumor pathologist in cancer assessments of tissue biopsies. However, inter-observer variability and the manual approach to this work hamper the accuracy of the assessment by pathologists. In this paper, we propose a computational method for prominent nucleoli pattern detection. Materials and Methods: Thirty-five hematoxylin and eosin stained images were acquired from prostate cancer, breast cancer, renal clear cell cancer and renal papillary cell cancer tissues. Prostate cancer images were used for the development of a computer-based automated prominent nucleoli pattern detector built on a cascade farm. An ensemble of approximately 1000 cascades was constructed by permuting different combinations of classifiers such as support vector machines, eXclusive component analysis, boosting, and logistic regression. The output of cascades was then combined using the RankBoost algorithm. The output of our prominent nucleoli pattern detector is a ranked set of detected image patches of patterns of prominent nucleoli. Results: The mean number of detected prominent nucleoli patterns in the top 100 ranked detected objects was 58 in the prostate cancer dataset, 68 in the breast cancer dataset, 86 in the renal clear cell cancer dataset, and 76 in the renal papillary cell cancer dataset. The proposed cascade farm performs twice as good as the use of a single cascade proposed in the seminal paper by Viola and Jones. For comparison, a naive algorithm that randomly chooses a pixel as a nucleoli pattern would detect five correct patterns in the first 100 ranked objects. Conclusions: Detection of sparse nucleoli patterns in a large background of highly variable tissue patterns is a difficult challenge our method has overcome. This study developed an accurate prominent nucleoli pattern detector with the potential to be used in the clinical settings.

  19. Topic prominence in Chinese EFL learners’ interlanguage

    Directory of Open Access Journals (Sweden)

    Shaopeng Li

    2014-01-01

    Full Text Available The present study aims to investigate the general characteristics of topicprominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from a discourse perspective. Topic structures mainly appear in Chinese discourse in the form of topic chains (Wang, 2002; 2004. The research target are the topic chain, which is the main topic-prominent structure in Chinese discourse, and zero anaphora, which is the most common topic anaphora in the topic chain. Two important findings emerged from the present study. First, the characteristics of Chinese topic chains are transferrable to the interlanguage of Chinese EFL learners, thus resulting in overgeneralization of the zero anaphora. Second, the interlanguage discourse of Chinese EFL learners reflects a change of the second language acquisition process from topic-prominence to subject-prominence, thus lending support to the discourse transfer hypothesis.

  20. EUV observations of quiescent prominences from Skylab

    International Nuclear Information System (INIS)

    Moe, O.K.

    1979-01-01

    The authors report measurements of line intensities and line widths for three quiescent prominences observed with the Naval Research Laboratory slit spectrograph on ATM/Skylab. The wavelengths of the observed lines cover the range 1175 A to 1960 A. The measured intensities have been calibrated to within approximately a factor 2 and are average intensities over a 2 arc sec by 60 arc set slit. Nonthermal velocities are derived from the measured line widths. The nonthermal velocity is found to increase with temperature in the prominence transition zone. Electron densities and pressures are derived from density sensitive line ratios. Electron pressures for two of the prominences are found to lie in the range 0.04-0.08 dyn cm -2 , while values for the third and most intense and active of the three prominences are in the range 0.07-0.22 dyn cm -2 . (Auth.)

  1. Multispacecraft observations of a prominence eruption

    Directory of Open Access Journals (Sweden)

    A. Bemporad

    2009-10-01

    Full Text Available On 9 May 2007 a prominence eruption occurred at the West limb. Remarkably, the event was observed by the STEREO/EUVI telescopes and by the HINODE/EIS and SOHO/UVCS spectrometers. We present results from all these instruments. High-cadence (~37 s data from STEREO/EUVI A and B in the He II λ304 line were used to study the 3-D shape and expansion of the prominence. The high spatial resolution EUVI images (~1.5"/pixel have been used to infer via triangulation the 3-D shape and orientation of the prominence 12 min after the eruption onset. At this time the prominence has mainly the shape of a "hook" highly inclined southward, has an average thickness of 0.068 R⊙, a length of 0.43 R⊙ and lies, in first approximation, on a plane. Hence, the prominence is mainly a 2-D structure and there is no evidence for a twisted flux rope configuration. HINODE/EIS was scanning with the 2" slit the region where the filament erupted. The EIS spectra show during the eruption remarkable non-thermal broadening (up to ~100 km s−1 in the region crossed by the filament in spectral lines emitted at different temperatures, possibly with differences among lines from higher Fe ionization stages. The CME was also observed by the SOHO/UVCS instrument: the spectrograph slit was centered at 1.7 R⊙, at a latitude of 5° SW and recorded a sudden increase in the O VI λλ1032–1037 and Si XII λ520 spectral line intensities, representative of the CME front transit.

  2. Static current-sheet models of quiescent prominences

    Science.gov (United States)

    Wu, F.; Low, B. C.

    1986-12-01

    A particular class of theoretical models idealize the prominence to be a discrete flat electric-current sheet suspended vertically in a potential magnetic field. The weight of the prominence is supported by the Lorentz force in the current sheet. These models can be extended to have curved electric-current sheets and to vary three-dimensionally. The equation for force balance is 1 over 4 pi (del times B) times Bdel p- p9 z=zero. Using Cartesian coordinates we take, for simplicity, a uniform gravity with constant acceleration g in the direction -z. If we are interested not in the detailed internal structure of the prominence, but in the global magnetic configuration around the prominence, we may take prominence plasma to be cold. Consideration is given to how such equilibrium states can be constructed. To simplify the mathematical problem, suppose there is no electric current in the atmosphere except for the discrete currents in the cold prominence sheet. Let us take the plane z =0 to be the base of the atmosphere and restrict our attention to the domain z greater than 0. The task we have is to solve for a magnetic field which is everywhere potential except on some free surface S, subject to suit able to boundary conditions. The surface S is determined by requiring that it possesses a discrete electric current density such that the Lorentz force on it is everywhere vertically upward to balance the weight of the material m(S). Since the magnetic field is potential in the external atmosphere, the latter is decoupled from the magnetic field and its plane parallel hydrostatic pressure and density can be prescribed.

  3. Neutral Atom Diffusion in a Partially Ionized Prominence Plasma

    Science.gov (United States)

    Gilbert, Holly

    2010-01-01

    The support of solar prominences is normally described in terms of a magnetic force on the prominence plasma that balances the solar gravitational force. Because the prominence plasma is only partially ionized. it is necessary to consider in addition the support of the neutral component of the prominence plasma. This support is accomplished through a frictional interaction between the neutral and ionized components of the plasma, and its efficacy depends strongly on the degree of ionization of the plasma. More specifically, the frictional force is proportional to the relative flow of neutral and ion species, and for a sufficiently weakly ionized plasma, this flow must be relatively large to produce a frictional force that balances gravity. A large relative flow, of course, implies significant draining of neutral particles from the prominence. We evaluate the importance of this draining effect for a hydrogen-helium plasma, and consider the observational evidence for cross-field diffusion of neutral prominence material,

  4. TORNADO-LIKE EVOLUTION OF A KINK-UNSTABLE SOLAR PROMINENCE

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wensi; Liu, Rui; Wang, Yuming, E-mail: rliu@ustc.edu.cn [CAS Key Laboratory of Geospace Environment, Department of Geophysics and Planetary Sciences, University of Science and Technology of China, Hefei 230026 (China)

    2017-01-01

    We report on the tornado-like evolution of a quiescent prominence on 2014 November 1. The eastern section of the prominence first rose slowly, transforming into an arch-shaped structure as high as ∼150 Mm above the limb; the arch then writhed moderately in a left-handed sense, while the original dark prominence material emitted in the Fe ix 171 Å passband, and a braided structure appeared at the eastern edge of the warped arch. The unraveling of the braided structure was associated with a transient brightening in the EUV and apparently contributed to the formation of a curtain-like structure (CLS). The CLS consisted of myriad thread-like loops rotating counterclockwise about the vertical if viewed from above. Heated prominence material was observed to slide along these loops and land outside the filament channel. The tornado eventually disintegrated and the remaining material flew along a left-handed helical path constituting approximately a full turn, as corroborated through stereoscopic reconstruction, into the cavity of the stable, western section of the prominence. We suggest that the tornado-like evolution of the prominence was governed by the helical kink instability, and that the CLS formed through magnetic reconnections between the prominence field and the overlying coronal field.

  5. Solar Tornado Prominences: Plasma Motions Along Filament Barbs

    Science.gov (United States)

    Panasenco, Olga; Velli, Marco; Martin, Sara F.; Rappazzo, Franco

    2013-03-01

    Recent high-resolution observations from the Solar Dynamic Observatory (SDO) have reawakened interest in the old and fascinating phenomenon of solar tornado prominences. This class of prominences was first introduced by E. Pettit in 1932, who studied them over many years up to 1950. High resolution and high cadence multi-wavelength data obtained by SDO reveal that the tornado-like properties of these prominences are mainly an illusion due to projection effects. We show that counterstreaming plasma motions with projected velocities up to +/- 45 km/sec along the prominence spine and barbs create a tornado-like impression when viewed at the limb. We demonstrate that barbs are often rooted at the intersection between 4-5 supergranular cells. We discuss the observed oscillations along the vertical parts of barbs and whether they may be related to vortex flows coming from the convection downdrafts at the intersection of supergranules (and possibly smaller convective cells) in the photosphere and their entrained magnetic field. The unwinding of magnetic threads near the photosphere via reconnection might be a source of the waves which are observed as oscillations in prominence barbs.

  6. MAGNETIC FIELD IN ATYPICAL PROMINENCE STRUCTURES: BUBBLE, TORNADO, AND ERUPTION

    Energy Technology Data Exchange (ETDEWEB)

    Levens, P. J.; Labrosse, N. [SUPA School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Schmieder, B. [LESIA, Observatoire de Paris, PSL Research University, CNRS, Sorbonne Universités, UPMC Univ. Paris 06, Univ. Paris Diderot, Sorbonne Paris Cité, 5 place Jules Janssen, F-92195 Meudon (France); López Ariste, A. [IRAP—CNRS UMR 5277, 14, Av. E. Belin, F-31400 Toulouse (France); Dalmasse, K. [CISL/HAO, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307-3000 (United States); Gelly, B., E-mail: p.levens.1@research.gla.ac.uk, E-mail: brigitte.schmieder@obspm.fr [CNRS UMR 3718 THEMIS, La Laguna, Tenerife (Spain)

    2016-08-01

    Spectropolarimetric observations of prominences have been obtained with the THEMIS telescope during four years of coordinated campaigns. Our aim is now to understand the conditions of the cool plasma and magnetism in “atypical” prominences, namely when the measured inclination of the magnetic field departs, to some extent, from the predominantly horizontal field found in “typical” prominences. What is the role of the magnetic field in these prominence types? Are plasma dynamics more important in these cases than the magnetic support? We focus our study on three types of “atypical” prominences (tornadoes, bubbles, and jet-like prominence eruptions) that have all been observed by THEMIS in the He i D{sub 3} line, from which the Stokes parameters can be derived. The magnetic field strength, inclination, and azimuth in each pixel are obtained by using the inversion method of principal component analysis on a model of single scattering in the presence of the Hanle effect. The magnetic field in tornadoes is found to be more or less horizontal, whereas for the eruptive prominence it is mostly vertical. We estimate a tendency toward higher values of magnetic field strength inside the bubbles than outside in the surrounding prominence. In all of the models in our database, only one magnetic field orientation is considered for each pixel. While sufficient for most of the main prominence body, this assumption appears to be oversimplified in atypical prominence structures. We should consider these observations as the result of superposition of multiple magnetic fields, possibly even with a turbulent field component.

  7. The Computational Processing of Intonational Prominence: A Functional Prosody Perspective

    OpenAIRE

    Nakatani, Christine Hisayo

    1997-01-01

    Intonational prominence, or accent, is a fundamental prosodic feature that is said to contribute to discourse meaning. This thesis outlines a new, computational theory of the discourse interpretation of prominence, from a FUNCTIONAL PROSODY perspective. Functional prosody makes the following two important assumptions: first, there is an aspect of prominence interpretation that centrally concerns discourse processes, namely the discourse focusing nature of prominence; and second, the role of p...

  8. Magnetic Field-Vector Measurements in Quiescent Prominences via the Hanle Effect: Analysis of Prominences Observed at Pic-Du-Midi and at Sacramento Peak

    Science.gov (United States)

    Bommier, V.; Leroy, J. L.; Sahal-Brechot, S.

    1985-01-01

    The Hanle effect method for magnetic field vector diagnostics has now provided results on the magnetic field strength and direction in quiescent prominences, from linear polarization measurements in the He I E sub 3 line, performed at the Pic-du-Midi and at Sacramento Peak. However, there is an inescapable ambiguity in the field vector determination: each polarization measurement provides two field vector solutions symmetrical with respect to the line-of-sight. A statistical analysis capable of solving this ambiguity was applied to the large sample of prominences observed at the Pic-du-Midi (Leroy, et al., 1984); the same method of analysis applied to the prominences observed at Sacramento Peak (Athay, et al., 1983) provides results in agreement on the most probable magnetic structure of prominences; these results are detailed. The statistical results were confirmed on favorable individual cases: for 15 prominences observed at Pic-du-Midi, the two-field vectors are pointing on the same side of the prominence, and the alpha angles are large enough with respect to the measurements and interpretation inaccuracies, so that the field polarity is derived without any ambiguity.

  9. PROMINENCE ACTIVATION BY CORONAL FAST MODE SHOCK

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Takuya [Department of Astronomy, Kyoto University, Sakyo, Kyoto, 606-8502 (Japan); Asai, Ayumi [Unit of Synergetic Studies for Space, Kyoto University, Yamashina, Kyoto 607-8471 (Japan); Shibata, Kazunari, E-mail: takahashi@kwasan.kyoto-u.ac.jp [Kwasan and Hida Observatories, Kyoto University, Yamashina, Kyoto 607-8471 (Japan)

    2015-03-01

    An X5.4 class flare occurred in active region NOAA11429 on 2012 March 7. The flare was associated with a very fast coronal mass ejection (CME) with a velocity of over 2500 km s{sup −1}. In the images taken with the Solar Terrestrial Relations Observatory-B/COR1, a dome-like disturbance was seen to detach from an expanding CME bubble and propagated further. A Type-II radio burst was also observed at the same time. On the other hand, in extreme ultraviolet images obtained by the Solar Dynamic Observatory/Atmospheric Imaging Assembly (AIA), the expanding dome-like structure and its footprint propagating to the north were observed. The footprint propagated with an average speed of about 670 km s{sup −1} and hit a prominence located at the north pole and activated it. During the activation, the prominence was strongly brightened. On the basis of some observational evidence, we concluded that the footprint in AIA images and the ones in COR1 images are the same, that is, the MHD fast mode shock front. With the help of a linear theory, the fast mode Mach number of the coronal shock is estimated to be between 1.11 and 1.29 using the initial velocity of the activated prominence. Also, the plasma compression ratio of the shock is enhanced to be between 1.18 and 2.11 in the prominence material, which we consider to be the reason for the strong brightening of the activated prominence. The applicability of linear theory to the shock problem is tested with a nonlinear MHD simulation.

  10. Magnetohydrodynamic interpretation of the motion of prominences

    International Nuclear Information System (INIS)

    Sakurai, Takashi

    1976-01-01

    We study three types of prominence eruptions, which we will call the arch type, the loop type, and the gigantic arch type, respectively, from their shapes. If we regard the prominence as a magnetic flux tube, the onset of its ascending motion can be interpreted as the motion due to the screw-mode instability, which is the most unstable mode of instabilities of a magnetofluid column (pinch). The growth rate of this mode is evaluated and is shown to be consistent with the time scale of the initial stage of the eruption. In order to study the nonlinear stage of the instability, we propose a method of numerical calculation based on a variational technique known as Ritz's method. The result shows that the characteristic motion of the arch-, loop-, and gigantic arch-type eruptions may be reproduced by perturbing a model sequence with decreasing pitch angles of the unperturbed helical magnetic field lines. This conclusion seems to be supported by the pitch angles of observed threads in each type of prominence and also by the fact that the observed time profiles of the rising velocity of the prominences of each type agree well with those predicted from model calculations. (auth.)

  11. Development of potent inhibitors of the coxsackievirus 3C protease

    International Nuclear Information System (INIS)

    Lee, Eui Seung; Lee, Won Gil; Yun, Soo-Hyeon; Rho, Seong Hwan; Im, Isak; Yang, Sung Tae; Sellamuthu, Saravanan; Lee, Yong Jae; Kwon, Sun Jae; Park, Ohkmae K.; Jeon, Eun-Seok; Park, Woo Jin; Kim, Yong-Chul

    2007-01-01

    Coxsackievirus B3 (CVB3) 3C protease (3CP) plays essential roles in the viral replication cycle, and therefore, provides an attractive therapeutic target for treatment of human diseases caused by CVB3 infection. CVB3 3CP and human rhinovirus (HRV) 3CP have a high degree of amino acid sequence similarity. Comparative modeling of these two 3CPs revealed one prominent distinction; an Asn residue delineating the S2' pocket in HRV 3CP is replaced by a Tyr residue in CVB3 3CP. AG7088, a potent inhibitor of HRV 3CP, was modified by substitution of the ethyl group at the P2' position with various hydrophobic aromatic rings that are predicted to interact preferentially with the Tyr residue in the S2' pocket of CVB3 3CP. The resulting derivatives showed dramatically increased inhibitory activities against CVB3 3CP. In addition, one of the derivatives effectively inhibited the CVB3 proliferation in vitro

  12. Engineered Promoters for Potent Transient Overexpression.

    Directory of Open Access Journals (Sweden)

    Dan Y Even

    Full Text Available The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3, which combines four core promoter elements (the TATA box, Inr, MTE and DPE into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long-term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods.

  13. Solar Magnetized Tornadoes: Rotational Motion in a Tornado-like Prominence

    Science.gov (United States)

    Su, Yang; Gömöry, Peter; Veronig, Astrid; Temmer, Manuela; Wang, Tongjiang; Vanninathan, Kamalam; Gan, Weiqun; Li, YouPing

    2014-04-01

    Su et al. proposed a new explanation for filament formation and eruption, where filament barbs are rotating magnetic structures driven by underlying vortices on the surface. Such structures have been noticed as tornado-like prominences when they appear above the limb. They may play a key role as the source of plasma and twist in filaments. However, no observations have successfully distinguished rotational motion of the magnetic structures in tornado-like prominences from other motions such as oscillation and counter-streaming plasma flows. Here we report evidence of rotational motions in a tornado-like prominence. The spectroscopic observations in two coronal lines were obtained from a specifically designed Hinode/EIS observing program. The data revealed the existence of both cold and million-degree-hot plasma in the prominence leg, supporting the so-called prominence-corona transition region. The opposite velocities at the two sides of the prominence and their persistent time evolution, together with the periodic motions evident in SDO/AIA dark structures, indicate a rotational motion of both cold and hot plasma with a speed of ~5 km s-1.

  14. Morphology and Dynamics of Solar Prominences from 3D MHD Simulations

    Science.gov (United States)

    Terradas, J.; Soler, R.; Luna, M.; Oliver, R.; Ballester, J. L.

    2015-01-01

    In this paper we present a numerical study of the time evolution of solar prominences embedded in sheared magnetic arcades. The prominence is represented by a density enhancement in a background-stratified atmosphere and is connected to the photosphere through the magnetic field. By solving the ideal magnetohydrodynamic equations in three dimensions, we study the dynamics for a range of parameters representative of real prominences. Depending on the parameters considered, we find prominences that are suspended above the photosphere, i.e., detached prominences, but also configurations resembling curtain or hedgerow prominences whose material continuously connects to the photosphere. The plasma-β is an important parameter that determines the shape of the structure. In many cases magnetic Rayleigh-Taylor instabilities and oscillatory phenomena develop. Fingers and plumes are generated, affecting the whole prominence body and producing vertical structures in an essentially horizontal magnetic field. However, magnetic shear is able to reduce or even to suppress this instability.

  15. MORPHOLOGY AND DYNAMICS OF SOLAR PROMINENCES FROM 3D MHD SIMULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Terradas, J.; Soler, R.; Oliver, R.; Ballester, J. L. [Departament de Física, Universitat de les Illes Balears, E-07122 Palma de Mallorca (Spain); Luna, M., E-mail: jaume.terradas@uib.es [Instituto de Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain)

    2015-01-20

    In this paper we present a numerical study of the time evolution of solar prominences embedded in sheared magnetic arcades. The prominence is represented by a density enhancement in a background-stratified atmosphere and is connected to the photosphere through the magnetic field. By solving the ideal magnetohydrodynamic equations in three dimensions, we study the dynamics for a range of parameters representative of real prominences. Depending on the parameters considered, we find prominences that are suspended above the photosphere, i.e., detached prominences, but also configurations resembling curtain or hedgerow prominences whose material continuously connects to the photosphere. The plasma-β is an important parameter that determines the shape of the structure. In many cases magnetic Rayleigh-Taylor instabilities and oscillatory phenomena develop. Fingers and plumes are generated, affecting the whole prominence body and producing vertical structures in an essentially horizontal magnetic field. However, magnetic shear is able to reduce or even to suppress this instability.

  16. Reconnection–Condensation Model for Solar Prominence Formation

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Takafumi [Institute for Space-Earth Environmental Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601 (Japan); Yokoyama, Takaaki, E-mail: kaneko@isee.nagoya-u.ac.jp [Department of Earth and Planetary Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2017-08-10

    We propose a reconnection–condensation model in which topological change in a coronal magnetic field via reconnection triggers radiative condensation, thereby resulting in prominence formation. Previous observational studies have suggested that reconnection at a polarity inversion line of a coronal arcade field creates a flux rope that can sustain a prominence; however, they did not explain the origin of cool dense plasmas of prominences. Using three-dimensional magnetohydrodynamic simulations, including anisotropic nonlinear thermal conduction and optically thin radiative cooling, we demonstrate that reconnection can lead not only to flux rope formation but also to radiative condensation under a certain condition. In our model, this condition is described by the Field length, which is defined as the scale length for thermal balance between radiative cooling and thermal conduction. This critical condition depends weakly on the artificial background heating. The extreme ultraviolet emissions synthesized with our simulation results have good agreement with observational signatures reported in previous studies.

  17. Physics of solar prominences. Proceedings of the Colloquium, Oslo, Norway, August 14-18, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, E; Maltby, P

    1979-01-01

    These papers deal with recent theoretical and observational studies of the physics of solar prominences. Specific topics include reviews of prominence spectra and their interpretation, polarimetric observations and magnetic-field determination in prominences, observations of the prominence-corona interface, theories on the formation and stability of quiescent prominences, prominence classifications, observations of active prominences, observations and interpretations of coronal manifestations of eruptive prominences, and models of prominence structure and dynamics. Other contributions discuss simultaneous observations of Ca II and hydrogen Balmer lines in quiescent prominences, recent results in quiescent-prominence spectroscopy, the solar helium abundance obtained from optical spectra of quiescent prominences, and Stokes polarimetry of quiescent prominences in the He I D3 line. Magnetic-field determination based on the Hanle effect is also examined, along with the orientation of prominence microstructure relative to magnetic-field direction, radio observations of quiescent-prominence filaments at centimeter and millimeter wavelengths, EUV observations of filaments, and a magnetic-field reconnection model of quiescent prominences.

  18. Study of a Large Helical Eruptive Prominence Associated with ...

    Indian Academy of Sciences (India)

    2001-04-21

    Apr 21, 2001 ... morphology of the event, energy budget of the prominence and associated. CMEs. ... magnetically driven and internally powered. Key words. ... Solar prominences are ribbons of cool (∼8000 K) dense gas (∼10. −11 gcm. −3. ) ...

  19. SOLAR MAGNETIZED TORNADOES: ROTATIONAL MOTION IN A TORNADO-LIKE PROMINENCE

    Energy Technology Data Exchange (ETDEWEB)

    Su, Yang; Veronig, Astrid; Temmer, Manuela; Vanninathan, Kamalam [IGAM-Kanzelhöhe Observatory, Institute of Physics, University of Graz, Universitätsplatz 5, A-8010 Graz (Austria); Gömöry, Peter [Astronomical Institute of the Slovak Academy of Sciences, SK-05960 Tatranská Lomnica (Slovakia); Wang, Tongjiang [Department of Physics, the Catholic University of America, Washington, DC 20064 (United States); Gan, Weiqun; Li, YouPing, E-mail: yang.su@uni-graz.at [Key Laboratory of Dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Sciences, Nanjing 210008 (China)

    2014-04-10

    Su et al. proposed a new explanation for filament formation and eruption, where filament barbs are rotating magnetic structures driven by underlying vortices on the surface. Such structures have been noticed as tornado-like prominences when they appear above the limb. They may play a key role as the source of plasma and twist in filaments. However, no observations have successfully distinguished rotational motion of the magnetic structures in tornado-like prominences from other motions such as oscillation and counter-streaming plasma flows. Here we report evidence of rotational motions in a tornado-like prominence. The spectroscopic observations in two coronal lines were obtained from a specifically designed Hinode/EIS observing program. The data revealed the existence of both cold and million-degree-hot plasma in the prominence leg, supporting the so-called prominence-corona transition region. The opposite velocities at the two sides of the prominence and their persistent time evolution, together with the periodic motions evident in SDO/AIA dark structures, indicate a rotational motion of both cold and hot plasma with a speed of ∼5 km s{sup –1}.

  20. SOLAR MAGNETIZED TORNADOES: ROTATIONAL MOTION IN A TORNADO-LIKE PROMINENCE

    International Nuclear Information System (INIS)

    Su, Yang; Veronig, Astrid; Temmer, Manuela; Vanninathan, Kamalam; Gömöry, Peter; Wang, Tongjiang; Gan, Weiqun; Li, YouPing

    2014-01-01

    Su et al. proposed a new explanation for filament formation and eruption, where filament barbs are rotating magnetic structures driven by underlying vortices on the surface. Such structures have been noticed as tornado-like prominences when they appear above the limb. They may play a key role as the source of plasma and twist in filaments. However, no observations have successfully distinguished rotational motion of the magnetic structures in tornado-like prominences from other motions such as oscillation and counter-streaming plasma flows. Here we report evidence of rotational motions in a tornado-like prominence. The spectroscopic observations in two coronal lines were obtained from a specifically designed Hinode/EIS observing program. The data revealed the existence of both cold and million-degree-hot plasma in the prominence leg, supporting the so-called prominence-corona transition region. The opposite velocities at the two sides of the prominence and their persistent time evolution, together with the periodic motions evident in SDO/AIA dark structures, indicate a rotational motion of both cold and hot plasma with a speed of ∼5 km s –1

  1. Prominence-corona interface compared with the chromosphere-corona transition region

    Energy Technology Data Exchange (ETDEWEB)

    Orrall, F Q; Schmahl, E J [Harvard Coll. Observatory, Cambridge, Mass. (USA)

    1976-11-01

    The intensities of 52 EUV emission lines from each of 9 hedgerow prominences observed at the limb with the Harvard experiment on ATM-Skylab have been compared with intensities from the interior of network cells at the center of the disk, in order to compare the prominence-corona (P-C) interface with the chromosphere-corona (C-C) transition region. The intensity ratio Isub(cell)/Isub(prominence) for each line varies systematically (in all of the prominences observed), with the temperature of formation of the line as approximately Tsup(-0.6). The density sensitive C III (formed at T approximately 9x10/sup 4/ K) line ratio Isub(lambda1175)/Isub(lambda977) implies an average density 1.3x10/sup 9/ electrons cm/sup -3/ in the P-C interface and approximately 4 times this value in the C-C transition of the cells. The total optical thickness at the head of the Lyman continuum is < approximately 10 in most of the prominences studied; in two of the prominences, however, the possibility that tau/sub 0/ is large cannot be rejected. Methods of analysis of these EUV data are developed assuming both a resolved and an unresolved internal prominence structure. Although the systematic differences between the P-C interface and the C-C transition are stressed, the similarities are probably more remarkable and may be a result of fine structure in the C-C transition.

  2. Potent inhibition of HIV-1 replication by a Tat mutant.

    Directory of Open Access Journals (Sweden)

    Luke W Meredith

    Full Text Available Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection.

  3. MULTI-LINE STOKES INVERSION FOR PROMINENCE MAGNETIC-FIELD DIAGNOSTICS

    International Nuclear Information System (INIS)

    Casini, R.; Lopez Ariste, A.; Paletou, F.; Leger, L.

    2009-01-01

    We present test results on the simultaneous inversion of the Stokes profiles of the He I lines at 587.6 nm (D 3 ) and 1083.0 nm in prominences (90 deg. scattering). We created data sets of synthetic Stokes profiles for the case of quiescent prominences (B -3 of the peak intensity for the polarimetric sensitivity of the simulated observations. In this work, we focus on the error analysis for the inference of the magnetic field vector, under the usual assumption that the prominence can be assimilated to a slab of finite optical thickness with uniform magnetic and thermodynamic properties. We find that the simultaneous inversion of the two lines significantly reduces the errors on the inference of the magnetic field vector, with respect to the case of single-line inversion. These results provide a solid justification for current and future instrumental efforts with multi-line capabilities for the observations of solar prominences and filaments.

  4. Physics of Solar Prominences: I-Spectral Diagnostics and Non-LTE Modelling

    Science.gov (United States)

    Labrosse, N.; Heinzel, P.; Vial, J.-C,; Kucera, T.; Parenti, S.; Gunar, S.; Schmieder, B.; Kilper, G.

    2010-01-01

    This review paper outlines background information and covers recent advances made via the analysis of spectra and images of prominence plasma and the increased sophistication of non-LTE (i.e. when there is a departure from Local Thermodynamic Equilibrium) radiative transfer models. We first describe the spectral inversion techniques that have been used to infer the plasma parameters important for the general properties of the prominence plasma in both its cool core and the hotter prominence-corona transition region. We also review studies devoted to the observation of bulk motions of the prominence plasma and to the determination of prominence mass. However, a simple inversion of spectroscopic data usually fails when the lines become optically thick at certain wavelengths. Therefore, complex

  5. Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.

    Directory of Open Access Journals (Sweden)

    Fang Miao

    Full Text Available Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl oxy] phenol, D-Arb is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ. At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.

  6. Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.

    Science.gov (United States)

    Miao, Fang; Shi, Ying; Fan, Zhi-Feng; Jiang, Shan; Xu, Shi-Zheng; Lei, Tie-Chi

    2016-01-01

    Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.

  7. Solar Prominence Modelling and Plasma Diagnostics at ALMA Wavelengths

    Science.gov (United States)

    Rodger, Andrew; Labrosse, Nicolas

    2017-09-01

    Our aim is to test potential solar prominence plasma diagnostics as obtained with the new solar capability of the Atacama Large Millimeter/submillimeter Array (ALMA). We investigate the thermal and plasma diagnostic potential of ALMA for solar prominences through the computation of brightness temperatures at ALMA wavelengths. The brightness temperature, for a chosen line of sight, is calculated using the densities of electrons, hydrogen, and helium obtained from a radiative transfer code under non-local thermodynamic equilibrium (non-LTE) conditions, as well as the input internal parameters of the prominence model in consideration. Two distinct sets of prominence models were used: isothermal-isobaric fine-structure threads, and large-scale structures with radially increasing temperature distributions representing the prominence-to-corona transition region. We compute brightness temperatures over the range of wavelengths in which ALMA is capable of observing (0.32 - 9.6 mm), however, we particularly focus on the bands available to solar observers in ALMA cycles 4 and 5, namely 2.6 - 3.6 mm (Band 3) and 1.1 - 1.4 mm (Band 6). We show how the computed brightness temperatures and optical thicknesses in our models vary with the plasma parameters (temperature and pressure) and the wavelength of observation. We then study how ALMA observables such as the ratio of brightness temperatures at two frequencies can be used to estimate the optical thickness and the emission measure for isothermal and non-isothermal prominences. From this study we conclude that for both sets of models, ALMA presents a strong thermal diagnostic capability, provided that the interpretation of observations is supported by the use of non-LTE simulation results.

  8. ON THE MAGNETISM AND DYNAMICS OF PROMINENCE LEGS HOSTING TORNADOES

    International Nuclear Information System (INIS)

    Martínez González, M. J.; Ramos, A. Asensio; Arregui, I.; Collados, M.; Beck, C.; Rodríguez, J. de la Cruz

    2016-01-01

    Solar tornadoes are dark vertical filamentary structures observed in the extreme ultraviolet associated with prominence legs and filament barbs. Their true nature and relationship to prominences requires an understanding of their magnetic structure and dynamic properties. Recently, a controversy has arisen: is the magnetic field organized forming vertical, helical structures or is it dominantly horizontal? And concerning their dynamics, are tornadoes really rotating or is it just a visual illusion? Here we analyze four consecutive spectro-polarimetric scans of a prominence hosting tornadoes on its legs, which helps us shed some light on their magnetic and dynamical properties. We show that the magnetic field is very smooth in all the prominence, which is probably an intrinsic property of the coronal field. The prominence legs have vertical helical fields that show slow temporal variation that is probably related to the motion of the fibrils. Concerning the dynamics, we argue that (1) if rotation exists, it is intermittent, lasting no more than one hour, and (2) the observed velocity pattern is also consistent with an oscillatory velocity pattern (waves).

  9. ON THE MAGNETISM AND DYNAMICS OF PROMINENCE LEGS HOSTING TORNADOES

    Energy Technology Data Exchange (ETDEWEB)

    Martínez González, M. J.; Ramos, A. Asensio; Arregui, I.; Collados, M. [Instituto de Astrofísica de Canarias, Vía Láctea s/n, E-38205 La Laguna, Tenerife (Spain); Beck, C. [National Solar Observatory, Sacramento Peak P.O. Box 62, Sunspot, NM 88349 (United States); Rodríguez, J. de la Cruz [Institute for Solar Physics, Department of Astronomy, Stockholm University, Albanova University Center, SE-10691 Stockholm (Sweden)

    2016-07-10

    Solar tornadoes are dark vertical filamentary structures observed in the extreme ultraviolet associated with prominence legs and filament barbs. Their true nature and relationship to prominences requires an understanding of their magnetic structure and dynamic properties. Recently, a controversy has arisen: is the magnetic field organized forming vertical, helical structures or is it dominantly horizontal? And concerning their dynamics, are tornadoes really rotating or is it just a visual illusion? Here we analyze four consecutive spectro-polarimetric scans of a prominence hosting tornadoes on its legs, which helps us shed some light on their magnetic and dynamical properties. We show that the magnetic field is very smooth in all the prominence, which is probably an intrinsic property of the coronal field. The prominence legs have vertical helical fields that show slow temporal variation that is probably related to the motion of the fibrils. Concerning the dynamics, we argue that (1) if rotation exists, it is intermittent, lasting no more than one hour, and (2) the observed velocity pattern is also consistent with an oscillatory velocity pattern (waves).

  10. Aesthetic Refinements in Patients with Prominent Eyes.

    Science.gov (United States)

    Richter, Dirk F; Schwaiger, Nina; Wiedner, Maria

    2015-12-01

    The treatment of prominent eyes is still a challenging task. As well as the surgery, proper preoperative diagnosis differentiating between patients with and without Graves ophthalmopathy plays an important role. In functionally asymptomatic patients with Graves disease suffering from the aesthetic impairment of prominent eyes, the transpalpebral decompression by intraorbital fat removal technique has been proved to be reliable, effective, safe, and easily performed by a trained and experienced oculoplastic surgeon. This technique provides long-lasting results, leading to improvement not only in visual function but also in personal well-being and in the patient's social life, with a high benefit-to-risk ratio. The most powerful tool to treat the lower lid deformity and malar bags in patients without Graves disease is the subperiosteal midface lift. It shortens the lid-cheek junction and blends the retaining periorbital ligaments. Furthermore, it adds volume to the lower lid and gives a stable support. By the nature of the procedure, it also turns a negative into a positive vector. In experienced hands, Olivari's orbital decompression and Hester's midface lift are ideal options for the treatment of prominent eyes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Brandburg Prominance, Namibia, Africa

    Science.gov (United States)

    1993-01-01

    The Brandburg Prominance, Namibia (21.0S, 14.5E) is a round basaltic plug and is the highest feature (over 8,000 ft) in the country. Wind streaks on the surface of the coastal desert, aligned northeast to southwest, are the result of frequent sand storms. Coastal stratus clouds provide most of the life supporting moisture as fog droplets in this arid land where annual rainfall may be less than a quarter of an inch for decades at a time.

  12. A STATISTICAL STUDY OF TRANSVERSE OSCILLATIONS IN A QUIESCENT PROMINENCE

    Energy Technology Data Exchange (ETDEWEB)

    Hillier, A. [Kwasan and Hida Observatories, Kyoto University, Kyoto 607-8471 (Japan); Morton, R. J. [Mathematics and Information Science, Northumbria University, Pandon Building, Camden Street, Newcastle upon Tyne NE1 8ST (United Kingdom); Erdélyi, R., E-mail: andrew@kwasan.kyoto-u.ac.jp [Solar Physics and Space Plasma Research Centre (SP2RC), University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom)

    2013-12-20

    The launch of the Hinode satellite has allowed for seeing-free observations at high-resolution and high-cadence making it well suited to study the dynamics of quiescent prominences. In recent years it has become clear that quiescent prominences support small-amplitude transverse oscillations, however, sample sizes are usually too small for general conclusions to be drawn. We remedy this by providing a statistical study of transverse oscillations in vertical prominence threads. Over a 4 hr period of observations it was possible to measure the properties of 3436 waves, finding periods from 50 to 6000 s with typical velocity amplitudes ranging between 0.2 and 23 km s{sup –1}. The large number of observed waves allows the determination of the frequency dependence of the wave properties and derivation of the velocity power spectrum for the transverse waves. For frequencies less than 7 mHz, the frequency dependence of the velocity power is consistent with the velocity power spectra generated from observations of the horizontal motions of magnetic elements in the photosphere, suggesting that the prominence transverse waves are driven by photospheric motions. However, at higher frequencies the two distributions significantly diverge, with relatively more power found at higher frequencies in the prominence oscillations. These results highlight that waves over a large frequency range are ubiquitous in prominences, and that a significant amount of the wave energy is found at higher frequency.

  13. A STATISTICAL STUDY OF TRANSVERSE OSCILLATIONS IN A QUIESCENT PROMINENCE

    International Nuclear Information System (INIS)

    Hillier, A.; Morton, R. J.; Erdélyi, R.

    2013-01-01

    The launch of the Hinode satellite has allowed for seeing-free observations at high-resolution and high-cadence making it well suited to study the dynamics of quiescent prominences. In recent years it has become clear that quiescent prominences support small-amplitude transverse oscillations, however, sample sizes are usually too small for general conclusions to be drawn. We remedy this by providing a statistical study of transverse oscillations in vertical prominence threads. Over a 4 hr period of observations it was possible to measure the properties of 3436 waves, finding periods from 50 to 6000 s with typical velocity amplitudes ranging between 0.2 and 23 km s –1 . The large number of observed waves allows the determination of the frequency dependence of the wave properties and derivation of the velocity power spectrum for the transverse waves. For frequencies less than 7 mHz, the frequency dependence of the velocity power is consistent with the velocity power spectra generated from observations of the horizontal motions of magnetic elements in the photosphere, suggesting that the prominence transverse waves are driven by photospheric motions. However, at higher frequencies the two distributions significantly diverge, with relatively more power found at higher frequencies in the prominence oscillations. These results highlight that waves over a large frequency range are ubiquitous in prominences, and that a significant amount of the wave energy is found at higher frequency

  14. Quiescent Prominences in the Era of ALMA. II. Kinetic Temperature Diagnostics

    Science.gov (United States)

    Gunár, Stanislav; Heinzel, Petr; Anzer, Ulrich; Mackay, Duncan H.

    2018-01-01

    We provide the theoretical background for diagnostics of the thermal properties of solar prominences observed by the Atacama Large Millimeter/submillimeter Array (ALMA). To do this, we employ the 3D Whole-Prominence Fine Structure (WPFS) model that produces synthetic ALMA-like observations of a complex simulated prominence. We use synthetic observations derived at two different submillimeter/millimeter (SMM) wavelengths—one at a wavelength at which the simulated prominence is completely optically thin and another at a wavelength at which a significant portion of the simulated prominence is optically thick—as if these were the actual ALMA observations. This allows us to develop a technique for an analysis of the prominence plasma thermal properties from such a pair of simultaneous high-resolution ALMA observations. The 3D WPFS model also provides detailed information about the distribution of the kinetic temperature and the optical thickness along any line of sight. We can thus assess whether the measure of the kinetic temperature derived from observations accurately represents the actual kinetic temperature properties of the observed plasma. We demonstrate here that in a given pixel the optical thickness at the wavelength at which the prominence plasma is optically thick needs to be above unity or even larger to achieve a sufficient accuracy of the derived information about the kinetic temperature of the analyzed plasma. Information about the optical thickness cannot be directly discerned from observations at the SMM wavelengths alone. However, we show that a criterion that can identify those pixels in which the derived kinetic temperature values correspond well to the actual thermal properties in which the observed prominence can be established.

  15. Identification of a potent endothelium-derived angiogenic factor.

    Directory of Open Access Journals (Sweden)

    Vera Jankowski

    Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

  16. Fabrication of micro-prominences on PTFE surface using proton beam writing

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Akane, E-mail: ogawa.akane@jaea.go.jp [Department of Advanced Radiation Technology, Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233 Watanuki-Machi, Takasaki, Gunma 370-1292 (Japan); Satoh, Takahiro; Koka, Masashi [Department of Advanced Radiation Technology, Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233 Watanuki-Machi, Takasaki, Gunma 370-1292 (Japan); Kobayashi, Tomohiro [Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 350-0198 (Japan); Kamiya, Tomihiro [Department of Advanced Radiation Technology, Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233 Watanuki-Machi, Takasaki, Gunma 370-1292 (Japan)

    2013-07-01

    Polytetrafluoroethylene (PTFE) is a typical fluoropolymer and it has several desirable technological properties such as electrical insulation, solid lubrication etc. However, the conventional microstructuring methods have not been well applied to PTFE due to its chemical inertness. Some effective micromachining using synchrotron radiation or ion beam irradiation has been reported. In this study, we create micro-prominences by raising the original surface using proton beam writing (PBW) without chemical etching. A conical prominence was formed by spiral drawing from the center with a 3 MeV proton beam. The body was porous, and the bulk PTFE below the prominence changed to fragmented structures. With decreasing writing speed, the prominence became taller but the height peaked. The prominence gradually reduced in size after the speed reached the optimum value. We expect that these porous projections with high aspect ratio will be versatile in medical fields and microelectromechanical systems (MEMS) technology.

  17. Potent Antioxidative Activity of Lycopene: A Potential Role in Scavenging Hypochlorous Acid †

    OpenAIRE

    Pennathur, Subramaniam; Maitra, Dhiman; Byun, Jaeman; Sliskovic, Inga; Abdulhamid, Ibrahim; Saed, Ghassan M.; Diamond, Michael P.; Abu-Soud, Husam M.

    2010-01-01

    Lycopene, a carotenoid found in tomatoes, is a proven anti-oxidant that may lower the risk of certain disorders including heart disease and cancer. Hypochlorous acid (HOCl) is an oxidant linked to tissue oxidation in cardiovascular disease and other inflammatory disorders through its ability to modify proteins, deoxyribonucleic acid, ribonucleic acid and lipids. Here we show that lycopene can function as a potent scavenger of HOCl at a wide range of concentrations that span various pathophysi...

  18. ARE TORNADO-LIKE MAGNETIC STRUCTURES ABLE TO SUPPORT SOLAR PROMINENCE PLASMA?

    Energy Technology Data Exchange (ETDEWEB)

    Luna, M.; Moreno-Insertis, F. [Instituto de Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain); Priest, E. [Mathematics Institute, University of St Andrews, St Andrews KY16 9SS (United Kingdom)

    2015-07-20

    Recent high-resolution and high-cadence observations have surprisingly suggested that prominence barbs exhibit apparent rotating motions suggestive of a tornado-like structure. Additional evidence has been provided by Doppler measurements. The observations reveal opposite velocities for both hot and cool plasma on the two sides of a prominence barb. This motion is persistent for several hours and has been interpreted in terms of rotational motion of prominence feet. Several authors suggest that such barb motions are rotating helical structures around a vertical axis similar to tornadoes on Earth. One of the difficulties of such a proposal is how to support cool prominence plasma in almost-vertical structures against gravity. In this work we model analytically a tornado-like structure and try to determine possible mechanisms to support the prominence plasma. We have found that the Lorentz force can indeed support the barb plasma provided the magnetic structure is sufficiently twisted and/or significant poloidal flows are present.

  19. ARE TORNADO-LIKE MAGNETIC STRUCTURES ABLE TO SUPPORT SOLAR PROMINENCE PLASMA?

    International Nuclear Information System (INIS)

    Luna, M.; Moreno-Insertis, F.; Priest, E.

    2015-01-01

    Recent high-resolution and high-cadence observations have surprisingly suggested that prominence barbs exhibit apparent rotating motions suggestive of a tornado-like structure. Additional evidence has been provided by Doppler measurements. The observations reveal opposite velocities for both hot and cool plasma on the two sides of a prominence barb. This motion is persistent for several hours and has been interpreted in terms of rotational motion of prominence feet. Several authors suggest that such barb motions are rotating helical structures around a vertical axis similar to tornadoes on Earth. One of the difficulties of such a proposal is how to support cool prominence plasma in almost-vertical structures against gravity. In this work we model analytically a tornado-like structure and try to determine possible mechanisms to support the prominence plasma. We have found that the Lorentz force can indeed support the barb plasma provided the magnetic structure is sufficiently twisted and/or significant poloidal flows are present

  20. Are Tornado-Like Magnetic Structures Able to Support Solar Prominence Plasma?

    Science.gov (United States)

    Ogunjo, S. T.; Luna Bennasar, M.; Moreno-Insertis, F.; Priest, E. R.

    2015-12-01

    Recent high-resolution and high-cadence observations have surprisingly suggested that prominence barbs exhibit apparent rotating motions suggestive of a tornado-like structure. Additional evidence has been provided by Doppler measurements. The observations reveal opposite velocities for both hot and cool plasma on the two sides of a prominence barb. This motion is persistent for several hours and has been interpreted in terms of rotational motion of prominence feet. Several authors suggest that such barb motions are rotating helical structures around a vertical axis similar to tornadoes on Earth. One of the difficulties of such a proposal is how to support cool prominence plasma in almost-vertical structures against gravity. In this work we model analytically a tornado-like structure and try to determine possible mechanisms to support the prominence plasma. We have found that the Lorentz force can indeed support the barb plasma provided the magnetic structure is sufficiently twisted and/or significant poloidal flows are present.

  1. Unintended exposure in radiotherapy: Identification of prominent causes

    International Nuclear Information System (INIS)

    Boadu, Mary; Rehani, Madan Mohan

    2009-01-01

    Background and purpose: Unintended exposures in radiotherapy are likely to occur when certain conditions that favour such exposures exist. Based on the frequency of occurrence of various causes of 100 events of unintended exposures in radiotherapy as derived from the analysis of published reports, a checklist for assessing the vulnerability of radiotherapy facilities for potential accidents has been prepared. The list presents items to be considered for safety critical assessments of a radiotherapy department for the improvement of patient safety and the entire radiotherapy processes. Materials and methods: The resources used for this paper consist of 100 unintended radiotherapy exposures and were derived from existing published reports. The analysis was performed by forming two templates: one consisting of 10 initiating events and another of 35 contributing factors. Results: Four most prominent initiating events were identified and together accounted for about 70% of all the unintended exposure events. Ten most prominent contributing factors were also identified and together accounted for about 70% of all the radiotherapy unintended exposure events covered under this study. Conclusion: With this knowledge of high frequency of occurrences, the identified four prominent initiating events and the 10 most prominent contributing factors must be checked and dealt with as a matter of priority when assessing the safety of a radiotherapy facility. A simple checklist for checking the quality assurance programmes of a radiotherapy department for every aspect of the design and delivery of radiation have been provided.

  2. Piecewise mass flows within a solar prominence observed by the New Vacuum Solar Telescope

    Science.gov (United States)

    Li, Hongbo; Liu, Yu; Tam, Kuan Vai; Zhao, Mingyu; Zhang, Xuefei

    2018-06-01

    The material of solar prominences is often observed in a state of flowing. These mass flows (MF) are important and useful for us to understand the internal structure and dynamics of prominences. In this paper, we present a high resolution Hα observation of MFs within a quiescent solar prominence. From the observation, we find that the plasma primarily has a circular motion and a downward motion separately in the middle section and legs of the prominence, which creates a piecewise mass flow along the observed prominence. Moreover, the observation also shows a clear displacement of MF's velocity peaks in the middle section of the prominence. All of these provide us with a detailed record of MFs within a solar prominence and show a new approach to detecting the physical properties of prominence.

  3. Cylindrical prominences and the magnetic influence of the photospheric boundary

    International Nuclear Information System (INIS)

    Lerche, I.; Chicago Univ., IL; Low, B.C.

    1980-01-01

    We construct exact, non-linear, solutions for an horizontal, cylindrical, current-carrying, prominence supported against solar gravity by the action of a Lorentz force. The solutions incorporate the photosphere boundary condition, proposed by van Tend and Kuperus (1978), and analyzed by them for line filaments. Our solutions have finite radius for the prominence material and, as well as satisfying the equations of magnetostatic equilibrium, they allow for the continuity of gas pressure, and of the normal and tangential components of magnetic field across the circular prominence boundary. We show that an infinity of solutions is possible and we illustrate the basic behavior by investigation of a special case. We also give a prescription for constructing equilibrium fields for any horizontal prominence with arbitrary cross-section and with an arbitrary external magnetic field. The prescription is ideally suited for numerical codes and we suggest that both the equilibrium of such shapes can easily be accomplished numerically together with their evolutionary history. (orig.)

  4. The most prominent safety guarantees

    International Nuclear Information System (INIS)

    Lucenet, G.

    1978-01-01

    The Creys-Malville Nuclear Centre has been designed using the safety analysis implemented since the beginning of the developments of breeder reactors in France and the Super Phenix follows almost the same safety regulations as its predecessor the Phenix reactor. These regulations are based on: 'Recommendations for the safety standards of the Super Phenix' drawn up by the French Safety Authorities in July 1973. The prominent points are summarised. (C.F.)

  5. A Discourse Perspective of Topic-prominence in Chinese EFL Learners’ Interlanguage

    Directory of Open Access Journals (Sweden)

    Shaopeng Li

    2014-07-01

    Full Text Available The present study aims to investigate the general characteristics of topic-prominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from the discourse perspective. We have selected as the research target “topic chain” which is the main topic-prominent structure in Chinese discourse and “zero anaphora” which is the most common topic anaphor of topic chain. Topic structures mainly appear in Chinese discourse in the form of “topic chain” (Wang, 2002; 2004. Actually, in the event of a topic chain, research on topic structures should go into the typical range of discourse. Two important findings were yielded by the present study. First, the characteristics of Chinese topic chain are transferrable to the interlanguage of Chinese EFL learners, thus resulting in overgeneralization of zero anaphora; second, interlanguage discourse of Chinese EFL learners reflects the characteristics of a second language acquisition process from topic-prominence to subject-prominence, thus lending support to the discourse transfer hypothesis.

  6. Dioscorea bulbifera Mediated Synthesis of Novel AucoreAgshell Nanoparticles with Potent Antibiofilm and Antileishmanial Activity

    Directory of Open Access Journals (Sweden)

    Sougata Ghosh

    2015-01-01

    Full Text Available Dioscorea bulbifera is a potent medicinal plant used in both Indian and Chinese traditional medicine owing to its rich phytochemical diversity. Herein, we report the rapid synthesis of novel AucoreAgshell nanoparticles by D. bulbifera tuber extract (DBTE. AucoreAgshell NPs synthesis was completed within 5 h showing a prominent peak at 540 nm. HRTEM analysis revealed 9 nm inner core of elemental gold covered by a silver shell giving a total particle diameter upto 15 nm. AucoreAgshellNPs were comprised of 57.34±1.01% gold and 42.66±0.97% silver of the total mass. AucoreAgshellNPs showed highest biofilm inhibition upto 83.68±0.09% against A. baumannii. Biofilms of P. aeruginosa, E. coli, and S. aureus were inhibited up to 18.93±1.94%, 22.33±0.56%, and 30.70±1.33%, respectively. Scanning electron microscopy (SEM and atomic force microscopy (AFM confirmed unregulated cellular efflux through pore formation leading to cell death. Potent antileishmanial activity of AucoreAgshellNPs (MIC=32 µg/mL was confirmed by MTT assay. Further SEM micrographs showed pronounced deformity in the spindle shaped cellular morphology changing to spherical. This is the first report of synthesis, characterization, antibiofilm, and antileishmanial activity of AucoreAgshellNPs synthesized by D. bulbifera.

  7. Prominence Bubbles and Plumes: Thermo-magnetic Buoyancy in Coronal Cavity Systems

    Science.gov (United States)

    Berger, Thomas; Hurlburt, N.

    2009-05-01

    The Hinode/Solar Optical Telescope continues to produce high spatial and temporal resolution images of solar prominences in both the Ca II 396.8 nm H-line and the H-alpha 656.3 nm line. Time series of these images show that many quiescent prominences produce large scale (50 Mm) dark "bubbles" that "inflate" into, and sometimes burst through, the prominence material. In addition, small-scale (2--5 Mm) dark plumes are seen rising into many quiescent prominences. We show typical examples of both phenomena and argue that they originate from the same mechanism: concentrated and heated magnetic flux that rises due to thermal and magnetic buoyancy to equilibrium heights in the prominence/coronal-cavity system. More generally, these bubbles and upflows offer a source of both magnetic flux and mass to the overlying coronal cavity, supporting B.C. Low's theory of CME initiation via steadily increasing magnetic buoyancy breaking through the overlying helmut streamer tension forces. Quiescent prominences are thus seen as the lowermost parts of the larger coronal cavity system, revealing through thermal effects both the cooled downflowing "drainage" from the cavity and the heated upflowing magnetic "plasmoids" supplying the cavity. We compare SOT movies to new 3D compressible MHD simulations that reproduce the dark turbulent plume dynamics to establish the magnetic and thermal character of these buoyancy-driven flows into the corona.

  8. Modeling of prominence threads in magnetic fields: Levitation by incompressible MHD waves

    Science.gov (United States)

    Pécseli, Hans; Engvold, OddbjØrn

    2000-05-01

    The nature of thin, highly inclined threads observed in quiescent prominences has puzzled solar physicists for a long time. When assuming that the threads represent truly inclined magnetic fields, the supporting mechanism of prominence plasma against gravity has remained an open issue. This paper examines the levitation of prominence plasma exerted by weakly damped MHD waves in nearly vertical magnetic flux tubes. It is shown that the wave damping, and resulting `radiation pressure', caused predominantly by ion-neutral collisions in the `cold' prominence plasma, may balance the acceleration of gravity provided the oscillation frequency is ω~ 2 rad s^-1 (f~0.5 Hz). Such short wave periods may be the result of small-scale magnetic reconnections in the highly fragmentary magnetic field of quiescent prominences. In the proposed model, the wave induced levitation acts predominantly on plasma - neutral gas mixtures.

  9. Comparative Amino Acid Decomposition Analysis of Potent Type I P38α Inhibitors

    Directory of Open Access Journals (Sweden)

    Ahmad Ebadi

    2013-05-01

    Full Text Available Background and purpose of the study:p38α is a member of mitogen-activated protein kinases (MAPK considered as a prominent target in development of anti-inflammatory agents. Any abnormality in the phosphorylation process leads to the different human diseases such as cancer, diabetes and inflammatory diseases. Several small molecule p38α inhibitors have been developed up to now. In this regard, structural elucidation of p38 inhibitors needs to be done enabling us in rational lead development strategies.Methods:Various interactions of three potent inhibitors with p38α active site have been evaluated in terms of binding energies and bond lengths via density function theory and MD simulations.Results:Our comparative study showed that both ab initio and MD simulation led to the relatively similar results in pharmacophore discrimination of p38α inhibitors.Conclusion:The results of the present study may find their usefulness in pharmacophore based modification of p38α inhibitors.

  10. Automatic detection of prominence (as defined by listeners' judgements) in read aloud Dutch sentences

    NARCIS (Netherlands)

    Streefkerk, B.M.; Pols, L.C.W.; ten Bosch, L.F.M.

    1998-01-01

    This paper describes a first step towards the automatic classification of prominence (as defined by native listeners). As a result of a listening experiment each word in 500 sentences was marked with a rating scale between `0' (non-prominent) and `10' (very prominent). These prominence labels are

  11. Motions in Prominence Barbs as observed by Hinode/SOT and IRIS

    Science.gov (United States)

    Kucera, Therese A.; Ofman, Leon; Tarbell, Theodore D.

    2016-05-01

    We discuss observations of prominence barb dynamics as observed by Hinode/SOT and IRIS. Prominence barbs extend outwards to the side of the main prominence spine and downwards towards the chromosphere. Their properties, including the structure of their magnetic field and the nature of the motions observed in them are a subject of current debate. We use a combination of high cadence, high resolution imaging, H-alpha Doppler, and Mg II line profile data to analyze and understand waves and flows in barbs and discuss their ramifications in terms of a model of the barb magnetic field as collection of dipped field lines.

  12. CRITICAL HEIGHT FOR THE DESTABILIZATION OF SOLAR PROMINENCES: STATISTICAL RESULTS FROM STEREO OBSERVATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Liu Kai; Wang Yuming; Wang Shui; Shen Chenglong, E-mail: ymwang@ustc.edu.cn [CAS Key Laboratory of Geospace Environment, Department of Geophysics and Planetary Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China)

    2012-01-10

    At which height is a prominence inclined to be unstable, or where is the most probable critical height for the prominence destabilization? This question was statistically studied based on 362 solar limb prominences well recognized by Solar Limb Prominence Catcher and Tracker from 2007 April to the end of 2009. We found that there are about 71% disrupted prominences (DPs), among which about 42% of them did not erupt successfully and about 89% of them experienced a sudden destabilization process. After a comprehensive analysis of the DPs, we discovered the following: (1) Most DPs become unstable at a height of 0.06-0.14 R{sub Sun} from the solar surface, and there are two most probable critical heights at which a prominence is very likely to become unstable, the first one is 0.13 R{sub Sun} and the second one is 0.19 R{sub Sun }. (2) An upper limit for the erupting velocity of eruptive prominences (EPs) exists, which decreases following a power law with increasing height and mass; accordingly, the kinetic energy of EPs has an upper limit too, which decreases as the critical height increases. (3) Stable prominences are generally longer and heavier than DPs, and not higher than 0.4 R{sub Sun }. (4) About 62% of the EPs were associated with coronal mass ejections (CMEs); but there is no difference in apparent properties between EPs associated with CMEs and those that are not.

  13. CRITICAL HEIGHT FOR THE DESTABILIZATION OF SOLAR PROMINENCES: STATISTICAL RESULTS FROM STEREO OBSERVATIONS

    International Nuclear Information System (INIS)

    Liu Kai; Wang Yuming; Wang Shui; Shen Chenglong

    2012-01-01

    At which height is a prominence inclined to be unstable, or where is the most probable critical height for the prominence destabilization? This question was statistically studied based on 362 solar limb prominences well recognized by Solar Limb Prominence Catcher and Tracker from 2007 April to the end of 2009. We found that there are about 71% disrupted prominences (DPs), among which about 42% of them did not erupt successfully and about 89% of them experienced a sudden destabilization process. After a comprehensive analysis of the DPs, we discovered the following: (1) Most DPs become unstable at a height of 0.06-0.14 R ☉ from the solar surface, and there are two most probable critical heights at which a prominence is very likely to become unstable, the first one is 0.13 R ☉ and the second one is 0.19 R ☉ . (2) An upper limit for the erupting velocity of eruptive prominences (EPs) exists, which decreases following a power law with increasing height and mass; accordingly, the kinetic energy of EPs has an upper limit too, which decreases as the critical height increases. (3) Stable prominences are generally longer and heavier than DPs, and not higher than 0.4 R ☉ . (4) About 62% of the EPs were associated with coronal mass ejections (CMEs); but there is no difference in apparent properties between EPs associated with CMEs and those that are not.

  14. Cell-Penetrating Ability of Peptide Hormones: Key Role of Glycosaminoglycans Clustering

    Directory of Open Access Journals (Sweden)

    Armelle Tchoumi Neree

    2015-11-01

    Full Text Available Over the last two decades, the potential usage of cell-penetrating peptides (CPPs for the intracellular delivery of various molecules has prompted the identification of novel peptidic identities. However, cytotoxic effects and unpredicted immunological responses have often limited the use of various CPP sequences in the clinic. To overcome these issues, the usage of endogenous peptides appears as an appropriate alternative approach. The hormone pituitary adenylate-cyclase-activating polypeptide (PACAP38 has been recently identified as a novel and very efficient CPP. This 38-residue polycationic peptide is a member of the secretin/glucagon/growth hormone-releasing hormone (GHRH superfamily, with which PACAP38 shares high structural and conformational homologies. In this study, we evaluated the cell-penetrating ability of cationic peptide hormones in the context of the expression of cell surface glycosaminoglycans (GAGs. Our results indicated that among all peptides evaluated, PACAP38 was unique for its potent efficiency of cellular uptake. Interestingly, the abilities of the peptides to reach the intracellular space did not correlate with their binding affinities to sulfated GAGs, but rather to their capacity to clustered heparin in vitro. This study demonstrates that the uptake efficiency of a given cationic CPP does not necessarily correlate with its affinity to sulfated GAGs and that its ability to cluster GAGs should be considered for the identification of novel peptidic sequences with potent cellular penetrating properties.

  15. STRUCTURE OF PROMINENCE LEGS: PLASMA AND MAGNETIC FIELD

    Energy Technology Data Exchange (ETDEWEB)

    Levens, P. J.; Labrosse, N. [SUPA School of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ (United Kingdom); Schmieder, B. [Observatoire de Paris, Meudon, F-92195 (France); Ariste, A. López, E-mail: p.levens.1@research.gla.ac.uk [Institut de Recherche en Astrophysique et Planétologie, Toulouse (France)

    2016-02-10

    We investigate the properties of a “solar tornado” observed on 2014 July 15, and aim to link the behavior of the plasma to the internal magnetic field structure of the associated prominence. We made multi-wavelength observations with high spatial resolution and high cadence using SDO/AIA, the Interface Region Imaging Spectrograph (IRIS) spectrograph, and the Hinode/Solar Optical Telescope (SOT) instrument. Along with spectropolarimetry provided by the Télescope Héliographique pour l’Etude du Magnétisme et des Instabilités Solaires telescope we have coverage of both optically thick emission lines and magnetic field information. AIA reveals that the two legs of the prominence are strongly absorbing structures which look like they are rotating, or oscillating in the plane of the sky. The two prominence legs, which are both very bright in Ca ii (SOT), are not visible in the IRIS Mg ii slit-jaw images. This is explained by the large optical thickness of the structures in Mg ii, which leads to reversed profiles, and hence to lower integrated intensities at these locations than in the surroundings. Using lines formed at temperatures lower than 1 MK, we measure relatively low Doppler shifts on the order of ±10 km s{sup −1} in the tornado-like structure. Between the two legs we see loops in Mg ii, with material flowing from one leg to the other, as well as counterstreaming. It is difficult to interpret our data as showing two rotating, vertical structures that are unrelated to the loops. This kind of “tornado” scenario does not fit with our observations. The magnetic field in the two legs of the prominence is found to be preferentially horizontal.

  16. Non-LTE hydrogen-line formation in moving prominences

    Science.gov (United States)

    Heinzel, P.; Rompolt, B.

    1986-01-01

    The behavior of hydrogen-line brightness variations, depending on the prominence-velocity changes were investigated. By solving the NON-Local thermodynamic equilibrium (LTE) problem for hydrogen researchers determine quantitatively the effect of Doppler brightening and/or Doppler dimming (DBE, DDE) in the lines of Lyman and Balmer series. It is demonstrated that in low-density prominence plasmas, DBE in H alpha and H beta lines can reach a factor of three for velocities around 160 km/sec, while the L alpha line exhibits typical DDE. L beta brightness variations follow from a combined DBE in the H alpha and DDE in L alpha and L beta itself, providing that all relevant multilevel interlocking processes are taken into account.

  17. PATTERNS OF FLOWS IN AN INTERMEDIATE PROMINENCE OBSERVED BY HINODE

    International Nuclear Information System (INIS)

    Ahn, Kwangsu; Chae, Jongchul; Cao Wenda; Goode, Philip R.

    2010-01-01

    The investigation of plasma flows in filaments/prominences gives us clues to understanding their magnetic structures. We studied the patterns of flows in an intermediate prominence observed by Hinode/SOT. By examining a time series of Hα images and Ca II H images, we have found horizontal flows in the spine and vertical flows in the barb. Both of these flows have a characteristic speed of 10-20 km s -1 . The horizontal flows displayed counterstreaming. Our detailed investigation revealed that most of the moving fragments in fact reversed direction at the end point of the spine near a footpoint close to the associated active region. These returning flows may be one possible explanation of the well-known counterstreaming flows in prominences. In contrast, we have found vertical flows-downward and upward-in the barb. Most of the horizontal flows in the spine seem to switch into vertical flows when they approach the barb, and vice versa. We propose that the net force resulting from a small deviation from magnetohydrostatic equilibrium, where magnetic fields are predominantly horizontal, may drive these patterns of flow. In the prominence studied here, the supposed magnetohydrostatic configuration is characterized by magnetic field lines sagging with angles of 13 0 and 39 0 in the spine and the barb, respectively.

  18. Extreme-ultraviolet limb spectra of a prominence observed from SKYLAB

    International Nuclear Information System (INIS)

    Mariska, J.T.; Doschek, G.A.; Feldman, U.

    1979-01-01

    Line profiles of extreme ultraviolet emission lines observed in a solar prominence at positions above the white-light limb with the NRL slit spectrograph on Skylab are discussed. Absolute line intensities and full widths at half-maximum are presented for lines formed over the temperature range approx.1 x 10 4 to 2.2 x 10 5 K. The volume emission measures calculated using resonance line intensities are greater than quiet-Sun emission measures at the same height above the limb and indicate a somewhat different distribution of material with temperature in the prominence compared to the quiet-Sun emission measure at +8''. Electron densities in the prominence determined using the calculated emission measures and the intensities of density-sensitive intersystem lines are between the quiet-Sun electron density and half the quiet-Sun electron density. Random mass-motion velocities calculated from the measured full widths at half-maximum show a range of velocities. For T/sub e/> or approx. =4 x 10 4 K, the nonthermal velocity decreases with increasing height in the prominence. For T/sub e/ 4 K, the calculated mass motions are near zero. From the He II 1640 A line profile we derive an average temperature of 27,000 K for the region in which He II is emitted

  19. EVIDENCE FOR ROTATIONAL MOTIONS IN THE FEET OF A QUIESCENT SOLAR PROMINENCE

    International Nuclear Information System (INIS)

    Orozco Suárez, D.; Asensio Ramos, A.; Trujillo Bueno, J.

    2012-01-01

    We present observational evidence of apparent plasma rotational motions in the feet of a solar prominence. Our study is based on spectroscopic observations taken in the He I 1083.0 nm multiplet with the Tenerife Infrared Polarimeter attached to the German Vacuum Tower Telescope. We recorded a time sequence of spectra with 34 s cadence placing the slit of the spectrograph almost parallel to the solar limb and crossing two feet of an intermediate size, quiescent hedgerow prominence. The data show opposite Doppler shifts, ±6 km s –1 , at the edges of the prominence feet. We argue that these shifts may be interpreted as prominence plasma rotating counterclockwise around the vertical axis to the solar surface as viewed from above. The evolution of the prominence seen in EUV images taken with the Solar Dynamics Observatory provided us with clues to interpret the results as swirling motions. Moreover, time-distance images taken far from the central wavelength show plasma structures moving parallel to the solar limb with velocities of about 10-15 km s –1 . Finally, the shapes of the observed intensity profiles suggest the presence of, at least, two components at some locations at the edges of the prominence feet. One of them is typically Doppler shifted (up to ∼20 km s –1 ) with respect to the other, thus suggesting the existence of supersonic counter-streaming flows along the line of sight.

  20. On Lyman-line asymmetries in quiescent prominences

    Czech Academy of Sciences Publication Activity Database

    Gunár, Stanislav; Heinzel, Petr; Anzer, U.; Schmieder, B.

    2008-01-01

    Roč. 490, č. 1 (2008), s. 307-313 ISSN 0004-6361 Grant - others:EU(XE) ESA-PECS project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : Sun prominences * radiative transfer * line profiles Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.153, year: 2008

  1. Topic Prominence in Chinese EFL Learners' Interlanguage

    Science.gov (United States)

    Li, Shaopeng; Yang, Lianrui

    2014-01-01

    The present study aims to investigate the general characteristics of topicprominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from a discourse perspective. Topic structures mainly appear in Chinese discourse in the form of topic chains (Wang, 2002; 2004). The…

  2. Clinico-Epidemiological Comparison of Delusion-Prominent and Hallucination-Prominent Clinical Subgroups of Paranoid Schizophrenia.

    Science.gov (United States)

    Kreinin, Anatoly; Krishtul, Vladimir; Kirsh, Zvi; Menuchin, Michael

    2015-01-01

    Though hallucinations and delusions are prominent basic impairments in schizophrenia, reports of the relationship between hallucinatory and delusional symptoms among schizophrenia patients are scant. To examine the epidemiological and clinical differences between mainly hallucinatory and mainly delusional subgroups of paranoid schizophrenia patients. One hundred schizophrenia patients, paranoid type, were recruited. In a cross-sectional study, participants were divided into Mainly Hallucinatory (H) and Mainly Delusional (D) subgroups. Demographic variables were compared and clinical characteristics were evaluated using the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression Scale. The Quality-of-Life Enjoyment and Satisfaction Questionnaire-18 was used to assess quality of life. Clinically, the H group was more heterogeneous as expressed by the broader range of scores that described the clinical picture of patients in that subgroup (in 43 of 78 variables, 55.13%) and similar ranges of scores (31 of 78 variables, 39.74%) for patients in the D group. Duration of hospitalization was significantly longer in group H than in group D (p=0.047). There was no statistically significant difference between the H and D subgroups in demographic characteristics. There are distinct epidemiological and clinical differences between the H and D subgroups, with more severe positive and negative symptoms and greater functional impairment in the H group. Paranoid schizophrenia patients with prominent hallucinations have poorer prognosis and need intensive therapeutic rehabilitation beginning with onset-of-illness. Further genetic studies and comparisons of fMRI and/or PET findings are warranted to investigate additional distinctive characteristics of these subgroups.

  3. The Development of Preschool Children's Musical Abilities through Specific Types of Musical Activities

    Science.gov (United States)

    Stolic, Jasmina

    2015-01-01

    The goal of the conducted research was to explore how much preschool teachers value certain types of musical activities, which positively influence the development of preschool children's musical abilities. The assumption in the research was that preschool teachers would choose musical games as the most prominent activity type in their educational…

  4. Quiescent Prominence Dynamics Observed with the Hinode Solar Optical Telescope. I. Turbulent Upflow Plumes

    Science.gov (United States)

    Berger, Thomas E.; Slater, Gregory; Hurlburt, Neal; Shine, Richard; Tarbell, Theodore; Title, Alan; Lites, Bruce W.; Okamoto, Takenori J.; Ichimoto, Kiyoshi; Katsukawa, Yukio; Magara, Tetsuya; Suematsu, Yoshinori; Shimizu, Toshifumi

    2010-06-01

    Hinode/Solar Optical Telescope (SOT) observations reveal two new dynamic modes in quiescent solar prominences: large-scale (20-50 Mm) "arches" or "bubbles" that "inflate" from below into prominences, and smaller-scale (2-6 Mm) dark turbulent upflows. These novel dynamics are related in that they are always dark in visible-light spectral bands, they rise through the bright prominence emission with approximately constant speeds, and the small-scale upflows are sometimes observed to emanate from the top of the larger bubbles. Here we present detailed kinematic measurements of the small-scale turbulent upflows seen in several prominences in the SOT database. The dark upflows typically initiate vertically from 5 to 10 Mm wide dark cavities between the bottom of the prominence and the top of the chromospheric spicule layer. Small perturbations on the order of 1 Mm or less in size grow on the upper boundaries of cavities to generate plumes up to 4-6 Mm across at their largest widths. All plumes develop highly turbulent profiles, including occasional Kelvin-Helmholtz vortex "roll-up" of the leading edge. The flows typically rise 10-15 Mm before decelerating to equilibrium. We measure the flowfield characteristics with a manual tracing method and with the Nonlinear Affine Velocity Estimator (NAVE) "optical flow" code to derive velocity, acceleration, lifetime, and height data for several representative plumes. Maximum initial speeds are in the range of 20-30 km s-1, which is supersonic for a ~10,000 K plasma. The plumes decelerate in the final few Mm of their trajectories resulting in mean ascent speeds of 13-17 km s-1. Typical lifetimes range from 300 to 1000 s (~5-15 minutes). The area growth rate of the plumes (observed as two-dimensional objects in the plane of the sky) is initially linear and ranges from 20,000 to 30,000 km2 s-1 reaching maximum projected areas from 2 to 15 Mm2. Maximum contrast of the dark flows relative to the bright prominence plasma in SOT images

  5. QUIESCENT PROMINENCE DYNAMICS OBSERVED WITH THE HINODE SOLAR OPTICAL TELESCOPE. I. TURBULENT UPFLOW PLUMES

    International Nuclear Information System (INIS)

    Berger, Thomas E.; Slater, Gregory; Hurlburt, Neal; Shine, Richard; Tarbell, Theodore; Title, Alan; Lites, Bruce W.; Okamoto, Takenori J.; Ichimoto, Kiyoshi; Katsukawa, Yukio; Magara, Tetsuya; Suematsu, Yoshinori; Shimizu, Toshifumi

    2010-01-01

    Hinode/Solar Optical Telescope (SOT) observations reveal two new dynamic modes in quiescent solar prominences: large-scale (20-50 Mm) 'arches' or 'bubbles' that 'inflate' from below into prominences, and smaller-scale (2-6 Mm) dark turbulent upflows. These novel dynamics are related in that they are always dark in visible-light spectral bands, they rise through the bright prominence emission with approximately constant speeds, and the small-scale upflows are sometimes observed to emanate from the top of the larger bubbles. Here we present detailed kinematic measurements of the small-scale turbulent upflows seen in several prominences in the SOT database. The dark upflows typically initiate vertically from 5 to 10 Mm wide dark cavities between the bottom of the prominence and the top of the chromospheric spicule layer. Small perturbations on the order of 1 Mm or less in size grow on the upper boundaries of cavities to generate plumes up to 4-6 Mm across at their largest widths. All plumes develop highly turbulent profiles, including occasional Kelvin-Helmholtz vortex 'roll-up' of the leading edge. The flows typically rise 10-15 Mm before decelerating to equilibrium. We measure the flowfield characteristics with a manual tracing method and with the Nonlinear Affine Velocity Estimator (NAVE) 'optical flow' code to derive velocity, acceleration, lifetime, and height data for several representative plumes. Maximum initial speeds are in the range of 20-30 km s -1 , which is supersonic for a ∼10,000 K plasma. The plumes decelerate in the final few Mm of their trajectories resulting in mean ascent speeds of 13-17 km s -1 . Typical lifetimes range from 300 to 1000 s (∼5-15 minutes). The area growth rate of the plumes (observed as two-dimensional objects in the plane of the sky) is initially linear and ranges from 20,000 to 30,000 km 2 s -1 reaching maximum projected areas from 2 to 15 Mm 2 . Maximum contrast of the dark flows relative to the bright prominence plasma in

  6. Prominence Bubble Shear Flows and the Coupled Kelvin-Helmholtz — Rayleigh-Taylor Instability

    Science.gov (United States)

    Berger, Thomas; Hillier, Andrew

    2017-08-01

    Prominence bubbles are large arched structures that rise from below into quiescent prominences, often growing to heights on the order of 10 Mm before going unstable and generating plume upflows. While there is general agreement that emerging flux below pre-existing prominences causes the structures, there is lack of agreement on the nature of the bubbles and the cause of the instability flows. One hypothesis is that the bubbles contain coronal temperature plasma and rise into the prominence above due to both magnetic and thermal buoyancy, eventually breaking down via a magnetic Rayleigh-Taylor (RT) instability to release hot plasma and magnetic flux and helicity into the overlying coronal flux rope. Another posits that the bubbles are actually just “arcades” in the prominence indicating a magnetic separator line between the bipole and the prominence fields with the observed upflows and downflows caused by reconnection along the separator. We analyze Hinode/SOT, SDO/AIA, and IRIS observations of prominence bubbles, focusing on characteristics of the bubble boundary layers that may discriminate between the two hypotheses. We find speeds on the order of 10 km/s in prominence plasma downflows and lateral shear flows along the bubble boundary. Inflows to the boundary gradually increase the thickness and brightness of the layer until plasma drains from there, apparently around the dome-like bubble domain. In one case, shear flow across the bubble boundary develops Kelvin-Helmholtz (KH) vortices that we use to infer flow speeds in the low-density bubble on the order of 100 km/sec. IRIS spectra indicate that plasma flows on the bubble boundary at transition region temperatures achieve Doppler speeds on the order of 50 km/s, consistent with this inference. Combined magnetic KH-RT instability analysis leads to flux density estimates of 10 G with a field angle of 30° to the prominence, consistent with vector magnetic field measurements. In contrast, we find no evidence

  7. Eruptive prominences and long-delay geomagnetic storms

    International Nuclear Information System (INIS)

    Wright, C.S.

    1983-01-01

    The relationship between disappearing solar fragments and geomagnetic disturbances was investigated. It is shown that long-delay storms are associated with filaments well removed from the disc centre, and particularly in the case of large filaments and prominences, the proportion of events that produce long-delay storms increases with angular distance from the centre

  8. EUV lines observed with EIS/Hinode in a solar prominence

    Science.gov (United States)

    Labrosse, N.; Schmieder, B.; Heinzel, P.; Watanabe, T.

    2011-07-01

    Context. During a multi-wavelength observation campaign with Hinode and ground-based instruments, a solar prominence was observed for three consecutive days as it crossed the western limb of the Sun in April 2007. Aims: We report on observations obtained on 26 April 2007 using EIS (Extreme ultraviolet Imaging Spectrometer) on Hinode. They are analysed to provide a qualitative diagnostic of the plasma in different parts of the prominence. Methods: After correcting for instrumental effects, the rasters at different wavelengths are presented. Several regions within the same prominence are identified for further analysis. Selected profiles for lines with formation temperatures between log (T) = 4.7 and log (T) = 6.3, as well as their integrated intensities, are given. The profiles of coronal, transition region, and He ii lines are discussed. We pay special attention to the He ii line, which is blended with coronal lines. Results: Some quantitative results are obtained by analysing the line profiles. They confirm that depression in EUV lines can be interpreted in terms of two mechanisms: absorption of coronal radiation by the hydrogen and neutral helium resonance continua, and emissivity blocking. We present estimates of the He ii line integrated intensity in different parts of the prominence according to different scenarios for the relative contribution of absorption and emissivity blocking to the coronal lines blended with the He ii line. We estimate the contribution of the He ii 256.32 Å line to the He ii raster image to vary between ~44% and 70% of the raster's total intensity in the prominence according to the different models used to take into account the blending coronal lines. The inferred integrated intensities of the He ii 256 Å line are consistent with the theoretical intensities obtained with previous 1D non-LTE radiative transfer calculations, yielding a preliminary estimate of the central temperature of 8700 K, a central pressure of 0.33 dyn cm-2, and a

  9. Observation of the Kelvin–Helmholtz Instability in a Solar Prominence

    Science.gov (United States)

    Yang, Heesu; Xu, Zhi; Lim, Eun-Kyung; Kim, Sujin; Cho, Kyung-Suk; Kim, Yeon-Han; Chae, Jongchul; Cho, Kyuhyoun; Ji, Kaifan

    2018-04-01

    Many solar prominences end their lives in eruptions or abrupt disappearances that are associated with dynamical or thermal instabilities. Such instabilities are important because they may be responsible for energy transport and conversion. We present a clear observation of a streaming kink-mode Kelvin–Helmholtz Instability (KHI) taking place in a solar prominence using the Hα Lyot filter installed at the New Vacuum Solar Telescope, Fuxian-lake Solar Observatory in Yunnan, China. On one side of the prominence, a series of plasma blobs floated up from the chromosphere and streamed parallel to the limb. The plasma stream was accelerated to about 20–60 km s‑1 and then undulated. We found that 2″- and 5″-size vortices formed, floated along the stream, and then broke up. After the 5″-size vortex, a plasma ejection out of the stream was detected in the Solar Dynamics Observatory/Atmospheric Imaging Assembly images. Just before the formation of the 5″-size vortex, the stream displayed an oscillatory transverse motion with a period of 255 s with the amplitude growing at the rate of 0.001 s‑1. We attribute this oscillation of the stream and the subsequent formation of the vortex to the KHI triggered by velocity shear between the stream, guided by the magnetic field and the surrounding media. The plasma ejection suggests the transport of prominence material into the upper layer by the KHI in its nonlinear stage.

  10. Boletus edulis ribonucleic acid - a potent apoptosis inducer in human colon adenocarcinoma cells.

    Science.gov (United States)

    Lemieszek, Marta Kinga; Ribeiro, Miguel; Guichard Alves, Helena; Marques, Guilhermina; Nunes, Fernando Milheiro; Rzeski, Wojciech

    2016-07-13

    Despite the large popularity of the Boletus edulis mushroom, little is known about its influence on human health and the possibilities of its therapeutic use. Nevertheless, several reports revealed the usefulness of biopolymers isolated from it in cancer treatment. Our previous studies have shown that B. edulis water soluble biopolymers are not toxic against normal colon epithelial cells (CCD841 CoTr) and at the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells (LS180) which was accompanied with cell cycle arrest in the G0/G1 phase. The purpose of the present study was to verify the proapoptotic properties of a selected fraction from B. edulis - BE3, as well as determine its chemical nature. The BE3 fraction was extracted with hot water and purified by anion-exchange chromatography. Further chemical examinations revealed that BE3 consists mainly of ribonucleic acid (59.1%). The ability of BE3 to induce programmed cell death was examined in human colon cancer cell lines LS180 and HT-29 by measuring caspase activation, DNA fragmentation and expression of BAX, BCL2, TP53 and CDKN1A genes. The sensitivity of colon cancer cells with silenced BAX, TP53 and CDKN1A expression to BE3 treatment was also evaluated. We have demonstrated for the first time that the BE3 fraction is a potent apoptosis inducer in human colon cancer cells. The revealed mechanism of apoptosis triggering was dependent on the presence of functional p53 and consequently was a little different in investigated cell lines. Our results indicated that BE3 stimulated proapoptotic genes BAX (LS180, HT-29), TP53 (LS180) and CDKN1A (HT-29) while at the same time silenced the expression of the key prosurvival gene BCL2 (LS180, HT-29). The obtained results indicate the high therapeutic potential of the BE3 fraction against colon cancer, yet it is necessary to further confirm fraction efficacy and safety in animal and clinical studies.

  11. Lines of MgI Detected in Solar Prominences

    Czech Academy of Sciences Publication Activity Database

    Heinzel, Petr; Kupryakov, Yu. A.; Schwartz, P.

    2016-01-01

    Roč. 40, č. 1 (2016), s. 87-91 ISSN 1845-8319. [Hvar Astrophysical Colloquium /14./. Hvar, 26.09.2016-30.09.2016] Institutional support: RVO:67985815 Keywords : prominences * limb-flare * MgI emession Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  12. Prominence and tornado dynamics observed with IRIS and THEMIS

    Science.gov (United States)

    Schmieder, Brigitte; Levens, Peter; Labrosse, Nicolas; Mein, Pierre; Lopez Ariste, Arturo; Zapior, Maciek

    2017-08-01

    Several prominences were observed during campaigns in September 2013 and July 2014 with the IRIS spectrometer and the vector magnetograph THEMIS (Tenerife). SDO/AIA and IRIS provided images and spectra of prominences and tornadoes corresponding to different physical conditions of the transition region between the cool plasma and the corona. The vector magnetic field was derived from THEMIS observations by using the He D3 depolarisation due to the magnetic field. The inversion code (PCA) takes into account the Hanle and Zeeman effects and allows us to compute the strength and the inclination of the magnetic field which is shown to be mostly horizontal in prominences as well as in tornadoes. Movies from SDO/AIA in 304 A and Hinode/SOT in Ca II show the highly dynamic nature of the fine structures. From spectra in Mg II and Si IV lines provided by IRIS and H-alpha observed by the Multi-channel Subtractive Double Pass (MSDP) spectrograph in the Meudon Solar Tower we derived the Doppler shifts of the fine structures and reconstructed the 3D structure of tornadoes. We conclude that the apparent rotation of AIA tornadoes is due to large-scale quasi-periodic oscillations of the plasma along more or less horizontal magnetic structures.

  13. PROPAGATING WAVES TRANSVERSE TO THE MAGNETIC FIELD IN A SOLAR PROMINENCE

    Energy Technology Data Exchange (ETDEWEB)

    Schmieder, B. [Observatoire de Paris, LESIA, UMR 8109 (CNRS), F-92195 Meudon (France); Kucera, T. A.; Knizhnik, K. [Code 671, NASA' s GSFC, Greenbelt, MD 20771 (United States); Luna, M. [Instituto de Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain); Lopez-Ariste, A. [THEMIS, CNRS-UPS853, E-38205 La Laguna (Spain); Toot, D. [Alfred University, Alfred, NY 14802 (United States)

    2013-11-10

    We report an unusual set of observations of waves in a large prominence pillar that consist of pulses propagating perpendicular to the prominence magnetic field. We observe a huge quiescent prominence with the Solar Dynamics Observatory Atmospheric Imaging Assembly in EUV on 2012 October 10 and only a part of it, the pillar, which is a foot or barb of the prominence, with the Hinode Solar Optical Telescope (SOT; in Ca II and Hα lines), Sac Peak (in Hα, Hβ, and Na-D lines), and THEMIS ({sup T}élescope Héliographique pour l' Etude du Magnétisme et des Instabilités Solaires{sup )} with the MTR (MulTi-Raies) spectropolarimeter (in He D{sub 3} line). The THEMIS/MTR data indicates that the magnetic field in the pillar is essentially horizontal and the observations in the optical domain show a large number of horizontally aligned features on a much smaller scale than the pillar as a whole. The data are consistent with a model of cool prominence plasma trapped in the dips of horizontal field lines. The SOT and Sac Peak data over the four hour observing period show vertical oscillations appearing as wave pulses. These pulses, which include a Doppler signature, move vertically, perpendicular to the field direction, along thin quasi-vertical columns in the much broader pillar. The pulses have a velocity of propagation of about 10 km s{sup –1}, a period of about 300 s, and a wavelength around 2000 km. We interpret these waves in terms of fast magnetosonic waves and discuss possible wave drivers.

  14. A twisted flux-tube model for solar prominences. I. General properties

    International Nuclear Information System (INIS)

    Priest, E.R.; Hood, A.W.; Anzer, U.

    1989-01-01

    It is proposed that a solar prominence consists of cool plasma supported in a large-scale curved and twisted magnetic flux tube. As long as the flux tube is untwisted, its curvature is concave toward the solar surface, and so it cannot support dense plasma against gravity. However, when it is twisted sufficiently, individual field lines may acquire a convex curvature near their summits and so provide support. Cool plasma then naturally tends to accumulate in such field line dips either by injection from below or by thermal condensation. As the tube is twisted up further or reconnection takes place below the prominence, one finds a transition from normal to inverse polarity. When the flux tube becomes too long or is twisted too much, it loses stability and its true magnetic geometry as an erupting prominence is revealed more clearly. 56 refs

  15. DYNAMICS OF A PROMINENCE-HORN STRUCTURE DURING ITS EVAPORATION IN THE SOLAR CORONA

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bing; Chen, Yao; Fu, Jie; Li, Bo [Shandong Provincial Key Laboratory of Optical Astronomy and Solar-Terrestrial Environment, and Institute of Space Sciences, Shandong University, Weihai 264209 (China); Li, Xing [Department of Physics, Aberystwyth University, Aberystwyth, Ceredigion, SY23 3BZ (United Kingdom); Liu, Wei, E-mail: yaochen@sdu.edu.cn [Stanford-Lockheed Institute for Space Research, Stanford University, Stanford, CA 94305 (United States)

    2016-08-20

    The physical connections among and formation mechanisms of various components of the prominence-horn cavity system remain elusive. Here we present observations of such a system, focusing on a section of the prominence that rises and separates gradually from the main body. This forms a configuration sufficiently simple to yield clues regarding the above issues. It is characterized by embedding horns, oscillations, and a gradual disappearance of the separated material. The prominence-horn structure exhibits a large-amplitude longitudinal oscillation with a period of ∼150 minutes and an amplitude of ∼30 Mm along the trajectory defined by the concave horn structure. The horns also experience a simultaneous transverse oscillation with a much smaller amplitude (∼3 Mm) and a shorter period (∼10–15 minutes), likely representative of a global mode of the large-scale magnetic structure. The gradual disappearance of the structure indicates that the horn, an observational manifestation of the field-aligned transition region separating the cool and dense prominence from the hot and tenuous corona, is formed due to the heating and diluting process of the central prominence mass; most previous studies suggested that it is the opposite process, i.e., the cooling and condensation of coronal plasmas, that formed the horn. This study also demonstrates how the prominence transports magnetic flux to the upper corona, a process essential for the gradual build-up of pre-eruption magnetic energy.

  16. A review of machines and devices to potentize homeopathic medicines.

    Science.gov (United States)

    Basu, Abhirup; Suresh, Akkihebbal Krishnamurthy; Kane, Shantaram Govind; Bellare, Jayesh Ramesh

    2017-11-01

    Potentization, consisting of serial dilution and succussion, is a key step in the manufacture of homeopathic medicines. Originally prescribed as a manual process, several attempts at mechanization have been published, patented and even commercialised in order to remove the human element and introduce reproducibility without drudgery. Various machines have been used over the years to prepare homeopathic medicines. Although these machines follow the same principles, i.e. energetically mixing the medicines and diluting them significantly, their mode of operation is different from each other. This review paper surveys the main methods of preparation of homeopathic medicines. The main machines discussed are: Boericke's potentizer, Tyler Kent's instrument, John Alphonse's machine and the fluxion potentizer, which were used in the past, as well as more recent potentizers like arm-and-weight instruments, the K-Tronic potentizer and Quinn's machine. We review the construction and operating principle of each of these machines, along with their advantages and limitations. A scheme for relative performance assessment of these machines is proposed based on the parameters mechanical efficiency, physico-chemical efficiency, turbulence generation, energy dissipation, and accuracy of dilution. Quinn's machine and the arm-and-weight potentizer perform well for generating turbulence due to high impaction forces, while John Alphonse's machine is much more accurate in diluting the homeopathic medicines at every step. Both the commercial potentizers, Quinn's machine and the K-Tronic potentizer, are completely automated and therefore reduce the manual labour and variation in succussive forces during each step, which may produce uniformity in physico-chemical changes within the resulting homeopathic medicines. Copyright © 2017. Published by Elsevier Ltd.

  17. ARE GIANT TORNADOES THE LEGS OF SOLAR PROMINENCES?

    Energy Technology Data Exchange (ETDEWEB)

    Wedemeyer, Sven; Scullion, Eamon; Rouppe van der Voort, Luc; Bosnjak, Antonija [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Antolin, Patrick, E-mail: sven.wedemeyer@astro.uio.no [Centre for Mathematical Plasma Astrophysics, Department of Mathematics, KU Leuven, Celestijnenlaan 200B, bus 2400, B-3001 Leuven (Belgium)

    2013-09-10

    Observations in the 171 A channel of the Atmospheric Imaging Assembly of the space-borne Solar Dynamics Observatory show tornado-like features in the atmosphere of the Sun. These giant tornadoes appear as dark, elongated, and apparently rotating structures in front of a brighter background. This phenomenon is thought to be produced by rotating magnetic field structures that extend throughout the atmosphere. We characterize giant tornadoes through a statistical analysis of properties such as spatial distribution, lifetimes, and sizes. A total number of 201 giant tornadoes are detected in a period of 25 days, suggesting that, on average, about 30 events are present across the whole Sun at a time close to solar maximum. Most tornadoes appear in groups and seem to form the legs of prominences, thus serving as plasma sources/sinks. Additional H{alpha} observations with the Swedish 1 m Solar Telescope imply that giant tornadoes rotate as a structure, although they clearly exhibit a thread-like structure. We observe tornado groups that grow prior to the eruption of the connected prominence. The rotation of the tornadoes may progressively twist the magnetic structure of the prominence until it becomes unstable and erupts. Finally, we investigate the potential relation of giant tornadoes to other phenomena, which may also be produced by rotating magnetic field structures. A comparison to cyclones, magnetic tornadoes, and spicules implies that such events are more abundant and short-lived the smaller they are. This comparison might help to construct a power law for the effective atmospheric heating contribution as a function of spatial scale.

  18. ARE GIANT TORNADOES THE LEGS OF SOLAR PROMINENCES?

    International Nuclear Information System (INIS)

    Wedemeyer, Sven; Scullion, Eamon; Rouppe van der Voort, Luc; Bosnjak, Antonija; Antolin, Patrick

    2013-01-01

    Observations in the 171 Å channel of the Atmospheric Imaging Assembly of the space-borne Solar Dynamics Observatory show tornado-like features in the atmosphere of the Sun. These giant tornadoes appear as dark, elongated, and apparently rotating structures in front of a brighter background. This phenomenon is thought to be produced by rotating magnetic field structures that extend throughout the atmosphere. We characterize giant tornadoes through a statistical analysis of properties such as spatial distribution, lifetimes, and sizes. A total number of 201 giant tornadoes are detected in a period of 25 days, suggesting that, on average, about 30 events are present across the whole Sun at a time close to solar maximum. Most tornadoes appear in groups and seem to form the legs of prominences, thus serving as plasma sources/sinks. Additional Hα observations with the Swedish 1 m Solar Telescope imply that giant tornadoes rotate as a structure, although they clearly exhibit a thread-like structure. We observe tornado groups that grow prior to the eruption of the connected prominence. The rotation of the tornadoes may progressively twist the magnetic structure of the prominence until it becomes unstable and erupts. Finally, we investigate the potential relation of giant tornadoes to other phenomena, which may also be produced by rotating magnetic field structures. A comparison to cyclones, magnetic tornadoes, and spicules implies that such events are more abundant and short-lived the smaller they are. This comparison might help to construct a power law for the effective atmospheric heating contribution as a function of spatial scale

  19. Morphology Of A Hot Prominence Cavity Observed with Hinode/XRT and SDO/AIA

    Science.gov (United States)

    Weber, Mark A.; Reeves, K. K.; Gibson, S. E.; Kucera, T. A.

    2012-01-01

    Prominence cavities appear as circularly shaped voids in coronal emission over polarity inversion lines where a prominence channel is straddling the solar limb. The presence of chromospheric material suspended at coronal altitudes is a common but not necessary feature within these cavities. These voids are observed to change shape as a prominence feature rotates around the limb. We use a morphological model projected in cross-sections to fit the cavity emission in Hinode/XRT passbands, and then apply temperature diagnostics to XRT and SDO/AIA data to investigate the thermal structure. We find significant evidence that the prominence cavity is hotter than the corona immediately outside the cavity boundary. This investigation follows upon "Thermal Properties of A Solar Coronal Cavity Observed with the X-ray Telescope on Hinode" by Reeves et al., 2012, ApJ, in press.

  20. Multi-Wavelength Eclipse Observations of a Quiescent Prominence

    Czech Academy of Sciences Publication Activity Database

    Jejčič, S.; Heinzel, Petr; Zapiór, M.; Druckmüller, M.; Gunár, Stanislav; Kotrč, Pavel

    2014-01-01

    Roč. 289, č. 7 (2014), s. 2487-2501 ISSN 0038-0938 R&D Projects: GA ČR GAP209/12/0906 Institutional support: RVO:67985815 Keywords : eclipse observations * prominences * quiescent Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.039, year: 2014

  1. Contribution of psychological, social, and mechanical work exposures to low work ability: a prospective study.

    Science.gov (United States)

    Emberland, Jan S; Knardahl, Stein

    2015-03-01

    To determine the contribution of specific psychological, social, and mechanical work exposures to the self-reported low level of work ability. Employees from 48 organizations were surveyed over a 2-year period (n = 3779). Changes in 16 work exposures and 3 work ability measures-the work ability index score, perceived current, and future work ability-were tested with Spearman rank correlations. Binary logistic regressions were run to determine contribution of work exposures to low work ability. Role conflict, human resource primacy, and positive challenge were the most consistent predictors of low work ability across test designs. Role clarity and fair leadership were less consistent but prominent predictors. Mechanical exposures were not predictive. To protect employee work ability, work place interventions would benefit from focusing on reducing role conflicts and on promoting positive challenges and human resource primacy.

  2. HELICAL MOTIONS OF FINE-STRUCTURE PROMINENCE THREADS OBSERVED BY HINODE AND IRIS

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, Takenori J. [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan); Liu, Wei [Bay Area Environmental Research Institute, 625 2nd Street, Suite 209, Petaluma, CA 94952 (United States); Tsuneta, Saku, E-mail: joten.okamoto@nao.ac.jp [ISAS/JAXA, Sagamihara, Kanagawa 252-5210 (Japan)

    2016-11-10

    Fine-structure dynamics in solar prominences holds critical clues to understanding their physical nature of significant space-weather implications. We report evidence of rotational motions of horizontal helical threads in two active-region prominences observed by the Hinode and/or Interface Region Imaging Spectrograph satellites at high resolution. In the first event, we found transverse motions of brightening threads at speeds up to 55 km s{sup -1} seen in the plane of the sky. Such motions appeared as sinusoidal space–time trajectories with a typical period of ∼390 s, which is consistent with plane-of-sky projections of rotational motions. Phase delays at different locations suggest the propagation of twists along the threads at phase speeds of 90–270 km s{sup -1}. At least 15 episodes of such motions occurred in two days, none associated with an eruption. For these episodes, the plane-of-sky speed is linearly correlated with the vertical travel distance, suggestive of a constant angular speed. In the second event, we found Doppler velocities of 30–40 km s{sup -1} in opposite directions in the top and bottom portions of the prominence, comparable to the plane-of-sky speed. The moving threads have about twice broader line widths than stationary threads. These observations, when taken together, provide strong evidence for rotations of helical prominence threads, which were likely driven by unwinding twists triggered by magnetic reconnection between twisted prominence magnetic fields and ambient coronal fields.

  3. Liking goes with liking: An intuitive congruence between preference and prominence.

    Science.gov (United States)

    Morvinski, Coby; Amir, On

    2018-03-26

    In a series of 8 experiments, we demonstrate the existence of a "labeling effect" wherein people intuitively relate preferred choices to prominently labeled cues (such as heads as opposed to tails in a coin toss) and vice versa. Importantly, the observed congruence is asymmetric-it does not manifest for nonprominent cues and nonpreferred choices. This is because the congruence is driven by a process of evaluative matching: prominent cues are liked, but nonprominent cues are neutral or at most slightly negative in contrast. When we test prominent, yet truly negatively labeled cues, we indeed find a matching with less liked products. We discuss the theoretical contributions to the study of preferences and decision making, as well as demonstrate the practical implications to researchers and practitioners by using this process to assess intuitive preferences and reduce the compromise effect. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. Topics and topic prominence in two sign languages

    NARCIS (Netherlands)

    Kimmelman, V.

    2015-01-01

    In this paper we describe topic marking in Russian Sign Language (RSL) and Sign Language of the Netherlands (NGT) and discuss whether these languages should be considered topic prominent. The formal markers of topics in RSL are sentence-initial position, a prosodic break following the topic, and

  5. Class of analytic solutions for the thermally balanced magnetostatic prominence sheet

    International Nuclear Information System (INIS)

    Low, B.C.; Wu, S.T.

    1981-01-01

    This is a theoretical study of the nonlinear interplay between magnetostatic equilibrium and energy balance in a Kippenhahn-Schlueter type prominence sheet. The basic effects are illustrated explicitly with an analytic model in which a radiative loss proportional to rho 2 T balances against wave heating proportional to rho, with thermal conduction confined along magnetic field lines, where rho and T denote the plasma density and temperature, respectively. The particular choices of heat sink and source enable us to integrate the governing equations exactly while they are of the basic mathematical forms to simulate radiative loss in an optically thin plasma which is heated by wave dissipation. The steady solutions exhibit three different basic behaviors, characterized by the total wave heating in the prominence sheet being more than, equal to, or less than the total radiative loss. It is the compaction of the plasma along the field lines under its own weight combined with the effects of energy transport that determines which of the three basic behaviors obtains in a particular situation. The implications of the steady solutions for the formation of prominences are discussed. The exact solutions presented do not support the conclusion of Milne, Priest, and Roberts that there is an upper bound on the plasma beta for an equilibrium of the Kippenhahn-Schlueter prominence

  6. Quiescent and Eruptive Prominences at Solar Minimum: A Statistical Study via an Automated Tracking System

    Science.gov (United States)

    Loboda, I. P.; Bogachev, S. A.

    2015-07-01

    We employ an automated detection algorithm to perform a global study of solar prominence characteristics. We process four months of TESIS observations in the He II 304Å line taken close to the solar minimum of 2008-2009 and mainly focus on quiescent and quiescent-eruptive prominences. We detect a total of 389 individual features ranging from 25×25 to 150×500 Mm2 in size and obtain distributions of many of their spatial characteristics, such as latitudinal position, height, size, and shape. To study their dynamics, we classify prominences as either stable or eruptive and calculate their average centroid velocities, which are found to rarely exceed 3 km/s. In addition, we give rough estimates of mass and gravitational energy for every detected prominence and use these values to estimate the total mass and gravitational energy of all simultaneously existing prominences (1012 - 1014 kg and 1029 - 1031 erg). Finally, we investigate the form of the gravitational energy spectrum of prominences and derive it to be a power-law of index -1.1 ± 0.2.

  7. Heating of an Erupting Prominence Associated with a Solar Coronal Mass Ejection on 2012 January 27

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin-Yi; Moon, Yong-Jae; Kim, Kap-Sung [Department of Astronomy and Space Science, Kyung Hee University, Yongin-si, Gyeonggi-do, 17104 (Korea, Republic of); Raymond, John C.; Reeves, Katharine K. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States)

    2017-07-20

    We investigate the heating of an erupting prominence and loops associated with a coronal mass ejection and X-class flare. The prominence is seen as absorption in EUV at the beginning of its eruption. Later, the prominence changes to emission, which indicates heating of the erupting plasma. We find the densities of the erupting prominence using the absorption properties of hydrogen and helium in different passbands. We estimate the temperatures and densities of the erupting prominence and loops seen as emission features using the differential emission measure method, which uses both EUV and X-ray observations from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory and the X-ray Telescope on board Hinode . We consider synthetic spectra using both photospheric and coronal abundances in these calculations. We verify the methods for the estimation of temperatures and densities for the erupting plasmas. Then, we estimate the thermal, kinetic, radiative loss, thermal conduction, and heating energies of the erupting prominence and loops. We find that the heating of the erupting prominence and loop occurs strongly at early times in the eruption. This event shows a writhing motion of the erupting prominence, which may indicate a hot flux rope heated by thermal energy release during magnetic reconnection.

  8. Observations of apparent superslow wave propagation in solar prominences

    Science.gov (United States)

    Raes, J. O.; Van Doorsselaere, T.; Baes, M.; Wright, A. N.

    2017-06-01

    Context. Phase mixing of standing continuum Alfvén waves and/or continuum slow waves in atmospheric magnetic structures such as coronal arcades can create the apparent effect of a wave propagating across the magnetic field. Aims: We observe a prominence with SDO/AIA on 2015 March 15 and find the presence of oscillatory motion. We aim to demonstrate that interpreting this motion as a magneto hydrodynamic (MHD) wave is faulty. We also connect the decrease of the apparent velocity over time with the phase mixing process, which depends on the curvature of the magnetic field lines. Methods: By measuring the displacement of the prominence at different heights to calculate the apparent velocity, we show that the propagation slows down over time, in accordance with the theoretical work of Kaneko et al. We also show that this propagation speed drops below what is to be expected for even slow MHD waves for those circumstances. We use a modified Kippenhahn-Schlüter prominence model to calculate the curvature of the magnetic field and fit our observations accordingly. Results: Measuring three of the apparent waves, we get apparent velocities of 14, 8, and 4 km s-1. Fitting a simple model for the magnetic field configuration, we obtain that the filament is located 103 Mm below the magnetic centre. We also obtain that the scale of the magnetic field strength in the vertical direction plays no role in the concept of apparent superslow waves and that the moment of excitation of the waves happened roughly one oscillation period before the end of the eruption that excited the oscillation. Conclusions: Some of the observed phase velocities are lower than expected for slow modes for the circumstances, showing that they rather fit with the concept of apparent superslow propagation. A fit with our magnetic field model allows for inferring the magnetic geometry of the prominence. The movie attached to Fig. 1 is available at http://www.aanda.org

  9. Potent heme-degrading action of antimony and antimony-containing parasiticidal agents.

    Science.gov (United States)

    Drummond, G S; Kappas, A

    1981-02-01

    The ability of antimony and antimony-containing parasiticidal agents to enhance the rate of heme degradation in liver and kidney was investigated. Trivalent antimony was shown to be an extremely potent inducer of heme oxygenase, the initial and rate-limiting enzyme in heme degradation, in both organs, whereas the pentavalent form was a weak inducer of this enzyme. The ability of antimony to induce heme oxygenase was dose-dependent, independent of the salt used, and not a result of a direct activation of the enzyme in vitro. Concomitant with heme oxygenase induction by antimony, microsomal heme and cytochrome P-450 contents decreased, the cyto-chrome P-450-dependent mixed function oxidase system was impaired, and delta-ami-nolevulinate synthase (ALAS), the rate-limiting enzyme of heme synthesis, underwent the sequential changes-initial inhibition followed by rebound induction-usually associated with the administration of transition elements such as cobalt. Antimony induction of heme oxygenase however, unlike the enzyme induction elicited by cobalt, was not prevented either by cysteine administered orally or as a cysteine metal complex, or by simultaneous zinc administration. Desferoxamine also did not block heme oxygenase induction by antimony, but this chelator did prevent the rebound increase in ALAS activity associated with antimony or cobalt treatment. Antimony-containing parasiticidal drugs were also potent inducers of heme oxygenase in liver and kidney. The heme degradative action of these drugs may be related in part to the jaundice commonly associated with the prolonged therapeutic use of these agents. The heme-oxygenase-inducing action of antimony-containing parasiticidal drugs is a newly defined biological property of these compounds. The relation between the parasiticidal and the heme-oxygenase-inducing actions of such drugs is unknown. However, certain parasites contain hemoproteins or require heme compounds during their life cycle. It may therefore be

  10. Synthetic differential emission measure curves of prominence fine structures. II. The SoHO/SUMER prominence of 8 June 2004

    Czech Academy of Sciences Publication Activity Database

    Gunár, Stanislav; Parenti, S.; Anzer, U.; Heinzel, Petr; Vial, J. C.

    2011-01-01

    Roč. 535, November (2011), A122/1-A122/11 ISSN 0004-6361 R&D Projects: GA ČR GP205/09/P554; GA ČR GA205/09/1705; GA ČR GAP209/10/1706 Institutional research plan: CEZ:AV0Z10030501 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.587, year: 2011

  11. LARGE-SCALE FLOWS IN PROMINENCE CAVITIES

    International Nuclear Information System (INIS)

    Schmit, D. J.; Gibson, S. E.; Tomczyk, S.; Reeves, K. K.; Sterling, Alphonse C.; Brooks, D. H.; Williams, D. R.; Tripathi, D.

    2009-01-01

    Regions of rarefied density often form cavities above quiescent prominences. We observed two different cavities with the Coronal Multichannel Polarimeter on 2005 April 21 and with Hinode/EIS on 2008 November 8. Inside both of these cavities, we find coherent velocity structures based on spectral Doppler shifts. These flows have speeds of 5-10 km s -1 , occur over length scales of tens of megameters, and persist for at least 1 hr. Flows in cavities are an example of the nonstatic nature of quiescent structures in the solar atmosphere.

  12. Prominent crista terminalis mimicking a right atrial mass: case report

    Directory of Open Access Journals (Sweden)

    Lange Peter

    2010-10-01

    Full Text Available Abstract The crista terminalis is a normal anatomical structure within the right atrium that is not normally visualised in the standard views obtained while performing a transthoracic echocardiogram. In this case report, transthoracic echocardiography suggested the presence of a right atrial mass in a patient with end stage renal disease. However, subsequent transesophageal echocardiography revealed that the right atrial mass was actually a thick muscular bridge in the right atrium consistent with a prominent crista terminalis. An understanding of the anatomy and the echocardiographic appearance of a prominent crista terminalis will minimize the misdiagnosis of this structure avoiding unnecessary expensive additional tests.

  13. ERRATUM: Propagating Waves Transverse to the Magnetic Field in a Solar Prominence

    Science.gov (United States)

    Schmieder, B.; Kucera, T. A.; Knizhnik, K.; Luna, M.; Lopez-Ariste, A.; Toot, D.

    2014-01-01

    We report an unusual set of observations of waves in a large prominence pillar that consist of pulses propagating perpendicular to the prominence magnetic field. We observe a huge quiescent prominence with the Solar Dynamics Observatory Atmospheric Imaging Assembly in EUV on 2012 October 10 and only a part of it, the pillar, which is a foot or barb of the prominence, with the Hinode Solar Optical Telescope (SOT; in Ca II and Halpha lines), Sac Peak (in Ha, Hß, and Na-D lines), and THEMIS ("Télescope Héliographique pour l' Etude du Magnétisme et des Instabilités Solaires") with the MTR (MulTi-Raies) spectropolarimeter (in He D3 line). The THEMIS/MTR data indicates that the magnetic field in the pillar is essentially horizontal and the observations in the optical domain show a large number of horizontally aligned features on a much smaller scale than the pillar as a whole. The data are consistent with a model of cool prominence plasma trapped in the dips of horizontal field lines. The SOT and Sac Peak data over the four hour observing period show vertical oscillations appearing as wave pulses. These pulses, which include a Doppler signature, move vertically, perpendicular to the field direction, along thin quasi-vertical columns in the much broader pillar. The pulses have a velocity of propagation of about 10 km/s, a period of about 300 s, and a wavelength around 2000 km. We interpret these waves in terms of fast magnetosonic waves and discuss possible wave drivers.

  14. The Fate of Cool Material in the Hot Corona: Solar Prominences and Coronal Rain

    Science.gov (United States)

    Liu, Wei; Antolin, Patrick; Sun, Xudong; Vial, Jean-Claude; Berger, Thomas

    2017-08-01

    As an important chain of the chromosphere-corona mass cycle, some of the million-degree hot coronal mass undergoes a radiative cooling instability and condenses into material at chromospheric or transition-region temperatures in two distinct forms - prominences and coronal rain (some of which eventually falls back to the chromosphere). A quiescent prominence usually consists of numerous long-lasting, filamentary downflow threads, while coronal rain consists of transient mass blobs falling at comparably higher speeds along well-defined paths. It remains puzzling why such material of similar temperatures exhibit contrasting morphologies and behaviors. We report recent SDO/AIA and IRIS observations that suggest different magnetic environments being responsible for such distinctions. Specifically, in a hybrid prominence-coronal rain complex structure, we found that the prominence material is formed and resides near magnetic null points that favor the radiative cooling process and provide possibly a high plasma-beta environment suitable for the existence of meandering prominence threads. As the cool material descends, it turns into coronal rain tied onto low-lying coronal loops in a likely low-beta environment. Such structures resemble to certain extent the so-called coronal spiders or cloud prominences, but the observations reported here provide critical new insights. We will discuss the broad physical implications of these observations for fundamental questions, such as coronal heating and beyond (e.g., in astrophysical and/or laboratory plasma environments).

  15. Whole genome microarray analysis of chicken embryo facial prominences

    Czech Academy of Sciences Publication Activity Database

    Buchtová, Marcela; Kuo, W. P.; Nimmagadda, S.; Benson, S. L.; Geetha-Loganathan, P.; Logan, C.; Au-Yeung, T.; Chiang, E.; Fu, K.; Richman, J. M.

    2010-01-01

    Roč. 239, - (2010), s. 574-591 ISSN 1058-8388 Institutional research plan: CEZ:AV0Z50450515 Keywords : pharyngeal arch * mandibular arch * maxillary prominence Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.864, year: 2010

  16. The Most Prominent Roles of an ESP Teacher

    Science.gov (United States)

    Ghafournia, Narjes; Sabet, Shokoofeh Ahmadian

    2014-01-01

    One prominent feature of many ESP (English for Specific Purposes) courses, which make them rather different from EGP (English for General Purposes) courses, is the presence of adult learners, who are primary workers and secondary learners. As ESP is a highly learner-cantered approach, paying close attention to the multidimensional needs of…

  17. Further Validation of the Coach Identity Prominence Scale

    Science.gov (United States)

    Pope, J. Paige; Hall, Craig R.

    2014-01-01

    This study was designed to examine select psychometric properties of the Coach Identity Prominence Scale (CIPS), including the reliability, factorial validity, convergent validity, discriminant validity, and predictive validity. Coaches (N = 338) who averaged 37 (SD = 12.27) years of age, had a mean of 13 (SD = 9.90) years of coaching experience,…

  18. SOLAR LIMB PROMINENCE CATCHER AND TRACKER (SLIPCAT): AN AUTOMATED SYSTEM AND ITS PRELIMINARY STATISTICAL RESULTS

    International Nuclear Information System (INIS)

    Wang Yuming; Cao Hao; Chen Junhong; Zhang Tengfei; Yu Sijie; Zheng Huinan; Shen Chenglong; Wang, S.; Zhang Jie

    2010-01-01

    In this paper, we present an automated system, which has the capability to catch and track solar limb prominences based on observations from the extreme-ultraviolet (EUV) 304 A passband. The characteristic parameters and their evolution, including height, position angle, area, length, and brightness, are obtained without manual interventions. By applying the system to the STEREO-B/SECCHI/EUVI 304 A data during 2007 April-2009 October, we obtain a total of 9477 well-tracked prominences and a catalog of these events available online. A detailed analysis of these prominences suggests that the system has a rather good performance. We have obtained several interesting statistical results based on the catalog. Most prominences appear below the latitude of 60 0 and at the height of about 26 Mm above the solar surface. Most of them are quite stable during the period they are tracked. Nevertheless, some prominences have an upward speed of more than 100 km s -1 , and some others show significant downward and/or azimuthal speeds. There are strong correlations among the brightness, area, and height. The expansion of a prominence is probably one major cause of its fading during the rising or erupting process.

  19. Hydrogen line formation in the quescent prominences

    International Nuclear Information System (INIS)

    Tsovookhuu, Ch.

    1980-01-01

    Equations of transfer and statistical equilibrium for hydronen atom with eight bound levels and continuum are solved simultaneously. A plane-parallel layer located perpendicular to the Sun surface is taken as a geometrical model. Input parameters of the physical model are optical thickness in the center of Hsub(α) line, electron temperature and concentration in the layer center are well as temperature and density gradients. Functions of sources, line profiles, total energies and the Balmer decrements, which are compared with observations and theoretical calculations made by other authors, have been calculated. The comparison shows that the results are quite acceptable and can be used when analyzing the spectrum and determining physical parameters of solar prominences. Dependence of different performances of the line (equivalent width, central intensity, halfwidth, depth of central depression etc.) on values of initial model parameters is investigated. Line halfwidth is more sensitive to the temperatuu value in the layer center, while central intensity - to the value of temperature gradient and a depth of central depression - to electron concentration. Calculated were shares of primary sources responsible for different excitation mechanism depending on total optical thickness as well as mean probabilities of quantum yield out of a medium which can be used during parametric accountancy of radiation diffusion in solar prominences [ru

  20. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors.

    Science.gov (United States)

    Zhong, Min; Bui, Minna; Shen, Wang; Baskaran, Subramanian; Allen, Darin A; Elling, Robert A; Flanagan, W Michael; Fung, Amy D; Hanan, Emily J; Harris, Shannon O; Heumann, Stacey A; Hoch, Ute; Ivy, Sheryl N; Jacobs, Jeffrey W; Lam, Stuart; Lee, Heman; McDowell, Robert S; Oslob, Johan D; Purkey, Hans E; Romanowski, Michael J; Silverman, Jeffrey A; Tangonan, Bradley T; Taverna, Pietro; Yang, Wenjin; Yoburn, Josh C; Yu, Chul H; Zimmerman, Kristin M; O'Brien, Tom; Lew, Willard

    2009-09-01

    This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.

  1. SYNTHETIC HYDROGEN SPECTRA OF OSCILLATING PROMINENCE SLABS IMMERSED IN THE SOLAR CORONA

    International Nuclear Information System (INIS)

    Zapiór, M.; Heinzel, P.; Oliver, R.; Ballester, J. L.

    2016-01-01

    We study the behavior of H α and H β spectral lines and their spectral indicators in an oscillating solar prominence slab surrounded by the solar corona, using an MHD model combined with a 1D radiative transfer code taken in the line of sight perpendicular to the slab. We calculate the time variation of the Doppler shift, half-width, and maximum intensity of the H α and H β spectral lines for different modes of oscillation. We find a non-sinusoidal time dependence of some spectral parameters with time. Because H α and H β spectral indicators have different behavior for different modes, caused by differing optical depths of formation and different plasma parameter variations in time and along the slab, they may be used for prominence seismology, especially to derive the internal velocity field in prominences.

  2. SYNTHETIC HYDROGEN SPECTRA OF OSCILLATING PROMINENCE SLABS IMMERSED IN THE SOLAR CORONA

    Energy Technology Data Exchange (ETDEWEB)

    Zapiór, M.; Heinzel, P. [Astronomical Institute, The Czech Academy of Sciences, 25165 Ondřejov, The Czech Republic (Czech Republic); Oliver, R.; Ballester, J. L. [Universitat de les Illes Balears. Cra. de Valldemossa, km 7.5. Palma (Illes Balears), E-07122 (Spain)

    2016-08-20

    We study the behavior of H α and H β spectral lines and their spectral indicators in an oscillating solar prominence slab surrounded by the solar corona, using an MHD model combined with a 1D radiative transfer code taken in the line of sight perpendicular to the slab. We calculate the time variation of the Doppler shift, half-width, and maximum intensity of the H α and H β spectral lines for different modes of oscillation. We find a non-sinusoidal time dependence of some spectral parameters with time. Because H α and H β spectral indicators have different behavior for different modes, caused by differing optical depths of formation and different plasma parameter variations in time and along the slab, they may be used for prominence seismology, especially to derive the internal velocity field in prominences.

  3. Prominent extraaxial CSF space on cranial ultrasound in infants: correlation with neurodevelopmental outcome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bo Kyung; Lee, Mun Hyang; Yoon, Hye Kyung; Jung, Kyung Jae; Park, Won Soon; Chang, Yun Sil; Kim, Chan Gyo [Sungkyunkwan Univ. School of Medicine, Seoul (Korea, Republic of)

    1999-08-01

    To determine the clinical significance of prominent extra-axial CSF space (EACSFS) in infants, as seen on cranial ultrasound. Between March 1996 and November 1997, all infants who had undergone head ultrasound at our institution and were found to have prominent EACSFS were evaluated. The width of the interhemispheric fissure was measured at three locations at the level of the frontal horn, body and atrium of the lateral ventricles. The depth of the CSF space over the convexity was also measured. The average of these measurements was calculated and each patient was assigned to one of three groups: mild, moderate, or marked. Ultrasound findings were evaluated for other associated abnormalities. Clinical neurodevelopment was evaluated by a pediatric neurologist, and ultrasound and neurodevelopmental findings were correlated. Prominent EACSFS was found in 153 patients, and neurodevelopmental evaluation up to a corrected age of 9 months was available in 133. One hundred and eight of 117 infants with normal neurodevelopment had no other associated abnormality(n=81), or abnormality associated only with grade I subependymal hemorrhage or cyst(n=27). Twelve of 16 infants with an abnormal neurodevelopmental outcome had major abnormalities including PVL, grade IV hemorrhage, and marked ventriculomegaly. Prominent EACSFS alone does not appear to be clinically significant. An abnormal neurodevelopmental outcome is associated with major abnormalities seen on ultrasound. Follow-up examination for prominent EACSFS is not indicated unless the associated abnormality requires further evaluations.

  4. Prominent extraaxial CSF space on cranial ultrasound in infants: correlation with neurodevelopmental outcome

    International Nuclear Information System (INIS)

    Kim, Bo Kyung; Lee, Mun Hyang; Yoon, Hye Kyung; Jung, Kyung Jae; Park, Won Soon; Chang, Yun Sil; Kim, Chan Gyo

    1999-01-01

    To determine the clinical significance of prominent extra-axial CSF space (EACSFS) in infants, as seen on cranial ultrasound. Between March 1996 and November 1997, all infants who had undergone head ultrasound at our institution and were found to have prominent EACSFS were evaluated. The width of the interhemispheric fissure was measured at three locations at the level of the frontal horn, body and atrium of the lateral ventricles. The depth of the CSF space over the convexity was also measured. The average of these measurements was calculated and each patient was assigned to one of three groups: mild, moderate, or marked. Ultrasound findings were evaluated for other associated abnormalities. Clinical neurodevelopment was evaluated by a pediatric neurologist, and ultrasound and neurodevelopmental findings were correlated. Prominent EACSFS was found in 153 patients, and neurodevelopmental evaluation up to a corrected age of 9 months was available in 133. One hundred and eight of 117 infants with normal neurodevelopment had no other associated abnormality(n=81), or abnormality associated only with grade I subependymal hemorrhage or cyst(n=27). Twelve of 16 infants with an abnormal neurodevelopmental outcome had major abnormalities including PVL, grade IV hemorrhage, and marked ventriculomegaly. Prominent EACSFS alone does not appear to be clinically significant. An abnormal neurodevelopmental outcome is associated with major abnormalities seen on ultrasound. Follow-up examination for prominent EACSFS is not indicated unless the associated abnormality requires further evaluations

  5. Solar Prominences Embedded in Flux Ropes: Morphological Features and Dynamics from 3D MHD Simulations

    Science.gov (United States)

    Terradas, J.; Soler, R.; Luna, M.; Oliver, R.; Ballester, J. L.; Wright, A. N.

    2016-04-01

    The temporal evolution of a solar prominence inserted in a three-dimensional magnetic flux rope is investigated numerically. Using the model of Titov & Démoulin under the regime of weak twist, the cold and dense prominence counteracts gravity by modifying the initially force-free magnetic configuration. In some cases a quasi-stationary situation is achieved after the relaxation phase, characterized by the excitation of standing vertical oscillations. These oscillations show a strong attenuation with time produced by the mechanism of continuum damping due to the inhomogeneous transition between the prominence and solar corona. The characteristic period of the vertical oscillations does not depend strongly on the twist of the flux rope. Nonlinearity is responsible for triggering the Kelvin-Helmholtz instability associated with the vertical oscillations and that eventually produces horizontal structures. Contrary to other configurations in which the longitudinal axis of the prominence is permeated by a perpendicular magnetic field, like in unsheared arcades, the orientation of the prominence along the flux rope axis prevents the development of Rayleigh-Taylor instabilities and therefore the appearance of vertical structuring along this axis.

  6. Synthesis and SAR studies of potent imidazopyridine anticoccidial agents.

    Science.gov (United States)

    Liang, Gui-Bai; Qian, Xiaoxia; Feng, Dennis; Fisher, Michael; Brown, Christine M; Gurnett, Anne; Leavitt, Penny Sue; Liberator, Paul A; Misura, Andrew S; Tamas, Tamas; Schmatz, Dennis M; Wyvratt, Matthew; Biftu, Tesfaye

    2007-07-01

    Diaryl imidazo[1,2-a]pyridine derivatives, such as 6a and 7i, have been synthesized and found to be potent inhibitors of parasite PKG activity. The most potent compounds are the 7-isopropylaminomethyl analog 6a and 2-isopropylamino analog 7i. These compounds are also fully active in in vivo assay as anticoccidial agents at 25 ppm in feed.

  7. Prominence modelling: from observed emission measures to temperature profiles

    Czech Academy of Sciences Publication Activity Database

    Anzer, U.; Heinzel, Petr

    2008-01-01

    Roč. 480, č. 2 (2008), s. 537-542 ISSN 0004-6361 Grant - others:EU(XE) ESA-PECS Project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : Sun * prominences * transition region Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.153, year: 2008

  8. Word-level prominence in Persian: An Experimental Study.

    Science.gov (United States)

    Sadeghi, Vahid

    2017-12-01

    Previous literature on the phonetics of stress in Persian has reported that fundamental frequency is the only reliable acoustic correlate of stress, and that stressed and unstressed syllables are not differentiated from each other in the absence of accentuation. In this study, the effects of lexical stress on duration, overall intensity and spectral tilt were examined in Persian both in the accented and unaccented conditions. Results showed that syllable duration is consistently affected by stress in Persian in both the accented and unaccented conditions across all vowel types. Unlike duration, the results for overall intensity and spectral tilt were significant only in the accented condition, suggesting that measures of intensity are not a correlate of stress in Persian but they are mainly caused by the presence of a pitch movement. The findings are phonologically interpreted as suggesting that word-level prominence in Persian is typologically similar to 'stress accent' languages, in which multiple phonetic cues are used to signal the prominence contrast in the accented condition, and stressed and unstressed syllables are different from each other even when the word is not pitch-accented.

  9. Amnion: a potent graft source for cell therapy in stroke.

    Science.gov (United States)

    Yu, Seong Jin; Soncini, Maddalena; Kaneko, Yuji; Hess, David C; Parolini, Ornella; Borlongan, Cesar V

    2009-01-01

    Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.

  10. Tic Tac TOE: Effects of Predictability and Importance on Acoustic Prominence in Language Production

    Science.gov (United States)

    Watson, Duane G.; Arnold, Jennifer E.; Tanenhaus, Michael K.

    2008-01-01

    Importance and predictability each have been argued to contribute to acoustic prominence. To investigate whether these factors are independent or two aspects of the same phenomenon, naive participants played a verbal variant of Tic Tac Toe. Both importance and predictability contributed independently to the acoustic prominence of a word, but in…

  11. Electron densities in quiescent prominences derived from eclipse observations

    Czech Academy of Sciences Publication Activity Database

    Jejčič, S.; Heinzel, Petr

    2009-01-01

    Roč. 254, č. 1 (2009), s. 89-100 ISSN 0038-0938 Grant - others:EU(XE) ESA-PECS project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : prominences quiescent * eclipse observations * visible spectrum Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 3.628, year: 2009

  12. SOLAR PROMINENCES EMBEDDED IN FLUX ROPES: MORPHOLOGICAL FEATURES AND DYNAMICS FROM 3D MHD SIMULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Terradas, J.; Soler, R.; Oliver, R.; Ballester, J. L. [Departament de Física, Universitat de les Illes Balears, E-07122 Palma de Mallorca (Spain); Luna, M. [Instituto de Astrofsíca de Canarias, E-38205 La Laguna, Tenerife (Spain); Wright, A. N., E-mail: jaume.terradas@uib.es [School of Mathematics and Statistics, University of St Andrews, St Andrews, KY16 9SS (United Kingdom)

    2016-04-01

    The temporal evolution of a solar prominence inserted in a three-dimensional magnetic flux rope is investigated numerically. Using the model of Titov and Démoulin under the regime of weak twist, the cold and dense prominence counteracts gravity by modifying the initially force-free magnetic configuration. In some cases a quasi-stationary situation is achieved after the relaxation phase, characterized by the excitation of standing vertical oscillations. These oscillations show a strong attenuation with time produced by the mechanism of continuum damping due to the inhomogeneous transition between the prominence and solar corona. The characteristic period of the vertical oscillations does not depend strongly on the twist of the flux rope. Nonlinearity is responsible for triggering the Kelvin–Helmholtz instability associated with the vertical oscillations and that eventually produces horizontal structures. Contrary to other configurations in which the longitudinal axis of the prominence is permeated by a perpendicular magnetic field, like in unsheared arcades, the orientation of the prominence along the flux rope axis prevents the development of Rayleigh–Taylor instabilities and therefore the appearance of vertical structuring along this axis.

  13. Veridical mapping in savant abilities, absolute pitch, and synesthesia: An autism case study

    Directory of Open Access Journals (Sweden)

    Lucie eBouvet

    2014-02-01

    Full Text Available An enhanced role and autonomy of perception are prominent in autism. Furthermore, savant abilities, absolute pitch, and synesthesia are all more commonly found in autistic individuals than in the typical population. The mechanism of veridical mapping has been proposed to account for how enhanced perception in autism leads to the high prevalence of these three phenomena and their structural similarity. Veridical mapping entails functional rededication of perceptual brain regions to higher order cognitive operations, allowing the enhanced detection and memorization of isomorphisms between perceptual and non-perceptual structures across multiple scales. In this paper, we present FC, an autistic individual who possesses several savant abilities in addition to both absolute pitch and synesthesia-like associations. The co-occurrence in FC of abilities, some of them rare, which share the same structure, as well as FC’s own accounts of their development, together suggest the importance of veridical mapping in the atypical range and nature of abilities displayed by autistic people.

  14. Magnetic field re-arrangement after prominence eruption

    International Nuclear Information System (INIS)

    Kopp, R.A.; Poletto, G.

    1986-01-01

    It has long been known that magnetic reconnection plays a fundamental role in a variety of solar events. Although mainly invoked in flare problems, large-scale loops interconnecting active regions, evolving coronal hole boundaries, the solar magnetic cycle itself, provide different evidence of phenomena which involve magnetic reconnection. A further example might be given by the magnetic field rearrangement which occurs after the eruption of a prominence. Since most often a prominence reforms after its disappearance and may be observed at about the same position it occupied before erupting, the magnetic field has to undergo a temporary disruption to relax back, via reconnection, to a configuration similar to the previous one. The above sequence of events is best observable in the case of two-ribbon (2-R) flares but most probably is associated with all filament eruptions. Even if the explanation of the magnetic field rearrangement after 2-R flares in terms of reconnection is generally accepted, the lack of a three-dimensional model capable of describing the field reconfiguration, has prevented, up to now, a thorough analysis of its topology as traced by Hα/x-ray loops. The purpose of the present work is to present a numerical technique which enables one to predict and visualize the reconnected configuration, at any time t, and therefore allows one to make a significant comparison of observations and model predictions throughout the whole process. 5 refs., 3 figs

  15. Highly Potent Antibacterial Organometallic Peptide Conjugates

    NARCIS (Netherlands)

    Albada, Bauke; Metzler-Nolte, Nils

    2017-01-01

    ConspectusResistance of pathogenic bacteria against currently marketed antibiotics is again increasing. To meet the societal need for effective cures, scientists are faced with the challenge of developing more potent but equally bacteria-specific drugs. Currently, most efforts are directed toward

  16. Aminopurvalanol A, a Potent, Selective, and Cell Permeable Inhibitor of Cyclins/Cdk Complexes, Causes the Reduction of in Vitro Fertilizing Ability of Boar Spermatozoa, by Negatively Affecting the Capacitation-Dependent Actin Polymerization

    Directory of Open Access Journals (Sweden)

    Nicola Bernabò

    2017-12-01

    Full Text Available The adoption of high-througput technologies demonstrated that in mature spermatozoa are present proteins that are thought to be not present or active in sperm cells, such as those involved in control of cell cycle. Here, by using an in silico approach based on the application of networks theory, we found that Cyclins/Cdk complexes could play a central role in signal transduction active during capacitation. Then, we tested this hypothesis in the vitro model. With this approach, spermatozoa were incubated under capacitating conditions in control conditions (CTRL or in the presence of Aminopurvalanol A a potent, selective and cell permeable inhibitor of Cyclins/Cdk complexes at different concentrations (2, 10, and 20 μM. We found that this treatment caused dose-dependent inhibition of sperm fertilizing ability. We attribute this event to the loss of acrosome integrity due to the inhibition of physiological capacitation-dependent actin polymerization, rather than to a detrimental effect on membrane lipid remodeling or on other signaling pathways such as tubulin reorganization or MAPKs activation. In our opinion, these data could revamp the knowledge on biochemistry of sperm capacitation and could suggest new perspectives in studying male infertility.

  17. Vaginal orgasm is more prevalent among women with a prominent tubercle of the upper lip.

    Science.gov (United States)

    Brody, Stuart; Costa, Rui Miguel

    2011-10-01

    Recent studies have uncovered multiple markers of vaginal orgasm history (unblocked pelvic movement during walking, less use of immature psychological defense mechanisms, greater urethrovaginal space). Other markers (perhaps of prenatal origin) even without obvious mechanistic roles in vaginal orgasm might exist, and a clinical observation led to the novel hypothesis that a prominent tubercle of the upper lip is such a marker. To examine the hypothesis that a prominent tubercle of the upper lip is associated specifically with greater likelihood of experiencing vaginal orgasm (orgasm elicited by penile-vaginal intercourse [PVI] without concurrent masturbation). Women (N = 258, predominantly Scottish) completed an online survey reporting their frequencies of various sexual activities and corresponding orgasms, age, and the prominence of the tubercle of their upper lip. Social desirability response bias was also assessed. Multivariate associations of lip tubercle prominence with vaginal orgasm (ever and past month consistency) and with orgasm by other means. RESULTS.: A prominent and sharply raised lip tubercle was associated with greater odds (odds ratio = 12.3) of ever having a vaginal orgasm, and also with greater past month vaginal orgasm consistency (an effect driven by the women who never had a vaginal orgasm), than less prominent lip tubercle categories. Lip tubercle was not associated with social desirability responding, or with orgasm triggered by masturbation during PVI, solitary or partner clitoral or vaginal masturbation, vibrator, or cunnilingus. The results are discussed in light of the unique nature of vaginal orgasm and the possibility of prenatal developmental influences. © 2011 International Society for Sexual Medicine.

  18. Prominent cerebral veins on susceptibility-weighted imaging (SWI) in pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Oeztoprak, Bilge [Cumhuriyet University School of Medicine, Department of Radiology, Sivas (Turkey)

    2017-07-15

    Clinical applications of susceptibility-weighted imaging (SWI) are increasing steadily. The aim of this study is to investigate the appearance of cerebral veins on SWI, which is very sensitive to the deoxyhaemoglobin level in vessels, in pulmonary embolism (PE). The cranial SWI images of 19 patients with PE and 22 controls from September 2013 through March 2016 were retrospectively examined for the presence of prominent cerebral veins. MRI findings were correlated with blood oxygen levels. 12 of 19 patients with PE had hypoxemia and SWI images of 11 of these hypoxemic patients depicted prominent cerebral veins in the form of increased number, diameter, and elongation. The mean PaO{sub 2} and SaO{sub 2} in these patients were 48.5 ± 9.1 mmHg and 75.2 ± 8.0 %, respectively. There was a significant correlation between the presence of prominent veins on SWI and hypoxemia (p < 0.05). Of the 7 patients with normal blood oxygen pressure and saturation, 1 also showed an augmented appearance of cerebral veins on SWI. In the presence of neurological symptoms suggestive of an intracranial pathology in patients with PE, a SWI added to the conventional MRI sequences may predict hypoxemia and exclude other intracranial pathologies. (orig.)

  19. Looking Like a Leader–Facial Shape Predicts Perceived Height and Leadership Ability

    Science.gov (United States)

    Re, Daniel E.; Hunter, David W.; Coetzee, Vinet; Tiddeman, Bernard P.; Xiao, Dengke; DeBruine, Lisa M.; Jones, Benedict C.; Perrett, David I.

    2013-01-01

    Judgments of leadership ability from face images predict the outcomes of actual political elections and are correlated with leadership success in the corporate world. The specific facial cues that people use to judge leadership remain unclear, however. Physical height is also associated with political and organizational success, raising the possibility that facial cues of height contribute to leadership perceptions. Consequently, we assessed whether cues to height exist in the face and, if so, whether they are associated with perception of leadership ability. We found that facial cues to perceived height had a strong relationship with perceived leadership ability. Furthermore, when allowed to manually manipulate faces, participants increased facial cues associated with perceived height in order to maximize leadership perception. A morphometric analysis of face shape revealed that structural facial masculinity was not responsible for the relationship between perceived height and perceived leadership ability. Given the prominence of facial appearance in making social judgments, facial cues to perceived height may have a significant influence on leadership selection. PMID:24324651

  20. Perceptions of Social Responsibility of Prominent Animal Welfare Groups.

    Science.gov (United States)

    Widmar, Nicole J Olynk; Morgan, Carissa J; Croney, Candace C

    2018-01-01

    Nonhuman animal welfare is an increasingly important component of consumer expectations of corporate social responsibility (CSR). The extent to which prominent animal welfare or protection organizations may influence people's perceptions of food industry CSR may be related to an organization's perceived social responsibility. Data from an online survey of 300 U.S. residents were used to explore relationships between demographics/lifestyle choices and perceptions of prominent animal welfare organizations (using best-worst scaling methodology). Overall, the American Society for the Prevention of Cruelty to Animals was perceived to be the most socially responsible organization analyzed, followed by the Humane Society of the United States and the American Humane Association (AHA). Results suggest that the perceived social responsibility of animal protection organizations in this study was not strongly linked to personally (financially) supporting them, with 2 exceptions: the perceptions of People for the Ethical Treatment of Animals and AHA. Improved understanding of the perception of animal welfare or protection organizations can inform decision making by organizations interested in furthering animal welfare causes.

  1. The EU and Climate Change Policy: Law, Politics and Prominence at Different Levels

    Directory of Open Access Journals (Sweden)

    Chad David Damro

    2008-11-01

    Full Text Available The European Union (EU is a prominent player in the politics of climate change, operating as an authoritative regional actor that influences policy-making at the national and international levels. The EU’s climate change policies are thus subjected to multiple pressures that arise from the domestic politics of its twenty-seven individual member states and the international politics of non-EU states with which it negotiates. Facing these multiple pressures, how and why could such a non-traditional actor develop into a prominent player at different levels of climate change policy-making? This article argues that the EU’s rise to prominence can be understood by tracking a number of historical-legal institutional developments at the domestic and international levels. The article also provides a preliminary investigation of the EU emissions trading scheme, a new institutional mechanism that illustrates the policy pressures arising from different levels.

  2. A-C Estrogens as Potent and Selective Estrogen Receptor-Beta Agonists (SERBAs) to Enhance Memory Consolidation under Low-Estrogen Conditions.

    Science.gov (United States)

    Hanson, Alicia M; Perera, K L Iresha Sampathi; Kim, Jaekyoon; Pandey, Rajesh K; Sweeney, Noreena; Lu, Xingyun; Imhoff, Andrea; Mackinnon, Alexander Craig; Wargolet, Adam J; Van Hart, Rochelle M; Frick, Karyn M; Donaldson, William A; Sem, Daniel S

    2018-06-04

    Estrogen receptor-beta (ERβ) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERβ agonists (SERBAs) with in vivo efficacy that are A-C estrogens, lacking the B and D estrogen rings. The most potent and selective A-C estrogen is selective for activating ER relative to seven other nuclear hormone receptors, with a surprising 750-fold selectivity for the β over α isoform and with EC 50 s of 20-30 nM in cell-based and direct binding assays. Comparison of potency in different assays suggests that the ER isoform selectivity is related to the compound's ability to drive the productive conformational change needed to activate transcription. The compound also shows in vivo efficacy after microinfusion into the dorsal hippocampus and after intraperitoneal injection (0.5 mg/kg) or oral gavage (0.5 mg/kg). This simple yet novel A-C estrogen is selective, brain penetrant, and facilitates memory consolidation.

  3. In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase

    OpenAIRE

    Kamil Musilek; Kamil Kuca; Daniel Jun; Lucie Musilova

    2011-01-01

    We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylcholinesterase (BChE) with the aim of finding a potent oxime, suitable to serve as a “pseudocatalytic...

  4. Eliciting extra prominence in read-speech tasks: The effects of different text-highlighting methods on acoustic cues to perceived prominence

    DEFF Research Database (Denmark)

    Berger, Stephanie; Niebuhr, Oliver; Fischer, Kerstin

    2018-01-01

    The research initiative Innovating Speech EliCitation Techniques (INSPECT) aims to describe and quantify how recording methods, situations and materials influence speech produc-tion in lab-speech experiments. On this basis, INSPECT aims to develop methods that reliably stimulate specific patterns...... and styles of speech, like expressive or conversational speech or different types emphatic accents. The present study investigates if and how different text highlighting methods (yellow background, bold, capital letter, italics, and underlining) make speakers reinforce the level of perceived prominence...

  5. Fronto-Parietal Network Reconfiguration Supports the Development of Reasoning Ability.

    Science.gov (United States)

    Wendelken, Carter; Ferrer, Emilio; Whitaker, Kirstie J; Bunge, Silvia A

    2016-05-01

    The goal of this fMRI study was to examine how well developmental improvements in reasoning ability can be explained by changes in functional connectivity between specific nodes in prefrontal and parietal cortices. To this end, we examined connectivity within the lateral fronto-parietal network (LFPN) and its relation to reasoning ability in 132 children and adolescents aged 6-18 years, 56 of whom were scanned twice over the course of 1.5 years. Developmental changes in strength of connections within the LFPN were most prominent in late childhood and early adolescence. Reasoning ability was related to functional connectivity between left rostrolateral prefrontal cortex (RLPFC) and inferior parietal lobule (IPL), but only among 12-18-year olds. For 9-11-year olds, reasoning ability was most strongly related to connectivity between left and right RLPFC; this relationship was mediated by working memory. For 6-8-year olds, significant relationships between connectivity and performance were not observed; in this group, processing speed was the primary mediator of improvement in reasoning ability. We conclude that different connections best support reasoning at different points in development and that RLPFC-IPL connectivity becomes an important predictor of reasoning during adolescence. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. The relative cueing power of F0 and duration in German prominence perception

    DEFF Research Database (Denmark)

    Niebuhr, Oliver; Winkler, Jana

    2017-01-01

    hierarchy further by putting numbers on the interplay of duration and F0. German listeners indirectly judged through lexical identification the relative prominence levels of two neighboring syllables. Results show that an increase in F0 of between 0.49 and 0.76 st is required to outweigh the prominence...... effect of a 30% increase in duration of a neighboring syllable. These numbers are fairly stable across a large range of absolute F0 and duration levels and hence useful in speech technology....

  7. Comparing UV/EUV line parameters and magnetic field in a quiescent prominence with tornadoes

    Science.gov (United States)

    Levens, P. J.; Labrosse, N.; Schmieder, B.; López Ariste, A.; Fletcher, L.

    2017-10-01

    Context. Understanding the relationship between plasma and the magnetic field is important for describing and explaining the observed dynamics of solar prominences. Aims: We determine if a close relationship can be found between plasma and magnetic field parameters, measured at high resolution in a well-observed prominence. Methods: A prominence observed on 15 July 2014 by the Interface Region Imaging Spectrograph (IRIS), Hinode, the Solar Dynamics Observatory (SDO), and the Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires (THEMIS) is selected. We perform a robust co-alignment of data sets using a 2D cross-correlation technique. Magnetic field parameters are derived from spectropolarimetric measurements of the He I D3 line from THEMIS. Line ratios and line-of-sight velocities from the Mg II h and k lines observed by IRIS are compared with magnetic field strength, inclination, and azimuth. Electron densities are calculated using Fe xii line ratios from the Hinode Extreme-ultraviolet Imaging Spectrometer, which are compared to THEMIS and IRIS data. Results: We find Mg II k/h ratios of around 1.4 everywhere, similar to values found previously in prominences. Also, the magnetic field is strongest ( 30 G) and predominantly horizontal in the tornado-like legs of the prominence. The k3 Doppler shift is found to be between ±10 km s-1 everywhere. Electron densities at a temperature of 1.5 × 106 K are found to be around 109 cm-3. No significant correlations are found between the magnetic field parameters and any of the other plasma parameters inferred from spectroscopy, which may be explained by the large differences in the temperatures of the lines used in this study. Conclusions: This is the first time that a detailed statistical study of plasma and magnetic field parameters has been performed at high spatial resolution in a prominence. Our results provide important constraints on future models of the plasma and magnetic field in

  8. Beat gestures and prosodic prominence: impact on learning

    OpenAIRE

    Kushch, Olga

    2018-01-01

    Previous research has shown that gestures are beneficial for language learning. This doctoral thesis centers on the effects of beat gestures– i.e., hand and arm gestures that are typically associated with prosodically prominent positions in speech - on such processes. Little is known about how the two central properties of beat gestures, namely how they mark both information focus and rhythmic positions in speech, can be beneficial for learning either a first or a second language. The main go...

  9. Errors of Students Learning With React Strategy in Solving the Problems of Mathematical Representation Ability

    Directory of Open Access Journals (Sweden)

    Delsika Pramata Sari

    2017-06-01

    Full Text Available The purpose of this study was to investigate the errors experienced by students learning with REACT strategy and traditional learning in solving problems of mathematical representation ability. This study used quasi experimental pattern with static-group comparison design. The subjects of this study were 47 eighth grade students of junior high school in Bandung consisting of two samples. The instrument used was a test to measure students' mathematical representation ability. The reliability coefficient about the mathematical representation ability was 0.56. The most prominent errors of mathematical representation ability of students learning with REACT strategy and traditional learning, was on indicator that solving problem involving arithmetic symbols (symbolic representation. In addition, errors were also experienced by many students with traditional learning on the indicator of making the image of a real world situation to clarify the problem and facilitate its completion (visual representation.

  10. Holdaway's analysis of the nose prominence of an adult Nigerian ...

    African Journals Online (AJOL)

    The nose prominence was assessed using Holdaway's analysis. Twenty radiographs randomly selected, were retraced to assess for errors. Data analysis included descriptive statistics, Student's t‑tests and analysis of variance using the Statistical Package for Social Sciences. Results: The mean value recorded for the nose ...

  11. Head turning as a prominent motor symptom in status epilepticus.

    Science.gov (United States)

    Bauer, Gerhard; Broessner, Gregor; Unterberger, Iris; Walser, Gerald; Pfausler, Bettina; Trinka, Eugen

    2008-06-01

    Head and eye turning is frequently observed during seizures. Versions with tonic and/or clonic symptoms can be differentiated from smooth head deviations. Head turning as a prominent symptom of status epilepticus has not previously been reported. We present eight case reports, (7 women/1 man, mean age 41 years, median 41.5, range 10 to 74), of status epilepticus (SE), with head turning as a prominent motor symptom. Six were accompanied by continuous frontal, occipital and temporal ictal epileptiform discharges. Furthermore, two patients had absence status with rhythmic and clonic head versions. While the localizing significance of head turnings in SE is low, in our cases, the direction was away from the discharging hemisphere in all cases of focal SE regardless of whether the turning was classified as version (three cases) or deviation (three cases). In this small series of SE, the classical observation of a patient looking away from the discharging hemisphere is still valid.

  12. 77 FR 3779 - Guidance for Industry on Product Name Placement, Size, and Prominence in Advertising and...

    Science.gov (United States)

    2012-01-25

    ... Advertising and Promotional Labeling; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... entitled ``Product Name Placement, Size, and Prominence in Advertising and Promotional Labeling.'' The..., prominence, and frequency in promotional labeling and advertising for prescription human and animal drugs and...

  13. Children’s responses to online advergames: the role of persuasion knowledge, brand prominence and game involvement

    NARCIS (Netherlands)

    van Reijmersdal, E.; Rozendaal, E.; Buijzen, M.

    2011-01-01

    This study examined the effects of three factors typically associated with advergames: brand prominence, game involvement, and (limited) persuasion knowledge on cognitive and affective responses. An experiment (N = 104, 7-12 year olds) showed that game involvement and brand prominence influenced

  14. Establishing the Thematic Structure and Investigating the most Prominent Theta Roles Used in Sindhi Language

    Directory of Open Access Journals (Sweden)

    Zahid Ali Veesar

    2015-07-01

    Full Text Available This study focuses on the thematic structure of the Sindhi verbs to find theta roles in the Sindhi language. The study tries to answer the research questions; “What are the thematic structures of Sindhi verbs?” and “What are the prominent theta roles in the Sindhi language?” It examines the argument/thematic structure of Sindhi verbs and also finds the theta roles assigned by the Sindhi verbs to their arguments along with the most prominent theta roles used in the Sindhi language. The data come from the two interviews taken from two young native Sindhi speakers, which consist of 2 hours conversation having 1,669 sentences in natural spoken version of the Sindhi language. Towards the end, it has been found that the Sindhi language has certain theta roles which are assigned by the verbs to their arguments in sentences. Each verb phrase in our data is thus examined and studied in detail in terms of Argument/Thematic structure in order to find theta roles in Sindhi language. Thus, in this regard, each verb phrase (in a sentence has been examined with the help of Carnie’s theoretical framework (Thematic Relation and Theta Roles: 2006 in order to find the prominent theta roles in the Sindhi language. The data have been examined and analysed on the basis of the Carnie’s theoretical framework. The study finds that the Sindhi language has all (09 theta roles which have been proposed by Carnie (2006. It has been found that six prominent theta roles out of nine are used prominently in Sindhi. The six prominent theta roles in Sindhi language are: agent, theme, beneficiary, recipient, locative and goal.

  15. The association between loss of work ability and depression: a focus on employment status.

    Science.gov (United States)

    Lee, Sang Ah; Ju, Yeong Jun; Han, Kyu-Tae; Choi, Jae Woo; Yoon, Hyo Jung; Park, Eun-Cheol

    2017-01-01

    Work-related factors are one of the known risk factors for depression. Given that the ability to work is considered an important aspect of well-being and health status, we investigated the association between the loss of work ability and depression. We further examined the association stratified by employment status. We used data from the Korea Welfare Panel Study. The dependent variable of the present study was depression, which is measured by the Center for Epidemiologic Studies Depression Scale. Work ability transition from the previous year was divided into three categories: maintained, loss, and complete loss. A linear mixed-effects model was performed for the analysis. The work ability loss group (β = 2.071, p work ability completely loss group (β = 2.651, p = 0.015) had higher depression scores compared to those who maintained their work ability from the previous year. Specifically, those who lost their work ability and their job (β = 3.685, p = 0.0068) had the highest depression scores compared to those who maintained their work ability and job. We found that those who lost their ability to work may be at risk of depression, and this finding was particularly prominent among those who also became unemployed. Therefore, psychological support is needed for these individuals to overcome the negative influence of the loss of work ability.

  16. Energy release from a stream of infalling prominence debris on 2011 September 7-8

    Science.gov (United States)

    Inglis, A. R.; Gilbert, H. R.; Ofman, L.

    2017-12-01

    In recent years high-resolution and high-cadence EUV imaging has revealed a new phenomenon, impacting prominence debris, where prominence material from failed or partial eruptions can impact the lower atmosphere and release energy. We present a clear example of this phenomenon occurring on 2011 September 7-8. The initial eruption of prominence material was associated with an X1.8-class flare from AR11283, occurring at 22:30 UT on 2011 September 7, resulting in a semi-continuous stream of this material returning to the solar surface between 00:20 - 00:40 UT on 2011 September 8. A substantial area remote from the original active region experienced brightening in multiple EUV channels observed by SDO/AIA. Using the differential emission measure, we estimated the energetic properties of this event. We found that the radiated energy of the impacted plasma was of order 10^27 ergs, while the upper limit on the thermal energy peaked at 10^28 ergs. Based on these estimates we were able to determine the mass content of the debris to be in the range 2x10^14 energy release takes place during these events, and that such impacts may be used as a novel diagnostic tool for investigating prominence material properties.

  17. EUV lines observed with EIS/Hinode in a solar prominence

    Czech Academy of Sciences Publication Activity Database

    Labrosse, N.; Schmieder, B.; Heinzel, Petr; Watanabe, T.

    2011-01-01

    Roč. 531, July (2011), A69/1-A69/11 ISSN 0004-6361 Grant - others:EU(XE) ESA- PECS project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.587, year: 2011

  18. Effect of the prominent catalyst layer surface on reactant gas transport and cell performance at the cathodic side of a PEMFC

    International Nuclear Information System (INIS)

    Perng, Shiang-Wuu; Wu, Horng-Wen

    2010-01-01

    The cell performance enhancement of a proton exchange membrane fuel cell (PEMFC) has been numerically investigated with the prominence-like form catalyst layer surface of the same composition at the cathodic half-cell of a PEMFC. The geometries of the prominence-like form catalyst layer surface are assigned as one prominence, three prominences, and five prominences catalyst layer surfaces with constant distance between two prominences in the same gas diffusion layer (GDL) for the purpose of investigating the cell performance. To confine the current investigation to two-dimensional incompressible flows, we assume that the fluid flow is laminar with a low Reynolds number 15. The results indicate that the prominence-like form catalyst layer surface can effectively enhance the local cell performance of a PEMFC.

  19. Celebrity Patients, VIPs, and Potentates.

    Science.gov (United States)

    Groves, James E.; Dunderdale, Barbara A.; Stern, Theodore A.

    2002-12-01

    BACKGROUND: During the second half of the 20th century, the literature on the doctor-patient relationship mainly dealt with the management of "difficult" (personality-disordered) patients. Similar problems, however, surround other types of "special" patients. METHOD: An overview and analysis of the literature were conducted. As a result, such patients can be subcategorized by their main presentations; each requires a specific management strategy. RESULTS: Three types of "special" patients stir up irrational feelings in their caregivers. Sick celebrities threaten to focus public scrutiny on the private world of medical caregivers. VIPs generate awe in caregivers, with loss of the objectivity essential to the practice of scientific medicine. Potentates unearth narcissism in the caregiver-patient relationship, which triggers a struggle between power and shame. Pride, privacy, and the staff's need to be in control are all threatened by introduction of the special patient into medicine's closed culture. CONCLUSION: The privacy that is owed to sick celebrities should be extended to protect overexposed staff. The awe and loss of medical objectivity that VIPs generate are counteracted by team leadership dedicated to avoiding any deviation from standard clinical procedure. Moreover, the collective ill will surrounding potentates can be neutralized by reassuring them that they are "special"-and by caregivers mending their own vulnerable self-esteem.

  20. Subcision Using a Spinal Needle Cannula and a Thread for Prominent Nasolabial Fold Correction

    Directory of Open Access Journals (Sweden)

    Sang-Yeul Lee

    2013-05-01

    Full Text Available Deepening of the nasolabial crease is an esthetically unpleasing aging phenomenon occurring in the midface. Various treatment modalities have been introduced to improve the appearance of prominent nasolabial folds, all of which have pros and cons. Currently, a minimally invasive technique using synthetic dermal fillers is most commonly used. A simple and easy subcision procedure using a wire scalpel has also been used and reported to be effective for prominent nasolabial fold correction, with minimal complications. As an alternative to the wire scalpel, we used a 20-gauge metal type spinal needle cannula (Hakko Co. and 4-0 Vicryl suture (Ethicon Inc. for subcision of nasolabial folds. This technique is less expensive than the use of a wire scalpel and easily available when needed. Therefore, on the basis of favorable results, our modified subcision technique may be considered effective for prominent nasolabial fold correction.

  1. The role of prominence in determining the scope of boundary-related lengthening in Greek.

    Science.gov (United States)

    Katsika, Argyro

    2016-03-01

    This study aims at examining and accounting for the scope of the temporal effect of phrase boundaries. Previous research has indicated that there is an interaction between boundary-related lengthening and prominence such that the former extends towards the nearby prominent syllable. However, it is unclear whether this interaction is due to lexical stress and/or phrasal prominence (marked by pitch accent) and how far towards the prominent syllable the effect extends. Here, we use an electromagnetic articulography (EMA) study of Greek to examine the scope of boundary-related lengthening as a function of lexical stress and pitch accent separately. Boundaries are elicited by the means of a variety of syntactic constructions.. The results show an effect of lexical stress. Phrase-final lengthening affects the articulatory gestures of the phrase-final syllable that are immediately adjacent to the boundary in words with final stress, but is initiated earlier within phrase-final words with non-final stress. Similarly, the articulatory configurations during inter-phrasal pauses reach their point of achievement later in words with final stress than in words with non-final stress. These effects of stress hold regardless of whether the phrase-final word is accented or de-accented. Phrase-initial lengthening, on the other hand, is consistently detected on the phrase-initial constriction, independently of where the stress is within the preceding, phrase-final, word. These results indicate that the lexical aspect of prominence plays a role in determining the scope of boundary-related lengthening in Greek. Based on these results, a gestural account of prosodic boundaries in Greek is proposed in which lexical and phrasal prosody interact in a systematic and coordinated fashion. The cross-linguistic dimensions of this account and its implications for prosodic structure are discussed.

  2. Flotation process control optimisation at Prominent Hill

    International Nuclear Information System (INIS)

    Lombardi, Josephine; Muhamad, Nur; Weidenbach, M.

    2012-01-01

    OZ Minerals' Prominent Hill copper- gold concentrator is located 130 km south east of the town of Coober Pedy in the Gawler Craton of South Australia. The concentrator was built in 2008 and commenced commercial production in early 2009. The Prominent Hill concentrator is comprised of a conventional grinding and flotation processing plant with a 9.6 Mtpa ore throughput capacity. The flotation circuit includes six rougher cells, an IseMill for regrinding the rougher concentrate and a Jameson cell heading up the three stage conventional cell cleaner circuit. In total there are four level controllers in the rougher train and ten level controllers in the cleaning circuit for 18 cells. Generic proportional — integral and derivative (PID) control used on the level controllers alone propagated any disturbances downstream in the circuit that were generated from the grinding circuit, hoppers, between cells and interconnected banks of cells, having a negative impact on plant performance. To better control such disturbances, FloatStar level stabiliser was selected for installation on the flotation circuit to account for the interaction between the cells. Multivariable control was also installed on the five concentrate hoppers to maintain consistent feed to the cells and to the IsaMill. An additional area identified for optimisation in the flotation circuit was the mass pull rate from the rougher cells. FloatStar flow optimiser was selected to be installed subsequent to the FloatStar level stabiliser. This allowed for a unified, consistent and optimal approach to running the rougher circuit. This paper describes the improvement in the stabilisation of the circuit achieved by the FloatStar level stabiliser by using the interaction matrix between cell level controllers and the results and benefits of implementing the FloatStar flow optimiser on the rougher train.

  3. Magnetohydrodynamic waves in two-dimensional prominences embedded in coronal arcades

    International Nuclear Information System (INIS)

    Terradas, J.; Soler, R.; Díaz, A. J.; Oliver, R.; Ballester, J. L.

    2013-01-01

    Solar prominence models used so far in the analysis of MHD waves in two-dimensional structures are quite elementary. In this work, we calculate numerically magnetohydrostatic models in two-dimensional configurations under the presence of gravity. Our interest is in models that connect the magnetic field to the photosphere and include an overlying arcade. The method used here is based on a relaxation process and requires solving the time-dependent nonlinear ideal MHD equations. Once a prominence model is obtained, we investigate the properties of MHD waves superimposed on the structure. We concentrate on motions purely two-dimensional, neglecting propagation in the ignorable direction. We demonstrate how, by using different numerical tools, we can determine the period of oscillation of stable waves. We find that vertical oscillations, linked to fast MHD waves, are always stable and have periods in the 4-10 minute range. Longitudinal oscillations, related to slow magnetoacoustic-gravity waves, have longer periods in the range of 28-40 minutes. These longitudinal oscillations are strongly influenced by the gravity force and become unstable for short magnetic arcades.

  4. Co-localization of a CD1d-binding glycolipid with an adenovirus-based malaria vaccine for a potent adjuvant effect.

    Science.gov (United States)

    Li, Xiangming; Huang, Jing; Kawamura, Akira; Funakoshi, Ryota; Porcelli, Steven A; Tsuji, Moriya

    2017-05-31

    A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. In the present study, 7DW8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a Plasmodium yoelii circumsporozoite protein (PyCSP), AdPyCS, has led to a co-localization of 7DW8-5 and a PyCSP in draining lymph nodes (dLNs), particularly in dendritic cells (DCs). This occurrence initiates a cascade of events, such as the recruitment of DCs to dLNs and their activation and maturation, and the enhancement of the ability of DCs to prime CD8+ T cells induced by AdPyCS and ultimately leading to a potent adjuvant effect and protection against malaria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. A model of 'disparitions brusques' (sudden disappearance of eruptive prominences) as an instability driven by MHD waves

    International Nuclear Information System (INIS)

    Sakai, J.; Nishikawa, K.-I.

    1982-04-01

    A mode of 'disparitions brusques' (sudden disappearance of eruptive prominences) is discussed based on the Kippenhahn and Schluter configuration. It is shown that Kippenhahn and Schluter's current sheet is very weakly unstable against magnetic reconnecting modes during the lifetime of quiescent prominences. Disturbances in the form of fast magnetosonic waves originating from nearby active regions or the changes of whole magnetic configuration due to newly emerged magnetic flux may trigger a rapid growing instability associated with magnetic field reconnection. This instability gives rise to disruptions of quiescent prominences and also generates high energy particles. (author)

  6. 78 FR 69691 - Draft Guidance for Industry on Product Name Placement, Size, and Prominence in Advertising and...

    Science.gov (United States)

    2013-11-20

    ...] Draft Guidance for Industry on Product Name Placement, Size, and Prominence in Advertising and... entitled ``Product Name Placement, Size, and Prominence in Advertising and Promotional Labeling.'' When... promotional labeling and advertising for prescription human drugs, including biological drug products, and...

  7. AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor

    DEFF Research Database (Denmark)

    Hatse, Sigrid; Princen, Katrien; De Clercq, Erik

    2005-01-01

    The chemokine receptors CCR5 and CXCR4 function as coreceptors for human immunodeficiency virus (HIV) and are attractive targets for the development of anti-HIV drugs. The most potent CXCR4 antagonists described until today are the bicyclams. The prototype compound, AMD3100, exhibits potent and s...

  8. The Apparent Critical Decay Index at the Onset of Solar Prominence Eruptions

    Science.gov (United States)

    Zuccarello, F. P.; Aulanier, G.; Gilchrist, S. A.

    2016-04-01

    A magnetic flux rope (MFR) embedded in a line-tied external magnetic field that decreases with height as {z}-n is unstable to perturbations if the decay index of the field n is larger than a critical value. The onset of this instability, called torus instability, is one of the main mechanisms that can initiate coronal mass ejections. Since flux ropes often possess magnetic dips that can support prominence plasma, this is also a valuable mechanism to trigger prominence eruptions. Magnetohydrodynamic (MHD) simulations of the formation and/or emergence of MFRs suggest a critical value for the onset of the instability in the range [1.4-2]. However, detailed observations of prominences suggest a value in the range [0.9-1.1]. In this Letter, by using a set of MHD simulations, we show why the large discrepancy between models and observations is only apparent. Our simulations indeed show that the critical decay index at the onset of the eruption is n=1.4+/- 0.1 when computed at the apex of the flux rope axis, while it is n=1.1+/- 0.1 when it is computed at the altitude of the topmost part of the distribution of magnetic dips. The discrepancy only arises because weakly twisted curved flux ropes do not have dips up to the altitude of their axis.

  9. From Wilhelm von Humboldt to Hitler-are prominent people more prone to have Parkinson's disease?

    Science.gov (United States)

    Horowski; Horowski; Calne; Calne

    2000-10-01

    We describe Parkinsonism in prominent people, where Wilhelm von Humboldt and Adolf Hitler provide just two spectacular, opposing examples. In both of them, there is little if any evidence that the disease did influence their life ambitions, methods of achieving them or cognitive function in general. Thus, Hitler's Parkinsonism should remain a 'footnote' to history, and historians should acknowledge that in his last years, his trembling, his curbed posture, his slow walking, mask-like face and low voice did not indicate remorse, fear or depression as a consequence of his crimes, but were mere expressions of his disease which, until the end, had no impact on his intellectual skills and methods. The apparently higher incidence of Parkinsonism in prominent people may be just due to their higher visibility, or a consequence of disease-related personality traits (e.g. ambition, perfectionism, rigidity) which may contribute to becoming, e.g., a prominent authoritarian person. Perhaps even some early behaviour pattern (such as repressed emotions or acting in public-which could even increase the risk of some infection) contributes to a greater vulnerability for developing Parkinsonism. Further studying other prominent cases might lead us to better understanding of risk factors and the expression of early Parkinsonism.

  10. Three-Dimensional Morphology of a Coronal Prominence Cavity

    Science.gov (United States)

    Gibson, S. E.; Kucera, T. A.; Rastawicki, D.; Dove, J.; deToma, G.; Hao, J.; Hill, S.; Hudson, H. S.; Marque, C.; McIntosh, P. S.; hide

    2010-01-01

    We present a three-dimensional density model of coronal prominence cavities, and a morphological fit that has been tightly constrained by a uniquely well-observed cavity. Observations were obtained as part of an International Heliophysical Year campaign by instruments from a variety of space- and ground-based observatories, spanning wavelengths from radio to soft-X-ray to integrated white light. From these data it is clear that the prominence cavity is the limb manifestation of a longitudinally-extended polar-crown filament channel, and that the cavity is a region of low density relative to the surrounding corona. As a first step towards quantifying density and temperature from campaign spectroscopic data, we establish the three-dimensional morphology of the cavity. This is critical for taking line-of-sight projection effects into account, since cavities are not localized in the plane of the sky and the corona is optically thin. We have augmented a global coronal streamer model to include a tunnel-like cavity with elliptical cross-section and a Gaussian variation of height along the tunnel length. We have developed a semi-automated routine that fits ellipses to cross-sections of the cavity as it rotates past the solar limb, and have applied it to Extreme Ultraviolet Imager (EUVI) observations from the two Solar Terrestrial Relations Observatory (STEREO) spacecraft. This defines the morphological parameters of our model, from which we reproduce forward-modeled cavity observables. We find that cavity morphology and orientation, in combination with the viewpoints of the observing spacecraft, explains the observed variation in cavity visibility for the east vs. west limbs

  11. MUC2 is the prominent colonic mucin expressed in ulcerative colitis

    NARCIS (Netherlands)

    Tytgat, K. M.; Opdam, F. J.; Einerhand, A. W.; Büller, H. A.; Dekker, J.

    1996-01-01

    BACKGROUND: It has been shown that MUC2 is the prominent mucin synthesised in healthy colon. AIM: To identify the predominant mucins in ulcerative colitis (UC) and to study their biosynthesis. METHODS AND RESULTS: Mucin was purified from UC resection specimens. This mucin on sodium dodecylsulphate

  12. Orthodontic treatment for prominent lower front teeth (Class III malocclusion) in children.

    Science.gov (United States)

    Watkinson, Simon; Harrison, Jayne E; Furness, Susan; Worthington, Helen V

    2013-09-30

    Prominent lower front teeth (termed reverse bite; under bite; Class III malocclusion) may be due to a combination of the jaw or tooth positions or both. The upper jaw (maxilla) can be too far back or the lower jaw (mandible) too far forward, or both. Prominent lower front teeth can also occur if the upper front teeth (incisors) are tipped back or the lower front teeth are tipped forwards, or both. Various treatment approaches have been described to correct prominent lower front teeth in children and adolescents. To assess the effects of orthodontic treatment for prominent lower front teeth in children and adolescents. We searched the following databases: Cochrane Oral Health Group's Trials Register (to 7 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE via OVID (1946 to 7 January 2013), and EMBASE via OVID (1980 to 7 January 2013). Randomised controlled trials (RCTs) recruiting children or adolescents or both (aged 16 years or less) receiving any type of orthodontic treatment to correct prominent lower front teeth (Class III malocclusion). Orthodontic treatments were compared with control groups who received either no treatment, delayed treatment or a different active intervention. Screening of references, identification of included and excluded studies, data extraction and assessment of the risk of bias of the included studies was performed independently and in duplicate by two review authors. The mean differences with 95% confidence intervals were calculated for continuous data. Meta-analysis was only undertaken when studies of similar comparisons reported comparable outcome measures. A fixed-effect model was used. The I2 statistic was used as a measure of statistical heterogeneity. Seven RCTs with a total of 339 participants were included in this review. One study was assessed as at low risk of bias, three studies were at high risk of bias, and in the remaining three studies risk of bias

  13. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably

  14. SAH derived potent and selective EZH2 inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Kung, Pei-Pei; Huang, Buwen; Zehnder, Luke; Tatlock, John; Bingham, Patrick; Krivacic, Cody; Gajiwala, Ketan; Diehl, Wade; Yu, Xiu; Maegley, Karen A.

    2015-04-01

    A series of novel enhancer of zeste homolog 2 (EZH2) inhibitors was designed based on the chemical structure of the histone methyltransferase (HMT) inhibitor SAH (S-adenosyl-l-homocysteine). These nucleoside-based EZH2 inhibitors blocked the methylation of nucleosomes at H3K27 in biochemical assays employing both WT PRC2 complex as well as a Y641N mutant PRC2 complex. The most potent compound, 27, displayed IC50’s against both complexes of 270 nM and 70 nM, respectively. To our knowledge, compound 27 is the most potent SAH-derived inhibitor of the EZH2 PRC2 complex yet identified. This compound also displayed improved potency, lipophilic efficiency (LipE), and selectivity profile against other lysine methyltransferases compared with SAH.

  15. Open questions on prominences from coordinated observations by IRIS, Hinode, SDO/AIA, THEMIS, and the Meudon/MSDP

    Science.gov (United States)

    Schmieder, B.; Tian, H.; Kucera, T.; López Ariste, A.; Mein, N.; Mein, P.; Dalmasse, K.; Golub, L.

    2014-09-01

    Context. A large prominence was observed by multiple instruments on the ground and in space during an international campaign on September 24, 2013, for three hours (12:12 UT -15:12 UT). Instruments used in the campaign included the newly launched (June 2013) Interface Region Imaging Spectrograph (IRIS), THEMIS (Tenerife), the Hinode Solar Optical Telescope (SOT), the Solar Dynamic Observatory's Atmospheric Imaging Assembly (SDO/AIA), and the Multichannel Subtractive Double Pass spectrograph (MSDP) in the Meudon Solar Tower. The movies obtained in 304 Å with the EUV imager SDO/AIA, and in Ca II line by SOT show the dynamic nature of the prominence. Aims: The aim of this work is to study the dynamics of the prominence fine structures in multiple wavelengths to understand their formation. Methods: The spectrographs IRIS and MSDP provided line profiles with a high cadence in Mg II h (2803.5 Å) and k (2796.4 Å) lines along four slit positions (IRIS), and in Hα in a 2D field of view (MSDP). The spectropolarimetry of THEMIS (Tenerife) allowed us to derive the magnetic field of the prominence using the He D3 line depolarization (Hanle effect combined with the Zeeman effect). Results: The magnetic field is found to be globally horizontal with a relatively weak field strength (8-15 Gauss). On the other hand, the Ca II movie reveals turbulent-like motion that is not organized in specific parts of the prominence. We tested the addition of a turbulent magnetic component. This model is compatible with the polarimetric observations at those places where the plasma turbulence peaks. On the other hand, the Mg II line profiles show multiple peaks well separated in wavelength. This is interpreted by the existence of small threads along the line of sight with a large dispersion of discrete values of Doppler shifts, from 5 km s-1 (a quasi-steady component) to 60-80 km s-1. Each peak corresponds to a Gaussian profile, and not to a reversed profile as was expected by the present non

  16. Biaryls as potent, tunable dual neurokinin 1 receptor antagonists and serotonin transporter inhibitors.

    Science.gov (United States)

    Degnan, Andrew P; Tora, George O; Han, Ying; Rajamani, Ramkumar; Bertekap, Robert; Krause, Rudolph; Davis, Carl D; Hu, Joanna; Morgan, Daniel; Taylor, Sarah J; Krause, Kelly; Li, Yu-Wen; Mattson, Gail; Cunningham, Melissa A; Taber, Matthew T; Lodge, Nicholas J; Bronson, Joanne J; Gillman, Kevin W; Macor, John E

    2015-08-01

    Depression is a serious illness that affects millions of patients. Current treatments are associated with a number of undesirable side effects. Neurokinin 1 receptor (NK1R) antagonists have recently been shown to potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs) in a number of animal models. Herein we describe the optimization of a biaryl chemotype to provide a series of potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors. Through the choice of appropriate substituents, the SERT/NK1R ratio could be tuned to afford a range of target selectivity profiles. This effort culminated in the identification of an analog that demonstrated oral bioavailability, favorable brain uptake, and efficacy in the gerbil foot tap model. Ex vivo occupancy studies with compound 58 demonstrated the ability to maintain NK1 receptor saturation (>88% occupancy) while titrating the desired level of SERT occupancy (11-84%) via dose selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Magnetic field vector and electron density diagnostics from linear polarization measurements in 14 solar prominences

    Science.gov (United States)

    Bommier, V.

    1986-01-01

    The Hanle effect is the modification of the linear polarization parameters of a spectral line due to the effect of the magnetic field. It has been successfully applied to the magnetic field vector diagnostic in solar prominences. The magnetic field vector is determined by comparing the measured polarization to the polarization computed, taking into account all the polarizing and depolarizing processes in line formation and the depolarizing effect of the magnetic field. The method was applied to simultaneous polarization measurements in the Helium D3 line and in the hydrogen beta line in 14 prominences. Four polarization parameters are measured, which lead to the determination of the three coordinates of the magnetic field vector and the electron density, owing to the sensitivity of the hydrogen beta line to the non-negligible effect of depolarizing collisions with electrons and protons of the medium. A mean value of 1.3 x 10 to the 10th power cu. cm. is derived in 14 prominences.

  18. Self-presentation in Online Professional Networks: Men's Higher and Women's Lower Facial Prominence in Self-created Profile Images.

    Science.gov (United States)

    Sczesny, Sabine; Kaufmann, Michèle C

    2017-01-01

    Men are presented with higher facial prominence than women in the media, a phenomenon that is called face-ism . In naturalistic settings, face-ism effects could be driven by gender biases of photographers and/or by gender differences in self-presentation. The present research is the first to investigate whether women and men themselves create this different facial prominence. In a controlled laboratory study, 61 participants prepared a picture of themselves from a half-body photograph, allegedly to be uploaded to their profile for an online professional network. As expected, men cropped their photos with higher facial prominence than women did. However, women and men did not differ in the self-presentational motivations, goals, strategies, and personality variables under investigation, so that the observed face-ism effect could not be explained with these variables. Generally, the higher participants' physical appearance self-esteem, the higher was their self-created facial prominence.

  19. DYNAMICS OF A SOLAR PROMINENCE TORNADO OBSERVED BY SDO/AIA ON 2012 NOVEMBER 7–8

    Energy Technology Data Exchange (ETDEWEB)

    Mghebrishvili, Irakli; Zaqarashvili, Teimuraz V.; Kukhianidze, Vasil; Ramishvili, Giorgi [Abastumani Astrophysical Observatory at Ilia State University, University St. 2, Tbilisi, Georgia (United States); Shergelashvili, Bidzina [Space Research Institute, Austrian Academy of Sciences, Schmiedlstrasse 6, A-8042 Graz (Austria); Veronig, Astrid [IGAM-Kanzelhöhe Observatory, Institute of Physics, University of Graz, Universitätsplatz 5, A-8010 Graz (Austria); Poedts, Stefaan, E-mail: teimuraz.zaqarashvili@oeaw.ac.at [Centre for Mathematical Plasma Astrophysics, Celestijnenlaan 200B, B-3001 Leuven (Belgium)

    2015-09-10

    We study the detailed dynamics of a solar prominence tornado using time series of 171, 304, 193, and 211 Å spectral lines obtained by the Solar Dynamics Observatory/Atmospheric Imaging Assembly during 2012 November 7–8. The tornado first appeared at 08:00 UT, November 07, near the surface, gradually rose upwards with the mean speed of ∼1.5 km s{sup −1} and persisted over 30 hr. Time–distance plots show two patterns of quasi-periodic transverse displacements of the tornado axis with periods of 40 and 50 minutes at different phases of the tornado evolution. The first pattern occurred during the rising phase and can be explained by the upward motion of the twisted tornado. The second pattern occurred during the later stage of evolution when the tornado already stopped rising and could be caused either by MHD kink waves in the tornado or by the rotation of two tornado threads around a common axis. The later hypothesis is supported by the fact that the tornado sometimes showed a double structure during the quasi-periodic phase. 211 and 193 Å spectral lines show a coronal cavity above the prominence/tornado, which started expansion at ∼13:00 UT and continuously rose above the solar limb. The tornado finally became unstable and erupted together with the corresponding prominence as coronal mass ejection (CME) at 15:00 UT, November 08. The final stage of the evolution of the cavity and the tornado-related prominence resembles the magnetic breakout model. On the other hand, the kink instability may destabilize the twisted tornado, and consequently prominence tornadoes can be used as precursors for CMEs.

  20. Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.

    Science.gov (United States)

    Conroy, Trent; Guo, Jin T; Elias, Nabiha; Cergol, Katie M; Gut, Jiri; Legac, Jennifer; Khatoon, Lubna; Liu, Yang; McGowan, Sheena; Rosenthal, Philip J; Hunt, Nicholas H; Payne, Richard J

    2014-12-26

    Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents.

  1. Prominent papilla of vater at CT: differentiation between benign and malignant lesion

    International Nuclear Information System (INIS)

    Park, Sun Won; Han, Joon Koo; Choi, Byung Ihn and others

    1998-01-01

    To establish the criteria for differential diagnosis between malignant tumor and benign prominence of papilla of Vater, as seen on CT. Sixteen consecutive patients with prominent patilla of Vater, as seen on CT during a ten-month period were included in this study. Final diagnosis was papilla of Vater cancer (n=3D5), chronic inflammation (n=3D3), benign tumor (n=3D3), or and normal (n=3D5), and this was confirmed by surgery in 11 cases, and endoscopy in five. Papilla size and attenuation, the presence of accompanied dilatation of the bile or pancreatic duct, and lymph node enlargement were analyzed by two experienced radiologists, who reached a concensus. A past history of stone disease, laboratory findings such as serum bilirubin, serum alkaline phosphatase, or endoscopic findings of duodenal diverticulum were additionally analyzed. Papilla size was the only significantly different CT finding between malignant and benign lesions, and serum alkaline phosphatase levels were also significantly different between the two groups. The smallest malignant tumor was 18 mm and the largest benign lesion was 15 mm. The presence of bile or pancreatic duct dilatation, serum bilirubin level, attenuation of the mass, a history of stone disease, and lymph node enlargement were not significantly different between the two groups. In patients with prominent papilla of Vater, as seen on CT, a mass larger than 18 mm is the only reliable radiologic finding to indicate malignant tumor of papilla of Vater. Serum alkaline phosphatase levels can, in addition, be helpful for the differential diagnosis of benign and malignant lesions.=20

  2. Physics of Solar Prominences: I-Spectral Diagnostics and Non-LTE Modelling

    Czech Academy of Sciences Publication Activity Database

    Labrosse, N.; Heinzel, Petr; Vial, J. C.; Kucera, T.; Parenti, S.; Gunár, Stanislav; Schmieder, B.; Kilper, G.

    2010-01-01

    Roč. 151, č. 4 (2010), s. 243-332 ISSN 0038-6308 R&D Projects: GA ČR GA205/07/1100 Grant - others:ESA(XE) ESA- PECS project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : solar prominences * spectroscopy * radiative transfer Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 4.433, year: 2010

  3. On the Visibility of Prominence Fine Structures at Radio Millimeter Wavelengths

    Czech Academy of Sciences Publication Activity Database

    Heinzel, Petr; Berlicki, Arkadiusz; Bárta, Miroslav; Karlický, Marian; Rudawy, P.

    2015-01-01

    Roč. 290, č. 7 (2015), s. 1981-2000 ISSN 0038-0938 R&D Projects: GA ČR GAP209/12/0906; GA ČR GAP209/12/0103; GA ČR GA13-24782S Institutional support: RVO:67985815 Keywords : prominences * quiescent * radio emission Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 2.862, year: 2015

  4. Self-presentation in Online Professional Networks: Men's Higher and Women's Lower Facial Prominence in Self-created Profile Images

    Science.gov (United States)

    Sczesny, Sabine; Kaufmann, Michèle C.

    2018-01-01

    Men are presented with higher facial prominence than women in the media, a phenomenon that is called face-ism. In naturalistic settings, face-ism effects could be driven by gender biases of photographers and/or by gender differences in self-presentation. The present research is the first to investigate whether women and men themselves create this different facial prominence. In a controlled laboratory study, 61 participants prepared a picture of themselves from a half-body photograph, allegedly to be uploaded to their profile for an online professional network. As expected, men cropped their photos with higher facial prominence than women did. However, women and men did not differ in the self-presentational motivations, goals, strategies, and personality variables under investigation, so that the observed face-ism effect could not be explained with these variables. Generally, the higher participants' physical appearance self-esteem, the higher was their self-created facial prominence. PMID:29387029

  5. Self-presentation in Online Professional Networks: Men's Higher and Women's Lower Facial Prominence in Self-created Profile Images

    Directory of Open Access Journals (Sweden)

    Sabine Sczesny

    2018-01-01

    Full Text Available Men are presented with higher facial prominence than women in the media, a phenomenon that is called face-ism. In naturalistic settings, face-ism effects could be driven by gender biases of photographers and/or by gender differences in self-presentation. The present research is the first to investigate whether women and men themselves create this different facial prominence. In a controlled laboratory study, 61 participants prepared a picture of themselves from a half-body photograph, allegedly to be uploaded to their profile for an online professional network. As expected, men cropped their photos with higher facial prominence than women did. However, women and men did not differ in the self-presentational motivations, goals, strategies, and personality variables under investigation, so that the observed face-ism effect could not be explained with these variables. Generally, the higher participants' physical appearance self-esteem, the higher was their self-created facial prominence.

  6. An ayurvedic formulation Sankat Mochan: A potent anthelmintic medicine

    Directory of Open Access Journals (Sweden)

    Khomendra Kumar Sarwa

    2017-01-01

    Full Text Available Aim and Object: Sankat Mochan is an ayurvedic formulation used in the urban and rural area of India. This polyherbal formulation is used for general stomach problems including abdominal cramping and diarrhea. The present investigation evaluated the anthelmintic activity of an aqueous solution of an ayurvedic medicine Sankat Mochan. Materials and Method: Various concentrations (1%, 5%, and 10% of medicine were used for anthelmintic activity on Pheretima posthuma. Piperazine citrate (10 mg/ml was used as a reference standard and distilled water as a control. Result and Conclusion: The result showed that the Sankat Mochan possess anthelmintic activity more potent than that of piperazine citrate. Thus, Sankat Mochan may be used as a potent anthelmintic agent against helminthiasis.

  7. Total mass of six quiescent prominences estimated from their multi-spectral observations

    Czech Academy of Sciences Publication Activity Database

    Schwartz, Pavol; Heinzel, Petr; Kotrč, Pavel; Fárník, František; Kupryakov, Yu. A.; DeLuca, E. E.; Golub, L.

    2015-01-01

    Roč. 574, February (2015), A62/1-A62/18 ISSN 0004-6361 R&D Projects: GA ČR GAP209/12/0906 Institutional support: RVO:67985815 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

  8. Canonical Wnts, specifically Wnt-10b, show ability to maintain dermal papilla cells

    Energy Technology Data Exchange (ETDEWEB)

    Ouji, Yukiteru, E-mail: oujix@naramed-u.ac.jp; Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide, E-mail: myoshika@naramed-u.ac.jp

    2013-08-30

    Highlights: •First report on effects of various Wnts on DP cells. •Wnt-10b promoted trichogenesis, while Wnt-3a showed to a limited extent. •Canonical Wnts, specifically Wnt-10b, is important for DP cells maintenance. -- Abstract: Although Wnts are expressed in hair follicles (HFs) and considered to be crucial for maintaining dermal papilla (DP) cells, the functional differences among them remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, 5a, 10b, 11) on the proliferation of mouse-derived primary DP cells in vitro as well as their trichogenesis-promoting ability using an in vivo skin reconstitution protocol. Wnt-10b promoted cell proliferation and trichogenesis, while Wnt-3a showed those abilities to a limited extent, and Wnt-5a and 11 had no effects. Furthermore, we investigated the effects of these Wnts on cultured DP cells obtained from versican-GFP transgenic mice and found that Wnt-10b had a potent ability to sustain their GFP-positivity. These results suggest that canonical Wnts, specifically Wnt-10b, play important roles in the maintenance of DP cells and trichogenesis.

  9. Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine

    Energy Technology Data Exchange (ETDEWEB)

    Annesley, Thomas M.; Cooks, Robert G.; Herold, David A.; Hoofnagle, Andrew N.

    2016-01-04

    Each year the journal Clinical Chemistry publishes a January special issue on a topic that is relevant to the laboratory medicine community. In January 2016 the topic is mass spectrometry, and the issue is entitled “Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine”. One popular feature in our issues is a Q&A on a topic, clearly in this case mass spectrometry. The journal is assembling a panel of 5-6 experts from various areas of mass spectrometry ranging from instrument manufacturing to practicing clinical chemists. Dick Smith is one of the scientist requested to participate in this special issue Q&A on Mass Spectrometry. The Q&A Transcript is attached

  10. Synthetic Hydrogen Spectra of Oscillating Prominence Slabs Immersed in the Solar Corona

    Czech Academy of Sciences Publication Activity Database

    Zapiór, Maciej; Oliver, R.; Ballester, J.L.; Heinzel, Petr

    2016-01-01

    Roč. 827, č. 2 (2016), 131/1-131/7 ISSN 0004-637X R&D Projects: GA ČR(CZ) GA16-18495S Institutional support: RVO:67985815 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 5.533, year: 2016

  11. Economy diversification: a potent tool for tourism development in ...

    African Journals Online (AJOL)

    Economy diversification: a potent tool for tourism development in Nigeria. ... AFRREV STECH: An International Journal of Science and Technology ... The diversity of cultural attractions, the friendly disposition of the people, revamped National ...

  12. The lattice dynamics of six prominent B.C.C. transition metals

    International Nuclear Information System (INIS)

    Brescansin, L.M.; Padial, N.T.; Shukla, M.M.

    1975-01-01

    The frequency versus wave vector dispersion relations along the three principal symmetry directions, [xi00], [xixi0] and [xixixi], of six prominent body centered cubic transition metals, namely that of molybdenum, α-iron, tungsten, tantalum, niobium and that of chromium, have been computed on the basis of a phenomenological model. The calculated results are in very good agreements to the experimental findings

  13. Late cutaneous effects of a local potent steroid during adjuvant radiotherapy for breast cancer

    DEFF Research Database (Denmark)

    Ulff, Eva; Maroti, Marianne; Serup, Jörgen

    2017-01-01

    Purpose: The aim of this study was to evaluate whether treatment with a local potent corticosteroid during adjuvant external radiotherapy (ERT) of breast cancer is associated with late skin toxicity. Material and methods: Sixty patients (32 treated with potent corticoid cream versus 28 controls t...

  14. ON THE RELATIONSHIP BETWEEN A HOT-CHANNEL-LIKE SOLAR MAGNETIC FLUX ROPE AND ITS EMBEDDED PROMINENCE

    International Nuclear Information System (INIS)

    Cheng, X.; Ding, M. D.; Zhang, J.; Guo, Y.; Chen, P. F.; Sun, J. Q.; Srivastava, A. K.

    2014-01-01

    A magnetic flux rope (MFR) is a coherent and helical magnetic field structure that has recently been found likely to appear as an elongated hot channel prior to a solar eruption. In this Letter, we investigate the relationship between the hot channel and the associated prominence through analysis of a limb event on 2011 September 12. In the early rise phase, the hot channel was initially cospatial with the prominence. It then quickly expanded, resulting in a separation of the top of the hot channel from that of the prominence. Meanwhile, they both experienced an instantaneous morphology transformation from a Λ shape to a reversed-Y shape and the top of these two structures showed an exponential increase in height. These features are a good indication of the occurrence of kink instability. Moreover, the onset of kink instability is found to coincide in time with the impulsive enhancement of flare emission underneath the hot channel, suggesting that ideal kink instability likely also plays an important role in triggering fast flare reconnection besides initiating the impulsive acceleration of the hot channel and distorting its morphology. We conclude that the hot channel is most likely the MFR system and the prominence only corresponds to the cool materials that are collected in the bottom of the helical field lines of the MFR against gravity

  15. Identification of a potent endothelium-derived angiogenic factor

    DEFF Research Database (Denmark)

    Jankowski, Vera; Tölle, Markus; Tran, Thi Nguyet Anh

    2013-01-01

    The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelia...

  16. Chloroatranol, an extremely potent allergen hidden in perfumes

    DEFF Research Database (Denmark)

    Johansen, Jeanne Duus; Andersen, Klaus Ejner; Svedman, Cecilia

    2003-01-01

    Oak moss absolute is a long-known, popular natural extract widely used in perfumes. It is reported as the cause of allergic reactions in a significant number of those with perfume allergy. Oak moss absolute has been the target of recent research to identify its allergenic components. Recently...... an open test simulating the use of perfumes on the volar aspect of the forearms in a randomized and double-blinded design. A solution with 5 p.p.m. chloroatranol was used for 14 days, and, in case of no reaction, the applications were continued for another 14 days with a solution containing 25 p.p.m. All....... The dose eliciting a reaction in 50% of the test subjects at patch testing was 0.2 p.p.m. In conclusion, the hidden exposure to a potent allergen widely used in perfumes has caused a highly sensitized cohort of individuals. Judged from the elicitation profile, chloroatranol is the most potent allergen...

  17. RAM, an RGDS analog, exerts potent anti-melanoma effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Maria Simona Aguzzi

    Full Text Available Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum-induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a mouse metastatic melanoma in vivo model, increasing doses of RAM significantly reduce up to about 80% lung metastases development, while comparable doses of RGDS are less potent. In conclusion these data show that RAM is a potent inhibitor of melanoma growth in vitro, strongly reduces melanoma metastases development in vivo and represents a novel candidate for further in vivo investigations in the cancer treatment field.

  18. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function

    DEFF Research Database (Denmark)

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis

    2013-01-01

    antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic...... of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r...... dermatitis), topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased...

  19. Prominent porto-systemic collateral pathways in patients with portal hypertension: demonstration by gadolinium-enhanced magnetic resonance angiography

    International Nuclear Information System (INIS)

    Caldana, Rogerio Pedreschi; Bezerra, Alexandre Araujo Sergio; Cecin, Alexnadre Oliveira; Souza, Luis Ronan Marques Ferreira de; Goldman, Susan Menasce; D'Ippolito, Giuseppe; Szejnfeld, Jacob

    2003-01-01

    To demonstrate the usefulness of gadolinium-enhanced magnetic resonance angiography in the evaluation of prominent porto-systemic collateral pathways. We reviewed the images from 40 patients with portal hypertension studied with gadolinium-enhanced magnetic resonance angiography and selected illustrative cases of prominent porto-systemic collateral pathways. The scans were performed using high field equipment (1.5 Tesla) and a 3 D volume technique. Image were obtained after intravenous injection of paramagnetic contrast media using a power injector. Magnetic resonance angiography demonstrated with precision the porto-systemic collateral pathways, particularly when investigating extensive territories or large vessels. The cases presented show the potential of this method in the investigation of patients with portal hypertension. Gadolinium-enhanced magnetic resonance angiography is a useful method for the evaluation of patients with portal hypertension and prominent collateral pathways. (author)

  20. The Spider Venom Peptide Lycosin-II Has Potent Antimicrobial Activity against Clinically Isolated Bacteria

    Directory of Open Access Journals (Sweden)

    Yongjun Wang

    2016-04-01

    Full Text Available Antimicrobial peptides have been accepted as excellent candidates for developing novel antibiotics against drug-resistant bacteria. Recent studies indicate that spider venoms are the source for the identification of novel antimicrobial peptides. In the present study, we isolated and characterized an antibacterial peptide named lycosin-II from the venom of the spider Lycosa singoriensis. It contains 21 amino acid residue lacking cysteine residues and forms a typical linear amphipathic and cationic α-helical conformation. Lycosin-II displays potent bacteriostatic effect on the tested drug-resistant bacterial strains isolated from hospital patients, including multidrug-resistant A. baumannii, which has presented a huge challenge for the infection therapy. The inhibitory ability of lycosin-II might derive from its binding to cell membrane, because Mg2+ could compete with the binding sites to reduce the bacteriostatic potency of lycosin-II. Our data suggest that lycosin-II might be a lead in the development of novel antibiotics for curing drug-resistant bacterial infections.

  1. 1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

    Science.gov (United States)

    Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

    1980-10-01

    The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.

  2. Effects of risk disclosure prominence in direct-to-consumer advertising (DTCA) of prescription drugs: An integrative cognitive process model.

    Science.gov (United States)

    Ju, Ilwoo; Park, Jin Seong

    2018-01-01

    The literature shows that the prominence of risk disclosure influences consumer responses to direct-to-consumer advertising of prescription drugs. However, little is known about the psychological process whereby disclosure prominence exerts its influences on health beliefs and behavior. Based on a review of the literature on health cognition and behavior, the current study proposed and tested a model to show that risk disclosure prominence affects consumers' drug choice intention through the mediating roles of awareness of drug adverse reactions (ARs), perceived control over ARs, and perceived risk of ARs. The findings were discussed in terms of their theoretical and managerial implications.

  3. A SOLAR TORNADO OBSERVED BY AIA/SDO: ROTATIONAL FLOW AND EVOLUTION OF MAGNETIC HELICITY IN A PROMINENCE AND CAVITY

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xing; Morgan, Huw; Leonard, Drew; Jeska, Lauren, E-mail: xxl@aber.ac.uk [Sefydliad Mathemateg a Ffiseg, Prifysgol Aberystwyth, Ceredigion, Cymru SY23 3BZ (United Kingdom)

    2012-06-20

    During 2011 September 24, as observed by the Atmospheric Imaging Assembly instrument of the Solar Dynamic Observatory and ground-based H{alpha} telescopes, a prominence and associated cavity appeared above the southwest limb. On 2011 September 25 8:00 UT, material flows upward from the prominence core along a narrow loop-like structure, accompanied by a rise ({>=}50,000 km) of the prominence core and the loop. As the loop fades by 10:00, small blobs and streaks of varying brightness rotate around the top part of the prominence and cavity, mimicking a cyclone. The most intense and coherent rotation lasts for over three hours, with emission in both hot ({approx}1 MK) and cold (hydrogen and helium) lines. We suggest that the cyclonic appearance and overall evolution of the structure can be interpreted in terms of the expansion of helical structures into the cavity, and the movement of plasma along helical structures which appears as a rotation when viewed along the helix axis. The coordinated movement of material between prominence and cavity suggests that they are structurally linked. Complexity is great due to the combined effect of these actions and the line-of-sight integration through the structure which contains tangled fields.

  4. A self-consistent model of a thermally balanced quiescent prominence in magnetostatic equilibrium in a uniform gravitational field

    International Nuclear Information System (INIS)

    Lerche, I.; Low, B.C.

    1977-01-01

    A theoretical model of quiescent prominences in the form of an infinite vertical sheet is presented. Self-consistent solutions are obtained by integrating simultaneously the set of nonlinear equations of magnetostatic equilibrium and thermal balance. The basic features of the models are: (1) The prominence matter is confined to a sheet and supported against gravity by a bowed magnetic field. (2) The thermal flux is channelled along magnetic field lines. (3) The thermal flux is everywhere balanced by Low's (1975) hypothetical heat sink which is proportional to the local density. (4) A constant component of the magnetic field along the length of the prominence shields the cool plasma from the hot surrounding. It is assumed that the prominence plasma emits more radiation than it absorbes from the radiation fields of the photosphere, chromosphere and corona, and the above hypothetical heat sink is interpreted to represent the amount of radiative loss that must be balanced by a nonradiative energy input. Using a central density and temperature of 10 11 particles cm -3 and 5000 K respectively, a magnetic field strength between 2 to 10 gauss and a thermal conductivity that varies linearly with temperature, the physical properties implied by the model are discussed. The analytic treatment can also be carried out for a class of more complex thermal conductivities. These models provide a useful starting point for investigating the combined requirements of magnetostatic equilibrium and thermal balance in the quiescent prominence. (Auth.)

  5. Nanosilver: Potent antimicrobial agent and its biosynthesis | Sarsar ...

    African Journals Online (AJOL)

    The synthesis of silver nanoparticles has been reported using chemical and physical methods. This review describes a cost effective and ecofriendly approach for the synthesis of silver nanoparticles. Thus, in this review we focus on the role of microorganisms and plants in the synthesis of nanosilver and their potent ...

  6. Non-LTE modelling of prominence fine structures using hydrogen Lyman-line profiles

    Czech Academy of Sciences Publication Activity Database

    Schwartz, Pavol; Gunár, S.; Curdt, W.

    2015-01-01

    Roč. 577, May (2015), A92/1-A92/10 ISSN 0004-6361 R&D Projects: GA ČR GAP209/12/0906 Grant - others:SAV(SK) VEGA 2/0108/12 Institutional support: RVO:67985815 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

  7. Potent antitumor activity of a urokinase-activated engineered anthrax toxin

    Science.gov (United States)

    Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

    2003-01-01

    The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

  8. Physical and technical performances are not associated with tactical prominence in U14 soccer matches.

    Science.gov (United States)

    Clemente, Filipe Manuel; Figueiredo, António José; Martins, Fernando Manuel Lourenço; Mendes, Rui Sousa; Wong, Del P

    2016-01-01

    The aim of this study was to analyse the association between physical/technical variables and the tactical prominence variables in U14 soccer matches. Twenty-two young amateur soccer players (13.5 [Formula: see text] 0.5 years old, 5.4 [Formula: see text] 0.5 years of practice, 163.3 [Formula: see text] 9.8 cm in body height) from two teams of the Portuguese regional league volunteered for the study. Our results showed positive and moderate correlation between dribbling test and betweenness centrality (r = 0.324; p = 0.142), and negative moderate correlation between %fatigue index and betweenness centrality (r = -0.390; p = 0.073). Physical and technical variables had no statistical differences among tactical positions. Nevertheless, when tactical prominence of players from four tactical positions were compared, significant differences were found in terms of degree prestige (p = 0.001) and degree centrality (p = 0.002). This pilot study did not find strong correlations between physical/technical levels and tactical prominence in soccer matches.

  9. Reconstruction of a helical prominence in 3D from IRIS spectra and images

    Czech Academy of Sciences Publication Activity Database

    Schmieder, B.; Zapiór, Maciej; Ariste, A.L.; Levens, P.; Labrosse, N.; Gravet, R.

    2017-01-01

    Roč. 606, October (2017), A30/1-A30/13 E-ISSN 1432-0746 Institutional support: RVO:67985815 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy , Celestial Mechanics, Astrophysics OBOR OECD: Astronomy (including astrophysics,space science) Impact factor: 5.014, year: 2016

  10. Development of short and highly potent self-assembling elastin-derived pentapeptide repeats containing aromatic amino acid residues.

    Science.gov (United States)

    Taniguchi, Suguru; Watanabe, Noriko; Nose, Takeru; Maeda, Iori

    2016-01-01

    Tropoelastin is the primary component of elastin, which forms the elastic fibers that make up connective tissues. The hydrophobic domains of tropoelastin are thought to mediate the self-assembly of elastin into fibers, and the temperature-mediated self-assembly (coacervation) of one such repetitive peptide sequence (VPGVG) has been utilized in various bio-applications. To elucidate a mechanism for coacervation activity enhancement and to develop more potent coacervatable elastin-derived peptides, we synthesized two series of peptide analogs containing an aromatic amino acid, Trp or Tyr, in addition to Phe-containing analogs and tested their functional characteristics. Thus, position 1 of the hydrophobic pentapeptide repeat of elastin (X(1)P(2)G(3)V(4)G(5)) was substituted by Trp or Tyr. Eventually, we acquired a novel, short Trp-containing elastin-derived peptide analog (WPGVG)3 with potent coacervation ability. From the results obtained during this process, we determined the importance of aromaticity and hydrophobicity for the coacervation potency of elastin-derived peptide analogs. Generally, however, the production of long-chain synthetic polypeptides in quantities sufficient for commercial use remain cost-prohibitive. Therefore, the identification of (WPGVG)3, which is a 15-mer short peptide consisting simply of five natural amino acids and shows temperature-dependent self-assembly activity, might serve as a foundation for the development of various kinds of biomaterials. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  11. Hydroxychavicol: a potent xanthine oxidase inhibitor obtained from the leaves of betel, Piper betle.

    Science.gov (United States)

    Murata, Kazuya; Nakao, Kikuyo; Hirata, Noriko; Namba, Kensuke; Nomi, Takao; Kitamura, Yoshihisa; Moriyama, Kenzo; Shintani, Takahiro; Iinuma, Munekazu; Matsuda, Hideaki

    2009-07-01

    The screening of Piperaceous plants for xanthine oxidase inhibitory activity revealed that the extract of the leaves of Piper betle possesses potent activity. Activity-guided purification led us to obtain hydroxychavicol as an active principle. Hydroxychavicol is a more potent xanthine oxidase inhibitor than allopurinol, which is clinically used for the treatment of hyperuricemia.

  12. Development and Parameters of a Non-Self-Similar CME Caused by the Eruption of a Quiescent Prominence

    Science.gov (United States)

    Kuzmenko, I. V.; Grechnev, V. V.

    2017-10-01

    The eruption of a large quiescent prominence on 17 August 2013 and an associated coronal mass ejection (CME) were observed from different vantage points by the Solar Dynamics Observatory (SDO), the Solar-Terrestrial Relations Observatory (STEREO), and the Solar and Heliospheric Observatory (SOHO). Screening of the quiet Sun by the prominence produced an isolated negative microwave burst. We estimated the parameters of the erupting prominence from a radio absorption model and measured them from 304 Å images. The variations of the parameters as obtained by these two methods are similar and agree within a factor of two. The CME development was studied from the kinematics of the front and different components of the core and their structural changes. The results were verified using movies in which the CME expansion was compensated for according to the measured kinematics. We found that the CME mass (3.6 × 10^{15} g) was mainly supplied by the prominence (≈ 6 × 10^{15} g), while a considerable part drained back. The mass of the coronal-temperature component did not exceed 10^{15} g. The CME was initiated by the erupting prominence, which constituted its core and remained active. The structural and kinematical changes started in the core and propagated outward. The CME structures continued to form during expansion, which did not become self-similar up to 25 R_{⊙}. The aerodynamic drag was insignificant. The core formed during the CME rise to 4 R_{⊙} and possibly beyond. Some of its components were observed to straighten and stretch outward, indicating the transformation of tangled structures of the core into a simpler flux rope, which grew and filled the cavity as the CME expanded.

  13. Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.

    Science.gov (United States)

    Feng, Song; Hong, Di; Wang, Baoxia; Zheng, Xiufang; Miao, Kun; Wang, Lisha; Yun, Hongying; Gao, Lu; Zhao, Shuhai; Shen, Hong C

    2015-03-12

    A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. The most potent compound 8jm showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of 8jm appeared to be superior to BMS433771, and supported further optimization.

  14. Possible Correlation Between Bile Salt Hydrolysis and AHL Deamidation: Staphylococcus epidermidis RM1, a Potent Quorum Quencher and Bile Salt Hydrolase Producer.

    Science.gov (United States)

    Mukherji, Ruchira; Prabhune, Asmita

    2015-05-01

    The aim of the present work was to isolate a bile salt hydrolase (BSH) producer from fermented soy curd and explore the ability of the BSH produced to cleave bacterial quorum sensing signals. Bacterial isolates with possible ability to deconjugate bile salts were enriched and isolated on De Man, Rogosa and Sharpe (MRS) medium containing 0.2% bile salts. BSH-producing positive isolate with orange-pink-pigmented colonies was isolated and was identified as a strain of Staphylococcus epidermidis using biochemical and phylogenetic tools. S. epidermidis RM1 was shown to possess both potent BSH and N-acyl homoserine lactone (AHL) cleavage activity. Genetic basis of this dual-enzyme activity was explored by means of specific primers designed using S. epidermidis ATCC 12228 genome as template. It was observed that a single enzyme was not responsible for both the activity. Two different genetic elements corresponding to each of the enzymatic activity were successfully amplified from the genomic DNA of the isolate.

  15. Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge.

    Science.gov (United States)

    Jung, Jaeyun; Yeom, Chanjoo; Choi, Yeon-Sook; Kim, Sinae; Lee, EunJi; Park, Min Ji; Kang, Sang Wook; Kim, Sung Bae; Chang, Suhwan

    2015-08-21

    The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.

  16. PRE-FLARE CORONAL JET AND EVOLUTIONARY PHASES OF A SOLAR ERUPTIVE PROMINENCE ASSOCIATED WITH THE M1.8 FLARE: SDO AND RHESSI OBSERVATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Bhuwan; Kushwaha, Upendra [Udaipur Solar Observatory, Physical Research Laboratory, Udaipur 313001 (India); Veronig, Astrid M. [Kanzelhöhe Observatory/Institute of Physics, University of Graz, Universitätsplatz 5, A-8010 Graz (Austria); Cho, K.-S., E-mail: bhuwan@prl.res.in [Korea Astronomy and Space Science Institute, Daejeon 305-348 (Korea, Republic of)

    2016-12-01

    We investigate the triggering, activation, and ejection of a solar eruptive prominence that occurred in a multi-polar flux system of active region NOAA 11548 on 2012 August 18 by analyzing data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory , the Reuven Ramaty High Energy Solar Spectroscopic Imager , and the Extreme Ultraviolet Imager/Sun Earth Connection Coronal and Heliospheric Investigation on board the Solar Terrestrial Relation Observatory . Prior to the prominence activation, we observed striking coronal activities in the form of a blowout jet, which is associated with the rapid eruption of a cool flux rope. Furthermore, the jet-associated flux rope eruption underwent splitting and rotation during its outward expansion. These coronal activities are followed by the prominence activation during which it slowly rises with a speed of ∼12 km s{sup −1} while the region below the prominence emits gradually varying EUV and thermal X-ray emissions. From these observations, we propose that the prominence eruption is a complex, multi-step phenomenon in which a combination of internal (tether-cutting reconnection) and external (i.e., pre-eruption coronal activities) processes are involved. The prominence underwent catastrophic loss of equilibrium with the onset of the impulsive phase of an M1.8 flare, suggesting large-scale energy release by coronal magnetic reconnection. We obtained signatures of particle acceleration in the form of power-law spectra with hard electron spectral index ( δ  ∼ 3) and strong HXR footpoint sources. During the impulsive phase, a hot EUV plasmoid was observed below the apex of the erupting prominence that ejected in the direction of the prominence with a speed of ∼177 km s{sup −1}. The temporal, spatial, and kinematic correlations between the erupting prominence and the plasmoid imply that the magnetic reconnection supported the fast ejection of prominence in the lower corona.

  17. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.

    Directory of Open Access Journals (Sweden)

    Anna Figueiredo

    2006-11-01

    Full Text Available Nonnucleoside reverse transcriptase inhibitors (NNRTIs target HIV-1 reverse transcriptase (RT by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.

  18. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Manchukonda

    Full Text Available Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol than the parent compound, noscapine (-5.505 kCal/mol and its existing derivatives (-5.563 to -6.412 kCal/mol. Free energy (ΔG bind calculations based on the linear interaction energy (LIE empirical equation utilizing Surface Generalized Born (SGB continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol. Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol. The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl noscapine (6f binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM, which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM. All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  19. Direct Detection of the Helical Magnetic Field Geometry from 3D Reconstruction of Prominence Knot Trajectories

    Science.gov (United States)

    Zapiór, Maciej; Martínez-Gómez, David

    2016-02-01

    Based on the data collected by the Vacuum Tower Telescope located in the Teide Observatory in the Canary Islands, we analyzed the three-dimensional (3D) motion of so-called knots in a solar prominence of 2014 June 9. Trajectories of seven knots were reconstructed, giving information of the 3D geometry of the magnetic field. Helical motion was detected. From the equipartition principle, we estimated the lower limit of the magnetic field in the prominence to ≈1-3 G and from the Ampère’s law the lower limit of the electric current to ≈1.2 × 109 A.

  20. 2D radiative-magnetohydrostatic model of a prominence observed by Hinode, SoHO/SUMER and Meudon/MSDP

    Science.gov (United States)

    Berlicki, A.; Gunar, S.; Heinzel, P.; Schmieder, B.; Schwartz, P.

    2011-06-01

    Aims: Prominences observed by Hinode show very dynamical and intriguing structures. To understand the mechanisms that are responsible for these moving structures, it is important to know the physical conditions that prevail in fine-structure threads. In the present work we analyse a quiescent prominence with fine structures, which exhibits dynamic behaviour, which was observed in the hydrogen Hα line with Hinode/SOT, Meudon/MSDP and Ondřejov/HSFA2, and simultaneously in hydrogen Lyman lines with SoHO/SUMER during a coordinated campaign. We derive the fine-structure physical parameters of this prominence and also address the questions of the role of the magnetic dips and of the interpretation of the flows. Methods: We calibrate the SoHO/SUMER and Meudon/MSDP data and obtain the line profiles of the hydrogen Lyman series (Lβ to L6), the Ciii (977.03 Å) and Svi (933.40 Å), and Hα along the slit of SoHO/SUMER that crosses the Hinode/SOT prominence. We employ a complex 2D radiation-magnetohydrostatic (RMHS) modelling technique to properly interpret the observed spectral lines and derive the physical parameters of interest. The model was constrained not only with integrated intensities of the lines, but also with the hydrogen line profiles. Results: The slit of SoHO/SUMER is crossing different prominence structures: threads and dark bubbles. Comparing the observed integrated intensities, the depressions of Hα bubbles are clearly identified in the Lyman, Ciii, and Svi lines. To fit the observations, we propose a new 2D model with the following parameters: T = 8000 K, pcen = 0.035 dyn cm-2, B = 5 Gauss, ne = 1010 cm-3, 40 threads each 1000 km wide, plasma β is 3.5 × 10-2. Conclusions: The analysis of Ciii and Svi emission in dark Hα bubbles allows us to conclude that there is no excess of a hotter plasma in these bubbles. The new 2D model allows us to diagnose the orientation of the magnetic field versus the LOS. The 40 threads are integrated along the LOS. We

  1. Prominent deep medullary veins: a predictive biomarker for stroke risk from transient ischemic attack?

    Science.gov (United States)

    Duan, Yang; Xu, Zhihua; Li, Hongyi; Cai, Xiaonan; Chang, Cancan; Yang, Benqiang

    2018-05-01

    Background Deep medullary veins (DMVs) are a biomarker of severity and prognosis in patients with acute cerebral infarction. However, their clinical significance remains unclear in patients with transient ischemic attack (TIA). Purpose To determine whether prominent deep medullary veins (PDMVs) are a predictive biomarker for stroke risk after TIA. Material and Methods Clinical and imaging data of 49 patients with TIA and 49 sex- and age-matched controls were studied. PDMVs were defined as DMVs with a score of 3 (TDMVs) or asymmetric DMVs (ADMVs), and the relationship between PDMVs and clinical features was analyzed. The DMV score based on susceptibility weighted imaging (SWI) ranged from 0 (not visible) to 3 (very prominent) and was calculated for both hemispheres separately. A different score in each hemisphere was defined as ADMVs and an equal score was defined as symmetric DMVs. The asymmetry and score of DMVs were compared between the two groups and with respect to the time from TIA onset to imaging analysis. Results Agreement between neuroradiologists for the DMV asymmetry/score on SWI was excellent. The frequency of ADMVs and TDMVs was significantly higher in patients with TIA than controls ( P  0.05); PDMVs were not correlated with age, blood pressure, or diabetes. However, PDMVs were associated with the ABCD2 score (≥4), clinical symptoms, and duration of TIA (≥10 min). Conclusion Prominent deep medullary veins is a predictive biomarker for the risk of stroke in many patients having suffered from TIA.

  2. Structural optimization and docking studies of anatoxin-a: A potent ...

    African Journals Online (AJOL)

    , structural properties and molecular interaction of anatoxin-a, a naturally occurring potent neurotoxin. The geometry of the anatoxin-a was fully optimized in terms of density functional theory Gaussian 09. Calculations for structural parameters ...

  3. Potent inhibition of tau fibrillization with a multivalent ligand

    International Nuclear Information System (INIS)

    Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

    2007-01-01

    Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at ∼80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors

  4. Prominent Determinants of Consumer-Based Brand Equity

    Directory of Open Access Journals (Sweden)

    Elisa Battistoni

    2013-08-01

    Full Text Available In this paper we investigate the most prominent drivers of brand equity, from a consumerbased point of view. We present a new approach for measuring brand equity, which can be applied regardless of the brand sector and is based on the Analytic Hierarchy Process. This approach has the main advantage of allowing for comparisons to be made between non‐directly measurable elements and also has the advantage of enabling the ranking of intangible criteria, such as consumers’ feelings or purchase intentions. We focus on the fashion industry, since we believe in the higher value of our approach when applied to brands which offer products with less tangible characteristics. Thanks to a case study – which involved about 250 interviewees – we succeed in finding and prioritizing the elements which can have an impact on the brand value. We also provide a global ranking for three apparel brands: Gap, H&M and Zara. The results from our model are consistent with other popular ratings and can be extremely useful for brand managers.

  5. microRNA-101 is a potent inhibitor of autophagy

    DEFF Research Database (Denmark)

    Frankel, Lisa B; Wen, Jiayu; Lees, Michael

    2011-01-01

    performed a functional screen in search of microRNAs (miRNAs), which regulate the autophagic flux in breast cancer cells. In this study, we identified the tumour suppressive miRNA, miR-101, as a potent inhibitor of basal, etoposide- and rapamycin-induced autophagy. Through transcriptome profiling, we...

  6. Sulfoximines as potent RORγ inverse agonists.

    Science.gov (United States)

    Ouvry, Gilles; Bihl, Franck; Bouix-Peter, Claire; Christin, Olivier; Defoin-Platel, Claire; Deret, Sophie; Feret, Christophe; Froude, David; Hacini-Rachinel, Feriel; Harris, Craig S; Hervouet, Catherine; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Parnet, Veronique; Pascau, Coralie; Pascau, Jonathan; Pierre, Romain; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent F

    2018-05-01

    Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. How shall we know them? Trainee teachers’ perceptions of their learners’ abilities

    Directory of Open Access Journals (Sweden)

    Rushton, Ian

    2011-01-01

    Full Text Available This article, being the final one in a series of three for this journal, is concerned with trainee teachers’ changing perceptions of their learners and focuses on two areas: trainees’ perceptions of their learners’ abilities and how they are formed by their own experiences as learners; and the changes in trainees’ perceptions over the duration of their two year Initial Teacher Education (ITE course in the Lifelong Learning Sector (LLS. Working within a multi-method approach to action research, this small-scale study found that trainees’ perceptions were influenced not so much by their own identities and habitus, although social capital was a prominent feature, but by a problematic mix of competing cultures and the impact of casualisation in the sector.

  8. Bicyclams, selective antagonists of the human chemokine receptor CXCR4, potently inhibit feline immunodeficiency virus replication

    NARCIS (Netherlands)

    Horzinek, M.C.; Egberink, H.F.; Clercq, E. de; Vliet, A.L.W. van; Balzarini, J.; Bridger, G.J.; Henson, G.; Schols, D.

    1999-01-01

    Bicyclams are low-molecular-weight anti-human immunodeficiency virus (HIV) agents that have been shown to act as potent and selective CXC chemokine receptor 4 (CXCR4) antagonists. Here, we demonstrate that bicyclams are potent inhibitors of feline immunodeficiency virus (FIV) replication when

  9. DIRECT DETECTION OF THE HELICAL MAGNETIC FIELD GEOMETRY FROM 3D RECONSTRUCTION OF PROMINENCE KNOT TRAJECTORIES

    Energy Technology Data Exchange (ETDEWEB)

    Zapiór, Maciej; Martinez-Gómez, David, E-mail: zapior.maciek@gmail.com [Physics Department, University of the Balearic Islands, Cra. de Valldemossa, km 7.5. Palma (Illes Balears), E-07122 (Spain)

    2016-02-01

    Based on the data collected by the Vacuum Tower Telescope located in the Teide Observatory in the Canary Islands, we analyzed the three-dimensional (3D) motion of so-called knots in a solar prominence of 2014 June 9. Trajectories of seven knots were reconstructed, giving information of the 3D geometry of the magnetic field. Helical motion was detected. From the equipartition principle, we estimated the lower limit of the magnetic field in the prominence to ≈1–3 G and from the Ampère’s law the lower limit of the electric current to ≈1.2 × 10{sup 9} A.

  10. A potent steroid cream is superior to emollients in reducing acute radiation dermatitis in breast cancer patients treated with adjuvant radiotherapy. A randomised study of betamethasone versus two moisturizing creams

    International Nuclear Information System (INIS)

    Ulff, Eva; Maroti, Marianne; Serup, Jörgen; Falkmer, Ursula

    2013-01-01

    Background and purpose: The aim was to investigate whether treatment with potent local steroids can reduce signs and symptoms of acute radiation dermatitis in breast cancer patients undergoing adjuvant radiotherapy (RT) compared to emollient creams. Material and methods: The study was randomised and double-blinded. Patients with breast cancer who had undergone mastectomy or breast-conserving surgery were included when they started adjuvant 3-D planned RT. In all, 104 patients were randomised 2:1:1 to three treatment groups, i.e. betamethasone + Essex® cream, Essex® cream or Canoderm® cream. The patients themselves treated the irradiated area during the radiation period (5 weeks) and two weeks after cessation of RT. Signs of RT dermatitis were measured qualitatively with RTOG clinical scoring and quantitatively by colorimeter. In addition, the patients’ symptoms were recorded as well as the Fitzpatrick skin type. There was a statistically significant difference (p = 0.05) in skin reactions when assessed with RTOG in favour of the group treated with the potent steroid. Patient-related symptoms did not differ between the treatment groups. The effect of the steroid was prominent in three subgroups, i.e. (i) patients treated with ablation of the breast, (ii) patients receiving RT to the armpit and the supraclavicular fossa, and (iii) patients with Fitzpatrick skin type 1. Conclusions: Treatment with betamethasone cream is more efficient than moisturizers for the control of acute RT dermatitis in patients treated with adjuvant RT for breast cancer

  11. Naturin: a potent bio-immunomodifier

    International Nuclear Information System (INIS)

    Rong Nian Shen; Li Lu; Homayoon Shidnia; Xiao Qing Jia

    1995-01-01

    Mechanism of the efficacy of naturin in enhancement and rejuvenation in natural immunity including NK cells, LAK cell activity and CD4 + T-cell function against cancer and infectious diseases is still not known. However, the immunomodulating effect of naturin is similar or even better than the results of IL-1α and IL-7. It is intriguing to speculate that the potent immunomodifier effect of naturin may be mediated either entirely or partially due to a mechanism involving cytokines. Our experiments suggest that naturin plays a role in the restoration of cellular immunosuppression induced by a number of different stresses. This in turn may reflect the fact that naturin possesses a potential regulatory role in induction of some immune cytokines. 31 refs., 4 figs., 4 tabs

  12. Investigation of the prominent barriers to lean manufacturing implementation in Malaysian food and beverages industry using Rasch Model

    Science.gov (United States)

    Khusaini, N. S.; Ismail, A.; Rashid, A. A.

    2016-02-01

    This paper presents a preliminary study on the prominent barriers to lean manufacturing implementation in Malaysian Food and Beverages Industry. A survey was carried out to determine the most prominent barriers of lean manufacturing implementation that are currently being faced in this industry. The amount of barriers identified for this study is twenty seven. Out of 1309 available organizations, a total of 300 organizations have been randomly selected as respondents, and 53 organizations responded. From the variable map, the analysis shows that, the negative perception towards lean manufacturing top the list as the most agreeable barrier, while the technical barriers came after it. It can also be seen from the variable map that averagely, lack of vision and direction is the barrier that is being faced. Finally, this is perhaps the first attempt in investigating the prominent barriers to Lean Manufacturing implementation in Malaysian food and beverages industry using Rasch Model.

  13. Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.

    Science.gov (United States)

    Wagner, Steven L; Rynearson, Kevin D; Duddy, Steven K; Zhang, Can; Nguyen, Phuong D; Becker, Ann; Vo, Uyen; Masliah, Deborah; Monte, Louise; Klee, Justin B; Echmalian, Corinne M; Xia, Weiming; Quinti, Luisa; Johnson, Graham; Lin, Jiunn H; Kim, Doo Y; Mobley, William C; Rissman, Robert A; Tanzi, Rudolph E

    2017-07-01

    Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid- β peptide (A β ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the A β 42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred t γ -secretase modulatoro as γ -secretase modulators that inhibited the production of the A β 42 peptide and to a lesser degree the A β 40 peptide while concomitantly increasing the production of the carboxyl-truncated A β 38 and A β 37 peptides. These modulators potently lower A β 42 levels without inhibiting the γ -secretase-mediated proteolysis of Notch or causing accumulation of carboxyl-terminal fragments of APP. In this study, we report a large number of pharmacological studies and early assessment of toxicology characterizing a highly potent γ -secretase modulator (GSM), ( S )- N -(1-(4-fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1 H -imidazol-1-yl)pyridin-2-yl)-4-methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to significantly lower A β 42 levels in the central nervous system of rats and mice at doses as low as 5-10 mg/kg, significantly reduce A β neuritic plaque load in an AD transgenic mouse model, and significantly reduce levels of insoluble A β 42 and pThr181 tau in a three-dimensional human neural cell culture model. Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose toxicity studies in nonhuman primates have designated this GSM for 28-day Investigational New Drug-enabling good laboratory practice studies and positioned it as a candidate for human clinical trials. Copyright © 2017 by The Author(s).

  14. Differences between Doppler velocities of ions and neutral atoms in a solar prominence

    Science.gov (United States)

    Anan, T.; Ichimoto, K.; Hillier, A.

    2017-05-01

    Context. In astrophysical systems with partially ionized plasma, the motion of ions is governed by the magnetic field while the neutral particles can only feel the magnetic field's Lorentz force indirectly through collisions with ions. The drift in the velocity between ionized and neutral species plays a key role in modifying important physical processes such as magnetic reconnection, damping of magnetohydrodynamic waves, transport of angular momentum in plasma through the magnetic field, and heating. Aims: This paper aims to investigate the differences between Doppler velocities of calcium ions and neutral hydrogen in a solar prominence to look for velocity differences between the neutral and ionized species. Methods: We simultaneously observed spectra of a prominence over an active region in H I 397 nm, H I 434 nm, Ca II 397 nm, and Ca II 854 nm using a high dispersion spectrograph of the Domeless Solar Telescope at Hida observatory. We compared the Doppler velocities, derived from the shift of the peak of the spectral lines presumably emitted from optically-thin plasma. Results: There are instances when the difference in velocities between neutral atoms and ions is significant, for example 1433 events ( 3% of sets of compared profiles) with a difference in velocity between neutral hydrogen atoms and calcium ions greater than 3σ of the measurement error. However, we also found significant differences between the Doppler velocities of two spectral lines emitted from the same species, and the probability density functions of velocity difference between the same species is not significantly different from those between neutral atoms and ions. Conclusions: We interpreted the difference of Doppler velocities as being a result of the motions of different components in the prominence along the line of sight, rather than the decoupling of neutral atoms from plasma. The movie attached to Fig. 1 is available at http://www.aanda.org

  15. Marine-derived fungi: Source of biologically potent and novel compounds

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Parvatkar, R.R.; Tilvi, S.; Gawas, S.G.

    -83) showed potent anti-mycobacterial activity against Mycobacterium smegmatis, M. bovisand M. tuberculosis, with MIC values in the range 0.02–2.0 mg/mL, and were effective against both actively growing and dormant states. Trichodermaquinone (84...

  16. OBSERVATIONAL DETECTION OF DRIFT VELOCITY BETWEEN IONIZED AND NEUTRAL SPECIES IN SOLAR PROMINENCES

    Energy Technology Data Exchange (ETDEWEB)

    Khomenko, Elena; Collados, Manuel [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain); Díaz, Antonio J., E-mail: khomenko@iac.es, E-mail: mcv@iac.es, E-mail: aj.diaz@uib.es [Universitat de les Illes Balears, 07122, Crta Valldemossa, km 7.5, Palma de Mallorca (Spain)

    2016-06-01

    We report the detection of differences in the ion and neutral velocities in prominences using high-resolution spectral data obtained in 2012 September at the German Vacuum Tower Telescope (Observatorio del Teide, Tenerife). A time series of scans of a small portion of a solar prominence was obtained simultaneously with high cadence using the lines of two elements with different ionization states, namely, Ca ii 8542 Å and He i 10830 Å. The displacements, widths, and amplitudes of both lines were carefully compared to extract dynamical information about the plasma. Many dynamical features are detected, such as counterstreaming flows, jets, and propagating waves. In all of the cases, we find a very strong correlation between the parameters extracted from the lines of both elements, confirming that both lines trace the same plasma. Nevertheless, we also find short-lived transients where this correlation is lost. These transients are associated with ion-neutral drift velocities of the order of several hundred m s{sup −1}. The patches of non-zero drift velocity show coherence in time–distance diagrams.

  17. Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

    Science.gov (United States)

    Swedberg, Joakim E; Harris, Jonathan M

    2011-10-04

    Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

  18. D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.

    Science.gov (United States)

    Zask, Arie; Birnberg, Gary; Cheung, Katherine; Kaplan, Joshua; Niu, Chuan; Norton, Emily; Yamashita, Ayako; Beyer, Carl; Krishnamurthy, Girija; Greenberger, Lee M; Loganzo, Frank; Ayral-Kaloustian, Semiramis

    2004-08-16

    Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI-286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant cell lines expressing P-glycoprotein. Amides derived from proline had potency comparable to HTI-286. Reduction of the carboxylic acid to ketones and alcohols or its conversion to acidic heterocycles also gave potent analogs. Synthetic modifications of the carboxylic acid could be carried out selectively using a wide range of synthetic reagents. Proline analog 3 was found to be effective in a human xenograft model in athymic mice.

  19. Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

    OpenAIRE

    Zuo, Jun; Quinn, Kevin K.; Kye, Steve; Cooper, Paige; Damoiseaux, Robert; Krogstad, Paul

    2012-01-01

    No antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and prot...

  20. Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

    Energy Technology Data Exchange (ETDEWEB)

    Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.; Stewart, Deirdre S.; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E.; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S. (Harvard-Med); (Mass. Gen. Hosp.); (UIC)

    2012-12-10

    We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

  1. The magnetic field configuration of a solar prominence inferred from spectropolarimetric observations in the He i 10 830 Å triplet

    Science.gov (United States)

    Orozco Suárez, D.; Asensio Ramos, A.; Trujillo Bueno, J.

    2014-06-01

    Context. Determining the magnetic field vector in quiescent solar prominences is possible by interpreting the Hanle and Zeeman effects in spectral lines. However, observational measurements are scarce and lack high spatial resolution. Aims: We determine the magnetic field vector configuration along a quiescent solar prominence by interpreting spectropolarimetric measurements in the He i 1083.0 nm triplet obtained with the Tenerife Infrared Polarimeter installed at the German Vacuum Tower Telescope of the Observatorio del Teide. Methods: The He i 1083.0 nm triplet Stokes profiles were analyzed with an inversion code that takes the physics responsible for the polarization signals in this triplet into account. The results are put into a solar context with the help of extreme ultraviolet observations taken with the Solar Dynamic Observatory and the Solar Terrestrial Relations Observatory satellites. Results: For the most probable magnetic field vector configuration, the analysis depicts a mean field strength of 7 gauss. We do not find local variations in the field strength except that the field is, on average, lower in the prominence body than in the prominence feet, where the field strength reaches ~25 gauss. The averaged magnetic field inclination with respect to the local vertical is ~77°. The acute angle of the magnetic field vector with the prominence main axis is 24° for the sinistral chirality case and 58° for the dextral chirality. These inferences are in rough agreement with previous results obtained from the analysis of data acquired with lower spatial resolutions. A movie is available in electronic form at http://www.aanda.org

  2. Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

    Science.gov (United States)

    Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

    2016-02-26

    Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

  3. Gender parity trends for invited speakers at four prominent virology conference series.

    Science.gov (United States)

    Kalejta, Robert F; Palmenberg, Ann C

    2017-06-07

    Scientific conferences are most beneficial to participants when they showcase significant new experimental developments, accurately summarize the current state of the field, and provide strong opportunities for collaborative networking. A top-notch slate of invited speakers, assembled by conference organizers or committees, is key to achieving these goals. The perceived underrepresentation of female speakers at prominent scientific meetings is currently a popular topic for discussion, but one that often lacks supportive data. We compiled the full rosters of invited speakers over the last 35 years for four prominent international virology conferences, the American Society for Virology Annual Meeting (ASV), the International Herpesvirus Workshop (IHW), the Positive-Strand RNA Virus Symposium (PSR), and the Gordon Research Conference on Viruses & Cells (GRC). The rosters were cross-indexed by unique names, gender, year, and repeat invitations. When plotted as gender-dependent trends over time, all four conferences showed a clear proclivity for male-dominated invited speaker lists. Encouragingly, shifts toward parity are emerging within all units, but at different rates. Not surprisingly, both selection of a larger percentage of first time participants and the presence of a woman on the speaker selection committee correlated with improved parity. Session chair information was also collected for the IHW and GRC. These visible positions also displayed a strong male dominance over time that is eroding slowly. We offer our personal interpretation of these data to aid future organizers achieve improved equity among the limited number of available positions for session moderators and invited speakers. IMPORTANCE Politicians and media members have a tendency to cite anecdotes as conclusions without any supporting data. This happens so frequently now, that a name for it has emerged: fake news. Good science proceeds otherwise. The under representation of women as invited

  4. The temporal behaviour of MHD waves in a partially ionized prominence-like plasma: Effect of heating and cooling

    Science.gov (United States)

    Ballester, J. L.; Carbonell, M.; Soler, R.; Terradas, J.

    2018-01-01

    Context. During heating or cooling processes in prominences, the plasma microscopic parameters are modified due to the change of temperature and ionization degree. Furthermore, if waves are excited on this non-stationary plasma, the changing physical conditions of the plasma also affect wave dynamics. Aims: Our aim is to study how temporal variation of temperature and microscopic plasma parameters modify the behaviour of magnetohydrodynamic (MHD) waves excited in a prominence-like hydrogen plasma. Methods: Assuming optically thin radiation, a constant external heating, the full expression of specific internal energy, and a suitable energy equation, we have derived the profiles for the temporal variation of the background temperature. We have computed the variation of the ionization degree using a Saha equation, and have linearized the single-fluid MHD equations to study the temporal behaviour of MHD waves. Results: For all the MHD waves considered, the period and damping time become time dependent. In the case of Alfvén waves, the cut-off wavenumbers also become time dependent and the attenuation rate is completely different in a cooling or heating process. In the case of slow waves, while it is difficult to distinguish the slow wave properties in a cooling partially ionized plasma from those in an almost fully ionized plasma, the period and damping time of these waves in both plasmas are completely different when the plasma is heated. The temporal behaviour of the Alfvén and fast wave is very similar in the cooling case, but in the heating case, an important difference appears that is related with the time damping. Conclusions: Our results point out important differences in the behaviour of MHD waves when the plasma is heated or cooled, and show that a correct interpretation of the observed prominence oscillations is very important in order to put accurate constraints on the physical situation of the prominence plasma under study, that is, to perform prominence

  5. 2-Arylbenzo[b]furan derivatives as potent human lipoxygenase inhibitors.

    Science.gov (United States)

    Lang, Li; Dong, Ningning; Wu, Deyan; Yao, Xue; Lu, Weiqiang; Zhang, Chen; Ouyang, Ping; Zhu, Jin; Tang, Yun; Wang, Wei; Li, Jian; Huang, Jin

    2016-01-01

    Human lipoxygenases (LOXs) have been emerging as effective therapeutic targets for inflammatory diseases. In this study, we found that four natural 2-arylbenzo[b]furan derivatives isolated from Artocarpus heterophyllus exhibited potent inhibitory activities against human LOXs, including moracin C (1), artoindonesianin B-1 (2), moracin D (3), moracin M (4). In our in vitro experiments, compound 1 was identified as the most potent LOX inhibitor and the moderate subtype selective inhibitor of 12-LOX. Compounds 1 and 2 act as competitive inhibitors of LOXs. Moreover, 1 significantly inhibits LTB4 production and chemotactic capacity of neutrophils, and is capable of protecting vascular barrier from plasma leakage in vivo. In addition, the preliminary structure-activity relationship analysis was performed based on the above four naturally occurring (1-4) and six additional synthetic 2-arylbenzo[b]furan derivatives. Taken together, these 2-arylbenzo[b]furan derivatives, as LOXs inhibitors, could represent valuable leads for the future development of therapeutic agents for inflammatory diseases.

  6. Honokiol trimers and dimers via biotransformation catalyzed by Momordica charantia peroxidase: novel and potent α-glucosidase inhibitors.

    Science.gov (United States)

    He, Ye; Wang, Xiao-Bing; Fan, Bo-Yi; Kong, Ling-Yi

    2014-01-15

    Ten honokiol oligomers (1-10), including four novel trimers (1-4) and four novel dimers (5-8), were obtained by means of biotransformation of honokiol catalyzed by Momordica charantia peroxidase (MCP) for the first time. Their structures were established on the basis of spectroscopic methods. The biological results demonstrated that most of the oligomers were capable of inhibiting α-glucosidase with significant abilities, which were one to two orders of magnitude more potent than the substrate, honokiol. In particular, compound 2, the honokiol trimer, displayed the greatest inhibitory activity against α-glucosidase with an IC50 value of 1.38μM. Kinetic and CD studies indicated that 2 inhibited α-glucosidase in a reversible, mixed-type manner and caused conformational changes in the secondary structure of the enzyme protein. These findings suggested that 2 might be exploited as a promising drug candidate for the treatment of diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

    Science.gov (United States)

    Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

    2009-06-01

    In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

  8. F0-based rhythm effects on the perception of local syllable prominence

    DEFF Research Database (Denmark)

    Niebuhr, Oliver

    2009-01-01

    of the global rhythmic context with regard to both the prominence and the F(0) patterns. Two conclusions were drawn on this basis. First, listeners use speech rhythm to predict the perceptual properties of syllables, which is in line with the guide function that speech rhythm is assumed to have in German...

  9. On the formation of Mg II h and k lines in solar prominences

    Czech Academy of Sciences Publication Activity Database

    Heinzel, Petr; Vial, J. C.; Anzer, U.

    2014-01-01

    Roč. 564, April (2014), A132/1-A132/10 ISSN 0004-6361 R&D Projects: GA ČR GAP209/12/0906; GA ČR(CZ) GAP209/11/2463; GA ČR GA205/09/1705 Institutional support: RVO:67985815 Keywords : line: profiles * line: formation * Sun: filaments, prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

  10. Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor.

    Science.gov (United States)

    Lin, Wenwei; Yang, Lei; Chai, Sergio C; Lu, Yan; Chen, Taosheng

    2016-01-27

    Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) are master regulators of endobiotic and xenobiotic metabolism and disposition. Because CAR is constitutively active in certain cellular contexts, inhibiting CAR might reduce drug-induced hepatotoxicity and resensitize drug-resistant cancer cells to chemotherapeutic drugs. We recently reported a novel CAR inhibitor/inverse agonist CINPA1 (11). Here, we have obtained or designed 54 analogs of CINPA1 and used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate their CAR inhibition potency. Many of the 54 analogs showed CAR inverse agonistic activities higher than those of CINPA1, which has an IC50 value of 687 nM. Among them, 72 has an IC50 value of 11.7 nM, which is about 59-fold more potent than CINPA1 and over 10-fold more potent than clotrimazole (an IC50 value of 126.9 nM), the most potent CAR inverse agonist in a biochemical assay previously reported by others. Docking studies provide a molecular explanation of the structure-activity relationship (SAR) observed experimentally. To our knowledge, this effort is the first chemistry endeavor in designing and identifying potent CAR inverse agonists based on a novel chemical scaffold, leading to 72 as the most potent CAR inverse agonist so far. The 54 chemicals presented are novel and unique tools for characterizing CAR's function, and the SAR information gained from these 54 analogs could guide future efforts to develop improved CAR inverse agonists. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Relating a Prominence Observed from the Solar Optical Telescope on the Hinode Satellite to Known 3-D Structures of Filaments

    Science.gov (United States)

    Martin, S. F.; Panasenco, O.; Agah, Y.; Engvold, O.; Lin, Y.

    2009-12-01

    We address only a first step in relating limb and disk observations by illustrating and comparing the spines and barbs of three different quiescent prominences and filaments observed in Hα by three different telescopes. Although the appearance of the three quiescent prominences is quite different, we show that each consists of a spine, barbs extending from the spine, and arcs at the base of some of the curtains of barb threads.

  12. A Concise Total Synthesis of (R)-Fluoxetine, a Potent and Selective Serotonin Reuptake Inhibitor

    OpenAIRE

    de Fátima, Ângelo; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A.

    2005-01-01

    (R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (R)-Fluoxetina, um inibidor potente e seletivo da recaptação da serotonina, foi sintetizada em seis etapas, 50% de rendimento total e 99% de excesso enantiomérico a partir do benzaldeído via alilação catalítica assimétrica empregando-se o sistema catalítico desenvolvido por Maruoka e...

  13. Imidazopyridine derivatives as potent and selective Polo-like kinase (PLK) inhibitors.

    Science.gov (United States)

    Sato, Yoshiyuki; Onozaki, Yu; Sugimoto, Tetsuya; Kurihara, Hideki; Kamijo, Kaori; Kadowaki, Chie; Tsujino, Toshiaki; Watanabe, Akiko; Otsuki, Sachie; Mitsuya, Morihiro; Iida, Masato; Haze, Kyosuke; Machida, Takumitsu; Nakatsuru, Yoko; Komatani, Hideya; Kotani, Hidehito; Iwasawa, Yoshikazu

    2009-08-15

    A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model.

  14. Alkylsulfanyl analogs as potent α2δ ligands.

    Science.gov (United States)

    Shimada, Kousei; Ohata, Yasuo; Kobayashi, Jun; Onishi, Yoshiyuki; Kawamura, Asuka; Domon, Yuki; Arakawa, Naohisa; Inoue, Tatsuya; Kitano, Yutaka; Matsuda, Fumihiko; Abe, Yuki; Deguchi, Tsuneo

    2018-06-15

    We identified novel (3R, 5S)-3-aminomethyl-5-methanesulfanyl hexanoic acid (5a: DS75091588) and (3R, 5S)-3-aminomethyl-5-ethanesulfanyl hexanoic acid (6a: DS18430756) as sulfur-containing γ-amino acid derivatives that were useful for the treatment of neuropathic pain. These two compounds exhibited a potent analgesic effect in animal models of both type I diabetes and type II diabetes, and good pharmacokinetics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Anxiety and Antisocial Behavior: The Moderating Role of Perceptions of Social Prominence among Incarcerated Females

    Science.gov (United States)

    Monahan, Kathryn C.; Goldweber, Aska; Meyer, Kristen; Cauffman, Elizabeth

    2012-01-01

    The present study examines how perceptions of social prominence and attitudes toward antisocial behavior among peers moderate the association between anxiety and antisocial behavior among incarcerated females. Latent profile analysis identified two classes of females distinguished by their perceptions and attitudes. Individuals in both classes…

  16. Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

    Directory of Open Access Journals (Sweden)

    Matthias G. J. Baud

    2013-01-01

    Full Text Available There has been significant interest in the bioactivity of the natural product psammaplin A, most recently as a potent and isoform selective HDAC inhibitor. Here we report our preliminary studies on thioester HDAC inhibitors derived from the active monomeric (thiol form of psammaplin A, as a means to improve compound delivery into cells. We have discovered that such compounds exhibit both potent cytotoxicity and enzymatic inhibitory activity against recombinant HDAC1. The latter effect is surprising since previous SAR suggested that modification of the thiol functionality should detrimentally affect HDAC potency. We therefore also report our preliminary studies on the mechanism of action of this observed effect.

  17. Old World frog and bird vocalizations contain prominent ultrasonic harmonics

    Science.gov (United States)

    Narins, Peter M.; Feng, Albert S.; Lin, Wenyu; Schnitzler, Hans-Ulrich; Denzinger, Annette; Suthers, Roderick A.; Xu, Chunhe

    2004-02-01

    Several groups of mammals such as bats, dolphins and whales are known to produce ultrasonic signals which are used for navigation and hunting by means of echolocation, as well as for communication. In contrast, frogs and birds produce sounds during night- and day-time hours that are audible to humans; their sounds are so pervasive that together with those of insects, they are considered the primary sounds of nature. Here we show that an Old World frog (Amolops tormotus) and an oscine songbird (Abroscopus albogularis) living near noisy streams reliably produce acoustic signals that contain prominent ultrasonic harmonics. Our findings provide the first evidence that anurans and passerines are capable of generating tonal ultrasonic call components and should stimulate the quest for additional ultrasonic species.

  18. Whole body application of a potent topical corticosteroid for bullous pemphigoid

    NARCIS (Netherlands)

    Terra, J. B.; Potze, W. J. B.; Jonkman, M. F.

    BackgroundCurrent standard of treatment of bullous pemphigoid (BP) is systemic oral corticosteroids (CS). However, significant iatrogenic morbidity and mortality is reported. Studies have shown that topical potent CS is safer than oral prednisolone in BP. ObjectivesTo examine the local and systemic

  19. Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity.

    Science.gov (United States)

    Vanaerschot, Manu; Lucantoni, Leonardo; Li, Tao; Combrinck, Jill M; Ruecker, Andrea; Kumar, T R Santha; Rubiano, Kelly; Ferreira, Pedro E; Siciliano, Giulia; Gulati, Sonia; Henrich, Philipp P; Ng, Caroline L; Murithi, James M; Corey, Victoria C; Duffy, Sandra; Lieberman, Ori J; Veiga, M Isabel; Sinden, Robert E; Alano, Pietro; Delves, Michael J; Lee Sim, Kim; Winzeler, Elizabeth A; Egan, Timothy J; Hoffman, Stephen L; Avery, Vicky M; Fidock, David A

    2017-10-01

    Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress Plasmodium berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR-Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasite resistance to HHQs. Haemoglobin and haem fractionation assays suggest a mode of action that results in reduced haemozoin levels and might involve inhibition of host haemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs, including lumefantrine, confirming that HHQs have a different mode of action to other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria.

  20. Hexahydroquinolines are Antimalarial Candidates with Potent Blood Stage and Transmission-Blocking Activity

    Science.gov (United States)

    Vanaerschot, Manu; Lucantoni, Leonardo; Li, Tao; Combrinck, Jill M.; Ruecker, Andrea; Kumar, T.R. Santha; Rubiano, Kelly; Ferreira, Pedro E.; Siciliano, Giulia; Gulati, Sonia; Henrich, Philipp P.; Ng, Caroline L.; Murithi, James M.; Corey, Victoria C.; Duffy, Sandra; Lieberman, Ori J.; Veiga, M. Isabel; Sinden, Robert E.; Alano, Pietro; Delves, Michael J.; Sim, Kim Lee; Winzeler, Elizabeth A.; Egan, Timothy J.; Hoffman, Stephen L.; Avery, Vicky M.; Fidock, David A.

    2017-01-01

    Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress P. berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR/Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 as a determinant of parasite resistance to HHQs. Hemoglobin and heme fractionation assays suggest a mode of action that results in reduced hemozoin levels and might involve inhibition of host hemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs including lumefantrine, confirming that HHQs have a different mode of action than other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria. PMID:28808258

  1. Vaccination elicits a prominent acute phase response in horses.

    Science.gov (United States)

    Andersen, Susanne A; Petersen, Henrik H; Ersbøll, Annette K; Falk-Rønne, Jørgen; Jacobsen, Stine

    2012-02-01

    European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vaccine. Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. Vaccination induced a prominent APR with increased WBC, elevated blood levels of SAA and fibrinogen, and decreased serum iron concentrations. The ISCOM vaccine caused significantly (Phorse owners about convalescence after vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI.

    Science.gov (United States)

    Kim, Yong-Woo; Kim, Hak Jin; Choi, Seon Hee; Kim, Dong Chan

    2014-10-01

    The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute

  3. In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Kamil Musilek

    2011-03-01

    Full Text Available We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6 to reactivate human acetylcholinesterase (AChE, inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos. We also tested reactivation of human butyrylcholinesterase (BChE with the aim of finding a potent oxime, suitable to serve as a “pseudocatalytic” bioscavenger in combination with this enzyme. Such a combination could allow an increase of prophylactic and therapeutic efficacy of the administered enzyme. According to our results, the best broad-spectrum AChE reactivators were trimedoxime and obidoxime in the case of paraoxon, leptophos-oxon, and methamidophos-inhibited AChE. Methamidophos and leptophos-oxon were quite easily reactivatable by all tested reactivators. In the case of methamidophos-inhibited AChE, the lower oxime concentration (10−5 M had higher reactivation ability than the 10−4 M concentration. Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10−3–10−7 M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10−5 M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for “pseudocatalytic” bioscavengers with BChE.

  4. Nodular hidradenocarcinoma with prominent squamous differentiation: case report and immunohistochemical study.

    Science.gov (United States)

    Park, H J; Kim, Y C; Cinn, Y W

    2000-09-01

    We report the case of a 24-year-old woman with nodular hidradenocarcinoma on the scalp. While histopathology of the tumor showed a circumscribed, lobulated intradermal mass with prominent squamous differentiation, the immunohistochemical study with antibodies to cytokeratins, CAM 5.2 and 19, epithelial membrane antigen, carcinoembryonic antigen, S-100 protein and p53 all demonstrated positivity. These findings confirmed that the tumor was of eccrine sweat gland origin and it was thought to be a nodular hidradenocarcinoma differentiating toward the eccrine duct and/or secretory portions. She was treated with a wide local excision and no recurrence was observed 18 months after excision.

  5. Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

    Directory of Open Access Journals (Sweden)

    Mehul M. Patel

    2014-01-01

    Full Text Available Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl-2-(substituted-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT by Schrodinger’s Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections.

  6. Carrageenan is a potent inhibitor of papillomavirus infection.

    Directory of Open Access Journals (Sweden)

    Christopher B Buck

    2006-07-01

    Full Text Available Certain sexually transmitted human papillomavirus (HPV types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate-independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs.

  7. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.

    Science.gov (United States)

    Chen, D Z; Patel, D V; Hackbarth, C J; Wang, W; Dreyer, G; Young, D C; Margolis, P S; Wu, C; Ni, Z J; Trias, J; White, R J; Yuan, Z

    2000-02-15

    Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

  8. Combined surgical management of mandibular angle prominence and microgenia

    International Nuclear Information System (INIS)

    Portelles Masso, Ayelen Maria; Berger Kohn, Carlos

    2010-01-01

    Chin play a very important role in facial aesthetics. Different deformities of volume and of position may occur at this level and it is the microgenia one of the more frequent. Treatment options include the use of silicone, alloplasty materials and autologous bone graft. Authors report the use of the bone removed from mandibular angle to increase the chin. This is the case of a white female patient aged 18 seen by the Orthognathics Multidisciplinary Staff of 'V. I. Lenin' Hospital due to its uncommon face width. The corresponding physical examination as well as the complementary ones diagnosed a bilateral prominence of mandibular angle associated with a microgenia. Surgery carried out was of remodeling type of both mandibular angles and genioplasty of height increase and a discrete advancement using the bone removed from the gonion. There were satisfactory aesthetic results without evidence of bone reabsorption. We conclude that use of autologous graft of mandibular angle is an effective treatment alternative for correction of microgenia. (author)

  9. The challenges to the consolidation of Brazil’s international prominence: education and culture

    Directory of Open Access Journals (Sweden)

    Elizabete Sanches Rocha

    2012-04-01

    Full Text Available Over the last years, Brazil has gained international visibility especially due to the capacity of its economical development and the progress of its public policies on fighting poverty. Though there reason for celebration exists with respect to the country’s recent achievements, Brazil still has a lot to do if it wants to gain international prominence. In this paper, we address two issues that are fundamental for Brazil to achieve real leadership: education and culture.

  10. Red mold rice ameliorates impairment of memory and learning ability in intracerebroventricular amyloid beta-infused rat by repressing amyloid beta accumulation.

    Science.gov (United States)

    Lee, Chun-Lin; Kuo, Tzong-Fu; Wang, Jyh-Jye; Pan, Tzu-Ming

    2007-11-01

    Amyloid beta (Abeta) peptide related to the onset of Alzheimer's disease (AD) damaged neurons and further resulted in dementia. Monascus-fermented red mold rice (RMR), a traditional Chinese medicine as well as health food, includes monacolins (with the same function as statins) and multifunctional metabolites. In this study, ethanol extract of RMR (RE) was used to evaluate neuroprotection against Abeta40 neurotoxicity in PC12 cells. Furthermore, the effects of dietary administration of RMR on memory and learning abilities are confirmed in an animal model of AD rats infused with Abeta40 into the cerebral ventricle. During continuous Abeta40 infusion for 28 days, the rats of test groups were administered RMR or lovastatin. Memory and learning abilities were evaluated in the water maze and passive avoidance tasks. After sacrifice, cerebral cortex and hippocampus were collected for the examination of AD risk factors. The in vitro results clearly indicate that RE provides stronger neuroprotection in rescuing cell viability as well as repressing inflammatory response and oxidative stress. RMR administration potently reverses the memory deficit in the memory task. Abeta40 infusion increases acetylcholinesterase activity, reactive oxygen species, and lipid peroxidation and decreases total antioxidant status and superoxide dismutase activity in brain, but these damages were potently reversed by RMR administration, and the protection was more significant than that with lovastatin administration. The protection provided by RMR is able to prevent Abeta fibrils from being formed and deposited in hippocampus and further decrease Abeta40 accumulation, even though Abeta40 solution was infused into brain continuously. (c) 2007 Wiley-Liss, Inc.

  11. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    International Nuclear Information System (INIS)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela; Martinelli, Diego; Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella; Dionisi-Vici, Carlo; Nobili, Valerio; Francalanci, Paola; Boldrini, Renata; Callea, Francesco; Santorelli, Filippo Maria; Bertini, Enrico

    2011-01-01

    Highlights: ► Expanded array of mtDNA deletions. ► Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. ► Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. ► Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  12. Asymmetric mesoporous silica nanoparticles as potent and safe immunoadjuvants provoke high immune responses.

    Science.gov (United States)

    Abbaraju, Prasanna Lakshmi; Jambhrunkar, Manasi; Yang, Yannan; Liu, Yang; Lu, Yao; Yu, Chengzhong

    2018-02-20

    Asymmetric mesoporous silica nanoparticles with a head-tail structure are potent immunoadjuvants for delivering a peptide antigen, generating a higher antibody immune response in mice compared to their symmetric counterparts.

  13. Communicative dynamism and prosodic prominence in presentation sentences with initial rhematic subjects

    Directory of Open Access Journals (Sweden)

    Martin Adam

    2017-08-01

    Full Text Available Within the framework of the theory of functional sentence perspective (Firbas 1992, the distinction between presentation and quality scale sentences plays a vital role. The present paper proposes to shed light on one of the most common configurations of presentation sentences, viz. structures with initial rhematic subject (e.g. an uninvited dwarf came, examining the way native speakers place the intonation centre in such structures, i.e. to map the correspondence between the degrees of communicative dynamism and prosodic prominence. For the purpose of the investigation selected chapters from Tolkien’s The Hobbit are used.

  14. The Effects of Magnetic-Field Geometry on Longitudinal Oscillations of Solar Prominences: Cross-Sectional Area Variation for Thin Tubes

    Science.gov (United States)

    Luna, M.; Diaz, A. J.; Oliver, R.; Terradas, J.; Karpen, J.

    2016-01-01

    Solar prominences are subject to both field-aligned (longitudinal) and transverse oscillatory motions, as evidenced by an increasing number of observations. Large-amplitude longitudinal motions provide valuable information on the geometry of the filament channel magnetic structure that supports the cool prominence plasma against gravity. Our pendulum model, in which the restoring force is the gravity projected along the dipped field lines of the magnetic structure, best explains these oscillations. However, several factors can influence the longitudinal oscillations, potentially invalidating the pendulum model. Aims. The aim of this work is to study the influence of large-scale variations in the magnetic field strength along the field lines, i.e., variations of the cross-sectional area along the flux tubes supporting prominence threads. Methods. We studied the normal modes of several flux tube configurations, using linear perturbation analysis, to assess the influence of different geometrical parameters on the oscillation properties. Results. We found that the influence of the symmetric and asymmetric expansion factors on longitudinal oscillations is small.Conclusions. We conclude that the longitudinal oscillations are not significantly influenced by variations of the cross-section of the flux tubes, validating the pendulum model in this context.

  15. Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen

    International Nuclear Information System (INIS)

    Cimica, Velasco; Smith, Melissa E; Zhang, Zhikai; Mathur, Deepti; Mani, Sridhar; Kalpana, Ganjam V

    2010-01-01

    Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam) in order to reduce the concentration of flavopiridol needed for inhibition of RTs. The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i) cell survival assays, ii) FACS analysis, iii) caspase activity assays, and iv) immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA) analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined. We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G 2 arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G 2 arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G 2 arrest, but enhanced flavopiridol- (but not 4OH-Tam-) mediated apoptosis, by enhancing caspase 2 and 3 activities. Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was enhanced by abrogation of p53. Our results warrant further

  16. Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Cimica, Velasco; Smith, Melissa E; Zhang, Zhikai; Mathur, Deepti [Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Mani, Sridhar [Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Albert Einstein Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Kalpana, Ganjam V [Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Albert Einstein Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States)

    2010-11-19

    Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam) in order to reduce the concentration of flavopiridol needed for inhibition of RTs. The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i) cell survival assays, ii) FACS analysis, iii) caspase activity assays, and iv) immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA) analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined. We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G{sub 2} arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G{sub 2} arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G{sub 2} arrest, but enhanced flavopiridol- (but not 4OH-Tam-) mediated apoptosis, by enhancing caspase 2 and 3 activities. Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was enhanced by abrogation of p53. Our results

  17. Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen

    Directory of Open Access Journals (Sweden)

    Mani Sridhar

    2010-11-01

    Full Text Available Abstract Background Rhabdoid Tumors (RTs are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam in order to reduce the concentration of flavopiridol needed for inhibition of RTs. Methods The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i cell survival assays, ii FACS analysis, iii caspase activity assays, and iv immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined. Results We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G2 arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G2 arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G2 arrest, but enhanced flavopiridol- (but not 4OH-Tam- mediated apoptosis, by enhancing caspase 2 and 3 activities. Conclusions Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was

  18. A concise synthesis of the potent inflammatory mediator 5-oxo-ETE

    DEFF Research Database (Denmark)

    Tyagi, Rahul; Shimpukade, Bharat; Blättermann, Stefanie

    2012-01-01

    A concise and practical method for synthesis of the potent inflammatory mediator 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE, 1) from arachidonic acid in four steps and 70% overall yield is reported. Stability studies indicate that 1 can be safely handled without rigorous precautions...

  19. Genetic immunization in the lung induces potent local and systemic immune responses

    NARCIS (Netherlands)

    Song, Kaimei; Bolton, Diane L.; Wilson, Robert L.; Camp, Jeremy V.; Bao, Saran; Mattapallil, Joseph J.; Herzenberg, Leonore A.; Herzenberg, Leonard A.; Andrews, Charla A.; Sadoff, Jerald C.; Goudsmit, Jaap; Pau, Maria Grazia; Seder, Robert A.; Kozlowski, Pamela A.; Nabel, Gary J.; Roederer, Mario; Rao, Srinivas S.

    2010-01-01

    Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver

  20. Analogues of the Potent Antitumor Compound Leiodermatolide from a Deep-Water Sponge of the Genus Leiodermatium.

    Science.gov (United States)

    Wright, Amy E; Roberts, Jill C; Guzmán, Esther A; Pitts, Tara P; Pomponi, Shirley A; Reed, John K

    2017-03-24

    Two new analogues of the potent antitumor compound leiodermatolide, which we call leiodermatolides B and C, have been isolated from specimens of a deep-water sponge of the genus Leiodermatium collected off Florida. The compounds were purified using standard chromatographic methods, and the structures defined through interpretation of the HRMS and 1D and 2D NMR data. Leiodermatolide B (2) lacks the C-21 hydroxy group found in leiodermatolide and has equal potency as the parent compound, providing a simpler analogue for possible clinical development. It inhibits the proliferation of the AsPC-1 human pancreatic adenocarcinoma cell line with an IC 50 of 43 nM. Leiodermatolide C (3) has a modified macrolide ring and is over 85-fold less potent with an IC 50 of 3.7 μM against the same cell line. These compounds add to the knowledge of the pharmacophore of this class of potent antitumor agents.

  1. A model on CME/Flare initiation: Loss of Equilibrium caused by mass loss of quiescent prominences

    Science.gov (United States)

    Miley, George; Chon Nam, Sok; Kim, Mun Song; Kim, Jik Su

    2015-08-01

    Coronal Mass Ejections (CMEs) model should give an answer to enough energy storage for giant bulk plasma into interplanetary space to escape against the sun’s gravitation and its explosive eruption. Advocates of ‘Mass Loading’ model (e.g. Low, B. 1996, SP, 167, 217) suggested a simple mechanism of CME initiation, the loss of mass from a prominence anchoring magnetic flux rope, but they did not associate the mass loss with the loss of equilibrium. The catastrophic loss of equilibrium model is considered as to be a prospective CME/Flare model to explain sudden eruption of magnetic flux systems. Isenberg, P. A., et al (1993, ApJ, 417, 368)developed ideal magnetohydrodynamic theory of the magnetic flux rope to show occurrence of catastrophic loss of equilibrium according to increasing magnetic flux transported into corona.We begin with extending their study including gravity on prominence’s material to obtain equilibrium curves in case of given mass parameters, which are the strengths of the gravitational force compared with the characteristic magnetic force. Furthermore, we study quasi-static evolution of the system including massive prominence flux rope and current sheet below it to obtain equilibrium curves of prominence’s height according to decreasing mass parameter in a properly fixed magnetic environment. The curves show equilibrium loss behaviors to imply that mass loss result in equilibrium loss. Released fractions of magnetic energy are greater than corresponding zero-mass case. This eruption mechanism is expected to be able to apply to the eruptions of quiescent prominences, which is located in relatively weak magnetic environment with 105 km of scale length and 10G of photospheric magnetic field.

  2. Work ability assessment in a worker population: comparison and determinants of Work Ability Index and Work Ability score.

    Science.gov (United States)

    El Fassi, Mehdi; Bocquet, Valery; Majery, Nicole; Lair, Marie Lise; Couffignal, Sophie; Mairiaux, Philippe

    2013-04-08

    Public authorities in European countries are paying increasing attention to the promotion of work ability throughout working life and the best method to monitor work ability in populations of workers is becoming a significant question. The present study aims to compare the assessment of work ability based on the use of the Work Ability Index (WAI), a 7-item questionnaire, with another one based on the use of WAI's first item, which consists in the worker's self-assessment of his/her current work ability level as opposed to his/her lifetime best, this single question being termed "Work Ability score" (WAS). Using a database created by an occupational health service, the study intends to answer the following questions: could the assessment of work ability be based on a single-item measure and which are the variables significantly associated with self-reported work ability among those systematically recorded by the occupational physician during health examinations? A logistic regression model was used in order to estimate the probability of observing "poor" or "moderate" WAI levels depending on age, gender, body mass index, smoking status, position held, firm size and diseases reported by the worker in a population of workers aged 40 to 65 and examined between January 2006 and June 2010 (n=12389). The convergent validity between WAS and WAI was statistically significant (rs=0.63). In the multivariable model, age (pwork ability. A work position characterized by the predominance of mental activity (OR=0.71, 95%CI [0.61-0.84]) had a favourable impact on work ability. These relations were observed regardless of the work ability measurement tool used. The convergent validity and the similarity in results between WAI and WAS observed in a large population of employed workers should thus foster the use of WAS for systematic screening of work ability. Ageing, overweight, decline in health status, holding a mostly physical job and working in a large-sized firm increase the

  3. Characterization of the binding of [3H]-(+/-)-L-364,718: a new potent, nonpeptide cholecystokinin antagonist radioligand selective for peripheral receptors

    International Nuclear Information System (INIS)

    Chang, R.S.; Lotti, V.J.; Chen, T.B.; Kunkel, K.A.

    1986-01-01

    [3H]-(+/-)-L-364,718 a new, potent and selective nonpeptide peripheral cholecystokinin (CCK) antagonist bound saturably and reversibly to rat pancreatic membranes. The radioligand recognized a single class of binding sites with a high affinity (Kd = 0.23 nM). The binding of [ 3 H]-(+/-)-L-364,718 was stereospecific in that the more biologically active (-)-enantiomer demonstrated greater potency than the (+)-enantiomer. The rank order of potency of various CCK agonists and antagonists in displacing [ 3 H]-(+/-)-L-364,718 correlated with their ability to displace [ 125 I]CCK-8 and their known pharmacological activities in peripheral tissues. However, the absolute potencies of agonists were greater in displacing [ 125 I]CCK-8 than [ 3 H]-(+/-)-L-364,718. As described for other physiologically relevant receptor systems, the potency for displacement of [ 3 H]-(+/-)-L-364,718 binding by CCK agonists, but not antagonists, was reduced by guanosine 5'-(beta, gamma-imido)triphosphate and NaCl and enhanced by MgCl 2 . [ 3 H]-(+/-)-L-364,718 also demonstrated specific binding to bovine gall bladder tissue but not guinea pig brain or gastric glands, consistent with its selectivity as a peripheral CCK antagonist. [ 3 H]-(+/-)-L-364,718 binding to pancreatic membranes was not affected by various pharmacological agents known to interact with other common peptide and nonpeptide receptor systems. These data indicate that [ 3 H]-(+/-)-L-364,718 represents a new potent nonpeptide antagonist radioligand for the study of peripheral CCK receptors which may allow differentiation of agonist and antagonist interactions

  4. Statistical comparison of the observed and synthetic hydrogen Lyman line profiles in solar prominences

    Czech Academy of Sciences Publication Activity Database

    Gunár, Stanislav; Schwartz, Pavol; Schmieder, B.; Heinzel, Petr; Anzer, U.

    2010-01-01

    Roč. 514, May (2010), A43/1-A43/11 ISSN 0004-6361 R&D Projects: GA ČR GP205/09/P554; GA ČR GA205/07/1100; GA AV ČR 1QS300120506 Grant - others:ESA(XE) ESA- PECS project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : Sun filaments * prominences * radiative transfer Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.410, year: 2010

  5. Isolation and identification of a new homoisoflavan with potent antioxidant activity from Commelina Elegans

    International Nuclear Information System (INIS)

    Kabbash, A.; Yagi, A.; Ishizu, T.; Haraguchi, H.; Fujioka, T.; Moustafa, S.M.; El-Bassouny, Ashraf A.

    2008-01-01

    Potent antioxidative compounds have been isolated from the ethyl acetate extract of Commelina Elegans, Commelinaceae, using a repeated column chromatography. On the basis of spectral analysis, the compounds were identified as brazilin, brazilein and the new homoisoflavan-3, 7, 9, 3, 4-ol (4-4) dimer with X- and Y-conformers. The compounds inhibited both enzymatic lipid peroxidation using a rat liver microsomes and mitochondria and non-enzymatic reactions. The compounds completely protected the activities of the mitochondrial enzymes NADH- and succinate-cytochrome c reductase. Furthermore, radical scavenging activity on enzymatically and non-enzymatically generated superoxide anion was investigated. Electron spin resonance using spin trapping method suggested that the compounds have potent superoxide anion scavenging activities. (author)

  6. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  7. Work ability as prognostic risk marker of disability pension : Single-item work ability score versus multi-item work ability index

    NARCIS (Netherlands)

    Roelen, C.A.M.; Rhenen, van W.; Groothoff, J.W.; Klink, van der J.J.L.; Twisk, W.R.; Heymans, M.W.

    2014-01-01

    Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP.

  8. NUMERICAL SIMULATIONS OF THE MAGNETIC RAYLEIGH-TAYLOR INSTABILITY IN THE KIPPENHAHN-SCHLÜTER PROMINENCE MODEL. I. FORMATION OF UPFLOWS

    International Nuclear Information System (INIS)

    Hillier, Andrew; Isobe, Hiroaki; Shibata, Kazunari; Berger, Thomas

    2012-01-01

    The launch of the Hinode satellite led to the discovery of rising plumes, dark in chromospheric lines, that propagate from large (∼10 Mm) bubbles that form at the base of quiescent prominences. The plumes move through a height of approximately 10 Mm while developing highly turbulent profiles. The magnetic Rayleigh-Taylor instability was hypothesized to be the mechanism that drives these flows. In this study, using three-dimensional (3D) MHD simulations, we investigate the nonlinear stability of the Kippenhahn-Schlüter prominence model for the interchange mode of the magnetic Rayleigh-Taylor instability. The model simulates the rise of a buoyant tube inside the quiescent prominence model, where the interchange of magnetic field lines becomes possible at the boundary between the buoyant tube and the prominence. Hillier et al. presented the initial results of this study, where upflows of constant velocity (maximum found 6 km s –1 ) and a maximum plume width ≈1.5 Mm which propagate through a height of approximately 6 Mm were found. Nonlinear interaction between plumes was found to be important for determining the plume dynamics. In this paper, using the results of ideal MHD simulations, we determine how the initial parameters for the model and buoyant tube affect the evolution of instability. We find that the 3D mode of the magnetic Rayleigh-Taylor instability grows, creating upflows aligned with the magnetic field of constant velocity (maximum found 7.3 km s –1 ). The width of the upflows is dependent on the initial conditions, with a range of 0.5-4 Mm which propagate through heights of 3-6 Mm. These results are in general agreement with the observations of the rising plumes.

  9. Hot prominence detected in the core of a coronal mass ejection. II. Analysis of the C III line detected by SOHO/UVCS

    Science.gov (United States)

    Jejčič, S.; Susino, R.; Heinzel, P.; Dzifčáková, E.; Bemporad, A.; Anzer, U.

    2017-11-01

    Context. We study the physics of erupting prominences in the core of coronal mass ejections (CMEs) and present a continuation of a previous analysis. Aims: We determine the kinetic temperature and microturbulent velocity of an erupting prominence embedded in the core of a CME that occurred on August 2, 2000 using the Ultraviolet Coronagraph and Spectrometer observations (UVCS) on board the Solar and Heliospheric Observatory (SOHO) simultaneously in the hydrogen Lα and C III lines. We develop the non-LTE (departures from the local thermodynamic equilibrium - LTE) spectral diagnostics based on Lα and Lβ measured integrated intensities to derive other physical quantities of the hot erupting prominence. Based on this, we synthesize the C III line intensity to compare it with observations. Methods: Our method is based on non-LTE modeling of eruptive prominences. We used a general non-LTE radiative-transfer code only for optically thin prominence points because optically thick points do not allow the direct determination of the kinetic temperature and microturbulence from the line profiles. The input parameters of the code were the kinetic temperature and microturbulent velocity derived from the Lα and C III line widths, as well as the integrated intensity of the Lα and Lβ lines. The code runs in three loops to compute the radial flow velocity, electron density, and effective thickness as the best fit to the Lα and Lβ integrated intensities within the accuracy defined by the absolute radiometric calibration of UVCS data. Results: We analyzed 39 observational points along the whole erupting prominence because for these points we found a solution for the kinetic temperature and microturbulent velocity. For these points we ran the non-LTE code to determine best-fit models. All models with τ0(Lα) ≤ 0.3 and τ0(C III) ≤ 0.3 were analyzed further, for which we computed the integrated intensity of the C III line using a two-level atom. The best agreement between

  10. Work ability as prognostic risk marker of disability pension: single-item work ability score versus multi-item work ability index

    NARCIS (Netherlands)

    Roelen, C.A.M.; van Rhenen, W.; Groothoff, J.W.; van der Klink, J.J.L.; Twisk, J.W.R.; Heymans, M.W.

    2014-01-01

    Objectives Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP. Methods This

  11. Work ability as prognostic risk marker of disability pension : single-item work ability score versus multi-item work ability index

    NARCIS (Netherlands)

    Roelen, Corne A. M.; van Rhenen, Willem; Groothoff, Johan W.; van der Klink, Jac J. L.; Twisk, Jos W. R.; Heymans, Martijn W.

    Objectives Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP. Methods This

  12. Exploring Primary Student’s Problem-Solving Ability by Doing Tasks Like PISA's Question

    Directory of Open Access Journals (Sweden)

    Rita Novita

    2012-07-01

    Full Text Available Problem solving plays an important role in mathematics and should have a prominent role in the mathematics education. The term “problem solving” refers to mathematics tasks that have the potential to provide intellectual challenges for enhancing students’ mathematical understanding and development. In addition, the contextual problem that requires students to connect their mathematical knowledge in solving mathematical situational problem is believed to be an impact on the development students’ problem-solving ability. The tasks that have been developed by PISA meet both of these criteria. As stated by the NCTM, that problem-solving skill and ability should be developed to students when they were in primary school (K5-8, therefore, it is important to do an effort to guide students in developing problem-solving ability from primary school such as accustom students to do some mathematical solving-problem tasks. Thus, in this research we tried to investigate how to develop mathematical problem-solving tasks like PISA’s question that have potential effect toward students’ mathematical problem-solving abilities?. We used a  formative evaluation type of development research as an mean  to achieve this research goal. This type of research is conducted in two steps, namely preliminary stage and formative evaluation stage covering self evaluation, prototyping (expert reviews, one-to-one, and small group, and  field test. This research involve four primary schools in Palembang, there are SD Muhammadiyah 6 Palembang, MIN 1 & MIN 2 Palembang, and SDN 179 Palembang. The result of this research showed that the mathematical problem-solving tasks  that have been developed have potential effect in exploring mathematical problem-solving ability of the primary school students. It  is shown from their work in solving problem where all of the indicators of problem solving competency have emerged quite well category. In addition, based on interview

  13. "Appearance potent"? A content analysis of UK gay and straight men's magazines.

    Science.gov (United States)

    Jankowski, Glen S; Fawkner, Helen; Slater, Amy; Tiggemann, Marika

    2014-09-01

    With little actual appraisal, a more 'appearance potent' (i.e., a reverence for appearance ideals) subculture has been used to explain gay men's greater body dissatisfaction in comparison to straight men's. This study sought to assess the respective appearance potency of each subculture by a content analysis of 32 issues of the most read gay (Attitude, Gay Times) and straight men's magazines (Men's Health, FHM) in the UK. Images of men and women were coded for their physical characteristics, objectification and nudity, as were the number of appearance adverts and articles. The gay men's magazines featured more images of men that were appearance ideal, nude and sexualized than the straight men's magazines. The converse was true for the images of women and appearance adverts. Although more research is needed to understand the effect of this content on the viewer, the findings are consistent with a more appearance potent gay male subculture. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  14. Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.

    Science.gov (United States)

    Karlberg, Ann-Therese; Börje, Anna; Duus Johansen, Jeanne; Lidén, Carola; Rastogi, Suresh; Roberts, David; Uter, Wolfgang; White, Ian R

    2013-12-01

    Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists

    DEFF Research Database (Denmark)

    Mohsen, Amal M Y; Mandour, Yasmine M; Sarukhanyan, Edita

    2016-01-01

    of the crystal structure of the α3 glycine receptor indicated the same orientation of the strychnine core for all analogues. For the most potent oxime ethers, the ether substituent was accommodated in a lipophilic receptor binding pocket. The findings identify the oxime hydroxy group as a suitable attachment...

  16. A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

    International Nuclear Information System (INIS)

    Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A.

    2005-01-01

    (R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)

  17. A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Perez, H D; Goldstein, I M

    1983-12-25

    We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

  18. Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.

    Science.gov (United States)

    Gungor, Bilgi; Yagci, Fuat Cem; Gursel, Ihsan; Gursel, Mayda

    Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon α (IFNα) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity.

  19. Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication

    Directory of Open Access Journals (Sweden)

    Mélanie Bourjot

    2014-03-01

    Full Text Available Trigocherrierin A (1 and trigocherriolide E (2, two new daphnane diterpenoid orthoesters (DDOs, and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7.

  20. Discovery of a potent and selective GPR120 agonist

    DEFF Research Database (Denmark)

    Shimpukade, Bharat; Hudson, Brian D; Hovgaard, Christine Kiel

    2012-01-01

    GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation...... is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist....

  1. Exploring H2O Prominence in Reflection Spectra of Cool Giant Planets

    Science.gov (United States)

    MacDonald, Ryan J.; Marley, Mark S.; Fortney, Jonathan J.; Lewis, Nikole K.

    2018-05-01

    The H2O abundance of a planetary atmosphere is a powerful indicator of formation conditions. Inferring H2O in the solar system giant planets is challenging, due to condensation depleting the upper atmosphere of water vapor. Substantially warmer hot Jupiter exoplanets readily allow detections of H2O via transmission spectroscopy, but such signatures are often diminished by the presence of clouds composed of other species. In contrast, highly scattering water clouds can brighten planets in reflected light, enhancing molecular signatures. Here, we present an extensive parameter space survey of the prominence of H2O absorption features in reflection spectra of cool (T eff clouds brighten the planet: T eff ∼ 150 K, g ≳ 20 ms‑2, f sed ≳ 3, m ≲ 10× solar. In contrast, planets with g ≲ 20 ms‑2 and T eff ≳ 180 K display substantially prominent H2O features embedded in the Rayleigh scattering slope from 0.4 to 0.73 μm over a wide parameter space. High f sed enhances H2O features around 0.94 μm, and enables these features to be detected at lower temperatures. High m results in dampened H2O absorption features, due to water vapor condensing to form bright, optically thick clouds that dominate the continuum. We verify these trends via self-consistent modeling of the low-gravity exoplanet HD 192310c, revealing that its reflection spectrum is expected to be dominated by H2O absorption from 0.4 to 0.73 μm for m ≲ 10× solar. Our results demonstrate that H2O is manifestly detectable in reflected light spectra of cool giant planets only marginally warmer than Jupiter, providing an avenue to directly constrain the C/O and O/H ratios of a hitherto unexplored population of exoplanetary atmospheres.

  2. A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica]. E-mail: pilli@iqm.unicamp.br

    2005-05-15

    (R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)

  3. Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Win-Shwe, Tin-Tin, E-mail: tin.tin.win.shwe@nies.go.jp [Center for Environmental Health Sciences, National Institute for Environmental Studies, 16‐2 Onogawa, Tsukuba, Ibaraki 305‐8506 (Japan); Fujimaki, Hidekazu; Fujitani, Yuji; Hirano, Seishiro [Center for Environmental Risk Research, National Institute for Environmental Studies, 16‐2 Onogawa, Tsukuba, Ibaraki 305‐8506 (Japan)

    2012-08-01

    Recently, our laboratory reported that exposure to nanoparticle-rich diesel exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning ability and up-regulated the expressions of memory function-related genes in the hippocampus of female mice. However, whether NRDE affects the hippocampus-dependent non-spatial learning ability and the mechanism of NRDE-induced neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE, 47 μg/m{sup 3}), high-dose NRDE (H-NRDE, 129 μg/m{sup 3}), or filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE exposure on non-spatial learning ability and the expression of genes related to glutamate neurotransmission using a novel object recognition test and a real-time RT-PCR analysis, respectively. We also examined microglia marker Iba1 immunoreactivity in the hippocampus using immunohistochemical analyses. Mice exposed to H-NRDE or F-DE could not discriminate between familiar and novel objects. The control and M-NRDE-exposed groups showed a significantly increased discrimination index, compared to the H-NRDE-exposed group. Although no significant changes in the expression levels of the NMDA receptor subunits were observed, the expression of glutamate transporter EAAT4 was decreased and that of glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE-exposed mice, compared with the expression levels in control mice. We also found that microglia activation was prominent in the hippocampal area of the H-NRDE-exposed mice, compared with the other groups. These results indicated that exposure to NRDE for 3 months impaired the novel object recognition ability. The present study suggests that genes related to glutamate metabolism may be involved in the NRDE-induced neurotoxicity observed in the present mouse model. -- Highlights: ► The effects of nanoparticle-induced neurotoxicity remain unclear. ► We investigated the effect of exposure to

  4. Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust

    International Nuclear Information System (INIS)

    Win-Shwe, Tin-Tin; Fujimaki, Hidekazu; Fujitani, Yuji; Hirano, Seishiro

    2012-01-01

    Recently, our laboratory reported that exposure to nanoparticle-rich diesel exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning ability and up-regulated the expressions of memory function-related genes in the hippocampus of female mice. However, whether NRDE affects the hippocampus-dependent non-spatial learning ability and the mechanism of NRDE-induced neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE, 47 μg/m 3 ), high-dose NRDE (H-NRDE, 129 μg/m 3 ), or filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE exposure on non-spatial learning ability and the expression of genes related to glutamate neurotransmission using a novel object recognition test and a real-time RT-PCR analysis, respectively. We also examined microglia marker Iba1 immunoreactivity in the hippocampus using immunohistochemical analyses. Mice exposed to H-NRDE or F-DE could not discriminate between familiar and novel objects. The control and M-NRDE-exposed groups showed a significantly increased discrimination index, compared to the H-NRDE-exposed group. Although no significant changes in the expression levels of the NMDA receptor subunits were observed, the expression of glutamate transporter EAAT4 was decreased and that of glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE-exposed mice, compared with the expression levels in control mice. We also found that microglia activation was prominent in the hippocampal area of the H-NRDE-exposed mice, compared with the other groups. These results indicated that exposure to NRDE for 3 months impaired the novel object recognition ability. The present study suggests that genes related to glutamate metabolism may be involved in the NRDE-induced neurotoxicity observed in the present mouse model. -- Highlights: ► The effects of nanoparticle-induced neurotoxicity remain unclear. ► We investigated the effect of exposure to

  5. Work ability assessment in a worker population: comparison and determinants of Work Ability Index and Work Ability score

    OpenAIRE

    El Fassi, Mehdi; Bocquet, Valery; Majery, Nicole; Lair, Marie Lise; Couffignal, Sophie; Mairiaux, Philippe

    2013-01-01

    Background Public authorities in European countries are paying increasing attention to the promotion of work ability throughout working life and the best method to monitor work ability in populations of workers is becoming a significant question. The present study aims to compare the assessment of work ability based on the use of the Work Ability Index (WAI), a 7-item questionnaire, with another one based on the use of WAI?s first item, which consists in the worker?s self-assessment of his/he...

  6. Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity.

    Science.gov (United States)

    Ting, Kai Yiu; Leung, Christina F P; Graeff, Richard M; Lee, Hon Cheung; Hao, Quan; Kotaka, Masayo

    2016-03-01

    Cyclic ADP-ribose (cADPR) mobilizes intracellular Ca(2+) stores and activates Ca(2+) influx to regulate a wide range of physiological processes. It is one of the products produced from the catalysis of NAD(+) by the multifunctional CD38/ADP-ribosyl cyclase superfamily. After elimination of the nicotinamide ring by the enzyme, the reaction intermediate of NAD(+) can either be hydrolyzed to form linear ADPR or cyclized to form cADPR. We have previously shown that human CD38 exhibits a higher preference towards the hydrolysis of NAD(+) to form linear ADPR while Aplysia ADP-ribosyl cyclase prefers cyclizing NAD(+) to form cADPR. In this study, we characterized the enzymatic properties of porcine CD38 and revealed that it has a prominent secondary NAD(+) cyclase activity producing cADPR. We also determined the X-ray crystallographic structures of porcine CD38 and were able to observe conformational flexibility at the base of the active site of the enzyme which allow the NAD(+) reaction intermediate to adopt conformations resulting in both hydrolysis and cyclization forming linear ADPR and cADPR respectively. © 2016 The Protein Society.

  7. Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors.

    Science.gov (United States)

    Kwiatkowski, Jacek; Liu, Boping; Tee, Doris Hui Ying; Chen, Guoying; Ahmad, Nur Huda Binte; Wong, Yun Xuan; Poh, Zhi Ying; Ang, Shi Hua; Tan, Eldwin Sum Wai; Ong, Esther Hq; Nurul Dinie; Poulsen, Anders; Pendharkar, Vishal; Sangthongpitag, Kanda; Lee, May Ann; Sepramaniam, Sugunavathi; Ho, Soo Yei; Cherian, Joseph; Hill, Jeffrey; Keller, Thomas H; Hung, Alvin W

    2018-05-24

    Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.

  8. Competing risk bias was common in Kaplan-Meier risk estimates published in prominent medical journals.

    Science.gov (United States)

    van Walraven, Carl; McAlister, Finlay A

    2016-01-01

    Risk estimates from Kaplan-Meier curves are well known to medical researchers, reviewers, and editors. In this study, we determined the proportion of Kaplan-Meier analyses published in prominent medical journals that are potentially biased because of competing events ("competing risk bias"). We randomly selected 100 studies that had at least one Kaplan-Meier analysis and were recently published in prominent medical journals. Susceptibility to competing risk bias was determined by examining the outcome and potential competing events. In susceptible studies, bias was quantified using a previously validated prediction model when the number of outcomes and competing events were given. Forty-six studies (46%) contained Kaplan-Meier analyses susceptible to competing risk bias. Sixteen studies (34.8%) susceptible to competing risk cited the number of outcomes and competing events; in six of these studies (6/16, 37.5%), the outcome risk from the Kaplan-Meier estimate (relative to the true risk) was biased upward by 10% or more. Almost half of Kaplan-Meier analyses published in medical journals are susceptible to competing risk bias and may overestimate event risk. This bias was found to be quantitatively important in a third of such studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

    Science.gov (United States)

    Wiesenberg-Boettcher, I; Schweizer, A; Green, J R; Mueller, K; Maerki, F; Pfeilschifter, J

    1989-01-01

    CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.) and pronounced analgesic and antipyretic activity in acute models in mice and rats (ED50 2-5 mg/kg, p.o.), but has clear advantages over reference NSAIDs with respect to gastro-intestinal tolerability. Threshold doses for gastro-intestinal ulcerogenicity in rats after single and repeated (10x) doses were found to be 30 mg/kg, p.o., and prostaglandin (PGE2) production in rat gastric and ileal mucosa was only marginally inhibited (ED50 greater than 30 mg/kg, p.o.). On the other hand, PGE2 production in rat inflammatory exudate and thromboxane synthesis in rat blood were inhibited with ED50 values of less than or equal to 2 mg/kg, p.o. Although CGP28238 does not inhibit cyclooxygenase in bovine seminal vesicle microsomal preparations (IC50 greater than 10(-3) mol/l), potent inhibition of prostaglandin synthesis was shown in various in vitro systems using human and animal cells with IC50 values of less than 10(-6) mol/l. IL-1-stimulated bone resorption and PGE2 production in murine calvarial cultures were inhibited with IC50 values of 3 x 10(-7) and 2 x 10(-8) mol/l, respectively. 5-Lipoxygenase (murine macrophages), phospholipase A2 (human PMN) and phospholipase C (human platelets) were not inhibited. CGP 28238 may represent a novel highly potent anti-inflammatory compound with improved gastro-intestinal safety.

  10. Effect of polarized radiative transfer on the Hanle magnetic field determination in prominences: Analysis of hydrogen H alpha line observations at Pic-du-Midi

    Science.gov (United States)

    Bommier, V.; Deglinnocenti, E. L.; Leroy, J. L.; Sahal-Brechot, S.

    1985-01-01

    The linear polarization of the Hydrogen H alpha line of prominences has been computed, taking into account the effect of a magnetic field (Hanle effect), of the radiative transfer in the prominence, and of the depolarization due to collisions with the surrounding electrons and protons. The corresponding formalisms are developed in a forthcoming series of papers. In this paper, the main features of the computation method are summarized. The results of computation have been used for interpretation in terms of magnetic field vector measurements from H alpha polarimetric observations in prominences performed at Pic-du-Midi coronagraph-polarimeter. Simultaneous observations in one optically thin line (He I D(3)) and one optically thick line (H alpha) give an opportunity for solving the ambiguity on the field vector determination.

  11. "Ode Ori": a culture-bound disorder with prominent somatic features in Yoruba Nigerian patients.

    Science.gov (United States)

    Makanjuola, R O

    1987-03-01

    Thirty patients diagnosed by Nigerian Yoruba traditional healers as suffering from a condition termed "Ode Ori" are described. The chief complaints were of a crawling sensation in the head and body, noises in the ears, palpitations and various other somatic complaints. Anxiety and depressive symptoms were prominent in all the patients and indeed the most common DSM-III diagnoses were of depressive and anxiety disorders. The significance of the disorder and its features is discussed in the context of the socio-cultural background of the patients.

  12. Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors.

    Science.gov (United States)

    Wang, Qi-Qin; Cheng, Ning; Zheng, Xiao-Wei; Peng, Sheng-Ming; Zou, Xiao-Qing

    2013-07-15

    Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC50 values ranging from (0.099±0.008) μM to (2.833±0.102) μM. O(7)-Nitrooxyethyl-O(3'),O(4')-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50=(0.099±0.008) μM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Fragment-based discovery of a potent NAMPT inhibitor.

    Science.gov (United States)

    Korepanova, Alla; Longenecker, Kenton L; Pratt, Steve D; Panchal, Sanjay C; Clark, Richard F; Lake, Marc; Gopalakrishnan, Sujatha M; Raich, Diana; Sun, Chaohong; Petros, Andrew M

    2017-12-12

    NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Dynamics of quiescent prominence fine structures analyzed by 2D non-LTE modelling of the Hα line

    Czech Academy of Sciences Publication Activity Database

    Gunár, Stanislav; Mein, P.; Schmieder, B.; Heinzel, Petr; Mein, N.

    2012-01-01

    Roč. 543, July (2012), A93/1-A93/15 ISSN 0004-6361 R&D Projects: GA ČR GP205/09/P554; GA ČR GAP209/12/0906 Institutional support: RVO:67985815 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 5.084, year: 2012

  15. MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38.

    Directory of Open Access Journals (Sweden)

    Xue Liang

    Full Text Available Dendritic cells (DCs play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22 as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.

  16. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  17. Specific Abilities May Increment Psychometric g for High Ability Populations

    Science.gov (United States)

    2016-04-14

    tend to sort themselves into jobs that are commensurate with their ability level ( McCormick , DeNisi, & Staw, 1979; McCormick , Jeanneret, & Mecham...of Genetic Psychology, 153, 229-230. Specific abilities, g, & high ability populations 14 McCormick , E. J., DeNisi, A. S., & Shaw, J. B... McCormick , E. J., Jeanneret, P. R., & Mecham, R. C. (1972). A study of job characteristics and job dimensions as based on the Position Analysis Questionnaire

  18. Discovery of potent and selective CDK8 inhibitors through FBDD approach.

    Science.gov (United States)

    Han, Xingchun; Jiang, Min; Zhou, Chengang; Zhou, Zheng; Xu, Zhiheng; Wang, Lisha; Mayweg, Alexander V; Niu, Rui; Jin, Tai-Guang; Yang, Song

    2017-09-15

    A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors. Optimization of a fragment hit guided by co-crystal structures led to identification of a novel series of potent CDK8 inhibitors which are highly ligand efficient, kinase selective and cellular active. Compound 16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein.

    Science.gov (United States)

    Petros, Andrew M; Swann, Steven L; Song, Danying; Swinger, Kerren; Park, Chang; Zhang, Haichao; Wendt, Michael D; Kunzer, Aaron R; Souers, Andrew J; Sun, Chaohong

    2014-03-15

    Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.

    Science.gov (United States)

    Reader, John C; Matthews, Thomas P; Klair, Suki; Cheung, Kwai-Ming J; Scanlon, Jane; Proisy, Nicolas; Addison, Glynn; Ellard, John; Piton, Nelly; Taylor, Suzanne; Cherry, Michael; Fisher, Martin; Boxall, Kathy; Burns, Samantha; Walton, Michael I; Westwood, Isaac M; Hayes, Angela; Eve, Paul; Valenti, Melanie; de Haven Brandon, Alexis; Box, Gary; van Montfort, Rob L M; Williams, David H; Aherne, G Wynne; Raynaud, Florence I; Eccles, Suzanne A; Garrett, Michelle D; Collins, Ian

    2011-12-22

    Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.

  1. Discovery, synthesis, selectivity modulation and DMPK characterization of 5-azaspiro[2.4]heptanes as potent orexin receptor antagonists.

    Science.gov (United States)

    Stasi, Luigi Piero; Artusi, Roberto; Bovino, Clara; Buzzi, Benedetta; Canciani, Luca; Caselli, Gianfranco; Colace, Fabrizio; Garofalo, Paolo; Giambuzzi, Silvia; Larger, Patrice; Letari, Ornella; Mandelli, Stefano; Perugini, Lorenzo; Pucci, Sabrina; Salvi, Matteo; Toro, PierLuigi

    2013-05-01

    Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Language mastery, narrative abilities and oral expression abilities in ...

    African Journals Online (AJOL)

    The importance of language and language mastery for science learning has been the object of extensive investigation in recent decades, leading to ample recognition. However, specific focus on the role of narrative abilities is still scarce. This work focuses on the relevance of narrative abilities for chemistry learning.

  3. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor

    Directory of Open Access Journals (Sweden)

    Qureshi Asaf A

    2012-07-01

    Full Text Available Abstract Background Altered immune function during ageing results in increased production of nitric oxide (NO and other inflammatory mediators. Recently, we have reported that NO production was inhibited by naturally-occurring proteasome inhibitors (quercetin, δ-tocotrienol, and riboflavin in lipopolysaccharide (LPS-stimulated RAW264.7 cells, and thioglycolate-elicited peritoneal macrophages from C57BL/6 mice. In a continuous effort to find more potent, non-toxic, commercially available, naturally-occurring proteasome inhibitors that suppress inflammation, the present study was carried out to describe the inhibition of NF-κB activation and NO, TNF-α, IL-6, IL-1β, and iNOS expression by trans-resveratrol, trans-pterostilbene, morin hydrate, and nicotinic acid in LPS-induced RAW 264.7 cells and thioglycolate-elicited peritoneal macrophages from C57BL/6 and BALB/c mice. Results The present results indicate that resveratrol, pterostilbene, and morin hydrate caused significant inhibition (>70% to 90%; P 40%; P 60%; P 40%; P P  Conclusions The present results clearly demonstrate that resveratrol and pterostilbene are particularly potent proteasome inhibitors that suppress expression of genes, and production of inflammatory products in LPS-stimulated RAW 264.7 cells, and macrophages from C57BL/6 and BALB/c mice. Resveratrol and pterostilbene which are present in grapes, blueberries, and red wine, have been implicated as contributing factors to the lower incidence of cardiovascular disease in the French population, despite their relatively high dietary fat intake. Consequently, it appears likely that the beneficial nutritional effects of resveratrol and pterostilbene are due at least in part, to their ability to inhibit NF-κB activation by the proteasome, thereby suppressing activation of pro-inflammatory cytokines and iNOS genes, resulting in decreased secretion of TNF-α, IL-1β, IL-6, and NO levels, in response to inflammatory stimuli

  4. Multi-potent Natural Scaffolds Targeting Amyloid Cascade: In Search of Alzheimer's Disease Therapeutics.

    Science.gov (United States)

    Chakraborty, Sandipan

    2017-01-01

    Alzheimer's Disease (AD) once considered a rare disorder emerges as a major health concern in recent times. The disease pathogenesis is very complex and yet to be understood completely. However, "Amyloid Cascade" is the central event in disease pathogenesis. Several proteins of the amyloid cascade are currently being considered as potential targets for AD therapeutics discovery. Many potential compounds are in clinical trials, but till now there is no known cure for the disease. Recent years have witnessed remarkable research interest in the search of novel concepts in drug designing for AD. Multi-targeted ligand design is a paradigm shift in conventional drug discovery. In this process rather than designing ligands targeting a single receptor, novel ligands have been designed/ synthesized that can simultaneously target many pathways involved in disease pathogenesis. Here, recent developments in computational drug designing protocols to identify multi-targeted ligand for AD have been discussed. Therapeutic potential of different multi-potent compounds also has been discussed briefly. Prime emphasis has been given to multi-potent ligand from natural resources. Polyphenols are an interesting group of compounds which show efficacy against a wide range of disease and have the property to exhibit multi-potency. Several groups attempted to identify novel multi-potent phytochemicals for AD therapy. Multi-potency of several polyphenols or compounds synthesized using the poly-phenolic scaffolds have been briefly discussed here. However, the multi-targeted drug designing for AD is still in early stages, more advancement in drug designing method/algorithm developments is urgently required to discover more efficient compounds for AD therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Tea Contains Potent Inhibitors of Tyrosine Phosphatase PTP1B

    OpenAIRE

    Ma, Junfeng; Li, Zhe; Xing, Shu; Ho, Wanting Tina; Fu, Xueqi; Zhao, Zhizhuang Joe

    2011-01-01

    Tea is widely consumed all over the world. Studies have demonstrated the role of tea in prevention and treatment of various chronic diseases including diabetes and obesity, but the underlying mechanism is unclear. PTP1B is a widely expressed tyrosine phosphatase which has been defined as a target for therapeutic drug development to treat diabetes and obesity. In screening for inhibitors of PTP1B, we found that aqueous extracts of teas exhibited potent PTP1B inhibitory effects with an IC50 val...

  6. Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents.

    Science.gov (United States)

    Biftu, Tesfaye; Feng, Dennis; Fisher, Michael; Liang, Gui-Bai; Qian, Xiaoxia; Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Liberator, Paul A; Brown, Chris; Gurnett, Anne; Leavitt, Penny S; Thompson, Donald; Mathew, John; Misura, Andrew; Samaras, Samantha; Tamas, Tamas; Sina, Joseph F; McNulty, Kathleen A; McKnight, Crystal G; Schmatz, Dennis M; Wyvratt, Matthew

    2006-05-01

    Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies.

  7. Nanomaterial N-CP/DLPLG as potent1onal tissue graft in osteoreparation in combination with bone marrow cells on subcutaneous implantation model

    Directory of Open Access Journals (Sweden)

    Janićijević Jelena M.

    2008-01-01

    Full Text Available The need for bone graft materials in osteoreparation is tremendous. Many researches have shown that calcium-phosphate bioceramics have good biocompatibility and osteoconductivity. We used nanocomposite biomaterial calcium phosphate coated with poly (dl-lactide-co-glycolide or N-CP/DLPLG. The goal of this investigation was to examine weather N-CP/DLPLG has ability to sustain growth of bone marrow cells after subcutaneous implantation in Balb/c mice. For that purpose N-CP/DLPLG implants with and without bone marrow cells (control were made. Implants were extracted after eight days and eight weeks. In implants loaded with bone marrow cells after eight days and eight weeks we observed fields rich in cells, angiogenesis and collagen genesis. These results showed that N-CP/DLPLG has property of tissue scaffold which sustain bone marrow cells growth and collagen production. This represents a good way for further examination of N-CP/DLPLG as potentional tissue scaffold in osteoreparation.

  8. Quantifying the cepstral peak prominence, a measure of dysphonia.

    Science.gov (United States)

    Heman-Ackah, Yolanda D; Sataloff, Robert T; Laureyns, Griet; Lurie, Deborah; Michael, Deirdre D; Heuer, Reinhardt; Rubin, Adam; Eller, Robert; Chandran, Swapna; Abaza, Mona; Lyons, Karen; Divi, Venu; Lott, Joanna; Johnson, Jennifer; Hillenbrand, James

    2014-11-01

    The purpose of this study is to establish normative values for the smoothed cepstral peak prominence (CPPS) and its sensitivity and specificity as a measure of dysphonia. Prospective cohort study. Voice samples of running speech were obtained from 835 patients and 50 volunteers. Eight laryngologists and four speech-language pathologists performed perceptual ratings of the voice samples on the degree of dysphonia/normality using an analog scale. The mean of their perceptual ratings was used as the gold standard for the detection of the presence or absence of dysphonia. CPPS was measured using the CPPS algorithm of Hillenbrand, and the cut-off value for positivity that has the highest sensitivity and specificity for discriminating between normal and severely dysphonia voices was determined based on ROC-curve analysis. The cut-off value for normal for CPPS was set at 4.0 or higher, which gave a sensitivity of 92.4%, a specificity of 79%, a positive predictive value of 82.5%, and a negative predictive value of 90.8%. The area under the receiver operating characteristic (ROC) curve was 0.937 (P dysphonia, with the normal value of CPPS (Hillenbrand algorithm) of a running speech sample being defined as a value of 4.0 or higher. Copyright © 2014 The Voice Foundation. All rights reserved.

  9. Anti-topoisomerase drugs as potent inducers of chromosomal aberrations

    Directory of Open Access Journals (Sweden)

    Loredana Bassi

    2000-12-01

    Full Text Available DNA topoisomerases catalyze topological changes in DNA that are essential for normal cell cycle progression and therefore they are a preferential target for the development of anticancer drugs. Anti-topoisomerase drugs can be divided into two main classes: "cleavable complex" poisons and catalytic inhibitors. The "cleavable complex" poisons are very effective as anticancer drugs but are also potent inducers of chromosome aberrations so they can cause secondary malignancies. Catalytic inhibitors are cytotoxic but they do not induce chromosome aberrations. Knowledge about the mechanism of action of topoisomerase inhibitors is important to determine the best anti-topoisomerase combinations, with a reduced risk of induction of secondary malignancies.As topoisomerases de DNA catalisam alterações topológicas no DNA que são essenciais para a progressão do ciclo celular normal e, portanto, são um alvo preferencial para o desenvolvimento de drogas anticâncer. Drogas anti-topoisomerases podem ser divididas em duas classes principais: drogas anti-"complexos cliváveis" e inibidores catalíticos. As drogas anti-"complexos cliváveis" são muito eficazes como drogas anticancerígenas, mas são também potentes indutores de aberrações cromossômicas, podendo causar neoplasias malignas secundárias. Inibidores catalíticos são citotóxicos mas não induzem aberrações cromossômicas. Conhecimento a respeito do mecanismo de ação de inibidores de topoisomerases é importante para determinar as melhores combinações anti-topoisomerases, com um reduzido risco de indução de neoplasias malignas secundárias.

  10. Highly potent fibrinolytic serine protease from Streptomyces.

    Science.gov (United States)

    Uesugi, Yoshiko; Usuki, Hirokazu; Iwabuchi, Masaki; Hatanaka, Tadashi

    2011-01-05

    We introduce a highly potent fibrinolytic serine protease from Streptomyces omiyaensis (SOT), which belongs to the trypsin family. The fibrinolytic activity of SOT was examined using in vitro assays and was compared with those of known fibrinolytic enzymes such as plasmin, tissue-type plasminogen activator (t-PA), urokinase, and nattokinase. Compared to other enzymes, SOT showed remarkably higher hydrolytic activity toward mimic peptides of fibrin and plasminogen. The fibrinolytic activity of SOT is about 18-fold higher than that of plasmin, and is comparable to that of t-PA by fibrin plate assays. Furthermore, SOT had some plasminogen activator-like activity. Results show that SOT and nattokinase have very different fibrinolytic and fibrinogenolytic modes, engendering significant synergetic effects of SOT and nattokinase on fibrinolysis. These results suggest that SOT presents important possibilities for application in the therapy of thrombosis. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. A Potent In Vivo Antitumor Efficacy of Novel Recombinant Type I Interferon.

    Science.gov (United States)

    Zhang, Kang-Jian; Yin, Xiao-Fei; Yang, Yuan-Qin; Li, Hui-Ling; Xu, Yan-Ni; Chen, Lie-Yang; Liu, Xi-Jun; Yuan, Su-Jing; Fang, Xian-Long; Xiao, Jing; Wu, Shuai; Xu, Hai-Neng; Chu, Liang; Katlinski, Kanstantsin V; Katlinskaya, Yuliya V; Guo, Rong-Bing; Wei, Guang-Wen; Wang, Da-Cheng; Liu, Xin-Yuan; Fuchs, Serge Y

    2017-04-15

    Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I. Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK-STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models. Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK-STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8 + T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice. Conclusions: These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038-49. ©2016 AACR . ©2016 American Association for Cancer Research.

  12. Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.

    Science.gov (United States)

    Apfel, C; Banner, D W; Bur, D; Dietz, M; Hirata, T; Hubschwerlen, C; Locher, H; Page, M G; Pirson, W; Rossé, G; Specklin, J L

    2000-06-15

    Low-molecular-weight beta-sulfonyl- and beta-sulfinylhydroxamic acid derivatives have been synthesized and found to be potent inhibitors of Escherichia coli peptide deformylase (PDF). Most of the compounds synthesized and tested displayed antibacterial activities that cover several pathogens found in respiratory tract infections, including Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The potential of these compounds as antibacterial agents is discussed with respect to selectivity, intracellular concentrations in bacteria, and potential for resistance development.

  13. Ophiamides A-B, new potent urease inhibitory sphingolipids from Heliotropium ophioglossum.

    Science.gov (United States)

    Firdous, Sadiqa; Ansari, Nida Hassan; Fatima, Itrat; Malik, Abdul; Afza, Nighat; Iqbal, Lubna; Lateef, Mehreen

    2012-07-01

    Ophiamides A (1) and B (2), two new sphingolipids have been isolated from the n-hexane subfraction of the MeOH extract of the whole plant of Heliotropium ophioglossum along with glycerol monopalmitate (3) and β-sitosterol 3-O-β-D: -glucoside (4) reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy. Both the compounds 1 and 2 showed potent inhibitory activity against the enzyme urease.

  14. Prominent soft x-ray lines of Sr-like Au41+ in low-energy EBIT spectrum

    International Nuclear Information System (INIS)

    Vilkas, Marius Jonas; Ishikawa, Yasuyuki; Traebert, Elmar

    2007-01-01

    Relativistic multireference Moeller-Plesset perturbation theory has been employed to calculate with high accuracy the energy levels and transition probabilities of Cu- to Sr-like gold ions. The many-body calculations were carried out to identify the unassigned blended lines in the 35-40 A region of the low-energy EBIT spectrum of the gold ions [Traebert et al 2001 Can. J. Phys.79153]. Most of the prominent lines in the 35-40 A region were identified as the emission lines in Sr-like gold

  15. Aurintricarboxylic acid is a potent inhibitor of phosphofructokinase.

    Science.gov (United States)

    McCune, S A; Foe, L G; Kemp, R G; Jurin, R R

    1989-01-01

    Aurintricarboxylic acid (ATA) was found to be a very potent inhibitor of purified rabbit liver phosphofructokinase (PFK), giving 50% inhibition at 0.2 microM. The inhibition was in a manner consistent with interaction at the citrate-inhibitory site of the enzyme. The data suggest that inhibition of PFK by ATA was not due to denaturation of the enzyme or the irreversible binding of inhibitor, since the inhibition could be reversed by addition of allosteric activators of PFK, i.e. fructose 2,6-bisphosphate or AMP. Two other tricarboxylic acids, agaric acid and (-)-hydroxycitrate, were found to inhibit PFK. ATA at much higher concentrations (500 microM) was shown to inhibit fatty acid synthesis from endogenous glycogen in rat hepatocytes; however, protein synthesis was not altered. PMID:2525029

  16. Red wine contains a potent inhibitor of phenolsulphotransferase.

    Science.gov (United States)

    Littlewood, J T; Glover, V; Sandler, M

    1985-01-01

    Many ethanolic drinks, especially red wine, contain potent inhibitors of phenolsulphotransferase. At a dilution of 1/75 from the original beverage, extracts from six types of red wine inhibited human platelet phenolsulphotransferase P by a mean of 99% and human platelet phenolsulphotransferase M by 12%. Such extracts had no significant effect on rat liver monoamine oxidase A or human platelet monoamine oxidase B. The inhibitors, which have not yet been identified, can be extracted into ethyl acetate at acid or neutral pH. Thus, they are not monoamines. Flavonoid phenols are plausible candidates. As phenolsulphotransferase M and P are involved in the metabolism of many phenols, including drugs, the inhibition of these enzymes could result in the enhancement of pharmacological potency and have important clinical consequences. PMID:3857069

  17. Loss of ability to work and ability to live independently in Parkinson's disease.

    Science.gov (United States)

    Jasinska-Myga, Barbara; Heckman, Michael G; Wider, Christian; Putzke, John D; Wszolek, Zbigniew K; Uitti, Ryan J

    2012-02-01

    Ability to work and live independently is of particular concern for patients with Parkinson's disease (PD). We studied a series of PD patients able to work or live independently at baseline, and evaluated potential risk factors for two separate outcomes: loss of ability to work and loss of ability to live independently. The series comprised 495 PD patients followed prospectively. Ability to work and ability to live independently were based on clinical interview and examination. Cox regression models adjusted for age and disease duration were used to evaluate associations of baseline characteristics with loss of ability to work and loss of ability to live independently. Higher UPDRS dyskinesia score, UPDRS instability score, UPDRS total score, Hoehn and Yahr stage, and presence of intellectual impairment at baseline were all associated with increased risk of future loss of ability to work and loss of ability to live independently (P ≤ 0.0033). Five years after initial visit, for patients ≤70 years of age with a disease duration ≤4 years at initial visit, 88% were still able to work and 90% to live independently. These estimates worsened as age and disease duration at initial visit increased; for patients >70 years of age with a disease duration >4 years, estimates at 5 years were 43% able to work and 57% able to live independently. The information provided in this study can offer useful information for PD patients in preparing for future ability to perform activities of daily living. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Design and synthesis of potent, orally-active DGAT-1 inhibitors containing a dioxino[2,3-d]pyrimidine core.

    Science.gov (United States)

    Dow, Robert L; Andrews, Melissa; Aspnes, Gary E; Balan, Gayatri; Michael Gibbs, E; Guzman-Perez, Angel; Karki, Kapil; Laperle, Jennifer L; Li, Jian-Cheng; Litchfield, John; Munchhof, Michael J; Perreault, Christian; Patel, Leena

    2011-10-15

    A novel series of potent DGAT-1 inhibitors was developed originating from the lactam-based clinical candidate PF-04620110. Incorporation of a dioxino[2,3-d]pyrimidine-based core afforded good alignment of pharmacophore features and resulted in improved passive permeability. Development of an efficient, homochiral synthesis of these targets facilitated confirmation of predictions regarding the stereochemical-dependence of DGAT-1 inhibition for this series. Compound 10 was shown to be a potent inhibitor of human DGAT-1 (10 nM) and to suppress triglyceride synthesis at oral doses of <3mg/kg. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Prominent Optic Disc Featured in Inherited Retinopathy.

    Science.gov (United States)

    Todorova, M G; Bojinova, R I; Valmaggia, C; Schorderet, D F

    2017-04-01

    Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology. Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1 . In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1 . In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4 . In the fourth family, POD with "mulberry-like" deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A , and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1 . In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS , thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease. Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out. Georg Thieme Verlag KG Stuttgart · New York.

  20. Measuring Work Ability with Its Antecedents: Evaluation of the Work Ability Survey.

    Science.gov (United States)

    Voltmer, Jan-Bennet; Deller, Jürgen

    2017-07-24

    Purpose The revised version of the Work Ability Survey (WAS-R) assesses work ability on several sub-scales at the intersection of personal and organizational capacity, thus adding to the measurement of work ability by integrating the holistic model. It, therefore, improves on two features of the current standard measurement tool of work ability, the Work Ability Index (WAI): (1) a ceiling effect and (2) limited detail due to a focus on physical health and personal capacity. Method In two samples (n 1  = 1093, n 2  = 359), psychometric properties and the structure of the WAS-R were analyzed. To evaluate construct validity, inter-correlations of the WAS-R and WAI, sickness absence, expected and desired retirement age, and post-retirement work intention were calculated. Results The WAS-R was found to be distributed closer to normality than the WAI. The structural analyses yielded acceptable results for the hypothesized model. The WAS-R was adequately correlated with the WAI, negatively with sickness absence, and positively with desired retirement age. Conclusions The WAS-R extends the measurement of work ability, reflecting organizations' work demands. Its broad sub-scales lead to high acceptance of the results within the participating companies. In particular, the organizational capacity scales can be used to guide interventions aiming at organizational characteristics to improve work ability.

  1. Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

    Science.gov (United States)

    Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

    2010-04-22

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  2. eCD4-Ig variants that more potently neutralize HIV-1.

    Science.gov (United States)

    Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

    2018-03-28

    The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig, and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral lifecycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the

  3. Measuring Creative Imagery Abilities

    Directory of Open Access Journals (Sweden)

    Dorota M. Jankowska

    2015-10-01

    Full Text Available Over the decades, creativity and imagination research developed in parallel, but they surprisingly rarely intersected. This paper introduces a new theoretical model of creative imagination, which bridges creativity and imagination research, as well as presents a new psychometric instrument, called the Test of Creative Imagery Abilities (TCIA, developed to measure creative imagery abilities understood in accordance with this model. Creative imagination is understood as constituted by three interrelated components: vividness (the ability to create images characterized by a high level of complexity and detail, originality (the ability to produce unique imagery, and transformativeness (the ability to control imagery. TCIA enables valid and reliable measurement of these three groups of abilities, yielding the general score of imagery abilities and at the same time making profile analysis possible. We present the results of eight studies on a total sample of more than 1,700 participants, showing the factor structure of TCIA using confirmatory factor analysis, as well as provide data confirming this instrument’s validity and reliability. The availability of TCIA for interested researchers may result in new insights and possibilities of integrating the fields of creativity and imagination science.

  4. Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors

    Directory of Open Access Journals (Sweden)

    Sadrerafi K

    2018-04-01

    Full Text Available Keivan Sadrerafi, Emilia O Mason, Mark W Lee Jr Department of Chemistry, University of Missouri, Columbia, MO, USA Purpose: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl-7-(4′-(trans-3″-(3‴-pyridylacrylamidobutyl-1,7-dicarbadodecaborane (hm-MC4-PPEA, was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt. Nampt has been shown to be upregulated in most cancers and is a promising target for the treatment of many different types of cancers, including breast cancers. Patients and methods: To increase the selectivity of hm-MC4-PPEA toward cancer cells, three prodrugs were synthesized with different hydrolyzable linkers: ester, carbonate, and carbamate. Using click chemistry a fluorophore was attached to these prodrugs to act as a model for our conjugation strategy and to serve as an aid for prodrug stability studies. The stabilities of these drug conjugates were tested in phosphate-buffered saline (PBS at normothermia (37°C using three different pH levels, 5.5, 7.5, and 9.5, as well as in horse serum at physiological pH. The stability of each was monitored using reversed-phase HPLC equipped with both diode array and fluorescence detection. The inhibitory activity of hm-MC4-PPEA was also measured using a commercially available colorimetric assay. The biological activities of the drug conjugates as well as those of the free drug (hm-MC4-PPEA, were evaluated using the MTT assay against the human breast cancer cell lines T47D and MCF7, as well as the noncancerous, transformed, Nampt-dependent human breast epithelium cell line 184A1.Results: hm-MC4-PPEA showed to be a potent inhibitor of recombinant Nampt activity, exhibiting an IC50 concentration of 6.8 nM. The prodrugs showed great stability towards hydrolytic degradation under neutral, mildly acidic and mildly basic conditions. The carbamate prodrug also showed to be stable in rat serum. However, the carbonate and the ester prodrug

  5. Sustainable Competitiveness of the SME Sector Formed by Collaboration: The Prominent Role of HR

    Directory of Open Access Journals (Sweden)

    Tamás Molnár

    2016-04-01

    Full Text Available Human resources play a prominent role in the analysis of the development and competitiveness of the SME sector, therefore the discussion of the human resources is inevitable during the general characterisation of the sector. The development of and application of the appropriate organisational culture, motivation, competence are fundamental competitiveness factors of the success of SMEs. Maslow’s hierarchy of needs can be adapted to the SMEs. The role of the state is necessary for the success of SMEs. The European Union continues to give special emphasis to the SME sector in the future, as one of the key business sectors influencing the economic success of a nation.

  6. Triazolophostins: a library of novel and potent agonists of IP3 receptors.

    Science.gov (United States)

    Vibhute, Amol M; Konieczny, Vera; Taylor, Colin W; Sureshan, Kana M

    2015-06-28

    IP3 receptors are channels that mediate the release of Ca(2+) from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of synthetic conditions for each analog. Such lengthy one-at-a-time syntheses limit access to AdA analogs. We have addressed this problem by synthesizing a library of triazole-based AdA analogs, triazolophostins, by employing click chemistry. An advanced intermediate having all the necessary phosphates and a β-azide at the anomeric position was reacted with various alkynes under Cu(i) catalysis to yield triazoles, which upon deprotection gave triazolophostins. All eleven triazolophostins synthesized are more potent than IP3 and some are equipotent with AdA in functional analyses of IP3 receptors. We show that a triazole ring can replace adenine without compromising the potency of AdA and provide facile routes to novel AdA analogs.

  7. The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28.

    Directory of Open Access Journals (Sweden)

    Kristin E Murphy

    Full Text Available KRAB domain Zinc finger proteins are one of the most abundant families of transcriptional regulators in higher vertebrates. The prevailing view is that KRAB domain proteins function as potent transcriptional repressors by recruiting TRIM28 and promoting heterochromatin spreading. However, the extent to which all KRAB domain proteins are TRIM28-dependent transcriptional repressors is currently unclear. Our studies on mouse ZFP568 revealed that TRIM28 recruitment by KRAB domain proteins is not sufficient to warrant transcriptional repressive activity. By using luciferase reporter assays and yeast two-hybrid experiments, we tested the ability of ZFP568 and other mouse KRAB domain proteins to repress transcription and bind TRIM28. We found that some mouse KRAB domain proteins are poor transcriptional repressors despite their ability to recruit TRIM28, while others showed strong KRAB-dependent transcriptional repression, but no TRIM28 binding. Together, our results show that the transcriptional repressive activity of KRAB-ZNF proteins does not correlate with their ability to recruit TRIM28, and provide evidence that KRAB domains can regulate transcription in a TRIM28-independent fashion. Our findings challenge the current understanding of the molecular mechanisms used by KRAB domain proteins to control gene expression and highlight that a high percentage of KRAB domain proteins in the mouse genome differ from the consensus KRAB sequence at amino acid residues that are critical for TRIM28 binding and/or repressive activity.

  8. Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1

    Directory of Open Access Journals (Sweden)

    Li-Wei Zou

    2017-06-01

    Full Text Available Human carboxylesterase 1 (hCE1, one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs were assayed using D-Luciferin methyl ester (DME and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB as specific optical substrate for hCE1, and hCE2, respectively. Following screening of a series of natural triterpenoids, oleanolic acid (OA, and ursolic acid (UA were found with strong inhibitory effects on hCE1 and relative high selectivity over hCE2. In order to get the highly selective and potent inhibitors of hCE1, a series of OA and UA derivatives were synthesized from OA and UA by chemical modifications including oxidation, reduction, esterification, and amidation. The inhibitory effects of these derivatives on hCEs were assayed and the structure-activity relationships of tested triterpenoids as hCE1 inhibitors were carefully investigated. The results demonstrated that the carbonyl group at the C-28 site is essential for hCE1 inhibition, the modifications of OA or UA at this site including esters, amides and alcohols are unbeneficial for hCE1 inhibition. In contrast, the structural modifications on OA and UA at other sites, such as converting the C-3 hydroxy group to 3-O-β-carboxypropionyl (compounds 20 and 22, led to a dramatically increase of the inhibitory effects against hCE1 and very high selectivity over hCE2. 3D-QSAR analysis of all tested triterpenoids including OA and UA derivatives provide new insights into the fine relationships linking between the inhibitory effects on hCE1 and the steric-electrostatic properties of triterpenoids. Furthermore, both inhibition kinetic analyses and docking

  9. Prominent ears: the effect of reconstructive surgery on self-esteem and social interaction in children with a minor defect compared to children with a major orthopedic defect.

    Science.gov (United States)

    Niemelä, Birgitta Johansson; Hedlund, Anders; Andersson, Gerhard; Wahlsten, Viveka Sundelin

    2008-11-01

    In a prospective study of patients with prominent ears, the effect of reconstructive surgery on self-esteem and social interaction was examined 1 year after surgery. Of 42 patients with prominent ears aged 7 to 15 years, 21 were matched with a comparison group of orthopedic patients (leg lengthening) and a control group of schoolchildren. Psychological measures evaluated self-esteem, depression, anxiety, cognition, parents' ratings of child behavior and symptoms, and parent anxiety. Semistructured interviews with the child and parents were also conducted. The motivation to be operated on was pain, teasing, and feelings of being different. The satisfaction rate with the result of reconstructive surgery was high. The psychological measures of the prominent ears group had results close to those of the control group, although the leg lengthening group had lower self-esteem and higher depression and anxiety scores. With few exceptions, all patients had scores within the normal range on self-rating scales. Parents reported less activity at leisure time in both patient groups than in the control group. After surgery, parents reported improved behavior on the Child Behavior Checklist total problem score. Patients with minor defects had fewer self-reported psychological and behavior problems than the major defect group. Interestingly, prominent ears patients also had low activity levels. Reconstructive surgery had no adverse effect on the prominent ears patients in this interim study but rather resulted in improved well-being. It is important to investigate further the effect of reconstructive surgery on children's self-esteem and social interaction.

  10. Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors

    DEFF Research Database (Denmark)

    Sangwan, Payare L; Koul, Jawahir L; Koul, Surrinder

    2008-01-01

    Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like...... reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors....

  11. Potent host-directed small-molecule inhibitors of myxovirus RNA-dependent RNA-polymerases.

    Directory of Open Access Journals (Sweden)

    Stefanie A Krumm

    Full Text Available Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections. Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum. Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited. To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families. This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains. After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs. The compound shows high metabolic stability when exposed to human S-9 hepatocyte subcellular fractions. Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target. While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity. Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp activity. Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays. In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity. Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid

  12. Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM).

    Science.gov (United States)

    Elkamhawy, Ahmed; Viswanath, Ambily Nath Indu; Pae, Ae Nim; Kim, Hyeon Young; Heo, Jin-Chul; Park, Woo-Kyu; Lee, Chong-Ock; Yang, Heekyoung; Kim, Kang Ho; Nam, Do-Hyun; Seol, Ho Jun; Cho, Heeyeong; Roh, Eun Joo

    2015-10-20

    Herein, we report new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells. Low micromolar IC₅₀ values were exhibited over a panel of three primary GBM patient-derived cell cultures belonging to proneural (GBM-1), mesenchymal (GBM-2), and classical (GBM-3) subtypes. Eight compounds showed excellent selectivity indices for GBM cells comparing to a normal astrocyte cell line. In JC-1 assay, analogues 11, 12, 20, 22, and 24 exerted promising rates of mPTP opening induction towards proneural GBM subtype. Compounds 11, 20, and 24 bound to the translocator protein 18 kDa (TSPO) in submicromolar range using [(3)H] PK-11195 binding affinity assay. A homology model was built and docked models of 11, 12, 20, 22 and 24 were generated for describing their plausible binding modes in TSPO. In 3D clonogenic assay, compound 20 manifested potent tumoricidal effects on TMZ-resistant GBM cells even at submicromolar concentrations. In addition, CYP450 and hERG assays presented a safe toxicity profile of 20. Taken as a whole, this report presents compound 20 as a potent, selective and safe GBM cytotoxic agent which constitutes a promising direction against TMZ-resistant GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Prominent reflector beneath around the segmentation boundary between Tonankai-Nankai earthquake area

    Science.gov (United States)

    Nakanishi, A.; Shimomura, N.; Fujie, G.; Kodaira, S.; Obana, K.; Takahashi, T.; Yamamoto, Y.; Yamashita, M.; Takahashi, N.; Kaneda, Y.; Mochizuki, K.; Kato, A.; Iidaka, T.; Kurashimo, E.; Shinohara, M.; Takeda, T.; Shiomi, K.

    2013-12-01

    In the Nankai Trough subduction seismogenic zone, the Nankai and Tonankai earthquakes had often occurred simultaneously, and caused a great event. In most cases, first break of such large events of Nankai Trough usually begins from southwest off the Kii Peninsula so far. The idea of split Philippine Sea plate between the Kii Peninsula and the Shikoku Island, which explains seismicity, tectonic background, receiver function image and historical plate motion, was previously suggested. Moreover, between the Kii Peninsula and the Shikoku Island, there is a gap of deep low-frequency events observed in the belt-like zone along the strike of the subducting Philippine Sea plate. In 2010 and 2011, we conducted the large-scale high-resolution wide-angle and reflection (MCS) seismic study, and long-term observation from off Shikoku and Kii Peninsula. Marine active source seismic data have been acquired along grid two-dimensional profiles having the total length of ~800km/year. A three-dimensional seismic tomography using active and passive seismic data observed both land and ocean bottom stations have been also performed. From those data, we found a possible prominent reflector imaged in the offshore side in the Kii channel at the depth of ~18km. The velocity just beneath the reflector cannot be determined due to the lack of ray paths. Based of the amplitude information, we interpret the reflector as the forearc Moho based on the velocity gap (from ~6.4km/s to ~7.4km/s). However, the reflector is shallower than the forearc Moho of other area along the Nankai Trough. Similar reflectors are recognized along other seismic profiles around the Kii channel. In this presentation, we will show the result of structure analysis to understand the peculiar structure including the prominent reflector around the Kii channel. Relation between the structure and the existence of the segmentation of the Nankai megathrust earthquake or seismic gap of the deep low-frequency events will be also

  14. Metofluthrin: a potent new synthetic pyrethroid with high vapor activity against mosquitoes.

    Science.gov (United States)

    Ujihara, Kazuya; Mori, Tatsuya; Iwasaki, Tomonori; Sugano, Masayo; Shono, Yoshinori; Matsuo, Noritada

    2004-01-01

    (1R)-trans-Norchrysanthemic acid fluorobenzyl esters are synthesized and their structure-activity relationships are discussed. These esters show outstanding insecticidal activity against mosquitoes. In particular, the 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl analog (metofluthrin) exhibits the highest potency, being approximately forty times as potent as d-allethrin in a mosquito coil formulation when tested against southern house mosquitoes (Culex quinquefasciatus). Metofluthrin also exhibits a significant vapor action at room temperature.

  15. Demethoxycurcumin is a potent inhibitor of P-type ATPases from diverse kingdoms of life

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Sehgal, Pankaj; Thanh Tung, Truong

    2016-01-01

    the curcuminoids, demethoxycurcumin was the most potent inhibitor of all tested P-type ATPases from fungal (Pma1p; H+-ATPase), plant (AHA2; H+-ATPase) and animal (SERCA; Ca2+-ATPase) cells. All three curcuminoids acted as non-competitive antagonist to ATP and hence may bind to a highly conserved allosteric site...

  16. DESTABILIZATION OF A SOLAR PROMINENCE/FILAMENT FIELD SYSTEM BY A SERIES OF EIGHT HOMOLOGOUS ERUPTIVE FLARES LEADING TO A CME

    Energy Technology Data Exchange (ETDEWEB)

    Panesar, Navdeep K.; Moore, Ronald L. [Center for Space Plasma and Aeronomic Research (CSPAR), UAH, Huntsville, AL 35805 (United States); Sterling, Alphonse C. [Heliophysics and Planetary Science Office, ZP13, Marshall Space Flight Center, Huntsville, AL 35812 (United States); Innes, Davina E., E-mail: navdeep.k.panesar@nasa.gov [Max Planck Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany)

    2015-09-20

    Homologous flares are flares that occur repetitively in the same active region, with similar structure and morphology. A series of at least eight homologous flares occurred in active region NOAA 11237 over 2011 June 16–17. A nearby prominence/filament was rooted in the active region, and situated near the bottom of a coronal cavity. The active region was on the southeast solar limb as seen from the Solar Dynamics Observatory/Atmospheric Imaging Assembly, and on the disk as viewed from the Solar TErrestrial RElations Observatory/EUVI-B. The dual perspective allows us to study in detail behavior of the prominence/filament material entrained in the magnetic field of the repeatedly erupting system. Each of the eruptions were mainly confined, but expelled hot material into the prominence/filament cavity system (PFCS). The field carrying and containing the ejected hot material interacted with the PFCS and caused it to inflate, resulting in a step-wise rise of the PFCS approximately in step with the homologous eruptions. The eighth eruption triggered the PFCS to move outward slowly, accompanied by a weak coronal dimming. As this slow PFCS eruption was underway, a final “ejective” flare occurred in the core of the active region, resulting in strong dimming in the EUVI-B images and expulsion of a coronal mass ejection (CME). A plausible scenario is that the repeated homologous flares could have gradually destabilized the PFCS, and its subsequent eruption removed field above the acitive region and in turn led to the ejective flare, strong dimming, and CME.

  17. Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors.

    Science.gov (United States)

    Choi, Jun Yong; Fuerst, Rita; Knapinska, Anna M; Taylor, Alexander B; Smith, Lyndsay; Cao, Xiaohang; Hart, P John; Fields, Gregg B; Roush, William R

    2017-07-13

    We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13·inhibitor complexes followed by molecular design and synthesis of potent but nonselective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn 2+ chelating unit was replaced with nonchelating polar residues that bridged over the Zn 2+ binding site and reached into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b, which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn 2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.

  18. Application of computerised penile arterial waveform analysis in the diagnosis of arteriogenic impotence. An initial study in potent and impotent men.

    Science.gov (United States)

    Desai, K M; Gingell, J C; Skidmore, R; Follett, D H

    1987-11-01

    A new method is described for evaluating arteriogenic impotence by means of noninvasive quantification of penile Doppler arterial waveforms using computerised analysis based on the Laplace Transform model. The haemodynamic changes occurring during a papaverine-induced erection in healthy potent volunteers have been recorded by this technique, which has also been shown to be capable of discriminating between a normal and an abnormal penile arterial supply in an initial study of potent and impotent men.

  19. FINE MAGNETIC STRUCTURE AND ORIGIN OF COUNTER-STREAMING MASS FLOWS IN A QUIESCENT SOLAR PROMINENCE

    International Nuclear Information System (INIS)

    Shen, Yuandeng; Liu, Yu; Xu, Zhi; Liu, Zhong; Liu, Ying D.; Chen, P. F.; Su, Jiangtao

    2015-01-01

    We present high-resolution observations of a quiescent solar prominence that consists of a vertical and a horizontal foot encircled by an overlying spine and has ubiquitous counter-streaming mass flows. While the horizontal foot and the spine were connected to the solar surface, the vertical foot was suspended above the solar surface and was supported by a semicircular bubble structure. The bubble first collapsed, then reformed at a similar height, and finally started to oscillate for a long time. We find that the collapse and oscillation of the bubble boundary were tightly associated with a flare-like feature located at the bottom of the bubble. Based on the observational results, we propose that the prominence should be composed of an overlying horizontal spine encircling a low-lying horizontal and vertical foot, in which the horizontal foot consists of shorter field lines running partially along the spine and has ends connected to the solar surface, while the vertical foot consists of piling-up dips due to the sagging of the spine fields and is supported by a bipolar magnetic system formed by parasitic polarities (i.e., the bubble). The upflows in the vertical foot were possibly caused by the magnetic reconnection at the separator between the bubble and the overlying dips, which intruded into the persistent downflow field and formed the picture of counter-streaming mass flows. In addition, the counter-streaming flows in the horizontal foot were possibly caused by the imbalanced pressure at the both ends

  20. An interpretation of hydrogen and helium line spectra of the loop prominence observed on November 3, 1973

    International Nuclear Information System (INIS)

    Kureizumi, Takeshi; Kubota, Jun; Kawaguchi, Ichiro; Tamenaga, Tatsuo; Maeda, Koichiro.

    1977-01-01

    The H sub(I), He sub(I), and He sub(II) emission lines of the loop prominence observed on November 3, 1973 in the rapidly developing phase are analyzed. The difference in widths of these lines suggests they do not originate in the same volume. The estimated T sub(e) (8000-9000 K) and n sub(e) (-- 2 x 10 12 cm -3 ) in the loop from the Balmer lines do not change appreciably with time everywhere in the loop during our observation (00 sup(h)40 sup(m)-01 sup(h)10 sup(m)UT). The degree of ionization of hydrogen is estimated to be in the range of 0.8 to 1.0. The ionizing mechanisms may be attributed to the UV radiation (lambda<=912A) from the underlying flare region. Local thermodynamic equilibrium (LTE) is approximately established in the excited levels of He sub(I), but the singlet levels are somewhat overpopulated. The UV radiation field (lambda<=504A) from the surrounding coronal condensation is estimated from microwave and X-ray flux measurements of S sub(OLRAD)9. The ionization of He sub(I) (ionization degree 0.1-0.2) is mainly controlled by UV radiation from the coronal condensation. An adequate thread structure model of the loop prominence is suggested. (auth.)

  1. Prominent spectral features of Sm3+ ion in disordered zinc tellurite glass

    Directory of Open Access Journals (Sweden)

    Y.A. Tanko

    Full Text Available Trivalent rare earth doped glasses with modified spectroscopic features are essential for solid state lasers and diverse photonic applications. Glass composition optimisation may fulfil such demand. Stimulating the spectral properties of samarium (Sm3+ ions in tellurite glass host with desired enhancement is the key issue. Glasses with composition (80 − xTeO2–20ZnO–(xSm2O3, where 0 ⩽ x ⩽ 1.5 mol% are prepared using melt quenching method. The role of varying Sm3+ contents to improving the absorption and emission properties of the prepared glasses are determined. XRD pattern verifies amorphous nature of synthesised glasses. FTIR spectroscopy has been used to observe the structural modification of (TeO4 trigonal bipyramid structural units. DTA traces display prominent transition peaks for glass transition, crystallisation and melting temperature. Samples are discerned to be stable with desired Hruby parameter and superior glass forming ability. The UV–Vis–NIR absorption spectra reveals nine peaks centred at 470, 548, 947, 1085, 1238, 1385, 1492, 1550 and 1589 nm. These bands arise due to 6H5/2 → 4I11/2, 4G5/2, 6F11/2, 6F9/2, 6F7/2, 6F5/2, 6F3/2, 6H15/2 and 6F1/2 transitions, respectively. The direct, indirect band gap and Urbach energy calculated from the absorption edge of UV–Vis–NIR spectra are found to appear within (2.75–3.18 eV, (3.22–3.40 eV, and (0.20–0.31 eV, respectively. The observed increase in refractive index from 2.45 to 2.47 is ascribed to the generation of non-bridging oxygen atoms via the conversion of TeO4 into TeO3 units. Conversely the decrease in refractive index to 2.39 is attributed to the lower ionic radii (1.079 Å of Sm3+. PL spectra under the excitation of 452 nm display four emission bands centred at 563, 600, 644 and 705 nm corresponding to 4G5/2 → 6H5/2, 6H7/2, 6H9/2 and 6H11/2 transitions of samarium ions. Excellent features of the results nominate these compositions

  2. Readability and Reading Ability.

    Science.gov (United States)

    Wright, Benjamin D.; Stenner, A. Jackson

    This document discusses the measurement of reading ability and the readability of books by application of the Lexile framework. It begins by stating the importance of uniform measures. It then discusses the history of reading ability testing, based on the assumption that no researcher has been able to measure more than one kind of reading ability.…

  3. Potent human uric acid transporter 1 inhibitors: in vitro and in vivo metabolism and pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Wempe MF

    2012-11-01

    Full Text Available Michael F Wempe,1 Janet W Lightner,2 Bettina Miller,1 Timothy J Iwen,1 Peter J Rice,1 Shin Wakui,3 Naohiko Anzai,4 Promsuk Jutabha,4 Hitoshi Endou51Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA; 2Department of Pharmacology, East Tennessee State University, Johnson City, TN, USA; 3Department of Toxicology, Azabu University School of Veterinary Medicine, Chuo Sagamihara, Kanagawa, Japan; 4Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Shimotsuga, Tochigi, Japan; 5Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, JapanAbstract: Human uric acid transporter 1 (hURAT1; SLC22A12 is a very important urate anion exchanger. Elevated urate levels are known to play a pivotal role in cardiovascular diseases, chronic renal disease, diabetes, and hypertension. Therefore, the development of potent uric acid transport inhibitors may lead to novel therapeutic agents to combat these human diseases. The current study investigates small molecular weight compounds and their ability to inhibit 14C-urate uptake in oocytes expressing hURAT1. Using the most promising drug candidates generated from our structure–activity relationship findings, we subsequently conducted in vitro hepatic metabolism and pharmacokinetic (PK studies in male Sprague-Dawley rats. Compounds were incubated with rat liver microsomes containing cofactors nicotinamide adenine dinucleotide phosphate and uridine 5'-diphosphoglucuronic acid. In vitro metabolism and PK samples were analyzed using liquid chromatography/mass spectrometry-mass spectrometry methods. Independently, six different inhibitors were orally (capsule dosing or intravenously (orbital sinus administered to fasting male Sprague-Dawley rats. Blood samples were collected and analyzed; these data were used to compare in vitro and in vivo metabolism and to

  4. (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.

    Science.gov (United States)

    Knoll, J; Miklya, I; Knoll, B; Markó, R; Kelemen, K

    1996-01-01

    The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons). As a catecholaminergic activity enhancer (CAE) substance (-)deprenyl is about ten times more potent than its parent compound, (-)methamphetamine. While the (+)methamphetamine is 3-5 times more potent than (-)methamphetammine in releasing catecholamines, the (-)methamphetamine is the more potent CAE substance. The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of 3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box. The CAE effect was found to be unrelated: a) to the inhibition of MAO activity; b) to the inhibition of presynaptic catecholamine receptors; c) to the inhibition of the uptake of catecholamines; and d) to the release of catecholamines. It was concluded that (-)deprenyl and (-)PPAP act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons of the brain. We show that both (-)deprenyl and (-)PPAP enhance the inward Ca2+ current in sino-auricular fibers of the frog heart. (-)PPAP was much more potent than either (+)PPAP or (-)deprenyl in this test.

  5. Radiologic comparison of erosive polyarthritis with prominent interphalangeal involvement

    International Nuclear Information System (INIS)

    Gold, R.H.; Bassett, L.W.; Theros, E.G.

    1982-01-01

    Psoriatic arthritis, Reiter's disease, and multicentric reticulohistiocytosis may manifest prominent interphalangeal joint and cutaneous involvement. All three disorders may also affect the sacroiliac joints and spine. Despite these similarities, there are basic radiologic differences enabling distinction between the three disorders. Erosive osteoarthritis must also be considered in the differential diagnosis of interphalangeal erosive arthritis. Psoriatic erosions are characteristically ill defined, often bilaterally asymmetrical, usually unaccompanied by significant osteoporosis, and frequently associated with florid proliferation of subperiosteal new bone. An unilateral polyarticular pattern, which often occurs in a single ray, is the most prevalent of several patterns of involvement. Reiter's disease exhibits many clinical and radiologic similarities to psoriatic arthritis, but in the former there tends to be selective involvement of the joints of the lower limbs and particularly the feet, with relative sparing of the hands and wrists, while in the latter the joints of the upper and lower limbs tend to be involved to an equal extent. Multicentric reticulohistiocytosis (MR). Lesions predominate in skin and synovium and result in sharply circumscribed, rapidly progressive, strikingly bilaterally symmetrical erosions spreading from joint margins to articular surfaces. Most or all of the diarthrodial joints may be affected, but interphalangeal joint predominance and early and severe atlanto-axial involvement are characteristic. Erosive osteoarthritis is characterized by interphalangeal subchondral erosions, accompanying periosteal new bone that is more subtle than that of psoriatic arthritis, and interphalangeal bony ankylosis that occurs with the same frequency as that of psoriatic arthritis. (orig.)

  6. Prominent feature extraction for review analysis: an empirical study

    Science.gov (United States)

    Agarwal, Basant; Mittal, Namita

    2016-05-01

    Sentiment analysis (SA) research has increased tremendously in recent times. SA aims to determine the sentiment orientation of a given text into positive or negative polarity. Motivation for SA research is the need for the industry to know the opinion of the users about their product from online portals, blogs, discussion boards and reviews and so on. Efficient features need to be extracted for machine-learning algorithm for better sentiment classification. In this paper, initially various features are extracted such as unigrams, bi-grams and dependency features from the text. In addition, new bi-tagged features are also extracted that conform to predefined part-of-speech patterns. Furthermore, various composite features are created using these features. Information gain (IG) and minimum redundancy maximum relevancy (mRMR) feature selection methods are used to eliminate the noisy and irrelevant features from the feature vector. Finally, machine-learning algorithms are used for classifying the review document into positive or negative class. Effects of different categories of features are investigated on four standard data-sets, namely, movie review and product (book, DVD and electronics) review data-sets. Experimental results show that composite features created from prominent features of unigram and bi-tagged features perform better than other features for sentiment classification. mRMR is a better feature selection method as compared with IG for sentiment classification. Boolean Multinomial Naïve Bayes) algorithm performs better than support vector machine classifier for SA in terms of accuracy and execution time.

  7. Action in Perception: Prominent Visuo-Motor Functional Symmetry in Musicians during Music Listening.

    Directory of Open Access Journals (Sweden)

    Iballa Burunat

    Full Text Available Musical training leads to sensory and motor neuroplastic changes in the human brain. Motivated by findings on enlarged corpus callosum in musicians and asymmetric somatomotor representation in string players, we investigated the relationship between musical training, callosal anatomy, and interhemispheric functional symmetry during music listening. Functional symmetry was increased in musicians compared to nonmusicians, and in keyboardists compared to string players. This increased functional symmetry was prominent in visual and motor brain networks. Callosal size did not significantly differ between groups except for the posterior callosum in musicians compared to nonmusicians. We conclude that the distinctive postural and kinematic symmetry in instrument playing cross-modally shapes information processing in sensory-motor cortical areas during music listening. This cross-modal plasticity suggests that motor training affects music perception.

  8. Point-of-Sale Tobacco Advertising Remains Prominent in Mumbai, India.

    Science.gov (United States)

    Khariwala, Samir S; Garg, Apurva; Stepanov, Irina; Gupta, Prakash C; Ahluwalia, Jasjit S; Gota, Vikram; Chaturvedi, Pankaj

    2016-07-01

    In India, a 2003 law ("COPTA") banned tobacco advertising with the exception of "point of sale" and "on-pack" advertising. Given substantial evidence regarding the impact of point of sale advertising (PoS), we analyzed the prevalence of encountering such advertising in Mumbai, India. A survey was conducted of 199 current and recent former tobacco users recruited at the Tata Memorial Hospital (Mumbai). Enrollees were queried regarding their exposure to tobacco advertising in the last 30 days through multiple media sources. Descriptive epidemiologic techniques were used to characterize the data. Overall, 95% of participants were men and 5% were women (mean age=49 years). All were current tobacco users or quit using all forms of tobacco in the last 60 days. Participants' responses revealed that PoS tobacco advertising had been encountered in the last 30 days for cigarettes (61%), bidis (54%), and smokeless tobacco (59%). Other forms of tobacco advertising were virtually non-existent. PoS tobacco advertising remains prominent and highly visible to consumers in Mumbai, India, indicating corporate exploitation of a loophole in the COPTA legislation. Given the observed compliance with the currently imposed bans, revisions of COPTA to include all forms of tobacco promotion and advertising would be impactful.

  9. Efficient evaluation of hearing ability

    NARCIS (Netherlands)

    2009-01-01

    A system for establishing a hearing ability model of a hearing ability of a person, includes a data storage configured to store a representation of a distribution of a hearing ability of a population of individuals, and a processor configured to establish a hearing ability model representing a

  10. Innovative dynamics and competitive ability of Germany in green future markets; Innovationsdynamik und Wettbewerbsfaehigkeit Deutschlands in gruenen Zukunftsmaerkten

    Energy Technology Data Exchange (ETDEWEB)

    Walz, Rainer; Ostertag, Katrin; Doll, Claus [Fraunhofer Institut fuer System- und Innovationsforschung (ISI), Karlsruhe (DE)] (and others)

    2008-04-15

    The environmental protection and resources protection are very important nationally and internationally. For the economy in Europe and in Germany, environmental innovations set up substantial market potentials as well as chances for growth and occupation on the domestic and international markets. In a preceding project, four future markets and/or action fields were analysed. This view is extended in the contribution under consideration. Ten case studies are accomplished to individual technology lines. The innovation processes in the prominent countries are reconstructed in order to show starting points to the promotion of successful innovations. An international comparison of the efficiency and competitive ability with the most important European and non-European countries is performed. This regards the action fields: Energy production, energy efficiency, material efficiency, sustainable mobility, sustainable water management, waste management and recycling economy, white biotechnology, nanotechnology.

  11. The work ability continuum : Epidemiological studies of factors promoting sustainable work ability

    OpenAIRE

    Lindberg, Per

    2006-01-01

    For the individual, the workplace and society, there would be considerable gains if the number of people suffering from physical and mental disorders could be reduced. The overall aim of this thesis was to identify determinants for future work ability among gainfully employed women and men, with special reference to promotive factors at work. Work ability is in this thesis defined as the ability to work with respect to demands at work on health and physical and mental reso...

  12. As-CATH1-6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses.

    Science.gov (United States)

    Chen, Yan; Cai, Shasha; Qiao, Xue; Wu, Mali; Guo, Zhilai; Wang, Renping; Kuang, Yi-Qun; Yu, Haining; Wang, Yipeng

    2017-08-10

    Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1-6) were identified and characterized from the endangered Chinese alligator ( Alligator sinensis ). As-CATH1-6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1-3 adopt a random coil secondary conformation, whereas As-CATH4-6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4-6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4-6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2-6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1-6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1-6 partially reveal the powerful immune system of the Chinese alligator. © 2017 The Author(s). Published by Portland

  13. Observed IRIS Profiles of the h and k Doublet of Mg II and Comparison with Profiles from Quiescent Prominence NLTE Models

    Czech Academy of Sciences Publication Activity Database

    Vial, J. C.; Pelouze, G.; Heinzel, Petr; Kleint, L.; Anzer, U.

    2016-01-01

    Roč. 291, č. 1 (2016), s. 67-87 ISSN 0038-0938 Institutional support: RVO:67985815 Keywords : Mg II lines * non-LTE diagnostic * Sun prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 2.682, year: 2016

  14. Topicality and Text Pragmatic Prominence Five Hierarchies Regarding the Topic Suitability of Nominal Constituents

    DEFF Research Database (Denmark)

    Korzen, Iørn

    2015-01-01

    This paper presents and discusses a description of topicality and text pragmatic prominence of nominal discourse referents based on four hierarchies. These hierarchies concern the referent with respect to (a) its identifiability (± identifiable), (b) its referentiality (e.g. deictic, specific...... incorporation of the NP designating the referent, (2) the linguistic material of anaphors linked to the NP, and (3) various phenomena linked to the possible clefting of the NP. The paper also demonstrates that the proposed model and taxonomy is very well suited as tertium comparationis in a cross......-linguistic approach, not least in typological comparisons between for instance Romance and Germanic languages. The correlations described are viewed cross-linguistically with evidence from Italian, Danish, and English....

  15. Ability Grouping in Social Studies.

    Science.gov (United States)

    Social Education, 1992

    1992-01-01

    Presents a position statement of the National Council for the Social Studies (NCSS). Reports that the NCSS objects to ability grouping in social studies. Argues that ability grouping disadvantages minority, handicapped, and low ability students. Suggests that ability grouping undermines the democratic ideals that should be the basis of the social…

  16. Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8

    Science.gov (United States)

    2016-01-01

    Using Sorafenib as a starting point, a series of potent and selective inhibitors of CDK8 was developed. When cocrystallized with CDK8 and cyclin C, these compounds exhibit a Type-II (DMG-out) binding mode. PMID:27326333

  17. Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor

    International Nuclear Information System (INIS)

    Brone, Bert; Peeters, Pieter J.; Marrannes, Roger; Mercken, Marc; Nuydens, Ronny; Meert, Theo; Gijsen, Harrie J.M.

    2008-01-01

    The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target

  18. Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Anouar, El Hassane; Selvaraj, Manikandan; Jamil, Waqas; Ali, Muhammad; Kashif, Syed Muhammad; Rahim, Fazal; Khan, Khalid Mohammed; Adenan, Mohd Ilham

    2017-01-27

    Molecular hybridization yielded phenyl linked oxadiazole-benzohydrazones hybrids 6-35 and were evaluated for their antileishmanial potentials. Compound 10, a 3,4-dihydroxy analog with IC 50 value of 0.95 ± 0.01 μM, was found to be the most potent antileishmanial agent (7 times more active) than the standard drug pentamidine (IC 50  = 7.02 ± 0.09 μM). The current series 6-35 conceded in the identification of thirteen (13) potent antileishmanial compounds with the IC 50 values ranging between 0.95 ± 0.01-78.6 ± 1.78 μM. Molecular docking analysis against pteridine reductase (PTR1) were also performed to probe the mode of action. Selectivity index showed that compounds with higher number of hydroxyl groups have low selectivity index. Theoretical stereochemical assignment was also done for certain derivatives by using density functional calculations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Jesus R.; Becker, Christopher J.; Blackledge, Charles W.; Duquenne, Celine; Feng, Yanhong; Grant, Seth W.; Heerding, Dirk; Li, William H.; Miller, William H.; Romeril, Stuart P.; Scherzer, Daryl; Shu, Arthur; Bobko, Mark A.; Chadderton, Antony R.; Dumble, Melissa; Gardiner, Christine M.; Gilbert, Seth; Liu, Qi; Rabindran, Sridhar K.; Sudakin, Valery; Xiang, Hong; Brady, Pat G.; Campobasso, Nino; Ward, Paris; Axten, Jeffrey M. (GSKPA)

    2014-10-02

    Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

  20. IMPROVEMENT OF GRAPH INTERPRETATION ABILITY USING HYPERTEXT-ASSISTED KINEMATIC LEARNING AND FORMAL THINKING ABILITY

    Directory of Open Access Journals (Sweden)

    S. R. Manurung

    2018-01-01

    Full Text Available The effectiveness of hypertext media in improving graph interpretation ability is investigated in this paper. In addition, joint ability of the formal thinking to improve the graph ability of prospective students is considered. The research design used is the one-group pretest-posttest experimental design is carried out in the research by taking 36 students on from Physics Education Program in one institute for teacher education in Medan. The test consists of graph interpretation ability test in the topic of kinematics and Test of Logical Thinking (TOLT or formal thinking before learning and graph interpretation ability test after learning. The data are then analysed by using SPSS based two ways Analisys of Variance (ANOVA method. The results show that the ability to interpretate graph is significantly improved by using hypertext media assisted kinematic learning.

  1. Tune in to the Tone: Lexical Tone Identification is Associated with Vocabulary and Word Recognition Abilities in Young Chinese Children.

    Science.gov (United States)

    Tong, Xiuli; Tong, Xiuhong; McBride-Chang, Catherine

    2015-12-01

    Lexical tone is one of the most prominent features in the phonological representation of words in Chinese. However, little, if any, research to date has directly evaluated how young Chinese children's lexical tone identification skills contribute to vocabulary acquisition and character recognition. The present study distinguished lexical tones from segmental phonological awareness and morphological awareness in order to estimate the unique contribution of lexical tone in early vocabulary acquisition and character recognition. A sample of 199 Cantonese children aged 5-6 years was assessed on measures of lexical tone identification, segmental phonological awareness, morphological awareness, nonverbal ability, vocabulary knowledge, and Chinese character recognition. It was found that lexical tone awareness and morphological awareness were both associated with vocabulary knowledge and character recognition. However, there was a significant relationship between lexical tone awareness and both vocabulary knowledge and character recognition, even after controlling for the effects of age, nonverbal ability, segmental phonological awareness and morphological awareness. These findings suggest that lexical tone is a key factor accounting for individual variance in young children's lexical acquisition in Chinese, and that lexical tone should be considered in understanding how children learn new Chinese vocabulary words, in either oral or written forms.

  2. Balloon-Assisted Chemoembolization Using a Micro-Balloon Catheter Alongside a Microcatheter for a Hepatocellular Carcinoma with a Prominent Arterioportal Shunt: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Hoshiai, Sodai, E-mail: hoshiai@sb4.so-net.ne.jp; Mori, Kensaku; Ishiguro, Toshitaka; Konishi, Takahiro; Uchikawa, Yoko [University of Tsukuba Hospital, Department of Diagnostic and Interventional Radiology (Japan); Fukuda, Kuniaki [University of Tsukuba Hospital, Department of Gastroenterology (Japan); Minami, Manabu [University of Tsukuba Hospital, Department of Diagnostic and Interventional Radiology (Japan)

    2017-04-15

    Although transcatheter arterial chemoembolization is one of the established treatments for hepatocellular carcinoma (HCC), it is difficult to treat HCCs with prominent arterioportal (AP) shunts because anticancer drugs and embolic materials migrate into the non-tumorous liver through the AP shunts and may cause liver infarction. We developed a novel method of balloon-assisted chemoembolization using a micro-balloon catheter alongside a microcatheter simultaneously inserted through a single 4.5-Fr guiding sheath, comprising proximal chemoembolization with distal arterial balloon occlusion. We applied this method to treat an HCC with a prominent distal AP shunt induced by previous proton beam therapy and achieved successful chemoembolization without non-tumorous liver infarction under temporal balloon occlusion of a distal AP shunt.

  3. The formation of solar prominences by thermal instability in a current sheet

    International Nuclear Information System (INIS)

    Smith, E.A.; Priest, E.R.

    1977-01-01

    The energy balance equation for the upper chromosphere or lower corona contains a radiative loss term which is destabilizing, because of slight decrease in temperature from the equilibrium value causes more radiation and hence a cooling of the plasma; also a slight increase in temperature has the effect of heating the plasma. In spite of this tendency towards thermal instability, most of the solar atmosphere is remarkably stable, since thermal conduction is very efficient at equalizing any temperature irregularity which may arise. However, the effectiveness of thermal conduction in transporting heat is decreased considerably in a current sheet or a magnetic flux tube, since heat can be conducted quickly only along the magnetic field lines. This paper presents a simple model for the thermal equilibrium and stability of a current sheet. It is found that, when its length exceeds a certain maximum value, no equilibrium is possible and the plasma in the sheet cools. The results may be relevant for the formation of a quiescent prominence. (Auth.)

  4. Prominent blue emission through Tb3+ doped La2O3 nano-phosphors for white LEDs

    Science.gov (United States)

    Jain, Neha; Singh, Rajan Kr; Srivastava, Amit; Mishra, S. K.; Singh, Jai

    2018-06-01

    In this article, we report the tunable luminescence emission of Tb3+ doped La2O3 nanophosphors synthesized by a facile and effective Polyol method. The structural and surface morphological studies have been carried out by employing X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The XRD studies elucidate the proper phase formation and the results emanate from Raman spectroscopy of the as synthesized nanophosphor affirms it. The optical properties of the as fabricated nanoparticles have been investigated by Raman and photoluminescence (PL) spectroscopy. The PL spectroscopy shows the occurrence of excitation peaks at 305, 350 and 375 nm for 543 nm emissions, correspond to transition 5D4 →7F5. Emission spectra with 305 nm excitation exhibits characteristic emission peaks of Tb3+ion at 472, 487, 543 and 580 nm. The intensity of emission increases with Tb3+ concentration and is most prominent for 7 at% Tb3+ ion. The characteristic emissions of Tb3+ ion owes to the transition in which intensities of blue and green emission are prominent. The dominant intensity has been found for 472 nm (for blue emission). Commission international d 'Eclairage (CIE) co-ordinates have found in the light blue to green region. The research work provides a new interesting insight dealing with tunable properties with Tb3+ doping in La2O3 nanophosphors, to be useful for display devices, solar cells, LEDs and optoelectronic devices.

  5. A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells.

    Science.gov (United States)

    Hegde, Mahesh; Vartak, Supriya V; Kavitha, Chandagirikoppal V; Ananda, Hanumappa; Prasanna, Doddakunche S; Gopalakrishnan, Vidya; Choudhary, Bibha; Rangappa, Kanchugarakoppal S; Raghavan, Sathees C

    2017-05-31

    Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.

  6. Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    La Delfa, I.; Zhu, Q.M.; Mo, Z.; Blaschke, T.F.

    1989-01-01

    Fluconazole, a bis-triazole antifungal, is distinguished from imidazole antifungals (e.g. ketoconazole) by its potency and pharmacokinetic characteristics. Imidazole-containing compounds are well documented to inhibit the hepatic cytochrome P-450-dependent enzyme system; whether this effect occurs with a bis-triazole agent is unknown. The (/sup 14/C)antipyrine breath test was employed to investigate the effects of fluconazole on this enzyme system in CD-1 male mice. Control, ketoconazole (100 mg/kg), and fluconazole (1 and 10 mg/kg) were studied in single- and multiple-dose experiments. Fluconazole had potent inhibitory effects on the total (mean = -73% +/- 2%), demethylase (mean = -90% +/- 2%), and nondemethylase (mean = -60% +/- 4%) elimination rate constants (all p less than 0.001). The fraction of the administered radioactivity excreted as /sup 14/CO/sub 2/ was decreased by 50-80% in the fluconazole groups (p less than 0.001). These effects were seen after single- and multiple-dose studies; however, return to baseline occurred more quickly in the multiple-dose group. These effects were significantly more pronounced than those observed with equipotent doses of ketoconazole. These results provide evidence that fluconazole is a potent, partially selective, and reversible inhibitor of the cytochrome P-450-dependent enzyme system in mice. Future studies will be required to assess this property and possible interactions with drugs metabolized by this enzyme system in humans.

  7. Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Hudson, Brian D; Hansen, Anders Højgaard

    2016-01-01

    The free fatty acid receptor 1 (FFA1/GPR40) is a potential target for treatment of type 2 diabetes. Although several potent agonists have been described, there remains a strong need for suitable tracers to interrogate ligand binding to this receptor. We address this by exploring fluorophore-tethe...

  8. Structure-Based Design of a Novel Series of Potent, Selective Inhibitors of the Class I Phosphatidylinositol 3-Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Adrian L.; D’Angelo, Noel D.; Bo, Yunxin Y.; Booker, Shon K.; Cee, Victor J.; Herberich, Brad; Hong, Fang-Tsao; Jackson, Claire L.M.; Lanman, Brian A.; Liu, Longbin; Nishimura, Nobuko; Pettus, Liping H.; Reed, Anthony B.; Tadesse, Seifu; Tamayo, Nuria A.; Wurz, Ryan P.; Yang, Kevin; Andrews, Kristin L.; Whittington, Douglas A.; McCarter, John D.; Miguel, Tisha San; Zalameda, Leeanne; Jiang, Jian; Subramanian, Raju; Mullady, Erin L.; Caenepeel, Sean; Freeman, Daniel J.; Wang, Ling; Zhang, Nancy; Wu, Tian; Hughes, Paul E.; Norman, Mark H. (Amgen)

    2012-09-17

    A highly selective series of inhibitors of the class I phosphatidylinositol 3-kinases (PI3Ks) has been designed and synthesized. Starting from the dual PI3K/mTOR inhibitor 5, a structure-based approach was used to improve potency and selectivity, resulting in the identification of 54 as a potent inhibitor of the class I PI3Ks with excellent selectivity over mTOR, related phosphatidylinositol kinases, and a broad panel of protein kinases. Compound 54 demonstrated a robust PD-PK relationship inhibiting the PI3K/Akt pathway in vivo in a mouse model, and it potently inhibited tumor growth in a U-87 MG xenograft model with an activated PI3K/Akt pathway.

  9. Stereoselective total synthesis of the potent anti-asthmatic compound CMI-977 (LDP-977)

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Luiz Carlos; Farina, Lui Strambi; Ferreira, Marco Antonio Barbosa, E-mail: ldias@iqm.unicamp.br [Universidade de Campinas (UNICAMP), SP (Brazil). Instituto de Quimica

    2013-02-15

    A short and efficient stereoselective total synthesis of CMI-977 (LDP-977), a potent and orally active anti-asthmatic compound, was developed. The key steps involve a highly diastereoselective Mukaiyama oxidative cyclization, which provides the trans-THF (tetrahydrofuran) unit and a Seyferth-Gilbert homologation to construct the triple bond in the target molecule. The synthesis of the key chiral building block was performed using Jacobsen hydrolytic kinetic resolution. (author)

  10. Stereoselective total synthesis of the potent anti-asthmatic compound CMI-977 (LDP-977)

    International Nuclear Information System (INIS)

    Dias, Luiz Carlos; Farina, Lui Strambi; Ferreira, Marco Antonio Barbosa

    2013-01-01

    A short and efficient stereoselective total synthesis of CMI-977 (LDP-977), a potent and orally active anti-asthmatic compound, was developed. The key steps involve a highly diastereoselective Mukaiyama oxidative cyclization, which provides the trans-THF (tetrahydrofuran) unit and a Seyferth-Gilbert homologation to construct the triple bond in the target molecule. The synthesis of the key chiral building block was performed using Jacobsen hydrolytic kinetic resolution. (author)

  11. Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide derivatives.

    Science.gov (United States)

    Ogino, Masaki; Fukui, Seiji; Nakada, Yoshihisa; Tokunoh, Ryosuke; Itokawa, Shigekazu; Kakoi, Yuichi; Nishimura, Satoshi; Sanada, Tsukasa; Fuse, Hiromitsu; Kubo, Kazuki; Wada, Takeo; Marui, Shogo

    2011-01-01

    Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

  12. Work ability as prognostic risk marker of disability pension: single-item work ability score versus multi-item work ability index.

    Science.gov (United States)

    Roelen, Corné A M; van Rhenen, Willem; Groothoff, Johan W; van der Klink, Jac J L; Twisk, Jos W R; Heymans, Martijn W

    2014-07-01

    Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP. This prospective cohort study comprised 11 537 male construction workers, who completed the WAI at baseline and reported DP after a mean 2.3 years of follow-up. WAS and WAI were calibrated for DP risk predictions with the Hosmer-Lemeshow (H-L) test and their ability to discriminate between high- and low-risk construction workers was investigated with the area under the receiver operating characteristic curve (AUC). At follow-up, 336 (3%) construction workers reported DP. Both WAS [odds ratio (OR) 0.72, 95% confidence interval (95% CI) 0.66-0.78] and WAI (OR 0.57, 95% CI 0.52-0.63) scores were associated with DP at follow-up. The WAS showed miscalibration (H-L model χ (�)=10.60; df=3; P=0.01) and poorly discriminated between high- and low-risk construction workers (AUC 0.67, 95% CI 0.64-0.70). In contrast, calibration (H-L model χ �=8.20; df=8; P=0.41) and discrimination (AUC 0.78, 95% CI 0.75-0.80) were both adequate for the WAI. Although associated with the risk of future DP, the single-item WAS poorly identified male construction workers at risk of DP. We recommend using the multi-item WAI to screen for risk of DP in occupational health practice.

  13. Nanosulfur: A Potent Fungicide Against Food Pathogen, Aspergillus niger

    International Nuclear Information System (INIS)

    Choudhury, Samrat Roy; Goswami, Arunava; Nair, Kishore K.; Kumar, Rajesh; Gopal, Madhuban; Devakumar, C.; Gogoi, Robin; Srivastava, Chitra; Subhramanyam, B. S.

    2010-01-01

    Elemental sulfur (S 0 ), man's oldest eco-friendly fungicide for curing fungal infections in plants and animals, is registered in India as a non-systemic and contact fungicide. However due to its high volume requirement, Indian agrochemical industry and farmers could not effectively use this product till date. We hypothesize that intelligent nanoscience applications might increase the visibility of nanosulfur in Indian agriculture as a potent and eco-safe fungicide. Sulfur nanoparticles (NPs) were synthesized bottom-up via a liquid synthesis method with average particle size in the range of 50-80 nm and the shapes of the NPs were spherical. A comparative study of elemental and nano-sulfur produced has been tested against facultative fungal food pathogen, Aspergillus niger. Results showed that nanosulfur is more efficacious than its elemental form.

  14. Nanosulfur: A Potent Fungicide Against Food Pathogen, Aspergillus niger

    Science.gov (United States)

    Choudhury, Samrat Roy; Nair, Kishore K.; Kumar, Rajesh; Gogoi, Robin; Srivastava, Chitra; Gopal, Madhuban; Subhramanyam, B. S.; devakumar, C.; Goswami, Arunava

    2010-10-01

    Elemental sulfur (S0), man's oldest eco-friendly fungicide for curing fungal infections in plants and animals, is registered in India as a non-systemic and contact fungicide. However due to its high volume requirement, Indian agrochemical industry and farmers could not effectively use this product till date. We hypothesize that intelligent nanoscience applications might increase the visibility of nanosulfur in Indian agriculture as a potent and eco-safe fungicide. Sulfur nanoparticles (NPs) were synthesized bottom-up via a liquid synthesis method with average particle size in the range of 50-80 nm and the shapes of the NPs were spherical. A comparative study of elemental and nano-sulfur produced has been tested against facultative fungal food pathogen, Aspergillus niger. Results showed that nanosulfur is more efficacious than its elemental form.

  15. Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis.

    Science.gov (United States)

    Ouvry, Gilles; Atrux-Tallau, Nicolas; Bihl, Franck; Bondu, Aline; Bouix-Peter, Claire; Carlavan, Isabelle; Christin, Olivier; Cuadrado, Marie-Josée; Defoin-Platel, Claire; Deret, Sophie; Duvert, Denis; Feret, Christophe; Forissier, Mathieu; Fournier, Jean-François; Froude, David; Hacini-Rachinel, Fériel; Harris, Craig Steven; Hervouet, Catherine; Huguet, Hélène; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Ozello, Benjamin; Pascau, Coralie; Pascau, Jonathan; Parnet, Véronique; Peluchon, Guillaume; Pierre, Romain; Piwnica, David; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent François

    2018-02-20

    With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL-23-induced mouse skin inflammation model. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Swinholide J, a Potent Cytotoxin from the Marine Sponge Theonella swinhoei

    Directory of Open Access Journals (Sweden)

    Angela Zampella

    2011-06-01

    Full Text Available In our ongoing search for new pharmacologically active leads from Solomon organisms, we have examined the sponge Theonella swinhoei. Herein we report the isolation and structure elucidation of swinholide A (1 and one new macrolide, swinholide J (2. Swinholide J is an unprecedented asymmetric 44-membered dilactone with an epoxide functionality in half of the molecule. The structural determination was based on extensive interpretation of high-field NMR spectra and HRESIMS data. Swinholide J displayed potent in vitro cytotoxicity against KB cells (human nasopharynx cancer with an IC50 value of 6 nM.

  17. Epidemiological Studies of Potent Environmental Pathogen: Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Nazir A. Brohi

    2016-12-01

    Full Text Available A general survey for six months was undertaken for the prevalence of environmental bacterium Streptococcus pneumoniae among the different age groups (3-65 years including both sexes from various hospitals of Hyderabad city. Laboratory examinations revealed S. pneumoniae as most potent environmental pathogen from the sputum and throat swabs of old aged patients and children respectively. During observations, 39 specimens were growth positive; the biochemistry of isolates revealed that they were coagulase, catalase and oxidase negative, TSI, gel hydrolysis positive and were able to ferment glucose, lactose, maltose, galactose, fructose, sucrose, starch and raffinose. The results of antimicrobial activity showed that pneumococci were resistant to the cefspan, septran, cravit, pipemetic acid, azomax, bacitracin, and penicillin and a clear zone of inhibition was observed on clithromycin, optochin, cefizox, genatamycin, minocyclin, levoflaxacin, and vancomycin. There were intermediate zone of inhibition found on claforan, nalidixic acid, amoxycillin, fosfomycin, fortum, and erythromycin on Mueller Hinton’s agar after 24 hours incubation

  18. Epidemiological studies of potent environment pathogen streptococcus pneumoniae

    International Nuclear Information System (INIS)

    Brohi, N.A.; Tunio, S.A.

    2016-01-01

    A general survey for six months was undertaken for the prevalence of environmental bacterium Streptococcus pneumoniae among the different age groups (3-65 years) including both sexes from various hospitals of Hyderabad city. Laboratory examinations revealed S. pneumoniae as most potent environmental pathogen from the sputum and throat swabs of old aged patients and children respectively. During observations, 39 specimens were growth positive; the biochemistry of isolates revealed that they were coagulase, catalase and oxidase negative, TSI, gel hydrolysis positive and were able to ferment glucose, lactose, maltose, galactose, fructose, sucrose, starch and raffinose. The results of antimicrobial activity showed that pneumococci were resistant to the cefspan, septran, cravit, pipemetic acid, azomax, bacitracin, and penicillin and a clear zone of inhibition was observed on clithromycin, optochin, cefizox, genatamycin, minocyclin, levoflaxacin, and vancomycin. There were intermediate zone of inhibition found on claforan, nalidixic acid, amoxycillin, fosfomycin, fortum, and erythromycin on Mueller Hinton's agar after 24 hours incubation. (author)

  19. Prominent Midlatitude Circulation Signature in High Asia's Surface Climate During Monsoon

    Science.gov (United States)

    Mölg, Thomas; Maussion, Fabien; Collier, Emily; Chiang, John C. H.; Scherer, Dieter

    2017-12-01

    High Asia has experienced strong environmental changes in recent decades, as evident in records of glaciers, lakes, tree rings, and vegetation. The multiscale understanding of the climatic drivers, however, is still incomplete. In particular, few systematic assessments have evaluated to what degree, if at all, the midlatitude westerly circulation modifies local surface climates in the reach of the Indian Summer Monsoon. This paper shows that a southward shift of the upper-tropospheric westerlies contributes significantly to climate variability in the core monsoon season (July-September) by two prominent dipole patterns at the surface: cooling in the west of High Asia contrasts with warming in the east, while moist anomalies in the east and northwest occur with drying along the southwestern margins. Circulation anomalies help to understand the dipoles and coincide with shifts in both the westerly wave train and the South Asian High, which imprint on air mass advection and local energy budgets. The relation of the variabilities to a well-established index of midlatitude climate dynamics allows future research on climate proxies to include a fresh hypothesis for the interpretation of environmental changes.

  20. Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity.

    Science.gov (United States)

    Foote, Kevin M; Mortlock, Andrew A; Heron, Nicola M; Jung, Frédéric H; Hill, George B; Pasquet, Georges; Brady, Madeleine C; Green, Stephen; Heaton, Simon P; Kearney, Sarah; Keen, Nicholas J; Odedra, Rajesh; Wedge, Stephen R; Wilkinson, Robert W

    2008-03-15

    A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.

  1. Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound.

    Directory of Open Access Journals (Sweden)

    Ana Paula Martins

    Full Text Available Aquaporins (AQPs are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III complexes screened on human red blood cells (hRBC and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50 = 0.8±0.08 µM in hRBC. Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

  2. The coordination of boundary tones and its interaction with prominence.

    Science.gov (United States)

    Katsika, Argyro; Krivokapić, Jelena; Mooshammer, Christine; Tiede, Mark; Goldstein, Louis

    2014-05-01

    This study investigates the coordination of boundary tones as a function of stress and pitch accent. Boundary tone coordination has not been experimentally investigated previously, and the effect of prominence on this coordination, and whether it is lexical (stress-driven) or phrasal (pitch accent-driven) in nature is unclear. We assess these issues using a variety of syntactic constructions to elicit different boundary tones in an Electromagnetic Articulography (EMA) study of Greek. The results indicate that the onset of boundary tones co-occurs with the articulatory target of the final vowel. This timing is further modified by stress, but not by pitch accent: boundary tones are initiated earlier in words with non-final stress than in words with final stress regardless of accentual status. Visual data inspection reveals that phrase-final words are followed by acoustic pauses during which specific articulatory postures occur. Additional analyses show that these postures reach their achievement point at a stable temporal distance from boundary tone onsets regardless of stress position. Based on these results and parallel findings on boundary lengthening reported elsewhere, a novel approach to prosody is proposed within the context of Articulatory Phonology: rather than seeing prosodic (lexical and phrasal) events as independent entities, a set of coordination relations between them is suggested. The implications of this account for prosodic architecture are discussed.

  3. Triazolophostins: a library of novel and potent agonists of IP3 receptors

    OpenAIRE

    Vibhute, Amol M; Konieczny, Vera; Taylor, Colin William; Sureshan, Kana M

    2015-01-01

    IP3 receptors are channels that mediate the release of Ca2+ from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of sy...

  4. Imidazopyridine- and purine-thioacetamide derivatives: potent inhibitors of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1).

    Science.gov (United States)

    Chang, Lei; Lee, Sang-Yong; Leonczak, Piotr; Rozenski, Jef; De Jonghe, Steven; Hanck, Theodor; Müller, Christa E; Herdewijn, Piet

    2014-12-11

    Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) belongs to the family of ecto-nucleotidases, which control extracellular nucleotide, nucleoside, and (di)phosphate levels. To study the (patho)physiological roles of NPP1 potent and selective inhibitors with drug-like properties are required. Therefore, a compound library was screened for NPP1 inhibitors using a colorimetric assay with p-nitrophenyl 5'-thymidine monophosphate (p-Nph-5'-TMP) as an artificial substrate. This led to the discovery of 2-(3H-imidazo[4,5-b]pyridin-2-ylthio)-N-(3,4-dimethoxyphenyl)acetamide (5a) as a hit compound with a Ki value of 217 nM. Subsequent structure-activity relationship studies led to the development of purine and imidazo[4,5-b]pyridine analogues with high inhibitory potency (Ki values of 5.00 nM and 29.6 nM, respectively) when assayed with p-Nph-5'-TMP as a substrate. Surprisingly, the compounds were significantly less potent when tested versus ATP as a substrate, with Ki values in the low micromolar range. A prototypic inhibitor was investigated for its mechanism of inhibition and found to be competitive versus both substrates.

  5. The ability to mentally represent action is associated with low motor ability in children: a preliminary investigation.

    Science.gov (United States)

    Gabbard, Carl; Caçola, Priscila; Bobbio, Tatiana

    2012-05-01

    Theory and anatomical research suggest that the ability to mentally represent intended actions affect level of execution. This study presents preliminary data examining the association between children's ability to mentally represent action and general motor ability. Children aged 7- to 10 years were assessed for motor imagery ability using a simulation of reach task and motor ability via the Movement ABC-2. Motor ability values, based on percentile rank, ranged from 2 to 91, with a mean of 36. The overall correlation between mental representation and motor ability yielded a moderately positive relationship (r = .39). Interestingly, when looking at motor ability subcategories, only Balance was significant in the model, explaining 20% of the variance. These results provide preliminary evidence that children's motor ability and the ability to mentally represent action are associated in a positive direction. Furthermore, given the results for Balance, we speculate that there are clinical implications regarding work with potentially at-risk children. © 2011 Blackwell Publishing Ltd.

  6. Numerical approximation abilities correlate with and predict informal but not formal mathematics abilities.

    Science.gov (United States)

    Libertus, Melissa E; Feigenson, Lisa; Halberda, Justin

    2013-12-01

    Previous research has found a relationship between individual differences in children's precision when nonverbally approximating quantities and their school mathematics performance. School mathematics performance emerges from both informal (e.g., counting) and formal (e.g., knowledge of mathematics facts) abilities. It remains unknown whether approximation precision relates to both of these types of mathematics abilities. In the current study, we assessed the precision of numerical approximation in 85 3- to 7-year-old children four times over a span of 2years. In addition, at the final time point, we tested children's informal and formal mathematics abilities using the Test of Early Mathematics Ability (TEMA-3). We found that children's numerical approximation precision correlated with and predicted their informal, but not formal, mathematics abilities when controlling for age and IQ. These results add to our growing understanding of the relationship between an unlearned nonsymbolic system of quantity representation and the system of mathematics reasoning that children come to master through instruction. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Draft Genome Sequence of Bacillus velezensis GF610, a Producer of Potent Anti-Listeria Agents.

    Science.gov (United States)

    Gerst, Michelle M; Dudley, Edward G; Xiaoli, Lingzi; Yousef, Ahmed E

    2017-10-12

    Bacillus velezensis GF610 was isolated from soil in Illinois, USA, and found to produce amyloliquecidin GF610, a potent two-component antimicrobial peptide. We report here the GF610 strain draft genome sequence, which contains 4.29 Mb and an overall GC content of 45.91%. Copyright © 2017 Gerst et al.

  8. Imidazopyridine-5,6,7,8-tetrahydro-8-quinolinamine derivatives with potent activity against HIV-1.

    Science.gov (United States)

    Gudmundsson, Kristjan S; Boggs, Sharon D; Catalano, John G; Svolto, Angilique; Spaltenstein, Andrew; Thomson, Michael; Wheelan, Pat; Jenkinson, Stephen

    2009-11-15

    Synthesis of several novel imidazopyridine-5,6,7,8-tetrahydro-8-quinolinamine derivatives with potent activity against HIV are described. Synthetic approaches allowing for variation of the substitution pattern are outlined and resulting changes in antiviral activity and pharmacokinetics are highlighted. Several compounds with low nanomolar anti-HIV activity and oral bioavailability are described.

  9. Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity.

    Science.gov (United States)

    Gilson, Paul R; Tan, Cyrus; Jarman, Kate E; Lowes, Kym N; Curtis, Joan M; Nguyen, William; Di Rago, Adrian E; Bullen, Hayley E; Prinz, Boris; Duffy, Sandra; Baell, Jonathan B; Hutton, Craig A; Jousset Subroux, Helene; Crabb, Brendan S; Avery, Vicky M; Cowman, Alan F; Sleebs, Brad E

    2017-02-09

    Novel antimalarial therapeutics that target multiple stages of the parasite lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here, we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites comparable to the known antimalarials, chloroquine and mefloquine. During the optimization process, we defined the functionality necessary for activity and improved in vitro metabolism and solubility. The resultant lead compounds possess potent activity against a multidrug resistant strain of P. falciparum and arrest parasites at the ring phase of the asexual stage and also gametocytogensis. Finally, we show that the lead compounds are orally efficacious in a 4 day murine model of malaria disease burden.

  10. Orthodontic treatment for prominent upper front teeth (Class II malocclusion) in children and adolescents.

    Science.gov (United States)

    Batista, Klaus Bsl; Thiruvenkatachari, Badri; Harrison, Jayne E; O'Brien, Kevin D

    2018-03-13

    Prominent upper front teeth are a common problem affecting about a quarter of 12-year-old children in the UK. The condition develops when permanent teeth erupt. These teeth are more likely to be injured and their appearance can cause significant distress. Children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of their teeth. If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait and provide treatment in adolescence. To assess the effects of orthodontic treatment for prominent upper front teeth initiated when children are seven to 11 years old ('early treatment' in two phases) compared to in adolescence at around 12 to 16 years old ('late treatment' in one phase); to assess the effects of late treatment compared to no treatment; and to assess the effects of different types of orthodontic braces. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 27 September 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 8), MEDLINE Ovid (1946 to 27 September 2017), and Embase Ovid (1980 to 27 September 2017). The US National Institutes of Health Ongoing Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials of orthodontic treatments to correct prominent upper front teeth (Class II malocclusion) in children and adolescents. We included trials that compared early treatment in children (two-phase) with any type of orthodontic braces (removable, fixed, functional) or head-braces versus late treatment in adolescents (one-phase) with any type of orthodontic braces or head-braces, and trials that compared any

  11. Cognitive abilities of Alzheimer's disease transgenic mice are modulated by social context and circadian rhythm.

    Science.gov (United States)

    Kiryk, Anna; Mochol, Gabriela; Filipkowski, Robert K; Wawrzyniak, Marcin; Lioudyno, Victoria; Knapska, Ewelina; Gorkiewicz, Tomasz; Balcerzyk, Marcin; Leski, Szymon; Leuven, Fred Van; Lipp, Hans-Peter; Wojcik, Daniel K; Kaczmarek, Leszek

    2011-12-01

    In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12- and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.

  12. Historical Evolution of Spatial Abilities

    Directory of Open Access Journals (Sweden)

    A. Ardila

    1993-01-01

    Full Text Available Historical evolution and cross-cultural differences in spatial abilities are analyzed. Spatial abilities have been found to be significantly associated with the complexity of geographical conditions and survival demands. Although impaired spatial cognition is found in cases of, exclusively or predominantly, right hemisphere pathology, it is proposed that this asymmetry may depend on the degree of training in spatial abilities. It is further proposed that spatial cognition might have evolved in a parallel way with cultural evolution and environmental demands. Contemporary city humans might be using spatial abilities in some new, conceptual tasks that did not exist in prehistoric times: mathematics, reading, writing, mechanics, music, etc. Cross-cultural analysis of spatial abilities in different human groups, normalization of neuropsychological testing instruments, and clinical observations of spatial ability disturbances in people with different cultural backgrounds and various spatial requirements, are required to construct a neuropsychological theory of brain organization of spatial cognition.

  13. The Data Set on the Multiple Abilities

    DEFF Research Database (Denmark)

    Klynge, Alice Heegaard

    2008-01-01

    This paper presents a data set on multiple abilities. The abilities cover the Literacy and Math Ability, the Creative and Innovative Ability, the Learning Ability, the Communication Ability, the Social Competency, the Self-Management Ability, the Environmental Awareness, the Civic Competency......, the Intercultural Awareness, and the Health Awareness. The data stems from a unique cross-sectional survey carried out for the adult population in Denmark. Several dimensions and many questions pinpoint and measure every ability. The dimensions cover areas such as the individual behavior at work, the individual...... behavior in leisure, the motivation for using an ability, the working conditions for using an ability, and the educational conditions for using an ability. The paper defines every ability and describes the dimensions and the questions underlying the abilities. It reports the categories of answers...

  14. Information Processing and Human Abilities

    Science.gov (United States)

    Kirby, John R.; Das, J. P.

    1978-01-01

    The simultaneous and successive processing model of cognitive abilities was compared to a traditional primary mental abilities model. Simultaneous processing was found to be primarily related to spatial ability; and to a lesser extent, to memory and inductive reasoning. Subjects were 104 fourth-grade urban males. (Author/GD C)

  15. Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Roxanne Hastie

    2018-03-01

    Full Text Available Ectopic pregnancies complicate 1–2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies. As such, many ectopic pregnancies require surgical excision. We show that vinorelbine, an orally available chemotherapeutic agent, potently induced placental cell death but did not harm fertility in mice. Vinorelbine was 100–1000 times more potent than methotrexate in inducing placental cell death in vitro, and more potent than combination methotrexate and gefitinib (another proposed treatment for ectopic pregnancy being evaluated in phase III trials. Mechanistically, it caused microtubule condensation, blocked mitosis and activated the apoptosis cascade in placental cells. Vinorelbine was more efficacious than methotrexate ± gefitinib in reducing the volume of placental cell tumors xenografted subcutaneously in SCID mice. Mice exposed to vinorelbine and allowed to breed, following a four week washout period, displayed normal fertility, however long-term fertility was not assessed. Human Fallopian tubes treated with vinorelbine did not exhibit up-regulation of apoptosis molecules. Our findings show that placental cells appear sensitive to vinorelbine and it has potential as a tablet-only approach to treat ectopic pregnancy. Keywords: Ectopic pregnancy, Vinorelbine, Methotrexate, Placenta, Treatment

  16. THE EFFECTS OF MAGNETIC-FIELD GEOMETRY ON LONGITUDINAL OSCILLATIONS OF SOLAR PROMINENCES

    International Nuclear Information System (INIS)

    Luna, M.; Díaz, A. J.; Karpen, J.

    2012-01-01

    We investigate the influence of the geometry of the solar filament magnetic structure on the large-amplitude longitudinal oscillations. A representative filament flux tube is modeled as composed of a cool thread centered in a dipped part with hot coronal regions on either side. We have found the normal modes of the system and establish that the observed longitudinal oscillations are well described with the fundamental mode. For small and intermediate curvature radii and moderate to large density contrast between the prominence and the corona, the main restoring force is the solar gravity. In this full wave description of the oscillation a simple expression for the oscillation frequencies is derived in which the pressure-driven term introduces a small correction. We have also found that the normal modes are almost independent of the geometry of the hot regions of the tube. We conclude that observed large-amplitude longitudinal oscillations are driven by the projected gravity along the flux tubes and are strongly influenced by the curvature of the dips of the magnetic field in which the threads reside.

  17. The Effects of Magnetic-field Geometry on Longitudinal Oscillaitons of Solar Prominences

    Science.gov (United States)

    Luna, M.; Diaz, A. J.; Karpen, J.

    2013-01-01

    We investigate the influence of the geometry of the solar filament magnetic structure on the large-amplitude longitudinal oscillations. A representative filament flux tube is modeled as composed of a cool thread centered in a dipped part with hot coronal regions on either side.We have found the normal modes of the system and establish that the observed longitudinal oscillations are well described with the fundamental mode. For small and intermediate curvature radii and moderate to large density contrast between the prominence and the corona, the main restoring force is the solar gravity. In this full wave description of the oscillation a simple expression for the oscillation frequencies is derived in which the pressure-driven term introduces a small correction. We have also found that the normal modes are almost independent of the geometry of the hot regions of the tube. We conclude that observed large-amplitude longitudinal oscillations are driven by the projected gravity along the flux tubes and are strongly influenced by the curvature of the dips of the magnetic field in which the threads reside.

  18. Balance ability and athletic performance.

    Science.gov (United States)

    Hrysomallis, Con

    2011-03-01

    The relationship between balance ability and sport injury risk has been established in many cases, but the relationship between balance ability and athletic performance is less clear. This review compares the balance ability of athletes from different sports, determines if there is a difference in balance ability of athletes at different levels of competition within the same sport, determines the relationship of balance ability with performance measures and examines the influence of balance training on sport performance or motor skills. Based on the available data from cross-sectional studies, gymnasts tended to have the best balance ability, followed by soccer players, swimmers, active control subjects and then basketball players. Surprisingly, no studies were found that compared the balance ability of rifle shooters with other athletes. There were some sports, such as rifle shooting, soccer and golf, where elite athletes were found to have superior balance ability compared with their less proficient counterparts, but this was not found to be the case for alpine skiing, surfing and judo. Balance ability was shown to be significantly related to rifle shooting accuracy, archery shooting accuracy, ice hockey maximum skating speed and simulated luge start speed, but not for baseball pitching accuracy or snowboarding ranking points. Prospective studies have shown that the addition of a balance training component to the activities of recreationally active subjects or physical education students has resulted in improvements in vertical jump, agility, shuttle run and downhill slalom skiing. A proposed mechanism for the enhancement in motor skills from balance training is an increase in the rate of force development. There are limited data on the influence of balance training on motor skills of elite athletes. When the effectiveness of balance training was compared with resistance training, it was found that resistance training produced superior performance results for

  19. An analysis of concert saxophone vibrato through the examination of recordings by eight prominent soloists

    Science.gov (United States)

    Zinninger, Thomas

    This study examines concert saxophone vibrato through the analysis of several recordings of standard repertoire by prominent soloists. The vibrato of Vincent Abato, Arno Bornkamp, Claude Delangle, Jean-Marie Londeix, Marcel Mule, Otis Murphy, Sigurd Rascher, and Eugene Rousseau is analyzed with regards to rate, extent, shape, and discretionary use. Examination of these parameters was conducted through both general observation and precise measurements with the aid of a spectrogram. Statistical analyses of the results provide tendencies for overall vibrato use, as well as the effects of certain musical attributes (note length, tempo, dynamic, range) on vibrato. The results of this analysis are also compared among each soloist and against pre-existing theories or findings in vibrato research.

  20. In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

    Science.gov (United States)

    Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

    2006-01-01

    Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

  1. Lifestyle index and work ability.

    Science.gov (United States)

    Kaleta, Dorota; Makowiec-Dabrowska, Teresa; Jegier, Anna

    2006-01-01

    In many countries around the world, negative changes in lifestyles are observed. The aim of this study was to analyze the influence of selected lifestyle indicators on work ability among professionally active individuals. The study was performed in the randomly selected group of full-time employees (94 men and 93 women) living in the city of Lódź. Work ability was measured with the work ability index and lifestyle characteristic was assessed with the healthy lifestyle index. We analyzed four lifestyle indicators: non-smoking, healthy weight, fiber intake per day, and regular physical activity. Logistic regression was used to estimate odds ratios and 95% confidence intervals to control the effects of lifestyle and work ability. The analysis of lifestyle index indicated that 27.7, 30.9, 27.7 and 11.7% of men and 15.1, 21.5, 35.5 and 26.9% of women scored 0, 1, 2, 3 points, respectively. Only 2.1% of men and 1.1% of women met the criteria for the healthy lifestyle (score 4). Work ability was excellent, good and moderate in 38.3, 46.8 and 14.9% of men, and in 39.8, 14.9 and 19.3% of women, respectively. Poor work ability was found in 9.7% women. Work ability was strongly associated with lifestyle in both men and women. Among men with index score = 0, the risk of moderate work ability was nearly seven times higher than in men whose lifestyle index score exceeded 1 or more points (OR = 6.67; 95% CI: 1.94-22.90). Among women with lifestyle index score = 0, the risk of moderate or lower work ability was also highly elevated as compared to those with lifestyle index = 1 or higher (OR = 14.44; 95% CI: 3.53-59.04). Prophylactic schedules associated with the improvement of lifestyles should be addressed to all adults. Future programs aimed at increasing work ability should consider work- and lifestyle-related factors.

  2. Computational identification of potent inhibitors for Streptomycin 3″-adenylyltransferase of Serratia marcescens.

    Science.gov (United States)

    Prabhu, Dhamodharan; Vidhyavathi, Ramasamy; Jeyakanthan, Jeyaraman

    2017-02-01

    Serratia marcescens is an opportunistic pathogen responsible for the respiratory and urinary tract infections in humans. The antibiotic resistance mechanism of S. marcescens is mediated through aminoglycoside modification enzyme that transfer adenyl group from substrate to antibiotic through regiospecific transfers for the inactivation of antibiotics. Streptomycin 3 ″ -adenylyltransferase acts on the 3' position of the antibiotic and considered as a novel drug target to overcome bacterial antibiotic resistance. Till now, there is no experimentally solved crystal structure of Streptomycin 3″-adenylyltransferase in S. marcescens. Hence, the present study was initiated to construct the three dimensional structure of Streptomycin 3″-adenylyltransferase in order to understand the binding mechanism. The modeled structure was subjected to structure-based virtual screening to identify potent compounds from the five chemical structure databases. Furthermore, different computational methods such as molecular docking, molecular dynamics simulations, ADME toxicity assessment, free energy and density functional theory calculations predicted the structural, binding and pharmacokinetic properties of the best five compounds. Overall, the results suggested that stable binding confirmation of the five potent compounds were mediated through hydrophobic, π-π stacking, salt bridges and hydrogen bond interactions. The identified compounds could pave way for the development of anti-pathogenic agents as potential drug entities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Numerical ability predicts mortgage default.

    Science.gov (United States)

    Gerardi, Kristopher; Goette, Lorenz; Meier, Stephan

    2013-07-09

    Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one's mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage.

  4. Numerical ability predicts mortgage default

    Science.gov (United States)

    Gerardi, Kristopher; Goette, Lorenz; Meier, Stephan

    2013-01-01

    Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one’s mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage. PMID:23798401

  5. Potent P2Y(12) Inhibitors in Men Versus Women A Collaborative Meta-Analysis of Randomized Trials

    DEFF Research Database (Denmark)

    Lau, Emily S.; Braunwald, Eugene; Murphy, Sabina A.

    2017-01-01

    Background Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. Objectives The study investigated the efficacy and safety of the potent P2Y12 inhibitors i...

  6. Effect of Soy Sauce on Serum Uric Acid Levels in Hyperuricemic Rats and Identification of Flazin as a Potent Xanthine Oxidase Inhibitor.

    Science.gov (United States)

    Li, Huipin; Zhao, Mouming; Su, Guowan; Lin, Lianzhu; Wang, Yong

    2016-06-15

    This is the first report on the ability of soy sauce to effectively reduce the serum uric acid levels and xanthine oxidase (XOD) activities of hyperuricemic rats. Soy sauce was partitioned sequentially into ethyl acetate and water fractions. The ethyl acetate fraction with strong XOD inhibition effect was purified further. On the basis of xanthine oxidase inhibitory (XOI) activity-guided purification, nine compounds including 3,4-dihydroxy ethyl cinnamate, diisobutyl terephthalate, harman, daidzein, flazin, catechol, thymine, genistein, and uracil were obtained. It was the first time that 3,4-dihydroxy ethyl cinnamate and diisobutyl terephthalate had been identified from soy sauce. Flazin with hydroxymethyl furan ketone group at C-1 and carboxyl at C-3 exhibited the strongest XOI activity (IC50 = 0.51 ± 0.05 mM). According to fluorescence quenching and molecular docking experiments, flazin could enter into the catalytic center of XOD to interact with Lys1045, Gln1194, and Arg912 mainly by hydrophobic forces and hydrogen bonds. Flazin, catechol, and genistein not only were potent XOD inhibitors but also held certain antioxidant activities. According to ADME (absorption, distribution, metabolism, and excretion) simulation in silico, flazin had good oral bioavailability in vivo.

  7. Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities.

    Science.gov (United States)

    Witschel, Matthias C; Rottmann, Matthias; Schwab, Anatol; Leartsakulpanich, Ubolsree; Chitnumsub, Penchit; Seet, Michael; Tonazzi, Sandro; Schwertz, Geoffrey; Stelzer, Frank; Mietzner, Thomas; McNamara, Case; Thater, Frank; Freymond, Céline; Jaruwat, Aritsara; Pinthong, Chatchadaporn; Riangrungroj, Pinpunya; Oufir, Mouhssin; Hamburger, Matthias; Mäser, Pascal; Sanz-Alonso, Laura M; Charman, Susan; Wittlin, Sergio; Yuthavong, Yongyuth; Chaiyen, Pimchai; Diederich, François

    2015-04-09

    Several of the enzymes related to the folate cycle are well-known for their role as clinically validated antimalarial targets. Nevertheless for serine hydroxymethyltransferase (SHMT), one of the key enzymes of this cycle, efficient inhibitors have not been described so far. On the basis of plant SHMT inhibitors from an herbicide optimization program, highly potent inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) SHMT with a pyrazolopyran core structure were identified. Cocrystal structures of potent inhibitors with PvSHMT were solved at 2.6 Å resolution. These ligands showed activity (IC50/EC50 values) in the nanomolar range against purified PfSHMT, blood-stage Pf, and liver-stage P. berghei (Pb) cells and a high selectivity when assayed against mammalian cell lines. Pharmacokinetic limitations are the most plausible explanation for lack of significant activity of the inhibitors in the in vivo Pb mouse malaria model.

  8. Career or Family? The Fight of Two Prominent Scandinavian Feminist Politicians

    NARCIS (Netherlands)

    Ribberink, J.C.A.P.

    2017-01-01

    Internationally, in the twentieth century, women in higher and managerial occupations were confronted with barriers because they had to fight prejudices concerning their ability to maintain themselves in traditionally male occupations. This was the case for instance, with women politicians in the

  9. Ability Dispersion and Team Performance

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    What is the effect of dispersed levels of cognitive ability of members of a (business) team on their team's performance? This paper reports the results of a field experiment in which 573 students in 49 (student) teams start up and manage real companies under identical circumstances for one year. We...... ensured exogenous variation in otherwise random team composition by assigning students to teams based on their measured cognitive abilities. Each team performs a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of business teams first...... increases and then decreases with ability dispersion. We seek to understand this finding by developing a model in which team members of different ability levels form sub- teams with other team members with similar ability levels to specialize in different productive tasks. Diversity spreads production over...

  10. High Resolution, High-Speed Photography, an Increasingly Prominent Diagnostic in Ballistic Research Experiments

    International Nuclear Information System (INIS)

    Shaw, L.; Muelder, S.

    1999-01-01

    High resolution, high-speed photography is becoming a prominent diagnostic in ballistic experimentation. The development of high speed cameras utilizing electro-optics and the use of lasers for illumination now provide the capability to routinely obtain high quality photographic records of ballistic style experiments. The purpose of this presentation is to review in a visual manner the progress of this technology and how it has impacted ballistic experimentation. Within the framework of development at LLNL, we look at the recent history of large format high-speed photography, and present a number of photographic records that represent the state of the art at the time they were made. These records are primarily from experiments involving shaped charges. We also present some examples of current photographic technology, developed within the ballistic community, that has application to hydro diagnostic experimentation at large. This paper is designed primarily as an oral-visual presentation. This written portion is to provide general background, a few examples, and a bibliography

  11. ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Alonso, Mariana; Medina, Jorge H.; Pozzo-Miller, Lucas

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling…

  12. Functional morphology of the hallucal metatarsal with implications for inferring grasping ability in extinct primates.

    Science.gov (United States)

    Goodenberger, Katherine E; Boyer, Doug M; Orr, Caley M; Jacobs, Rachel L; Femiani, John C; Patel, Biren A

    2015-03-01

    Primate evolutionary morphologists have argued that selection for life in a fine branch niche resulted in grasping specializations that are reflected in the hallucal metatarsal (Mt1) morphology of extant "prosimians", while a transition to use of relatively larger, horizontal substrates explains the apparent loss of such characters in anthropoids. Accordingly, these morphological characters-Mt1 torsion, peroneal process length and thickness, and physiological abduction angle-have been used to reconstruct grasping ability and locomotor mode in the earliest fossil primates. Although these characters are prominently featured in debates on the origin and subsequent radiation of Primates, questions remain about their functional significance. This study examines the relationship between these morphological characters of the Mt1 and a novel metric of pedal grasping ability for a large number of extant taxa in a phylogenetic framework. Results indicate greater Mt1 torsion in taxa that engage in hallucal grasping and in those that utilize relatively small substrates more frequently. This study provides evidence that Carpolestes simpsoni has a torsion value more similar to grasping primates than to any scandentian. The results also show that taxa that habitually grasp vertical substrates are distinguished from other taxa in having relatively longer peroneal processes. Furthermore, a longer peroneal process is also correlated with calcaneal elongation, a metric previously found to reflect leaping proclivity. A more refined understanding of the functional associations between Mt1 morphology and behavior in extant primates enhances the potential for using these morphological characters to comprehend primate (locomotor) evolution. © 2014 Wiley Periodicals, Inc.

  13. Discovery of Highly Potent Tyrosinase Inhibitor, T1, with Significant Anti-Melanogenesis Ability by zebrafish in vivo Assay and Computational Molecular Modeling

    Science.gov (United States)

    Chen, Wang-Chuan; Tseng, Tien-Sheng; Hsiao, Nai-Wan; Lin, Yun-Lian; Wen, Zhi-Hong; Tsai, Chin-Chuan; Lee, Yu-Ching; Lin, Hui-Hsiung; Tsai, Keng-Chang

    2015-01-01

    Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 +/- 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.

  14. Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors

    DEFF Research Database (Denmark)

    Wu, Gaochan; Gao, Yun; Kang, Dongwei

    2018-01-01

    acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship...

  15. Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement.

    Science.gov (United States)

    Li, Xiao; Gao, Ping; Huang, Boshi; Zhou, Zhongxia; Yu, Zhao; Yuan, Zheng; Liu, Huiqing; Pannecouque, Christophe; Daelemans, Dirk; De Clercq, Erik; Zhan, Peng; Liu, Xinyong

    2017-01-27

    To further explore the chemical space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing N-substituted piperidine at indole-2-carboxamide were identified as potent HIV NNRTIs by structure-guided scaffold morphing and fragment rearrangement. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC 50 values ranging from 0.62 μM to 0.006 μM 8 (EC 50  = 6 nM) and 18 (EC 50  = 9 nM) were identified as the most potent compounds, which were more active than NVP and DLV, and reached the same order of EFV and ETV. Furthermore, most compounds maintained high activity agaist various single HIV-1 mutants (L100I, K103N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC 50 values in low-micromolar to double-digit nanomolar concentration ranges. Especially, 8 displayed outstanding potency against L100I (EC 50  = 17 nM with a 2.8-fold resistance ratio) and 18 was relatively more potent to E138K mutant (EC 50  = 43 nM with a 4.7-fold resistance ratio). Preliminary SARs and molecular modeling studies were also discussed in detail, which may provide valuable insights for further optimization. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Potent innate immune response to pathogenic leptospira in human whole blood.

    Directory of Open Access Journals (Sweden)

    Marga G A Goris

    Full Text Available BACKGROUND: Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. CONCLUSIONS/SIGNIFICANCE: Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.

  17. Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants.

    Science.gov (United States)

    Silvestri, Romano; Artico, Marino

    2005-01-01

    Indolyl aryl sulfones (IASs) are a potent class of NNRTIs developed from L-737,126, a lead agent discovered by Merck AG. IAS derivatives are endowed with inhibitory activities against wt HIV-1 in the low nanomolar concentration range. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of the aryl sulfonyl moiety furnished IAS derivatives such as 5-chloro- or 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide, which showed very potent and selective anti-HIV-1 activity against some mutants carrying NNRTI resistant mutations at positions 103 and 181 of the reverse transcriptase. IAS derivatives bearing 2-hydroxyethylcarboxyamide or 2-hydroxyethylcarboxyhydrazide groups at position 2 of the indole nucleus were more active than L-737,126 against the K103N-Y181C double mutant. A great improvement of antiviral activity against wt HIV-1 and resistant mutants was obtained by coupling 1-3 simple amino acids, such as glycine and alanine, in sequence, with the 3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carbonyl moiety. The transformation of the chain terminus into amide or hydrazide, produced short peptides with high selectivity and potent activity against wt HIV-1, and the viral mutants Y181C, K103N-Y181C and EFV(R). IAS having two halogen atoms at the indole showed potent inhibitory activity against the Y181C and the EFV(R) resistant mutant strains. In particular, the introduction of a fluorine atom at position 4 of the indole ring notably contributed to improve the antiviral activities against both wt and the related resistant mutants. 5-Nitro-IASs were highly active against wt HIV-1 and exhibited low cytotoxicity. Experimental data highlighted the class IAS derivatives as promising candidates for clinical trials.

  18. Identification of β-Amino alcohol grafted 1,4,5 trisubstituted 1,2,3-triazoles as potent antimalarial agents.

    Science.gov (United States)

    Devender, Nalmala; Gunjan, Sarika; Chhabra, Stuti; Singh, Kartikey; Pasam, Venkata Reddy; Shukla, Sanjeev K; Sharma, Abhisheak; Jaiswal, Swati; Singh, Sunil Kumar; Kumar, Yogesh; Lal, Jawahar; Trivedi, Arun Kumar; Tripathi, Renu; Tripathi, Rama Pati

    2016-02-15

    In a quest to discover new drugs, we have synthesized a series of novel β-amino alcohol grafted 1,2,3-triazoles and screened them for their in vitro antiplasmodial and in vivo antimalarial activity. Among them, compounds 16 and 25 showed potent activity against chloroquine-sensitive (Pf3D7) strain with IC50 of 0.87 and 0.3 μM respectively, while compounds 7 and 13 exhibited better activity in vitro than the reference drug against chloroquine-resistance strain (PfK1) with IC50 of 0.5 μM each. Compound 25 showed 86.8% in vivo antimalarial efficacy with favorable pharmacokinetic parameters. Mechanistic studies divulged that potent compounds significantly boosted p53 protein levels to exhibit the antimalarial activity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Discourse abilities in the structure of intelligence

    Directory of Open Access Journals (Sweden)

    Voronin A. N.

    2017-09-01

    Full Text Available Background. This article is devoted to empirical research on discourse abilities within the structure of cognitive abilities. Discourse abilities, as well as linguistic abilities, are part of language abilities, but they are directly linked with discourse practices and a certain communicative situation. Discourse abilities allow a person to effectively initiate, keep, expand, and complete the process of communication, using language appropriate to any given situation. These abilities contribute to making communication more effective and achieving mutual understanding between partners, while at the same time they speed up the process of forming an interaction strategy. the empirical verification of the construct “discourse abilities,” and the design of original diagnostic tests on them, led us to differentiate linguistic and discourse abilities. Objective. However, it is not yet clear what place discourse abilities occupy in the structure of cognitive abilities. This is the primary goal of our research. Method. The design of the study involved group testing (in groups of 15-35 people using the following methods: a discourse abilities test; a short selection test; a social intelligence test, and short variations of Torrance’s and Mednick’s tests. In total, 208 people (133 women and 75 men, ages 17 to 21 years participated in the study, all of them either first year humanities students or high school students from Moscow. Results and Discussion. The research results revealed that discourse abilities relevantly correlate with the majority of indicators of general and social intelligence and creativity (except non-verbal intelligence. Discourse abilities as part of the structure of cognitive capabilities form a discrete factor, and include relevant components such as verbal and general intelligence and indicators of social intelligence, such as the ability to group expressions. Structures indicative of cognitive abilities varied within the

  20. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist.

    Science.gov (United States)

    Arai, Kiyoshi; Homma, Tsuyoshi; Morikawa, Yuka; Ubukata, Naoko; Tsuruoka, Hiyoyuki; Aoki, Kazumasa; Ishikawa, Hirokazu; Mizuno, Makoto; Sada, Toshio

    2015-08-15

    The present study was designed to characterize the pharmacological profile of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist. In the radioligand-binding assay, CS-3150 inhibited (3)H-aldosterone binding to mineralocorticoid receptor with an IC50 value of 9.4nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 36 and 713nM, respectively. CS-3150 also showed at least 1000-fold higher selectivity for mineralocorticoid receptor over other steroid hormone receptors, glucocorticoid receptor, androgen receptor and progesterone receptor. In the reporter gene assay, CS-3150 inhibited aldosterone-induced transcriptional activation of human mineralocorticoid receptor with an IC50 value of 3.7nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 66 and 970nM, respectively. CS-3150 had no agonistic effect on mineralocorticoid receptor and did not show any antagonistic or agonistic effect on glucocorticoid receptor, androgen receptor and progesterone receptor even at the high concentration of 5μM. In adrenalectomized rats, single oral administration of CS-3150 suppressed aldosterone-induced decrease in urinary Na(+)/K(+) ratio, an index of in vivo mineralocorticoid receptor activation, and this suppressive effect was more potent and longer-lasting than that of spironolactone and eplerenone. Chronic treatment with CS-3150 inhibited blood pressure elevation induced by deoxycorticosterone acetate (DOCA)/salt-loading to rats, and this antihypertensive effect was more potent than that of spironolactone and eplerenone. These findings indicate that CS-3150 is a selective and highly potent mineralocorticoid receptor antagonist with long-lasting oral activity. This agent could be useful for the treatment of hypertension, cardiovascular and renal disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Ali, Muhammad; Rashid, Umer; Imran, Syahrul; Uddin, Nizam; Khan, Khalid Mohammed

    2017-04-01

    The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC 50 =0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Development of potent in vivo mutagenesis plasmids with broad mutational spectra.

    Science.gov (United States)

    Badran, Ahmed H; Liu, David R

    2015-10-07

    Methods to enhance random mutagenesis in cells offer advantages over in vitro mutagenesis, but current in vivo methods suffer from a lack of control, genomic instability, low efficiency and narrow mutational spectra. Using a mechanism-driven approach, we created a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that enhances mutation 322,000-fold over basal levels, surpassing the mutational efficiency and spectra of widely used in vivo and in vitro methods. We demonstrate that this system can be used to evolve antibiotic resistance in wild-type E. coli in mutagenesis of chromosomes, episomes and viruses in vivo, and are applicable to both bacterial and bacteriophage-mediated laboratory evolution platforms.

  3. Interleukin-17 is a potent immuno-modulator and regulator of normal human intestinal epithelial cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, S [Children' s Hospital, Mucosal Immunology Laboratory, University of Bonn, Bonn (Germany); Beaulieu, J F [Department of Cell Biology/Anatomy, University of Sherbrooke, Sherbrooke (Canada); Ruemmele, F M [Children' s Hospital, Mucosal Immunology Laboratory, University of Bonn, Bonn (Germany) and INSERM EMI0212, Faculte de Medecine Necker, University Paris V, Paediatric Gastroenterology Unit, Department of Paediatrics, Hopital Necker-Enfants Malades, Assistance-Publique-Hopitaux de Paris, Paris (France)

    2005-11-18

    Upregulation of the T-cell derived cytokine interleukin (IL-17) was reported in the inflamed intestinal mucosa of patients with inflammatory bowel disorders. In this study, we analyzed the effect of IL-17 on human intestinal epithelial cell (HIEC) turnover and functions. Proliferation and apoptosis in response to IL-17 was monitored in HIEC (cell counts, [{sup 3}H]thymidine incorporation method, and annexinV-PI-apoptosis assay). Signalling pathways were analyzed by Western blots, electromobility shift assay, and immunofluorescence studies. IL-17 proved to be a potent inhibitor of HIEC proliferation without any pro-apoptotic/necrotic effect. The growth inhibitory effect of IL-17 was mediated via the p38 stress kinase. Consequently, the p38-SAPkinase-inhibitor SB203580 abrogated this anti-mitotic effect. In parallel, IL-17 provoked the degradation of I{kappa}B{alpha}, allowing nuclear translocation of the p65 NF-{kappa}B subunit and induction of the NF-{kappa}B-controlled genes IL-6 and -8. IL-17 potently blocks epithelial cell turnover while at the same time amplifying an inflammatory response in a positive feedback manner.

  4. Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses.

    Science.gov (United States)

    Ichihashi, Toru; Satoh, Toshifumi; Sugimoto, Chihiro; Kajino, Kiichi

    2013-01-01

    To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs) in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL) induction capability. Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS) has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+)CD11b(+)MHCII(+) conventional dendritic cells (cDCs) compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo. This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

  5. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    Science.gov (United States)

    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. [Person-organization fit and work ability].

    Science.gov (United States)

    Merecz, Dorota; Andysz, Aleksandra

    2011-01-01

    Person-environment issue has long been in focus of researchers who explore the area of human labor. It is known that the level of fit is a predictor of many phenomena related to health and attitude to work. The aim of this study was to explore the association between the level of person- organization fit (P-O fit) and work ability, including indicators of somatic and mental health. Research was conducted on a representative sample of 600 Polish men and women at working age. The Person-Organization Fit Questionnaire was used to assess three dimensions of P-O fit (supplementary fit, complementary fit and identification with organization); mental health status was measured by GHQ-28; the number of diagnosed diseases was taken as an index of somatic health; work ability, ability to physical and mental efforts were measured by three items from the Work Ability Index. A significant relationship between P-O fit level and work ability was found. In men, work ability predictors were: age, supplementary fit and mental health status, which explained 25% of the variance in work ability. In women, work ability predictors were: the number of diagnosed somatic diseases, supplementary fit, age and complementary fit, which explained 27% of the variance in work ability. Some gender-related differences in the predictive value of variables under the study were also found. The results of this study indicate the importance of P-O fit in shaping the sense of work ability, a recognized predictor of workers' occupational activity and the frequency of taking sick leave in subsequent years. Therefore, this result may be a useful argument to motivate employers to employ workers adequately to their abilities and preferences.

  7. Characterization of potent odorants in male giant water bug (Lethocerus indicus Lep. and Serv.), an important edible insect of Southeast Asia.

    Science.gov (United States)

    Kiatbenjakul, Patthamawadi; Intarapichet, Kanok-Orn; Cadwallader, Keith R

    2015-02-01

    Potent odorants in frozen fresh (FFB) and salted boiled (SBB) male giant water bugs (Lethocerus indicus), or 'Maengdana' in Thai, were characterized by application of direct solvent extraction/solvent-assisted flavour evaporation (SAFE), gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), aroma extract dilution analysis (AEDA) and stable isotope dilution assays (SIDA). Twenty and 27 potent odorants were detected in FFB and SBB, respectively. Most odorants were lipid-derived compounds, including the two most abundant volatile components (E)-2-hexenyl acetate and (E)-2-hexenyl butanoate, which contributed banana-like odours. 2-Acetyl-1-pyrroline and 2-acetyl-2-thiazoline, responsible for popcorn-like odours, were detected in SBB only. An aroma reconstitution model of SBB was constructed in an oil-in-water emulsion matrix using 12 selected potent odorants based on the results of AEDA, accurate compound quantification and the calculated odour-activity values (OAV). Omission studies were carried out to verify the significance of esters, particularly (E)-2-hexenyl acetate was determined to be an important character-impact odorant in male giant water bug aroma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Is there a relationship between ultrasound scanning ability (sonography) and visuospatial perception or psychomotor ability?

    Science.gov (United States)

    Hagen, Suzanne; Gallagher, Helen

    2016-01-01

    Background Competent sonography is thought to include a unique combination of skills not yet fully defined. This presents challenges when recruiting the correct people for training. Skills are thought to include visuospatial perception and psychomotor skills, but little is known about the relationship between these aptitudes and scanning ability. This feasibility study explored such relationships, to identify evaluation techniques which may improve selection and recruitment. Methods A sample of 30 experienced ultrasound practitioners and 30 trainees at commencement and on completion of training were administered eight tests. Results No significant relationships between experienced practitioners’ or trainees’ visuospatial abilities or psychomotor abilities and scanning abilities were found. Results demonstrated that two of the visuospatial perception tests were not influenced by training and therefore, may be measuring the innate skills of ultrasound practitioners. As ultrasound practitioners had not performed any of the tests previously, ranges of scores for each of the eight tests were established for this group. This included measures for psychomotor skills which added to the current body of knowledge for sonography. Conclusions Although no significant correlations were found between participants’ visuospatial perception or psychomotor abilities and scanning ability, performance on the Obstetric Structured Assessment Test (combining all the skills required) pre-training gave the best indication of post-training scanning performance. The Obstetric Structured Assessment Test may prove a useful tool for initial assessment of potential trainees but abilities will require further investigation. PMID:27847536

  9. Development of arithmetical abilities

    Directory of Open Access Journals (Sweden)

    Tatjana Levstek

    2014-02-01

    Full Text Available Arithmetic (from the word 'arithmos' which means 'numbers' is an elementary branch of mathematics. Numeracy is essential for understanding mathematics, so the development of arithmetic abilities has been an area of scientific research for a long time. Recent research has shown that the development of arithmetic abilities is not based only on gaining experience and learning. Some arithmetic abilities, especially the sense of quantity, are innate. Even babies are able to distinguish between groups with different number of elements and they perceive numeracy amodally. Six-month-olds distinguish between two groups with the numeracy ratio of 1 : 2. With age this ratio improves rapidly. Five-year-old children already distinguish between groups with the number ratio 7 : 8. The ability to compare two quantities begins to develop after 15 months of age and children learn how to count spontaneously, together with the acquisition of language. Speech enables children to understand number in its abstract, symbolic sense, thus opening the way to symbolic arithmetic. During the preschool period children use intuition when doing calculations, but in school the arithmetic is based on the knowledge of arithmetical algorithms. So, in order to acquire mathematical knowledge, it is necessary to incorporate memory and automate arithmetical processes, without the use of intuition. However, research has shown that intuition is very important and is even a predictive factor for the development of mathematical abilities throughout the schooling process.

  10. NMR (1H and 13C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    International Nuclear Information System (INIS)

    Bag, Swarnendu; Banerjee, Deb Ranjan; Basak, Amit; Das, Amit Kumar; Pal, Mousumi; Banerjee, Rita; Paul, Ranjan Rashmi; Chatterjee, Jyotirmoy

    2015-01-01

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using 1 H and 13 C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ( 1 H and 13 C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate

  11. Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes.

    Science.gov (United States)

    Bae, Soo Hyeon; Kwon, Min Jo; Choi, Eu Jin; Zheng, Yu Fen; Yoon, Kee Dong; Liu, Kwang-Hyeon; Bae, Soo Kyung

    2013-09-05

    The present study was performed to evaluate the potency and specificity of sibutramine as an inhibitor of the activities of nine human CYP isoforms in liver microsomes. Using a cocktail assay, the effects of sibutramine on specific marker reactions of the nine CYP isoforms were measured in human liver microsomes. Sibutramine showed potent inhibition of CYP2B6-mediated bupropion 6-hydroxylation with an IC50 value of 1.61μM and Ki value of 0.466μM in a competitive manner at microsomal protein concentrations of 0.25mg/ml; this was 3.49-fold more potent than the typical CYP2B6 inhibitor thio-TEPA (Ki=1.59μM). In addition, sibutramine slightly inhibited CYP2C19 activity (Ki=16.6μM, noncompetitive inhibition) and CYP2D6 activity (Ki=15.7μM, noncompetitive inhibition). These observations indicated 35.6- and 33.7-fold decreases in inhibition potency, respectively, compared with that of CYP2B6 by sibutramine. However, no inhibition of CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, or CYP2E1 activities was observed. In addition, the CYP2B6 inhibitory potential of sibutramine was enhanced at a lower microsomal protein concentration of 0.05mg/ml. After 30min preincubation of human liver microsomes with sibutramine in the presence of NADPH, no shift in IC50 was observed in terms of inhibition of the activities of the nine CYPs, suggesting that sibutramine is not a time-dependent inactivator. These observations suggest that sibutramine is a selective and potent inhibitor of CYP2B6 in vitro, whereas inhibition of other CYPs is substantially lower. These in vitro data support the use of sibutramine as a well-known inhibitor of CYP2B6 for routine screening of P450 reversible inhibition when human liver microsomes are used as the enzyme source. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

    International Nuclear Information System (INIS)

    Cen, Ling; Hutzen, Brian; Ball, Sarah; DeAngelis, Stephanie; Chen, Chun-Liang; Fuchs, James R; Li, Chenglong; Li, Pui-Kai; Lin, Jiayuh

    2009-01-01

    Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have suggested that curcumin may serve as a potential preventive or therapeutic agent for colorectal cancer. We compared the inhibitory effects of curcumin and novel structural analogues, GO-Y030, FLLL-11, and FLLL-12, in three independent human colorectal cancer cell lines, SW480, HT-29, and HCT116. MTT cell viability assay was used to examine the cell viability/proliferation and western blots were used to determine the level of PARP cleavages. Half-Maximal inhibitory concentrations (IC 50 ) were calculated using Sigma Plot 9.0 software. Curcumin inhibited cell viability in all three of the human colorectal cancer cell lines studied with IC 50 values ranging between 10.26 μM and 13.31 μM. GO-Y030, FLLL-11, and FLLL-12 were more potent than curcumin in the inhibition of cell viability in these three human colorectal cancer cell lines with IC 50 values ranging between 0.51 μM and 4.48 μM. In addition, FLLL-11 and FLLL-12 exhibit low toxicity to WI-38 normal human lung fibroblasts with an IC-50 value greater than 1,000 μM. GO-Y030, FLLL-11, and FLLL-12 are also more potent than curcumin in the induction of apoptosis, as evidenced by cleaved PARP and cleaved caspase-3 in all three human colorectal cancer cell lines studied. The results indicate that the three curcumin analogues studied exhibit more potent inhibitory activity than curcumin in human colorectal cancer cells. Thus, they may have translational potential as chemopreventive or therapeutic agents for colorectal carcinoma

  13. A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics

    Directory of Open Access Journals (Sweden)

    Kirsten Tschapalda

    2016-06-01

    Full Text Available Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened >320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1, a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.

  14. Psychological Measures of Spatial Abilities

    Directory of Open Access Journals (Sweden)

    Aurel Ion Clinciu

    2009-12-01

    Full Text Available Spatial abilities are divided into three categories: mental rotation, spatial relation and visualization. Several tests are cited in foreign literature that are frequently used in order to assess these abilities, but for Romanian specialists they are not on hand. The present paper is introducing new assessment tools for static spatial abilities that were successfully used along with already validated instruments. Data on statistical qualities of the new instruments are also discussed.

  15. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections.

    Science.gov (United States)

    Lee, Sanghyun; Baldridge, Megan T

    2017-01-01

    Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.

  16. Targeting the Oxidative Stress Response System of Fungi with Redox-Potent Chemosensitizing Agents

    Science.gov (United States)

    Kim, Jong H.; Chan, Kathleen L.; Faria, Natália C. G.; Martins, M. de L.; Campbell, Bruce C.

    2012-01-01

    The cellular antioxidant system is a target in the antifungal action of amphotericin B (AMB) and itraconazole (ITZ), in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidant system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (a MAPK gene deletion mutant in the polyalcohol sugar utilization system). Complete fungal kill (≥99.9%) by ITZ or AMB was also achieved by much lower dosages for the sakAΔ mutant than for the other strains. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator) and sakA and/or mpkC (upstream MAPKs) are in the same stress response network under tert-butyl hydroperoxide (t-BuOOH)-, hydrogen peroxide (H2O2)- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens were also sensitive to t-BuOOH, showing a connection between ITZ sensitivity and antioxidant capacity of fungi. Enhanced antifungal activity of AMB or ITZ was achieved when these drugs were co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. We concluded that redox-potent compounds, which target the antioxidant system in fungi, possess a chemosensitizing capacity to enhance efficacy of conventional drugs. PMID:22438852

  17. Cyclocurcumin, a curcumin derivative, exhibits immune-modulating ability and is a potential compound for the treatment of rheumatoid arthritis as predicted by the MM-PBSA method.

    Science.gov (United States)

    Fu, Min; Chen, Lihui; Zhang, Limin; Yu, Xiao; Yang, Qingrui

    2017-05-01

    The control and treatment of rheumatoid arthritis is a challenge in today's world. Therefore, the pursuit of natural disease-modifying antirheumatic drugs (DMRDs) remains a top priority in rheumatology. The present study focused on curcumin and its derivatives in the search for new DMRDs. We focused on prominent p38 mitogen-activated protein (MAP) kinase p38α which is a prime regulator of tumor necrosis factor-α (TNF-α), a key mediator of rheumatoid arthritis. In the present study, we used the X-ray crystallographic structure of p38α for molecular docking simulations and molecular dynamic simulations to study the binding modes of curcumin and its derivatives with the active site of p38α. The ATP-binding domain was used for evaluating curcumin and its derivatives. Molecular docking simulation results were used to select 4 out of 8 compounds. These 4 compounds were simulated using GROMACS molecular simulation platform; the results generated were subjected to molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) calculations. The results showed cyclocurcumin as a potential natural compound for development of a potent DMRD. These data were further supported by inhibition of TNF-α release from lipopolysaccharide (LPS)-stimulated human macrophages following cyclocurcumin treatment.

  18. Muscle diseases with prominent joint contractures: Main entities and diagnostic strategy.

    Science.gov (United States)

    Eymard, B; Ferreiro, A; Ben Yaou, R; Stojkovic, T

    2013-01-01

    Muscle diseases may have various clinical manifestations including muscle weakness, atrophy or hypertrophy and joint contractures. A spectrum of non-muscular manifestations (cardiac, respiratory, cutaneous, central and peripheral nervous system) may be associated. Few of these features are specific. Limb joint contractures or spine rigidity, when prevailing over muscle weakness in ambulant patients, are of high diagnostic value for diagnosis orientation. Within this context, among several disorders, four groups of diseases should systematically come to mind including the collagen VI-related myopathies, the Emery-Dreifuss muscular dystrophies, the SEPN1 and FHL1 related myopathies. More rarely other genetic or acquired myopathies may present with marked contractures. Diagnostic work-up should include a comprehensive assessment including family history, neurological, cardiologic and respiratory evaluations. Paraclinical investigations should minimally include muscle imaging and electromyography. Muscle and skin biopsies as well as protein and molecular analyses usually help to reach a precise diagnosis. We will first describe the main muscle and neuromuscular junction diseases where contractures are typically a prominent symptom of high diagnostic value for diagnosis orientation. In the following chapters, we will present clues for the diagnostic strategy and the main measures to be taken when, at the end of the diagnostic work-up, no definite muscular disease has been identified. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. The coordination of boundary tones and its interaction with prominence1

    Science.gov (United States)

    Katsika, Argyro; Krivokapić, Jelena; Mooshammer, Christine; Tiede, Mark; Goldstein, Louis

    2014-01-01

    This study investigates the coordination of boundary tones as a function of stress and pitch accent. Boundary tone coordination has not been experimentally investigated previously, and the effect of prominence on this coordination, and whether it is lexical (stress-driven) or phrasal (pitch accent-driven) in nature is unclear. We assess these issues using a variety of syntactic constructions to elicit different boundary tones in an Electromagnetic Articulography (EMA) study of Greek. The results indicate that the onset of boundary tones co-occurs with the articulatory target of the final vowel. This timing is further modified by stress, but not by pitch accent: boundary tones are initiated earlier in words with non-final stress than in words with final stress regardless of accentual status. Visual data inspection reveals that phrase-final words are followed by acoustic pauses during which specific articulatory postures occur. Additional analyses show that these postures reach their achievement point at a stable temporal distance from boundary tone onsets regardless of stress position. Based on these results and parallel findings on boundary lengthening reported elsewhere, a novel approach to prosody is proposed within the context of Articulatory Phonology: rather than seeing prosodic (lexical and phrasal) events as independent entities, a set of coordination relations between them is suggested. The implications of this account for prosodic architecture are discussed. PMID:25300341

  20. Hidradenocarcinoma showing prominent mucinous and squamous differentiation and associated pagetoid cells.

    Science.gov (United States)

    Honda, Yumi; Tanigawa, Hiroki; Harada, Miho; Fukushima, Satoshi; Masuguchi, Shinichi; Ishihara, Tsuyoshi; Ihn, Hironobu; Iyama, Ken-ichi

    2013-05-01

    Herein, we report a 63-year-old man presenting with hidradenocarcinoma showing prominent mucinous and squamous differentiation on his back. The tumor was dermal-based, solid and cystic. Tumor cells with squamous differentiation and with keratin pearl formation were identified predominantly in the superficial dermis, and mucinous cells were identified principally in the cystic lesion in the deep dermis. Interestingly, the additional feature of pagetoid cells was identified in the overlying epidermis. Both the mucinous cells in hidradenocarcinoma and pagetoid cells had intracytoplasmic mucin; however, they had different histopathologic findings and immunophenotypes. Mucinous cells in hidradenocarcinoma had small nuclei and abundant intracytoplasmic mucin presenting goblet cells with low rate of positive immunostaining for p53 and Ki67. In contrast, pagetoid cells had larger nuclei with less intracytoplasmic mucin. Both p53- and Ki67-positive cells were increased in pagetoid cells. Additionally, mucinous cells in hidradenocarcinoma were MUC1(+)/MUC2(-)/MUC5AC(+)/MUC6(+), but pagetoid cells were MUC1(+; focal)/MUC2(-)/MUC5AC(-)/MUC6(+; focal). The derivation of pagetoid cells is unclear; however, the localized small region of pagetoid cells over the hidradenocarcinoma in the present case may suggest a common histogenesis of these two malignant neoplasms. Copyright © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  1. Learning-Ability Relations in Adulthood

    Science.gov (United States)

    Hultsch, David F.; And Others

    1976-01-01

    Two successive recall tasks and eight ability measures were presented to women of five age groups to investigate the changing relation between performance and ability measures at various stages of the learning process during adulthood. (MS)

  2. Artificial intelligence model for sustain ability measurement

    International Nuclear Information System (INIS)

    Navickiene, R.; Navickas, K.

    2012-01-01

    The article analyses the main dimensions of organizational sustain ability, their possible integrations into artificial neural network. In this article authors performing analyses of organizational internal and external environments, their possible correlations with 4 components of sustain ability, and the principal determination models for sustain ability of organizations. Based on the general principles of sustainable development organizations, a artificial intelligence model for the determination of organizational sustain ability has been developed. The use of self-organizing neural networks allows the identification of the organizational sustain ability and the endeavour to explore vital, social, antropogenical and economical efficiency. The determination of the forest enterprise sustain ability is expected to help better manage the sustain ability. (Authors)

  3. A novel bispecific antibody, S-Fab, induces potent cancer cell killing.

    Science.gov (United States)

    Li, Li; He, Ping; Zhou, Changhua; Jing, Li; Dong, Bin; Chen, Siqi; Zhang, Ning; Liu, Yawei; Miao, Ji; Wang, Zhong; Li, Qing

    2015-01-01

    Bispecific antibodies that engage immune cells to kill cancer cells have been actively studied in cancer immunotherapy. In this study, we present a novel bispecific format, S-Fab, fabricated by linking a single-domain anti-carcinoembryonic antigen VHH to a conventional anti-CD3 Fab. In contrast to most bispecific antibodies, the S-Fab bispecific antibody can be efficiently expressed and purified from bacteria. The purified S-Fab is stable in serum and is able to recruit T cells to drive potent cancer cell killing. In xenograft models, the S-Fab antibody suppresses tumor growth in the presence of human immune cells. Our study suggested that the bispecific S-Fab format can be applied to a wide range of immunotherapies.

  4. Hot prominence detected in the core of a coronal mass ejection: Analysis of SOHO/UVCS L alpha and SOHO/LASCO visible-light observations

    Czech Academy of Sciences Publication Activity Database

    Heinzel, Petr; Susino, R.; Jejčič, S.; Bemporad, A.; Anzer, U.

    2016-01-01

    Roč. 589, May (2016), A128/1-A128/11 ISSN 0004-6361 R&D Projects: GA ČR(CZ) GA16-18495S Institutional support: RVO:67985815 Keywords : Sun * filaments * prominences Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

  5. Stereochemistry and molecular pharmacology of (S)-thio-ATPA, a new potent and selective GluR5 agonist

    DEFF Research Database (Denmark)

    Stensbøl, T B; Jensen, H S; Nielsen, B

    2001-01-01

    )-Glu) receptors (EC(50)=14 microM), comparable in potency with ATPA (EC(50)=34 microM). Recent findings, that (S)-ATPA is a potent (EC(50)=0.48 microM) and selective agonist at homomerically expressed ionotropic GluR5, prompted us to resolve thio-ATPA using chiral chromatography and pharmacologically characterize...

  6. A qualitative approach to assessing work ability.

    Science.gov (United States)

    Tengland, Per-Anders

    2013-01-01

    We often need to be able to assess the extent to which individuals have or lack work ability. For this we need instruments. Most of the instruments available have flaws. They either lack validity or they use roundabout methods when collecting information about the individual's work ability. The aim of this paper is to present a conceptual model for constructing a questionnaire that can be used for assessing work ability. The methods used are philosophical, i.e. analytical and deductive. A conceptual theory is provided, and based on the resulting definition of the concept of "work ability" conclusions are drawn regarding how to assess work ability. When constructing quantitative instruments, we can increase validity through using a more strict definition of work ability. However, such an approach will only solve some of the problems noted above. The proposal is, instead, to create a qualitative questionnaire, founded on a definition of "work ability", which focuses on the concrete problems concerning the work ability of the individual. Finally, a sketch of such an instrument is provided, with questions covering all the relevant aspects of work ability. The qualitative questionnaire proposed is believed to be superior to more traditional (quantitative) instruments for assessing a person's work ability, as well as for finding solutions to her problems concerning work ability.

  7. What Should Be Taught in Secondary Schools’ Nutrition and Food Systems Education? Views from Prominent Food-Related Professionals in Australia

    Directory of Open Access Journals (Sweden)

    Sanaz Sadegholvad

    2017-11-01

    Full Text Available Education can help young people to attain the knowledge and the skills that they need to make proper food choices and develop lifelong healthy eating patterns. This study explored the perspectives of prominent food-related professionals in Australia regarding essential nutrition and food systems (N&FS education programs for adolescents during formal education. Semi-structured interviews were conducted with 21 prominent food-related professionals in Australia. Interview transcripts were analysed thematically. Four essential areas for N&FS education programs were identified. (1 Key nutrition messages to a healthy lifestyle; (2 Skill development programs to enhance health and wellbeing; (3 Ethical food-related lessons to support environmental sustainability, farm animal welfare, local producers, and food security; and, (4 Introductory lessons about foods from farm to plate to facilitate more informed food choices. Findings of this study may provide new insights for curriculum developers in Australia for further assessment of the current gaps in N&FS components of secondary school curriculum. Integration of these four areas into secondary school curricula has the potential to enhance adolescents’ knowledge of important scientific and ethical issues in a range of N&FS fields, and enable them to develop fundamental food-related life skills that are supportive of health and wellbeing.

  8. What Should Be Taught in Secondary Schools' Nutrition and Food Systems Education? Views from Prominent Food-Related Professionals in Australia.

    Science.gov (United States)

    Sadegholvad, Sanaz; Yeatman, Heather; Parrish, Anne-Maree; Worsley, Anthony

    2017-11-02

    Education can help young people to attain the knowledge and the skills that they need to make proper food choices and develop lifelong healthy eating patterns. This study explored the perspectives of prominent food-related professionals in Australia regarding essential nutrition and food systems (N&FS) education programs for adolescents during formal education. Semi-structured interviews were conducted with 21 prominent food-related professionals in Australia. Interview transcripts were analysed thematically. Four essential areas for N&FS education programs were identified. (1) Key nutrition messages to a healthy lifestyle; (2) Skill development programs to enhance health and wellbeing; (3) Ethical food-related lessons to support environmental sustainability, farm animal welfare, local producers, and food security; and, (4) Introductory lessons about foods from farm to plate to facilitate more informed food choices. Findings of this study may provide new insights for curriculum developers in Australia for further assessment of the current gaps in N&FS components of secondary school curriculum. Integration of these four areas into secondary school curricula has the potential to enhance adolescents' knowledge of important scientific and ethical issues in a range of N&FS fields, and enable them to develop fundamental food-related life skills that are supportive of health and wellbeing.

  9. Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

    Science.gov (United States)

    Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

    2018-06-11

    Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Cissampelos pareira Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes.

    Directory of Open Access Journals (Sweden)

    Ruchi Sood

    2015-12-01

    Full Text Available Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need.Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity. Our results show that the alcoholic extract of Cissampelos pariera Linn (Cipa extract was a potent inhibitor of all four DENVs in cell-based assays, assessed in terms of viral NS1 antigen secretion using ELISA, as well as viral replication, based on plaque assays. Virus yield reduction assays showed that Cipa extract could decrease viral titers by an order of magnitude. The extract conferred statistically significant protection against DENV infection using the AG129 mouse model. A preliminary evaluation of the clinical relevance of Cipa extract showed that it had no adverse effects on platelet counts and RBC viability. In addition to inherent antipyretic activity in Wistar rats, it possessed the ability to down-regulate the production of TNF-α, a cytokine implicated in severe dengue disease. Importantly, it showed no evidence of toxicity in Wistar rats, when administered at doses as high as 2g/Kg body weight for up to 1 week.Our findings above, taken in the context of the human safety of Cipa, based on its use in Indian traditional medicine, warrant further work to explore Cipa as a source for the development of an inexpensive herbal formulation for dengue therapy. This may be of practical relevance to a dengue-endemic resource-poor country such as India.

  11. Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant in CCl4 challenged rats

    Directory of Open Access Journals (Sweden)

    Bhuwan Chandra Joshi

    2015-01-01

    Full Text Available The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant against CCl4-induced hepatotoxicity in-vitro (HepG2 cells and in-vivo (rats model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF, ethyl acetate fraction (EAF, n-butanol fraction (NBF and aqueous fraction (AF were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF was subjected to in-vivo hepatoprotective potential against CCl4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and MS spectroscopy. Ethyl acetate fraction (EAF of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC50 78.99 ± 0.17 μg/ml and NO (IC50101.39 ± 0.30 μg/ml. The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl4-induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl4 induced hepatotoxicity in-vitro and in-vivo.

  12. Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl4 challenged rats.

    Science.gov (United States)

    Joshi, Bhuwan Chandra; Prakash, Atish; Kalia, Ajudhia N

    2015-01-01

    The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant) against CCl 4 -induced hepatotoxicity in-vitro (HepG2 cells) and in-vivo (rats) model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n -butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo hepatoprotective potential against CCl 4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1 H NMR, 13 C NMR and MS spectroscopy. Ethyl acetate fraction (EAF) of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC 50 78.99 ± 0.17 μg/ml) and NO (IC 50 101.39 ± 0.30 μg/ml). The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl 4 -induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF) lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl 4 induced hepatotoxicity in-vitro and in-vivo .

  13. Human monoamine oxidase is inhibited by tobacco smoke: β-carboline alkaloids act as potent and reversible inhibitors

    International Nuclear Information System (INIS)

    Herraiz, Tomas; Chaparro, Carolina

    2005-01-01

    Monoamine oxidase (MAO) is a mitochondrial outer-membrane flavoenzyme involved in brain and peripheral oxidative catabolism of neurotransmitters and xenobiotic amines, including neurotoxic amines, and a well-known target for antidepressant and neuroprotective drugs. Recently, positron emission tomography imaging has shown that smokers have a much lower activity of peripheral and brain MAO-A (30%) and -B (40%) isozymes compared to non-smokers. This MAO inhibition results from a pharmacological effect of smoke, but little is known about its mechanism. Working with mainstream smoke collected from commercial cigarettes we confirmed that cigarette smoke is a potent inhibitor of human MAO-A and -B isozymes. MAO inhibition was partly reversible, competitive for MAO-A, and a mixed-type inhibition for MAO-B. Two β-carboline alkaloids, norharman (β-carboline) and harman (1-methyl-β-carboline), were identified by GC-MS, quantified, and isolated from the mainstream smoke by solid phase extraction and HPLC. Kinetics analysis revealed that β-carbolines from cigarette smoke were competitive, reversible, and potent inhibitors of MAO enzymes. Norharman was an inhibitor of MAO-A (K i = 1.2 ± 0.18 μM) and MAO-B (K i = 1.12 ± 0.19 μM), and harman of MAO-A (K i = 55.54 ± 5.3 nM). β-Carboline alkaloids are psychopharmacologically active compounds that may occur endogenously in human tissues, including the brain. These results suggest that β-carboline alkaloids from cigarette smoke acting as potent reversible inhibitors of MAO enzymes may contribute to the MAO-reduced activity produced by tobacco smoke in smokers. The presence of MAO inhibitors in smoke like β-carbolines and others may help us to understand some of the purported neuropharmacological effects associated with smoking

  14. Development of potent ALK inhibitor and its molecular inhibitory mechanism against NSCLC harboring EML4-ALK proteins

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Chung Hyo [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Yun, Jeong In [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Lee, Kwangho [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Medicinal & Pharmaceutical Chemistry, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of); Lee, Chong Ock; Lee, Heung Kyoung [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Yun, Chang-Soo; Hwang, Jong Yeon; Cho, Sung Yun; Jung, Heejung; Kim, Pilho [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Medicinal & Pharmaceutical Chemistry, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of); Ha, Jae Du; Jeon, Jeong Hee; Choi, Sang Un [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Jeong, Hye Gwang [College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Kim, Hyoung Rae, E-mail: hyungrk@krict.re.kr [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Park, Chi Hoon, E-mail: chpark@krict.re.kr [Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600 (Korea, Republic of); Medicinal & Pharmaceutical Chemistry, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of)

    2015-08-28

    Here, we show the newly synthesized and potent ALK inhibitor having similar scaffold to KRCA-0008, which was reported previously, and its molecular mechanism against cancer cells harboring EML4-ALK fusion protein. Through ALK wild type enzyme assay, we selected two compounds, KRCA-0080 and KRCA-0087, which have trifluoromethyl instead of chloride in R2 position. We characterized these newly synthesized compounds by in vitro and in vivo assays. Enzyme assay shows that KRCA-0080 is more potent against various ALK mutants, including L1196M, G1202R, T1151-L1152insT, and C1156Y, which are seen in crizotinib-resistant patients, than KRCA-0008 is. Cell based assays demonstrate our compounds downregulate the cellular signaling, such as Akt and Erk, by suppressing ALK activity to inhibit the proliferation of the cells harboring EML4-ALK. Interestingly, our compounds induced strong G1/S arrest in H3122 cells leading to the apoptosis, which is proved by PARP-1 cleavage. In vivo H3122 xenograft assay, we found that KRCA-0080 shows significant reduction in tumor size compared to crizotinib and KRCA-0008 by 15–20%. Conclusively, we report a potent ALK inhibitor which shows significant in vivo efficacy as well as excellent inhibitory activity against various ALK mutants. - Highlights: • We synthesized KRCA-0008 derivatives having trifluoromethyl instead of chloride. • KRCA-0080 shows superior activity against several ALK mutants to KRCA-0008. • Cellular assays show our ALK inhibitors suppress only EML4-ALK positive cells. • Our ALK inhibitors induce G1/S arrest to lead apoptosis in H3122 cells. • KRCA-0080 has superior in vivo efficacy to crizotinib and KRCA-0008 by 15–20%.

  15. In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Al Muqarrabun, Laode Muhammad Ramadhan; Khan, Khalid Mohammed; Ghufran, Mehreen; Ali, Muhammad

    2016-10-01

    Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15μM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice.

    Directory of Open Access Journals (Sweden)

    Maxime Cazorla

    Full Text Available In the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the development of potent small ligands for the TrkB receptor has proven to be difficult. By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal activities. Finally, systemic administration of cyclotraxin-B to mice results in TrkB inhibition in the brain with specific anxiolytic-like behavioral effects and no antidepressant-like activity. This study demonstrates that cyclotraxin-B might not only be a powerful tool to investigate the role of BDNF and TrkB in physiology and pathology, but also represents a lead compound for the development of new therapeutic strategies to treat brain disorders.

  17. Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses.

    Directory of Open Access Journals (Sweden)

    Toru Ichihashi

    Full Text Available BACKGROUND: To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL induction capability. METHODOLOGY/PRINCIPAL FINDINGS: Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+CD11b(+MHCII(+ conventional dendritic cells (cDCs compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo. CONCLUSIONS/SIGNIFICANCE: This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

  18. Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies.

    Science.gov (United States)

    Tan, Fenlai; Shen, Xiaoyan; Wang, Dechang; Xie, Guojian; Zhang, Xiaodong; Ding, Lieming; Hu, Yunyan; He, Wei; Wang, Yanping; Wang, Yinxiang

    2012-05-01

    Icotinib, one of the leading compounds selected from our compound library, was found to be a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an IC(50) of 5 nM. When profiled with 88 kinases, Icotinib only showed meaningful inhibitory activity to EGFR and its mutants. Icotinib blocked EGFR-mediated intracellular tyrosine phosphorylation (IC(50)=45 nM) in the human epidermoid carcinoma A431 cell line and inhibits tumor cell proliferation. In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120 mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: NCT01040780). The data shows that Icotinib was non-inferior to Gefitinib in terms of median progression free survival (PFS) and safety superior favor to Icotinib compared to Gefitinib. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Minimal-length Synthetic shRNAs Formulated with Lipid Nanoparticles are Potent Inhibitors of Hepatitis C Virus IRES-linked Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Anne Dallas

    2013-01-01

    Full Text Available We previously identified short synthetic shRNAs (sshRNAs that target a conserved hepatitis C virus (HCV sequence within the internal ribosome entry site (IRES of HCV and potently inhibit HCV IRES-linked gene expression. To assess in vivo liver delivery and activity, the HCV-directed sshRNA, SG220 was formulated into lipid nanoparticles (LNP and injected i.v. into mice whose livers supported stable HCV IRES-luciferase expression from a liver-specific promoter. After a single injection, RNase protection assays for the sshRNA and 3H labeling of a lipid component of the nanoparticles showed efficient liver uptake of both components and long-lasting survival of a significant fraction of the sshRNA in the liver. In vivo imaging showed a dose-dependent inhibition of luciferase expression (>90% 1 day after injection of 2.5 mg/kg sshRNA with t1/2 for recovery of about 3 weeks. These results demonstrate the ability of moderate levels of i.v.-injected, LNP-formulated sshRNAs to be taken up by liver hepatocytes at a level sufficient to substantially suppress gene expression. Suppression is rapid and durable, suggesting that sshRNAs may have promise as therapeutic agents for liver indications.

  20. Fluoroethoxy-1,4-diphenethylpiperidine and piperazine derivatives: Potent and selective inhibitors of [3H]dopamine uptake at the vesicular monoamine transporter-2.

    Science.gov (United States)

    Hankosky, Emily R; Joolakanti, Shyam R; Nickell, Justin R; Janganati, Venumadhav; Dwoskin, Linda P; Crooks, Peter A

    2017-12-15

    A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [ 3 H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [ 3 H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [ 3 H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [ 3 H]DA uptake at VMAT2, Ki changes in the nanomolar range (K i  = 0.014-0.073 µM). Compound 15d exhibited the highest affinity (K i  = 0.014 µM) at VMAT2, and had 160-, 5-, and 60-fold greater selectivity for VMAT2 vs. DAT, SERT and hERG, respectively. Compound 15b exhibited the greatest selectivity (>60-fold) for VMAT2 relative to all the other targets evaluated, and 15b had high affinity for VMAT2 (K i  = 0.073 µM). Compound 15b was considered the lead compound from this analog series due to its high affinity and selectivity for VMAT2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Socioeconomic Position Across the Life Course and Cognitive Ability Later in Life: The Importance of Considering Early Cognitive Ability.

    Science.gov (United States)

    Foverskov, Else; Mortensen, Erik Lykke; Holm, Anders; Pedersen, Jolene Lee Masters; Osler, Merete; Lund, Rikke

    2017-11-01

    Investigate direct and indirect associations between markers of socioeconomic position (SEP) across the life course and midlife cognitive ability while addressing methodological limitations in prior work. Longitudinal data from the Danish Metropolit cohort of men born in 1953 ( N = 2,479) who completed ability tests at age 12, 18, and 56-58 linked to register-based information on paternal occupational class, educational attainment, and occupational level. Associations were assessed using structural equation models, and different models were estimated to examine the importance of accounting for childhood ability and measurement error. Associations between adult SEP measures and midlife ability decreased significantly when adjusting for childhood ability and measurement error. The association between childhood and midlife ability was by far the strongest. The impact of adult SEP on later life ability may be exaggerated when not accounting for the stability of individual differences in cognitive ability and measurement error in test scores.

  2. Assessing Professional Decision-Making Abilities.

    Science.gov (United States)

    McNergney, Robert; Hinson, Stephanie

    1985-01-01

    Describes Teacher Development Decision Exercises, a computer-based method of diagnosing abilities of elementary and secondary school supervisors (principals, staff developers, curriculum coordinators) to make professional preactive or planning decisions. This approval simulates assessment of supervisors' abilities to use professional knowledge to…

  3. Who Multi-Tasks and Why? Multi-Tasking Ability, Perceived Multi-Tasking Ability, Impulsivity, and Sensation Seeking

    OpenAIRE

    Sanbonmatsu, David M.; Strayer, David L.; Medeiros-Ward, Nathan; Watson, Jason M.

    2013-01-01

    The present study examined the relationship between personality and individual differences in multi-tasking ability. Participants enrolled at the University of Utah completed measures of multi-tasking activity, perceived multi-tasking ability, impulsivity, and sensation seeking. In addition, they performed the Operation Span in order to assess their executive control and actual multi-tasking ability. The findings indicate that the persons who are most capable of multi-tasking effectively are ...

  4. Assessing Algebraic Solving Ability: A Theoretical Framework

    Science.gov (United States)

    Lian, Lim Hooi; Yew, Wun Thiam

    2012-01-01

    Algebraic solving ability had been discussed by many educators and researchers. There exists no definite definition for algebraic solving ability as it can be viewed from different perspectives. In this paper, the nature of algebraic solving ability in terms of algebraic processes that demonstrate the ability in solving algebraic problem is…

  5. Structure of personality psychology based on cocitation analysis of prominent authors

    Directory of Open Access Journals (Sweden)

    Jevremov Tanja

    2007-01-01

    Full Text Available Traditional Author Cocitation Analysis was applied in order to map the personality psychology as a research field. A group of 25 authors were selected from the Haggbloom (1999, 2002 lists of the most cited and prominent psychologists, judged to be the main contributors to the field. All of their cocitations identified in the three year volumes of SSCI were downloaded to be analyzed by cluster analysis and MDS. The analysis resulted in four clusters comprising (1 theorists of individual differences amalgamated with authors of biological orientation with R. Cattell positioned centrally, (2 behaviorists joined by socio-cognitive theorists led by M.E.P. Seligman and A. Bandura, and (3 the group of psychoanalytic (dynamic theorists with A. Adler in the middle. In fourth cluster G. Allport, H. Murray, K. Lewin, W. Mischel, and D. Buss were found mixed together to make a rather heterogeneous group. In two-axes representation one of the dimensions was understood as reflecting methodological and the other one content-specific differences among the authors, although this interpretation is not univocal. The same procedure was repeated on citations given to the same authors in SocioFakt - the Serbian Citation Index for Social Sciences, revealing a reduced picture of the domain. At this portrait, some important authors are missing as a result of their low citation rate, suggesting that in the Serbian personality psychology entire research fields don’t exist. .

  6. Fascioperichondrial Flap with a Proximal Base Combined with Prominent Ear Surgery

    Directory of Open Access Journals (Sweden)

    Heval Selman Özkan

    2017-08-01

    Full Text Available Objective: In this article, we present a personalized surgical technique to relocate a fascioperichondrial flap with a proximal base as an additional measure to improve results and hide sharp edges which frequently occur following traditional otoplasty. Materials and Methods: Fascioperichondrial flap with a proximal base prepared from the dorsal side was transposed to the anterior helix and conchal excision side and secured with stitches to hide visible edges and reinforce Furnas sutures. Nine patients operated for prominent ear deformity using this modification were included in the study and follow-up period was at least 6 months. Conchal mastoid distances were calculated from the superior and middle third of the ears before and after the operation, also in follow-up controls to determine the efficiency of the method. Results: There were no suture extrusions, skin necrosis or infection. The mean difference for both the upper and middle third of the ears were considerably lower (p≤0.05 at the end of six month after the operation. There were no visible skin edges and discomfort described by the patients. Conclusion: Fascioperichondrial flap with a proximal base repositioning to conchal side is an easy procedure that can be applied simply as an adjunct to traditional techniques. Addition of this flap provides an additional tissue to reinforce suture repair and, the results seem to be more durable and strong. Another main advantage of this flap is eliminating the unnatural visible breakpoints in the conchal bowl.

  7. Discrimination ability of the Energy score

    DEFF Research Database (Denmark)

    Pinson, Pierre; Tastu, Julija

    as appealing since being proper, we show that its discrimination ability may be limited when focusing on the dependence structure of multivariate probabilistic forecasts. For the case of multivariate Gaussian process, a theoretical upper for such discrimination ability is derived and discussed. This limited...... discrimination ability may eventually get compromised by computational and sampling issues, as dimension increases....

  8. Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors.

    Science.gov (United States)

    Ayers, Benjamin J; Glawar, Andreas F G; Martínez, R Fernando; Ngo, Nigel; Liu, Zilei; Fleet, George W J; Butters, Terry D; Nash, Robert J; Yu, Chu-Yi; Wormald, Mark R; Nakagawa, Shinpei; Adachi, Isao; Kato, Atsushi; Jenkinson, Sarah F

    2014-04-18

    All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N-acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.

  9. Efficient evaluation of hearing ability

    NARCIS (Netherlands)

    2010-01-01

    The present invention relates to a method of establishing a hearing ability model for a person, the method including providing a representation of the distribution of hearing ability for a population of individuals. The method may comprise the steps) performing a hearing evaluation event, comprising

  10. Who multi-tasks and why? Multi-tasking ability, perceived multi-tasking ability, impulsivity, and sensation seeking.

    Science.gov (United States)

    Sanbonmatsu, David M; Strayer, David L; Medeiros-Ward, Nathan; Watson, Jason M

    2013-01-01

    The present study examined the relationship between personality and individual differences in multi-tasking ability. Participants enrolled at the University of Utah completed measures of multi-tasking activity, perceived multi-tasking ability, impulsivity, and sensation seeking. In addition, they performed the Operation Span in order to assess their executive control and actual multi-tasking ability. The findings indicate that the persons who are most capable of multi-tasking effectively are not the persons who are most likely to engage in multiple tasks simultaneously. To the contrary, multi-tasking activity as measured by the Media Multitasking Inventory and self-reported cell phone usage while driving were negatively correlated with actual multi-tasking ability. Multi-tasking was positively correlated with participants' perceived ability to multi-task ability which was found to be significantly inflated. Participants with a strong approach orientation and a weak avoidance orientation--high levels of impulsivity and sensation seeking--reported greater multi-tasking behavior. Finally, the findings suggest that people often engage in multi-tasking because they are less able to block out distractions and focus on a singular task. Participants with less executive control--low scorers on the Operation Span task and persons high in impulsivity--tended to report higher levels of multi-tasking activity.

  11. Who multi-tasks and why? Multi-tasking ability, perceived multi-tasking ability, impulsivity, and sensation seeking.

    Directory of Open Access Journals (Sweden)

    David M Sanbonmatsu

    Full Text Available The present study examined the relationship between personality and individual differences in multi-tasking ability. Participants enrolled at the University of Utah completed measures of multi-tasking activity, perceived multi-tasking ability, impulsivity, and sensation seeking. In addition, they performed the Operation Span in order to assess their executive control and actual multi-tasking ability. The findings indicate that the persons who are most capable of multi-tasking effectively are not the persons who are most likely to engage in multiple tasks simultaneously. To the contrary, multi-tasking activity as measured by the Media Multitasking Inventory and self-reported cell phone usage while driving were negatively correlated with actual multi-tasking ability. Multi-tasking was positively correlated with participants' perceived ability to multi-task ability which was found to be significantly inflated. Participants with a strong approach orientation and a weak avoidance orientation--high levels of impulsivity and sensation seeking--reported greater multi-tasking behavior. Finally, the findings suggest that people often engage in multi-tasking because they are less able to block out distractions and focus on a singular task. Participants with less executive control--low scorers on the Operation Span task and persons high in impulsivity--tended to report higher levels of multi-tasking activity.

  12. Who Multi-Tasks and Why? Multi-Tasking Ability, Perceived Multi-Tasking Ability, Impulsivity, and Sensation Seeking

    Science.gov (United States)

    Sanbonmatsu, David M.; Strayer, David L.; Medeiros-Ward, Nathan; Watson, Jason M.

    2013-01-01

    The present study examined the relationship between personality and individual differences in multi-tasking ability. Participants enrolled at the University of Utah completed measures of multi-tasking activity, perceived multi-tasking ability, impulsivity, and sensation seeking. In addition, they performed the Operation Span in order to assess their executive control and actual multi-tasking ability. The findings indicate that the persons who are most capable of multi-tasking effectively are not the persons who are most likely to engage in multiple tasks simultaneously. To the contrary, multi-tasking activity as measured by the Media Multitasking Inventory and self-reported cell phone usage while driving were negatively correlated with actual multi-tasking ability. Multi-tasking was positively correlated with participants’ perceived ability to multi-task ability which was found to be significantly inflated. Participants with a strong approach orientation and a weak avoidance orientation – high levels of impulsivity and sensation seeking – reported greater multi-tasking behavior. Finally, the findings suggest that people often engage in multi-tasking because they are less able to block out distractions and focus on a singular task. Participants with less executive control - low scorers on the Operation Span task and persons high in impulsivity - tended to report higher levels of multi-tasking activity. PMID:23372720

  13. Biophysical and biological properties of small linear peptides derived from crotamine, a cationic antimicrobial/antitumoral toxin with cell penetrating and cargo delivery abilities.

    Science.gov (United States)

    Dal Mas, C; Pinheiro, D A; Campeiro, J D; Mattei, B; Oliveira, V; Oliveira, E B; Miranda, A; Perez, K R; Hayashi, M A F

    2017-12-01

    Crotamine is a natural polypeptide from snake venom which delivers nucleic acid molecules into cells, besides having pronounced affinity for negatively charged membranes and antifungal activity. We previously demonstrated that crotamine derived short linear peptides were not very effective as antifungal, although the non-structured recombinant crotamine was overridingly more potent compared to the native structured crotamine. Aiming to identify the features necessary for the antifungal activity of crotamine, two linear short peptides, each comprising half of the total positively charged amino acid residues of the full-length crotamine were evaluated here to show that these linear peptides keep the ability to interact with lipid membrane model systems with different phospholipid compositions, even after forming complexes with DNA. Interestingly, the presence of cysteine residues in the structure of these linear peptides highly influenced the antifungal activity, which was not associated to the lipid membrane lytic activity. In addition to the importance of the positive charges, the crucial role of cysteine residues was noticed for these linear analogs of crotamine, although the tridimensional structure and lipid membrane lytic activity observed only for native crotamine was not essential for the antifungal activity. As these peptides still keep the ability to form complexes with DNA molecules with no prejudice to their ability to bind to lipid membranes, they may be potentially advantageous as membrane translocation vector, as they do not show lipid membrane lytic activity and may harbor or not antifungal activity, by keeping or not the semi-essential amino acid cysteine in their sequence. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. Structure-activity relationships and identification of potent and selective iGluR5 modulators

    DEFF Research Database (Denmark)

    Butini, Stefania; Pickering, Darryl S; Morelli, Elena

    2008-01-01

    (S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist. Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit iGluR5. Derivatives 5 and 7, with their unique pharmacolog...

  15. Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2013-05-01

    Full Text Available Antimicrobial peptides (AMPs, small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD. The majority of these AMPs (>86% possess 11–50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31–70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo design, and template-based design. Using these methods, we identified various potent peptides against human immunodeficiency virus type 1 (HIV-1 or methicillin-resistant Staphylococcus aureus (MRSA. While the stepwise designed anti-HIV peptide is disulfide-linked and rich in arginines, the ab initio designed anti-MRSA peptide is linear and rich in leucines. Thus, there are different requirements for antiviral and antibacterial peptides, which could kill pathogens via different molecular targets. The biased amino acid composition in the database-designed peptides, or natural peptides such as θ-defensins, requires the use of the improved two-dimensional NMR method for structural determination to avoid the publication of misleading structure and dynamics. In the case of human cathelicidin LL-37, structural determination requires 3D NMR techniques. The high-quality structure of LL-37 provides a solid basis for understanding its interactions with membranes of bacteria and other pathogens. In conclusion, the APD database is a comprehensive platform for storing, classifying, searching, predicting, and designing potent peptides against pathogenic bacteria, viruses, fungi, parasites, and cancer cells.

  16. The Effect of Dramatized Instruction on Speaking Ability of Imam Ali University EFL Learners

    Directory of Open Access Journals (Sweden)

    Sadegh Khosronejad

    2013-09-01

    Full Text Available Teaching language as a second or foreign language, undoubtedly, is so demanding and seeking to find methods for facilitating this prominent practice whets the appetite of any practitioner who works in this field. Research shows that using drama in the classroom as a means of teaching helps students learn socially, academically, and developmentally. This study was an attempt to determine the effect of dramatized instruction on the speaking ability of EFL learners of Imam Ali University. Sixty EFL male students at the intermediate level participated in the study. Their age range was 19-22. Two instruments were utilized in this study; pretest, and posttest.  The data were analyzed through t-test. The data analysis indicated that the mean scores of the experimental group students (M = 72.80 were significantly different (3.29>2; df = 58 from the control group students (M = 65.39. In other words, the experimental group outperformed the control group in the posttest significantly. Moreover, the findings indicated that dramatized instruction does have a great effect on the speaking skills. This study supported the idea of effectiveness of dramatized instruction on developing speaking skill and the teachers can help the learners at lower levels promote their speaking skill through dramatized instruction in EFL classes.

  17. The contribution of general cognitive abilities and number abilities to different aspects of mathematics in children.

    Science.gov (United States)

    Träff, Ulf

    2013-10-01

    This study examined the relative contributions of general cognitive abilities and number abilities to word problem solving, calculation, and arithmetic fact retrieval in a sample of 134 children aged 10 to 13 years. The following tasks were administered: listening span, visual matrix span, verbal fluency, color naming, Raven's Progressive Matrices, enumeration, number line estimation, and digit comparison. Hierarchical multiple regressions demonstrated that number abilities provided an independent contribution to fact retrieval and word problem solving. General cognitive abilities contributed to problem solving and calculation. All three number tasks accounted for a similar amount of variance in fact retrieval, whereas only the number line estimation task contributed unique variance in word problem solving. Verbal fluency and Raven's matrices accounted for an equal amount of variance in problem solving and calculation. The current findings demonstrate, in accordance with Fuchs and colleagues' developmental model of mathematical learning (Developmental Psychology, 2010, Vol. 46, pp. 1731-1746), that both number abilities and general cognitive abilities underlie 10- to 13-year-olds' proficiency in problem solving, whereas only number abilities underlie arithmetic fact retrieval. Thus, the amount and type of cognitive contribution to arithmetic proficiency varies between the different aspects of arithmetic. Furthermore, how closely linked a specific aspect of arithmetic is to the whole number representation systems is not the only factor determining the amount and type of cognitive contribution in 10- to 13-year-olds. In addition, the mathematical complexity of the task appears to influence the amount and type of cognitive support. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. An analysis of prominent prospect of in-situ sandstone type uranium deposits in Yanji basins group, Jilin province

    International Nuclear Information System (INIS)

    Peng Zhidong; Zhang Shuyi

    2003-01-01

    In Mesozoic-Cenozoic era, many medium-small-sized sedimentary basins had been formed in Yanbian draped-faulted region of Jilin Province. The basement of these basins is constituted of U-riched granite body produced during late Hercynian-early Yanshan period. Uranium-mineralization has been found in coal-bearing formation, oil-bearing formation and in tint layer of red formation. On the bases of analyzing of uranium source, geologic tectonic, paleoclimatology, paleogeography, hydrogeology and reconstruction, it is concluded that there is a prominent prospect to discover large in-situ sandstone-type uranium deposits in Yanji basins. (authors)

  19. High ability: Giftedness and talent

    Directory of Open Access Journals (Sweden)

    María Dolores Prieto Sánchez

    2010-04-01

    Full Text Available This special issue of the journal aims at putting together national and international research on high abilities, and is divided into three sections: 1 Roles and cognitive, emotional and professional competences of high ability students’ teachers, 2 Identification and assessment of high ability students, 3 Analysis of practices, programs and mentoring of high ability students’ attention to diversity.The articles are authored by scholars from nine different countries (Spain, Argentina, UK, USA, Russia, Brazil, Saudi Arabia, Portugal and Poland, from sixteen different Spanish and international universities: Alicante (Spain, Autónoma de Barcelona (Spain, Málaga (Spain, Murcia (Spain, Navarra (Spain, Oviedo (Spain, Tufts University (USA, Yale University (USA, Moscow State University (Russia, Nacional de La Plata (Argentina, University of Connecticut (USA, Universidade do Minho (Portugal, Universidade da Beira Interior (Portugal, Universidade do Estado do Rio de Janeiro (Brazil, King Faisal University (Saudi Arabia and Universidad de Szczecin (Poland.

  20. AVN-322 is a Safe Orally Bio-Available Potent and Highly Selective Antagonist of 5-HT6R with Demonstrated Ability to Improve Impaired Memory in Animal Models.

    Science.gov (United States)

    Ivachtchenko, Alexandre V; Ivanenkov, Yan A; Veselov, Mark S; Okun, I M

    2017-01-01

    In recent years, 5-hydroxytryptamine subtype 6 receptor (5-HT6 receptor, 5- HT6R) has emerged as a promising therapeutic target for the treatment of neuropathological disorders, including Alzheimer's disease (AD) and schizophrenia. 5-HT6 receptors were hypothesized to be implicated in the processes of learning, memory, and cognition with 5-HT6R antagonists being effective in animal models of cognition and memory impairment. Several selective 5-HT6R ligands are currently undergoing clinical trials for treatment of AD. We describe results of preclinical development of a novel and highly selective and potent 5- HT6R antagonist, AVN-322, as a clinical candidate for the treatment of AD to improve concurrent debilitation of memory and cognition in the AD patients, and schizophrenia as a substance with antipsychotic effect. In the manuscript, we present its in vitro and vivo efficacy, ADME, pharmacokinetics in animals and in humans, and toxicity. While having high binding affinity in medium picomolar range, the lead compound demonstrates substantially better selectivity index then the reference drug candidates currently being tested in clinical studies. AVN-322 showed high oral bioavailability and favorable blood-brain barrier (BBB) penetration. In vivo testing revealed its clear cognition enhancing effect. AVN-322 significantly restored both scopolamine- and MK-801-induced cognitive dysfunction and demonstrated antipsychotic potential. Taking into account its good safety profile and favorable pharmacokinetics, AVN-322 can be reasonably considered as a novel drug candidate for the treatment of neurological disorders such as AD and/or schizophrenia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.