Science.gov

Sample records for large a-fiber activity

  1. Active Q-switching of a fiber laser using a modulated fiber Fabry-Perot filter and a fiber Bragg grating

    NASA Astrophysics Data System (ADS)

    Martínez Manuel, Rodolfo; Kaboko, J. J. M.; Shlyagin, M. G.

    2016-02-01

    We propose and demonstrate a simple and robust actively Q-switched erbium-doped fiber ring cavity laser. The Q-switching is based on dynamic spectral overlapping of two filters, namely a fiber Bragg grating-based filter and a fiber Fabry-Perot tunable filter. Using 3.5 m of erbium-doped fiber and a pump power of only 60 mW, Q-switched pulses with a peak power of 9.7 W and a pulse duration of 500 ns were obtained. A pulse repetition rate can be continuously varied from a single shot to a few KHz.

  2. Observations of four types of pulses in a fiber laser with large net-normal dispersion.

    PubMed

    Wang, Leiran; Liu, Xueming; Gong, Yongkang; Mao, Dong; Duan, Lina

    2011-04-11

    Four different types of pulses are experimentally obtained in one erbium-doped all-fiber laser with large net-normal dispersion. The proposed laser can deliver the rectangular-spectrum (RS), Gaussian-spectrum (GS), broadband-spectrum (BS), and noise-like pulses by appropriately adjusting the polarization states. These kinds of pulses have distinctly different characteristics. The RS pulses can easily be compressed to femtosecond level whereas the pulse energy is restricted by the trend of multi-pulse shaping with excessive pump. The GS and BS pulses always maintain the single-pulse operation with much higher pulse-energy and accumulate much more chirp. After launching the pulses into the photonic-crystal fiber, the supercontinuum can be generated with the bandwidth of >700 nm by the BS pulses and of ~400 nm by the GS pulses, whereas it can hardly be generated by the RS pulses. The physical mechanisms behind the continuum generation are qualitatively investigated relating to different operating regimes. This work could help to a deeper insight of the normal-dispersion pulses.

  3. Pulse dynamics of dissipative soliton resonance with large duration-tuning range in a fiber ring laser.

    PubMed

    Luo, Zhi-Chao; Cao, Wen-Jun; Lin, Zhen-Bin; Cai, Ze-Rong; Luo, Ai-Ping; Xu, Wen-Cheng

    2012-11-15

    The pulse dynamics operating in dissipative soliton resonance (DSR) region is experimentally investigated in a fiber ring laser. With the increase of pump power, the pulse profile transit from sech-like to rectangular shape was observed. The generated pulse in DSR region exhibits the conventional soliton spectrum with sideband generation. The duration-tuning range of the rectangular pulse is up to the cavity roundtrip time. Particularly, during the process of pulse duration broadening it was found that the rectangular pulse would trap a weak pulse generated from cw background. The obtained results may be useful for better understanding the DSR phenomenon.

  4. Large-aperture CCD x-ray detector for protein crystallography using a fiber-optic taper

    NASA Astrophysics Data System (ADS)

    Strauss, Michael G.; Westbrook, Edwin M.; Naday, Istvan; Coleman, T. A.; Westbrook, Mary L.; Travis, D. J.; Sweet, Robert M.; Pflugrath, J. W.; Stanton, Martin J.

    1991-07-01

    A detector with a 114 mm aperture, based on a charge-coupled device (CCD), has been designed for x-ray diffraction studies in protein crystallography. The detector was tested on a beamline of the National Synchrotron Light Source at Brookhaven National Laboratory with a beam intensity greater than 10(superscript 9) x-ray photons/s. A fiber-optic taper, an image intensifier, and a lens demagnify, intensify, and focus the image onto a CCD having 512 X 512 pixels. A detective quantum efficiency (DQE) of 0.36 was obtained by evaluating the statistical uncertainty in the detector output. The dynamic range of a 4 X 4 pixel resolution element, comparable in size to a diffraction peak, was 10 (superscript 4). The point-spread function shows FWHM resolution of approximately 1 pixel, where a pixel on the detector face is 160 micrometers . A complete data set, consisting of forty-five 1 degree(s) rotation frames, was obtained in just 36 s of x-ray exposure to a crystal of chicken egg-white lysozyme. In a separate experiment, a lysozyme data set consisting of 495 0.1 degree(s) frames, was processed by the MADNES data reduction program, yielding symmetry R-factors for the data of 3.2- 3.5%. Diffraction images from crystals of the myosin S1 head (a equals 275 angstroms) were also recorded. The Bragg spots, only 5 pixels apart, were resolved but were not sufficiently separated to process these data. Changes in the detector design which will improve the DQE and spatial resolution are outlined. The overall performance showed that this type of detector is well suited for x-ray scattering investigations with synchrotron sources.

  5. The GMT-CFA-CARNEGIE-CATOLICA LARGE EARTH FINDER (G-CLEF): A Fiber-fed, Optical Echelle Spectrograph For The Giant Magellan Telescope

    NASA Astrophysics Data System (ADS)

    Szentgyorgyi, Andrew; Furesz, G.; Frebel, A.; Geary, J.; Evans, I.; Norton, T.; Hertz, E.; DePonte Evans, J.; Jordan, A.; Guzman, D.; Epps, H.; Barnes, S.; Crane, J.

    2011-01-01

    The GMT-CfA-Carnegie-Catolica Large Earth Finder (G-CLEF) is a fiber-fed optical echelle spectrograph in concept design study phase for first light at the Giant Magellan Telescope. G-CLEF is designed to be a multipurpose echelle spectrograph that operates in a number of modes so as to enable precision radial velocity (RV) measurements, detailed abundance studies, isotopic abundance measurements and probe the IGM and ISM at high Z. Four resolution modes are implemented with image and pupil slicing. Extremely precise RV will be achieved by vacuum enclosing the spectrograph, with advanced fiber scrambling and state-of-the-art calibrators, especially ultra stabilized etalons and possibly laser frequency combs. The optical design is a asymmetric white pupil design with two camera arms splitting the 350 nm - 950 nm passband into red and blue channels. G-CLEF will have an extremely large, mosaiced echelle grating and volume phase holograph cross dispersers.

  6. Active stabilization of a fiber-optic two-photon interferometer using continuous optical length control.

    PubMed

    Cho, Seok-Beom; Kim, Heonoh

    2016-05-16

    The practical realization of long-distance entanglement-based quantum communication systems strongly rely on the observation of highly stable quantum interference between correlated single photons. This task must accompany active stabilization of the optical path lengths within the single-photon coherence length. Here, we provide two-step interferometer stabilization methods employing continuous optical length control and experimentally demonstrate two-photon quantum interference using an actively stabilized 6-km-long fiber-optic Hong-Ou-Mandel interferometer. The two-step active control techniques are applied for measuring highly stable two-photon interference fringes by scanning the optical path-length difference. The obtained two-photon interference visibilities with and without accidental subtraction are found to be approximately 90.7% and 65.4%, respectively.

  7. Getting Active in the Large Lecture

    ERIC Educational Resources Information Center

    Huerta, Juan Carlos

    2007-01-01

    The benefits of active learning are well documented; nonetheless, the implementation of active learning strategies can be challenging in large lecture environments. The project will examine the research supporting active learning, present the implementation of simple active learning techniques in large lecture classes, and provide evidence to test…

  8. Patterns of seismic activity preceding large earthquakes

    NASA Technical Reports Server (NTRS)

    Shaw, Bruce E.; Carlson, J. M.; Langer, J. S.

    1992-01-01

    A mechanical model of seismic faults is employed to investigate the seismic activities that occur prior to major events. The block-and-spring model dynamically generates a statistical distribution of smaller slipping events that precede large events, and the results satisfy the Gutenberg-Richter law. The scaling behavior during a loading cycle suggests small but systematic variations in space and time with maximum activity acceleration near the future epicenter. Activity patterns inferred from data on seismicity in California demonstrate a regional aspect; increased activity in certain areas are found to precede major earthquake events. One example is given regarding the Loma Prieta earthquake of 1989 which is located near a fault section associated with increased activity levels.

  9. Single and large grain activities at Fermilab

    SciTech Connect

    Antoine, Claire; /Fermilab

    2006-01-01

    This paper describes the ongoing activities at Fermilab for large grains and monocrystalline niobium. In addition to acquisition of local fabrication expertise, we plan to develop an R&D program dedicated to evidence the possible influence of crystal orientation on physical and chemical properties of niobium, such as mechanical properties, magnetic properties or surface contamination. Some considerations are also given about the morphology at grain boundaries and its role on the behavior of superconducting cavities.

  10. Large Active Retrodirective Arrays for Space Applications

    NASA Technical Reports Server (NTRS)

    Chernoff, R. C.

    1978-01-01

    An active retrodirective array (ARA) electronically points a microwave beam back at the apparent source of an incident pilot signal. Retrodirectivity is the result of phase conjugation of the pilot signal received by each element of the array. The problem of supplying the correct phase reference to the phase conjugation circuit (PCC) associated with each element of the array is solved by central phasing. By eliminating the need for structural rigidity, central phasing confers a decisive advantage on ARA's as large spaceborne antennas. A new form of central phasing suitable for very large arrays is described. ARA's may easily be modified to serve both as transmitting and receiving arrays simultaneously. Two new kinds of exact, frequency translating PCC's are described. Such PCC's provide the ARA with input-output isolation and freedom from squint. The pointing errors caused by the radial and transverse components of the ARA's velocity, by the propagation medium, and by multipath are discussed. A two element ARA breadboard was built and tested at JPL. Its performance is limited primarily by multipath induced errors.

  11. Active optics in Large Synoptic Survey Telescope

    NASA Astrophysics Data System (ADS)

    Liang, Ming; Krabbendam, Victor; Claver, Charles F.; Chandrasekharan, Srinivasan; Xin, Bo

    2012-09-01

    The Large Synoptic Survey Telescope (LSST) has a 3.5º field of view and F/1.2 focus that makes the performance quite sensitive to the perturbations of misalignments and mirror surface deformations. In order to maintain the image quality, LSST has an active optics system (AOS) to measure and correct those perturbations in a closed loop. The perturbed wavefront errors are measured by the wavefront sensors (WFS) located at the four corners of the focal plane. The perturbations are solved by the non-linear least square algorithm by minimizing the rms variation of the measured and baseline designed wavefront errors. Then the correction is realized by applying the inverse of the perturbations to the optical system. In this paper, we will describe the correction processing in the LSST AOS. We also will discuss the application of the algorithm, the properties of the sensitivity matrix and the stabilities of the correction. A simulation model, using ZEMAX as a ray tracing engine and MATLAB as an analysis platform, is set up to simulate the testing and correction loop of the LSST AOS. Several simulation examples and results are presented.

  12. Silent Students' Participation in a Large Active Learning Science Classroom

    ERIC Educational Resources Information Center

    Obenland, Carrie A.; Munson, Ashlyn H.; Hutchinson, John S.

    2012-01-01

    Active learning in large science classrooms furthers opportunities for students to engage in the content and in meaningful learning, yet students can still remain anonymously silent. This study aims to understand the impact of active learning on these silent students in a large General Chemistry course taught via Socratic questioning and…

  13. ACTIVE SOIL DEPRESSURIZATION (ASD) DEMONSTRATION IN A LARGE BUILDING

    EPA Science Inventory

    The report gives results of an evaluation of the feasibility of implementing radon resistant construction techniques -- especially active soil depressurization (ASD) -- in new large buildings in Florida. Indoor radon concentrations and radon entry were monitored in a finished bui...

  14. 105-DR Large Sodium Fire Facility closure activities evaluation report

    SciTech Connect

    Adler, J.G.

    1996-04-11

    This report evaluates the closure activities at the 105-DR Large Sodium Fire Facility. The evaluation compares these activities to the regulatory requirements and closure plan requirements. The report concludes that the areas identified in the closure plan can be clean closed. This report summarizes and evaluates the closure activities performed in support of partial closure of the 105-DR Large Sodium Fire Facility (LSFF). This evaluation will be used in assessing the condition of the 105-DR LSFF for the purpose of meeting the partial clean closure conditions described in the 105-DR Large Sodium Fire Facility Closure Plan (DOE-RL 1995). Based on the evaluation of the decontamination activities, sampling activities, and sample data, it is has been determined that the partial clean closure conditions for the 105-DR LSFF have been met.

  15. Two Learning Activities for a Large Introductory Statistics Class

    ERIC Educational Resources Information Center

    Zacharopoulou, Hrissoula

    2006-01-01

    In a very large Introductory Statistics class, i.e. in a class of more than 300 students, instructors may hesitate to apply active learning techniques, discouraged by the volume of extra work. In this paper two such activities are presented that evoke student involvement in the learning process. The first is group peer teaching and the second is…

  16. Development and testing of an actively controlled large-aperture Cassegrain Telescope for spacecraft deployment

    NASA Astrophysics Data System (ADS)

    Boone, Bradley G.; Bruzzi, Jonathan R.; Kluga, Bernard E.; Rogala, Eric W.; Hale, R. D.; Chen, Peter C.

    2004-10-01

    The National Aeronautics and Space Administration (NASA) is planning future deep space missions requiring space-based imaging reconnaissance of planets and recovery of imagery from these missions via optical communications. Both applications have similar requirements that can be met by a common aperture. The Johns Hopkins University Applied Physics Laboratory in collaboration with commercial and academic partners is developing a new approach to deploying and controlling large aperture (meter-class) optical telescopes on spacecraft that can be rapidly launched and deployed. The deployment mechanism uses flexible longeron struts to deploy the secondary. The active control system uses a fiber-coupled laser array near the focal plane that reflects four collimated laser beams off of the periphery of the secondary to four equally-disposed quad cell sensors at the periphery of the primary to correct secondary-to-primary misalignments and enable motion compensation. We describe a compensation technique that uses tip/tilt and piston actuators for quasi-static bias correction and dynamic motion compensation. We also describe preliminary optical tests using a commercial Schmidt-Cassegrain telescope in lieu of an ultra-lightweight composite Cassegrain, which is under development by Composite Mirror Applications, Inc. Finite element and ray trace modeling results for a 40 cm composite telescope design will also be described.

  17. Large-scale multielectrode recording and stimulation of neural activity

    NASA Astrophysics Data System (ADS)

    Sher, A.; Chichilnisky, E. J.; Dabrowski, W.; Grillo, A. A.; Grivich, M.; Gunning, D.; Hottowy, P.; Kachiguine, S.; Litke, A. M.; Mathieson, K.; Petrusca, D.

    2007-09-01

    Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions.

  18. Large Roads Reduce Bat Activity across Multiple Species

    PubMed Central

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations. PMID:24823689

  19. Large roads reduce bat activity across multiple species.

    PubMed

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations.

  20. Active Learning in a Large General Physics Classroom.

    NASA Astrophysics Data System (ADS)

    Trousil, Rebecca

    2008-04-01

    In 2004, we launched a new calculus-based, introductory physics sequence at Washington University. Designed as an alternative to our traditional lecture-based sequence, the primary objectives for this new course were to actively engage students in the learning process, to significantly strengthen students' conceptual reasoning skills, to help students develop higher level quantitative problem solving skills necessary for analyzing ``real world'' problems, and to integrate modern physics into the curriculum. This talk will describe our approach, using The Six Ideas That Shaped Physics text by Thomas Moore, to creating an active learning environment in large classes as well as share our perspective on key elements for success and challenges that we face in the large class environment.

  1. The LATT way towards large active primaries for space telescopes

    NASA Astrophysics Data System (ADS)

    Briguglio, Runa; Arcidiacono, Carmelo; Xompero, Marco; Lisi, Franco; Riccardi, Armando; Biasi, Roberto; Patauner, Christian; Gallieni, Daniele; Lazzarini, Paolo; Tintori, Matteo; d'Amato, Francesco; Pucci, Mauro; Duò, Fabrizio; Vettore, Christian; Zuccaro Marchi, Alessandro

    2016-07-01

    The Large Aperture Telescope Technology (LATT) goes beyond the current paradigm of future space telescopes, based on a deformable mirror in the pupil relay. Through the LATT project we demonstrated the concept of a low-weight active primary mirror, whose working principle and control strategy benefit from two decades of advances in adaptive optics for ground-based telescopes. We developed a forty centimeter spherical mirror prototype, with an areal density lower than 17 kg/m2, controlled through contactless voice coil actuators with co-located capacitive position sensors. The prototype was subjected to thermo-vacuum, vibration and optical tests, to push its technical readiness toward level 5. In this paper we present the background and the outcomes of the LATT activities under ESA contract (TRP programme), exploring the concept of a lightweight active primary mirror for space telescopes. Active primaries will open the way to very large segmented apertures, actively shaped, which can be lightweight, deployable and accurately phased once in flight.

  2. Large area flexible SERS active substrates using engineered nanostructures

    NASA Astrophysics Data System (ADS)

    Chung, Aram J.; Huh, Yun Suk; Erickson, David

    2011-07-01

    Surface enhanced Raman scattering (SERS) is an analytical sensing method that provides label-free detection, molecularly specific information, and extremely high sensitivity. The Raman enhancement that makes this method attractive is mainly attributed to the local amplification of the incident electromagnetic field that occurs when a surface plasmon mode is excited at a metallic nanostructure. Here, we present a simple, cost effective method for creating flexible, large area SERS-active substrates using a new technique we call shadow mask assisted evaporation (SMAE). The advantage of large, flexible SERS substrates such as these is they have more area for multiplexing and can be incorporated into irregular surfaces such as clothing. We demonstrate the formation of four different types of nanostructure arrays (pillar, nib, ellipsoidal cylinder, and triangular tip) by controlling the evaporation angle, substrate rotation, and deposition rate of metals onto anodized alumina nanoporous membranes as large as 27 mm. In addition, we present experimental results showing how a hybrid structure comprising of gold nanospheres embedded in a silver nano-pillar structure can be used to obtain a 50× SERS enhancement over the raw nanoparticles themselves.Surface enhanced Raman scattering (SERS) is an analytical sensing method that provides label-free detection, molecularly specific information, and extremely high sensitivity. The Raman enhancement that makes this method attractive is mainly attributed to the local amplification of the incident electromagnetic field that occurs when a surface plasmon mode is excited at a metallic nanostructure. Here, we present a simple, cost effective method for creating flexible, large area SERS-active substrates using a new technique we call shadow mask assisted evaporation (SMAE). The advantage of large, flexible SERS substrates such as these is they have more area for multiplexing and can be incorporated into irregular surfaces such as

  3. Technologies for imaging neural activity in large volumes

    PubMed Central

    Ji, Na; Freeman, Jeremy; Smith, Spencer L.

    2017-01-01

    Neural circuitry has evolved to form distributed networks that act dynamically across large volumes. Collecting data from individual planes, conventional microscopy cannot sample circuitry across large volumes at the temporal resolution relevant to neural circuit function and behaviors. Here, we review emerging technologies for rapid volume imaging of neural circuitry. We focus on two critical challenges: the inertia of optical systems, which limits image speed, and aberrations, which restrict the image volume. Optical sampling time must be long enough to ensure high-fidelity measurements, but optimized sampling strategies and point spread function engineering can facilitate rapid volume imaging of neural activity within this constraint. We also discuss new computational strategies for the processing and analysis of volume imaging data of increasing size and complexity. Together, optical and computational advances are providing a broader view of neural circuit dynamics, and help elucidate how brain regions work in concert to support behavior. PMID:27571194

  4. Oxidative Regulation of Large Conductance Calcium-Activated Potassium Channels

    PubMed Central

    Tang, Xiang D.; Daggett, Heather; Hanner, Markus; Garcia, Maria L.; McManus, Owen B.; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

    2001-01-01

    Reactive oxygen/nitrogen species are readily generated in vivo, playing roles in many physiological and pathological conditions, such as Alzheimer's disease and Parkinson's disease, by oxidatively modifying various proteins. Previous studies indicate that large conductance Ca2+-activated K+ channels (BKCa or Slo) are subject to redox regulation. However, conflicting results exist whether oxidation increases or decreases the channel activity. We used chloramine-T, which preferentially oxidizes methionine, to examine the functional consequences of methionine oxidation in the cloned human Slo (hSlo) channel expressed in mammalian cells. In the virtual absence of Ca2+, the oxidant shifted the steady-state macroscopic conductance to a more negative direction and slowed deactivation. The results obtained suggest that oxidation enhances specific voltage-dependent opening transitions and slows the rate-limiting closing transition. Enhancement of the hSlo activity was partially reversed by the enzyme peptide methionine sulfoxide reductase, suggesting that the upregulation is mediated by methionine oxidation. In contrast, hydrogen peroxide and cysteine-specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity. Chloramine-T was much less effective when concurrently applied with the K+ channel blocker TEA, which is consistent with the possibility that the target methionine lies within the channel pore. Regulation of the Slo channel by methionine oxidation may represent an important link between cellular electrical excitability and metabolism. PMID:11222629

  5. Large area flexible SERS active substrates using engineered nanostructures.

    PubMed

    Chung, Aram J; Huh, Yun Suk; Erickson, David

    2011-07-01

    Surface enhanced Raman scattering (SERS) is an analytical sensing method that provides label-free detection, molecularly specific information, and extremely high sensitivity. The Raman enhancement that makes this method attractive is mainly attributed to the local amplification of the incident electromagnetic field that occurs when a surface plasmon mode is excited at a metallic nanostructure. Here, we present a simple, cost effective method for creating flexible, large area SERS-active substrates using a new technique we call shadow mask assisted evaporation (SMAE). The advantage of large, flexible SERS substrates such as these is they have more area for multiplexing and can be incorporated into irregular surfaces such as clothing. We demonstrate the formation of four different types of nanostructure arrays (pillar, nib, ellipsoidal cylinder, and triangular tip) by controlling the evaporation angle, substrate rotation, and deposition rate of metals onto anodized alumina nanoporous membranes as large as 27 mm. In addition, we present experimental results showing how a hybrid structure comprising of gold nanospheres embedded in a silver nano-pillar structure can be used to obtain a 50× SERS enhancement over the raw nanoparticles themselves.

  6. Active disturbance rejection in large flexible space structures

    NASA Technical Reports Server (NTRS)

    Parlos, Alexander G.; Sunkel, John W.

    1990-01-01

    The design of an active control law for the rejection of persistent disturbances, in large space structures is presented. The control system design approach is based on a deterministic model of the disturbances and it optimizes the magnitude of the disturbance that the structure can tolerate without violating certain predetermined constraints. In addition to closed-loop stability, the explicit treatment of state, control, and control rate constraints, such as structural displacement and control actuator effort, guarantees that the final design will exhibit desired performance characteristics. The technique is applied to a simple two-bay truss structure, and its response is compared with that obtained using a linear-quadratic-Gaussian/loop-transfer-recovery (LQG/LTR) compensator. Preliminary results indicate that the proposed control system can reject persistent disturbances of greater magnitude by utilizing most of the available control, while limiting the structural displacements to within desired tolerances.

  7. Structural and functional maturation of active zones in large synapses.

    PubMed

    Cano, Raquel; Torres-Benito, Laura; Tejero, Rocío; Biea, Anca I; Ruiz, Rocío; Betz, William J; Tabares, Lucía

    2013-02-01

    Virtually all functions of the nervous system rely upon synapses, the sites of communication between neurons and between neurons and other cells. Synapses are complex structures, each one comprising hundreds of different types of molecules working in concert. They are organized by adhesive and scaffolding molecules that align presynaptic vesicular release sites, namely, active zones, with postsynaptic neurotransmitter receptors, thereby allowing rapid and reliable intercellular communication. Most synapses are relatively small, and acting alone exerts little effect on their postsynaptic partners. Some, however, are much larger and stronger, reliably driving the postsynaptic cell to its action potential threshold, acting essentially as electrical relays of excitation. These large synapses are among the best understood, and two of these are the subject of this review, namely, the vertebrate neuromuscular junction and the calyx of Held synapse in the mammalian auditory pathway of the brain stem. Both synapses undergo through a complex and well-coordinated maturation process, during which time the molecular elements and the biophysical properties of the secretory machinery are continuously adjusted to the synapse size and to the functional requirements. We here review the morphological and functional changes occurring during postnatal maturation, noting particular similarities and differences between these two large synapses.

  8. Drop impact on a fiber

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Gil; Kim, Wonjung

    2016-04-01

    We present the results of a combined experimental and theoretical investigation of drop impact on a thin fiber. Using high-speed videography, we analyze the dynamics of droplet collision with a fiber. Based on the systematic experiments, we identify three outcomes of collision: capturing, single drop falling, and splitting. The outcomes are presented in a regime map, where the regime boundaries are explained through a scale analysis of forces. We also measure the liquid retention on the fiber after the droplet impact. By considering a liquid film on the fiber, we develop a mechanical model that predicts the residual water mass. Our model reveals that the residual mass depends critically on the fiber thickness and less on the impact speed. Our study can be extended to predicting the remaining droplet, critical problems in air filtration, water collection, and fiber coating.

  9. Large-Aperture Membrane Active Phased-Array Antennas

    NASA Technical Reports Server (NTRS)

    Karasik, Boris; McGrath, William; Leduc, Henry

    2009-01-01

    Large-aperture phased-array microwave antennas supported by membranes are being developed for use in spaceborne interferometric synthetic aperture radar systems. There may also be terrestrial uses for such antennas supported on stationary membranes, large balloons, and blimps. These antennas are expected to have areal mass densities of about 2 kg/sq m, satisfying a need for lightweight alternatives to conventional rigid phased-array antennas, which have typical areal mass densities between 8 and 15 kg/sq m. The differences in areal mass densities translate to substantial differences in total mass in contemplated applications involving aperture areas as large as 400 sq m. A membrane phased-array antenna includes patch antenna elements in a repeating pattern. All previously reported membrane antennas were passive antennas; this is the first active membrane antenna that includes transmitting/receiving (T/R) electronic circuits as integral parts. Other integral parts of the antenna include a network of radio-frequency (RF) feed lines (more specifically, a corporate feed network) and of bias and control lines, all in the form of flexible copper strip conductors on flexible polymeric membranes. Each unit cell of a prototype antenna (see Figure 1) contains a patch antenna element and a compact T/R module that is compatible with flexible membrane circuitry. There are two membrane layers separated by a 12.7-mm air gap. Each membrane layer is made from a commercially available flexible circuit material that, as supplied, comprises a 127-micron-thick polyimide dielectric layer clad on both sides with 17.5-micron-thick copper layers. The copper layers are patterned into RF, bias, and control conductors. The T/R module is located on the back side of the ground plane and is RF-coupled to the patch element via a slot. The T/R module is a hybrid multilayer module assembled and packaged independently and attached to the membrane array. At the time of reporting the information for

  10. Spatiotemporal dynamics of large-scale brain activity

    NASA Astrophysics Data System (ADS)

    Neuman, Jeremy

    Understanding the dynamics of large-scale brain activity is a tough challenge. One reason for this is the presence of an incredible amount of complexity arising from having roughly 100 billion neurons connected via 100 trillion synapses. Because of the extremely high number of degrees of freedom in the nervous system, the question of how the brain manages to properly function and remain stable, yet also be adaptable, must be posed. Neuroscientists have identified many ways the nervous system makes this possible, of which synaptic plasticity is possibly the most notable one. On the other hand, it is vital to understand how the nervous system also loses stability, resulting in neuropathological diseases such as epilepsy, a disease which affects 1% of the population. In the following work, we seek to answer some of these questions from two different perspectives. The first uses mean-field theory applied to neuronal populations, where the variables of interest are the percentages of active excitatory and inhibitory neurons in a network, to consider how the nervous system responds to external stimuli, self-organizes and generates epileptiform activity. The second method uses statistical field theory, in the framework of single neurons on a lattice, to study the concept of criticality, an idea borrowed from physics which posits that in some regime the brain operates in a collectively stable or marginally stable manner. This will be examined in two different neuronal networks with self-organized criticality serving as the overarching theme for the union of both perspectives. One of the biggest problems in neuroscience is the question of to what extent certain details are significant to the functioning of the brain. These details give rise to various spatiotemporal properties that at the smallest of scales explain the interaction of single neurons and synapses and at the largest of scales describe, for example, behaviors and sensations. In what follows, we will shed some

  11. Modelling large scale human activity in San Francisco

    NASA Astrophysics Data System (ADS)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  12. Large-scale field trials of active immunizing agents

    PubMed Central

    Cockburn, W. Charles

    1955-01-01

    In this discussion of the methods to be used in large-scale field trials of active immunizing agents and of the results to be expected from such trials, special emphasis is laid on pertussis vaccine trials in Great Britain. After a review of the criteria for strictly controlled field studies and of the investigation of typhoid vaccines conducted in 1904-08 by the Antityphoid Committee of the British Army, the author describes the pertussis vaccine studies which have been and are now being carried by the Whooping-Cough Immunization Committee of the Medical Research Council of Great Britain. The original strictly controlled trials have been completed and the results published. Studies are now being made of vaccines prepared by different methods and evaluated both in the field and in the laboratory. Each vaccine is given to some 2000-3000 children of 4-6 months to 4 years of age. By the end of the studies 30 000-40 000 children will have been followed up for a period of two years. Since in the current studies all the children are vaccinated and none are left as unvaccinated controls, the relative and not the absolute protective value of the vaccines will be measured. PMID:13270079

  13. Droplet impact on a fiber

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Gil; Kim, Taehong; Kim, Wonjung

    2015-11-01

    We present the results of a combined experimental and theoretical investigation of drop impact on a fiber. We use high-speed videography to characterize the dynamics of drops impacting fibers. Our systematical experiments reveal that the outcome of droplet collision critically depends on the relative magnitude of inertial to capillary forces and the ratio of the thickness of fiber to the diameter of the drop. We identify three outcomes of the collision using a non-dimensional regime map. The selection among the modes of single capturing, single drop falling, and divided drop falling is explained through a scale analysis of forces. We also examine the droplet retention on the fiber after impact. For each mode, we suggest the mathematical models to predict the amount of residual water on the fiber. Our study can be extended to predicting the remaining droplet, the critical problem in air filtration, water collection, and fiber coating. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (2009-0083510).

  14. Is Active Learning Like Broccoli? Student Perceptions of Active Learning in Large Lecture Classes

    ERIC Educational Resources Information Center

    Smith, C. Veronica; Cardaciotto, LeeAnn

    2011-01-01

    Although research suggests that active learning is associated with positive outcomes (e.g., memory, test performance), use of such techniques can be difficult to implement in large lecture-based classes. In the current study, 1,091 students completed out-of-class group exercises to complement course material in an Introductory Psychology class.…

  15. Multistability in Large Scale Models of Brain Activity

    PubMed Central

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-01-01

    Noise driven exploration of a brain network’s dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network’s capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain’s dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system’s attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the “resting state” condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  16. Reliability issues in active control of large flexible space structures

    NASA Technical Reports Server (NTRS)

    Vandervelde, W. E.

    1983-01-01

    The unreliability of control system components was investigated in our attempt to deal with that problem. This matter is of concern in large space structure control because of the large number of components required to achieve specified performance in some situations, and the long operating period required between maintenance visits. The detection and isolation of component failures during system operation, and algorithms for reconfiguring control systems following detection and isolation of a failure were emphasized.

  17. Large Strain Transparent Magneto-Active Polymer Nanocomposites

    NASA Technical Reports Server (NTRS)

    Yoonessi, Mitra (Inventor); Meador, Michael A (Inventor)

    2016-01-01

    A large strain polymer nanocomposite actuator is provided that upon subjected to an external stimulus, such as a magnetic field (static or electromagnetic field), an electric field, thermal energy, light, etc., will deform to thereby enable mechanical manipulations of structural components in a remote and wireless manner.

  18. ActiveSeismoPick3D - automatic first arrival determination for large active seismic arrays

    NASA Astrophysics Data System (ADS)

    Paffrath, Marcel; Küperkoch, Ludger; Wehling-Benatelli, Sebastian; Friederich, Wolfgang

    2016-04-01

    We developed a tool for automatic determination of first arrivals in active seismic data based on an approach, that utilises higher order statistics (HOS) and the Akaike information criterion (AIC), commonly used in seismology, but not in active seismics. Automatic picking is highly desirable in active seismics as the number of data provided by large seismic arrays rapidly exceeds of what an analyst can evaluate in a reasonable amount of time. To bring the functionality of automatic phase picking into the context of active data, the software package ActiveSeismoPick3D was developed in Python. It uses a modified algorithm for the determination of first arrivals which searches for the HOS maximum in unfiltered data. Additionally, it offers tools for manual quality control and postprocessing, e.g. various visualisation and repicking functionalities. For flexibility, the tool also includes methods for the preparation of geometry information of large seismic arrays and improved interfaces to the Fast Marching Tomography Package (FMTOMO), which can be used for the prediction of travel times and inversion for subsurface properties. Output files are generated in the VTK format, allowing the 3D visualization of e.g. the inversion results. As a test case, a data set consisting of 9216 traces from 64 shots was gathered, recorded at 144 receivers deployed in a regular 2D array of a size of 100 x 100 m. ActiveSeismoPick3D automatically checks the determined first arrivals by a dynamic signal to noise ratio threshold. From the data a 3D model of the subsurface was generated using the export functionality of the package and FMTOMO.

  19. Biofidelic Human Activity Modeling and Simulation with Large Variability

    DTIC Science & Technology

    2014-11-25

    capture data to replicate a human activity in 3D space. Since technologies for simultaneously capturing human motion and dynamic shapes are not yet ready...for practical use, a motion capture system can be used to capture markers on the body during motion and a 3D body scanner can be used to capture the...animation-capable model that can replicate a human activity in 3D space with the true shape and true motion of a human. Using this approach, a model

  20. Hydrodynamic Coating of a Fiber

    NASA Astrophysics Data System (ADS)

    Quéré, D.; de Ryck, A.

    We discuss how a solid (especially a fiber) is coated when drawn out of a bath of liquid. 1. For slow withdrawals out of pure viscous liquids, the data are found to be fitted by the famous Landau law: then, the coating results from a balance between viscosity and capillarity. For quicker withdrawals, the thickness of the entrained film suddenly diverges, at a velocity on order 1 m/s. Inertia is shown to be responsible for this effect. At still higher velocities, the thickness decreases with the velocity because the solid can only entrain the viscous boundary layer. 2. For complex fluids, surface effects are found in the low velocity regime: out of a surfactant solution, films are thicker than predicted by Landau, by a factor of order 2. The thickening factor is shown to be fixed by the Marangoni flow due to the presence of surfactants; out of an emulsion, the film can be enriched with oil , which can be understood by a simple model of capture; out of a polymer solution, a strong swelling of the film is observed if normal stresses are present. Hence, the problem has two families of solution: (i) at low velocity, the thickness of the layer is fixed by a balance between viscous and surface forces and thus is sensitive to the presence of surfactants, or other heterogeneities; (ii) at high velocity, inertia must be considered and the film thickness is fixed by the bulk properties of the liquid (density and viscosity). In these regimes, it is not affected by the presence of surfactants in the bath. Nous décrivons le dépôt de liquide sur un solide (le plus souvent une fibre) qui advient quand on tire ce solide d'un bain. 1. Si le retrait se fait lentement hors d'un liquide pur et visqueux, les données expérimentales suivent la loi de Landau : le dépôt résulte d'un compromis entre forces visqueuses et forces capillaires. Pour des retraits plus rapides, on observe que l'épaisseur du dépôt diverge, pour une vitesse de l'ordre du mètre par seconde. Nous montrons

  1. Active Commuting Patterns at a Large, Midwestern College Campus

    ERIC Educational Resources Information Center

    Bopp, Melissa; Kaczynski, Andrew; Wittman, Pamela

    2011-01-01

    Objective: To understand patterns and influences on active commuting (AC) behavior. Participants: Students and faculty/staff at a university campus. Methods: In April-May 2008, respondents answered an online survey about mode of travel to campus and influences on commuting decisions. Hierarchical regression analyses predicted variance in walking…

  2. Transparent Large Strain Thermoplastic Polyurethane Magneto-Active Nanocomposites

    NASA Technical Reports Server (NTRS)

    Yoonessi, Mitra; Carpen, Ileana; Peck, John; Sola, Francisco; Bail, Justin; Lerch, Bradley; Meador, Michael

    2010-01-01

    Smart adaptive materials are an important class of materials which can be used in space deployable structures, morphing wings, and structural air vehicle components where remote actuation can improve fuel efficiency. Adaptive materials can undergo deformation when exposed to external stimuli such as electric fields, thermal gradients, radiation (IR, UV, etc.), chemical and electrochemical actuation, and magnetic field. Large strain, controlled and repetitive actuation are important characteristics of smart adaptive materials. Polymer nanocomposites can be tailored as shape memory polymers and actuators. Magnetic actuation of polymer nanocomposites using a range of iron, iron cobalt, and iron manganese nanoparticles is presented. The iron-based nanoparticles were synthesized using the soft template (1) and Sun's (2) methods. The nanoparticles shape and size were examined using TEM. The crystalline structure and domain size were evaluated using WAXS. Surface modifications of the nanoparticles were performed to improve dispersion, and were characterized with IR and TGA. TPU nanocomposites exhibited actuation for approximately 2wt% nanoparticle loading in an applied magnetic field. Large deformation and fast recovery were observed. These nanocomposites represent a promising potential for new generation of smart materials.

  3. Large-Scale Activity Initiated BY Halo CMEs

    NASA Astrophysics Data System (ADS)

    Chertok, I.; Grechnev, V.

    We summarize results of our recent studies of CME-associated EUV dimmings and coronal waves by `derotated' fixed-difference SOHO/EIT heliograms at 195 Å with 12-min intervals and at 171, 195, 284, 304 Å with 6-h intervals. Correctness of the derotated fixed-difference technique is confirmed by the consideration of the Bastille Day 2000 event. We also demonstrate that long narrow channeled dimmings and anisotropic coronal waves are typical of the complex global solar magnetosphere near the solar cycle maximum. Homology of large-scale dimmings and coronal waves takes place in a series of recurrent eruptive events. Along with dimmings coinciding entirely or partially in all four EIT bands, there exist dimmings that appear different, mainly in the transition-region line of 304 Å and high-temperature coronal line of 284 Å.

  4. When and how to activate large new hydropower reservoirs

    NASA Astrophysics Data System (ADS)

    Geressu, Robel; Harou, Julien

    2016-04-01

    Water resources system planners are increasingly required to address multiple long and short-term management objectives and the trade-offs these imply. Expansion planning in hydropower reservoir systems, where assets either temporarily or permanently reduce each other's performance, is a complex and potentially conflictual task requiring attention to multiple impacts. This paper proposes a multi-criteria scheduling approach considering many objectives and their associated uncertainties. The method considers the coordination and flexibility of reservoir operation in different expansion stages. The impact of abstraction (i.e., during filling of new reservoirs) and regulation of inflows by upstream reservoirs, is represented by simultaneously optimizing the storage size of reservoirs. Sensitivity analysis of performance given financial uncertainty and hydrological variability reveals which expansion schedules are robust to a wide range of future conditions. This informs how alternative designs compare in multiple performance dimensions and can serve stakeholders with differing attitudes towards risk and opportunity. The method is applied to proposed Blue Nile hydropower reservoirs to find efficient new dam activation schedules considering energy revenues, downstream release requirements, and energy generation during reservoir filling periods. Results take the form of Pareto-optimal trade-offs where each point on the curve or surface represents asset choices, size, activation date, and filling period reservoir operating rules. The results help explore the complex planning and management issues involved in the Blue Nile and demonstrate a possible approach to negotiate the design, filling and coordinated use of hydropower reservoirs.

  5. LARGE PARTICLES IN ACTIVE ASTEROID P/2010 A2

    SciTech Connect

    Jewitt, David; Ishiguro, Masateru; Agarwal, Jessica

    2013-02-10

    The previously unknown asteroid P/2010 A2 rose to prominence in 2010 by forming a transient, comet-like tail consisting of ejected dust. The observed dust production was interpreted as the result of either a hypervelocity impact with a smaller body or a rotational disruption. We have re-observed this object, finding that large particles remain a full orbital period after the initial outburst. In the intervening years, particles smaller than {approx}3 mm in radius have been dispersed by radiation pressure, leaving only larger particles in the trail. Since the total mass is dominated by the largest particles, the radiation pressure filtering allows us to obtain a more reliable estimate of the debris mass than was previously possible. We find that the mass contained in the debris is {approx}5 Multiplication-Sign 10{sup 8} kg (assumed density 3000 kg m{sup -3}), the ratio of the total debris mass to the nucleus mass is {approx}0.1, and that events like P/2010 A2 contribute <3% to the Zodiacal dust production rate. Physical properties of the nucleus and debris are also determined.

  6. Multidisciplinary analysis of actively controlled large flexible spacecraft

    NASA Technical Reports Server (NTRS)

    Cooper, Paul A.; Young, John W.; Sutter, Thomas R.

    1986-01-01

    The control of Flexible Structures (COFS) program has supported the development of an analysis capability at the Langley Research Center called the Integrated Multidisciplinary Analysis Tool (IMAT) which provides an efficient data storage and transfer capability among commercial computer codes to aid in the dynamic analysis of actively controlled structures. IMAT is a system of computer programs which transfers Computer-Aided-Design (CAD) configurations, structural finite element models, material property and stress information, structural and rigid-body dynamic model information, and linear system matrices for control law formulation among various commercial applications programs through a common database. Although general in its formulation, IMAT was developed specifically to aid in the evaluation of the structures. A description of the IMAT system and results of an application of the system are given.

  7. Active assembly for large-scale manufacturing of integrated nanostructures.

    SciTech Connect

    Spoerke, Erik David; Bunker, Bruce Conrad; Orendorff, Christopher J.; Bachand, George David; Hendricks, Judy K.; Matzke, Carolyn M.

    2007-01-01

    Microtubules and motor proteins are protein-based biological agents that work cooperatively to facilitate the organization and transport of nanomaterials within living organisms. This report describes the application of these biological agents as tools in a novel, interdisciplinary scheme for assembling integrated nanostructures. Specifically, selective chemistries were used to direct the favorable adsorption of active motor proteins onto lithographically-defined gold electrodes. Taking advantage of the specific affinity these motor proteins have for microtubules, the motor proteins were used to capture polymerized microtubules out of suspension to form dense patterns of microtubules and microtubule bridges between gold electrodes. These microtubules were then used as biofunctionalized templates to direct the organization of functionalized nanocargo including single-walled carbon nanotubes and gold nanoparticles. This biologically-mediated scheme for nanomaterials assembly has shown excellent promise as a foundation for developing new biohybrid approaches to nanoscale manufacturing.

  8. Measurements in large pool fires with an actively cooled calorimeter

    SciTech Connect

    Koski, J.A.; Wix, S.D.

    1995-12-31

    The pool fire thermal test described in Safety Series 6 published by the International Atomic Energy Agency (IAEA) or Title 10, Code of Federal Regulations, Part 71 (10CFR71) in the United States is one of the most difficult tests that a container for larger ``Type B`` quantities of nuclear materials must pass. If retests of a container are required, costly redesign and project delays can result. Accurate measurements and modeling of the pool fire environment will ultimately lower container costs by assuring that containers past the pool fire test on the first attempt. Experiments indicate that the object size or surface temperature of the container can play a role in determining local heat fluxes that are beyond the effects predicted from the simple radiative heat transfer laws. An analytical model described by Nicolette and Larson 1990 can be used to understand many of these effects. In this model a gray gas represents soot particles present in the flame structure. Close to the container surface, these soot particles are convectively and radiatively cooled and interact with incident energy from the surrounding fire. This cooler soot cloud effectively prevents some thermal radiation from reaching the container surface, reducing the surface heat flux below the value predicted by a transparent medium model. With some empirical constants, the model suggested by Nicolette and Larson can be used to more accurately simulate the pool fire environment. Properly formulated, the gray gas approaches also fast enough to be used with standard commercial computer codes to analyze shipping containers. To calibrate this type of model, accurate experimental measurements of radiative absorption coefficients, flame temperatures, and other parameters are necessary. A goal of the calorimeter measurements described here is to obtain such parameters so that a fast, useful design tool for large pool fires can be constructed.

  9. Analysis and Management of Large-Scale Activities Based on Interface

    NASA Astrophysics Data System (ADS)

    Yang, Shaofan; Ji, Jingwei; Lu, Ligang; Wang, Zhiyi

    Based on the concepts of system safety engineering, life-cycle and interface that comes from American system safety standard MIL-STD-882E, and apply them to the process of risk analysis and management of large-scale activities. Identify the involved personnel, departments, funds and other contents throughout the life cycle of large-scale activities. Recognize and classify the ultimate risk sources of people, objects and environment of large-scale activities from the perspective of interface. Put forward the accident cause analysis model according to the previous large-scale activities' accidents and combine with the analysis of the risk source interface. Analyze the risks of each interface and summary various types of risks the large-scale activities faced. Come up with the risk management consciousness, policies and regulations, risk control and supervision departments improvement ideas.

  10. A novel method for the activity measurement of large-area beta reference sources.

    PubMed

    Stanga, D; De Felice, P; Keightley, J; Capogni, M; Ioan, M R

    2016-03-01

    A novel method has been developed for the activity measurement of large-area beta reference sources. It makes use of two emission rate measurements and is based on the weak dependence between the source activity and the activity distribution for a given value of transmission coefficient. The method was checked experimentally by measuring the activity of two ((60)Co and (137)Cs) large-area reference sources constructed from anodized aluminum foils. Measurement results were compared with the activity values measured by gamma spectrometry. For each source, they agree within one standard uncertainty and also agree within the same limits with the certified values of the source activity.

  11. [Coordination of the myoelectrical activity of the large and small intestine].

    PubMed

    Lychkova, A E

    2012-01-01

    Coordination of the myoelectrical activity of the large and small intestine was studied. Pacemaker cells of intestine are predominantly located at the proximal divisions of large and small intestine and have an increased spontaneous slow-wave activity, which ensures the distribution of excitation in smooth muscle underlying intestines. Due to the ileocecal coordination by sequential motor activity of small and large intestine is provided. The distal direction gradient of slow waves frequency reduction was established. Pacemaker cells possess certain structural specificity and is specialized in the spontaneous bioelectric activity.

  12. Large space antenna communications systems: Integrated Langley Research Center/Jet Propulsion Laboratory development activities. 2: Langley Research Center activities

    NASA Technical Reports Server (NTRS)

    Cambell, T. G.; Bailey, M. C.; Cockrell, C. R.; Beck, F. B.

    1983-01-01

    The electromagnetic analysis activities at the Langley Research Center are resulting in efficient and accurate analytical methods for predicting both far- and near-field radiation characteristics of large offset multiple-beam multiple-aperture mesh reflector antennas. The utilization of aperture integration augmented with Geometrical Theory of Diffraction in analyzing the large reflector antenna system is emphasized.

  13. Research on elastic large space structures as "plants' for active control

    NASA Technical Reports Server (NTRS)

    Ashley, H.; Vonflotow, A.

    1983-01-01

    Research on active control of large space structures is discussed. Intrinsic damping in monolithic metallic structures is discussed. Thermal relaxation and grain boundary relaxation are discussed, as are properties of thermal damping.

  14. A Fundamental Study for Efficient Implementaion of Online Collaborative Activities in Large-Scale Classes

    ERIC Educational Resources Information Center

    Matsuba, Ryuichi; Suzuki, Yusei; Kubota, Shin-Ichiro; Miyazaki, Makoto

    2015-01-01

    We study tactics for writing skills development through cross-disciplinary learning in online large-scale classes, and particularly are interested in implementation of online collaborative activities such as peer reviewing of writing. The goal of our study is to carry out collaborative works efficiently via online effectively in large-scale…

  15. Implementing Experiential Learning Activities in a Large Enrollment Introductory Food Science and Human Nutrition Course

    ERIC Educational Resources Information Center

    Bohn, Dawn M.; Schmidt, Shelly J.

    2008-01-01

    Experiential learning activities are often viewed as impractical, and potentially unfeasible, instructional tools to employ in a large enrollment course. Research has shown, though, that the metacognitive skills that students utilize while participating in experiential learning activities enable them to assess their true level of understanding and…

  16. Introductory Biology Courses: A Framework to Support Active Learning in Large Enrollment Introductory Science Courses

    ERIC Educational Resources Information Center

    Smith, Ann C.; Stewart, Richard; Shields, Patricia; Hayes-Klosteridis, Jennifer; Robinson, Paulette; Yuan, Robert

    2005-01-01

    Active learning and research-oriented activities have been increasingly used in smaller, specialized science courses. Application of this type of scientific teaching to large enrollment introductory courses has been, however, a major challenge. The general microbiology lecture/laboratory course described has been designed to incorporate published…

  17. ActivitySim: large-scale agent based activity generation for infrastructure simulation

    SciTech Connect

    Gali, Emmanuel; Eidenbenz, Stephan; Mniszewski, Sue; Cuellar, Leticia; Teuscher, Christof

    2008-01-01

    The United States' Department of Homeland Security aims to model, simulate, and analyze critical infrastructure and their interdependencies across multiple sectors such as electric power, telecommunications, water distribution, transportation, etc. We introduce ActivitySim, an activity simulator for a population of millions of individual agents each characterized by a set of demographic attributes that is based on US census data. ActivitySim generates daily schedules for each agent that consists of a sequence of activities, such as sleeping, shopping, working etc., each being scheduled at a geographic location, such as businesses or private residences that is appropriate for the activity type and for the personal situation of the agent. ActivitySim has been developed as part of a larger effort to understand the interdependencies among national infrastructure networks and their demand profiles that emerge from the different activities of individuals in baseline scenarios as well as emergency scenarios, such as hurricane evacuations. We present the scalable software engineering principles underlying ActivitySim, the socia-technical modeling paradigms that drive the activity generation, and proof-of-principle results for a scenario in the Twin Cities, MN area of 2.6 M agents.

  18. Large-scale assessment of activity landscape feature probabilities of bioactive compounds.

    PubMed

    Kayastha, Shilva; Dimova, Dilyana; Iyer, Preeti; Vogt, Martin; Bajorath, Jürgen

    2014-02-24

    Activity landscape representations integrate pairwise compound similarity and potency relationships and provide direct access to characteristic structure-activity relationship features in compound data sets. Because pairwise compound comparisons provide the foundation of activity landscape design, the assessment of specific landscape features such as activity cliffs has generally been confined to the level of compound pairs. A conditional probability-based approach has been applied herein to assign most probable activity landscape features to individual compounds. For example, for a given data set compound, it was determined if it would preferentially engage in the formation of activity cliffs or other landscape features. In a large-scale effort, we have determined conditional activity landscape feature probabilities for more than 160,000 compounds with well-defined activity annotations contained in 427 different target-based data sets. These landscape feature probabilities provide a detailed view of how different activity landscape features are distributed over currently available bioactive compounds.

  19. Structural-optical integrated analysis on the large aperture mirror with active mounting

    NASA Astrophysics Data System (ADS)

    Ren, Zhiyuan; Zhu, Jianqiang; Liu, Zhigang

    2016-11-01

    Deformation of the large aperture mirror caused by the external environment load seriously affects the optical performance of the optical system, and there is a limit to develop the shape quality of large aperture mirror with traditional mounting method. It is effective way to reduce the optical mirror distortion with active support method, and the structural-optical integrated method is the effective means to assess the merits of the mounting for large aperture mirror. Firstly, we proposes a new support scheme that uses specific boundary constraints on the large lens edges and imposes flexible torque to resist deformation induced by gravity to improve surface quantity of large aperture mirror. We calculate distortion of the large aperture mirror at the edges of the flexible torque respectively with the finite element method; secondly, we extract distortion value within clear aperture of the mirror with MATLAB, solve the corresponding Zernike polynomial coefficients; lastly, we obtain the peak-valley value (PV) and root mean square value (RMS) with optical-structural integrated analysis . The results for the 690x400x100mm mirror show that PV and RMS values within the clear aperture with 0.4MPa torques than the case without applying a flexible torque reduces 82.7% and 72.9% respectively. The active mounting on the edge of the large aperture mirror can greatly improve the surface quality of the large aperture mirror.

  20. A large-conductance calcium-activated potassium channel in potato (Solanum tuberosum) tuber mitochondria.

    PubMed

    Koszela-Piotrowska, Izabela; Matkovic, Karolina; Szewczyk, Adam; Jarmuszkiewicz, Wieslawa

    2009-11-11

    In the present study, we describe the existence of a novel potassium channel in the plant [potato (Solanum tuberosum) tuber] mitochondrial inner membrane. We found that substances known to modulate large-conductance calcium-activated potassium channel activity influenced the bioenergetics of potato tuber mitochondria. In isolated mitochondria, Ca2+ and NS1619 {1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-ben-zimidazole-2-one; a potassium channel opener} were found to depolarize the mitochondrial membrane potential and to stimulate resting respiration. These effects were blocked by iberiotoxin (a potassium channel inhibitor) in a potassium-dependent manner. Additionally, the electrophysiological properties of the large-conductance potassium channel present in the potato tuber inner mitochondrial membrane are described in a reconstituted system, using planar lipid bilayers. After incorporation in 50/450 mM KCl gradient solutions, we recorded large-conductance potassium channel activity with conductance from 502+/-15 to 615+/-12 pS. The probability of channel opening was increased by Ca2+ and reduced by iberiotoxin. Immunological analysis with antibodies raised against the mammalian plasma-membrane large-conductance Ca2+-dependent K+ channel identified a pore-forming alpha subunit and an auxiliary beta2 subunit of the channel in potato tuber mitochondrial inner membrane. These results suggest that a large-conductance calcium-activated potassium channel similar to that of mammalian mitochondria is present in potato tuber mitochondria.

  1. Large sample neutron activation analysis: a challenge in cultural heritage studies.

    PubMed

    Stamatelatos, Ion E; Tzika, Faidra

    2007-07-01

    Large sample neutron activation analysis compliments and significantly extends the analytical tools available for cultural heritage and authentication studies providing unique applications of non-destructive, multi-element analysis of materials that are too precious to damage for sampling purposes, representative sampling of heterogeneous materials or even analysis of whole objects. In this work, correction factors for neutron self-shielding, gamma-ray attenuation and volume distribution of the activity in large volume samples composed of iron and ceramic material were derived. Moreover, the effect of inhomogeneity on the accuracy of the technique was examined.

  2. Ages of calderas, large explosive craters and active volcanoes in the Kuril-Kamchatka region, Russia

    NASA Astrophysics Data System (ADS)

    Braitseva, O. A.; Melekestsev, I. V.; Ponomareva, V. V.; Sulerzhitsky, L. D.

    1995-12-01

    The ages of most of calderas, large explosive craters and active volcanoes in the Kuril-Kamchatka region have been determined by extensive geological, geomorphological, tephrochronological and isotopic geochronological studies, including more than 600 14C dates. Eight ‘Krakatoa-type’ and three ‘Hawaiian-type’ calderas and no less than three large explosive craters formed here during the Holocene. Most of the Late Pleistocene Krakatoa-type calderas were established around 30 000 40 000 years ago. The active volcanoes are geologically very young, with maximum ages of about 40 000 50 000 years. The overwhelming majority of recently active volcanic cones originated at the very end of the Late Pleistocene or in the Holocene. These studies show that all Holocene stratovolcanoes in Kamchatka were emplaced in the Holocene only in the Eastern volcanic belt. Periods of synchronous, intensified Holocene volcanic activity occurred within the time intervals of 7500 7800 and 1300 1800 14C years BP.

  3. Coherence and information in a fiber interferometer

    NASA Astrophysics Data System (ADS)

    Kellerer, Aglaé; Wright, Sidney; Lacour, Sylvestre

    2017-01-01

    We present an experiment based on a fibered Mach-Zehnder interferometer, with the aim of familiarizing students with fibered optics and interferometry, and of improving their understanding of optical amplification. The laboratory project has two parts. In the first, students modulate the optical path of the interferometer to study the spectra of light sources via Fourier Transform Spectroscopy. In the second, an optical amplifier is placed in one or both arms of the interferometer. The set-up uses monomode, polarization-maintaining fibers that propagate light with a wavelength of 1.5 μm. Here, we describe the set-up and the analysis of the measurements, and we present results from student reports.

  4. Support of an Active Science Project by a Large Information System: Lessons for the EOS Era

    NASA Technical Reports Server (NTRS)

    Angelici, Gary L.; Skiles, J. W.; Popovici, Lidia Z.

    1993-01-01

    The ability of large information systems to support the changing data requirements of active science projects is being tested in a NASA collaborative study. This paper briefly profiles both the active science project and the large information system involved in this effort and offers some observations about the effectiveness of the project support. This is followed by lessons that are important for those participating in large information systems that need to support active science projects or that make available the valuable data produced by these projects. We learned in this work that it is difficult for a large information system focused on long term data management to satisfy the requirements of an on-going science project. For example, in order to provide the best service, it is important for all information system staff to keep focused on the needs and constraints of the scientists in the development of appropriate services. If the lessons learned in this and other science support experiences are not applied by those involved with large information systems of the EOS (Earth Observing System) era, then the final data products produced by future science projects may not be robust or of high quality, thereby making the conduct of the project science less efficacious and reducing the value of these unique suites of data for future research.

  5. Implementation and Evaluation of a Values Clarification Activity for a Large Undergraduate Human Sexuality Course

    ERIC Educational Resources Information Center

    Lederer, Alyssa M.

    2016-01-01

    Values clarification is an important tool that helps individuals to clarify their beliefs about sexuality-related issues. This lesson plan provides instructions for a 1-hour values clarification activity for a large undergraduate human sexuality course that serves as an introduction to course content and tone, stimulates students' initial thinking…

  6. A Simple and Effective Protein Folding Activity Suitable for Large Lectures

    ERIC Educational Resources Information Center

    White, Brian

    2006-01-01

    This article describes a simple and inexpensive hands-on simulation of protein folding suitable for use in large lecture classes. This activity uses a minimum of parts, tools, and skill to simulate some of the fundamental principles of protein folding. The major concepts targeted are that proteins begin as linear polypeptides and fold to…

  7. Active Learning in a Large Medical Classroom Setting for Teaching Renal Physiology

    ERIC Educational Resources Information Center

    Dietz, John R.; Stevenson, Frazier T.

    2011-01-01

    In this article, the authors describe an active learning exercise which has been used to replace some lecture hours in the renal portion of an integrated, organ system-based curriculum for first-year medical students. The exercise takes place in a large auditorium with ~150 students. The authors, who are faculty members, lead the discussions,…

  8. Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

    PubMed Central

    Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

    2014-01-01

    Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

  9. Reported frequency of physical activity in a large epidemiological study: relationship to specific activities and repeatability over time

    PubMed Central

    2011-01-01

    Background How overall physical activity relates to specific activities and how reported activity changes over time may influence interpretation of observed associations between physical activity and health. We examine the relationships between various physical activities self-reported at different times in a large cohort study of middle-aged UK women. Methods At recruitment, Million Women Study participants completed a baseline questionnaire including questions on frequency of strenuous and of any physical activity. About 3 years later 589,896 women also completed a follow-up questionnaire reporting the hours they spent on a range of specific activities. Time spent on each activity was used to estimate the associated excess metabolic equivalent hours (MET-hours) and this value was compared across categories of physical activity reported at recruitment. Additionally, 18,655 women completed the baseline questionnaire twice, at intervals of up to 4 years; repeatability over time was assessed using the weighted kappa coefficient (κweighted) and absolute percentage agreement. Results The average number of hours per week women reported doing specific activities was 14.0 for housework, 4.5 for walking, 3.0 for gardening, 0.2 for cycling, and 1.4 for all strenuous activity. Time spent and the estimated excess MET-hours associated with each activity increased with increasing frequency of any or strenuous physical activity reported at baseline (tests for trend, P < 0.003), although the associations for housework were by far the weakest (Spearman correlations, 0.01 and -0.03 respectively for housework, and 0.11-0.37 for all other activities). Repeatability of responses to physical activity questions on the baseline questionnaire declined significantly over time. For strenuous activity, absolute agreement was 64% (κweighted = 0.71) for questionnaires administered less than 6 months apart, and 52% (κweighted = 0.51) for questionnaires more than 2 years apart. Corresponding

  10. Process effects on activated carbon with large specific surface area from corn cob.

    PubMed

    Cao, Qing; Xie, Ke-Chang; Lv, Yong-Kang; Bao, Wei-Ren

    2006-01-01

    The main factors that affect the large specific surface area (SSA) of the activated carbon from agricultural waste corn cobs were studied by chemically activated method with solution of KOH and soap which acted as surfactant. The experiment showed that not only the activation temperature, activation time and the mass ratio of KOH to the carbonized material, but also the activated methods using activator obviously influenced the SSA of activated carbon. The experimental operating conditions were as follows: the carbonized temperature being 450 degrees C and keeping time being 4 h using N2 as protective gas; the activation temperature being 850 degrees C and holding time being 1.2 h; the mass ratio of KOH to carbonized material being 4.0; the time of soaking carbonized material in the solution of KOH and soap being 30 min. Under the optimal conditions, the SSA of activated carbon from corn cobs reached 2700 m2/g. And the addition of the soap as surfactant may shorten the soaking time. The structure of the activated carbon prepared had narrow distribution of pore size and the micro-pores accounted for 78%. The advantages of the method described were easy and feasible.

  11. Large-scale filament formation inhibits the activity of CTP synthetase.

    PubMed

    Barry, Rachael M; Bitbol, Anne-Florence; Lorestani, Alexander; Charles, Emeric J; Habrian, Chris H; Hansen, Jesse M; Li, Hsin-Jung; Baldwin, Enoch P; Wingreen, Ned S; Kollman, Justin M; Gitai, Zemer

    2014-07-16

    CTP Synthetase (CtpS) is a universally conserved and essential metabolic enzyme. While many enzymes form small oligomers, CtpS forms large-scale filamentous structures of unknown function in prokaryotes and eukaryotes. By simultaneously monitoring CtpS polymerization and enzymatic activity, we show that polymerization inhibits activity, and CtpS's product, CTP, induces assembly. To understand how assembly inhibits activity, we used electron microscopy to define the structure of CtpS polymers. This structure suggests that polymerization sterically hinders a conformational change necessary for CtpS activity. Structure-guided mutagenesis and mathematical modeling further indicate that coupling activity to polymerization promotes cooperative catalytic regulation. This previously uncharacterized regulatory mechanism is important for cellular function since a mutant that disrupts CtpS polymerization disrupts E. coli growth and metabolic regulation without reducing CTP levels. We propose that regulation by large-scale polymerization enables ultrasensitive control of enzymatic activity while storing an enzyme subpopulation in a conformationally restricted form that is readily activatable.

  12. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions

    PubMed Central

    Luhmann, Heiko J.; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C.; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits. PMID:27252626

  13. Active Control of Combustion Instability in a Ramjet Using Large-Eddy Simulations

    DTIC Science & Technology

    1992-09-01

    INSTABILITY IN A RAMJET USING LARGE-EDDY SIMULATIONS S. Menon N.TIS CR.A,1i ()TiC TAB September 1992 1 , o -d 6 y ... . ... .. Prepared for t.Cft OFFICE OF...pressure oscillations initially show a large-aznplitude, low- frequency oscillatio that eventually decays o that a high-frequency oscillation at around...injec- tion were recently presented (M o ., 199•1) TP-276/02-91 10 4.1 Acsntlc Fedback Cesto l Active control through acoustic forcing was demonstrated

  14. A new robust adaptive controller for vibration control of active engine mount subjected to large uncertainties

    NASA Astrophysics Data System (ADS)

    Fakhari, Vahid; Choi, Seung-Bok; Cho, Chang-Hyun

    2015-04-01

    This work presents a new robust model reference adaptive control (MRAC) for vibration control caused from vehicle engine using an electromagnetic type of active engine mount. Vibration isolation performances of the active mount associated with the robust controller are evaluated in the presence of large uncertainties. As a first step, an active mount with linear solenoid actuator is prepared and its dynamic model is identified via experimental test. Subsequently, a new robust MRAC based on the gradient method with σ-modification is designed by selecting a proper reference model. In designing the robust adaptive control, structured (parametric) uncertainties in the stiffness of the passive part of the mount and in damping ratio of the active part of the mount are considered to investigate the robustness of the proposed controller. Experimental and simulation results are presented to evaluate performance focusing on the robustness behavior of the controller in the face of large uncertainties. The obtained results show that the proposed controller can sufficiently provide the robust vibration control performance even in the presence of large uncertainties showing an effective vibration isolation.

  15. Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma.

    PubMed

    Hailfinger, Stephan; Lenz, Georg; Ngo, Vu; Posvitz-Fejfar, Anita; Rebeaud, Fabien; Guzzardi, Montserrat; Penas, Eva-Maria Murga; Dierlamm, Judith; Chan, Wing C; Staudt, Louis M; Thome, Margot

    2009-11-24

    A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, the least curable subtype of DLBCL. Recent data suggest that MALT1 has proteolytic activity, but it is unknown whether this activity is relevant for tumor growth. Here we report that MALT1 is constitutively active in DLBCL lines of the ABC but not the GCB subtype. Inhibition of the MALT1 proteolytic activity led to reduced expression of growth factors and apoptosis inhibitors, and specifically affected the growth and survival of ABC DLBCL lines. These results demonstrate a key role for the proteolytic activity of MALT1 in DLBCL of the ABC subtype, and provide a rationale for the development of pharmacological inhibitors of MALT1 in DLBCL therapy.

  16. Function and regulation of large conductance Ca(2+)-activated K+ channel in vascular smooth muscle cells.

    PubMed

    Hu, Xiang-Qun; Zhang, Lubo

    2012-09-01

    Large conductance Ca(2+)-activated K(+) (BK(Ca)) channels are abundantly expressed in vascular smooth muscle cells. Activation of BK(Ca) channels leads to hyperpolarization of cell membrane, which in turn counteracts vasoconstriction. Therefore, BK(Ca) channels have an important role in regulation of vascular tone and blood pressure. The activity of BK(Ca) channels is subject to modulation by various factors. Furthermore, the function of BK(Ca) channels are altered in both physiological and pathophysiological conditions, such as pregnancy, hypertension and diabetes, which has dramatic impacts on vascular tone and hemodynamics. Consequently, compounds and genetic manipulation that alter activity and expression of the channel might be of therapeutic interest.

  17. Imaging large-scale cellular activity in spinal cord of freely behaving mice

    PubMed Central

    Sekiguchi, Kohei J.; Shekhtmeyster, Pavel; Merten, Katharina; Arena, Alexander; Cook, Daniela; Hoffman, Elizabeth; Ngo, Alexander; Nimmerjahn, Axel

    2016-01-01

    Sensory information from mechanoreceptors and nociceptors in the skin plays key roles in adaptive and protective motor behaviours. To date, very little is known about how this information is encoded by spinal cord cell types and their activity patterns, particularly under freely behaving conditions. To enable stable measurement of neuronal and glial cell activity in behaving mice, we have developed fluorescence imaging approaches based on two- and miniaturized one-photon microscopy. We show that distinct cutaneous stimuli activate overlapping ensembles of dorsal horn neurons, and that stimulus type and intensity is encoded at the single-cell level. In contrast, astrocytes show large-scale coordinated calcium responses to intense but not weak sensory inputs. Sensory-evoked activity is potently suppressed by anaesthesia. By revealing the cellular and computational logic of spinal cord networks under behaving conditions, our approach holds promise for better understanding of healthy and aberrant spinal cord processes. PMID:27121084

  18. Optical activities of large-area SU8 microspirals fabricated by multibeam holographic lithography.

    PubMed

    Wang, Xia; Gao, Wensheng; Hung, Jenny; Tam, Wing Yim

    2014-04-10

    We report on the fabrication of large-area microspirals in SU8 photoresist using a 6+1 beam holographic lithography (HL) technique involving the interference of six linearly polarized side beams and one circularly polarized central beam. In contrast to common photoresist-substrate (glass) configuration, the spirals are fabricated on a substrate with a precured thin SU8 photoresist. This SU8-SU8-glass configuration strengthens the attachment of the spirals to the substrate, and hence enhances the quality of the fabricated spirals. The fabricated SU8 microspirals exhibit large optical activities with a polarization rotation close to 10 deg and a circular dichroism of about 0.5 in the visible range. Our precured substrate method could lift the limitations of the HL method in fabricating large and uniform microstructures or nanostructures.

  19. Miniature microscopes for large-scale imaging of neuronal activity in freely behaving rodents.

    PubMed

    Ziv, Yaniv; Ghosh, Kunal K

    2015-06-01

    Recording neuronal activity in behaving subjects has been instrumental in studying how information is represented and processed by the brain. Recent advances in optical imaging and bioengineering have converged to enable time-lapse, cell-type specific recordings of neuronal activities from large neuronal populations in deep-brain structures of freely behaving rodents. We will highlight these advancements, with an emphasis on miniaturized integrated microscopy for large-scale imaging in freely behaving mice. This technology potentially enables studies that were difficult to perform using previous generation imaging and current electrophysiological techniques. These studies include longitudinal and population-level analyses of neuronal representations associated with different types of naturalistic behaviors and cognitive or emotional processes.

  20. CNTF-Treated Astrocyte Conditioned Medium Enhances Large-Conductance Calcium-Activated Potassium Channel Activity in Rat Cortical Neurons.

    PubMed

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

    2016-08-01

    Seizure activity is linked to astrocyte activation as well as dysfunctional cortical neuron excitability produced from changes in calcium-activated potassium (KCa) channel function. Ciliary neurotrophic factor-treated astrocyte conditioned medium (CNTF-ACM) can be used to investigate the peripheral effects of activated astrocytes upon cortical neurons. However, CNTF-ACM's effect upon KCa channel activity in cultured cortical neurons has not yet been investigated. Whole-cell patch clamp recordings were performed in rat cortical neurons to evaluate CNTF-ACM's effects upon charybdotoxin-sensitive large-conductance KCa (BK) channel currents and apamin-sensitive small-conductance KCa (SK) channel current. Biotinylation and RT-PCR were applied to assess CNTF-ACM's effects upon the protein and mRNA expression, respectively, of the SK channel subunits SK2 and SK3 and the BK channel subunits BKα1 and BKβ3. An anti-fibroblast growth factor-2 (FGF-2) monoclonal neutralizing antibody was used to assess the effects of the FGF-2 component of CNTF-ACM. CNTF-ACM significantly increased KCa channel current density, which was predominantly attributable to gains in BK channel activity (p < 0.05). CNTF-ACM produced a significant increase in BKα1 and BKβ3 expression (p < 0.05) but had no significant effect upon SK2 or SK3 expression (p > 0.05). Blocking FGF-2 produced significant reductions in KCa channel current density (p > 0.05) as well as BKα1 and BKβ3 expression in CNTF-ACM-treated neurons (p > 0.05). CNTF-ACM significantly enhances BK channel activity in rat cortical neurons and that FGF-2 is partially responsible for these effects. CNTF-induced astrocyte activation results in secretion of neuroactive factors which may affect neuronal excitability and resultant seizure activity in mammalian cortical neurons.

  1. CURRENT HELICITY OF ACTIVE REGIONS AS A TRACER OF LARGE-SCALE SOLAR MAGNETIC HELICITY

    SciTech Connect

    Zhang, H.; Gao, Y.; Xu, H.; Moss, D.; Kleeorin, N.; Rogachevskii, I.; Kuzanyan, K.; Sokoloff, D.

    2012-05-20

    We demonstrate that the current helicity observed in solar active regions traces the magnetic helicity of the large-scale dynamo generated field. We use an advanced two-dimensional mean-field dynamo model with dynamo saturation based on the evolution of the magnetic helicity and algebraic quenching. For comparison, we also studied a more basic two-dimensional mean-field dynamo model with simple algebraic alpha-quenching only. Using these numerical models we obtained butterfly diagrams both for the small-scale current helicity and also for the large-scale magnetic helicity, and compared them with the butterfly diagram for the current helicity in active regions obtained from observations. This comparison shows that the current helicity of active regions, as estimated by -A {center_dot} B evaluated at the depth from which the active region arises, resembles the observational data much better than the small-scale current helicity calculated directly from the helicity evolution equation. Here B and A are, respectively, the dynamo generated mean magnetic field and its vector potential. A theoretical interpretation of these results is given.

  2. Low Cost Hands-On Activities in Large Lecture Conceptual Physics Course

    NASA Astrophysics Data System (ADS)

    Dimiduk, Kathryn

    1998-10-01

    The student diversity in a university conceptual physic course presents a challenge to sustain the interest of all the students, to provide a solid conceptual basis for students continuing in science or engineering and to present science as an active subject rather than as vocabulary lists, rules and book knowledge. Combining ideas from the literature for teaching large lecture calculus based physics and science leary education majors in small class settings has resulted in a large (120 student) class format that mixes low cost (< $1,000 for term) hands-on activities, demonstrations, summary discussions and lectures. Hands-on activities are done in small groups which allows the diversity to become an asset. Several of these activities will be described in detail. The effectiveness of this teaching approach will be presented based on results of pre and post Force Concept Inventory test scores for this class and a comparison class that just used lecture and demonstrations for mechanics. The classes under comparison were taught by the same instructor, from the same book, were of similar size and neither had any additional teaching staff.

  3. Assessing Activity and Location of Individual Laying Hens in Large Groups Using Modern Technology

    PubMed Central

    Siegford, Janice M.; Berezowski, John; Biswas, Subir K.; Daigle, Courtney L.; Gebhardt-Henrich, Sabine G.; Hernandez, Carlos E.; Thurner, Stefan; Toscano, Michael J.

    2016-01-01

    Simple Summary Tracking of individual animals within large groups is increasingly possible offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors and track their activities across time and space with minimal intervention and disturbance. We describe several tracking systems that are currently in use for laying hens and review each, highlighting their strengths and weaknesses, as well as environments or conditions for which they may be most suited, and relevant issues to fit the best technology for the intended purpose. Abstract Tracking individual animals within large groups is increasingly possible, offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors within these large groups and track their activities across time and space with minimal intervention and disturbance. The development is particularly relevant to the poultry industry as, due to a shift away from battery cages, flock sizes are increasingly becoming larger and environments more complex. Many efforts have been made to track individual bird behavior and activity in large groups using a variety of methodologies with variable success. Of the technologies in use, each has associated benefits and detriments, which can make the approach more or less suitable for certain environments and experiments. Within this article, we have divided several tracking systems that are currently available into two major categories (radio frequency identification and radio signal strength) and review the strengths and weaknesses of each, as well as environments or conditions for which they may be most suitable. We also describe related topics including types of analysis for the data and concerns

  4. LARGE SOLAR ENERGETIC PARTICLE EVENTS ASSOCIATED WITH FILAMENT ERUPTIONS OUTSIDE ACTIVE REGIONS

    SciTech Connect

    Gopalswamy, N.; Mäkelä, P.; Akiyama, S.; Yashiro, S.; Xie, H.; Thakur, N.; Kahler, S. W.

    2015-06-10

    We report on four large filament eruptions (FEs) from solar cycles 23 and 24 that were associated with large solar energetic particle (SEP) events and interplanetary type II radio bursts. The post-eruption arcades corresponded mostly to C-class soft X-ray enhancements, but an M1.0 flare was associated with one event. However, the associated coronal mass ejections (CMEs) were fast (speeds ∼ 1000 km s{sup −1}) and appeared as halo CMEs in the coronagraph field of view. The interplanetary type II radio bursts occurred over a wide wavelength range, indicating the existence of strong shocks throughout the inner heliosphere. No metric type II bursts were present in three events, indicating that the shocks formed beyond 2–3 Rs. In one case, there was a metric type II burst with low starting frequency, indicating a shock formation height of ∼2 Rs. The FE-associated SEP events did have softer spectra (spectral index >4) in the 10–100 MeV range, but there were other low-intensity SEP events with spectral indices ≥4. Some of these events are likely FE-SEP events, but were not classified as such in the literature because they occurred close to active regions. Some were definitely associated with large active region flares, but the shock formation height was large. We definitely find a diminished role for flares and complex type III burst durations in these large SEP events. Fast CMEs and shock formation at larger distances from the Sun seem to be the primary characteristics of the FE-associated SEP events.

  5. Large Solar Energetic Particle Events Associated With Filament Eruptions Outside Active Regions

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Makela, P.; Akiyama, S.; Yashiro, S.; Xie, H.; Thakur, N.; Kahler, S. W.

    2015-01-01

    We report on four large filament eruptions (FEs) from solar cycles 23 and 24 that were associated with large solar energetic particle (SEP) events and interplanetary type II radio bursts. The post-eruption arcades corresponded mostly to C-class soft X-ray enhancements, but an M1.0 flare was associated with one event. However, the associated coronal mass ejections (CMEs) were fast (speeds approx. 1000 km/s) and appeared as halo CMEs in the coronagraph field of view. The interplanetary type II radio bursts occurred over a wide wavelength range, indicating the existence of strong shocks throughout the inner heliosphere. No metric type II bursts were present in three events, indicating that the shocks formed beyond 2-3 Rs. In one case, there was a metric type II burst with low starting frequency, indicating a shock formation height of approx.2 Rs. The FE-associated SEP events did have softer spectra (spectral index >4) in the 10-100 MeV range, but there were other low-intensity SEP events with spectral indices ?4. Some of these events are likely FE-SEP events, but were not classified as such in the literature because they occurred close to active regions. Some were definitely associated with large active region flares, but the shock formation height was large. We definitely find a diminished role for flares and complex type III burst durations in these large SEP events. Fast CMEs and shock formation at larger distances from the Sun seem to be the primary characteristics of the FE-associated SEP events.

  6. Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study

    PubMed Central

    Jackson, Dan; Hammerla, Nils; Granat, Malcolm H.; van Hees, Vincent T.; Trenell, Michael I.; Owen, Christoper G.; Preece, Stephen J.; Peakman, Tim; Brage, Soren

    2017-01-01

    Background Physical activity has not been objectively measured in prospective cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes. Technological advances now make this possible. We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study, and report variation by age, sex, day, time of day, and season. Methods Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them. Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration, removal of gravity and sensor noise, and identification of wear / non-wear episodes. We report age- and sex-specific wear-time compliance and accelerometer measured physical activity, overall and by hour-of-day, week-weekend day and season. Results 103,712 datasets were received (44.8% response), with a median wear-time of 6.9 days (IQR:6.5–7.0). 96,600 participants (93.3%) provided valid data for physical activity analyses. Vector magnitude, a proxy for overall physical activity, was 7.5% (2.35mg) lower per decade of age (Cohen’s d = 0.9). Women had a higher vector magnitude than men, apart from those aged 45-54yrs. There were major differences in vector magnitude by time of day (d = 0.66). Vector magnitude differences between week and weekend days (d = 0.12 for men, d = 0.09 for women) and between seasons (d = 0.27 for men, d = 0.15 for women) were small. Conclusions It is feasible to collect and analyse objective physical activity data in large studies. The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening. This work lays the foundation for studies of physical activity and its health consequences. Our summary variables are part of the UK Biobank dataset and can be used by researchers as

  7. Muscle activation described with a differential equation model for large ensembles of locally coupled molecular motors.

    PubMed

    Walcott, Sam

    2014-10-01

    Molecular motors, by turning chemical energy into mechanical work, are responsible for active cellular processes. Often groups of these motors work together to perform their biological role. Motors in an ensemble are coupled and exhibit complex emergent behavior. Although large motor ensembles can be modeled with partial differential equations (PDEs) by assuming that molecules function independently of their neighbors, this assumption is violated when motors are coupled locally. It is therefore unclear how to describe the ensemble behavior of the locally coupled motors responsible for biological processes such as calcium-dependent skeletal muscle activation. Here we develop a theory to describe locally coupled motor ensembles and apply the theory to skeletal muscle activation. The central idea is that a muscle filament can be divided into two phases: an active and an inactive phase. Dynamic changes in the relative size of these phases are described by a set of linear ordinary differential equations (ODEs). As the dynamics of the active phase are described by PDEs, muscle activation is governed by a set of coupled ODEs and PDEs, building on previous PDE models. With comparison to Monte Carlo simulations, we demonstrate that the theory captures the behavior of locally coupled ensembles. The theory also plausibly describes and predicts muscle experiments from molecular to whole muscle scales, suggesting that a micro- to macroscale muscle model is within reach.

  8. Assessing Activity and Location of Individual Laying Hens in Large Groups Using Modern Technology.

    PubMed

    Siegford, Janice M; Berezowski, John; Biswas, Subir K; Daigle, Courtney L; Gebhardt-Henrich, Sabine G; Hernandez, Carlos E; Thurner, Stefan; Toscano, Michael J

    2016-02-02

    Tracking individual animals within large groups is increasingly possible, offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors within these large groups and track their activities across time and space with minimal intervention and disturbance. The development is particularly relevant to the poultry industry as, due to a shift away from battery cages, flock sizes are increasingly becoming larger and environments more complex. Many efforts have been made to track individual bird behavior and activity in large groups using a variety of methodologies with variable success. Of the technologies in use, each has associated benefits and detriments, which can make the approach more or less suitable for certain environments and experiments. Within this article, we have divided several tracking systems that are currently available into two major categories (radio frequency identification and radio signal strength) and review the strengths and weaknesses of each, as well as environments or conditions for which they may be most suitable. We also describe related topics including types of analysis for the data and concerns with selecting focal birds.

  9. Alternative Patterning Process for Realization of Large-Area, Full-Color, Active Quantum Dot Display.

    PubMed

    Park, Joon-Suh; Kyhm, Jihoon; Kim, Hong Hee; Jeong, Shinyoung; Kang, JoonHyun; Lee, Song-Ee; Lee, Kyu-Tae; Park, Kisun; Barange, Nilesh; Han, JiYeong; Song, Jin Dong; Choi, Won Kook; Han, Il Ki

    2016-11-09

    Although various colloidal quantum dot (QD) coating and patterning techniques have been developed to meet the demands in optoelectronic applications over the past years, each of the previously demonstrated methods has one or more limitations and trade-offs in forming multicolor, high-resolution, or large-area patterns of QDs. In this study, we present an alternative QD patterning technique using conventional photolithography combined with charge-assisted layer-by-layer (LbL) assembly to solve the trade-offs of the traditional patterning processes. From our demonstrations, we show repeatable QD patterning process that allows multicolor QD patterns in both large-area and microscale. Also, we show that the QD patterns are robust against additional photolithography processes and that the thickness of the QD patterns can be controlled at each position. To validate that this process can be applied to actual device applications as an active material, we have fabricated inverted, differently colored, active QD light-emitting device (QD-LED) on a pixelated substrate, which achieved maximum electroluminescence intensity of 23 770 cd/m(2), and discussed the results. From our findings, we believe that our process provides a solution to achieving both high-resolution and large-scale QD pattern applicable to not only display, but also to practical photonic device research and development.

  10. Large-Scale Coronal Heating from "Cool" Activity in the Solar Magnetic Network

    NASA Technical Reports Server (NTRS)

    Falconer, D. A.; Moore, R. L.; Porter, J. G.; Hathaway, D. H.

    1999-01-01

    In Fe XII images from SOHO/EIT, the quiet solar corona shows structure on scales ranging from sub-supergranular (i.e., bright points and coronal network) to multi-supergranular (large-scale corona). In Falconer et al 1998 (Ap.J., 501, 386) we suppressed the large-scale background and found that the network-scale features are predominantly rooted in the magnetic network lanes at the boundaries of the supergranules. Taken together, the coronal network emission and bright point emission are only about 5% of the entire quiet solar coronal Fe XII emission. Here we investigate the relationship between the large-scale corona and the network as seen in three different EIT filters (He II, Fe IX-X, and Fe XII). Using the median-brightness contour, we divide the large-scale Fe XII corona into dim and bright halves, and find that the bright-half/dim half brightness ratio is about 1.5. We also find that the bright half relative to the dim half has 10 times greater total bright point Fe XII emission, 3 times greater Fe XII network emission, 2 times greater Fe IX-X network emission, 1.3 times greater He II network emission, and has 1.5 times more magnetic flux. Also, the cooler network (He II) radiates an order of magnitude more energy than the hotter coronal network (Fe IX-X, and Fe XII). From these results we infer that: 1) The heating of the network and the heating of the large-scale corona each increase roughly linearly with the underlying magnetic flux. 2) The production of network coronal bright points and heating of the coronal network each increase nonlinearly with the magnetic flux. 3) The heating of the large-scale corona is driven by widespread cooler network activity rather than by the exceptional network activity that produces the network coronal bright points and the coronal network. 4) The large-scale corona is heated by a nonthermal process since the driver of its heating is cooler than it is. This work was funded by the Solar Physics Branch of NASA's office of

  11. Patterns of Activity in the Human Frontal and Parietal Cortex Differentiate Large and Small Saccades

    PubMed Central

    Grosbras, Marie-Hélène

    2016-01-01

    A vast literature indicates that small and large saccades, respectively, subserve different perceptual and cognitive strategies and may rely on different programming modes. While it is well-established that in monkeys’ main oculomotor brain regions small and large eye movements are controlled by segregated neuronal populations, the representation of saccade amplitude in the human brain remains unclear. To address this question we used functional magnetic resonance imaging to scan participants while they performed saccades toward targets at either short (4°) or large (30°) eccentricity. A regional multivoxel pattern analysis reveals that patterns of activity in the frontal eye-field and parietal eye fields discriminate between the execution of large or small saccades. This was not the case in the supplementary eye-fields nor in the inferior precentral cortex. These findings provide the first evidence of a representation of saccadic eye movement size in the fronto-parietal occulomotor circuit. They shed light on the respective roles of the different cortical oculomotor regions with respect to space perception and exploration, as well as on the homology of eye movement control between human and non-human primates. PMID:27833536

  12. Modeling activities on the negative-ion-based Neutral Beam Injectors of the Large Helical Device

    SciTech Connect

    Agostinetti, P.; Antoni, V.; Chitarin, G.; Pilan, N.; Serianni, G.; Veltri, P.; Cavenago, M.; Nakano, H.; Takeiri, Y.; Tsumori, K.

    2011-09-26

    At the National Institute for Fusion Science (NIFS) large-scaled negative ion sources have been widely used for the Neutral Beam Injectors (NBIs) mounted on the Large Helical Device (LHD), which is the world-largest superconducting helical system. These injectors have achieved outstanding performances in terms of beam energy, negative-ion current and optics, and represent a reference for the development of heating and current drive NBIs for ITER.In the framework of the support activities for the ITER NBIs, the PRIMA test facility, which includes a RF-drive ion source with 100 keV accelerator (SPIDER) and a complete 1 MeV Neutral Beam system (MITICA) is under construction at Consorzio RFX in Padova.An experimental validation of the codes has been undertaken in order to prove the accuracy of the simulations and the soundness of the SPIDER and MITICA design. To this purpose, the whole set of codes have been applied to the LHD NBIs in a joint activity between Consorzio RFX and NIFS, with the goal of comparing and benchmarking the codes with the experimental data. A description of these modeling activities and a discussion of the main results obtained are reported in this paper.

  13. Evaluation of a large capacity heat pump concept for active cooling of hypersonic aircraft structure

    NASA Technical Reports Server (NTRS)

    Pagel, L. L.; Herring, R. L.

    1978-01-01

    Results of engineering analyses assessing the conceptual feasibility of a large capacity heat pump for enhancing active cooling of hypersonic aircraft structure are presented. A unique heat pump arrangement which permits cooling the structure of a Mach 6 transport to aluminum temperatures without the aid of thermal shielding is described. The selected concept is compatible with the use of conventional refrigerants, with Freon R-11 selected as the preferred refrigerant. Condenser temperatures were limited to levels compatible with the use of conventional refrigerants by incorporating a unique multipass condenser design, which extracts mechanical energy from the hydrogen fuel, prior to each subsequent pass through the condenser. Results show that it is technically feasible to use a large capacity heat pump in lieu of external shielding. Additional analyses are required to optimally apply this concept.

  14. Introductory Biology Courses: A Framework To Support Active Learning in Large Enrollment Introductory Science Courses

    PubMed Central

    2005-01-01

    Active learning and research-oriented activities have been increasingly used in smaller, specialized science courses. Application of this type of scientific teaching to large enrollment introductory courses has been, however, a major challenge. The general microbiology lecture/laboratory course described has been designed to incorporate published active-learning methods. Three major case studies are used as platforms for active learning. Themes from case studies are integrated into lectures and laboratory experiments, and in class and online discussions and assignments. Students are stimulated to apply facts to problem-solving and to learn research skills such as data analysis, writing, and working in teams. This course is feasible only because of its organizational framework that makes use of teaching teams (made up of faculty, graduate assistants, and undergraduate assistants) and Web-based technology. Technology is a mode of communication, but also a system of course management. The relevance of this model to other biology courses led to assessment and evaluation, including an analysis of student responses to the new course, class performance, a university course evaluation, and retention of course learning. The results are indicative of an increase in student engagement in research-oriented activities and an appreciation of real-world context by students. PMID:15917873

  15. Systematic detection of seismic activity before recent large earthquakes in China

    NASA Astrophysics Data System (ADS)

    Peng, Z.; Wang, B.; Ruan, X.; Meng, X.; Hongwei, T.; Long, F.; Su, J.

    2014-12-01

    Sometimes large shallow earthquakes are preceded by increased local seismic activity, known as "foreshocks". However, the exact relationship between foreshocks and mainshock nucleation is still in debate. Several studies have found accelerating or migrating foreshock activity right before recent large earthquakes along major plate boundary faults, indicating that foreshocks are likely driven by slow-slip events. However, it is still not
clear whether similar features could be observed for earthquakes that occur away from plate-boundary regions.
Here we conduct a systematic detection of possible foreshock activity around the times of 6 recent large earthquakes in China.
The candidate events include the 2008 Ms7.3 Yutian, Ms8.0 Wenchuan, the 2010 Ms7.0 Yushu,
the 2013 Ms7.0 Lushan, the 2014 Ms7.3 Yutian, and the 2014 Ms6.5 Zhaotong earthquakes. Among them, the 2010 Yushu and 2014 Yutian mainshocks had clear evidence of M4-5 immediate foreshocks listed in regional earthquake catalogs, while the rest
did not. In each case, we use waveforms of local earthquakes listed in the catalog as templates and scan through continuous waveforms recorded by both permanent and temporary seismic stations around the epicentral region of each mainshock. Our waveform matching method can detect at least a few times more events than listed in the catalog. Our initial results show a wide range of behaviors. For the 2010 Yushu and 2014 Yutian cases, the M4-5 foreshocks were followed by many smaller-size events that could be considered as their aftershocks. For the Wenchuan case, we did not observe any obvious foreshock in the immediate vicinity of the epicenter. However, we found one swarm sequence that shows systematic migration a few months before the Wenchuan mainshock. Our next step is to relocate these newly detected events to search for spatio-temporal evolutions before each mainshock, as well
as performing Epidemic Type Aftershock Sequence (ETAS) modeling to examine

  16. Conceiving semi-active control devices for large-size monolithic monuments

    NASA Astrophysics Data System (ADS)

    Casciati, Fabio; El Attar, Adel; Casciati, Sara

    2001-07-01

    CHIME is a research project, funded by the European Union, which investigates the adoption of innovative structural control techniques in view of the seismic rehabilitation of the wide monumental cultural heritage in Mediterranean countries as Egypt, Tunisia and Cyprus. The structural control devices are mainly of the semi-active type. In this particular paper one reports the first results achieved within a case study. It considers an Egyptian large size monolithic monument. Alternative solutions for its seismic rehabilitation are eventually conceived and discussed.

  17. A single intratumoral injection of a fiber-mutant adenoviral vector encoding interleukin 12 induces remarkable anti-tumor and anti-metastatic activity in mice with Meth-A fibrosarcoma.

    PubMed

    Gao, Jian-Qing; Sugita, Toshiki; Kanagawa, Naoko; Iida, Keisuke; Eto, Yusuke; Motomura, Yoshiaki; Mizuguchi, Hiroyuki; Tsutsumi, Yasuo; Hayakawa, Takao; Mayumi, Tadanori; Nakagawa, Shinsaku

    2005-03-25

    Cytokine-encoding viral vectors are considered to be promising in cancer gene immunotherapy. Interleukin 12 (IL-12) has been used widely for anti-tumor treatment, but the administration route and tumor characteristics strongly influence therapeutic efficiency. Meth-A fibrosarcoma has been demonstrated to be insensitive to IL-12 treatment via systemic administration. In the present study, we developed an IL-12-encoding fiber-mutant adenoviral vector (AdRGD-IL-12) that showed enhanced gene transfection efficiency in Meth-A tumor cells, and the production of IL-12 p70 in the culture supernatant from transfected cells was confirmed by ELISA. In therapeutic experiments, a single low-dose (2 x 10(7) plaque-forming units) intratumoral injection of AdRGD-IL-12 elicited pronounced anti-tumor activity and notably prolonged the survival of Meth-A fibrosarcoma-bearing mice. Immunohistochemical staining revealed that the IL-12 vector induced the accumulation of T cells in tumor tissue. Furthermore, intratumoral administration of the vector induced an anti-metastasis effect as well as long-term specific immunity against syngeneic tumor challenge.

  18. Molecular heterogeneity of large-conductance calcium-activated potassium channels in canine intracardiac ganglia.

    PubMed

    Selga, Elisabet; Pérez-Serra, Alexandra; Moreno-Asso, Alba; Anderson, Seth; Thomas, Kristen; Desai, Mayurika; Brugada, Ramon; Pérez, Guillermo J; Scornik, Fabiana S

    2013-01-01

    Large conductance calcium-activated potassium (BK) channels are widely expressed in the nervous system. We have recently shown that principal neurons from canine intracardiac ganglia (ICG) express a paxilline- and TEA-sensitive BK current, which increases neuronal excitability. In the present work, we further explore the molecular constituents of the BK current in canine ICG. We found that the β1 and β4 regulatory subunits are expressed in ICG. Single channel voltage-dependence at different calcium concentrations suggested that association of the BKα with a particular β subunit was not enough to explain the channel activity in this tissue. Indeed, we detected the presence of several splice variants of the BKα subunit. In conclusion, BK channels in canine ICG may result from the arrangement of different BKα splice variants, plus accessory β subunits. The particular combinations expressed in canine IC neurons likely rule the excitatory role of BK current in this tissue.

  19. Investigating Informatics Activity, Control, and Training Needs in Large, Medium, and Small Health Departments

    PubMed Central

    Arnold, Ryan; Yang, Biru

    2016-01-01

    Introduction: A recent National Association of City & County Health Officials survey shed light on informatics workforce development needs. Local health departments (LHDs) of various jurisdictional sizes and control over informatics may differ on training needs and activity. Understanding the precise nature of this variation will allow stakeholders to appropriately develop workforce development tools to advance the field. Objective: To understand the informatics training needs for LHDs of different jurisdictional sizes. Methods: Survey responses were analyzed by comparing training needs and LHD population size. Results: Larger health departments consistently reported having greater informatics-related capacity and informatics-related training needs. Quantitative data analysis was identified as a primary need for large LHDs. In addition, LHDs that report higher control of informatics/information technology were able to engage in more informatics activities. Conclusion: Smaller LHDs need additional resources to improve informatics-related capacity and engagement with the field. PMID:27684621

  20. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells

    PubMed Central

    Jong, Ambrose Y.; Wu, Chun-Hua; Li, Jingbo; Sun, Jianping; Fabbri, Muller; Wayne, Alan S.; Seeger, Robert C.

    2017-01-01

    ABSTRACT Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically. In this report, we present a simple, robust, and cost-effective method to isolate a large quantity of NK EVs. After propagating and activating NK cells ex vivo and then incubating them in exosome-free medium for 48 h, EVs were isolated using a polymer precipitation method. The isolated vesicles contain the tetraspanin CD63, an EV marker, and associated proteins (fibronectin), but are devoid of cytochrome C, a cytoplasmic marker. Nanoparticle tracking analysis showed a size distribution between 100 and 200 nm while transmission electron microscopy imaging displayed vesicles with an oval shape and comparable sizes, fulfilling the definition of EV. Importantly, isolated EV fractions were cytotoxic against cancer cells. Furthermore, our results demonstrate for the first time that isolated activated NK (aNK) cell EVs contain the cytotoxic proteins perforin, granulysin, and granzymes A and B, incorporated from the aNK cells. Activation of caspase -3, -7 and -9 was detected in cancer cells incubated with aNK EVs, and caspase inhibitors blocked aNK EV-induced cytotoxicity, suggesting that aNK EVs activate caspase pathways in target cells. The ability to isolate functional aNK EVs on a large scale may lead to new clinical applications. Abbreviations: NK: natural killer cells; activated NK (aNK) cells; EVs: extracellular vesicles; ALL: acute lymphoblastic leukaemia; aAPC: artificial antigen-presenting cell; TEM: transmission

  1. Seasonal prediction of lightning activity in North Western Venezuela: Large-scale versus local drivers

    NASA Astrophysics Data System (ADS)

    Muñoz, Á. G.; Díaz-Lobatón, J.; Chourio, X.; Stock, M. J.

    2016-05-01

    The Lake Maracaibo Basin in North Western Venezuela has the highest annual lightning rate of any place in the world (~ 200 fl km- 2 yr- 1), whose electrical discharges occasionally impact human and animal lives (e.g., cattle) and frequently affect economic activities like oil and natural gas exploitation. Lightning activity is so common in this region that it has a proper name: Catatumbo Lightning (plural). Although short-term lightning forecasts are now common in different parts of the world, to the best of the authors' knowledge, seasonal prediction of lightning activity is still non-existent. This research discusses the relative role of both large-scale and local climate drivers as modulators of lightning activity in the region, and presents a formal predictability study at seasonal scale. Analysis of the Catatumbo Lightning Regional Mode, defined in terms of the second Empirical Orthogonal Function of monthly Lightning Imaging Sensor (LIS-TRMM) and Optical Transient Detector (OTD) satellite data for North Western South America, permits the identification of potential predictors at seasonal scale via a Canonical Correlation Analysis. Lightning activity in North Western Venezuela responds to well defined sea-surface temperature patterns (e.g., El Niño-Southern Oscillation, Atlantic Meridional Mode) and changes in the low-level meridional wind field that are associated with the Inter-Tropical Convergence Zone migrations, the Caribbean Low Level Jet and tropical cyclone activity, but it is also linked to local drivers like convection triggered by the topographic configuration and the effect of the Maracaibo Basin Nocturnal Low Level Jet. The analysis indicates that at seasonal scale the relative contribution of the large-scale drivers is more important than the local (basin-wide) ones, due to the synoptic control imposed by the former. Furthermore, meridional CAPE transport at 925 mb is identified as the best potential predictor for lightning activity in the Lake

  2. Macro optical projection tomography for large scale 3D imaging of plant structures and gene activity.

    PubMed

    Lee, Karen J I; Calder, Grant M; Hindle, Christopher R; Newman, Jacob L; Robinson, Simon N; Avondo, Jerome J H Y; Coen, Enrico S

    2016-12-26

    Optical projection tomography (OPT) is a well-established method for visualising gene activity in plants and animals. However, a limitation of conventional OPT is that the specimen upper size limit precludes its application to larger structures. To address this problem we constructed a macro version called Macro OPT (M-OPT). We apply M-OPT to 3D live imaging of gene activity in growing whole plants and to visualise structural morphology in large optically cleared plant and insect specimens up to 60 mm tall and 45 mm deep. We also show how M-OPT can be used to image gene expression domains in 3D within fixed tissue and to visualise gene activity in 3D in clones of growing young whole Arabidopsis plants. A further application of M-OPT is to visualise plant-insect interactions. Thus M-OPT provides an effective 3D imaging platform that allows the study of gene activity, internal plant structures and plant-insect interactions at a macroscopic scale.

  3. Using a fiber loop and fiber bragg grating as a fiber optic sensor to simultaneously measure temperature and displacement.

    PubMed

    Chang, Yao-Tang; Yen, Chih-Ta; Wu, Yue-Shiun; Cheng, Hsu-Chih

    2013-05-16

    This study integrated a fiber loop manufactured by using commercial fiber (SMF-28, Corning) and a fiber Bragg grating (FBG) to form a fiber optic sensor that could simultaneously measure displacement and temperature. The fiber loop was placed in a thermoelectric cooling module with FBG affixed to the module, and, consequently, the center wavelength displacement of FBG was limited by only the effects of temperature change. Displacement and temperature were determined by measuring changes in the transmission of optical power and shifts in Bragg wavelength. This study provides a simple and economical method to measure displacement and temperature simultaneously.

  4. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma.

    PubMed

    Davis, R Eric; Ngo, Vu N; Lenz, Georg; Tolar, Pavel; Young, Ryan M; Romesser, Paul B; Kohlhammer, Holger; Lamy, Laurence; Zhao, Hong; Yang, Yandan; Xu, Weihong; Shaffer, Arthur L; Wright, George; Xiao, Wenming; Powell, John; Jiang, Jian-Kang; Thomas, Craig J; Rosenwald, Andreas; Ott, German; Muller-Hermelink, Hans Konrad; Gascoyne, Randy D; Connors, Joseph M; Johnson, Nathalie A; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Wilson, Wyndham H; Delabie, Jan; Smeland, Erlend B; Fisher, Richard I; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Dennis D; Chan, Wing C; Pierce, Susan K; Staudt, Louis M

    2010-01-07

    A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly 10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA interference genetic screen revealed that a BCR signalling component, Bruton's tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs in these ABC DLBCLs formed prominent clusters in the plasma membrane with low diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM) signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated. These mutations increased surface BCR expression and attenuated Lyn kinase, a feedback inhibitor of BCR signalling. These findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.

  5. Signatures of large-scale magnetic fields in active galactic nuclei jets: transverse asymmetries

    NASA Astrophysics Data System (ADS)

    Clausen-Brown, E.; Lyutikov, M.; Kharb, P.

    2011-08-01

    We investigate the emission properties that a large-scale helical magnetic field imprints on active galactic nuclei (AGN) jet synchrotron radiation. A cylindrically symmetric relativistic jet and large-scale helical magnetic field produce significant asymmetrical features in transverse profiles of fractional linear polarization, intensity, the Faraday rotation and spectral index. The asymmetrical features of these transverse profiles correlate with one another in ways specified by the handedness of the helical field, the jet viewing angle (θob) and the bulk Lorentz factor of the flow (Γ). Thus, these correlations may be used to determine the structure of the magnetic field in the jet. In the case of radio galaxies (θob˜ 1 rad) and a subclass of blazars with particularly small viewing angles (θob≪ 1/Γ), we find an edge-brightened intensity profile that is similar to that observed in the radio galaxy M87. We present observations of the AGNs 3C 78 and NRAO 140 that display the type of transverse asymmetries that may be produced by large-scale helical magnetic fields.

  6. Large-scale pattern formation in active particles suspensions: from interacting microtubules to swimming bacteria

    NASA Astrophysics Data System (ADS)

    Aranson, Igor

    2006-03-01

    We consider two biological systems of active particles exhibiting large-scale collective behavior: microtubules interacting with molecular motors and hydrodynamically entrained swimming bacteria. Starting from a generic stochastic microscopic model of inelastically colliding polar rods with an anisotropic interaction kernel, we derive set of equations for the local rods concentration and orientation. Above certain critical density of rods the model exhibits orientational instability and onset of large-scale coherence. For the microtubules and molecular motors system we demonstrate that the orientational instability leads to the formation of vortices and asters seen in recent experiments. Similar approach is applied to colonies of swimming bacteria Bacillus subtilis confined in thin fluid film. The model is formulated in term of two-dimensional equations for local density and orientation of bacteria coupled to the low Reynolds number Navier-Stokes equation for the fluid flow velocity. The collective swimming of bacteria is represented by additional source term in the Navier-Stokes equation. We demonstrate that this system exhibits formation of dynamic large-scale patterns with the typical scale determined by the density of bacteria.

  7. Large-activation-energy analysis of gaseous reactive flow in pipes

    NASA Astrophysics Data System (ADS)

    Moreno-Boza, Daniel; Iglesias, Immaculada; Sanchez, Antonio L.

    2016-11-01

    Frank-Kamenetskii's analysis of thermal explosions is applied, using also a single-reaction model with an Arrhenius rate having a large activation energy, to describe the evolution of an initially cold gaseous mixture flowing along a circular pipe with constant wall temperature for moderately large values of the relevant Reynolds number. The analysis shows two modes of combustion. There is a flameless slowly reacting mode for low wall temperatures or small pipe radii, when the temperature rise resulting from the heat released by the reaction is kept small by the heat-conduction losses to the wall, so as not to change significantly the order of magnitude of the reaction rate. In the other mode, the slow reaction rates occur only in an initial ignition stage, which ends abruptly when very large reaction rates cause a temperature runaway, or thermal explosion, at a well-defined ignition distance. The analysis determines the slow streamwise evolution for the flameless mode of combustion as well as the ignition distance for the explosive mode.

  8. Active self-testing noise measurement sensors for large-scale environmental sensor networks.

    PubMed

    Domínguez, Federico; Cuong, Nguyen The; Reinoso, Felipe; Touhafi, Abdellah; Steenhaut, Kris

    2013-12-13

    Large-scale noise pollution sensor networks consist of hundreds of spatially distributed microphones that measure environmental noise. These networks provide historical and real-time environmental data to citizens and decision makers and are therefore a key technology to steer environmental policy. However, the high cost of certified environmental microphone sensors render large-scale environmental networks prohibitively expensive. Several environmental network projects have started using off-the-shelf low-cost microphone sensors to reduce their costs, but these sensors have higher failure rates and produce lower quality data. To offset this disadvantage, we developed a low-cost noise sensor that actively checks its condition and indirectly the integrity of the data it produces. The main design concept is to embed a 13 mm speaker in the noise sensor casing and, by regularly scheduling a frequency sweep, estimate the evolution of the microphone's frequency response over time. This paper presents our noise sensor's hardware and software design together with the results of a test deployment in a large-scale environmental network in Belgium. Our middle-range-value sensor (around €50) effectively detected all experienced malfunctions, in laboratory tests and outdoor deployments, with a few false positives. Future improvements could further lower the cost of our sensor below €10.

  9. Large-deflection statics analysis of active cardiac catheters through co-rotational modelling.

    PubMed

    Peng Qi; Chen Qiu; Mehndiratta, Aadarsh; I-Ming Chen; Haoyong Yu

    2016-08-01

    This paper presents a co-rotational concept for large-deflection formulation of cardiac catheters. Using this approach, the catheter is first discretized with a number of equal length beam elements and nodes, and the rigid body motions of an individual beam element are separated from its deformations. Therefore, it is adequate for modelling arbitrarily large deflections of a catheter with linear elastic analysis at the local element level. A novel design of active cardiac catheter of 9 Fr in diameter at the beginning of the paper is proposed, which is based on the contra-rotating double helix patterns and is improved from the previous prototypes. The modelling section is followed by MATLAB simulations of various deflections when the catheter is exerted different types of loads. This proves the feasibility of the presented modelling approach. To the best knowledge of the authors, it is the first to utilize this methodology for large-deflection static analysis of the catheter, which will enable more accurate control of robot-assisted cardiac catheterization procedures. Future work would include further experimental validations.

  10. Active Self-Testing Noise Measurement Sensors for Large-Scale Environmental Sensor Networks

    PubMed Central

    Domínguez, Federico; Cuong, Nguyen The; Reinoso, Felipe; Touhafi, Abdellah; Steenhaut, Kris

    2013-01-01

    Large-scale noise pollution sensor networks consist of hundreds of spatially distributed microphones that measure environmental noise. These networks provide historical and real-time environmental data to citizens and decision makers and are therefore a key technology to steer environmental policy. However, the high cost of certified environmental microphone sensors render large-scale environmental networks prohibitively expensive. Several environmental network projects have started using off-the-shelf low-cost microphone sensors to reduce their costs, but these sensors have higher failure rates and produce lower quality data. To offset this disadvantage, we developed a low-cost noise sensor that actively checks its condition and indirectly the integrity of the data it produces. The main design concept is to embed a 13 mm speaker in the noise sensor casing and, by regularly scheduling a frequency sweep, estimate the evolution of the microphone's frequency response over time. This paper presents our noise sensor's hardware and software design together with the results of a test deployment in a large-scale environmental network in Belgium. Our middle-range-value sensor (around €50) effectively detected all experienced malfunctions, in laboratory tests and outdoor deployments, with a few false positives. Future improvements could further lower the cost of our sensor below €10. PMID:24351634

  11. Synthesis of extremely large mesoporous activated carbon and its unique adsorption for giant molecules

    SciTech Connect

    Tamai, Hisashi; Kakii, Takuhiro; Hirota, Yoshifumi

    1996-02-01

    The steam invigoration of pitches (softening points 85 and 280{degrees}C) homogenized with 1-3 wt% of organo rare0earth metal complexes such as Ln(C{sub 5}H{sub 5}){sub 3} or Ln(acac) (Ln=Y, Yb) at 930{degrees}C provided activated carbons with an extremely high mesopore ration, >70%. The resulted activated carbon selectively adsorbs giant molecules such as Vitamin B{sub 12}, blue acid 90 dye, dextran, nystatin, and humic acid, reflecting their large mesopore volumes. To understand what kind of carbon skeleton in pitch is suited for generation of high mesopore ration, the steam invigoration of a series of condensed polynuclear aromatics (COPNA) resins prepared from naphthlene, anthracene, phenanthrene, pyrene, or perylene and p-xylene-{alpha},{alpha}{prime}-diol were conducted in the presence of rare-earth metal complexes. As a result, COPNA resins containing phenanthrene, perylene, and pyrene generated large mesopore volume. 35 refs., 16 figs., 11 tabs.

  12. Simultaneous Solar Maximum Mission (SMM) and Very Large Array (VLA) observations of solar active regions

    NASA Technical Reports Server (NTRS)

    Willson, Robert F.

    1991-01-01

    Very Large Array observations at 20 cm wavelength can detect the hot coronal plasma previously observed at soft x ray wavelengths. Thermal cyclotron line emission was detected at the apex of coronal loops where the magnetic field strength is relatively constant. Detailed comparison of simultaneous Solar Maximum Mission (SMM) Satellite and VLA data indicate that physical parameters such as electron temperature, electron density, and magnetic field strength can be obtained, but that some coronal loops remain invisible in either spectral domain. The unprecedent spatial resolution of the VLA at 20 cm wavelength showed that the precursor, impulsive, and post-flare components of solar bursts originate in nearby, but separate loops or systems of loops.. In some cases preburst heating and magnetic changes are observed from loops tens of minutes prior to the impulsive phase. Comparisons with soft x ray images and spectra and with hard x ray data specify the magnetic field strength and emission mechanism of flaring coronal loops. At the longer 91 cm wavelength, the VLA detected extensive emission interpreted as a hot 10(exp 5) K interface between cool, dense H alpha filaments and the surrounding hotter, rarefield corona. Observations at 91 cm also provide evidence for time-correlated bursts in active regions on opposite sides of the solar equator; they are attributed to flare triggering by relativistic particles that move along large-scale, otherwise-invisible, magnetic conduits that link active regions in opposite hemispheres of the Sun.

  13. Corrugated paraffin nanocomposite films as large stroke thermal actuators and self-activating thermal interfaces.

    PubMed

    Copic, Davor; Hart, A John

    2015-04-22

    High performance active materials are of rapidly growing interest for applications including soft robotics, microfluidic systems, and morphing composites. In particular, paraffin wax has been used to actuate miniature pumps, solenoid valves, and composite fibers, yet its deployment is typically limited by the need for external volume constraint. We demonstrate that compact, high-performance paraffin actuators can be made by confining paraffin within vertically aligned carbon nanotube (CNT) films. This large-stroke vertical actuation is enabled by strong capillary interaction between paraffin and CNTs and by engineering the CNT morphology by mechanical compression before capillary-driven infiltration of the molten paraffin. The maximum actuation strain of the corrugated CNT-paraffin films (∼0.02-0.2) is comparable to natural muscle, yet the maximum stress is limited to ∼10 kPa by collapse of the CNT network. We also show how a CNT-paraffin film can serve as a self-activating thermal interface that closes a gap when it is heated. These new CNT-paraffin film actuators could be produced by large-area CNT growth, infiltration, and lamination methods, and are attractive for use in miniature systems due to their self-contained design.

  14. Active suspension design for a Large Space Structure ground test facility

    NASA Technical Reports Server (NTRS)

    Lange, Thomas J. H.; Schlegel, Clemens

    1993-01-01

    The expected future high performance requirements for Large Space Structures (LSS) enforce technology innovations such as active vibration damping techniques e.g., by means of structure sensors and actuators. The implementation of new technologies like that requires an interactive and integrated structural and control design with an increased effort in hardware validation by ground testing. During the technology development phase generic system tests will be most important covering verification and validation aspects up to the preparation and definition of relevant space experiments. For many applications using advanced designs it is deemed necessary to improve existing testing technology by further reducing disturbances and gravity coupling effects while maintaining high performance reliability. A key issue in this context is the improvement of suspension techniques. The ideal ground test facility satisfying these requirements completely will never be found. The highest degree of reliability will always be obtained by passive suspension methods taking into account severe performance limitations such as non-zero rigid body modes, restriction of degrees of freedom of motion and frequency response limitations. Passive compensation mechanisms, e.g., zero-spring-rate mechanisms, either require large moving masses or they are limited with respect to low-frequency performance by friction, stiction or other non-linear effects. With active suspensions these limitations can be removed to a large extent thereby increasing the range of applications. Despite an additional complexity which is associated with a potential risk in reliability their development is considered promising due to the amazing improvement of real-time control technology which is still continuing.

  15. Photoacoustic wave detection on water using a fiber optic transducer

    NASA Astrophysics Data System (ADS)

    Montoya, Jose P.; Munera, Natalia; Acuna-Herrera, Rodrigo

    2016-09-01

    In this work, a fiber optic microphone system was built and tested. The purpose of the fiber microphone is to sense photoacoustic waves produced by water molecules excited by an ultrafast laser. The use of a fiber sensor allows for ease of three-dimension measurement implementation for a 3-D imaging based on water amounts of different materials, this sensor can be directly submerged in water or a phantom gel without electromagnetic interference nor corrosion.

  16. Increasing ocean temperatures reduce activity patterns of a large commercially important coral reef fish.

    PubMed

    Johansen, J L; Messmer, V; Coker, D J; Hoey, A S; Pratchett, M S

    2014-04-01

    Large-bodied fish are critical for sustaining coral reef fisheries, but little is known about the vulnerability of these fish to global warming. This study examined the effects of elevated temperatures on the movement and activity patterns of the common coral trout Plectropomus leopardus (Serranidae), which is an important fishery species in tropical Australia and throughout the Indo West-Pacific. Adult fish were collected from two locations on Australia's Great Barrier Reef (23°S and 14°S) and maintained at one of four temperatures (24, 27, 30, 33 °C). Following >4 weeks acclimation, the spontaneous swimming speeds and activity patterns of individuals were recorded over a period of 12 days. At 24-27 °C, spontaneous swimming speeds of common coral trout were 0.43-0.45 body lengths per second (bls(-1)), but dropped sharply to 0.29 bls(-1) at 30 °C and 0.25 bls(-1) at 33 °C. Concurrently, individuals spent 9.3-10.6% of their time resting motionless on the bottom at 24-27 °C, but this behaviour increased to 14.0% at 30 °C and 20.0% of the time at 33 °C (mean ± SE). The impact of temperature was greatest for smaller individuals (<45 cm TL), showing significant changes to swimming speeds across every temperature tested, while medium (45-55 cm TL) and large individuals (>55 cm TL) were first affected by 30 °C and 33 °C, respectively. Importantly, there was some indication that populations can adapt to elevated temperature if presented with adequate time, as the high-latitude population decreased significantly in swimming speeds at both 30 °C and 33 °C, while the low-latitude population only showed significant reductions at 33 °C. Given that movement and activity patterns of large mobile species are directly related to prey encounter rates, ability to capture prey and avoid predators, any reductions in activity patterns are likely to reduce overall foraging and energy intake, limit the energy available for growth and reproduction, and affect the fitness and

  17. Horizon: A Proposal for Large Aperture, Active Optics in Geosynchronous Orbit

    NASA Technical Reports Server (NTRS)

    Chesters, Dennis; Jenstrom, Del

    2000-01-01

    In 1999, NASA's New Millennium Program called for proposals to validate new technology in high-earth orbit for the Earth Observing-3 (NMP EO3) mission to fly in 2003. In response, we proposed to test a large aperture, active optics telescope in geosynchronous orbit. This would flight-qualify new technologies for both Earth and Space science: 1) a future instrument with LANDSAT image resolution and radiometric quality watching continuously from geosynchronous station, and 2) the Next Generation Space Telescope (NGST) for deep space imaging. Six enabling technologies were to be flight-qualified: 1) a 3-meter, lightweight segmented primary mirror, 2) mirror actuators and mechanisms, 3) a deformable mirror, 4) coarse phasing techniques, 5) phase retrieval for wavefront control during stellar viewing, and 6) phase diversity for wavefront control during Earth viewing. Three enhancing technologies were to be flight- validated: 1) mirror deployment and latching mechanisms, 2) an advanced microcontroller, and 3) GPS at GEO. In particular, two wavefront sensing algorithms, phase retrieval by JPL and phase diversity by ERIM International, were to sense optical system alignment and focus errors, and to correct them using high-precision mirror mechanisms. Active corrections based on Earth scenes are challenging because phase diversity images must be collected from extended, dynamically changing scenes. In addition, an Earth-facing telescope in GEO orbit is subject to a powerful diurnal thermal and radiometric cycle not experienced by deep-space astronomy. The Horizon proposal was a bare-bones design for a lightweight large-aperture, active optical system that is a practical blend of science requirements, emerging technologies, budget constraints, launch vehicle considerations, orbital mechanics, optical hardware, phase-determination algorithms, communication strategy, computational burdens, and first-rate cooperation among earth and space scientists, engineers and managers

  18. WNK1 Activates Large-Conductance Ca2+-Activated K+ Channels through Modulation of ERK1/2 Signaling

    PubMed Central

    Liu, Yingli; Song, Xiang; Shi, Yanling; Shi, Zhen; Niu, Weihui; Feng, Xiuyan; Gu, Dingying; Bao, Hui-Fang; Ma, He-Ping; Eaton, Douglas C.

    2015-01-01

    With no lysine (WNK) kinases are members of the serine/threonine kinase family. We previously showed that WNK4 inhibits renal large-conductance Ca2+-activated K+ (BK) channel activity by enhancing its degradation through a lysosomal pathway. In this study, we investigated the effect of WNK1 on BK channel activity. In HEK293 cells stably expressing the α subunit of BK (HEK-BKα cells), siRNA-mediated knockdown of WNK1 expression significantly inhibited both BKα channel activity and open probability. Knockdown of WNK1 expression also significantly inhibited BKα protein expression and increased ERK1/2 phosphorylation, whereas overexpression of WNK1 significantly enhanced BKα expression and decreased ERK1/2 phosphorylation in a dose-dependent manner in HEK293 cells. Knockdown of ERK1/2 prevented WNK1 siRNA-mediated inhibition of BKα expression. Similarly, pretreatment of HEK-BKα cells with the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of WNK1 siRNA on BKα expression in a dose-dependent manner. Knockdown of WNK1 expression also increased the ubiquitination of BKα channels. Notably, mice fed a high-K+ diet for 10 days had significantly higher renal protein expression levels of BKα and WNK1 and lower levels of ERK1/2 phosphorylation compared with mice fed a normal-K+ diet. These data suggest that WNK1 enhances BK channel function by reducing ERK1/2 signaling-mediated lysosomal degradation of the channel. PMID:25145935

  19. Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons

    PubMed Central

    Pérez, Guillermo J.; Desai, Mayurika; Anderson, Seth

    2013-01-01

    We studied principal neurons from canine intracardiac (IC) ganglia to determine whether large-conductance calcium-activated potassium (BK) channels play a role in their excitability. We performed whole cell recordings in voltage- and current-clamp modes to measure ion currents and changes in membrane potential from isolated canine IC neurons. Whole cell currents from these neurons showed fast- and slow-activated outward components. Both current components decreased in the absence of calcium and following 1–2 mM tetraethylammonium (TEA) or paxilline. These results suggest that BK channels underlie these current components. Single-channel analysis showed that BK channels from IC neurons do not inactivate in a time-dependent manner, suggesting that the dynamic of the decay of the fast current component is akin to that of intracellular calcium. Immunohistochemical studies showed that BK channels and type 2 ryanodine receptors are coexpressed in IC principal neurons. We tested whether BK current activation in these neurons occurred via a calcium-induced calcium release mechanism. We found that the outward currents of these neurons were not affected by the calcium depletion of intracellular stores with 10 mM caffeine and 10 μM cyclopiazonic acid. Thus, in canine intracardiac neurons, BK currents are directly activated by calcium influx. Membrane potential changes elicited by long (400 ms) current injections showed a tonic firing response that was decreased by TEA or paxilline. These data strongly suggest that the BK current present in canine intracardiac neurons regulates action potential activity and could increase these neurons excitability. PMID:23195072

  20. Large-conductance Ca2+-activated potassium channels in secretory neurons.

    PubMed

    Lara, J; Acevedo, J J; Onetti, C G

    1999-09-01

    Large-conductance Ca2+-activated K+ channels (BK) are believed to underlie interburst intervals and contribute to the control of hormone release in several secretory cells. In crustacean neurosecretory cells, Ca2+ entry associated with electrical activity could act as a modulator of membrane K+ conductance. Therefore we studied the contribution of BK channels to the macroscopic outward current in the X-organ of crayfish, and their participation in electrophysiological activity, as well as their sensitivity toward intracellular Ca2+, ATP, and voltage, by using the patch-clamp technique. The BK channels had a conductance of 223 pS and rectified inwardly in symmetrical K+. These channels were highly selective to K+ ions; potassium permeability (PK) value was 2.3 x 10(-13) cm(3) s(-1). The BK channels were sensitive to internal Ca2+ concentration, voltage dependent, and activated by intracellular MgATP. Voltage sensitivity (k) was approximately 13 mV, and the half-activation membrane potentials depended on the internal Ca2+ concentration. Calcium ions (0.3-3 microM) applied to the internal membrane surface caused an enhancement of the channel activity. This activation of BK channels by internal calcium had a KD(0) of 0.22 microM and was probably due to the binding of only one or two Ca2+ ions to the channel. Addition of MgATP (0.01-3 mM) to the internal solution increased steady state-open probability. The dissociation constant for MgATP (KD) was 119 microM, and the Hill coefficient (h) was 0.6, according to the Hill analysis. Ca2+-activated K+ currents recorded from whole cells were suppressed by either adding Cd2+ (0.4 mM) or removing Ca2+ ions from the external solution. TEA (1 mM) or charybdotoxin (100 nM) blocked these currents. Our results showed that both BK and K(ATP) channels are present in the same cell. Even when BK and K(ATP) channels were voltage dependent and modulated by internal Ca2+ and ATP, the profile of sensitivity was quite different for each kind

  1. Laboratory demonstration of a primary active mirror for space with the LATT: large aperture telescope technology

    NASA Astrophysics Data System (ADS)

    Briguglio, Runa; Biasi, Roberto; Gallieni, Daniele; Vettore, Christian; d'Amato, Francesco; Xompero, Marco; Arcidiacono, Carmelo; Lisi, Franco; Riccardi, Armando; Patauner, Christian; Lazzarini, Paolo; Tintori, Matteo; Duò, Fabrizio; Pucci, Mauro; Zuccaro Marchi, Alessandro; Maresi, Luca

    2016-07-01

    The LATT project is an ESA contract under TRP programme to demonstrate the scalability of the technology from ground-based adaptive mirrors to space active primary mirrors. A prototype spherical mirror based on a 40 cm diameter 1 mm thin glass shell with 19 contactless, voice-coil actuators and co-located position sensors have been manufactured and integrated into a final unit with an areal density lower than 20 kg/m2. Laboratory tests demonstrated the controllability with very low power budget and the survival of the fragile glass shell exposed to launch accelerations, thanks to an electrostatic locking mechanism; such achievements pushes the technology readiness level toward 5. With this prototype, the LATT project explored the feasibility of using an active and lightweight primary for space telescopes. The concept is attractive for large segmented telescopes, with surface active control to shape and co-phase them once in flight. In this paper we will describe the findings of the technological advances and the results of the environmental and optical tests.

  2. Nature and timing of large landslides within an active orogen, eastern Pamir, China

    NASA Astrophysics Data System (ADS)

    Yuan, Zhaode; Chen, Jie; Owen, Lewis A.; Hedrick, Kathryn A.; Caffee, Marc W.; Li, Wenqiao; Schoenbohm, Lindsay M.; Robinson, Alexander C.

    2013-01-01

    Large-scale landsliding (involving ≫ 106 m3 in volume) is important in landscape development in high mountains. To assess the importance of large landslides in high mountains, four large landslides (Bulunkou, Muztagh, Taheman, and Yimake) were mapped in the NE Chinese Pamir at the westernmost end of the Himalayan-Tibetan orogen and dated using 10Be terrestrial cosmogenic nuclides. The Bulunkou landslide at the southernmost end of Muji Valley is composed of ~ 1.7 × 107 m3 of landslide debris and has an age of 2.0 ± 0.1 ka. The Muztagh landslide, located on the SW side of the massif Muztagh Ata, is composed of ~ 4.7 × 108 m3 of debris, and has an age of 14.3 ± 0.8 ka. The Taheman landslide, located south of Muztagh Ata, is composed of ~ 2.6 × 108 m3 of landslide debris and has an age of 6.8 ± 0.2 ka. The Yimake landslide, on the northern frontal range of the Pamir at the southwestern end of the Tarim basin, is composed of ~ 1.4 × 109 m3 of landslide debris and has an age of 7.1 ± 0.6 ka. Two other large landslides are present in the region, the Aerpa Aigezi (on a tributary of the Gez River) and the Bile Jiyi (on the Yarkand River) landslides, and are composed of ~ 1.6 × 107 m3 and ~ 5.2 × 106 m3 of landslide debris, respectively. However, the Aerpa Aigezi and Bile Jiyi landslides were not studied in as much detail or dated because of their inaccessibility. Given the tectonically active nature of this region, with numerous active faults, and the morphology of the landslides, these landslides were likely triggered by earthquakes. However, other causes — including long-term increased precipitation and geologic bedrock structure — could be important contributing factors in their formation.

  3. Determination of paleoseismic activity over a large time-scale: Fault scarp dating with 36Cl

    NASA Astrophysics Data System (ADS)

    Mozafari Amiri, Nasim; Tikhomirov, Dmitry; Sümer, Ökmen; Özkaymak, Çaǧlar; Uzel, Bora; Ivy-Ochs, Susan; Vockenhuber, Christof; Sözbilir, Hasan; Akçar, Naki

    2016-04-01

    Bedrock fault scarps are the most direct evidence of past earthquakes to reconstruct seismic activity in a large time-scale using cosmogenic 36Cl dating if built in carbonates. For this method, a surface along the fault scarp with a minimum amount of erosion is required to be chosen as an ideal target point. The section of the fault selected for sampling should cover at least two meters of the fault surface from the lower part of the scarp, where intersects with colluvium wedge. Ideally, sampling should be performed on a continuous strip along the direction of the fault slip direction. First, samples of 10 cm high and 15 cm wide are marked on the fault surface. Then, they are collected using cutters, hammer and chisel in a thickness of 3 cm. The main geometrical factors of scarp dip, scarp height, top surface dip and colluvium dip are also measured. Topographic shielding in the sampling spot is important to be estimated as well. Moreover, density of the fault scarp and colluvium are calculated. The physical and chemical preparations are carried in laboratory for AMS and chemical analysis of the samples. A Matlab® code is used for modelling of seismically active periods based on increasing production rate of 36Cl following each rupture, when a buried section of a fault is exposed. Therefore, by measuring the amount of cosmogenic 36Cl versus height, the timing of major ruptures and their offsets are determined. In our study, Manastır, Mugırtepe and Rahmiye faults in Gediz graben, Priene-Sazlı, Kalafat and Yavansu faults in Büyük Menderes graben and Ören fault in Gökava half-graben have been examined in the seismically active region of Western Turkey. Our results reconstruct at least five periods of high seismic activity during the Holocene time, three of which reveal seismic ruptures beyond the historical pre-existing data.

  4. Directed Evolution of RebH for Site Selective Halogenation of Large, Biologically Active Molecules**

    PubMed Central

    Payne, James T.; Poor, Catherine B.

    2015-01-01

    We recently characterized the substrate scope of wild-type RebH and evolved variants of this enzyme with improved stability for biocatalysis. The substrate scopes of both RebH and the stabilized variants, however, are limited primarily to compounds similar in size to tryptophan. We have now used a substrate walking approach to further evolve RebH variants with expanded substrate scope. Two particularly notable variants were identified: 3-SS, which provides high conversion of tricyclic tryptoline derivatives; and 4-V, which accepts a broad range of large indoles and carbazoles. This constitutes the first reported use of directed evolution to enable functionalization of substrates not accepted by wild-type RebH and demonstrates the utility of RebH variants for site-selective halogenation of biologically active compounds. PMID:25678465

  5. Stress-related noradrenergic activity prompts large-scale neural network reconfiguration.

    PubMed

    Hermans, Erno J; van Marle, Hein J F; Ossewaarde, Lindsey; Henckens, Marloes J A G; Qin, Shaozheng; van Kesteren, Marlieke T R; Schoots, Vincent C; Cousijn, Helena; Rijpkema, Mark; Oostenveld, Robert; Fernández, Guillén

    2011-11-25

    Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. β-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.

  6. Response of extratropical cyclone activity to the Kuroshio large meander in northern winter

    NASA Astrophysics Data System (ADS)

    Hayasaki, Masamitsu; Kawamura, Ryuichi; Mori, Masato; Watanabe, Masahiro

    2013-06-01

    We examined possible responses of cyclone activities to the bimodal path states of the Kuroshio Current [i.e., large meander (LM) and non-LM (NLM)] by using the long-term reanalysis data and the 20th century hindcast experiment of a high-resolution atmosphere-ocean coupled model. Compared with a seasonal mean cyclone track frequency for the LM and NLM periods, a primary cyclone track shifts southward in association with the meander of Kuroshio Current. Composite analyses of the hindcast experiment showed remarkable atmospheric responses accompanying the Kuroshio LM. The Kuroshio LM causes a decrease in latent heat flux in the south of Japan and a southward shift of the near-surface baroclinic zone. Distinctive decreases in thermodynamic fluxes inhibit the rapid development of cyclones in the meander region, eventually inducing positive sea level pressure anomalies downstream from that region.

  7. Correlation Analysis of Optical and Radio Light Curves for a Large Sample of Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Clements, S. D.; Smith, A. G.; Aller, H. D.; Aller, M. F.

    1995-08-01

    The Rosemary Hill Observatory has accumulated internally consistent light curves extending over as much as 26 years for a large sample of active galactic nuclei. Forty-six of these optical records have been compared with similar radio records from the University of Michigan Radio Astronomy Observatory and the Algonquin Radio Observatory. For 18 objects, pairs of records were sufficiently long and unconfused to allow reliable application of the Discrete Correlation Function analysis; this group included 8 BL Lacertids, 8 quasars, and 2 Seyfert galaxies. Nine of the 18 sources showed positive radio-optical correlations, with the radio events lagging the optical by intervals ranging from 0 to 14 months. Consistent with the relativistic beaming model of the BL Lacertids, the group displaying correlations was dominated by this type of object.

  8. Mapping the Daily Progression of Large Wildland Fires Using MODIS Active Fire Data

    NASA Technical Reports Server (NTRS)

    Veraverbeke, Sander; Sedano, Fernando; Hook, Simon J.; Randerson, James T.; Jin, Yufang; Rogers, Brendan

    2013-01-01

    High temporal resolution information on burned area is a prerequisite for incorporating bottom-up estimates of wildland fire emissions in regional air transport models and for improving models of fire behavior. We used the Moderate Resolution Imaging Spectroradiometer (MODIS) active fire product (MO(Y)D14) as input to a kriging interpolation to derive continuous maps of the evolution of nine large wildland fires. For each fire, local input parameters for the kriging model were defined using variogram analysis. The accuracy of the kriging model was assessed using high resolution daily fire perimeter data available from the U.S. Forest Service. We also assessed the temporal reporting accuracy of the MODIS burned area products (MCD45A1 and MCD64A1). Averaged over the nine fires, the kriging method correctly mapped 73% of the pixels within the accuracy of a single day, compared to 33% for MCD45A1 and 53% for MCD64A1.

  9. TFT-Based Active Pixel Sensors for Large Area Thermal Neutron Detection

    NASA Astrophysics Data System (ADS)

    Kunnen, George

    Due to diminishing availability of 3He, which is the critical component of neutron detecting proportional counters, large area flexible arrays are being considered as a potential replacement for neutron detection. A large area flexible array, utilizing semiconductors for both charged particle detection and pixel readout, ensures a large detection surface area in a light weight rugged form. Such a neutron detector could be suitable for deployment at ports of entry. The specific approach used in this research, uses a neutron converter layer which captures incident thermal neutrons, and then emits ionizing charged particles. These ionizing particles cause electron-hole pair generation within a single pixel's integrated sensing diode. The resulting charge is then amplified via a low-noise amplifier. This document begins by discussing the current state of the art in neutron detection and the associated challenges. Then, for the purpose of resolving some of these issues, recent design and modeling efforts towards developing an improved neutron detection system are described. Also presented is a low-noise active pixel sensor (APS) design capable of being implemented in low temperature indium gallium zinc oxide (InGaZnO) or amorphous silicon (a-Si:H) thin film transistor process compatible with plastic substrates. The low gain and limited scalability of this design are improved upon by implementing a new multi-stage self-resetting APS. For each APS design, successful radiation measurements are also presented using PiN diodes for charged particle detection. Next, detection array readout methodologies are modeled and analyzed, and use of a matched filter readout circuit is described as well. Finally, this document discusses detection diode integration with the designed TFT-based APSs.

  10. Raman Optical Activity Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    PubMed

    Jovan Jose, K V; Raghavachari, Krishnan

    2016-02-09

    We present an efficient method for the calculation of the Raman optical activity (ROA) spectra for large molecules through the molecules-in-molecules (MIM) fragment-based method. The relevant higher energy derivatives from smaller fragments are used to build the property tensors of the parent molecule to enable the extension of the MIM method for evaluating ROA spectra (MIM-ROA). Two factors were found to be particularly important in yielding accurate results. First, the link-atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, yielding a mathematically rigorous method. Second, the long-range interactions between fragments are taken into account by using a less computationally expensive lower level of theory. The performance of the MIM-ROA model is calibrated on the enantiomeric pairs of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and ROA intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-ROA method is employed to predict the ROA spectra of d-maltose, α-D-cyclodextrin, and cryptophane-A, yielding spectra in excellent agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-ROA model for exploring ROA spectra of large molecules.

  11. Heterogeneity-induced large deviations in activity and (in some cases) entropy production

    NASA Astrophysics Data System (ADS)

    Gingrich, Todd R.; Vaikuntanathan, Suriyanarayanan; Geissler, Phillip L.

    2014-10-01

    We solve a simple model that supports a dynamic phase transition and show conditions for the existence of the transition. Using methods of large deviation theory we analytically compute the probability distribution for activity and entropy production rates of the trajectories on a large ring with a single heterogeneous link. The corresponding joint rate function demonstrates two dynamical phases—one localized and the other delocalized, but the marginal rate functions do not always exhibit the underlying transition. Symmetries in dynamic order parameters influence the observation of a transition, such that distributions for certain dynamic order parameters need not reveal an underlying dynamical bistability. Solution of our model system furthermore yields the form of the effective Markov transition matrices that generate dynamics in which the two dynamical phases are at coexistence. We discuss the implications of the transition for the response of bacterial cells to antibiotic treatment, arguing that even simple models of a cell cycle lacking an explicit bistability in configuration space will exhibit a bistability of dynamical phases.

  12. Large-Scale Activity in the Bastille Day 2000 Solar Event

    NASA Astrophysics Data System (ADS)

    Chertok, I. M.; Grechnev, V. V.

    2005-06-01

    We have analyzed dimmings, i.e., regions of temporarily reduced brightness, and manifestations of a coronal wave in the famous event of 14 July 2000 using images produced with the EUV telescope SOHO/EIT. Our analysis was inspired by a paper by Andrews (2001, Solar Phys. 204, 181 (Paper I)), in which this event was studied using running-difference EIT images at 195 Å formed by subtraction of a previous image from each current one. Such images emphasize changes of the brightness, location, and configuration of observed structures occurring during the 12-min interval between two subsequent heliograms. However, they distort the picture of large-scale disturbances caused by a CME, particularly, dimmings. A real picture of dimmings can be obtained from fixed-base difference ‘de-rotated’ images. The latter are formed in two stages: first, the solar rotation is compensated using three-dimensional rotation of all images (‘de-rotation’) to the time of a pre-event heliogram, here 10:00 UT, and then the base heliogram is subtracted from all others. We show real dimmings to be essentially different from those described by Andrews (Paper I). The restructuring of large-scale magnetic fields in the corona in connection with the CME was accompanied by the appearance and growth of two large dimmings. One of them was located along the central meridian, southward of the eruption center, at the place of the pre-eruption arcade. Another dimming occupied the space between the flare region and a remote western active region. Several smaller dimmings were observed virtually over the whole solar disk, especially, within the northwest quadrant. We have also revealed a propagating disturbance with properties of a coronal wave in the northern polar sector, where no dimmings were observed. This fact is discussed in the context of probable association between dimmings and coronal waves. Having suppressed the ‘snowstorm’ produced in the EIT images by energetic particles, we have

  13. GMP Cryopreservation of Large Volumes of Cells for Regenerative Medicine: Active Control of the Freezing Process

    PubMed Central

    Massie, Isobel; Selden, Clare; Hodgson, Humphrey; Gibbons, Stephanie; Morris, G. John

    2014-01-01

    Cryopreservation protocols are increasingly required in regenerative medicine applications but must deliver functional products at clinical scale and comply with Good Manufacturing Process (GMP). While GMP cryopreservation is achievable on a small scale using a Stirling cryocooler-based controlled rate freezer (CRF) (EF600), successful large-scale GMP cryopreservation is more challenging due to heat transfer issues and control of ice nucleation, both complex events that impact success. We have developed a large-scale cryocooler-based CRF (VIA Freeze) that can process larger volumes and have evaluated it using alginate-encapsulated liver cell (HepG2) spheroids (ELS). It is anticipated that ELS will comprise the cellular component of a bioartificial liver and will be required in volumes of ∼2 L for clinical use. Sample temperatures and Stirling cryocooler power consumption was recorded throughout cooling runs for both small (500 μL) and large (200 mL) volume samples. ELS recoveries were assessed using viability (FDA/PI staining with image analysis), cell number (nuclei count), and function (protein secretion), along with cryoscanning electron microscopy and freeze substitution techniques to identify possible injury mechanisms. Slow cooling profiles were successfully applied to samples in both the EF600 and the VIA Freeze, and a number of cooling and warming profiles were evaluated. An optimized cooling protocol with a nonlinear cooling profile from ice nucleation to −60°C was implemented in both the EF600 and VIA Freeze. In the VIA Freeze the nucleation of ice is detected by the control software, allowing both noninvasive detection of the nucleation event for quality control purposes and the potential to modify the cooling profile following ice nucleation in an active manner. When processing 200 mL of ELS in the VIA Freeze—viabilities at 93.4%±7.4%, viable cell numbers at 14.3±1.7 million nuclei/mL alginate, and protein secretion at 10.5±1.7

  14. Active alignment and vibration control system for a large airborne optical system

    NASA Astrophysics Data System (ADS)

    Kienholz, David A.

    2000-04-01

    Airborne optical or electro-optical systems may be too large for all elements to be mounted on a single integrating structure, other than the aircraft fuselage itself. An active system must then be used to maintain the required alignment between elements. However the various smaller integrating structures (benches) must still be isolated from high- frequency airframe disturbances that could excite resonances outside the bandwidth of the alignment control system. The combined active alignment and vibration isolation functions must be performed by flight-weight components, which may have to operate in vacuum. A testbed system developed for the Air Force Airborne Laser program is described. The payload, a full-scale 1650-lb simulated bench, is mounted in six degrees- of-freedom to a vibrating platform by a set of isolator- actuators. The mounts utilize a combination of pneumatics and magnetics to perform the dual functions of low-frequency alignment and high-frequency isolation. Test results are given and future directions for development are described.

  15. Large Conductance Ca2+-Activated K+ Channels Modulate Uterine α1-Adrenergic Sensitivity in Ovine Pregnancy

    PubMed Central

    Hynan, Linda S.; Liu, Xiao-tie; Roy, Timothy

    2014-01-01

    The uteroplacental vasculature is refractory to α-adrenergic stimulation, and large conductance Ca2+-activated K+ channels (BKCa) may contribute. We examined the effects of uterine artery (UA) BKCa inhibition with tetraethylammonium (TEA) on hemodynamic responses to phenylephrine (PE) at 101 to 117 days and 135 to 147 days of ovine gestation, obtaining dose responses for mean arterial pressure (MAP), heart rate (HR), and uteroplacental blood flow (UPBF) and vascular resistance (UPVR) before and during UA TEA infusions. The UA α1-adrenergic receptors (α1-ARs) were assessed. The PE increased MAP and UPVR and decreased HR and UPBF dose dependently at both gestations (P < .001, analysis of variance). The %▵MAP was less at 135 to 147 days before and during TEA infusions (P ≤ .008); however, responses during TEA were greater (P ≤ .002). The PE increased %▵UPVR>>%▵MAP, thus %▵UPBF fell. The TEA enhanced PE-mediated increases in %▵UPVR at 135 to 147 days (P ≤ .03). The UA α1-AR expression was unchanged in pregnancy. Uterine vascular responses to PE exceed systemic vascular responses throughout pregnancy and are attenuated by BKCa activation, suggesting BKCa protect UPBF. PMID:24026311

  16. Antitumor activity of fucoidan against diffuse large B cell lymphoma in vitro and in vivo.

    PubMed

    Yang, Guang; Zhang, Qianqiao; Kong, Yuanyuan; Xie, Bingqian; Gao, Minjie; Tao, Yi; Xu, Hongwei; Zhan, Fenghuang; Dai, Bojie; Shi, Jumei; Wu, Xiaosong

    2015-11-01

    Fucoidan is one of the major sulfated polysaccharides isolated from brown seaweeds. In this study, we determined the anti-cancer activity of fucoidan on diffuse large B cell lymphoma (DLBCL) cells both in vitro and in vivo. Fucoidan inhibited the growth of DLBCL cells in a dose- and time-dependent manner, and fucoidan treatment provoked G0/G1 cell cycle arrest, which was accompanied by p21 up-regulation and cyclin D1, Cdk4, and Cdk6 down-regulation. Fucoidan also induced caspase-dependent cell apoptosis in DLBCL cell lines and primary DLBCL cell. In addition, fucoidan treatment caused the loss of mitochondrial membrane potential and the release of cytochrome c and apoptosis-inducing factor from the mitochondria into the cytosol. Fucoidan also potentiated the activities of carfilzomib in killing DLBCL cells. Oral administration of fucoidan effectively inhibited tumor growth in xenograft mouse models. Our findings reveal the novel function of fucoidan as an anti-DLBCL agent, which can be used in the clinical treatment of DLBCL.

  17. The influence of lightning activity and anthropogenic factors on large-scale characteristics of natural fires

    NASA Astrophysics Data System (ADS)

    Eliseev, A. V.; Mokhov, I. I.; Chernokulsky, A. V.

    2017-01-01

    A module for simulating of natural fires (NFs) in the climate model of the A.M. Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences (IAP RAS CM), is extended with respect to the influence of lightning activity and population density on the ignition frequency and fire suppression. The IAP RAS CM is used to perform numerical experiments in accordance with the conditions of the project that intercompares climate models, CMIP5 (Coupled Models Intercomparison Project, phase 5). The frequency of lightning flashes was assigned in accordance with the LIS/OTD satellite data. In the calculations performed, anthropogenic ignitions play an important role in NF occurrences, except for regions at subpolar latitudes and, to a lesser degree, tropical and subtropical regions. Taking into account the dependence of fire frequency on lightning activity and population density intensifies the influence of characteristics of natural fires on the climate changes in tropics and subtropics as compared to the version of the IAP RAS CM that does not take the influence of ignition sources on the large-scale characteristics of NFs into consideration.

  18. The large conductance calcium-activated K(+) channel interacts with the small GTPase Rab11b.

    PubMed

    Sokolowski, Sophia; Harvey, Margaret; Sakai, Yoshihisa; Jordan, Amy; Sokolowski, Bernd

    2012-09-21

    The transduction of sound by the receptor or hair cells of the cochlea leads to the activation of ion channels found in the basal and lateral regions of these cells. Thus, the processing of these transduced signals to the central nervous system is tied to the regulation of baso-lateral ion channels. The large conductance calcium-activated potassium or BK channel was revealed to interact with the small GTPase, Rab11b, which is one of many Rabs found in various endosomal pathways. Immunoelectron microscopy showed the colocalization of these two proteins in receptor cells and auditory neurons. Using Chinese hamster ovary cells as a heterologous expression system, Rab11b increased or decreased BK expression, depending on the overexpression or RNAi knockdown of Rab, respectively. Additional mutation analyses, using a yeast two-hybrid assay, suggested that this GTPase moderately interacts within a region of BK exclusive of the N- or C-terminal tails. These data suggest that this small GTPase regulates BK in a slow recycling process through the endocytic compartment and to the plasmalemma.

  19. The large conductance calcium-activated K+ channel interacts with the small GTPase Rab11b

    PubMed Central

    Sokolowski, Sophia; Harvey, Margaret; Sakai, Yoshihisa; Jordan, Amy; Sokolowski, Bernd

    2012-01-01

    The transduction of sound by the receptor or hair cells of the cochlea leads to the activation of ion channels found in the basal and lateral regions of these cells. Thus, the processing of these transduced signals to the central nervous system is tied to the regulation of baso-lateral ion channels. The large conductance calcium-activated potassium or BK channel was revealed to interact with the small GTPase, Rab11b, which is one of many Rabs found in various endosomal pathways. Immunoelectron microscopy showed the colocalization of these two proteins in receptor cells and auditory neurons. Using Chinese hamster ovary cells as a heterologous expression system, Rab11b increased or decreased BK expression, depending on the overexpression or RNAi knockdown of Rab, respectively. Additional mutation analyses, using a yeast two-hybrid assay, suggested that this GTPase moderately interacts within a region of BK exclusive of the N- or C-terminal tails. These data suggest that this small GTPase regulates BK in a slow recycling process through the endocytic compartment and to the plasmalemma. PMID:22935415

  20. The Large Conductance, Calcium-activated K+ (BK) Channel is regulated by Cysteine String Protein

    PubMed Central

    Kyle, Barry D.; Ahrendt, Eva; Braun, Andrew P.; Braun, Janice E. A.

    2013-01-01

    Large-conductance, calcium-activated-K+ (BK) channels are widely distributed throughout the nervous system, where they regulate action potential duration and firing frequency, along with presynaptic neurotransmitter release. Our recent efforts to identify chaperones that target neuronal ion channels have revealed cysteine string protein (CSPα) as a key regulator of BK channel expression and current density. CSPα is a vesicle-associated protein and mutations in CSPα cause the hereditary neurodegenerative disorder, adult-onset autosomal dominant neuronal ceroid lipofuscinosis (ANCL). CSPα null mice show 2.5 fold higher BK channel expression compared to wild type mice, which is not seen with other neuronal channels (i.e. Cav2.2, Kv1.1 and Kv1.2). Furthermore, mutations in either CSPα's J domain or cysteine string region markedly increase BK expression and current amplitude. We conclude that CSPα acts to regulate BK channel expression, and consequently CSPα-associated changes in BK activity may contribute to the pathogenesis of neurodegenerative disorders, such as ANCL. PMID:23945775

  1. Pituitary adenylate cyclase activating polypeptide (PACAP) dilates cerebellar arteries through activation of large-conductance Ca(2+)-activated (BK) and ATP-sensitive (K ATP) K (+) channels.

    PubMed

    Koide, Masayo; Syed, Arsalan U; Braas, Karen M; May, Victor; Wellman, George C

    2014-11-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent vasodilator of numerous vascular beds, including cerebral arteries. Although PACAP-induced cerebral artery dilation is suggested to be cyclic AMP (cAMP)-dependent, the downstream intracellular signaling pathways are still not fully understood. In this study, we examined the role of smooth muscle K(+) channels and hypothesized that PACAP-mediated increases in cAMP levels and protein kinase A (PKA) activity result in the coordinate activation of ATP-sensitive K(+) (KATP) and large-conductance Ca(2+)-activated K(+) (BK) channels for cerebral artery dilation. Using patch-clamp electrophysiology, we observed that PACAP enhanced whole-cell KATP channel activity and transient BK channel currents in freshly isolated rat cerebellar artery myocytes. The increased frequency of transient BK currents following PACAP treatment is indicative of increased intracellular Ca(2+) release events termed Ca(2+) sparks. Consistent with the electrophysiology data, the PACAP-induced vasodilations of cannulated cerebellar artery preparations were attenuated by approximately 50 % in the presence of glibenclamide (a KATP channel blocker) or paxilline (a BK channel blocker). Further, in the presence of both blockers, PACAP failed to cause vasodilation. In conclusion, our results indicate that PACAP causes cerebellar artery dilation through two mechanisms: (1) KATP channel activation and (2) enhanced BK channel activity, likely through increased Ca(2+) spark frequency.

  2. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance.

    PubMed

    Zhang, Yu-An; Tuft, Richard A; Lifshitz, Lawrence M; Fogarty, Kevin E; Singer, Joshua J; Zou, Hui

    2007-10-01

    Caffeine-activated, large-conductance, nonselective cation channels (LCCs) have been found in the plasma membrane of isolated cardiac myocytes in several species. However, little is known about the effects of opening these channels. To examine such effects and to further understand the caffeine-activation mechanism, we carried out studies using whole-cell patch-clamp techniques with freshly isolated cardiac myocytes from rats and mice. Unlike previous studies, thapsigargin was used so that both the effect of opening LCCs and the action of caffeine were independent of Ca(2+) release from intracellular stores. These Ca(2+)-permeable LCCs were found in a majority of the cells from atria and ventricles, with a conductance of approximately 370 pS in rat atria. Caffeine and all its direct metabolic products (theophylline, theobromine, and paraxanthine) activated the channel, while isocaffeine did not. Although they share some similarities with ryanodine receptors (RyRs, the openings of which give rise to Ca(2+) sparks), LCCs also showed some different characteristics. With simultaneous Ca(2+) imaging and current recording, the localized fluorescence increase due to Ca(2+) entry through a single opening of an LCC (SCCaFT) was detected. When membrane potential, instead of current, was recorded, SCCaFT-like fluorescence transients (indicating single LCC openings) were found to accompany membrane depolarizations. To our knowledge, this is the first report directly linking membrane potential changes to a single opening of an ion channel. Moreover, these events in cardiac cells suggest a possible additional mechanism by which caffeine and theophylline contribute to the generation of cardiac arrhythmias.

  3. Highly Active and Stable Large Catalase Isolated from a Hydrocarbon Degrading Aspergillus terreus MTCC 6324

    PubMed Central

    Vatsyayan, Preety; Goswami, Pranab

    2016-01-01

    A hydrocarbon degrading Aspergillus terreus MTCC 6324 produces a high level of extremely active and stable cellular large catalase (CAT) during growth on n-hexadecane to combat the oxidative stress caused by the hydrocarbon degrading metabolic machinery inside the cell. A 160-fold purification with specific activity of around 66 × 105 U mg−1 protein was achieved. The native protein molecular mass was 368 ± 5 kDa with subunit molecular mass of nearly 90 kDa, which indicates that the native CAT protein is a homotetramer. The isoelectric pH (pI) of the purified CAT was 4.2. BLAST aligned peptide mass fragments of CAT protein showed its highest similarity with the catalase B protein from other fungal sources. CAT was active in a broad range of pH 4 to 12 and temperature 25°C to 90°C. The catalytic efficiency (Kcat/Km) of 4.7 × 108 M−1 s−1 within the studied substrate range and alkaline pH stability (half-life, t1/2 at pH 12~15 months) of CAT are considerably higher than most of the extensively studied catalases from different sources. The storage stability (t1/2) of CAT at physiological pH 7.5 and 4°C was nearly 30 months. The haem was identified as haem b by electrospray ionization tandem mass spectroscopy (ESI-MS/MS). PMID:27057351

  4. Measurement of fumonisins in corn with a fiber optic fluoroimmunosensor

    NASA Astrophysics Data System (ADS)

    Thompson, Vicki S.; Maragos, Chris M.

    1997-05-01

    A fiber-optic immunosensor was used to determine concentrations of the mycotoxin fumonisin B1(FB1) in both spiked and naturally contaminated corn samples. Samples were extracted with a mixture of methanol/water. Two methods were used to prepare the methanolic corn extracts before introduction to the immunosensor: (1) simple dilution of the methanolic corn extract; or (2) affinity column cleanup. The sensor displayed an IC50 of 70 ng FB1/mL when toxin was introduced in phosphate buffered saline. Simple dilution of methanolic corn extracts yielded an assay with an IC50 equivalent to 25 (mu) gFB1/g corn and a limit of detection of 3.2 (mu) g/g corn, while affinity cleanup of corn extracts yielded an assay with an IC50 of 5 (mu) gFB1/g corn and a limit of detection of 0.4 (mu) gFB1/g corn. The difference in sensitivity between the two cleanup techniques was due to concentration of fumonisins obtained from the affinity cleanup procedure. Naturally contaminated corn samples were also analyzed after either simple dilution or affinity column cleanup. For comparison the naturally contaminated corn samples were analyzed with an HPLC method after isolation of the fumonisins with strong anion exchange (SAX) solid phase extraction cartridges. The SAX/HPLC method and the immunosensor method agreed well except when large amounts of other fumonisins (i.e. fumonisin B2) were present. This was due in part to the cross-reactivity of the monoclonal antibody with other fumonisins. The immunosensor has the potential to screen individual corn samples for fumonisins within six minutes, and is among the fastest of the currently available FB1 detection methods.

  5. A Case Study of How a Large Multilevel EFL Writing Class Experiences and Perceives Multiple Interaction Activities

    ERIC Educational Resources Information Center

    Lin, Hsien-Chuan

    2009-01-01

    The purpose of this study was to examine students' experiences and perceptions of multiple interaction activities (self-directed, peer, and teacher feedback) implemented in a large multilevel EFL writing class in one private technological university in the southern part of Taiwan. Large size writing classes, quite common in private institutions of…

  6. RADIO-SELECTED BINARY ACTIVE GALACTIC NUCLEI FROM THE VERY LARGE ARRAY STRIPE 82 SURVEY

    SciTech Connect

    Fu, Hai; Myers, A. D.; Djorgovski, S. G.; Yan, Lin; Wrobel, J. M.; Stockton, A.

    2015-01-20

    Galaxy mergers play an important role in the growth of galaxies and their supermassive black holes. Simulations suggest that tidal interactions could enhance black hole accretion, which can be tested by the fraction of binary active galactic nuclei (AGNs) among galaxy mergers. However, determining the fraction requires a statistical sample of binaries. We have identified kiloparsec-scale binary AGNs directly from high-resolution radio imaging. Inside the 92 deg{sup 2} covered by the high-resolution Very Large Array survey of the Sloan Digital Sky Survey (SDSS) Stripe 82 field, we identified 22 grade A and 30 grade B candidates of binary radio AGNs with angular separations less than 5'' (10 kpc at z = 0.1). Eight of the candidates have optical spectra for both components from the SDSS spectroscopic surveys and our Keck program. Two grade B candidates are projected pairs, but the remaining six candidates are all compelling cases of binary AGNs based on either emission line ratios or the excess in radio power compared to the Hα-traced star formation rate. Only two of the six binaries were previously discovered by an optical spectroscopic search. Based on these results, we estimate that ∼60% of our binary candidates would be confirmed once we obtain complete spectroscopic information. We conclude that wide-area high-resolution radio surveys offer an efficient method to identify large samples of binary AGNs. These radio-selected binary AGNs complement binaries identified at other wavelengths and are useful for understanding the triggering mechanisms of black hole accretion.

  7. Selectivity filter gating in large-conductance Ca(2+)-activated K+ channels.

    PubMed

    Thompson, Jill; Begenisich, Ted

    2012-03-01

    Membrane voltage controls the passage of ions through voltage-gated K (K(v)) channels, and many studies have demonstrated that this is accomplished by a physical gate located at the cytoplasmic end of the pore. Critical to this determination were the findings that quaternary ammonium ions and certain peptides have access to their internal pore-blocking sites only when the channel gates are open, and that large blocking ions interfere with channel closing. Although an intracellular location for the physical gate of K(v) channels is well established, it is not clear if such a cytoplasmic gate exists in all K(+) channels. Some studies on large-conductance, voltage- and Ca(2+)-activated K(+) (BK) channels suggest a cytoplasmic location for the gate, but other findings question this conclusion and, instead, support the concept that BK channels are gated by the pore selectivity filter. If the BK channel is gated by the selectivity filter, the interactions between the blocking ions and channel gating should be influenced by the permeant ion. Thus, we tested tetrabutyl ammonium (TBA) and the Shaker "ball" peptide (BP) on BK channels with either K(+) or Rb(+) as the permeant ion. When tested in K(+) solutions, both TBA and the BP acted as open-channel blockers of BK channels, and the BP interfered with channel closing. In contrast, when Rb(+) replaced K(+) as the permeant ion, TBA and the BP blocked both closed and open BK channels, and the BP no longer interfered with channel closing. We also tested the cytoplasmically gated Shaker K channels and found the opposite behavior: the interactions of TBA and the BP with these K(v) channels were independent of the permeant ion. Our results add significantly to the evidence against a cytoplasmic gate in BK channels and represent a positive test for selectivity filter gating.

  8. Radio-selected Binary Active Galactic Nuclei from the Very Large Array Stripe 82 Survey

    NASA Astrophysics Data System (ADS)

    Fu, Hai; Myers, A. D.; Djorgovski, S. G.; Yan, Lin; Wrobel, J. M.; Stockton, A.

    2015-01-01

    Galaxy mergers play an important role in the growth of galaxies and their supermassive black holes. Simulations suggest that tidal interactions could enhance black hole accretion, which can be tested by the fraction of binary active galactic nuclei (AGNs) among galaxy mergers. However, determining the fraction requires a statistical sample of binaries. We have identified kiloparsec-scale binary AGNs directly from high-resolution radio imaging. Inside the 92 deg2 covered by the high-resolution Very Large Array survey of the Sloan Digital Sky Survey (SDSS) Stripe 82 field, we identified 22 grade A and 30 grade B candidates of binary radio AGNs with angular separations less than 5'' (10 kpc at z = 0.1). Eight of the candidates have optical spectra for both components from the SDSS spectroscopic surveys and our Keck program. Two grade B candidates are projected pairs, but the remaining six candidates are all compelling cases of binary AGNs based on either emission line ratios or the excess in radio power compared to the Hα-traced star formation rate. Only two of the six binaries were previously discovered by an optical spectroscopic search. Based on these results, we estimate that ~60% of our binary candidates would be confirmed once we obtain complete spectroscopic information. We conclude that wide-area high-resolution radio surveys offer an efficient method to identify large samples of binary AGNs. These radio-selected binary AGNs complement binaries identified at other wavelengths and are useful for understanding the triggering mechanisms of black hole accretion. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

  9. Selectivity filter gating in large-conductance Ca2+-activated K+ channels

    PubMed Central

    Thompson, Jill

    2012-01-01

    Membrane voltage controls the passage of ions through voltage-gated K (Kv) channels, and many studies have demonstrated that this is accomplished by a physical gate located at the cytoplasmic end of the pore. Critical to this determination were the findings that quaternary ammonium ions and certain peptides have access to their internal pore-blocking sites only when the channel gates are open, and that large blocking ions interfere with channel closing. Although an intracellular location for the physical gate of Kv channels is well established, it is not clear if such a cytoplasmic gate exists in all K+ channels. Some studies on large-conductance, voltage- and Ca2+-activated K+ (BK) channels suggest a cytoplasmic location for the gate, but other findings question this conclusion and, instead, support the concept that BK channels are gated by the pore selectivity filter. If the BK channel is gated by the selectivity filter, the interactions between the blocking ions and channel gating should be influenced by the permeant ion. Thus, we tested tetrabutyl ammonium (TBA) and the Shaker “ball” peptide (BP) on BK channels with either K+ or Rb+ as the permeant ion. When tested in K+ solutions, both TBA and the BP acted as open-channel blockers of BK channels, and the BP interfered with channel closing. In contrast, when Rb+ replaced K+ as the permeant ion, TBA and the BP blocked both closed and open BK channels, and the BP no longer interfered with channel closing. We also tested the cytoplasmically gated Shaker K channels and found the opposite behavior: the interactions of TBA and the BP with these Kv channels were independent of the permeant ion. Our results add significantly to the evidence against a cytoplasmic gate in BK channels and represent a positive test for selectivity filter gating. PMID:22371364

  10. A Large-N Mixed Sensor Active + Passive Seismic Array near Sweetwater, TX

    NASA Astrophysics Data System (ADS)

    Barklage, M.; Hollis, D.; Gridley, J. M.; Woodward, R.; Spriggs, N.

    2014-12-01

    A collaborative high-density seismic survey using broadband and short period seismic sensors was conducted March 7 - April 30, 2014 near Sweetwater, TX. The objective of the survey was to use a combination of controlled source shot slices and passive seismic recordings recorded by multiple types of sensors with different bandwidths and sensitivities to image the subsurface. The broadband component of the survey consisted of 25 continuously recording seismic stations comprised of 20 Trillium Compact Posthole sensors from Nanometrics and 5 Polar Trillium 120PHQs from the IRIS/PASSCAL Instrument Center (PIC). The broadband stations also utilized 25 Centaur digitizers from Nanometrics as well as 25 polar quick deploy enclosures from the PIC. The broadband array was designed to maximize horizontal traveling seismic energy for surface wave analysis over the primary target area with sufficient offset for imaging objectives at depth. The short period component of the survey consisted of 2639 receiver locations using Zland nodes from NodalSeismic. The nodes are further divided into 3 sub-arrays: 1) outlier array 2) active source array 3) backbone array. The outlier array consisted of 25 continuously recording nodes distributed around the edge of the survey at a distance of ~5 km from the survey boundary, and provided valuable constraints to passive data analysis techniques at the edge of the survey boundary. The active source patch consisted of densely spaced nodes that were designed to record signals from a Vibroseis source truck for active source reflection processing and imaging. The backbone array consisted of 292 nodes that covered the entirety of the survey area to maximize the value of the passive data analysis. By utilizing continuous recording and smartly designed arrays for measuring local and regional earthquakes we can incorporate velocity information derived from passive data analysis into the active source processing workflow to produce a superior subsurface

  11. Gaining A Geological Perspective Through Active Learning in the Large Lecture Classroom

    NASA Astrophysics Data System (ADS)

    Kapp, J. L.; Richardson, R. M.; Slater, S. J.

    2008-12-01

    NATS 101 A Geological Perspective is a general education course taken by non science majors. We offer 600 seats per semester, with four large lecture sections taught by different faculty members. In the past we have offered optional once a week study groups taught by graduate teaching assistants. Students often feel overwhelmed by the science and associated jargon, and many are prone to skipping lectures altogether. Optional study groups are only attended by ~50% of the students. Faculty members find the class to be a lot of work, mainly due to the grading it generates. Activities given in lecture are often short multiple choice or true false assignments, limiting the depth of understanding we can evaluate. Our students often lack math and critical thinking skills, and we spend a lot of time in lecture reintroducing ideas students should have already gotten from the text. In summer 2007 we were funded to redesign the course. Our goals were to 1) cut the cost of running the course, and 2) improve student learning. Under our redesign optional study groups were replaced by once a week mandatory break out sessions where students complete activities that have been introduced in lecture. Break out sessions substitute for one hour of lecture, and are run by undergraduate preceptors and graduate teaching assistants (GTAs). During the lecture period, lectures themselves are brief with a large portion of the class devoted to active learning in small groups. Weekly reading quizzes are submitted via the online course management system. Break out sessions allow students to spend more time interacting with their fellow students, undergraduate preceptors, and GTAs. They get one on one help in break out sessions on assignments designed to enhance the lecture material. The active lecture format means less of their time is devoted to listening passively to a lecture, and more time is spent peer learning an interacting with the instructor. Completing quizzes online allows students

  12. Squeezed pulsed light from a fiber ring interferometer

    NASA Technical Reports Server (NTRS)

    Bergman, K.; Haus, H. A.

    1992-01-01

    Observation of squeezed noise, 5 +/- 0.3 dB below the shot noise level, generated with pulses in a fiber ring interferometer is reported. The interferometric geometry is used to separate the pump pulse from the squeezed vacuum radiation. A portion of the pump is reused as the local oscillator in a homodyne detection. The pump fluctuations are successfully subtracted and shot noise limited performance is achieved at low frequencies (35-85 KHz). A possible utilization of the generated squeezed vacuum in improving a fiber gyro's signal to noise ratio is discussed.

  13. Improved confinement region without large magnetohydrodynamic activity in TPE-RX reversed-field pinch plasma

    NASA Astrophysics Data System (ADS)

    Yambe, Kiyoyuki; Hirano, Yoichi; Sakakita, Hajime; Koguchi, Haruhisa

    2014-11-01

    We found that spontaneous improved confinement was brought about depending on the operating region in the Toroidal Pinch Experiment-Reversed eXperiment (TPE-RX) reversed-field pinch plasma [Y. Yagi et al., Fusion Eng. Des. 45, 421 (1999)]. Gradual decay of the toroidal magnetic field at plasma surface Btw reversal makes it possible to realize a prolonged discharge, and the poloidal beta value and energy confinement time increase in the latter half of the discharge, where reversal and pinch parameters become shallow and low, respectively. In the latter half of the discharge, the plasma current and volume-averaged toroidal magnetic field increase again, the electron density slowly decays, the electron temperature and soft X-ray radiation intensity increase, and the magnetic fluctuations are markedly reduced. In this period of improved confinement, the value of (-Btw)/Bpw, where Bpw is the poloidal magnetic field at the plasma surface, stays almost constant, which indicates that the dynamo action occurs without large magnetohydrodynamic activities.

  14. Improved confinement region without large magnetohydrodynamic activity in TPE-RX reversed-field pinch plasma

    SciTech Connect

    Yambe, Kiyoyuki; Hirano, Yoichi; Sakakita, Hajime; Koguchi, Haruhisa

    2014-11-15

    We found that spontaneous improved confinement was brought about depending on the operating region in the Toroidal Pinch Experiment-Reversed eXperiment (TPE-RX) reversed-field pinch plasma [Y. Yagi et al., Fusion Eng. Des. 45, 421 (1999)]. Gradual decay of the toroidal magnetic field at plasma surface B{sub tw} reversal makes it possible to realize a prolonged discharge, and the poloidal beta value and energy confinement time increase in the latter half of the discharge, where reversal and pinch parameters become shallow and low, respectively. In the latter half of the discharge, the plasma current and volume-averaged toroidal magnetic field 〈B{sub t}〉 increase again, the electron density slowly decays, the electron temperature and soft X-ray radiation intensity increase, and the magnetic fluctuations are markedly reduced. In this period of improved confinement, the value of (〈B{sub t}〉-B{sub tw})/B{sub pw}, where B{sub pw} is the poloidal magnetic field at the plasma surface, stays almost constant, which indicates that the dynamo action occurs without large magnetohydrodynamic activities.

  15. Active power control of solar PV generation for large interconnection frequency regulation and oscillation damping

    DOE PAGES

    Liu, Yong; Zhu, Lin; Zhan, Lingwei; ...

    2015-06-23

    Because of zero greenhouse gas emission and decreased manufacture cost, solar photovoltaic (PV) generation is expected to account for a significant portion of future power grid generation portfolio. Because it is indirectly connected to the power grid via power electronic devices, solar PV generation system is fully decoupled from the power grid, which will influence the interconnected power grid dynamic characteristics as a result. In this study, the impact of solar PV penetration on large interconnected power system frequency response and inter-area oscillation is evaluated, taking the United States Eastern Interconnection (EI) as an example. Furthermore, based on the constructedmore » solar PV electrical control model with additional active power control loops, the potential contributions of solar PV generation to power system frequency regulation and oscillation damping are examined. The advantages of solar PV frequency support over that of wind generator are also discussed. Finally, simulation results demonstrate that solar PV generations can effectively work as ‘actuators’ in alleviating the negative impacts they bring about.« less

  16. Active power control of solar PV generation for large interconnection frequency regulation and oscillation damping

    SciTech Connect

    Liu, Yong; Zhu, Lin; Zhan, Lingwei; Gracia, Jose R.; King, Thomas Jr.; Liu, Yilu

    2015-06-23

    Because of zero greenhouse gas emission and decreased manufacture cost, solar photovoltaic (PV) generation is expected to account for a significant portion of future power grid generation portfolio. Because it is indirectly connected to the power grid via power electronic devices, solar PV generation system is fully decoupled from the power grid, which will influence the interconnected power grid dynamic characteristics as a result. In this study, the impact of solar PV penetration on large interconnected power system frequency response and inter-area oscillation is evaluated, taking the United States Eastern Interconnection (EI) as an example. Furthermore, based on the constructed solar PV electrical control model with additional active power control loops, the potential contributions of solar PV generation to power system frequency regulation and oscillation damping are examined. The advantages of solar PV frequency support over that of wind generator are also discussed. Finally, simulation results demonstrate that solar PV generations can effectively work as ‘actuators’ in alleviating the negative impacts they bring about.

  17. Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons.

    PubMed

    Sun, P; Zhang, Q; Zhang, Y; Wang, F; Wang, L; Yamamoto, R; Sugai, T; Kato, N

    2015-01-01

    It was previously shown that depression-like behavior is accompanied with suppression of the large-conductance calcium activated potassium (BK) channel in cingulate cortex pyramidal cells. To test whether BK channels are also involved in fear conditioning, we studied neuronal properties of amygdala principal cells in fear conditioned mice. After behavior, we made brain slices containing the amygdala, the structure critically relevant to fear memory. The resting membrane potential in lateral amygdala (LA) neurons obtained from fear conditioned mice (FC group) was more depolarized than in neurons from naïve controls. The frequencies of spikes evoked by current injections were higher in neurons from FC mice, demonstrating that excitability of LA neurons was elevated by fear conditioning. The depolarization in neurons from FC mice was shown to depend on BK channels by using the BK channel blocker charybdotoxin. Suppression of BK channels in LA neurons from the FC group was further confirmed on the basis of the spike width, since BK channels affect the descending phase of spikes. Spikes were broader in the FC group than those in the naïve control in a manner dependent on BK channels. Consistently, quantitative real-time PCR revealed a decreased expression of BK channel mRNA. The present findings suggest that emotional disorder manifested in the forms of fear conditioning is accompanied with BK channel suppression in the amygdala, the brain structure critical to this emotional disorder.

  18. Hurricane activity and the large-scale pattern of spread of an invasive plant species.

    PubMed

    Bhattarai, Ganesh P; Cronin, James T

    2014-01-01

    Disturbances are a primary facilitator of the growth and spread of invasive species. However, the effects of large-scale disturbances, such as hurricanes and tropical storms, on the broad geographic patterns of invasive species growth and spread have not been investigated. We used historical aerial imagery to determine the growth rate of invasive Phragmites australis patches in wetlands along the Atlantic and Gulf Coasts of the United States. These were relatively undisturbed wetlands where P. australis had room for unrestricted growth. Over the past several decades, invasive P. australis stands expanded in size by 6-35% per year. Based on tropical storm and hurricane activity over that same time period, we found that the frequency of hurricane-force winds explained 81% of the variation in P. australis growth over this broad geographic range. The expansion of P. australis stands was strongly and positively correlated with hurricane frequency. In light of the many climatic models that predict an increase in the frequency and intensity of hurricanes over the next century, these results suggest a strong link between climate change and species invasion and a challenging future ahead for the management of invasive species.

  19. Denitrification in a large river: consideration of geomorphic controls on microbial activity and community structure.

    PubMed

    Tatariw, Corianne; Chapman, Elise L; Sponseller, Ryan A; Mortazavi, Behzad; Edmonds, Jennifer W

    2013-10-01

    Ecological theory argues that the controls over ecosystem processes are structured hierarchically, with broader-scale drivers acting as constraints over the interactions and dynamics at nested levels of organization. In river ecosystems, these interactions may arise from broadscale variation in channel form that directly shapes benthic habitat structure and indirectly constrains resource supply and biological activity within individual reaches. To evaluate these interactions, we identified sediment characteristics, water chemistry, and denitrifier community structure as factors influencing benthic denitrification rates in a sixth-order river that flows through two physiographic provinces and the transitional zone between them, each with distinct geomorphological properties. We found that denitrification rates tracked spatial changes in sediment characteristics and varied seasonally with expected trends in stream primary production. Highest rates were observed during the spring and summer seasons in the physiographic province dominated by fine-grained sediments, illustrating how large-scale changes in river structure can constrain the location of denitrification hotspots. In addition, nirS and nirK community structure each responded differently to variation in channel form, possibly due to changes in dissolved oxygen and organic matter supply. This shift in denitrifier community structure coincident with higher rates of N removal via denitrification suggests that microbial community structure may influence biogeochemical processes.

  20. DYNAMICS OF LARGE FRAGMENTS IN THE TAIL OF ACTIVE ASTEROID P/2010 A2

    SciTech Connect

    Agarwal, Jessica; Jewitt, David; Weaver, Harold

    2013-05-20

    We examine the motions of large fragments at the head of the dust tail of the active asteroid P/2010 A2. In previous work, we showed that these fragments were ejected from the primary nucleus in early 2009, either following a hypervelocity impact or by rotationally induced breakup. Here, we follow their positions through a series of Hubble Space Telescope images taken during the first half of 2010. The orbital evolution of each fragment allows us to constrain its velocity relative to the main nucleus after leaving its sphere of gravitational influence. We find that the fragments constituting a prominent X-shaped tail feature were emitted in a direction opposite to the motion of the asteroid and toward the south of its orbital plane. Derived emission velocities of these primary fragments range between 0.02 and 0.3 m s{sup -1}, comparable to the {approx}0.08 m s{sup -1} gravitational escape speed from the nucleus. Their sizes are on the order of decimeters or larger. We obtain the best fits to our data with ejection velocity vectors lying in a plane that includes the nucleus. This may suggest that the cause of the disruption of P/2010 A2 is rotational breakup.

  1. Oxygen-activated growth and bandgap tunability of large single-crystal bilayer graphene

    SciTech Connect

    Hao, Yufeng; Wang, Lei; Liu, Yuanyue; Chen, Hua; Wang, Xiaohan; Tan, Cheng; Nie, Shu; Suk, Ji Won; Jiang, Tengfei; Liang, Tengfei; Xiao, Junfeng; Ye, Wenjing; Dean, Cory R.; Yakobson, Boris I.; McCarty, Kevin F.; Kim, Philip; Hone, James; Colombo, Luigi; Ruoff, Rodney S.

    2016-02-01

    Bernal (AB)-stacked bilayer graphene (BLG) is a semiconductor whose bandgap can be tuned by a transverse electric field, making it a unique material for a number of electronic and photonic devices. A scalable approach to synthesize high-quality BLG is therefore critical, which requires minimal crystalline defects in both graphene layers and maximal area of Bernal stacking, which is necessary for bandgap tunability. Here we demonstrate that in an oxygen-activated chemical vapour deposition (CVD) process, half-millimetre size, Bernal-stacked BLG single crystals can be synthesized on Cu. Besides the traditional 'surface-limited' growth mechanism for SLG (1st layer), we discovered new microscopic steps governing the growth of the 2nd graphene layer below the 1st layer as the diffusion of carbon atoms through the Cu bulk after complete dehydrogenation of hydrocarbon molecules on the Cu surface, which does not occur in the absence of oxygen. Moreover, we found that the efficient diffusion of the carbon atoms present at the interface between Cu and the 1st graphene layer further facilitates growth of large domains of the 2nd layer. The CVD BLG has superior electrical quality, with a device on/off ratio greater than 104, and a tunable bandgap up to -100 meV at a displacement field of 0.9 V nm-1.

  2. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma

    PubMed Central

    Cardenas, Mariano G.; Yu, Wenbo; Beguelin, Wendy; Teater, Matthew R.; Geng, Huimin; Goldstein, Rebecca L.; Oswald, Erin; Hatzi, Katerina; Yang, Shao-Ning; Cohen, Joanna; Shaknovich, Rita; Vanommeslaeghe, Kenno; Cheng, Huimin; Liang, Dongdong; Cho, Hyo Je; Tam, Wayne; Du, Wei; Leonard, John P.; Elemento, Olivier; Cierpicki, Tomasz; Xue, Fengtian; MacKerell, Alexander D.; Melnick, Ari M.

    2016-01-01

    Diffuse large B cell lymphomas (DLBCLs) arise from proliferating B cells transiting different stages of the germinal center reaction. In activated B cell DLBCLs (ABC-DLBCLs), a class of DLBCLs that respond poorly to current therapies, chromosomal translocations and amplification lead to constitutive expression of the B cell lymphoma 6 (BCL6) oncogene. The role of BCL6 in maintaining these lymphomas has not been investigated. Here, we designed small-molecule inhibitors that display higher affinity for BCL6 than its endogenous corepressor ligands to evaluate their therapeutic efficacy for targeting ABC-DLBCL. We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor called FX1 that has 10-fold greater potency than endogenous corepressors and binds an essential region of the BCL6 lateral groove. FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. Low doses of FX1 induced regression of established tumors in mice bearing DLBCL xenografts. Furthermore, FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. These findings indicate that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands. PMID:27482887

  3. The First Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope

    NASA Astrophysics Data System (ADS)

    Abdo, A. A.; Ackermann, M.; Ajello, M.; Allafort, A.; Antolini, E.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Baughman, B. M.; Bechtol, K.; Bellazzini, R.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Bogart, J. R.; Bonamente, E.; Borgland, A. W.; Bouvier, A.; Bregeon, J.; Brez, A.; Brigida, M.; Bruel, P.; Buehler, R.; Burnett, T. H.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Cannon, A.; Caraveo, P. A.; Carrigan, S.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Çelik, Ö.; Celotti, A.; Charles, E.; Chekhtman, A.; Chen, A. W.; Cheung, C. C.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Conrad, J.; Costamante, L.; Cotter, G.; Cutini, S.; D'Elia, V.; Dermer, C. D.; de Angelis, A.; de Palma, F.; De Rosa, A.; Digel, S. W.; Silva, E. do Couto e.; Drell, P. S.; Dubois, R.; Dumora, D.; Escande, L.; Farnier, C.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Fortin, P.; Frailis, M.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giebels, B.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grandi, P.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guiriec, S.; Hadasch, D.; Harding, A. K.; Hayashida, M.; Hays, E.; Healey, S. E.; Hill, A. B.; Horan, D.; Hughes, R. E.; Iafrate, G.; Itoh, R.; Jóhannesson, G.; Johnson, A. S.; Johnson, R. P.; Johnson, T. J.; Johnson, W. N.; Kamae, T.; Katagiri, H.; Kataoka, J.; Kawai, N.; Kerr, M.; Knödlseder, J.; Kuss, M.; Lande, J.; Latronico, L.; Lavalley, C.; Lemoine-Goumard, M.; Llena Garde, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Makeev, A.; Malaguti, G.; Massaro, E.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; McGlynn, S.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nolan, P. L.; Norris, J. P.; Nuss, E.; Ohno, M.; Ohsugi, T.; Omodei, N.; Orlando, E.; Ormes, J. F.; Ozaki, M.; Paneque, D.; Panetta, J. H.; Parent, D.; Pelassa, V.; Pepe, M.; Pesce-Rollins, M.; Piranomonte, S.; Piron, F.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Reimer, A.; Reimer, O.; Reposeur, T.; Ripken, J.; Ritz, S.; Rodriguez, A. Y.; Romani, R. W.; Roth, M.; Ryde, F.; Sadrozinski, H. F.-W.; Sanchez, D.; Sander, A.; Saz Parkinson, P. M.; Scargle, J. D.; Sgrò, C.; Shaw, M. S.; Siskind, E. J.; Smith, P. D.; Spandre, G.; Spinelli, P.; Starck, J.-L.; Stawarz, Ł.; Strickman, M. S.; Suson, D. J.; Tajima, H.; Takahashi, H.; Takahashi, T.; Tanaka, T.; Taylor, G. B.; Thayer, J. B.; Thayer, J. G.; Thompson, D. J.; Tibaldo, L.; Torres, D. F.; Tosti, G.; Tramacere, A.; Ubertini, P.; Uchiyama, Y.; Usher, T. L.; Vasileiou, V.; Vilchez, N.; Villata, M.; Vitale, V.; Waite, A. P.; Wallace, E.; Wang, P.; Winer, B. L.; Wood, K. S.; Yang, Z.; Ylinen, T.; Ziegler, M.

    2010-05-01

    We present the first catalog of active galactic nuclei (AGNs) detected by the Large Area Telescope (LAT), corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes 671 γ-ray sources located at high Galactic latitudes (|b|>10°) that are detected with a test statistic greater than 25 and associated statistically with AGNs. Some LAT sources are associated with multiple AGNs, and consequently, the catalog includes 709 AGNs, comprising 300 BL Lacertae objects, 296 flat-spectrum radio quasars, 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazars based on their spectral energy distributions as archival radio, optical, and X-ray data permit. In addition to the formal 1LAC sample, we provide AGN associations for 51 low-latitude LAT sources and AGN "affiliations" (unquantified counterpart candidates) for 104 high-latitude LAT sources without AGN associations. The overlap of the 1LAC with existing γ-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties—such as γ-ray fluxes and photon power-law spectral indices, redshifts, γ-ray luminosities, variability, and archival radio luminosities—and their correlations are presented and discussed for the different blazar classes. We compare the 1LAC results with predictions regarding the γ-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequence.

  4. Large zinc cation occupancy of octahedral sites in mechanically activated zinc ferrite powders

    SciTech Connect

    Oliver, S. A.; Harris, V. G.; Hamdeh, H. H.; Ho, J. C.

    2000-05-08

    The cation site occupancy of a mechanically activated nanocrystalline zinc ferrite powder was determined as (Zn{sub 0.55}{sup 2+}Fe{sub 0.18}{sup 3+}){sub tet}[Zr{sub 0.45}{sup 2+}Fe{sub 1.82}{sup 3+}]{sub oct}O{sub 4} through analysis of extended x-ray absorption fine structure measurements, showing a large redistribution of cations between sites compared to normal zinc ferrite samples. The overpopulation of cations in the octahedral sites was attributed to the ascendance in importance of the ionic radii over the crystal energy and bonding coordination in determining which interstitial sites are occupied in this structurally disordered powder. Slight changes are observed in the local atomic environment about the zinc cations, but not the iron cations, with respect to the spinel structure. The presence of Fe{sup 3+} on both sites is consistent with the measured room temperature magnetic properties. (c) 2000 American Institute of Physics.

  5. Promotoras as Data Collectors in a Large Study of Physical Activity in Parks

    PubMed Central

    Marsh, Terry; Derose, Kathryn Pitkin; Rios, Muriel; Cohen, Deborah

    2015-01-01

    There is a large literature on promotores’ involvement in health promotion and a smaller literature on their roles in data collection, most often among predominantly Latino populations. But the extent to which promotores can be successful as the primary data collectors across racially/ethnically and socioeconomically diverse neighborhoods is less well documented. In a study of physical activity in 50 urban neighborhood parks, we found that a team of Spanish/English bilingual promotoras (female promotores) successfully implemented a direct observation protocol in all participant neighborhoods and achieved high interrater reliability (.80-.98). Overall, they were also effective in administering surveys to park users and residents across the racially/ethnically diverse neighborhoods. The promotoras brought to the project important language skills and cultural sensitivity, surveying experience, and familiarity with human subjects and confidentiality issues. Their extensive field experience gained over the course of a long-term collaborative effort helped improve survey and observation protocols. The promotoras reported gaining professional skills, which can strengthen their contributions to other projects. The promotoras were accustomed to being a source of information, and collecting rather than providing information was challenging for some and had to be addressed in order to avoid contamination across study groups. PMID:25649234

  6. Characteristics of active regions associated to large solar energetic proton events

    NASA Astrophysics Data System (ADS)

    Bronarska, K.; Michalek, G.

    2017-01-01

    The relationship between properties of active regions (ARs) and solar energetic particles (SEP events, protons with energy ⩾10 MeV) is examined. For this purpose we study 84 SEP events recorded during the SOHO era (1996-2014). We compare properties of these SEP events with associated ARs, flares and CMEs. The ARs are characterized by McIntosh classification. Statistical analysis demonstrates that SEP events are more likely to be associated to the ARs having complex magnetic structures and the most energetic SEPs are ejected only from the associated ARs having a large and asymmetric penumbra. This tendency is used to estimate intensities of potential SEP events. For this purpose we express a probability of occurrence of an SEP event from a given AR which is correlated with fluxes of associated SEPs. We find that SEP events associated with ARs from eastern longitudes have to be more complex to produce SEP events at Earth. On the other hand, SEP particles originating from mid-longitudes (30 ° < longitude < 70 °) on the west side of solar disk are associated to the least complex ARs. These results could be useful for forecasting of space weather.

  7. Promoting active learning using audience response system in large bioscience classes.

    PubMed

    Efstathiou, Nikolaos; Bailey, Cara

    2012-01-01

    This paper considers the challenges of bioscience teaching and learning in pre-registration nurse education. Effective learning requires active student participation which is problematic when teaching large groups of students. New technologies, such as the audience response system (ARS), have been introduced to increase student participation and support them in the understanding of complex bioscience concepts. Within one university department, an evaluation was undertaken to identify the perceptions of pre-registration nurse students on the use of ARS in the teaching and learning of bioscience. Our findings concur with others that ARS increases student participation and aids in identifying misconceptions and in correcting them. Students found ARS very useful and wanted ARS to be used in additional modules too. Although ARS did not seem to motivate students to study adequately before attending the relevant sessions, it increased discussion among students and awareness of their level of knowledge compared to their peers. Further research is required to identify the effectiveness of ARS in the teaching and learning of bioscience and its impact on the performance of the students in their final assessments.

  8. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.

    PubMed

    Cardenas, Mariano G; Yu, Wenbo; Beguelin, Wendy; Teater, Matthew R; Geng, Huimin; Goldstein, Rebecca L; Oswald, Erin; Hatzi, Katerina; Yang, Shao-Ning; Cohen, Joanna; Shaknovich, Rita; Vanommeslaeghe, Kenno; Cheng, Huimin; Liang, Dongdong; Cho, Hyo Je; Abbott, Joshua; Tam, Wayne; Du, Wei; Leonard, John P; Elemento, Olivier; Cerchietti, Leandro; Cierpicki, Tomasz; Xue, Fengtian; MacKerell, Alexander D; Melnick, Ari M

    2016-09-01

    Diffuse large B cell lymphomas (DLBCLs) arise from proliferating B cells transiting different stages of the germinal center reaction. In activated B cell DLBCLs (ABC-DLBCLs), a class of DLBCLs that respond poorly to current therapies, chromosomal translocations and amplification lead to constitutive expression of the B cell lymphoma 6 (BCL6) oncogene. The role of BCL6 in maintaining these lymphomas has not been investigated. Here, we designed small-molecule inhibitors that display higher affinity for BCL6 than its endogenous corepressor ligands to evaluate their therapeutic efficacy for targeting ABC-DLBCL. We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor called FX1 that has 10-fold greater potency than endogenous corepressors and binds an essential region of the BCL6 lateral groove. FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. Low doses of FX1 induced regression of established tumors in mice bearing DLBCL xenografts. Furthermore, FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. These findings indicate that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands.

  9. Active edge control in the precessions polishing process for manufacturing large mirror segments

    NASA Astrophysics Data System (ADS)

    Li, Hongyu; Zhang, Wei; Walker, David; Yu, Gouyo

    2014-09-01

    The segmentation of the primary mirror is the only promising solution for building the next generation of ground telescopes. However, manufacturing segmented mirrors presents its own challenges. The edge mis-figure impacts directly on the telescope's scientific output. The `Edge effect' significantly dominates the polishing precision. Therefore, the edge control is regarded as one of the most difficult technical issues in the segment production that needs to be addressed urgently. This paper reports an active edge control technique for the mirror segments fabrication using the Precession's polishing technique. The strategy in this technique requires that the large spot be selected on the bulk area for fast polishing, and the small spot is used for edge figuring. This can be performed by tool lift and optimizing the dell time to compensate for non-uniform material removal at the edge zone. This requires accurate and stable edge tool influence functions. To obtain the full tool influence function at the edge, we have demonstrated in previous work a novel hybrid-measurement method which uses both simultaneous phase interferometry and profilometry. In this paper, the edge effect under `Bonnet tool' polishing is investigated. The pressure distribution is analyzed by means of finite element analysis (FEA). According to the `Preston' equation, the shape of the edge tool influence functions is predicted. With this help, the multiple process parameters at the edge zone are optimized. This is demonstrated on a 200mm crosscorners hexagonal part with a result of PV less than 200nm for entire surface.

  10. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  11. Oxygen-activated growth and bandgap tunability of large single-crystal bilayer graphene

    NASA Astrophysics Data System (ADS)

    Hao, Yufeng; Wang, Lei; Liu, Yuanyue; Chen, Hua; Wang, Xiaohan; Tan, Cheng; Nie, Shu; Suk, Ji Won; Jiang, Tengfei; Liang, Tengfei; Xiao, Junfeng; Ye, Wenjing; Dean, Cory R.; Yakobson, Boris I.; McCarty, Kevin F.; Kim, Philip; Hone, James; Colombo, Luigi; Ruoff, Rodney S.

    2016-05-01

    Bernal (AB)-stacked bilayer graphene (BLG) is a semiconductor whose bandgap can be tuned by a transverse electric field, making it a unique material for a number of electronic and photonic devices. A scalable approach to synthesize high-quality BLG is therefore critical, which requires minimal crystalline defects in both graphene layers and maximal area of Bernal stacking, which is necessary for bandgap tunability. Here we demonstrate that in an oxygen-activated chemical vapour deposition (CVD) process, half-millimetre size, Bernal-stacked BLG single crystals can be synthesized on Cu. Besides the traditional ‘surface-limited’ growth mechanism for SLG (1st layer), we discovered new microscopic steps governing the growth of the 2nd graphene layer below the 1st layer as the diffusion of carbon atoms through the Cu bulk after complete dehydrogenation of hydrocarbon molecules on the Cu surface, which does not occur in the absence of oxygen. Moreover, we found that the efficient diffusion of the carbon atoms present at the interface between Cu and the 1st graphene layer further facilitates growth of large domains of the 2nd layer. The CVD BLG has superior electrical quality, with a device on/off ratio greater than 104, and a tunable bandgap up to ˜100 meV at a displacement field of 0.9 V nm-1.

  12. Cohort Profile of the Goals Study: A Large-Scale Research of Physical Activity in Dutch Students

    ERIC Educational Resources Information Center

    de Groot, Renate H. M.; van Dijk, Martin L.; Kirschner, Paul A.

    2015-01-01

    The GOALS study (Grootschalig Onderzoek naar Activiteiten van Limburgse Scholieren [Large-scale Research of Activities in Dutch Students]) was set up to investigate possible associations between different forms of physical activity and inactivity with cognitive performance, academic achievement and mental well-being. It was conducted at a…

  13. Large-Scale Investigation of the Role of Trait Activation Theory for Understanding Assessment Center Convergent and Discriminant Validity

    ERIC Educational Resources Information Center

    Lievens, Filip; Chasteen, Christopher S.; Day, Eric Anthony; Christiansen, Neil D.

    2006-01-01

    This study used trait activation theory as a theoretical framework to conduct a large-scale test of the interactionist explanation of the convergent and discriminant validity findings obtained in assessment centers. Trait activation theory specifies the conditions in which cross-situationally consistent and inconsistent candidate performances are…

  14. Baroreflexes of the rat. V. Tetanus-induced potentiation of ADN A-fiber responses at the NTS.

    PubMed

    Tang, Xiaorui; Dworkin, Barry R

    2007-12-01

    In a long-term neuromuscular blocked (NMB) rat preparation, tetanic stimulation of the aortic depressor nerve (ADN) enhanced the A-fiber evoked responses (ERs) in the cardiovascular region, the nucleus of the solitary tract (dmNTS). The potentiation persisted for at least several hours and may be a mechanism for adaptive adjustment of the gain of the baroreflex, with functional implications for blood pressure regulation. Using a capacitance electrode, we selectively stimulated A-fibers and acquired a stable 10-h "A-fiber only" ER baseline at the dmNTS. Following baseline, an A+C-fiber activating tetanus was applied to the ADN. The tetanus consisted of 1,000 "high current" pulses (10 trains; 300 mus, 100 Hz, 1 s), with intertrain interval of 9 s. A 10-h A-fiber only posttetanic test phase repeated the stimulus pattern of the baseline. Fourteen tetanus experiments were done in 12 rats. Compared with the baseline before tetanus, the A-fiber ER magnitudes of posttetanus hours were larger [F(13, 247) = 3.407, P < .001]; additionally, the 10-h posttetanus magnitude slopes were more positive than during 10 h before tetanus (df = 13; t = -3.47; P < 0.005); thus, an ADN A+C fiber-activating tetanus produced increases in the magnitude of the A-fiber ERs in the dmNTS that persisted for several hours. In an additional rat, application of an NMDA receptor antagonist, prior to the tetanus, blocked the potentiation effect. The stimulus protocols, magnitude and duration of the effect, and pharmacology resemble associative long-term potentiation (LTP).

  15. mTOR activity in AIDS-related diffuse large B-cell lymphoma

    PubMed Central

    Diaz-Perez, Julio A.; Preziosi, Michael; King, Charles C.; Jones, George A.; Jain, Sonia; Sun, Xiaoying; Reid, Erin G.; VandenBerg, Scott; Wang, Huan-You

    2017-01-01

    Background Patients infected with HIV have a significantly increased risk of developing non–Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway. Materials and methods We evaluated tissue samples from 126 patients with AR-DLBCL. Among them, 98 samples were from tissue microarrays (TMAs) supplied by the Aids and Cancer Specimen Resource (ACSR), the remaining 28 samples were from cases diagnosed and treated at the University of California, San Diego (UCSD). The presence of p70S6K was evaluated with two antibodies directed against the combined epitopes Ser235/236 and Ser240/244, respectively; and additional monoclonal anti-bodies were used to identify pPTEN and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40). The degree of intensity and percentage of cells positive for p70S6K and pPTEN were assessed in all the samples. In addition, a subgroup of 28 patients from UCSD was studied to assess the presence of pPRAS40, an insulin-regulated activator of the mTORC1. The expression of each of these markers was correlated with clinical and histopathologic features. Results The majority of the patients evaluated were males (88%); only two cases (1.6%) were older than 65 years of age. We found high levels of both p70S6K-paired epitopes studied, 48% positivity against Ser235/236 (44% in ACSR and 64% in UCSD group), and 86% positivity against Ser240/244 (82% in ACSR and 100% in UCSD group). We observed more positive cells and stronger intensity with epitope Ser240/244 in comparison to Ser235/236 (p<0.0001). The degree of intensity and percentage of cells positive

  16. M2 Muscarinic Receptors Induce Airway Smooth Muscle Activation via a Dual, Gβγ-mediated Inhibition of Large Conductance Ca2+-activated K+ Channel Activity*

    PubMed Central

    Zhou, Xiao-Bo; Wulfsen, Iris; Lutz, Susanne; Utku, Emine; Sausbier, Ulrike; Ruth, Peter; Wieland, Thomas; Korth, Michael

    2008-01-01

    Airway smooth muscle is richly endowed with muscarinic receptors of the M2 and M3 subtype. Stimulation of these receptors inhibits large conductance calcium-activated K+ (BK) channels, a negative feed back regulator, in a pertussis toxinsensitive manner and thus facilitates contraction. The underlying mechanism, however, is unknown. We therefore studied the activity of bovine trachea BK channels in HEK293 cells expressing the M2 or M3 receptor (M2RorM3R). In M2R- but not M3R-expressing cells, maximal effective concentrations of carbamoylcholine (CCh) inhibited whole cell BK currents by 53%. This M2R-induced inhibition was abolished by pertussis toxin treatment or overexpression of the Gβγ scavenger transducin-α. In inside-out patches, direct application of 300 nm purified Gβγ decreased channel open probability by 55%. The physical interaction of Gβγ with BK channels was confirmed by co-immunoprecipitation. Interestingly, inhibition of phospholipase C as well as protein kinase C activities also reversed the CCh effect but to a smaller (∼20%) extent. Mouse tracheal cells responded similarly to CCh, purified Gβγ and phospholipase C/protein kinase C inhibition as M2R-expressing HEK293 cells. Our results demonstrate that airway M2Rs inhibit BK channels by a dual, Gβγ-mediated mechanism, a direct membrane-delimited interaction, and the activation of the phospholipase C/protein kinase C pathway. PMID:18524769

  17. Upregulation of the large conductance voltage- and Ca2+-activated K+ channels by Janus kinase 2.

    PubMed

    Hosseinzadeh, Zohreh; Almilaji, Ahmad; Honisch, Sabina; Pakladok, Tatsiana; Liu, GuoXing; Bhavsar, Shefalee K; Ruth, Peter; Shumilina, Ekaterina; Lang, Florian

    2014-06-01

    The iberiotoxin-sensitive large conductance voltage- and Ca(2+)-activated potassium (BK) channels (maxi-K(+)-channels) hyperpolarize the cell membrane thus supporting Ca(2+) entry through Ca(2+)-release activated Ca(2+) channels. Janus kinase-2 (JAK2) has been identified as novel regulator of ion transport. To explore whether JAK2 participates in the regulation of BK channels, cRNA encoding Ca(2+)-insensitive BK channels (BK(M513I+Δ899-903)) was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, gain-of-function (V617F)JAK2, or inactive (K882E)JAK2. K(+) conductance was determined by dual electrode voltage clamp and BK-channel protein abundance by confocal microscopy. In A204 alveolar rhabdomyosarcoma cells, iberiotoxin-sensitive K(+) current was determined utilizing whole cell patch clamp. A204 cells were further transfected with JAK2 and BK-channel transcript, and protein abundance was quantified by RT-PCR and Western blotting, respectively. As a result, the K(+) current in BK(M513I+Δ899-903)-expressing oocytes was significantly increased following coexpression of JAK2 or (V617F)JAK2 but not (K882E)JAK2. Coexpression of the BK channel with (V617F)JAK2 but not (K882E)JAK2 enhanced BK-channel protein abundance in the oocyte cell membrane. Exposure of BK-channel and (V617F)JAK2-expressing oocytes to the JAK2 inhibitor AG490 (40 μM) significantly decreased K(+) current. Inhibition of channel insertion by brefeldin A (5 μM) decreased the K(+) current to a similar extent in oocytes expressing the BK channel alone and in oocytes expressing the BK channel and (V617F)JAK2. The iberiotoxin (50 nM)-sensitive K(+) current in rhabdomyosarcoma cells was significantly decreased by AG490 pretreatment (40 μM, 12 h). Moreover, overexpression of JAK2 in A204 cells significantly enhanced BK channel mRNA and protein abundance. In conclusion, JAK2 upregulates BK channels by increasing channel protein abundance in the cell membrane.

  18. Large historical earthquakes and tsunamis in a very active tectonic rift: the Gulf of Corinth, Greece

    NASA Astrophysics Data System (ADS)

    Triantafyllou, Ioanna; Papadopoulos, Gerassimos

    2014-05-01

    The Gulf of Corinth is an active tectonic rift controlled by E-W trending normal faults with an uplifted footwall in the south and a subsiding hangingwall with antithetic faulting in the north. Regional geodetic extension rates up to about 1.5 cm/yr have been measured, which is one of the highest for tectonic rifts in the entire Earth, while seismic slip rates up to about 1 cm/yr were estimated. Large earthquakes with magnitudes, M, up to about 7 were historically documented and instrumentally recorded. In this paper we have compiled historical documentation of earthquake and tsunami events occurring in the Corinth Gulf from the antiquity up to the present. The completeness of the events reported improves with time particularly after the 15th century. The majority of tsunamis were caused by earthquake activity although the aseismic landsliding is a relatively frequent agent for tsunami generation in Corinth Gulf. We focus to better understand the process of tsunami generation from earthquakes. To this aim we have considered the elliptical rupture zones of all the strong (M≥ 6.0) historical and instrumental earthquakes known in the Corinth Gulf. We have taken into account rupture zones determined by previous authors. However, magnitudes, M, of historical earthquakes were recalculated from a set of empirical relationships between M and seismic intensity established for earthquakes occurring in Greece during the instrumental era of seismicity. For this application the macroseismic field of each one of the earthquakes was identified and seismic intensities were assigned. Another set of empirical relationships M/L and M/W for instrumentally recorded earthquakes in the Mediterranean region was applied to calculate rupture zone dimensions; where L=rupture zone length, W=rupture zone width. The rupture zones positions were decided on the basis of the localities of the highest seismic intensities and co-seismic ground failures, if any, while the orientation of the maximum

  19. A fiber-bridging model with stress gradient effects

    NASA Astrophysics Data System (ADS)

    Yi, Sun; Tao, Li

    2000-05-01

    A fiber-bridging model with stress gradient effects is proposed for unidirectional fiber-reinforced composites. The stress gradient terms are introduced by solving a micromechanical model under a non-uniform stress loading. It is shown that the stress gradient effect is significant on both the fiber-bridging stress distribution and the value of the critical load of fiber failure.

  20. The Active and Periactive Zone Organization and the Functional Properties of Small and Large Synapses

    PubMed Central

    Cano, Raquel; Tabares, Lucia

    2016-01-01

    The arrival of an action potential (AP) at a synaptic terminal elicits highly synchronized quanta release. Repetitive APs produce successive synaptic vesicle (SV) fusions that require management of spent SV components in the presynaptic membrane with minimum disturbance of the secretory apparatus. To this end, the synaptic machinery is structured accordingly to the strength and the range of frequencies at which each particular synapse operates. This results in variations in the number and dimension of Active Zones (AZs), amount and distribution of SVs, and probably, in the primary endocytic mechanisms they use. Understanding better how these structural differences determine the functional response in each case has been a matter of long-term interest. Here we review the structural and functional properties of three distinct types of synapses: the neuromuscular junction (NMJ; a giant, highly reliable synapse that must exocytose a large number of quanta with each stimulus to guarantee excitation of the postsynaptic cell), the hippocampal excitatory small synapse (which most often has a single release site and a relatively small pool of vesicles), and the cerebellar mossy fiber-granule cell synapse (which possesses hundreds of release sites and is able to translocate, dock and prime vesicles at high speed). We will focus on how the release apparatus is organized in each case, the relative amount of vesicular membrane that needs to be accommodated within the periAZ upon stimulation, the different mechanisms for retrieving the excess of membrane and finally, how these factors may influence the functioning of the release sites. PMID:27252645

  1. Allosteric Gating of a Large Conductance Ca-activated K+ Channel

    PubMed Central

    Cox, D.H.; Cui, J.; Aldrich, R.W.

    1997-01-01

    Large-conductance Ca-activated potassium channels (BK channels) are uniquely sensitive to both membrane potential and intracellular Ca2+. Recent work has demonstrated that in the gating of these channels there are voltage-sensitive steps that are separate from Ca2+ binding steps. Based on this result and the macroscopic steady state and kinetic properties of the cloned BK channel mslo, we have recently proposed a general kinetic scheme to describe the interaction between voltage and Ca2+ in the gating of the mslo channel (Cui, J., D.H. Cox, and R.W. Aldrich. 1997. J. Gen. Physiol. In press.). This scheme supposes that the channel exists in two main conformations, closed and open. The conformational change between closed and open is voltage dependent. Ca2+ binds to both the closed and open conformations, but on average binds more tightly to the open conformation and thereby promotes channel opening. Here we describe the basic properties of models of this form and test their ability to mimic mslo macroscopic steady state and kinetic behavior. The simplest form of this scheme corresponds to a voltage-dependent version of the Monod-Wyman-Changeux (MWC) model of allosteric proteins. The success of voltage-dependent MWC models in describing many aspects of mslo gating suggests that these channels may share a common molecular mechanism with other allosteric proteins whose behaviors have been modeled using the MWC formalism. We also demonstrate how this scheme can arise as a simplification of a more complex scheme that is based on the premise that the channel is a homotetramer with a single Ca2+ binding site and a single voltage sensor in each subunit. Aspects of the mslo data not well fitted by the simplified scheme will likely be better accounted for by this more general scheme. The kinetic schemes discussed in this paper may be useful in interpreting the effects of BK channel modifications or mutations. PMID:9276753

  2. Intracellular Na(+) modulates large conductance Ca(2+)-activated K (+) currents in human umbilical vein endothelial cells.

    PubMed

    Liang, Guo Hua; Kim, Moon Young; Park, Seonghee; Kim, Ji Aee; Choi, Shinkyu; Suh, Suk Hyo

    2008-10-01

    We studied the effects of Na(+) influx on large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in cultured human umbilical vein endothelial cells (HUVECs) by means of patch clamp and SBFI microfluorescence measurements. In current-clamped HUVECs, extracellular Na(+) replacement by NMDG(+) or mannitol hyperpolarized cells. In voltage-clamped HUVECs, changing membrane potential from 0 mV to negative potentials increased intracellular Na(+) concentration ([Na(+)](i)) and vice versa. In addition, extracellular Na(+) depletion decreased [Na(+)](i). In voltage-clamped cells, BK(Ca) currents were markedly increased by extracellular Na(+) depletion. In inside-out patches, increasing [Na(+)](i) from 0 to 20 or 40 mM reduced single channel conductance but not open probability (NPo) of BK(Ca) channels and decreasing intracellular K(+) concentration ([K(+)](i)) gradually from 140 to 70 mM reduced both single channel conductance and NPo. Furthermore, increasing [Na(+)](i) gradually from 0 to 70 mM, by replacing K(+), markedly reduced single channel conductance and NPo. The Na(+)-Ca(2+) exchange blocker Ni(2+) or KB-R7943 decreased [Na(+)](i) and increased BK(Ca) currents simultaneously, and the Na(+) ionophore monensin completely inhibited BK(Ca) currents. BK(Ca) currents were significantly augmented by increasing extracellular K(+) concentration ([K(+)](o)) from 6 to 12 mM and significantly reduced by decreasing [K(+)](o) from 12 or 6 to 0 mM or applying the Na(+)-K(+) pump inhibitor ouabain. These results suggest that intracellular Na(+) inhibit single channel conductance of BK(Ca) channels and that intracellular K(+) increases single channel conductance and NPo.

  3. The Activity of Differentiation Factors Induces Apoptosis in Polyomavirus Large T-Expressing Myoblasts

    PubMed Central

    Fimia, Gian Maria; Gottifredi, Vanesa; Bellei, Barbara; Ricciardi, Maria Rosaria; Tafuri, Agostino; Amati, Paolo; Maione, Rossella

    1998-01-01

    It is commonly accepted that pathways that regulate proliferation/differentiation processes, if altered in their normal interplay, can lead to the induction of programmed cell death. In a previous work we reported that Polyoma virus Large Tumor antigen (PyLT) interferes with in vitro terminal differentiation of skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene product. This inhibition occurs after the activation of some early steps of the myogenic program. In the present work we report that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing myoblasts starts after growth factors removal, is promoted by cell confluence, and is temporally correlated with the expression of early markers of myogenic differentiation. The block of the initial events of myogenesis by transforming growth factor β or basic fibroblast growth factor prevents PyLT-induced apoptosis, while the acceleration of this process by the overexpression of the muscle-regulatory factor MyoD further increases cell death in this system. MyoD can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific genes but is unable to induce G00 arrest. Several markers of different phases of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated, indicating the occurrence of cell cycle progression. It has been frequently suggested that apoptosis can result from an unbalanced cell cycle progression in the presence of a contrasting signal, such as growth factor deprivation. Our data involve differentiation pathways, as a further contrasting signal, in the generation of this conflict during myoblast cell apoptosis. PMID:9614186

  4. THE SECOND CATALOG OF ACTIVE GALACTIC NUCLEI DETECTED BY THE FERMI LARGE AREA TELESCOPE

    SciTech Connect

    Ackermann, M.; Ajello, M.; Allafort, A.; Bechtol, K.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Borgland, A. W.; Bottacini, E.; Antolini, E.; Bonamente, E.; Atwood, W. B.; Bouvier, A.; Axelsson, M.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Ballet, J.; Bastieri, D. E-mail: sarac@slac.stanford.edu E-mail: charles.dermer@nrl.navy.mil; and others

    2011-12-20

    The second catalog of active galactic nuclei (AGNs) detected by the Fermi Large Area Telescope (LAT) in two years of scientific operation is presented. The second LAT AGN catalog (2LAC) includes 1017 {gamma}-ray sources located at high Galactic latitudes (|b| > 10 Degree-Sign ) that are detected with a test statistic (TS) greater than 25 and associated statistically with AGNs. However, some of these are affected by analysis issues and some are associated with multiple AGNs. Consequently, we define a Clean Sample which includes 886 AGNs, comprising 395 BL Lacertae objects (BL Lac objects), 310 flat-spectrum radio quasars (FSRQs), 157 candidate blazars of unknown type (i.e., with broadband blazar characteristics but with no optical spectral measurement yet), 8 misaligned AGNs, 4 narrow-line Seyfert 1 (NLS1s), 10 AGNs of other types, and 2 starburst galaxies. Where possible, the blazars have been further classified based on their spectral energy distributions (SEDs) as archival radio, optical, and X-ray data permit. While almost all FSRQs have a synchrotron-peak frequency <10{sup 14} Hz, about half of the BL Lac objects have a synchrotron-peak frequency >10{sup 15} Hz. The 2LAC represents a significant improvement relative to the first LAT AGN catalog (1LAC), with 52% more associated sources. The full characterization of the newly detected sources will require more broadband data. Various properties, such as {gamma}-ray fluxes and photon power-law spectral indices, redshifts, {gamma}-ray luminosities, variability, and archival radio luminosities and their correlations are presented and discussed for the different blazar classes. The general trends observed in 1LAC are confirmed.

  5. Estrogenic Activity and Estrogens of Surface Waters in Proximity to a Large Dairy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Large concentrated animal farms have been the subject of intense public scrutiny, in part due to concern about environmental release of endocrine disruptors. To assess the potential impact of a large dairy herd (greater than 2000 milking head) using best management practices, area surface waters and...

  6. Relationships between persistent large-scale flow anomalies and variation in synoptic-scale eddy activity and cyclogenesis

    NASA Technical Reports Server (NTRS)

    Dole, Randall M.; Neilley, Peter P.

    1988-01-01

    Observational analyses to study the relationships between large-scale flow anomalies and variations in synoptic-scale eddy activity and cyclogenesis are presented. The way in which changes in the large-scale flow influence the behavior of synoptic-scale eddies and the way in which changes in eddies may feedback to influence the large-scale flow anomalies are examined. Situations characterized by differing large-scale flows are compared, showing well-defined diferences in synoptic-scale eddy activity. The net forcings of anomalous mean flows by eddies as deduced from tendency methods and E-vector analyses suggest that synoptic-scale eddies may play an important role in maintaining certain anomalous flow patterns such as blocking.

  7. Continuous monitoring of a large active earth flow using an integrated GPS - automatic total station approach

    NASA Astrophysics Data System (ADS)

    Corsini, A.

    2009-04-01

    Landslide monitoring has evolved as a crucial tool in civil protection to mitigate and prevent disasters. The research presents an approach to continuous monitoring of a large-scale active earth flow using a system that integrates surface measurements obtained by a GPS and an automatic total station. With the data obtained from the system the landslide can be monitored in near-real-time and surface displacements can be directly utilized to provide early warning of slope movements and to study the behavior of the landslide, e.g. to predict timing and mechanisms of future failure. The Valoria landslide located in the northern Apennines of Italy was reactivated in 2001, 2005 and 2007 damaging roads and endangering houses. A monitoring system was installed in 2007-2008 in the frame of a civil protection plan aimed at risk mitigation. The system consists of an automatic total station measuring about 40 prisms located in the landslide to a maximum distance of 1.800 km; one double-frequency GPS receiver connects in streaming by wireless communication with 4 single-frequency GPS in side the flow. Until December 2007 the monitoring network was operated with periodic static surveying followed by the data post-processing. From September 2007 until March 2008 the landslide deformation was evaluated by periodic surveys with the total station and the GPS system. This first measure showed that the displacements were influenced by the rainfall events and by the snow melting. The total displacements measured vary from centimeter scale in the crown zone, where retrogressive movements were in progress, to over 50 m in the flow track zone. Starting in March 2008 data acquisition by the total station system and GPS were automated in order to allow continuous and near-real-time data processing. The displacement data collected in one and a half year of continuous operation show different acceleration and deceleration phases as a result of the pore water pressure distribution inside the

  8. Island of the Sharks Activity Guide To Accompany the Large-Format Film.

    ERIC Educational Resources Information Center

    Gowell, Elizabeth Tayntor

    This document targets upper elementary and middle school students and provides activities to understand what the ocean floor looks like, the interactions of ocean communities, and the true nature of sharks. The activities are developed at three levels: beginner, intermediate, and advanced. The twelve activities include: (1) "Ocean…

  9. Study of new FNAL-NICADD extruded scintillator as active media of large EMCal of ALICE at LHC

    SciTech Connect

    Oleg A. Grachov et al.

    2004-05-04

    The current conceptual design of proposed Large EMCal of ALICE at LHC is based largely on the scintillating mega-tile/fiber technology implemented in CDF Endplug upgrade project and in both barrel and endcap electromagnetic calorimeters of the STAR. The cost of scintillating material leads us to the choice of extruded polystyrene based scintillator, which is available in new FNAL-NICADD facility. Result of optical measurements, such as light yield and light yield variation, show that it is possible to use this material as active media of Large EMCal of ALICE at LHC.

  10. Thermal neutron self-shielding correction factors for large sample instrumental neutron activation analysis using the MCNP code

    NASA Astrophysics Data System (ADS)

    Tzika, F.; Stamatelatos, I. E.

    2004-01-01

    Thermal neutron self-shielding within large samples was studied using the Monte Carlo neutron transport code MCNP. The code enabled a three-dimensional modeling of the actual source and geometry configuration including reactor core, graphite pile and sample. Neutron flux self-shielding correction factors derived for a set of materials of interest for large sample neutron activation analysis are presented and evaluated. Simulations were experimentally verified by measurements performed using activation foils. The results of this study can be applied in order to determine neutron self-shielding factors of unknown samples from the thermal neutron fluxes measured at the surface of the sample.

  11. Similar brain activation during false belief tasks in a large sample of adults with and without autism.

    PubMed

    Dufour, Nicholas; Redcay, Elizabeth; Young, Liane; Mavros, Penelope L; Moran, Joseph M; Triantafyllou, Christina; Gabrieli, John D E; Saxe, Rebecca

    2013-01-01

    Reading about another person's beliefs engages 'Theory of Mind' processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults.

  12. Large Area Active Brazing of Multi-tile Ceramic-Metal Structures

    DTIC Science & Technology

    2012-05-01

    metal brazing . The active brazing alloys wet most materials (including ceramics and corrosion- resistant metals such as titanium alloys and stainless...bonding in ceramic-metal systems is active metal brazing . The active brazing alloys wet most materials (including ceramics and corrosion-resistant...an idea from the ‘50s by putting an “active” component, such as titanium, directly into a brazing alloy , typically a silver-copper eutectic, to

  13. Thalamic stimulation largely elicits orthodromic, rather than antidromic, cortical activation in an auditory thalamocortical slice.

    PubMed

    Rose, H J; Metherate, R

    2001-01-01

    Stimulation of the medial geniculate body in an auditory thalamocortical slice elicits a short-latency current sink in the middle cortical layers, as would be expected following activation of thalamocortical relay neurons. However, corticothalamic neurons can have axon collaterals that project to the middle layers, thus, a middle-layer current sink could also result from antidromic activation of corticothalamic neurons and their axon collaterals. The likelihood of thalamic stimulation activating corticothalamic neurons would be reduced substantially if the corticothalamic pathway was not well preserved in the slice, and/or if the threshold for antidromic activation was significantly higher than for orthodromic activation. To determine the prevalence and threshold of antidromic activation, we recorded intracellularly from day 14-17 mouse brain slices containing infragranular cortical neurons while stimulating the medial geniculate or thalamocortical pathway. Antidromic spikes were confirmed by spike collision and characterized according to spike latency "jitter" and the ability to follow a high-frequency (100 Hz) stimulus train. The ability to follow a 100-Hz tetanus was a reliable indicator of antidromic activation, but both antidromic and orthodromic spikes could have low jitter. Thalamic stimulation produced antidromic activation in two of 69 infragranular cortical neurons (<3%), indicating the presence of antidromic activity, but implying a limited corticothalamic connection in the slice. Antidromic spikes in 13 additional neurons were obtained by stimulating axons in the thalamocortical pathway. The antidromic threshold averaged 214+/-40.6 microA (range 6-475 microA), over seven times the orthodromic threshold for medial geniculate-evoked responses in layer IV extracellular (28+/-5.4 microA) or intracellular (27+/-5.6 microA) recordings. We conclude that medial geniculate stimulation activates relatively few corticothalamic neurons. Conversely, low

  14. Elasticity analysis and design for large metabolic responses produced by changes in enzyme activities.

    PubMed Central

    Ortega, Fernando; Acerenza, Luis

    2002-01-01

    Metabolic control analysis has been extensively used to describe how the sensitivity properties of the component enzymes in a metabolic pathway (represented by the elasticity coefficients) determine the way in which metabolic variables respond (described by the control coefficients). Similarly, metabolic control design addresses the inverse problem of obtaining the sensitivity properties of the component enzymes that are required for the system to show a pre-established pattern of responses. These formalisms, including what is called elasticity analysis and design, were developed for small, strictly speaking infinitesimal, changes. Here we extend them to large metabolic responses. The new approach can be applied to simple two-step pathways or to any arbitrary metabolic system divided into two groups linked by one intermediate. General expressions that relate control and elasticity coefficients for large changes are derived. Concentration and flux connectivity relationships are obtained. The relationships for large changes indicate that the pattern of responses is not necessarily the same as the one obtained with the traditional infinitesimal approach, in some cases the patterns being qualitatively different. The general analysis is used to study the control of ketogenesis in rat liver mitochondria, starting from data available in the literature. The control profile of the pathway subject to large changes shows both quantitative and qualitative differences from the one obtained from an analysis that is performed with infinitesimal coefficients. This exemplifies the type of errors that may be introduced when drawing conclusions about large metabolic responses from results obtained with an infinitesimal treatment. PMID:12084013

  15. Silent and Vocal Students in a Large Active Learning Chemistry Classroom: Comparison of Performance and Motivational Factors

    ERIC Educational Resources Information Center

    Obenland, Carrie A.; Munson, Ashlyn H.; Hutchinson, John S.

    2013-01-01

    Active learning is becoming more prevalent in large science classrooms, and this study shows the impact on performance of being vocal during Socratic questioning in a General Chemistry course. 800 college students over a two year period were given a pre and post-test using the Chemistry Concept Reasoning Test. The pre-test results showed that…

  16. Associations between Grades and Physical Activity and Food Choices: Results from YRBS from a Large Urban School District

    ERIC Educational Resources Information Center

    Snelling, Anastasia; Belson, Sarah Irvine; Beard, Jonathan; Young, Kathleen

    2015-01-01

    Purpose: The purpose of this paper is to explore the relationship between television viewing time, physical activity level, food consumption patterns, and academic performance of adolescents in a large urban school district in the USA where health disparities are prevalent, particularly among minority residents. Design/Methodology/Approach: The…

  17. Hot bending with a fiber coupled solid state laser

    NASA Astrophysics Data System (ADS)

    Bammer, F.; Schumi, T.; Schuöcker, D.

    2010-09-01

    For bending of brittle materials it is necessary to heat up the forming zone. This can be done with a fiber coupled solid state laser, whose beam is evenly distributed on the bending line with a beam splitter installed in the lower tool (die) of a bending press. With polarization optics the laser beam is divided there into partial beams that are evenly distributed on the bending line with lenses and prisms. A setup for a bending length of 200mm heated by a fiber-coupled 3kW Nd:YAG-laser shows the feasibility of the concept. Successful operation was shown for the Mg-alloy AZ31, which breaks during forming at room temperature, but can be well formed at temperatures in the range of 200-300°C. Other materials benefiting from this method are Ti-alloys, high-strength-Al-alloys, and high-strength-steels. Typical heating times are in the range of up to 5s and much of the heat input is generated during the bending operation where the laser continues to work. Laser Assisted Bending with a fiber coupled solid state laser is a straightforward way to perform the bending of brittle materials in a process as simple as cold bending.

  18. Sandia Laboratories in-house activities in support of solar thermal large power applications

    NASA Technical Reports Server (NTRS)

    Mar, R. W.

    1980-01-01

    The development of thermal energy storage subsystems for solar thermal large power applications is described. The emphasis is on characterizing the behavior of molten nitrate salts with regard to thermal decomposition, environmental interactions, and corrosion. Electrochemical techniques to determine the ionic species in the melt and for use in real time studies of corrosion are also briefly discussed.

  19. Transforming a Large-Lecture Course into an Active, Engaging, and Collaborative Learning Environment

    ERIC Educational Resources Information Center

    Stoerger, Sharon; Krieger, Denise

    2016-01-01

    Traditionally, a large lecture hall course follows a teacher-centered approach to instruction. This was the case for the "gateway" course in the undergraduate Information Technology and Informatics (ITI) major in the School of Communication and Information at Rutgers, The State University of New Jersey. This paper describes the journey…

  20. Measuring Student Interactions Using Networks: Insights into the Learning Community of a Large Active Learning Course

    ERIC Educational Resources Information Center

    Buchenroth-Martin, Cynthia; DiMartino, Trevor; Martin, Andrew P.

    2017-01-01

    Collaborative learning in small groups is commonly implemented as a part of student-centered curricula. In large-enrollment courses, details of the interactions among students as a consequence of working in collaborative groups are often unknown but are important because how students interact influences the effectiveness of peer learning. We…

  1. Activity Determinants of Helical Antimicrobial Peptides: A Large-Scale Computational Study

    PubMed Central

    He, Yi; Lazaridis, Themis

    2013-01-01

    Antimicrobial peptides (AMPs), produced by a wide range of organisms, have attracted attention due to their potential use as novel antibiotics. The majority of these peptides are cationic and are thought to function by permeabilizing the bacterial membrane, either by making pores or by dissolving it (‘carpet’ model). A key hypothesis in the literature is that antimicrobial and hemolytic activity correlate with binding affinity to anionic and zwitterionic membranes, respectively. Here we test this hypothesis by using binding free energy data collected from the literature and theoretical binding energies calculated from implicit membrane models for 53 helical AMPs. We indeed find a correlation between binding energy and biological activity, depending on membrane anionic content: antibacterial activity correlates best with transfer energy to membranes with anionic lipid fraction higher than 30% and hemolytic activity correlates best with transfer energy to a 10% anionic membrane. However, the correlations are weak, with correlation coefficient up to 0.4. Weak correlations of the biological activities have also been found with other physical descriptors of the peptides, such as surface area occupation, which correlates significantly with antibacterial activity; insertion depth, which correlates significantly with hemolytic activity; and structural fluctuation, which correlates significantly with both activities. The membrane surface coverage by many peptides at the MIC is estimated to be much lower than would be required for the ‘carpet’ mechanism. Those peptides that are active at low surface coverage tend to be those identified in the literature as pore-forming. The transfer energy from planar membrane to cylindrical and toroidal pores was also calculated for these peptides. The transfer energy to toroidal pores is negative in almost all cases while that to cylindrical pores is more favorable in neutral than in anionic membranes. The transfer energy to pores

  2. A method for determining Am-241 activity for large area contamination.

    PubMed

    Wilhelm, Emilien; Arbor, Nicolas; Gutierrez, Sébastien; Ménard, Stéphanie; Nourreddine, Abdel-Mjid

    2017-01-01

    Airborne gamma-ray spectrometry system HELINUC™ is used for different missions. Although well-developed for estimation of high energy emitters' activity, it is rarely used for low energy emitters. A new method for the determination of Am-241 activity over extended sites based both on statistical analysis of spectra and deconvolution of Am-241 signal with a reference library is presented. Results show a lowering of the detection threshold and a good agreement with ground level measurements.

  3. Pregnancy upregulates large-conductance Ca(2+)-activated K(+) channel activity and attenuates myogenic tone in uterine arteries.

    PubMed

    Hu, Xiang-Qun; Xiao, Daliao; Zhu, Ronghui; Huang, Xiaohui; Yang, Shumei; Wilson, Sean; Zhang, Lubo

    2011-12-01

    Uterine vascular tone significantly decreases whereas uterine blood flow dramatically increases during pregnancy. However, the complete molecular mechanisms remain elusive. We hypothesized that increased Ca(2+)-activated K(+) (BK(Ca)) channel activity contributes to the decreased myogenic tone of uterine arteries in pregnancy. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Electrophysiological studies revealed a greater whole-cell K(+) current density in pregnant compared with nonpregnant uterine arteries. Tetraethylammonium and iberiotoxin inhibited K(+) currents to the same extent in uterine arterial myocytes. The BK(Ca) channel current density was significantly increased in pregnant uterine arteries. In accordance, tetraethylammonium significantly increased pressure-induced myogenic tone in pregnant uterine arteries and abolished the difference in myogenic responses between pregnant and nonpregnant uterine arteries. Activation of protein kinase C produced a similar effect to tetraethylammonium by inhibiting BK(Ca) channel activity and increasing myogenic tone in pregnant uterine arteries. Chronic treatment of nonpregnant uterine arteries with physiologically relevant concentrations of 17β-estradiol and progesterone caused a significant increase in the BK(Ca) channel current density. Western blot analyses demonstrated a significant increase of the β1, but not α, subunit of BK(Ca) channels in pregnant uterine arteries. In accordance, steroid treatment of nonpregnant uterine arteries resulted in an upregulation of the β1, but not α, subunit expression. The results indicate that the steroid hormone-mediated upregulation of the β1 subunit and BK(Ca) channel activity may play a key role in attenuating myogenic tone of the uterine artery in pregnancy.

  4. Active Removal of Large Debris: System Approach of Desorbiting Concepts and Technological Issues

    NASA Astrophysics Data System (ADS)

    Couzin, Patrice; Rembala, Richard; Teti, Frank; Bakouche, Charles; Billot, Carole

    2013-08-01

    The threat induced by large space debris, dead satellites or rocket bodies, in Low Earth Orbit has been identified years ago. A first part of the Orbital Transfer Vehicle (OTV) study was dedicated to identify mission architectures that can fulfil the objective to eliminate the necessary number of critical debris. Those potential solutions and architectures have been compared taking into account cost considerations. The present paper reports the first results of the OTV step2 study funded by CNES that addresses different solutions for large debris removal. It compares different desorbiting concepts from selected single to multiple debris complying with the Space Law, i.e. able to ensure controlled re entries. Different capture options are presented, including sensors needs and an analysis of the problems posed by different solutions. The overall performances of the concepts are compared, showing the adequacy, the limits of each solutions and application domains.

  5. Holographic fiber bundle system for patterned optogenetic activation of large-scale neuronal networks

    PubMed Central

    Farah, Nairouz; Levinsky, Alexandra; Brosh, Inbar; Kahn, Itamar; Shoham, Shy

    2015-01-01

    Abstract. Optogenetic perturbation has become a fundamental tool in controlling activity in neurons. Used to control activity in cell cultures, slice preparations, anesthetized and awake behaving animals, optical control of cell-type specific activity enables the interrogation of complex systems. A remaining challenge in developing optical control tools is the ability to produce defined light patterns such that power-efficient, precise control of neuronal populations is obtained. Here, we describe a system for patterned stimulation that enables the generation of structured activity in neurons by transmitting optical patterns from computer-generated holograms through an optical fiber bundle. The system couples the optical system to versatile fiber bundle configurations, including coherent or incoherent bundles composed of hundreds of up to several meters long fibers. We describe the components of the system, a method for calibration, and a detailed power efficiency and spatial specificity quantification. Next, we use the system to precisely control single-cell activity as measured by extracellular electrophysiological recordings in ChR2-expressing cortical cell cultures. The described system complements recent descriptions of optical control systems, presenting a system suitable for high-resolution spatiotemporal optical control of wide-area neural networks in vitro and in vivo, yielding a tool for precise neural system interrogation. PMID:26793741

  6. Lessons learned with the Active Phasing Experiment: comparison of four optical phasing sensors on a segmented Very Large Telescope

    NASA Astrophysics Data System (ADS)

    Gonte, F.; Surdej, I.

    The adaptive optics capabilities are strongly limited by the quality of the phasing of the primary mirror of the extremely large telescope. Up to date, the Keck telescopes are the only segmented telescope phased with a quality enabling the application of adaptive optics. The Active Phasing Experiment has been installed at the Namyth focus of the Very Large Telescope Melipal during the last 6 months. Its purpose is to understand and compare different technological concepts for an optical phasing sensor dedicated to the European Extremely Large Telescope. The pupil of the telescope is segmented in 61 hexagonal segments by projecting it on an Active Segmented Mirror. The ASM is controlled by a dual wavenlength interferometer made by Fogale Nanotech with a nanometric precision. The segmented pupil is distributed in parallel to four optical phasing sensors. They are a pyramid sensor, a curvature sensor, a phase filtering sensor and a ShackHartmann sensor. They have been developed respectively by Istituto Nazionale di Astrofisica in Florenze, Instituto Astrofisica Canarias in Tenerife, Laboratoire d'Astrophysique de Marseille and ESO. The global behaviour of the optical phasing sensors will be described and preliminary results of the Active Phasing Experiments obtained on sky will be explained. The extrapolation of the results to the EELT and the potential consequences for the adaptive optics will be given. The Active Phasing Experiment has been financed by the European Union and the European Southern Observatory via the Sixth European Union Framework Program for Research and Technological Development under the contract number 011863.

  7. Quantifying the fingerprint descriptor dependence of structure-activity relationship information on a large scale.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2013-09-23

    It is well-known that different molecular representations, e.g., graphs, numerical descriptors, fingerprints, or 3D models, change the numerical results of molecular similarity calculations. Because the assessment of structure-activity relationships (SARs) requires similarity and potency comparisons of active compounds, this representation dependence inevitably also affects SAR analysis. But to what extent? How exactly does SAR information change when alternative fingerprints are used as descriptors? What is the proportion of active compounds with substantial changes in SAR information induced by different fingerprints? To provide answers to these questions, we have quantified changes in SAR information across many different compound classes using six different fingerprints. SAR profiling was carried out on 128 target-based data sets comprising more than 60,000 compounds with high-confidence activity annotations. A numerical measure of SAR discontinuity was applied to assess SAR information on a per compound basis. For ~70% of all test compounds, changes in SAR characteristics were detected when different fingerprints were used as molecular representations. Moreover, the SAR phenotype of ~30% of the compounds changed, and distinct fingerprint-dependent local SAR environments were detected. The fingerprints we compared were found to generate SAR models that were essentially not comparable. Atom environment and pharmacophore fingerprints produced the largest differences in compound-associated SAR information. Taken together, the results of our systematic analysis reveal larger fingerprint-dependent changes in compound-associated SAR information than would have been anticipated.

  8. Measuring activity in the ubiquitin-proteasome system: from large scale discoveries to single cells analysis.

    PubMed

    Melvin, Adam T; Woss, Gregery S; Park, Jessica H; Waters, Marcey L; Allbritton, Nancy L

    2013-09-01

    The ubiquitin-proteasome system (UPS) is the primary pathway responsible for the recognition and degradation of misfolded, damaged, or tightly regulated proteins in addition to performing essential roles in DNA repair, cell cycle regulation, cell migration, and the immune response. While traditional biochemical techniques have proven useful in the identification of key proteins involved in this pathway, the implementation of novel reporters responsible for measuring enzymatic activity of the UPS has provided valuable insight into the effectiveness of therapeutics and role of the UPS in various human diseases such as multiple myeloma and Huntington's disease. These reporters, usually consisting of a recognition sequence fused to an analytical handle, are designed to specifically evaluate enzymatic activity of certain members of the UPS including the proteasome, E3 ubiquitin ligases, and deubiquitinating enzymes. This review highlights the more commonly used reporters employed in a variety of scenarios ranging from high-throughput screening of novel inhibitors to single cell microscopy techniques measuring E3 ligase or proteasome activity. Finally, a recent study is presented highlighting the development of a novel degron-based substrate designed to overcome the limitations of current reporting techniques in measuring E3 ligase and proteasome activity in patient samples.

  9. Rotation, activity, and stellar obliquities in a large uniform sample of Kepler solar analogs

    NASA Astrophysics Data System (ADS)

    Buzasi, Derek; Lezcano, Andy; Preston, Heather L.

    2016-10-01

    In this study, we undertook a deep photometric examination of a narrowly-defined sample of solar analogs in the Kepler field, with the goals of producing a uniform and statistically meaningful sample of such stars, comparing the properties of planet hosts to those of the general stellar population, and examining the behavior of rotation and photometric activity among stars with similar overall physical parameters. We successfully derived photometric activity indicators and rotation periods for 95 planet hosts (Kepler objects of interest [KOIs]) and 954 solar analogs without detected planets; 573 of these rotation periods are reported here for the first time. Rotation periods average roughly 20 d, but the distribution has a wide dispersion, with a tail extending to P > 35 d which appears to be inconsistent with published gyrochronological relations. We observed a weak rotation-activity relation for stars with rotation periods less than about 12 d; for slower rotators, the relation is dominated by scatter. However, we are able to state that the solar activity level derived from Virgo data is consistent with the majority of stars with similar rotation periods in our sample. Finally, our KOI sample is consistently approximately 0.3 dex more variable than our non-KOIs; we ascribe the difference to a selection effect due to low orbital obliquity in the planet-hosting stars and derive a mean obliquity for our sample of χ = 6+5°-6, similar to that seen in the solar system.

  10. Thermal activation of 'allosteric-like' large-scale motions in a eukaryotic Lactate Dehydrogenase.

    PubMed

    Katava, Marina; Maccarini, Marco; Villain, Guillaume; Paciaroni, Alessandro; Sztucki, Michael; Ivanova, Oxana; Madern, Dominique; Sterpone, Fabio

    2017-01-23

    Conformational changes occurring during the enzymatic turnover are essential for the regulation of protein functionality. Individuating the protein regions involved in these changes and the associated mechanical modes is still a challenge at both experimental and theoretical levels. We present here a detailed investigation of the thermal activation of the functional modes and conformational changes in a eukaryotic Lactate Dehydrogenase enzyme (LDH). Neutron Spin Echo spectroscopy and Molecular Dynamics simulations were used to uncover the characteristic length- and timescales of the LDH nanoscale motions in the apo state. The modes involving the catalytic loop and the mobile region around the binding site are activated at room temperature, and match the allosteric reorganisation of bacterial LDHs. In a temperature window of about 15 degrees, these modes render the protein flexible enough and capable of reorganising the active site toward reactive configurations. On the other hand an excess of thermal excitation leads to the distortion of the protein matrix with a possible anti-catalytic effect. Thus, the temperature activates eukaryotic LDHs via the same conformational changes observed in the allosteric bacterial LDHs. Our investigation provides an extended molecular picture of eukaryotic LDH's conformational landscape that enriches the static view based on crystallographic studies alone.

  11. Thermal activation of ‘allosteric-like’ large-scale motions in a eukaryotic Lactate Dehydrogenase

    PubMed Central

    Katava, Marina; Maccarini, Marco; Villain, Guillaume; Paciaroni, Alessandro; Sztucki, Michael; Ivanova, Oxana; Madern, Dominique; Sterpone, Fabio

    2017-01-01

    Conformational changes occurring during the enzymatic turnover are essential for the regulation of protein functionality. Individuating the protein regions involved in these changes and the associated mechanical modes is still a challenge at both experimental and theoretical levels. We present here a detailed investigation of the thermal activation of the functional modes and conformational changes in a eukaryotic Lactate Dehydrogenase enzyme (LDH). Neutron Spin Echo spectroscopy and Molecular Dynamics simulations were used to uncover the characteristic length- and timescales of the LDH nanoscale motions in the apo state. The modes involving the catalytic loop and the mobile region around the binding site are activated at room temperature, and match the allosteric reorganisation of bacterial LDHs. In a temperature window of about 15 degrees, these modes render the protein flexible enough and capable of reorganising the active site toward reactive configurations. On the other hand an excess of thermal excitation leads to the distortion of the protein matrix with a possible anti-catalytic effect. Thus, the temperature activates eukaryotic LDHs via the same conformational changes observed in the allosteric bacterial LDHs. Our investigation provides an extended molecular picture of eukaryotic LDH’s conformational landscape that enriches the static view based on crystallographic studies alone. PMID:28112231

  12. Differential segmental strain during active lengthening in a large biarticular thigh muscle during running

    PubMed Central

    Carr, Jennifer A.; Ellerby, David J.; Marsh, Richard L.

    2011-01-01

    SUMMARY The iliotibialis lateralis pars postacetabularis (ILPO) is the largest muscle in the hindlimb of the guinea fowl and is thought to play an important role during the stance phase of running, both absorbing and producing work. Using sonomicrometry and electromyography, we examined whether the ILPO experiences differential strain between proximal, central and distal portions of the posterior fascicles. When the ILPO is being lengthened while active, the distal portion was found to lengthen significantly more than either the proximal or central portions of the muscle. Our data support the hypothesis that the distal segment lengthened farther and faster because it began activity at shorter sarcomere lengths on the ascending limb of the length–tension curve. Probably because of the self-stabilizing effects of operating on the ascending limb of the length–tension curve, all segments reached the end of lengthening and started shortening at the same sarcomere length. During shortening, this similarity in sarcomere length among the segments was maintained, as predicted from force–velocity effects, and shortening strain was similar in all segments. The differential active strain during active lengthening is thus ultimately determined by differences in strain during the passive portion of the cycle. The sarcomere lengths of all segments of the fascicles were similar at the end of active shortening, but after the passive portion of the cycle the distal segment was shorter. Differential strain in the segments during the passive portion of the cycle may be caused by differential joint excursions at the knee and hip acting on the ends of the muscle and being transmitted differentially by the passive visco-elastic properties of the muscle. Alternatively, the differential passive strain could be due to the action of active or passive muscles in the thigh that transmit force to the IPLO in shear. Based on basic sarcomere dynamics we predict that differential strain is

  13. The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation

    PubMed Central

    Absmeier, Eva; Wollenhaupt, Jan; Mozaffari-Jovin, Sina; Becke, Christian; Lee, Chung-Tien; Preussner, Marco; Heyd, Florian; Urlaub, Henning; Lührmann, Reinhard; Santos, Karine F.; Wahl, Markus C.

    2015-01-01

    The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6•U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation. PMID:26637280

  14. Large Scale Cortical Functional Networks Associated with Slow-Wave and Spindle-Burst-Related Spontaneous Activity

    PubMed Central

    McVea, David A.; Murphy, Timothy H.; Mohajerani, Majid H.

    2016-01-01

    Cortical sensory systems are active with rich patterns of activity during sleep and under light anesthesia. Remarkably, this activity shares many characteristics with those present when the awake brain responds to sensory stimuli. We review two specific forms of such activity: slow-wave activity (SWA) in the adult brain and spindle bursts in developing brain. SWA is composed of 0.5–4 Hz resting potential fluctuations. Although these fluctuations synchronize wide regions of cortex, recent large-scale imaging has shown spatial details of their distribution that reflect underlying cortical structural projections and networks. These networks are regulated, as prior awake experiences alter both the spatial and temporal features of SWA in subsequent sleep. Activity patterns of the immature brain, however, are very different from those of the adult. SWA is absent, and the dominant pattern is spindle bursts, intermittent high frequency oscillations superimposed on slower depolarizations within sensory cortices. These bursts are driven by intrinsic brain activity, which act to generate peripheral inputs, for example via limb twitches. They are present within developing sensory cortex before they are mature enough to exhibit directed movements and respond to external stimuli. Like in the adult, these patterns resemble those evoked by sensory stimulation when awake. It is suggested that spindle-burst activity is generated purposefully by the developing nervous system as a proxy for true external stimuli. While the sleep-related functions of both slow-wave and spindle-burst activity may not be entirely clear, they reflect robust regulated phenomena which can engage select wide-spread cortical circuits. These circuits are similar to those activated during sensory processing and volitional events. We highlight these two patterns of brain activity because both are prominent and well-studied forms of spontaneous activity that will yield valuable insights into brain function in

  15. Morphotectonic evolution of passive margins undergoing active surface processes: large-scale experiments using numerical models.

    NASA Astrophysics Data System (ADS)

    Beucher, Romain; Huismans, Ritske S.

    2016-04-01

    Extension of the continental lithosphere can lead to the formation of a wide range of rifted margins styles with contrasting tectonic and geomorphological characteristics. It is now understood that many of these characteristics depend on the manner extension is distributed depending on (among others factors) rheology, structural inheritance, thermal structure and surface processes. The relative importance and the possible interactions of these controlling factors is still largely unknown. Here we investigate the feedbacks between tectonics and the transfers of material at the surface resulting from erosion, transport, and sedimentation. We use large-scale (1200 x 600 km) and high-resolution (~1km) numerical experiments coupling a 2D upper-mantle-scale thermo-mechanical model with a plan-form 2D surface processes model (SPM). We test the sensitivity of the coupled models to varying crust-lithosphere rheology and erosional efficiency ranging from no-erosion to very efficient erosion. We discuss how fast, when and how the topography of the continents evolves and how it can be compared to actual passive margins escarpment morphologies. We show that although tectonics is the main factor controlling the rift geometry, transfers of masses at the surface affect the timing of faulting and the initiation of sea-floor spreading. We discuss how such models may help to understand the evolution of high-elevated passive margins around the world.

  16. Protein kinase activity associated with the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10).

    PubMed Central

    Chung, T D; Wymer, J P; Smith, C C; Kulka, M; Aurelian, L

    1989-01-01

    The large subunit of the herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (RR1) is demonstrated to possess serine/threonine-specific kinase activity. Computer-assisted sequence analysis identified regions within the amino terminus of ICP10 that are homologous to the catalytic domain of known protein kinases (PKs). An in vitro kinase assay confirmed the ability of ICP10, immunoprecipitated from either HSV-2-infected cells or from cells transfected with an ICP10 expression vector, to autophosphorylate and transphosphorylate exogenous substrates in the presence of ATP and Mg2+. The HSV-1 RR1 was shown to be negative for PK activity under these conditions. PK activity was localized to a 57-kDa amino-terminal region within ICP10 that lacked RR activity. Images PMID:2545912

  17. Epigenetic upregulation of large-conductance Ca2+-activated K+ channel expression in uterine vascular adaptation to pregnancy.

    PubMed

    Chen, Man; Dasgupta, Chiranjib; Xiong, Fuxia; Zhang, Lubo

    2014-09-01

    Our previous study demonstrated that pregnancy increased large-conductance Ca(2+)-activated potassium channel β1 subunit (BKβ1) expression and large-conductance Ca(2+)-activated potassium channel activity in uterine arteries, which were abrogated by chronic hypoxia. The present study tested the hypothesis that promoter methylation/demethylation is a key mechanism in epigenetic reprogramming of BKβ1 expression patterns in uterine arteries. Ovine BKβ1 promoter of 2315 bp spanning from -2211 to +104 of the transcription start site was cloned, and an Sp1-380 binding site that contains CpG dinucleotide in its core binding sequences was identified. Site-directed deletion of the Sp1 site significantly decreased the BKβ1 promoter activity. Estrogen receptor-α bound to the Sp1 site through tethering to Sp1 and upregulated the expression of BKβ1. The Sp1 binding site at BKβ1 promoter was highly methylated in uterine arteries of nonpregnant sheep, and methylation inhibited transcription factor binding and BKβ1 promoter activity. Pregnancy caused a significant decrease in CpG methylation at the Sp1 binding site and increased Sp1 binding to the BKβ1 promoter and BKβ1 mRNA abundance. Chronic hypoxia during gestation abrogated this pregnancy-induced demethylation and upregulation of BKβ1 expression. The results provide evidence of a novel mechanism of promoter demethylation in pregnancy-induced reprogramming of large-conductance Ca(2+)-activated potassium channel expression and function in uterine arteries and suggest new insights of epigenetic mechanisms linking gestational hypoxia to aberrant uteroplacental circulation and increased risk of preeclampsia.

  18. Distribution of serum paraoxon hydrolyzing activity in a large Spanish population using a routine automized method in clinical laboratory.

    PubMed

    Carrera, V; Llopis, I; Sastre, J; Sogorb, M A; Vilanova, E

    2003-01-01

    This work was performed to adapt the manual laboratory method of measuring serum paraoxonase activity using a routine automatized method in the clinical laboratory and to study the distribution of paraoxonase activity in a large population from Alcoy, a region of Spain. The serum samples for the study were obtained from extractions of blood from 2891 individuals, distributed by sex and age groups, in a routine check in a primary care facility of Alcoy. Paraoxonase activity was assayed by measuring the release of p-nitrophenol according to a previously published method adapted to an automatized analyzer. The mean paraoxonase activity recorder was 70.2 +/- 16.5 IU/L. Paraoxonase activity in children (both males and females) was significantly lower (p < 0.0005) than in older individuals. Paraoxonase activity detected in males and females older than 56 was slightly lower than that detected in younger individuals, although in this case the difference was not statistically significant. The paraoxonase activity shows higher mean values in females than in males (p < 0.0005). Human paraoxonase activity shows a unimodal distribution pattern in the studied population, which is in contrast with other studies showing bimodal distribution.

  19. Using Large Group Displays to Support Intensive Team Activities in C2

    DTIC Science & Technology

    2011-06-01

    Organization (DSTO) Edinburgh, PO Box 1500, Edinburgh SA 511 Australia (*) E-mail: : Point of contact information Denis.Gouin@drdc...Experiment (JEFX) 2004 exercises at Nellis Air Operations Center ( Darling & Means, 2005). This work echoes many of the considerations and challenges of...they use. For example, the DataWall evaluations ( Darling & Means, 2005) highlighted the need to use the displays to: “provide activity awareness to

  20. High speed large viewing angle shutters for triple-flash active glasses

    NASA Astrophysics Data System (ADS)

    Caillaud, B.; Bellini, B.; de Bougrenet de la Tocnaye, J.-L.

    2009-02-01

    We present a new generation of liquid crystal shutters for active glasses, well suited to 3-D cinema current trends, involving triple flash regimes. Our technology uses a composite smectic C* liquid crystal mixture1. In this paper we focus on the electro-optical characterization of composite smectic-based shutters, and compare their performance with nematic ones, demonstrating their advantages for the new generation of 3-D cinema and more generally 3-D HDTV.

  1. Active region 11748: Recurring X-class flares, large scale dimmings and waves.

    NASA Astrophysics Data System (ADS)

    Davey, Alisdair R.; Malanushenko, Anna; McIntosh, Scott W.

    2014-06-01

    AR 11748 was a relatively compact active region that crossed the solar disk between 05/14/2013 and 05/26/2013. Despite its size it produced a number X-class flares, and global scale eruptive events that were captured by the SDO Feature Finding Team's (FFT) Dimming Region Detector. Using the results of this module and other FFT modules, we present an analysis of the this AR region and investigate why it was so globally impactful.

  2. The architecture of the active surface control system of the Large Millimeter Telescope

    NASA Astrophysics Data System (ADS)

    Souccar, Kamal; Wallace, Gary; Grosslein, Ron; Schloerb, F. Peter

    2014-07-01

    One of the fundamental design principles of the LMT is that its segmented primary surface must be active: the position and orientation of each of the segments must be moved in order to maintain the precise parabolic surface that is required by the specifications. Consequently, a system of actuators, one at the corner of each segment, is used to move the segments to counteract surface deformations attributed to gravity or thermal effects. A new control system was designed and built within the project to implement an active surface at the LMT. The technical concept for the active surface control system is to provide a set of bus boxes with built-in control and I/O capabilities to run four actuators each. Bus boxes read the LVDT sensor position and limit switch status for each actuator and use this information to drive the actuator's DC motor, closing the position loop. Each bus box contains a DC power supply for the electronics, a second DC power supply for the motors, an embedded controller with I/O to close the position loop, and a custom printed circuit board to condition the LVDT signals and drive the motors. An interface printed circuit board resides in each actuator providing a single connector access to the LVDT, the motor, and the limit switches. During the fall of 2013, 84 bus boxes were commissioned to control the 336 actuators of the inner three rings of the telescope. The surface correction model was determined using holography measurements and the active surface system has been in regular use during the scientific observation at the LMT.

  3. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

    PubMed Central

    Welshons, Wade V; Thayer, Kristina A; Judy, Barbara M; Taylor, Julia A; Curran, Edward M; vom Saal, Frederick S

    2003-01-01

    Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. These doses are within the range of current exposures to numerous chemicals in wildlife and humans. These problems are exacerbated by the fact that the type of positive and negative controls appropriate to the study of endocrine responses are not part of traditional toxicological testing and are frequently omitted, or when present, have been misinterpreted. PMID:12826473

  4. Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance

    NASA Astrophysics Data System (ADS)

    Eggert, Silke; Walter, Thomas R.

    2009-06-01

    The study of volcanic triggering and interaction with the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of clustered eruptions and earthquakes may imply that interaction is important in some subregions. However, the subregions likely to suffer such clusters have not been systematically identified, and the processes responsible for the observed interaction remain unclear. We first review previous works about the clustered occurrence of eruptions and earthquakes, and describe selected events. We further elaborate available databases and confirm a statistically significant relationship between volcanic eruptions and earthquakes on the global scale. Moreover, our study implies that closed volcanic systems in particular tend to be activated in association with a tectonic earthquake trigger. We then perform a statistical study at the subregional level, showing that certain subregions are especially predisposed to concurrent eruption-earthquake sequences, whereas such clustering is statistically less significant in other subregions. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. The activity at volcanoes located in the predisposed subregions (e.g., Japan, Indonesia, Melanesia), however, often unexpectedly changes in association with either an imminent or a past earthquake.

  5. Space Active Optics: toward optimized correcting mirrors for future large spaceborne observatories

    NASA Astrophysics Data System (ADS)

    Laslandes, Marie; Hugot, Emmanuel; Ferrari, Marc; Lemaitre, Gérard; Liotard, Arnaud

    2011-10-01

    Wave-front correction in optical instruments is often needed, either to compensate Optical Path Differences, off-axis aberrations or mirrors deformations. Active optics techniques are developed to allow efficient corrections with deformable mirrors. In this paper, we will present the conception of particular deformation systems which could be used in space telescopes and instruments in order to improve their performances while allowing relaxing specifications on the global system stability. A first section will be dedicated to the design and performance analysis of an active mirror specifically designed to compensate for aberrations that might appear in future 3m-class space telescopes, due to lightweight primary mirrors, thermal variations or weightless conditions. A second section will be dedicated to a brand new design of active mirror, able to compensate for given combinations of aberrations with a single actuator. If the aberrations to be corrected in an instrument and their evolutions are known in advance, an optimal system geometry can be determined thanks to the elasticity theory and Finite Element Analysis.

  6. Large scale screening of commonly used Iranian traditional medicinal plants against urease activity

    PubMed Central

    2012-01-01

    Background and purpose of the study H. pylori infection is an important etiologic impetus usually leading to gastric disease and urease enzyme is the most crucial role is to protect the bacteria in the acidic environment of the stomach. Then urease inhibitors would increase sensitivity of the bacteria in acidic medium. Methods 137 Iranian traditional medicinal plants were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 50% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. Results 37 plants out of the 137 crude extracts revealed strong urease inhibitory activity (more than 70% inhibition against urease activity at 10 mg/ml concentration). Nine of the whole studied plants crude extracts were found as the most effective with IC50 values less than 500 μg/ml including; Rheum ribes, Sambucus ebulus, Pistachia lentiscus, Myrtus communis, Areca catechu, Citrus aurantifolia, Myristica fragrans, Cinnamomum zeylanicum and Nicotiana tabacum. Conclusions The most potent urease inhibitory was observed for Sambucus ebulus and Rheum ribes extracts with IC50 values of 57 and 92 μg/ml, respectively. PMID:23351780

  7. Large-scale, dynamic transformations in fuel moisture drive wildfire activity across southeastern Australia

    NASA Astrophysics Data System (ADS)

    Nolan, R. H.; Boer, M. M.; Resco de Dios, V.; Caccamo, G.; Bradstock, R. A.

    2016-05-01

    The occurrence of large, high-intensity wildfires requires plant biomass, or fuel, that is sufficiently dry to burn. This poses the question, what is "sufficiently dry"? Until recently, the ability to address this question has been constrained by the spatiotemporal scale of available methods to monitor the moisture contents of both dead and live fuels. Here we take advantage of recent developments in macroscale monitoring of fuel moisture through a combination of remote sensing and climatic modeling. We show there are clear thresholds of fuel moisture content associated with the occurrence of wildfires in forests and woodlands. Furthermore, we show that transformations in fuel moisture conditions across these thresholds can occur rapidly, within a month. Both the approach presented here, and our findings, can be immediately applied and may greatly improve fire risk assessments in forests and woodlands globally.

  8. Oxygen-Activated Growth and Bandgap Tunability of Large Single-Crystal Bilayer Graphene

    NASA Astrophysics Data System (ADS)

    Hao, Yufeng; Hone, James; Ruoff, Rodney; Colombo, Luigi; the Hone Group Team

    Distinct from zero-bandgap single-layer graphene, Bernal-stacked bilayer graphene (BLG) is a semiconductor whose bandgap can be tuned by a transverse electric field, making it a unique material for a number of electronic and photonic devices. In this presentation, we will focus on the most recent progress in the identification of new growth mechanisms towards large-area single-layer BLG on Copper: multiple control experiments and first-principles calculations are used to support the proposed mechanisms. We emphasize that trace amount of impurities on metal surface are critical to initiate graphene growth and affect the growth kinetics. Furthermore, contrary to the traditional viewpoint that graphene growth is always surface-limited process, our new observations strongly suggest that metal bulk plays a role to feed carbon species for graphene growth. State-of-the-art structural characterizations and electrical transport measurements of the CVD graphene layers will be presented as well.

  9. Simultaneous Solar Maximum Mission (SMM) and very large array observations of solar active regions

    NASA Technical Reports Server (NTRS)

    Lang, K. R.

    1986-01-01

    The research deals mainly with Very Large Array and Solar Maximum Mission observations of the ubiquitous coronal loops that dominate the structure of the low corona. As illustrated, the observations of thermal cyclotron lines at microwave wavelengths provide a powerful new method of accurately specifying the coronal magnetic field strength. Processes are delineated that trigger solar eruptions from coronal loops, including preburst heating and the magnetic interaction of coronal loops. Evidence for coherent burst mechanisms is provided for both the Sun and nearby stars, while other observations suggest the presence of currents that may amplify the coronal magnetic field to unexpectedly high levels. The existence is reported of a new class of compact, variable moving sources in regions of apparently weak photospheric field.

  10. Large loop conformation sampling using the activation relaxation technique, ART-nouveau method.

    PubMed

    St-Pierre, Jean-François; Mousseau, Normand

    2012-07-01

    We present an adaptation of the ART-nouveau energy surface sampling method to the problem of loop structure prediction. This method, previously used to study protein folding pathways and peptide aggregation, is well suited to the problem of sampling the conformation space of large loops by targeting probable folding pathways instead of sampling exhaustively that space. The number of sampled conformations needed by ART nouveau to find the global energy minimum for a loop was found to scale linearly with the sequence length of the loop for loops between 8 and about 20 amino acids. Considering the linear scaling dependence of the computation cost on the loop sequence length for sampling new conformations, we estimate the total computational cost of sampling larger loops to scale quadratically compared to the exponential scaling of exhaustive search methods.

  11. A peptide with potent antifungal and antiproliferative activities from Nepalese large red beans.

    PubMed

    Ma, D Z; Wang, H X; Ng, T B

    2009-12-01

    An antifungal defensin-like peptide with a molecular mass of 7.1kDa was isolated from dried Nepalese large red beans (Phaseolus angularis). The purification protocol employed included ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The antifungal peptide was unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and SP-Sepharose. The antifungal peptide inhibited mycelial growth in Fusarium oxysporum and Mycosphaerella arachidicola with an IC(50) value of 1.4 and 1.8 microM, respectively. It did not inhibit HIV-1 reverse transcriptase when tested up to 200 microM. It exerted an antiproliferative action on L1210 leukemia cells and MBL2 lymphoma cells with an IC(50) of 15 and 60 microM, respectively.

  12. NeuroCa: integrated framework for systematic analysis of spatiotemporal neuronal activity patterns from large-scale optical recording data

    PubMed Central

    Jang, Min Jee; Nam, Yoonkey

    2015-01-01

    Abstract. Optical recording facilitates monitoring the activity of a large neural network at the cellular scale, but the analysis and interpretation of the collected data remain challenging. Here, we present a MATLAB-based toolbox, named NeuroCa, for the automated processing and quantitative analysis of large-scale calcium imaging data. Our tool includes several computational algorithms to extract the calcium spike trains of individual neurons from the calcium imaging data in an automatic fashion. Two algorithms were developed to decompose the imaging data into the activity of individual cells and subsequently detect calcium spikes from each neuronal signal. Applying our method to dense networks in dissociated cultures, we were able to obtain the calcium spike trains of ∼1000 neurons in a few minutes. Further analyses using these data permitted the quantification of neuronal responses to chemical stimuli as well as functional mapping of spatiotemporal patterns in neuronal firing within the spontaneous, synchronous activity of a large network. These results demonstrate that our method not only automates time-consuming, labor-intensive tasks in the analysis of neural data obtained using optical recording techniques but also provides a systematic way to visualize and quantify the collective dynamics of a network in terms of its cellular elements. PMID:26229973

  13. A fiber optic temperature sensor for aerospace applications

    NASA Astrophysics Data System (ADS)

    Jensen, Stephen C.; Tilstra, Shelle D.; Barnabo, Geoffrey A.; Thomas, David C.; Phillips, Richard W.

    1991-02-01

    A fiber-optic temperature sensor has been developed for aerospace applications on the basis of the time rate of decay (TRD) principle, with a view to an operational temperature range of -60 to 350 C. This TRD system has completed qualification testing and will then undergo flight tests. Attention is presently given to the design and performance of four low temperature sensors that are subelements of the larger sensor system; in order to convert analog signals into over/under temperature indications, simple comparators are implemented in software.

  14. Use of a fiber optic probe for organic species determination

    DOEpatents

    Ekechukwu, Amy A.

    1996-01-01

    A fiber optic probe for remotely detecting the presence and concentration organic species in aqueous solutions. The probe includes a cylindrical housing with an organic species indicator, preferably diaminonaphthyl sulfonic acid adsorbed in a silica gel (DANS-modified gel), contained in the probe's distal end. The probe admits aqueous solutions to the probe interior for mixing within the DANS-modified gel. An optical fiber transmits light through the DANS-modified gel while the indicator reacts with organic species present in the solution, thereby shifting the location of the fluorescent peak. The altered light is reflected to a receiving fiber that carries the light to a spectrophotometer or other analysis device.

  15. Raman imaging with a fiber-coupled multichannel spectrograph.

    PubMed

    Schmälzlin, Elmar; Moralejo, Benito; Rutowska, Monika; Monreal-Ibero, Ana; Sandin, Christer; Tarcea, Nicolae; Popp, Jürgen; Roth, Martin M

    2014-11-20

    Until now, spatially resolved Raman Spectroscopy has required to scan a sample under investigation in a time-consuming step-by-step procedure. Here, we present a technique that allows the capture of an entire Raman image with only one single exposure. The Raman scattering arising from the sample was collected with a fiber-coupled high-performance astronomy spectrograph. The probe head consisting of an array of 20 × 20 multimode fibers was linked to the camera port of a microscope. To demonstrate the high potential of this new concept, Raman images of reference samples were recorded. Entire chemical maps were received without the need for a scanning procedure.

  16. A large family of anti-activators accompanying XylS/AraC family regulatory proteins.

    PubMed

    Santiago, Araceli E; Yan, Michael B; Tran, Minh; Wright, Nathan; Luzader, Deborah H; Kendall, Melissa M; Ruiz-Perez, Fernando; Nataro, James P

    2016-07-01

    AraC Negative Regulators (ANR) suppress virulence genes by directly down-regulating AraC/XylS members in Gram-negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR-activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC-like member AggR. ANR-AggR binding disrupted AggR dimerization and prevented AggR-DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α-helices. Site-directed mutagenesis studies suggest that at least predicted α-helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners.

  17. A large family of anti‐activators accompanying XylS/AraC family regulatory proteins

    PubMed Central

    Yan, Michael B.; Tran, Minh; Wright, Nathan; Luzader, Deborah H.; Kendall, Melissa M.; Ruiz‐Perez, Fernando; Nataro, James P.

    2016-01-01

    Summary AraC Negative Regulators (ANR) suppress virulence genes by directly down‐regulating AraC/XylS members in Gram‐negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR‐activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC‐like member AggR. ANR‐AggR binding disrupted AggR dimerization and prevented AggR‐DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α‐helices. Site‐directed mutagenesis studies suggest that at least predicted α‐helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners. PMID:27038276

  18. Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance

    NASA Astrophysics Data System (ADS)

    Eggert, S.; Walter, T. R.

    2009-04-01

    The study of volcanic triggering and coupling to the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of volcano-earthquake interactions in, e.g., Europe and Japan, may imply that clustered occurrence is important in some regions. However, the regions likely to suffer clustered eruption-earthquake activity have not been systematically identified, and the processes responsible for the observed interaction are debated. We first review previous works about the correlation of volcanic eruptions and earthquakes, and describe selected local clustered events. Following an overview of previous statistical studies, we further elaborate the databases of correlated eruptions and earthquakes from a global perspective. Since we can confirm a relationship between volcanic eruptions and earthquakes on the global scale, we then perform a statistical study on the regional level, showing that time and distance between events follow a linear relationship. In the time before an earthquake, a period of volcanic silence often occurs, whereas in the time after, an increase in volcanic activity is evident. Our statistical tests imply that certain regions are especially predisposed to concurrent eruption-earthquake pairs, e.g., Japan, whereas such pairing is statistically less significant in other regions, such as Europe. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. Volcanoes located in the predisposed regions (e.g., Japan, Indonesia, Melanesia), however, indeed often have unexpectedly changed in association with either an imminent or a past earthquake.

  19. Large scale study on measurement of respiration activity (AT(4)) by Sapromat and OxiTop.

    PubMed

    Binner, Erwin; Böhm, Katharina; Lechner, Peter

    2012-10-01

    In the run-up for amending the Austrian landfill ordinance, parameters were developed to assess the stability/reactivity of mechanically-biologically pretreated residual wastes. The Landfill Ordinance 2008 regulates limit values for Respiration Activity (="Atmungsaktivität") RA(4) (AT(4))<7mgO(2)*(g dry matter (DM))(-1), Gas Generation Sum GS(21)<20Nl*kgDM(-1) and alternatively Gas Evolution (="Gasbildung") GB(21)<20Nl*kgDM(-1). Methods for analysing these parameters were established by the Austrian Standards Institute (2004). As laboratory practice shows, these methods also are used for the assessment of other wastes (sewage sludge, commercial waste, material from abandoned sites, biowaste compost). For measurement of respiration activity in Austria mainly two methods are used: the Sapromat®-method and the OxiTop®-method. Whether respectively to what extent these two methods give same results, is discussed in this paper. Since 2009 at ABF-BOKU 169 respiration activity tests of samples taken from different stages of MBT - as well as biowaste composting processes, materials from landfills as well as abandoned sites and residues from anaerobic treatment plants were analysed parallel by Sapromat® and OxiTop®. The results manifest very strong correlation between the Sapromat® and OxiTop® method. The correlation coefficient is 0.993. As a very clear tendency OxiTop® gives lower amounts than Sapromat®. In average the lower values of OxiTop® are around 88%.

  20. Synthesis, characterization and catalytic activity of novel large network polystyrene-immobilized organic bases

    DOE PAGES

    Tassi, Marco; Bartollini, Elena; Adriaensens, Peter; ...

    2015-12-07

    In view of searching for efficient polymeric supports for organic bases to be used in environmentally friendly reaction conditions, novel gel-type cross-linked polystyrenes functionalized with diethylamine and 1,5,7-triazabicyclo[4.4.0]dec-5-ene, have been prepared. Moreover, the structural properties and morphology of these catalysts have been determined by extensive solid state NMR experiments, FTIR spectroscopy and SEM/TEM microscopy. SPACeR-supported bases were found to exhibit high catalytic activity in the epoxide ring opening by phenols. Finally, a range of β-substituted alcohols have been readily and regioselectively synthesized.

  1. Observation of the activity of selected Oort Cloud comets with perihelia at large distances from the Sun

    NASA Astrophysics Data System (ADS)

    Kulyk, Iryna; Rousselot, Philippe; Korsun, Pavlo

    2016-10-01

    Many comets exhibit considerable level of activity at large distances from the Sun, where sublimation of crystalline water ice cannot account for observable comae. Different patterns of physical activity already observed at large heliocentric distances may be related to the primordial differences in the composition of comet nuclei. Therefore, monitoring of physical activity in the wide range of heliocentric distances can potentially contribute to understanding of internal structure of comet-like bodies. We have observed ten long periodic comets with orbital perihelia lying beyond the "water ice sublimation zone" to quantify the level of physical activity in the wide range of heliocentric distances. Pre-perihelion observations were made when targets moved between 16.7 and 6.5 au from the Sun; post perihelion activity was monitored between 5.2 and 10.6 au. The bulk of the data were gathered with the 2-m Robotic Liverpool Telescope (Observatorio del Roque de Los Muchachos, La Palma, Spain). Some targets were observed with the 2-m RC Telescope located at Peak Terskol Observatory and the 6-m Telescope of the Special Astrophysical Observatory (Northern Caucasus, Russia). Since most of recently obtained spectra of distant active objects are continuum dominated, we use B, V, R images to estimate dust production rates, an upper limit on nucleus radii, and color indices of near nucleus region. The comets C/2005 L3 (McNaught) and C/2006 S3 (Boattini), which exhibit the considerable level of activity, have been repeatedly observed. This enables us to infer the heliocentric dependence of dust production rates, perihelion brightness asymmetries, and color variations over the comae caused possibly by small changes in dust particle properties.

  2. APE: the Active Phasing Experiment to test new control system and phasing technology for a European Extremely Large Optical Telescope

    NASA Astrophysics Data System (ADS)

    Gonte, F.; Yaitskova, N.; Derie, F.; Constanza, A.; Brast, R.; Buzzoni, B.; Delabre, B.; Dierickx, P.; Dupuy, C.; Esteves, R.; Frank, C.; Guisard, S.; Karban, R.; Koenig, E.; Kolb, J.; Nylund, M.; Noethe, L.; Surdej, I.; Courteville, A.; Wilhelm, R.; Montoya, L.; Reyes, M.; Esposito, S.; Pinna, E.; Dohlen, K.; Ferrari, M.; Langlois, M.

    2005-08-01

    The future European Extremely Large Telescope will be composed of one or two giant segmented mirrors (up to 100 m of diameter) and of several large monolithic mirrors (up to 8 m in diameter). To limit the aberrations due to misalignments and defective surface quality it is necessary to have a proper active optics system. This active optics system must include a phasing system to limit the degradation of the PSF due to misphasing of the segmented mirrors. We will present the lastest design and development of the Active Phasing Experiment that will be tested in laboratory and on-sky connected to a VLT at Paranal in Chile. It includes an active segmented mirror, a static piston plate to simulate a secondary segmented mirror and of four phasing wavefront sensors to measure the piston, tip and tilt of the segments and the aberrations of the VLT. The four phasing sensors are the Diffraction Image Phase Sensing Instrument developed by Instituto de Astrofisica de Canarias, the Pyramid Phasing Sensor developed by Arcetri Astrophysical Observatory, the Shack-Hartmann Phasing Sensor developed by the European Southern Observatory and the Zernike Unit for Segment phasing developed by Laboratoire d'Astrophysique de Marseille. A reference measurement of the segmented mirror is made by an internal metrology developed by Fogale Nanotech. The control system of Active Phasing Experiment will perform the phasing of the segments, the guiding of the VLT and the active optics of the VLT. These activities are included in the Framework Programme 6 of the European Union.

  3. A large difference in the progenitor masses of active and passive galaxies in the EAGLE simulation

    NASA Astrophysics Data System (ADS)

    Clauwens, Bart; Franx, Marijn; Schaye, Joop

    2016-11-01

    Cumulative number density matching of galaxies is a method to observationally connect descendent galaxies to their typical main progenitors at higher redshifts and thereby to assess the evolution of galaxy properties. The accuracy of this method is limited due to galaxy merging and scatter in the stellar mass growth history of individual galaxies. Behroozi et al. have introduced a refinement of the method, based on abundance matching of observed galaxies to the Bolshoi dark matter-only simulation. The EAGLE cosmological hydrosimulation is well suited to test this method, because it reproduces the observed evolution of the galaxy stellar mass function and the passive fraction. We find agreement with the Behroozi et al. method for the complete sample of main progenitors of z = 0 galaxies, but we also find a strong dependence on the current star formation rate. Passive galaxies with a stellar mass up to 1010.75 M⊙ have a completely different median mass history than active galaxies of the same mass. This difference persists if we only select central galaxies. This means that the cumulative number density method should be applied separately to active and passive galaxies. Even then, the typical main progenitor of a z = 0 galaxy already spans two orders of magnitude in stellar mass at z = 2.

  4. Simultaneous SMM flat crystal spectrometer and Very Large Array observations of solar active regions

    NASA Technical Reports Server (NTRS)

    Lang, Kenneth R.; Willson, Robert F.; Smith, Kermit L.; Strong, Keith T.

    1987-01-01

    High-resolution images of the quiescent emission from two solar active regions at 20 cm (VLA) and soft X-ray (SMM FCS) wavelengths are compared. There are regions where the X-ray coronal loops have been completely imaged at 20 cm wavelength. In other regions, the X-ray radiation was detected without detectable 20 cm radiation, and vice versa. The X-ray data were used to infer average electron temperatures of about 3-million K and average electron densities of about 2.5 x 10 to the 9th/cu cm for the X-ray emitting plasma in the two active regions. The thermal bremsstrahlung of the X-ray emitting plasma is optically thin at 20 cm wavelength. The 20 cm brightness temperatures were always less than T(e), which is consistent with optically thin bremsstrahlung. The low T(B) can be explained if a higher, cooler plasma covers the hotter X-ray emitting plasma. Thermal gyroresonance radiation must account for the intense 20 cm radiation near and above sunspots where no X-ray radiation is detected.

  5. The challenge of "teaching" large groups of learners: strategies to increase active participation and learning.

    PubMed

    Nierenberg, D W

    1998-01-01

    While teaching in a tutorial, seminar, or problem-based learning group format may be the most fun and most active/interactive for both learner and faculty mentor, there are situations in medical student education in which various constraints require the use of the "lecture" format. Similar constraints may occur in the field of continuing medical education, or graduate medical education, as well. When this occurs, the faculty mentor can increase the active participation of the learners in the audience by continuously stressing seven key pedagogical (androgogical) principles. These include: 1) begin the learning exercise with a clinical example or anecdote to show the relevance of the material to the student; 2) frequently ask the students whether they have ever seen examples of what you describe in their previous experience with patients, personal experience, experience with relatives, etc.; 3) ask students frequently whether they have heard similar material presented differently in other courses; 4) recruit students to help solve "mystery cases"; 5) show examples of similar material from real life (e.g., patient descriptions, or even excerpts from favorite TV shows); 6) ask students to help summarize key points at the end of the session; and 7) allow, or even encourage, whispering during the class. Using some or all of these techniques can help turn a "lecture format" into a much more fun, interactive, and valuable session that emphasizes "learning" rather than "teaching."

  6. Conformable, flexible, large-area networks of pressure and thermal sensors with organic transistor active matrixes

    NASA Astrophysics Data System (ADS)

    Someya, Takao; Kato, Yusaku; Sekitani, Tsuyoshi; Iba, Shingo; Noguchi, Yoshiaki; Murase, Yousuke; Kawaguchi, Hiroshi; Sakurai, Takayasu

    2005-08-01

    Skin-like sensitivity, or the capability to recognize tactile information, will be an essential feature of future generations of robots, enabling them to operate in unstructured environments. Recently developed large-area pressure sensors made with organic transistors have been proposed for electronic artificial skin (E-skin) applications. These sensors are bendable down to a 2-mm radius, a size that is sufficiently small for the fabrication of human-sized robot fingers. Natural human skin, however, is far more complex than the transistor-based imitations demonstrated so far. It performs other functions, including thermal sensing. Furthermore, without conformability, the application of E-skin on three-dimensional surfaces is impossible. In this work, we have successfully developed conformable, flexible, large-area networks of thermal and pressure sensors based on an organic semiconductor. A plastic film with organic transistor-based electronic circuits is processed to form a net-shaped structure, which allows the E-skin films to be extended by 25%. The net-shaped pressure sensor matrix was attached to the surface of an egg, and pressure images were successfully obtained in this configuration. Then, a similar network of thermal sensors was developed with organic semiconductors. Next, the possible implementation of both pressure and thermal sensors on the surfaces is presented, and, by means of laminated sensor networks, the distributions of pressure and temperature are simultaneously obtained. Author contributions: T. Someya designed research; T. Someya, Y.K., T. Sekitani, S.I., Y.N., Y.M., H.K., and T. Sakurai performed research; and T. Someya wrote the paper.This paper was submitted directly (Track II) to the PNAS office.Freely available online through the PNAS open access option.Abbreviations: E-skin, electronic artificial skin; IDS, source-drain current; PTCDI, 3,4,9,10-perylene-tetracarboxylic-diimide; parylene, polychloro-para-xylylene; CuPc, copper

  7. Molecular Information of charybdotoxin blockade in the large conductance calcium-activated potassium channel.

    PubMed

    Qiu, Su; Yi, Hong; Liu, Hui; Cao, Zhijian; Wu, Yingliang; Li, Wenxin

    2009-07-01

    The scorpion toxin, charybdotoxin (ChTX), is the first identified peptide inhibitor for the large-conductance Ca2+ and voltage-dependent K+ (BK) channel, and the chemical information of the interaction between ChTX and BK channel remains unclear today. Using combined computational methods, we obtained a ChTX-BK complex structure model, which correlated well with the mutagenesis data. In this complex, ChTX mainly used its beta-sheet domains to associate the BK channel with a conserved pore-blocking Lys27. Another crucial Tyr36 residue of ChTX lied over the loop connecting selectivity filter and S6 helix of BK channel, forming a hydrogen bond with Gly291 of BK channel. Besides, the unique turret region of BK channel was found to be far away from bound ChTX, which could explain the fact that many BK channel blockers show less selectivity over Kv channels. Together, all these information is helpful to reveal the diverse interactions between scorpion toxins and potassium channels and can accelerate the molecular engineering of specific inhibitor design.

  8. Acute lymphoblastic leukaemia cells produce large extracellular vesicles containing organelles and an active cytoskeleton

    PubMed Central

    Johnson, Suzanne M.; Dempsey, Clare; Parker, Catriona; Mironov, Aleksandr; Bradley, Helen; Saha, Vaskar

    2017-01-01

    ABSTRACT Extracellular vesicles have been described in non-paracrine cellular interactions in cancer. We report a similar phenomenon in B-cell precursor (BCP) acute lymphoblastic leukaemia (ALL). Using advanced microscopy and high throughput screening, we further characterise a subset of large vesicles (LEVs) identified in cell lines, murine models of human BCP-ALL and clinical samples. Primary ALL blasts and cell lines released heterogeneous anucleate vesicles <6 micron into extracellular fluids. Larger LEVs were enclosed in continuous membranes, contained intact organelles and demonstrated an organised cytoskeleton. An excess of circulating CD19-positive LEVs were observed in diagnostic samples and isolated from mice engrafted with BCP-ALL primary cells. LEVs exhibited dynamic shape change in vitro and were internalised by other leukaemic cell lines leading to phenotypic transformation analogous to the cell of origin. In patient-derived xenografts, LEVs were released by primary ALL cells into extracellular spaces and internalised by murine mesenchymal cells in vivo. Collectively these data highlight the heterogeneity but accessibility of LEVs in clinical samples and their potential to provide a unique insight into the biology of the cell of origin and to their development as novel biomarkers to aid diagnosis and improve therapeutic outcomes. PMID:28386390

  9. Antibacterial activity of large-area monolayer graphene film manipulated by charge transfer.

    PubMed

    Li, Jinhua; Wang, Gang; Zhu, Hongqin; Zhang, Miao; Zheng, Xiaohu; Di, Zengfeng; Liu, Xuanyong; Wang, Xi

    2014-03-12

    Graphene has attracted increasing attention for potential applications in biotechnology due to its excellent electronic property and biocompatibility. Here we use both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) to investigate the antibacterial actions of large-area monolayer graphene film on conductor Cu, semiconductor Ge and insulator SiO2. The results show that the graphene films on Cu and Ge can surprisingly inhibit the growth of both bacteria, especially the former. However, the proliferation of both bacteria cannot be significantly restricted by the graphene film on SiO2. The morphology of S. aureus and E. coli on graphene films further confirms that the direct contact of both bacteria with graphene on Cu and Ge can cause membrane damage and destroy membrane integrity, while no evident membrane destruction is induced by graphene on SiO2. From the viewpoint of charge transfer, a plausible mechanism is proposed here to explain this phenomenon. This study may provide new insights for the better understanding of antibacterial actions of graphene film and for the better designing of graphene-based antibiotics or other biomedical applications.

  10. A fiber Bragg grating sensor system for estimating the large deflection of a lightweight flexible beam

    NASA Astrophysics Data System (ADS)

    Peng, Te; Yang, Yangyang; Ma, Lina; Yang, Huayong

    2016-10-01

    A sensor system based on fiber Bragg grating (FBG) is presented which is to estimate the deflection of a lightweight flexible beam, including the tip position and the tip rotation angle. In this paper, the classical problem of the deflection of a lightweight flexible beam of linear elastic material is analysed. We present the differential equation governing the behavior of a physical system and show that this equation although straightforward in appearance, is in fact rather difficult to solve due to the presence of a non-linear term. We used epoxy glue to attach the FBG sensors to specific locations upper and lower surface of the beam in order to measure local strain measurements. A quasi-distributed FBG static strain sensor network is designed and established. The estimation results from FBG sensors are also compared to reference displacements from the ANSYS simulation results and the experimental results obtained in the laboratory in the static case. The errors of the estimation by FBG sensors are analysed for further error-correction and option-design. When the load weight is 20g, the precision is the highest, the position errors ex and ex are 0.19%, 0.14% respectively, the rotation error eθ, is 1.23%.

  11. Phase-B activities for the Large Isotope Spectrometer for Astromag

    NASA Technical Reports Server (NTRS)

    Mewaldt, Richard A.; Stone, E. C.

    1995-01-01

    The scientific objectives of the LISA experiment are to (1) extend measurements of the isotopic composition of cosmic ray elements from Be to Ni (Z = 4 to 28) into the energy range beyond 1 GeV per nucleon; (2) to measure the energy spectra of heavy elements up to energies greater than 100 GeV/nucleon with good statistical accuracy; and (3) to search for heavy anti-matter with Z greater than 2 in cosmic rays. This grant focussed on defining the Cherenkov subsystem of the LISA experiment. The Phase-B efforts included the following activities: (1) definition of the LISA Cherenkov counters for the Space Station version of Astromag; (2) testing of the 5-inch fine mesh photomultipliers; (3) development of the aerogel radiator; and (4) study of a free-flyer version of Astromag.

  12. Enhancing Cognitive Abilities with Comprehensive Training: A Large, Online, Randomized, Active-Controlled Trial

    PubMed Central

    Hardy, Joseph L.; Nelson, Rolf A.; Thomason, Moriah E.; Sternberg, Daniel A.; Katovich, Kiefer; Farzin, Faraz; Scanlon, Michael

    2015-01-01

    Background A variety of studies have demonstrated gains in cognitive ability following cognitive training interventions. However, other studies have not shown such gains, and questions remain regarding the efficacy of specific cognitive training interventions. Cognitive training research often involves programs made up of just one or a few exercises, targeting limited and specific cognitive endpoints. In addition, cognitive training studies typically involve small samples that may be insufficient for reliable measurement of change. Other studies have utilized training periods that were too short to generate reliable gains in cognitive performance. Methods The present study evaluated an online cognitive training program comprised of 49 exercises targeting a variety of cognitive capacities. The cognitive training program was compared to an active control condition in which participants completed crossword puzzles. All participants were recruited, trained, and tested online (N = 4,715 fully evaluable participants). Participants in both groups were instructed to complete one approximately 15-minute session at least 5 days per week for 10 weeks. Results Participants randomly assigned to the treatment group improved significantly more on the primary outcome measure, an aggregate measure of neuropsychological performance, than did the active control group (Cohen’s d effect size = 0.255; 95% confidence interval = [0.198, 0.312]). Treatment participants showed greater improvements than controls on speed of processing, short-term memory, working memory, problem solving, and fluid reasoning assessments. Participants in the treatment group also showed greater improvements on self-reported measures of cognitive functioning, particularly on those items related to concentration compared to the control group (Cohen’s d = 0.249; 95% confidence interval = [0.191, 0.306]). Conclusion Taken together, these results indicate that a varied training program composed of a number of

  13. Activation of large form galanin-LI by extracellular processing in small cell lung carcinoma tissue.

    PubMed

    Yamamoto, Hiroyuki; Iguchi, Kazuaki; Ohno, Satoshi; Yokogawa, Takashi; Nishikawa, Kazuya; Hoshino, Minoru

    2011-10-01

    Galanin is a neuropeptide that is widely distributed in the central and peripheral nervous systems. Some small cell lung carcinoma (SCLC) cell lines such as SBC-3A release only the high-molecular-mass form, with lower molecular mass forms being undetectable. To investigate the mechanism of processing of progalanin to active peptide, we studied galanin-LI in both the culture media of SBC-3A cells and in extracts from in vivo mouse SBC-3A tumors. SBC-3A cells were found to release high molecular mass galanin, but did not release active peptides. In contrast, tumor extract contained both high-molecular-mass galanin, and a cleaved lower-molecular-mass form of the peptide (8, 5 and 2 kDa). The lower-molecular-mass peptide was identified as galanin(1-20) by MALDI-TOF mass spectrometry. We then looked at MMP-2 and MMP-9 release from SBC-3A cells and tumor tissue treated with galanin and progalanin, as revealed by gelatin zymography. Galanin elicited pro-MMP-2 and pro-MMP-9 release from SBC-3A cells and tumor tissue; however, recombinant progalanin induced pro-MMP-2 and pro-MMP-9 release from tumor tissue only. This study has shown that the galanin-LI released from SCLC SBC-3A cells consisted of the high-molecular-mass peptide form, and was processed extracellularly to galanin(1-20). Furthermore, galanin was seen to induce pro-MMP-2 and pro-MMP-9 release from SBC-3A cells.

  14. Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

    PubMed

    Rogers, R D; Owen, A M; Middleton, H C; Williams, E J; Pickard, J D; Sahakian, B J; Robbins, T W

    1999-10-15

    Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

  15. Large-scale performance and design for construction activity erosion control best management practices.

    PubMed

    Faucette, L B; Scholl, B; Beighley, R E; Governo, J

    2009-01-01

    The National Pollutant Discharge Elimination System (NPDES) Phase II requires construction activities to have erosion and sediment control best management practices (BMPs) designed and installed for site storm water management. Although BMPs are specified on storm water pollution prevention plans (SWPPPs) as part of the construction general permit (GP), there is little evidence in the research literature as to how BMPs perform or should be designed. The objectives of this study were to: (i) comparatively evaluate the performance of common construction activity erosion control BMPs under a standardized test method, (ii) evaluate the performance of compost erosion control blanket thickness, (iii) evaluate the performance of compost erosion control blankets (CECBs) on a variety of slope angles, and (iv) determine Universal Soil Loss Equation (USLE) cover management factors (C factors) for these BMPs to assist site designers and engineers. Twenty-three erosion control BMPs were evaluated using American Society of Testing and Materials (ASTM) D-6459, standard test method for determination of ECB performance in protecting hill slopes from rainfall induced erosion, on 4:1 (H:V), 3:1, and 2:1 slopes. Soil loss reduction for treatments exposed to 5 cm of rainfall on a 2:1 slope ranged from-7 to 99%. For rainfall exposure of 10 cm, treatment soil loss reduction ranged from 8 to 99%. The 2.5 and 5 cm CECBs significantly reduced erosion on slopes up to 2:1, while CECBs < 2.5 cm are not recommended on slopes >or= 4:1 when rainfall totals reach 5 cm. Based on the soil loss results, USLE C factors ranged from 0.01 to 0.9. These performance and design criteria should aid site planners and designers in decision-making processes.

  16. Linking anti-predator behaviour to prey demography reveals limited risk effects of an actively hunting large carnivore

    USGS Publications Warehouse

    Middleton, Arthur D.; Kauffman, Matthew J.; McWhirter, Douglas E.; Jimenez, Michael D.; Cook, Rachel C.; Cook, John G.; Albeke, Shannon E.; Sawyer, Hall; White, P.J.

    2013-01-01

    Ecological theory predicts that the diffuse risk cues generated by wide-ranging, active predators should induce prey behavioural responses but not major, population- or community-level consequences. We evaluated the non-consumptive effects (NCEs) of an active predator, the grey wolf (Canis lupus), by simultaneously tracking wolves and the behaviour, body fat, and pregnancy of elk (Cervus elaphus), their primary prey in the Greater Yellowstone Ecosystem. When wolves approached within 1 km, elk increased their rates of movement, displacement and vigilance. Even in high-risk areas, however, these encounters occurred only once every 9 days. Ultimately, despite 20-fold variation in the frequency of encounters between wolves and individual elk, the risk of predation was not associated with elk body fat or pregnancy. Our findings suggest that the ecological consequences of actively hunting large carnivores, such as the wolf, are more likely transmitted by consumptive effects on prey survival than NCEs on prey behaviour.

  17. Linking anti-predator behaviour to prey demography reveals limited risk effects of an actively hunting large carnivore.

    PubMed

    Middleton, Arthur D; Kauffman, Matthew J; McWhirter, Douglas E; Jimenez, Michael D; Cook, Rachel C; Cook, John G; Albeke, Shannon E; Sawyer, Hall; White, P J

    2013-08-01

    Ecological theory predicts that the diffuse risk cues generated by wide-ranging, active predators should induce prey behavioural responses but not major, population- or community-level consequences. We evaluated the non-consumptive effects (NCEs) of an active predator, the grey wolf (Canis lupus), by simultaneously tracking wolves and the behaviour, body fat, and pregnancy of elk (Cervus elaphus), their primary prey in the Greater Yellowstone Ecosystem. When wolves approached within 1 km, elk increased their rates of movement, displacement and vigilance. Even in high-risk areas, however, these encounters occurred only once every 9 days. Ultimately, despite 20-fold variation in the frequency of encounters between wolves and individual elk, the risk of predation was not associated with elk body fat or pregnancy. Our findings suggest that the ecological consequences of actively hunting large carnivores, such as the wolf, are more likely transmitted by consumptive effects on prey survival than NCEs on prey behaviour.

  18. Large-scale investigation of the role of trait activation theory for understanding assessment center convergent and discriminant validity.

    PubMed

    Lievens, Filip; Chasteen, Christopher S; Day, Eric Anthony; Christiansen, Neil D

    2006-03-01

    This study used trait activation theory as a theoretical framework to conduct a large-scale test of the interactionist explanation of the convergent and discriminant validity findings obtained in assessment centers. Trait activation theory specifies the conditions in which cross-situationally consistent and inconsistent candidate performances are likely to occur. Results obtained by aggregating correlations across 30 multitrait-multimethod matrices supported the propositions of trait activation theory, shedding a more positive light on the construct validity puzzle in assessment centers. Overall, convergence among assessment center ratings was better between exercises that provided an opportunity to observe behavior related to the same trait, and discrimination among ratings within exercises was generally better for dimensions that were not expressions of the same underlying traits. Implications for assessment center research and practice are discussed.

  19. Active large sector collapse and architectural evolution of the Pico Island (Azores)

    NASA Astrophysics Data System (ADS)

    Marques, F. O.; Hildenbrand, A.; Catalao Fernandes, J.; Catita, C. M.; Costa, A. C.; Sibrant, A.

    2011-12-01

    Volcanic ocean islands are particularly prone to flank instability. Episodes of flank destabilization can remove great amounts of volcanic material, either as creeping rotational landslides along a deep detachment, or in the form of fast running debris avalanches produced by the sudden flank rupture. Based on high-resolution DEM, fieldwork, GPS, InSAR and geochronological data, we put in evidence ongoing collapse of the southeast flank of the Pico volcanic Ridge (Azores) and its architectural evolution. OUR Data show that: (1) the collapsing sector is several cubic kilometres in dimension; (2) the collapse structure involves several curved scarps with a geometry and kinematics typical of normal faults; (3) the central part of the collapse is experiencing little horizontal displacement toward the sea (< 3 mm/yr) but significant downward movement (7-12 mm/yr); (4) motion of the island flank is not accommodated by a low-angle deep basal detachment such as observed elsewhere on typical slumps; (5) the outer part of Pico SE flank is experiencing faster subsidence than the inner parts, which likely reflects recent individualization of a steep seaward-dipping fault in the distal part of the moving mass; (6) evolution of the deformation along this accident could involve the sudden detachment of a large distal block, possibly followed by the gradual destabilization of the whole collapse area. Such scenario would have hazardous consequences for the local population and could trigger a major tsunami, which may impact the surrounding coastal environments and cause considerable damage; (7) the architectural evolution of the island has been made by short periods of volcanic construction, followed by longer periods of destruction by mass wasting episodes like the one here described.

  20. Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries

    PubMed Central

    Inglese, James; Auld, Douglas S.; Jadhav, Ajit; Johnson, Ronald L.; Simeonov, Anton; Yasgar, Adam; Zheng, Wei; Austin, Christopher P.

    2006-01-01

    High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently generate pharmacological data from the primary screen and reliably profile the range of biological activities associated with large chemical libraries. Traditional HTS, which tests compounds at a single concentration, is not suited to this task, because HTS is burdened by frequent false positives and false negatives and requires extensive follow-up testing. We have developed a paradigm, quantitative HTS (qHTS), tested with the enzyme pyruvate kinase, to generate concentration–response curves for >60,000 compounds in a single experiment. We show that this method is precise, refractory to variations in sample preparation, and identifies compounds with a wide range of activities. Concentration–response curves were classified to rapidly identify pyruvate kinase activators and inhibitors with a variety of potencies and efficacies and elucidate structure–activity relationships directly from the primary screen. Comparison of qHTS with traditional single-concentration HTS revealed a high prevalence of false negatives in the single-point screen. This study demonstrates the feasibility of qHTS for accurately profiling every compound in large chemical libraries (>105 compounds). qHTS produces rich data sets that can be immediately mined for reliable biological activities, thereby providing a platform for chemical genomics and accelerating the identification of leads for drug discovery. PMID:16864780

  1. A Large Sample of Magnetically-Active Stars Observed With Kepler

    NASA Astrophysics Data System (ADS)

    Wells, Mark; Neff, J. E.; Brown, A.; Ayres, T. R.; Basri, G. S.; Berdyugina, S.; Harper, G.; Hawley, S. L.; Korhonen, H.; Kowalski, A.; Micela, G.; Piskunov, N. E.; Ramsey, L. W.; Saar, S. H.; Walkowicz, L. M.

    2013-01-01

    We have observed about 325 stars in our Kepler Guest Observer programs (Cycles 1 through 4). For most of these targets, we are analyzing extremely high-precision light curves that have been continuously sampled every 30 minutes for up to 3 years. Our sample of candidate magnetically-active stars was selected primarily using GALEX colors. Starspots, pulsations, and variations due to eclipsing and contact binaries combine to produce a rich variety of light curves. We have developed semi-automated procedures to characterize this variability and thus to classify the targets and identify the physical mechanisms that dominate their Kepler light curves. We will describe these procedures and discuss the range of physical properties covered by our final classification scheme. We are using this Kepler database of variability over timescales of minutes to years to provide diagnostics of flares, starspot formation, evolution, migration, and ultimately of stellar cycles in general. This work contains results obtained using the NASA Kepler satellite and from the Apache Point Observatory, the MMT (using NOAO community access time), and the Hobby-Eberly Telescope. Funding is provided by NASA Kepler grants NNX10AC51G, NNX11AC79G, and NNX12AC85G to the University of Colorado, by NSF grant AST-1109695 to the College of Charleston, and by a grant from the South Carolina Space Grant consortium.

  2. Vagal control of cardiac electrical activity and wall motion during ventricular fibrillation in large animals.

    PubMed

    Naggar, Isaac; Nakase, Ko; Lazar, Jason; Salciccioli, Louis; Selesnick, Ivan; Stewart, Mark

    2014-07-01

    Vagal inputs control pacemaking and conduction systems in the heart. Anatomical evidence suggests a direct ventricular action, but functional evidence that separates direct and indirect (via the conduction system) vagal actions is less well established. We studied vagus nerve stimulation (VNS) during sinus rhythm and ventricular fibrillation (VF) in pigs and sheep to determine: 1) the range of unilateral and bilateral actions (inotropic and chronotropic) and 2) whether VNS alters left ventricular motion and/or electrical activity during VF, a model of abnormal electrical conduction of the left ventricle that excludes sinus and atrioventricular nodal function. Adult pigs (N=8) and sheep (N=10) were anesthetized with urethane and mechanically ventilated. VNS was performed in animals at 1, 2, 5, 10, 20, 50, and 100Hz for 20s. VF was induced with direct current to the ventricles or occlusion of the left anterior descending coronary artery. In 4 pigs and 3 sheep, left ventricular wall motion was assessed from endocardial excursion in epicardial echocardiography. In sheep and pigs, the best frequency among those tested for VNS during sinus rhythm to produce sustained electrical and mechanical ventricular standstill was 50Hz for unilateral or bilateral stimulation. When applied during VF, bilateral VNS increased the variability of the dominant VF frequency, indicating a direct impact on the excitability of ventricular myocytes, and decreased endocardial excursion by more than 50% during VF. We conclude that the vagus nerve directly modulates left ventricular function independently from its effects on the conduction system.

  3. Measuring the Impact of Active Learning in a Redesigned Large-enrollment Introductory Geoscience Survey Course

    NASA Astrophysics Data System (ADS)

    Slater, T. F.; Slater, S. J.; Lyons, D. J.; Manhart, K.; Wehunt, M.; Kapp, J.; Richardson, R. M.

    2008-12-01

    Over the past two years, faculty in the UA Geosciences engaged in a major course redesign effort with the goal of improving student learning and attitudes while, at the same time, dramatically reducing costs of offering such a course. The course serves as an undergraduate general education science requirement. Using a reformed teaching framework of learner-centered education, the large-enrollment, introductory geosciences survey course was overhauled to include interactive lectures, just-in-time online quizzes, a next- generation textbook, and weekly discussions lead by graduate students and undergraduate peer mentors. The Geosciences Concept Inventory (GCI) was given as a pre-test/post-test to students in the pre-modified course and the reformed course to compare student learning in terms of gain scores. Although the entire 78-items were administered, divided into three forms, only the 36-items that most directly related to course content were used for analysis. Students in the unmodified course had a pre-test GCI percentage correct of 28.67 (SD=11.45, n=96) which increased to 45.26 (SD=11.76, n=84) on the post-test. After course redesign, students had a pre-test GCI percentage correct of 38.62 (SD=8.42, n=144) which increased a post-test GCI score of 48.73 (SD=7.49, n=132). Although the gains from pre-test to post-test are statistically significant, the different in post-test GCI scores between the two groups is not. This is interpreted as students' knowledge levels, insofar as the GCI can measure, were equivalent in both courses. The Likert-style Attitudes Toward Science Survey was given as an end-of-class post-test to students in the pre-modified course and as a pre-test post-test the reformed course to compare student attitudes between the courses. The average ranking on a 5-point scale as a pre-test was 3.454 (SD=1.259, n=508) whereas the post-tests for the unmodified course was 3.49 (SD=1.05, n=101) and 3.50 (SD=1.127, n=369) for the reformed course. As is

  4. Were Holocene large slumps in Lake Geneva off the city of Lausanne caused by fault activity?

    NASA Astrophysics Data System (ADS)

    Correia Demand, Jehanne; Marillier, François; Kremer, Katrina; Girardclos, Stéphanie

    2014-05-01

    Lake Geneva is set in an area where glacier advances and retreats have carved Tertiary Molasse rocks in front of the Alpine units. Glacial and lacustrine sediments have accumulated in the lake on top of the Molasse. Within Holocene sedimentary layers, seismic studies in the central part of Lake Geneva ("Grand-Lac") have shown the presence of several mass transport deposits (MTD). A large one, MTD A, is observed off the city of Lausanne. The depth of the associated failure scars (100 m water depth), its volume (~ 0.13 km3), and the occurrence of other smaller MTDs that were possibly co-deposited with MTD A point to the occurrence of a major slide event in the lake, most likely associated with an earthquake. Based on 14C dating, the sediment age model for MTD A gives an age interval of 1865-1608 BC (Kremer et al. 2014). To resolve the details of the MTDs off Lausanne, and to better understand its geological context different seismic systems were used. These were a 3.5 KHz pinger with a theoretical vertical resolution of 0.15 m and a multichannel system with water-gun or air-gun seismic sources with vertical resolution of 0.6 m and 1.1 m, respectively. After a first pass processing, the multi-channel data were reprocessed in order to take into account the shape of the streamer in the water and to enhance the results of migration. In addition to typical seismic images of MTDs observed in other alpine lakes such as chaotic or transparent seismic character between well-organized reflections, two intriguing positive water-bottom topographic features associated with apparent sub-vertical offsets are revealed by the seismic data. They are located in the near vicinity of the depot centers of the MTDs and conspicuously located near faults in the Tertiary Molasse. These are thrust faults that are offset by small strike-slip faults, and we suggest that the positive topographic features are linked to a compressive component within the sediments due to displacements along these

  5. Flow and active mixing have a strong impact on bacterial growth dynamics in the proximal large intestine

    NASA Astrophysics Data System (ADS)

    Cremer, Jonas; Segota, Igor; Yang, Chih-Yu; Arnoldini, Markus; Groisman, Alex; Hwa, Terence

    2016-11-01

    More than half of fecal dry weight is bacterial mass with bacterial densities reaching up to 1012 cells per gram. Mostly, these bacteria grow in the proximal large intestine where lateral flow along the intestine is strong: flow can in principal lead to a washout of bacteria from the proximal large intestine. Active mixing by contractions of the intestinal wall together with bacterial growth might counteract such a washout and allow high bacterial densities to occur. As a step towards understanding bacterial growth in the presence of mixing and flow, we constructed an in-vitro setup where controlled wall-deformations of a channel emulate contractions. We investigate growth along the channel under a steady nutrient inflow. Depending on mixing and flow, we observe varying spatial gradients in bacterial density along the channel. Active mixing by deformations of the channel wall is shown to be crucial in maintaining a steady-state bacterial population in the presence of flow. The growth-dynamics is quantitatively captured by a simple mathematical model, with the effect of mixing described by an effective diffusion term. Based on this model, we discuss bacterial growth dynamics in the human large intestine using flow- and mixing-behavior having been observed for humans.

  6. A large hydrothermal reservoir beneath Taal Volcano (Philippines) revealed by magnetotelluric observations and its implications to the volcanic activity.

    PubMed

    Alanis, Paul K B; Yamaya, Yusuke; Takeuchi, Akihiro; Sasai, Yoichi; Okada, Yoshihiro; Nagao, Toshiyasu

    2013-01-01

    Taal Volcano is one of the most active volcanoes in the Philippines. The magnetotelluric 3D forward analyses indicate the existence of a large high resistivity anomaly (∼100 Ω·m) with a volume of at least 3 km×3 km×3 km, which is capped by a conductive layer (∼10 Ω·m), beneath the Main Crater. This high resistivity anomaly is hypothesized to be a large hydrothermal reservoir, consisting of the aggregate of interconnected cracks in rigid and dense host rocks, which are filled with hydrothermal fluids coming from a magma batch below the reservoir. The hydrothermal fluids are considered partly in gas phase and liquid phase. The presence of such a large hydrothermal reservoir and the stagnant magma below may have influences on the volcano's activity. Two possibilities are presented. First, the 30 January 1911 explosion event was a magmatic hydrothermal eruption rather than a base-surge associated with a phreato-magmatic eruption. Second, the earlier proposed four eruption series may be better interpreted by two cycles, each consisting of series of summit and flank eruptions.

  7. A large hydrothermal reservoir beneath Taal Volcano (Philippines) revealed by magnetotelluric observations and its implications to the volcanic activity

    PubMed Central

    ALANIS, Paul K. B.; YAMAYA, Yusuke; TAKEUCHI, Akihiro; SASAI, Yoichi; OKADA, Yoshihiro; NAGAO, Toshiyasu

    2013-01-01

    Taal Volcano is one of the most active volcanoes in the Philippines. The magnetotelluric 3D forward analyses indicate the existence of a large high resistivity anomaly (∼100 Ω·m) with a volume of at least 3 km × 3 km × 3 km, which is capped by a conductive layer (∼10 Ω·m), beneath the Main Crater. This high resistivity anomaly is hypothesized to be a large hydrothermal reservoir, consisting of the aggregate of interconnected cracks in rigid and dense host rocks, which are filled with hydrothermal fluids coming from a magma batch below the reservoir. The hydrothermal fluids are considered partly in gas phase and liquid phase. The presence of such a large hydrothermal reservoir and the stagnant magma below may have influences on the volcano’s activity. Two possibilities are presented. First, the 30 January 1911 explosion event was a magmatic hydrothermal eruption rather than a base-surge associated with a phreato-magmatic eruption. Second, the earlier proposed four eruption series may be better interpreted by two cycles, each consisting of series of summit and flank eruptions. PMID:24126286

  8. Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells.

    PubMed

    Ferch, Uta; Kloo, Bernhard; Gewies, Andreas; Pfänder, Vera; Düwel, Michael; Peschel, Christian; Krappmann, Daniel; Ruland, Jürgen

    2009-10-26

    Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma in humans. The aggressive activated B cell-like (ABC) subtype of DLBCL is characterized by constitutive NF-kappaB activity and requires signals from CARD11, BCL10, and the paracaspase MALT1 for survival. CARD11, BCL10, and MALT1 are scaffold proteins that normally associate upon antigen receptor ligation. Signal-induced CARD11-BCL10-MALT1 (CBM) complexes couple upstream events to IkappaB kinase (IKK)/NF-kappaB activation. MALT1 also possesses a recently recognized proteolytic activity that cleaves and inactivates the negative NF-kappaB regulator A20 and BCL10 upon antigen receptor ligation. Yet, the relevance of MALT1 proteolytic activity for malignant cell growth is unknown. Here, we demonstrate preassembled CBM complexes and constitutive proteolysis of the two known MALT1 substrates in ABC-DLBCL, but not in germinal center B cell-like (GCB) DLBCL. ABC-DLBCL cell treatment with a MALT1 protease inhibitor blocks A20 and BCL10 cleavage, reduces NF-kappaB activity, and decreases the expression of NF-kappaB targets genes. Finally, MALT1 paracaspase inhibition results in death and growth retardation selectively in ABC-DLBCL cells. Thus, our results indicate a growth-promoting role for MALT1 paracaspase activity in ABC-DLBCL and suggest that a pharmacological MALT1 protease inhibition could be a promising approach for lymphoma treatment.

  9. Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447

    PubMed Central

    Peters, Tara L.; Li, Lingxiao; Tula-Sanchez, Ana A.; Pongtornpipat, Praechompoo; Schatz, Jonathan H.

    2016-01-01

    The PIM family kinases promote growth and survival of tumor cells and are expressed in a wide variety of human cancers. Their potential as therapeutic targets, however, is complicated by overlapping activities with multiple other pathways and remains poorly defined in most clinical scenarios. Here we explore activity of the new pan-PIM inhibitor PIM447 in a variety of lymphoid-derived tumors. We find strong activity in cell lines derived from the activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Sensitive lines show lost activation of the mTORC1 signaling complex and subsequent lost activation of cap-dependent protein translation. In addition, we characterize recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases. PMID:27556513

  10. Solar-terrestrial effect controls seismic activity to a large extent (Invited)

    NASA Astrophysics Data System (ADS)

    Duma, G.

    2010-12-01

    Several observational results and corresponding publications in the 20 century indicate that earthquakes in many regions happen systematically in dependence on the time of day and on the season as well. In the recent decade, studies on this topic have also been intensively performed at the Central Institute for Meteorology and Geodynamics (ZAMG), Vienna. Any natural effect on Earth which systematically appears at certain hours of the day or at a special season can solely be caused by a solar or lunar influence. And actually, statistic results on seismic activity reveal a correlation with the solar cycles. Examples of this seismic performance are shown. To gain more clarity about these effects, the three-hour magnetic index Kp, which characterizes the magnetic field disturbances, mainly caused by the solar particle radiation, the solar wind, was correlated with the seismic energy released by earthquakes over decades. Kp is determined from magnetic records of 13 observatories worldwide and continuously published by ISGI, France. It is demonstrated that a highly significant correlation between the geomagnetic index Kp and the annual seismic energy release in regions at latitudes between 35 and 60° N exists. Three regions of continental size were investigated, using the USGS (PDE) earthquake catalogue data. In the period 1974-2009 the Kp cycle periods range between 9 and 12 years, somewhat different to the sunspot number cycles of 11 years. Seismicity follows the Kp cycles with high coincidence. A detailed analysis of this correlation for N-America reveals, that the sum of released energy by earthquakes per year changes by a factor up to 100 with Kp. It is shown that during years of high Kp there happen e.g. 1 event M7, 4 events M6 and 30 events M5 per year, instead of only 10 events M5 in years with lowest Kp. Almost the same relation appears in other regions of continental size, with the same significance. The seismicity in S-America clearly follows the Kp cycles

  11. The Third Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope

    NASA Astrophysics Data System (ADS)

    Ackermann, M.; Ajello, M.; Atwood, W. B.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Becerra Gonzalez, J.; Bellazzini, R.; Bissaldi, E.; Blandford, R. D.; Bloom, E. D.; Bonino, R.; Bottacini, E.; Brandt, T. J.; Bregeon, J.; Britto, R. J.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Caragiulo, M.; Caraveo, P. A.; Carpenter, B.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Chiaro, G.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Cominsky, L. R.; Conrad, J.; Cutini, S.; D'Abrusco, R.; D'Ammando, F.; de Angelis, A.; Desiante, R.; Digel, S. W.; Di Venere, L.; Drell, P. S.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Finke, J.; Focke, W. B.; Franckowiak, A.; Fuhrmann, L.; Fukazawa, Y.; Furniss, A. K.; Fusco, P.; Gargano, F.; Gasparrini, D.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Grove, J. E.; Guiriec, S.; Hewitt, J. W.; Hill, A. B.; Horan, D.; Itoh, R.; Jóhannesson, G.; Johnson, A. S.; Johnson, W. N.; Kataoka, J.; Kawano, T.; Krauss, F.; Kuss, M.; La Mura, G.; Larsson, S.; Latronico, L.; Leto, C.; Li, J.; Li, L.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Mayer, M.; Mazziotta, M. N.; McEnery, J. E.; Michelson, P. F.; Mizuno, T.; Moiseev, A. A.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nuss, E.; Ohno, M.; Ohsugi, T.; Ojha, R.; Omodei, N.; Orienti, M.; Orlando, E.; Paggi, A.; Paneque, D.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Romani, R. W.; Salvetti, D.; Schaal, M.; Schinzel, F. K.; Schulz, A.; Sgrò, C.; Siskind, E. J.; Sokolovsky, K. V.; Spada, F.; Spandre, G.; Spinelli, P.; Stawarz, L.; Suson, D. J.; Takahashi, H.; Takahashi, T.; Tanaka, Y.; Thayer, J. G.; Thayer, J. B.; Tibaldo, L.; Torres, D. F.; Torresi, E.; Tosti, G.; Troja, E.; Uchiyama, Y.; Vianello, G.; Winer, B. L.; Wood, K. S.; Zimmer, S.

    2015-09-01

    The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented. It is based on the third Fermi-LAT catalog (3FGL) of sources detected between 100 MeV and 300 GeV with a Test Statistic greater than 25, between 2008 August 4 and 2012 July 31. The 3LAC includes 1591 AGNs located at high Galactic latitudes (| b| \\gt 10^\\circ ), a 71% increase over the second catalog based on 2 years of data. There are 28 duplicate associations, thus 1563 of the 2192 high-latitude gamma-ray sources of the 3FGL catalog are AGNs. Most of them (98%) are blazars. About half of the newly detected blazars are of unknown type, i.e., they lack spectroscopic information of sufficient quality to determine the strength of their emission lines. Based on their gamma-ray spectral properties, these sources are evenly split between flat-spectrum radio quasars (FSRQs) and BL Lacs. The most abundant detected BL Lacs are of the high-synchrotron-peaked (HSP) type. About 50% of the BL Lacs have no measured redshifts. A few new rare outliers (HSP-FSRQs and high-luminosity HSP BL Lacs) are reported. The general properties of the 3LAC sample confirm previous findings from earlier catalogs. The fraction of 3LAC blazars in the total population of blazars listed in BZCAT remains non-negligible even at the faint ends of the BZCAT-blazar radio, optical, and X-ray flux distributions, which hints that even the faintest known blazars could eventually shine in gamma-rays at LAT-detection levels. The energy-flux distributions of the different blazar populations are in good agreement with extrapolation from earlier catalogs.

  12. Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Stronach, M. W.; Ketner, R. J.; Hurley, T. B.

    1995-01-01

    Aliphatic amines react with phosphoimidazolide-activated derivatives of guanosine and cytidine (ImpN) by replacing the imidazole group. The kinetics of reaction of guanosine 5'-phospho-2-methylimidazolide (2-MeImpG) with glycine ethyl ester, glycinamide, 2-methoxyethylamine, n-butylamine, morpholine, dimethylamine (Me2NH), ethylmethylamine (EtNHMe), diethylamine (Et2NH), pyrrolidine, and piperidine were determined in water at 37 degrees C. With primary amines, a plot of the logarithm of the rate constant for attack by the amine on the protonated substrate, log kSH(A), versus the pKa of the amine exhibits a good linear correlation with a Bronsted slope, beta nuc = 0.48. Most of the secondary amines tested react with slightly higher reactivity than primary amines of similar pKa. Interestingly, some secondary amines show substantially lower reactivity than might be expected: EtNHMe reacts about eight times, and Et2NH at least 100 times, more slowly than Me2NH although all three amines are of similar basicity. For comparison, the kinetics of reaction of guanosine 5'-phosphoimidazolide (ImpG) and cytidine 5'-phosphoimidazolide (ImpC) were determined with Me2NH, EtNHMe, and Et2NH, and similar results were obtained. These results establish that the increased steric hindrance observed with the successive addition of ethyl groups are not due to any special steric requirements imposed by the guanosine or the methyl on the 2-methylimidazole leaving group of 2-MeImpG. It is concluded that addition of ethyl and, perhaps, groups larger than ethyl dramatically increases the kinetic barrier for addition of aliphatic secondary amines to the P-N bond of ImpN. This study supports the observation that the primary amino groups on the natural polyamines are at least 2 orders of magnitude more reactive than the secondary amino groups in the reaction with ImpN.

  13. Magnetic Properties of Solar Active Regions That Govern Large Solar Flares and Eruptions

    NASA Astrophysics Data System (ADS)

    Toriumi, Shin; Schrijver, Carolus J.; Harra, Louise K.; Hudson, Hugh; Nagashima, Kaori

    2017-01-01

    Solar flares and coronal mass ejections (CMEs), especially the larger ones, emanate from active regions (ARs). With the aim of understanding the magnetic properties that govern such flares and eruptions, we systematically survey all flare events with Geostationary Orbiting Environmental Satellite levels of ≥M5.0 within 45° from disk center between 2010 May and 2016 April. These criteria lead to a total of 51 flares from 29 ARs, for which we analyze the observational data obtained by the Solar Dynamics Observatory. More than 80% of the 29 ARs are found to exhibit δ-sunspots, and at least three ARs violate Hale’s polarity rule. The flare durations are approximately proportional to the distance between the two flare ribbons, to the total magnetic flux inside the ribbons, and to the ribbon area. From our study, one of the parameters that clearly determine whether a given flare event is CME-eruptive or not is the ribbon area normalized by the sunspot area, which may indicate that the structural relationship between the flaring region and the entire AR controls CME productivity. AR characterization shows that even X-class events do not require δ-sunspots or strong-field, high-gradient polarity inversion lines. An investigation of historical observational data suggests the possibility that the largest solar ARs, with magnetic flux of 2 × 1023 Mx, might be able to produce “superflares” with energies of the order of 1034 erg. The proportionality between the flare durations and magnetic energies is consistent with stellar flare observations, suggesting a common physical background for solar and stellar flares.

  14. QSAR prediction of estrogen activity for a large set of diverse chemicals under the guidance of OECD principles.

    PubMed

    Liu, Huanxiang; Papa, Ester; Gramatica, Paola

    2006-11-01

    A large number of environmental chemicals, known as endocrine-disrupting chemicals, are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones, and such chemicals may pose a serious threat to the health of humans and wildlife. They are thought to act through a variety of mechanisms, mainly estrogen-receptor-mediated mechanisms of toxicity. However, it is practically impossible to perform thorough toxicological tests on all potential xenoestrogens, and thus, the quantitative structure--activity relationship (QSAR) provides a promising method for the estimation of a compound's estrogenic activity. Here, QSAR models of the estrogen receptor binding affinity of a large data set of heterogeneous chemicals have been built using theoretical molecular descriptors, giving full consideration to the new OECD principles in regulation for QSAR acceptability, during model construction and assessment. An unambiguous multiple linear regression (MLR) algorithm was used to build the models, and model predictive ability was validated by both internal and external validation. The applicability domain was checked by the leverage approach to verify prediction reliability. The results obtained using several validation paths indicate that the proposed QSAR model is robust and satisfactory, and can provide a feasible and practical tool for the rapid screening of the estrogen activity of organic compounds.

  15. Endogenous peroxidase activity in brush cell-like cells in the large intestine of the bullfrog tadpole, Rana catesbeiana.

    PubMed

    Sugimoto, K; Ichikawa, Y; Nakamura, I

    1983-01-01

    A special cell type was identified in the mucosal epithelium of the large intestine of the tadpole of the bullfrog, Rana catesbeiana. It is a slender, columnar cell, with a dark, basally situated nucleus. By electron microscopy the cell displays prominent bundles of filaments emerging from each microvillus and extending deep into the cytoplasm without ending in the terminal web. It has longer and more crowded microvilli than the absorptive cell. The specialized cell is also characterized by the presence of many apical vesicles and numerous subapical dense bodies. These cytological features suggest that it may be a brush cell (Rhodin and Dalhamn 1956). These cells displayed endogenous peroxidase activity in smooth and rough endoplasmic reticulum, in the well-developed Golgi apparatus and in apical vesicles. Furthermore, peroxidase reaction product was frequently observed on their luminal surface membrane. These findings suggest that the brush cell in the large intestine of the bullfrog tadpole may be a secretory cell.

  16. The influence of hypotonicity on large-conductance calcium-activated potassium channels in human retinal pigment epithelial cells.

    PubMed

    Sheu, Shwu-Jiuan; Wu, Sheng-Nan; Hu, Dan-Ning; Chen, Jane-Fane

    2004-12-01

    The aim of this study was to characterize the effects of hypotonicity on the activity of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in human retinal pigment epithelial (RPE R-50) cells. Effects of hypotonicity on ion currents were investigated with the aid of the patch-clamp technique. A regulatory volume decrease in response to a hypotonic solution (200 mOsm/L) was observed that could be blunted by paxilline. In whole-cell current recordings, a hypotonic solution (200 mOsm/L) reversibly increased the amplitude of K+ outward currents (I(K)). The increase of I(K) could be reversed by iberiotoxin (200 nM), paxilline (1 microM), or tetrandrine (5 microM), but not by glibenclamide (10 microM), disulphonic acid (DIDS) (100 microM), or dequalinium dichloride (10 microM). In RPE R-50 cells pretreated with thapsigargin, aristolochic acid, or pertussis toxin, the increased amplitude of I(K) in response to hypotonicity was unaltered. In cell-attached patches, an increase in BK(Ca)-channel activity was observed during hypotonicity-induced cell swelling. The enhanced channel activity elicited under this condition was mainly mediated by an increase in the number of long-lived openings. These findings support the evidence for the coupling of volume swelling to the functional activity of BK(Ca) channels.

  17. Dietary fibres modulate the composition and activity of butyrate-producing bacteria in the large intestine of suckling piglets.

    PubMed

    Mu, Chunlong; Zhang, Lingli; He, Xiangyu; Smidt, Hauke; Zhu, Weiyun

    2017-02-04

    Dietary fibres have been shown to affect early-life microbiota colonization in the large intestine of suckling piglets, however, much less is known as to whether they also modulate the composition and activity of butyrate-producing bacteria. Here, we investigated the effect of dietary fibres on the abundance, composition, and activity of butyrate-producing bacteria in suckling piglets. Piglets were fed a control diet or creep feeds containing alfalfa, wheat bran, or pure cellulose, respectively, from postnatal day 7 to 22. Large intestinal digesta and mucosa samples were collected for quantitative analysis of bacterial group-specific 16S ribosomal RNA- and butyrate production-related genes, and digesta samples for quantification of short-chain fatty acids. The alfalfa diet increased (P < 0.05) Clostridium cluster XIVa abundance, copies of genes encoding proteins involved in butyrate production (butyryl-CoA:acetate CoA-transferase, butyrate kinase), and butyrate concentration compared to the wheat bran diet in the digesta of the proximal colon. In the distal colonic digesta, animals fed the alfalfa diet had the highest number of butyryl-CoA:acetate CoA-transferase gene copies (P < 0.05) and numerically the highest butyrate concentration, albeit not significant (P > 0.05), compared to other groups. In the distal colonic mucosa, the cellulose diet increased (P < 0.05) the abundance of Clostridium cluster XIVa and copies of the butyryl-CoA:acetate CoA-transferase gene compared to the alfalfa diet. These results indicated that dietary fibres modulate the abundance and activity of butyrate-producing bacteria in the large intestine of suckling piglets, and that a moderate supplementation of alfalfa and cellulose may benefit early-life gut health through the delivery of butyrate to the mucosa.

  18. North-south asymmetry in small and large sunspot group activity and violation of even-odd solar cycle rule

    NASA Astrophysics Data System (ADS)

    Javaraiah, J.

    2016-07-01

    According to Gnevyshev-Ohl (G-O) rule an odd-numbered cycle is stronger than its preceding even-numbered cycle. In the modern time the cycle pair (22, 23) violated this rule. By using the combined Greenwich Photoheliographic Results (GPR) and Solar Optical Observing Network (SOON) sunspot group data during the period 1874-2015, and Debrecen Photoheliographic Data (DPD) of sunspot groups during the period 1974-2015, here we have found that the solar cycle pair (22, 23) violated the G-O rule because, besides during cycle 23 a large deficiency of small sunspot groups in both the northern and the southern hemispheres, during cycle 22 a large abundance of small sunspot groups in the southern hemisphere. In the case of large and small sunspot groups the cycle pair (22, 23) violated the G-O rule in the northern and southern hemispheres, respectively, suggesting the north-south asymmetry in solar activity has a significant contribution in the violation of G-O rule. The amplitude of solar cycle 24 is smaller than that of solar cycle 23. However, Coronal Mass Ejections (CMEs) rate in the rising phases of the cycles 23 and 24 are almost same (even slightly large in cycle 24). From both the SOON and the DPD sunspot group data here we have also found that on the average the ratio of the number (counts) of large sunspot groups to the number of small sunspot groups is larger in the rising phase of cycle 24 than that in the corresponding phase of cycle 23. We suggest this could be a potential reason for the aforesaid discrepancy in the CME rates during the rising phases of cycles 23 and 24. These results have significant implication on solar cycle mechanism.

  19. Reconciling the discrepancies on the involvement of large-conductance Ca(2+)-activated K channels in glioblastoma cell migration.

    PubMed

    Catacuzzeno, Luigi; Caramia, Martino; Sforna, Luigi; Belia, Silvia; Guglielmi, Luca; D'Adamo, Maria Cristina; Pessia, Mauro; Franciolini, Fabio

    2015-01-01

    Glioblastoma (GBM) is the most common and aggressive primary brain tumor, and is notable for spreading so effectively through the brain parenchyma to make complete surgical resection virtually impossible, and prospect of life dismal. Several ion channels have been involved in GBM migration and invasion, due to their critical role in supporting volume changes and Ca(2+) influx occuring during the process. The large-conductance, Ca(2+)-activated K (BK) channels, markedly overexpressed in biopsies of patients with GBMs and in GBM cell lines, have attracted much interest and have been suggested to play a central role in cell migration and invasion as candidate channels for providing the ion efflux and consequent water extrusion that allow cell shrinkage during migration. Available experimental data on the role of BK channel in migration and invasion are not consistent though. While BK channels block typically resulted in inhibition of cell migration or in no effect, their activation would either enhance or inhibit the process. This short review reexamines the relevant available data on the topic, and presents a unifying paradigm capable of reconciling present discrepancies. According to this paradigm, BK channels would not contribute to migration under conditions where the [Ca(2+)] i is too low for their activation. They will instead positively contribute to migration for intermediate [Ca(2+)] i , insufficient as such to activate BK channels, but capable of predisposing them to cyclic activation following oscillatory [Ca(2+)] i increases. Finally, steadily active BK channels because of prolonged high [Ca(2+)] i would inhibit migration as their steady activity would be unsuitable to match the cyclic cell volume changes needed for proper cell migration.

  20. The effects of season and sand mining activities on thermal regime and water quality in a large shallow tropical lake.

    PubMed

    Sharip, Zati; Zaki, Ahmad Taqiyuddin Ahmad

    2014-08-01

    Thermal structure and water quality in a large and shallow lake in Malaysia were studied between January 2012 and June 2013 in order to understand variations in relation to water level fluctuations and in-stream mining activities. Environmental variables, namely temperature, turbidity, dissolved oxygen, pH, electrical conductivity, chlorophyll-A and transparency, were measured using a multi-parameter probe and a Secchi disk. Measurements of environmental variables were performed at 0.1 m intervals from the surface to the bottom of the lake during the dry and wet seasons. High water level and strong solar radiation increased temperature stratification. River discharges during the wet season, and unsustainable sand mining activities led to an increased turbidity exceeding 100 NTU, and reduced transparency, which changed the temperature variation and subsequently altered the water quality pattern.

  1. Characterization of large area ZnS(Ag) detector for gross alpha and beta activity measurements in tap water plants

    SciTech Connect

    Lunardon, M.; Cester, D.; Mistura, G.; Moretto, S.; Stevanato, L.; Viesti, G.; Schotanus, P.; Bodewits, E.

    2015-07-01

    In this work we present the characterization of a large area 200 x 200 mm{sup 2} EJ-444 scintillation detector to be used for monitoring gross alpha and beta activity in tap water plants. Specific tests were performed to determine the best setup to readout the light from the detector side in order to have the possibility to stack many detectors and get a compact device with total active area of the order of 1 m{sup 2}. Alpha/Beta discrimination, efficiency and homogeneity tests were carried out with alpha and beta sources. Background from ambient radioactivity was measured as well. Alpha/beta real-time monitoring in drinking water is a goal of the EU project TAWARA{sub R}TM. (authors)

  2. Product-selective blot: a technique for measuring enzyme activities in large numbers of samples and in native electrophoresis gels

    SciTech Connect

    Thompson, G.A.; Davies, H.M.; McDonald, N.

    1985-08-01

    A method termed product-selective blotting has been developed for screening large numbers of samples for enzyme activity. The technique is particularly well suited to detection of enzymes in native electrophoresis gels. The principle of the method was demonstrated by blotting samples from glutaminase or glutamate synthase reactions into an agarose gel embedded with ion-exchange resin under conditions favoring binding of product (glutamate) over substrates and other substances in the reaction mixture. After washes to remove these unbound substances, the product was measured using either fluorometric staining or radiometric techniques. Glutaminase activity in native electrophoresis gels was visualized by a related procedure in which substrates and products from reactions run in the electrophoresis gel were blotted directly into a resin-containing image gel. Considering the selective-binding materials available for use in the image gel, along with the possible detection systems, this method has potentially broad application.

  3. Velocity difference measurement with a fiber-optic coupler.

    PubMed

    Du, Y; Ackerson, B J; Tong, P

    1998-09-01

    Two single-mode fibers collect light with the same scattered wave vector from two spatially separated regions in a sample. These regions are illuminated by a single coherent laser beam, so that the collected signals interfere when combined by means of a fiber-optic coupler, before they are directed to a photomultiplier tube. The fibers and the coupler are polarization preserving to guarantee a high signal-to-noise ratio. The measured intensity fluctuations are used to determine the velocity difference omega v(L) for spatial separations L in the sample. Specifically, an intensity autocorrelation function is calculated theoretically for rigid body rotation and is tested experimentally. Experimental results span two orders of magnitude in L and agree with theoretical predictions with an error of less than 5%. This new technique will be very useful in the study of turbulent flow and particle settling dynamics.

  4. Use of a fiber optic probe for organic species determination

    DOEpatents

    Ekechukwu, A.A.

    1996-12-10

    A fiber optic probe is described for remotely detecting the presence and concentration organic species in aqueous solutions. The probe includes a cylindrical housing with an organic species indicator, preferably diaminonaphthyl sulfonic acid adsorbed in a silica gel (DANS-modified gel), contained in the probe`s distal end. The probe admits aqueous solutions to the probe interior for mixing within the DANS-modified gel. An optical fiber transmits light through the DANS-modified gel while the indicator reacts with organic species present in the solution, thereby shifting the location of the fluorescent peak. The altered light is reflected to a receiving fiber that carries the light to a spectrophotometer or other analysis device. 5 figs.

  5. Composite impact strength improvement through a fiber/matrix interphase

    NASA Technical Reports Server (NTRS)

    Cavano, P. J.; Winters, W. E.

    1975-01-01

    Research was conducted to improve the impact strength and toughness of fiber/resin composites by means of a fiber coating interphase. Graphite fiber/epoxy resin composites were fabricated with four different fiber coating systems introduced in a matrix-fiber interphase. Two graphite fibers, a high strength and a high modulus type, were studied with the following coating systems: chemical vapor deposited boron, electroless nickel, a polyamide-imide resin and a thermoplastic polysulfone resin. Evaluation methods included the following tests: Izod, flexure, shear fracture toughness, longitudinal and transverse tensile, and transverse and longitudinal compression. No desirable changes could be effected with the high strength fiber, but significant improvements in impact performance were observed with the polyamide-imide resin coated high modulus fiber with no loss in composite modulus.

  6. Preliminary Development of a Fiber Optic Sensor for Measuring Bilirubin

    PubMed Central

    Babin, Steven M; Sova, Raymond M

    2014-01-01

    Preliminary development of a fiber optic bilirubin sensor is described, where an unclad sensing portion is used to provide evanescent wave interaction of the transmitted light with the chemical environment. By using a wavelength corresponding to a bilirubin absorption peak, the Beer–Lambert Law can be used to relate the concentration of bilirubin surrounding the sensing portion to the amount of absorbed light. Initial testing in vitro suggests that the sensor response is consistent with the results of bulk absorption measurements as well as the Beer–Lambert Law. In addition, it is found that conjugated and unconjugated bilirubin have different peak absorption wavelengths, so that two optical frequencies may potentially be used to measure both types of bilirubin. Future development of this device could provide a means of real-time, point-of-care monitoring of intravenous bilirubin in critical care neonates with hyperbilirubinemia. PMID:25057239

  7. Buckling of a fiber bundle embedded in epoxy

    NASA Technical Reports Server (NTRS)

    Hahn, H. T.; Sohi, M. M.

    1986-01-01

    Buckling of a fiber bundle embedded in epoxy resin was studied to gain insight into compressive failure mechanisms in unidirectional composites. The fibers used were E-glass, T300 graphite, T700 graphite, and P75 graphite. These fibers were combined with two different resins: Epon 815/V140 and Epon 828/Z. In both resins the failure mode of the bundle was found to be microbuckling of fibers for the first three types of fibers; however, the high-modulus P75 fibers failed in shear without any sign of microbuckling. The strains at which microbuckling occurred were higher than the compressive failure strains of the corresponding unidirectional composites. In the soft resin, Epon 815/V140, fibers buckled at lower strains than in the stiff resin, Epon 828/Z. The buckling strains and the segment lengths followed the trends predicted for a single filament embedded in an infinite matrix.

  8. Raman Imaging with a Fiber-Coupled Multichannel Spectrograph

    PubMed Central

    Schmälzlin, Elmar; Moralejo, Benito; Rutowska, Monika; Monreal-Ibero, Ana; Sandin, Christer; Tarcea, Nicolae; Popp, Jürgen; Roth, Martin M.

    2014-01-01

    Until now, spatially resolved Raman Spectroscopy has required to scan a sample under investigation in a time-consuming step-by-step procedure. Here, we present a technique that allows the capture of an entire Raman image with only one single exposure. The Raman scattering arising from the sample was collected with a fiber-coupled high-performance astronomy spectrograph. The probe head consisting of an array of 20 × 20 multimode fibers was linked to the camera port of a microscope. To demonstrate the high potential of this new concept, Raman images of reference samples were recorded. Entire chemical maps were received without the need for a scanning procedure. PMID:25420149

  9. A fiber-optic current sensor for aerospace applications

    NASA Technical Reports Server (NTRS)

    Patterson, Richard L.; Rose, A. H.; Tang, D.; Day, G. W.

    1990-01-01

    A robust, accurate, broadband, alternating current sensor using fiber optics is being developed for space applications at power frequencies as high as 20 kHz. It can also be used in low- and high-voltage 60-Hz terrestrial power systems and in 400-Hz aircraft systems. It is intrinsically EMI (electromagnetic interference) immune and has the added benefit of excellent isolation. The sensor uses the Faraday effect in optical fiber and standard polarimetric measurements to sense electrical current. The primary component of the sensor is a specially treated coil of single-mode optical fiber, through which the current carrying conductor passes. Improved precision is accomplished by temperature compensation by means of signals from a fiber-optic temperature sensor embedded in the sensing head. The authors report on the technology contained in the sensor and also relate the results of precision tests conducted at various temperatures within the wide operating range. The results of early EMI tests are shown.

  10. Design of a fiber-optic multiphoton microscopy handheld probe

    PubMed Central

    Zhao, Yuan; Sheng, Mingyu; Huang, Lin; Tang, Shuo

    2016-01-01

    We have developed a fiber-optic multiphoton microscopy (MPM) system with handheld probe using femtosecond fiber laser. Here we present the detailed optical design and analysis of the handheld probe. The optical systems using Lightpath 352140 and 352150 as objective lens were analyzed. A custom objective module that includes Lightpath 355392 and two customized corrective lenses was designed. Their performances were compared by wavefront error, field curvature, astigmatism, F-θ error, and tolerance in Zemax simulation. Tolerance analysis predicted the focal spot size to be 1.13, 1.19 and 0.83 µm, respectively. Lightpath 352140 and 352150 were implemented in experiment and the measured lateral resolution was 1.22 and 1.3 µm, respectively, which matched with the prediction. MPM imaging by the handheld probe were conducted on leaf, fish scale and rat tail tendon. The MPM resolution can potentially be improved by the custom objective module. PMID:27699109

  11. Large-conductance Ca²⁺-activated potassium channel in mitochondria of endothelial EA.hy926 cells.

    PubMed

    Bednarczyk, Piotr; Koziel, Agnieszka; Jarmuszkiewicz, Wieslawa; Szewczyk, Adam

    2013-06-01

    In the present study, we describe the existence of a large-conductance Ca²⁺-activated potassium (BKCa) channel in the mitochondria of the human endothelial cell line EA.hy926. A single-channel current was recorded from endothelial mitoplasts (i.e., inner mitochondrial membrane) using the patch-clamp technique in the mitoplast-attached mode. A potassium-selective current was recorded with a mean conductance equal to 270 ± 10 pS in a symmetrical 150/150 mM KCl isotonic solution. The channel activity, which was determined as the open probability, increased with the addition of calcium ions and the potassium channel opener NS1619. Conversely, the activity of the channel was irreversibly blocked by paxilline and iberiotoxin, BKCa channel inhibitors. The open-state probability was found to be voltage dependent. The substances known to modulate BKCa channel activity influenced the bioenergetics of mitochondria isolated from human endothelial EA.hy926 cells. In isolated mitochondria, 100 μM Ca²⁺, 10 μM NS1619, and 0.5 μM NS11021 depolarized the mitochondrial membrane potential and stimulated nonphosphorylating respiration. These effects were blocked by iberiotoxin and paxilline in a potassium-dependent manner. Under phosphorylating conditions, NS1619-induced, iberiotoxin-sensitive uncoupling diverted energy from ATP synthesis during the phosphorylating respiration of the endothelial mitochondria. Immunological analysis with antibodies raised against proteins of the plasma membrane BKCa channel identified a pore-forming α-subunit and an auxiliary β₂-subunit of the channel in the endothelial mitochondrial inner membrane. In conclusion, we show for the first time that the inner mitochondrial membrane in human endothelial EA.hy926 cells contains a large-conductance calcium-dependent potassium channel with properties similar to those of the surface membrane BKCa channel.

  12. Establishing a fiber-optic-based optical neural interface.

    PubMed

    Adamantidis, Antoine R; Zhang, Feng; de Lecea, Luis; Deisseroth, Karl

    2014-08-01

    Selective expression of opsins in genetically defined neurons makes it possible to control a subset of neurons without affecting nearby cells and processes in the intact brain, but light must still be delivered to the target brain structure. Light scattering limits the delivery of light from the surface of the brain. For this reason, we have developed a fiber-optic-based optical neural interface (ONI), which allows optical access to any brain structure in freely moving mammals. The ONI system is constructed by modifying the small animal cannula system from PlasticsOne. The system for bilateral stimulation consists of a bilateral cannula guide that has been stereotactically implanted over the target brain region, a screw cap for securing the optical fiber to the animal's head, a fiber guard modified from the internal cannula adapter, and a bare fiber whose length is customized based on the depth of the target region. For unilateral stimulation, a single-fiber system can be constructed using unilateral cannula parts from PlasticsOne. We describe here the preparation of the bilateral ONI system and its use in optical stimulation of the mouse or rat brain. Delivery of opsin-expressing virus and implantation of the ONI may be conducted in the same surgical session; alternatively, with a transgenic animal no opsin virus is delivered during the surgery. Similar procedures are useful for deep or superficial injections (even for neocortical targets, although in some cases surface light-emitting diodes or cortex-apposed fibers can be used for the most superficial cortical targets).

  13. Density matrix renormalization group (DMRG) method as a common tool for large active-space CASSCF/CASPT2 calculations

    NASA Astrophysics Data System (ADS)

    Nakatani, Naoki; Guo, Sheng

    2017-03-01

    This paper describes an interface between the density matrix renormalization group (DMRG) method and the complete active-space self-consistent field (CASSCF) method and its analytical gradient, as well as an extension to the second-order perturbation theory (CASPT2) method. This interfacing allows large active-space multi-reference computations to be easily performed. The interface and its extension are both implemented in terms of reduced density matrices (RDMs) which can be efficiently computed via the DMRG sweep algorithm. We also present benchmark results showing that, in practice, the DMRG-CASSCF calculations scale with active-space size in a polynomial manner in the case of quasi-1D systems. Geometry optimization of a binuclear iron-sulfur cluster using the DMRG-CASSCF analytical gradient is demonstrated, indicating that the inclusion of the valence p-orbitals of sulfur and double-shell d-orbitals of iron lead to non-negligible changes in the geometry compared to the results of small active-space calculations. With the exception of the selection of M values, many computational settings in these practical DMRG calculations have been tuned and black-boxed in our interface, and so the resulting DMRG-CASSCF and DMRG-CASPT2 calculations are now available to novice users as a common tool to compute strongly correlated electronic wavefunctions.

  14. External copper inhibits the activity of the large-conductance calcium- and voltage-sensitive potassium channel from skeletal muscle.

    PubMed

    Morera, F J; Wolff, D; Vergara, C

    2003-03-01

    We have characterized the effect of external copper on the gating properties of the large-conductance calcium- and voltage-sensitive potassium channel from skeletal muscle, incorporated into artificial bilayers. The effect of Cu2+ was evaluated as changes in the gating kinetic properties of the channel after the addition of this ion. We found that, from concentrations of 20 microM and up, copper induced a concentration- and time-dependent decrease in channel open probability. The inhibition of channel activity by Cu2+ could not be reversed by washing or by addition of the copper chelator, bathocuproinedisulfonic acid. However, channel activity was appreciably restored by the sulfhydryl reducing agent dithiothreitol. The effect of copper was specific since other transition metal divalent cations such as Ni2+, Zn2+ or Cd2+ did not affect BK(Ca) channel activity in the same concentration range. These results suggest that external Cu2+-induced inhibition of channel activity was due to direct or indirect oxidation of key amino-acid sulfhydryl groups that might have a role in channel gating.

  15. Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function

    PubMed Central

    Edgerton, Jeremy R; Reinhart, Peter H

    2003-01-01

    The cerebellum is important for many aspects of behaviour, from posture maintenance and goal-oriented reaching movements to timing tasks and certain forms of learning. In every case, information flowing through the cerebellum passes through Purkinje neurons, which receive input from the two primary cerebellar afferents and generate continuous streams of action potentials that constitute the sole output from the cerebellar cortex to the deep nuclei. The tonic firing behaviour observed in Purkinje neurons in vivo is maintained in brain slices even when synaptic inputs are blocked, suggesting that Purkinje neuron activity relies to a significant extent on intrinsic conductances. Previous research has suggested that the interplay between Ca2+ currents and Ca2+-activated K+ channels (KCa channels) is important for Purkinje cell activity, but how many different KCa channel types are present and what each channel type contributes to cell behaviour remains unclear. In order to better understand the ionic mechanisms that control the behaviour of these neurons, we investigated the effects of different Ca2+ channel and KCa channel antagonists on Purkinje neurons in acute slices of rat cerebellum. Our data show that Ca2+ entering through P-type voltage-gated Ca2+ channels activates both small-conductance (SK) and large-conductance (BK) KCa channels. SK channels play a role in setting the intrinsic firing frequency, while BK channels regulate action potential shape and may contribute to the unique climbing fibre response. PMID:12576503

  16. Testing promotes long-term learning via stabilizing activation patterns in a large network of brain areas.

    PubMed

    Keresztes, Attila; Kaiser, Daniel; Kovács, Gyula; Racsmány, Mihály

    2014-11-01

    The testing effect refers to the phenomenon that repeated retrieval of memories promotes better long-term retention than repeated study. To investigate the neural correlates of the testing effect, we used event-related functional magnetic resonance imaging methods while participants performed a cued recall task. Prior to the neuroimaging experiment, participants learned Swahili-German word pairs, then half of the word pairs were repeatedly studied, whereas the other half were repeatedly tested. For half of the participants, the neuroimaging experiment was performed immediately after the learning phase; a 1-week retention interval was inserted for the other half of the participants. We found that a large network of areas identified in a separate 2-back functional localizer scan were active during the final recall of the word pair associations. Importantly, the learning strategy (retest or restudy) of the word pairs determined the manner in which the retention interval affected the activations within this network. Recall of previously restudied memories was accompanied by reduced activation within this network at long retention intervals, but no reduction was observed for previously retested memories. We suggest that retrieval promotes learning via stabilizing cue-related activation patterns in a network of areas usually associated with cognitive and attentional control functions.

  17. When and where the aftershock activity was depressed: Contrasting decay patterns of the proximate large earthquakes in southern California

    USGS Publications Warehouse

    Ogata, Y.; Jones, L.M.; Toda, S.

    2003-01-01

    Seismic quiescence has attracted attention as a possible precursor to a large earthquake. However, sensitive detection of quiescence requires accurate modeling of normal aftershock activity. We apply the epidemic-type aftershock sequence (ETAS) model that is a natural extension of the modified Omori formula for aftershock decay, allowing further clusters (secondary aftershocks) within an aftershock sequence. The Hector Mine aftershock activity has been normal, relative to the decay predicted by the ETAS model during the 14 months of available data. In contrast, although the aftershock sequence of the 1992 Landers earthquake (M = 7.3), including the 1992 Big Bear earthquake (M = 6.4) and its aftershocks, fits very well to the ETAS up until about 6 months after the main shock, the activity showed clear lowering relative to the modeled rate (relative quiescence) and lasted nearly 7 years, leading up to the Hector Mine earthquake (M = 7.1) in 1999. Specifically, the relative quiescence occurred only in the shallow aftershock activity, down to depths of 5-6 km. The sequence of deeper events showed clear, normal aftershock activity well fitted to the ETAS throughout the whole period. We argue several physical explanations for these results. Among them, we strongly suspect aseismic slips within the Hector Mine rupture source that could inhibit the crustal relaxation process within "shadow zones" of the Coulomb's failure stress change. Furthermore, the aftershock activity of the 1992 Joshua Tree earthquake (M = 6.1) sharply lowered in the same day of the main shock, which can be explained by a similar scenario.

  18. Heart rate variability characteristics in a large group of active-duty Marines and relationship to posttraumatic stress

    PubMed Central

    Minassian, Arpi; Geyer, Mark A.; Baker, Dewleen G.; Nievergelt, Caroline M.; O'Connor, Daniel T.; Risbrough, Victoria B.

    2014-01-01

    Objective Heart rate variability (HRV), thought to reflect autonomic nervous system function, is lowered in conditions such as posttraumatic stress disorder (PTSD). The potential confounding effects of traumatic brain injury (TBI) and depression in the relationship between HRV and PTSD have not been elucidated in a large cohort of military service members. Here we describe HRV associations with stress disorder symptoms in a large study of Marines, while accounting for well-known covariates of HRV and PTSD including TBI and depression. Methods Four battalions of male active-duty Marines (N=2430) were assessed 1-2 months prior to a combat deployment. HRV was measured during 5 minutes of rest. Depression and PTSD were assessed using the Beck Depression Inventory and Clinician Administered PTSD scale respectively. Results After accounting for covariates including TBI, a regression indicated that lower levels of high frequency (HF) HRV were associated with a diagnosis of PTSD (beta = -.20, p=.035). Depression and PTSD severity were correlated (r= .49, p <.001), however participants with PTSD but relatively low depression scores exhibited reduced HF compared to controls (p=.012). Marines with deployment experience (n=1254) had lower HRV than those with no experience (p = .033). Conclusions This cross-sectional analysis of a large cohort supports associations between PTSD and reduced HRV when accounting for TBI and depression symptoms. Future post-deployment assessments will be used to determine whether pre-deployment HRV can predict vulnerability and resilience to the serious psychological and physiological consequences of combat exposure. PMID:24804881

  19. Property of large conductance Ca(2+)-activated K+ channels from Fasciola hepatica incorporated into planar lipid bilayer.

    PubMed

    Jang, Jung Hee; Park, Jin Bong; Kim, Sun Don; Lee, So Yeong; Hong, Sung-Jong; Ryu, Pan Dong

    2012-05-25

    Fasciola hepatica causes biliary epithelial hyperplasia and obstructive jaundice in humans and animals. Using a planar lipid bilayer technique, we further characterized the single channel property of large conductance K(+)-permeable channels that were previously identified from F. hepatica. The single channel conductance was 254.7±17.9 pS under a symmetrical 200/200 mM (cis/trans) KCl gradient. Open state probability (P(o)) varied from channel to channel at a given membrane potential and Ca(2+) concentration, but increased with voltage (-60 to +40 mV) and cis Ca(2+) (1-200 μM). Under a near bi-ionic condition of 200 mM [K(+)](cis)/200 mM [Na(+)](trans), the permeability ratio of K(+) to Na(+) was 5.0. Charybdotoxin (1 μM) inhibited P(o), whereas tetraethylammonium reduced the conductance (K(D)=67.8mM). Taken together, the results show that the single channel properties of the large conductance K(+)-permeable channels in F. hepatica are similar to those of large conductance Ca(2+)-activated K(+) (BK) channels in general, but distinct from typical BK channels in the extent of voltage- and Ca(2+)-dependence, as well as permeability to Na(+). This study further reveals a variant BK channel in F. hepatica that could serve as a new drug target to treat fascioliasis.

  20. The Properties of Large Amplitude Whistler Mode Waves in the Magnetosphere: Propagation and Relationship with Geomagnetic Activity

    NASA Technical Reports Server (NTRS)

    Wilson, L. B., III; Cattell, C. A.; Kellogg, P. J.; Wygant, J. R.; Goetz, K.; Breneman, A.; Kersten, K.

    2011-01-01

    Wepresent resultsof a studyof the characteristicsof very large amplitude whistler mode waves inside the terrestrial magnetosphere at radial distances of less than 15 RE using waveform capture data from the Wind spacecraft. We observed 247 whistler mode waves with at least one electric field component (105/247 had !80 mV/m peak!to!peak amplitudes) and 66 whistler mode waves with at least one search coil magnetic field component (38/66 had !0.8 nT peak!to!peak amplitudes). Wave vectors determined from events with three magnetic field components indicate that 30/46 propagate within 20 of the ambient magnetic field, though some are more oblique (up to "50 ). No relationship was observed between wave normal angle and GSM latitude. 162/247 of the large amplitude whistler mode waves were observed during magnetically active periods (AE > 200 nT). 217 out of 247 total whistler mode waves examined were observed inside the radiation belts. We present a waveform capture with the largest whistler wave magnetic field amplitude (^8 nT peak!to!peak) ever reported in the radiation belts. The estimated Poynting flux magnitude associated with this wave is ^300 mW/m2, roughly four orders of magnitude above estimates from previous satellite measurements. Such large Poynting flux values are consistent with rapid energization of electrons.

  1. Synthesis and photocatalytic activity of stable nanocrystalline TiO(2) with high crystallinity and large surface area.

    PubMed

    Tian, Guohui; Fu, Honggang; Jing, Liqiang; Tian, Chungui

    2009-01-30

    Superior photoactive TiO(2) nanopowders with high crystallinity and large surface area were synthesized by a hydrothermal process in the presence of cetyltrimethylammonium bromide and a post-treatment with ammonia. The prepared photocatalysts were characterized by X-ray diffraction (XRD), Raman spectroscopy, N(2) adsorption-desorption, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), UV-vis diffuse reflectance spectra (DRS) and surface photovoltage spectroscopy (SPS). The prepared nanocrystallites were highly resistant to thermal sintering, and the calcinations up to 900 degrees C were shown to enhance the crystallinity of the anatase phase without any rutile phase and the separation rate of photoinduced charges of TiO(2) particles. It remained as large as 196 and 125 m(2)/g even after calcinations at 700 and 800 degrees C, respectively. The photocatalytic activity of prepared photocatalysts was obviously higher than that of commercial Degussa P25 on the photodegradation of methylene blue and phenol in water under ultraviolet-light irradiation, and the sample calcined at 800 degrees C afforded the highest photocatalytic activity.

  2. Enhancement of Polymerase Activity of the Large Fragment in DNA Polymerase I from Geobacillus stearothermophilus by Site-Directed Mutagenesis at the Active Site

    PubMed Central

    Ma, Yi; Zhang, Beilei; Wang, Meng; Ou, Yanghui

    2016-01-01

    The large fragment of DNA polymerase I from Geobacillus stearothermophilus GIM1.543 (Bst DNA polymerase) with 5′-3′ DNA polymerase activity while in absence of 5′-3′ exonuclease activity possesses high thermal stability and polymerase activity. Bst DNA polymerase was employed in isothermal multiple self-matching initiated amplification (IMSA) which amplified the interest sequence with high selectivity and was widely applied in the rapid detection of human epidemic diseases. However, the detailed information of commercial Bst DNA polymerase is unpublished and well protected by patents, which makes the high price of commercial kits. In this study, wild-type Bst DNA polymerase (WT) and substitution mutations for improving the efficiency of DNA polymerization were expressed and purified in E. coli. Site-directed substitutions of four conserved residues (Gly310, Arg412, Lys416, and Asp540) in the activity site of Bst DNA polymerase influenced efficiency of polymerizing dNTPs. The substitution of residue Gly310 by alanine or leucine and residue Asp540 by glutamic acid increased the efficiency of polymerase activity. All mutants with higher polymerizing efficiency were employed to complete the rapid detection of EV71-associated hand, foot, and mouth disease (HFMD) by IMSA approach with relatively shorter period which is suitable for the primary diagnostics setting in rural and underdeveloped areas. PMID:27981047

  3. Activation of large-conductance Ca(2+)-activated K(+) channels inhibits glutamate-induced oxidative stress through attenuating ER stress and mitochondrial dysfunction.

    PubMed

    Yan, Xiao-Hua; Guo, Xiang-Yang; Jiao, Fu-Yong; Liu, Xuan; Liu, Yong

    2015-11-01

    Large-conductance Ca(2+)-activated K(+) channels (BK channels) are widely expressed throughout the vertebrate nervous system, and are involved in the regulation of neurotransmitter release and neuronal excitability. Here, the neuroprotective effects of NS11021, a selective and chemically unrelated BK channel activator, and potential molecular mechanism involved have been studied in rat cortical neurons exposed to glutamate in vitro. Pretreatment with NS11021 significantly inhibited the loss of neuronal viability, LDH release and neuronal apoptosis in a dose-dependent manner. All these protective effects were fully antagonized by the BK-channel inhibitor paxilline. NS11021-induced neuroprotection was associated with reduced oxidative stress, as evidenced by decreased reactive oxygen species (ROS) generation, lipid peroxidation and preserved activity of antioxidant enzymes. Moreover, NS11021 significantly attenuated the glutamate-induced endoplasmic reticulum (ER) calcium release and activation of ER stress markers, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12. Pretreatment with NS11021 also mitigated the mitochondrial membrane potential (MMP) collapse, cytochrome c release, and preserved mitochondrial Ca(2+) buffering capacity and ATP synthesis after glutamate exposure. Taken together, these results suggest that activation of BK channels via NS11021 protects cortical neurons against glutamate-induced excitatory damage, which may be dependent on the inhibition of ER stress and preservation of mitochondrial dysfunction.

  4. Wanderlust kinetics and variable Ca(2+)-sensitivity of Drosophila, a large conductance Ca(2+)-activated K+ channel, expressed in oocytes.

    PubMed Central

    Silberberg, S D; Lagrutta, A; Adelman, J P; Magleby, K L

    1996-01-01

    Cloned large conductance Ca(2+)-activated K+ channels (BK or maxi-K+ channels) from Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised membrane patches with the patch-clamp technique. Both a natural variant and a mutant that eliminated a putative cyclic AMP-dependent protein kinase phosphorylation site exhibited large, slow fluctuations in open probability with time. These fluctuations, termed "wanderlust kinetics," occurred with a time course of tens of seconds to minutes and had kinetic properties inconsistent with simple gating models. Wanderlust kinetics was still observed in the presence of 5 mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the solution was increased by the addition of 5 mM HEDTA, suggesting that the wanderlust kinetics did not arise from Ca2+ release from caffeine and thapsigargin sensitive internal stores in the excised patch. The slow changes in kinetics associated with wanderlust kinetics could be generated with a discrete-state Markov model with transitions among three or more kinetic modes with different levels of open probability. To average out the wanderlust kinetics, large amounts of data were analyzed and demonstrated up to a threefold difference in the [Ca2+]i required for an open probability of 0.5 among channels expressed from the same injected mRNA. These findings indicate that cloned dSlo channels in excised patches from Xenopus oocytes can exhibit large variability in gating properties, both within a single channel and among channels. PMID:8744301

  5. Measuring the thermal sensitivity of a fiber Fabry-Pérot interferometer

    NASA Astrophysics Data System (ADS)

    Jennings, Jeff; Halverson, Samuel; Diddams, Scott A.; Terrien, Ryan; Ycas, Gabriel; Mahadevan, Suvrath

    2016-08-01

    We introduce a general technique for frequency stability characterization of Fabry-Perot etalons that are being explored for astronomical spectrograph calibration. In our approach a frequency-stabilized laser frequency comb is employed as a reference for a scanning CW laser measurement of the temperature sensitivity of a fiber Fabry-Perot interferometer (FFP). For an in-house constructed, actively stabilized FFP, we observe the thermal sensitivity of a resonance mode at 1319 nm of 7.4 GHz C-1, which corresponds to a fractional thermal sensitivity of 3.2 × 10-5 C-1. We compare these results to a simple model and discuss further the materials construction and stabilization of the FFP. Our measurement technique is one step toward a broad characterization of Fabry-Perot instruments, and this FFP in particular is currently being investigated as a wavelength calibration source in precision radial velocity spectroscopy to discover terrestrial-mass exoplanets.

  6. Optical generation of millimeter-wave pulses using a fiber Bragg grating in a fiber-optics system.

    PubMed

    Ye, Qing; Qu, Ronghui; Fang, Zujie

    2007-04-10

    A scheme is proposed to transform an optical pulse into a millimeter-wave frequency modulation pulse by using a weak fiber Bragg grating (FBG) in a fiber-optics system. The Fourier transformation method is used to obtain the required spectrum response function of the FBG for the Gaussian pulse, soliton pulse, and Lorenz shape pulse. On the condition of the first-order Born approximation of the weak fiber grating, the relation of the refractive index distribution and the spectrum response function of the FBG satisfies the Fourier transformation, and the corresponding refractive index distribution forms are obtained for single-frequency modulation and linear-frequency modulation millimeter-wave pulse generation. The performances of the designed fiber gratings are also studied by a numerical simulation method for a supershort pulse transmission.

  7. Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase.

    PubMed

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

    2013-06-15

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

  8. A Very Large Number of GABAergic Neurons Are Activated in the Tuberal Hypothalamus during Paradoxical (REM) Sleep Hypersomnia

    PubMed Central

    Sapin, Emilie; Bérod, Anne; Léger, Lucienne; Herman, Paul A.; Luppi, Pierre-Hervé; Peyron, Christelle

    2010-01-01

    We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD67 in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD+, Fos-ir/MCH+, and GAD+/MCH+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis. PMID:20668680

  9. Active stall control for large offshore horizontal axis wind turbines; a conceptual study considering different actuation methods

    NASA Astrophysics Data System (ADS)

    Pereira, R.; van Bussel, G. J. W.; Timmer, W. A.

    2014-12-01

    The increasing size of Horizontal Axis Wind Turbines and the trend to install wind farms further offshore demand more robust design options. If the pitch system could be eliminated, the availability of Horizontal Axis Wind Turbines should increase. This research investigates the use of active stall control to regulate power production in replacement of the pitch system. A feasibility study is conducted using a blade element momentum code and taking the National Renewable Energy Laboratory 5 MW turbine as baseline case. Considering half of the blade span is equipped with actuators, the required change in the lift coefficient to regulate power was estimated in ΔCl = 0.7. Three actuation technologies are investigated, namely Boundary Layer Transpiration, Trailing Edge Jets and Dielectric Barrier Discharge actuators. Results indicate the authority of the actuators considered is not sufficient to regulate power, since the change in the lift coefficient is not large enough. Active stall control of Horizontal Axis Wind Turbines appears feasible only if the rotor is re-designed from the start to incorporate active-stall devices.

  10. The unique N terminus of the herpes simplex virus type 1 large subunit is not required for ribonucleotide reductase activity.

    PubMed

    Conner, J; Macfarlane, J; Lankinen, H; Marsden, H

    1992-01-01

    Using purified bacterially expressed herpes simplex virus type 1 ribonucleotide reductase large subunit (R1) and the proteolytic enzymes chymotrypsin and trypsin, we have generated stable N-terminal truncations. Chymotrypsin removes 246 amino acids from the amino terminus to produce a fragment (dN246R1) which retains full enzymic activity and affinity for the small subunit (R2). Treatment of R1 with trypsin produces a 120K protein and a cleavage at amino acid residue 305 to produce a fragment (dN305R1) which remains associated with a 33K N-terminal polypeptide. Although this 33K-dN305R1 complex retains full binding affinity for R2 its reductase activity is reduced by approximately 50%. Increasing the concentration of trypsin removes the 33K N-terminal polypeptide resulting in dN305R1 which, when bound to R2, has full ribonucleotide reductase activity. Like R1, dN246R1 and dN305R1 each exist as dimers showing that the first 305 amino acids of R1 are not necessary for dimer formation. These results indicate that, in structural studies of subunit interaction, dN246R1 or dN305R1 can be considered as suitable replacements for intact R1.

  11. Nicotine addiction reduces the large-conductance Ca(2+)-activated potassium channels expression in the nucleus accumbens.

    PubMed

    Ma, Lan; Wu, Yu-Mei; Guo, Yan-Yan; Yang, Qi; Feng, Bin; Song, Qian; Liu, Shui-Bing; Zhao, Da-Qing; Zhao, Ming-Gao

    2013-06-01

    Large-conductance Ca(2+)-activated K(+) channels (BKCa) are widely expressed in the central nervous system and play important roles in neural activities. Nicotine exposure leads to long-lasting changes in behavioral and neuronal plasticity. However, little is known the roles of BKCa in the development of nicotine addiction. In the present study, a significant reduction in BKCa channel expression was found in nucleus accumbens (NAc) from nicotine addiction mice. Whole-cell patch-clamp recordings from NAc neurons of the addicted animals revealed a pronounced reduction in the fast after-hyperpolarization of action potentials mediated by BKCa channels that led to hyperexcitability of the NAc neurons. Activation of BKCa channels in the NAc reversed drug-seeking behaviors which were detected by conditioned place preference test. Furthermore, knockdown of BKCa channels using short hairpin RNAs significantly increased the drug-seeking behavior. These findings provide direct evidence that alterations of BKCa channels in the NAc play critical roles in the development of nicotine addiction and that modulation of the BKCa channels may be potential therapeutics for drug addiction.

  12. Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells.

    PubMed

    Liu, Yu; Savtchouk, Iaroslav; Acharjee, Shoana; Liu, Siqiong June

    2011-07-01

    Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors (AMPAR) that are permeable to Ca(2+) and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca(2+)-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca(2+)-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca(2+) entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca(2+) entry in cerebellar stellate cells.

  13. Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

    PubMed Central

    Liu, Yu; Savtchouk, Iaroslav; Acharjee, Shoana

    2011-01-01

    Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors (AMPAR) that are permeable to Ca2+ and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca2+-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca2+-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca2+ entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca2+ entry in cerebellar stellate cells. PMID:21562198

  14. Using active learning strategies to investigate student learning and attitudes in a large enrollment, introductory geology course

    NASA Astrophysics Data System (ADS)

    Berry, Stacy Jane

    There has been an increased emphasis for college instruction to incorporate more active and collaborative involvement of students in the learning process. These views have been asserted by The Association of American Colleges (AAC), the National Science Foundation (NSF), and The National Research Counsel (NRC), which are advocating for the modification of traditional instructional techniques to allow students the opportunity to be more cooperative (Task Group on General Education, 1988). This has guided educators and facilitators into shifting teaching paradigms from a teacher centered to a more student-centered curriculum. The present study investigated achievement outcomes and attitudes of learners in a large enrollment (n ~ 200), introductory geology course using a student centered learning cycle format of instruction versus another similar section that used a traditional lecture format. Although the course is a recruiting class for majors, over 95% of the students that enroll are non-majors. Measurements of academic evaluation were through four unit exams, classroom communication systems, weekly web-based homework, in-class activities, and a thematic collaborative poster/paper project and presentation. The qualitative methods to investigate the effectiveness of the teaching design included: direct observation, self-reporting about learning, and open-ended interviews. By disaggregating emerging data, we tried to concentrate on patterns and causal relationships between achievement performance and attitudes regarding learning geology. Statistical analyses revealed positive relationships between student engagement in supplemental activities and achievement mean scores within and between the two sections. Completing weekly online homework had the most robust relationship with overall achievement performance. Contrary to expectations, a thematic group project only led to modest gains in achievement performance, although the social and professional gains could be

  15. RNA-seq pinpoints a Xanthomonas TAL-effector activated resistance gene in a large-crop genome.

    PubMed

    Strauss, Tina; van Poecke, Remco M P; Strauss, Annett; Römer, Patrick; Minsavage, Gerald V; Singh, Sylvia; Wolf, Christina; Strauss, Axel; Kim, Seungill; Lee, Hyun-Ah; Yeom, Seon-In; Parniske, Martin; Stall, Robert E; Jones, Jeffrey B; Choi, Doil; Prins, Marcel; Lahaye, Thomas

    2012-11-20

    Transcription activator-like effector (TALE) proteins of the plant pathogenic bacterial genus Xanthomonas bind to and transcriptionally activate host susceptibility genes, promoting disease. Plant immune systems have taken advantage of this mechanism by evolving TALE binding sites upstream of resistance (R) genes. For example, the pepper Bs3 and rice Xa27 genes are hypersensitive reaction plant R genes that are transcriptionally activated by corresponding TALEs. Both R genes have a hallmark expression pattern in which their transcripts are detectable only in the presence and not the absence of the corresponding TALE. By transcriptome profiling using next-generation sequencing (RNA-seq), we tested whether we could avoid laborious positional cloning for the isolation of TALE-induced R genes. In a proof-of-principle experiment, RNA-seq was used to identify a candidate for Bs4C, an R gene from pepper that mediates recognition of the Xanthomonas TALE protein AvrBs4. We identified one major Bs4C candidate transcript by RNA-seq that was expressed exclusively in the presence of AvrBs4. Complementation studies confirmed that the candidate corresponds to the Bs4C gene and that an AvrBs4 binding site in the Bs4C promoter directs its transcriptional activation. Comparison of Bs4C with a nonfunctional allele that is unable to recognize AvrBs4 revealed a 2-bp polymorphism within the TALE binding site of the Bs4C promoter. Bs4C encodes a structurally unique R protein and Bs4C-like genes that are present in many solanaceous genomes seem to be as tightly regulated as pepper Bs4C. These findings demonstrate that TALE-specific R genes can be cloned from large-genome crops with a highly efficient RNA-seq approach.

  16. Detection of triazole deicing additives in soil samples from airports with low, mid, and large volume aircraft deicing activities.

    PubMed

    McNeill, K S; Cancilla, D A

    2009-03-01

    Soil samples from three USA airports representing low, mid, and large volume users of aircraft deicing fluids (ADAFs) were analyzed by LC/MS/MS for the presence of triazoles, a class of corrosion inhibitors historically used in ADAFs. Triazoles, specifically the 4-methyl-1H-benzotriazole and the 5-methyl-1H-benzotriazole, were detected in a majority of samples and ranged from 2.35 to 424.19 microg/kg. Previous studies have focused primarily on ground and surface water impacts of larger volume ADAF users. The detection of triazoles in soils at low volume ADAF use airports suggests that deicing activities may have a broader environmental impact than previously considered.

  17. The development of a fiber optics communication network for controlling a Multidegree-Of-Freedom Serpentine Truss

    NASA Technical Reports Server (NTRS)

    Andrawis, Alfred S.

    1994-01-01

    The problem addressed by this report is the large size and heavy weight of the cable bundle, used for controlling a Multidegree-Of-Freedom Serpentine Truss Manipulator arm, which imposes limitations on the manipulator arm maneuverability. This report covers a design of an optical fiber network to replace the existing copper wire network of the Serpentine Truss Manipulator. This report proposes a fiber network design which significantly reduces the bundle size into two phases. The first phase does not require any modifications for the manipulator architecture, while the other requires major modifications. Design philosophy, hardware details and schematic diagrams are presented.

  18. The Radio/Gamma-Ray Connection in Active Galactic Nuclei in the Era of the Fermi Large Area Telescope

    NASA Technical Reports Server (NTRS)

    Ackermann, M.; Ajello, M.; Allafort, A.; Angelakis, E.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Borgland, A. W.; Bouvier, A.; Bregeon, J.; Brez, A.; Brigida, M.; Bruel, P.; Gehrels, N.; Hays, E.; MeEnery, J. E.; Scargle, J. D.; Thompson, D. J.

    2011-01-01

    We present a detailed statistical analysis of the correlation between radio and gamma-ray emission of the active galactic nuclei (AGNs) detected by Fermi during its first year of operation, with the largest data sets ever used for this purpose.We use both archival interferometric 8.4 GHz data (from the Very Large Array and ATCA, for the full sample of 599 sources) and concurrent single-dish 15 GHz measurements from the OwensValley RadioObservatory (OVRO, for a sub sample of 199 objects). Our unprecedentedly large sample permits us to assess with high accuracy the statistical significance of the correlation, using a surrogate data method designed to simultaneously account for common-distance bias and the effect of a limited dynamical range in the observed quantities. We find that the statistical significance of a positive correlation between the centimeter radio and the broadband (E > 100 MeV) gamma-ray energy flux is very high for the whole AGN sample, with a probability of <10(exp -7) for the correlation appearing by chance. Using the OVRO data, we find that concurrent data improve the significance of the correlation from 1.6 10(exp -6) to 9.0 10(exp -8). Our large sample size allows us to study the dependence of correlation strength and significance on specific source types and gamma-ray energy band. We find that the correlation is very significant (chance probability < 10(exp -7)) for both flat spectrum radio quasars and BL Lac objects separately; a dependence of the correlation strength on the considered gamma-ray energy band is also present, but additional data will be necessary to constrain its significance.

  19. Development activities on NIR large format MCT detectors for astrophysics and space science at CEA and SOFRADIR

    NASA Astrophysics Data System (ADS)

    Boulade, Olivier; Moreau, Vincent; Mulet, Patrick; Gravrand, Olivier; Cervera, Cyril; Zanatta, Jean-Paul; Castelein, Pierre; Guellec, Fabrice; Fièque, Bruno; Chorier, Philippe; Roumegoux, Julien

    2016-07-01

    CEA and SOFRADIR have been manufacturing and characterizing near infrared detectors in the frame of ESA's near infrared large format sensor array roadmap to develop a 2Kx2K large format low flux low noise device for space applications such as astrophysics. These detectors use HgCdTe as the absorbing material and p/n diode technology. The technological developments (photovoltaic technology, readout circuit, ...) are shared between CEA/LETI and SOFRADIR, both in Grenoble, while most of the performances are evaluated at CEA/IRFU in Saclay where a dedicated test facility has been developed, in particular to measure very low dark currents. The paper will present the current status of these developments at the end of ESA's NIRLFSA phase 2. The performances of the latest batch of devices meet or are very close to all the requirements (quantum efficiency, dark current, cross talk, readout noise, ...) even though a glow induced by the ROIC prevents the accurate measurement of the dark current. The current devices are fairly small, 640x512 15μm pixels, and the next phase of activity will target the development of a full size 2Kx2K detector. From the design and development, to the manufacturing and finally the testing, that type of detector requests a high level of mastering. An appropriate manufacturing and process chain compatible with such a size is needed at industrial level and results obtained with CEA technology coupled with Sofradir industrial experience and work on large dimension detector allow French actors to be confident to address this type of future missions.

  20. Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway

    NASA Technical Reports Server (NTRS)

    Solomon, V.; Baracos, V.; Sarraf, P.; Goldberg, A. L.

    1998-01-01

    The rapid loss of muscle mass that accompanies many disease states, such as cancer or sepsis, is primarily a result of increased protein breakdown in muscle, and several observations have suggested an activation of the ubiquitin-proteasome system. Accordingly, in extracts of atrophying muscles from tumor-bearing or septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were found to be higher than in control extracts. On the other hand, in extracts of muscles from hypothyroid rats, where overall proteolysis is reduced below normal, the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and treatment with triiodothyronine (T3) restored ubiquitination to control levels. Surprisingly, the N-end rule pathway, which selectively degrades proteins with basic or large hydrophobic N-terminal residues, was found to be responsible for most of these changes in ubiquitin conjugation. Competitive inhibitors of this pathway that specifically block the ubiquitin ligase, E3alpha, suppressed most of the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and septic rats. These inhibitors also suppressed ubiquitination in normal extracts toward levels in hypothyroid extracts, which showed little E3alpha-dependent ubiquitination. Thus, the inhibitors eliminated most of the differences in ubiquitination under these different pathological conditions. Moreover, 125I-lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in extracts from tumor-bearing and septic rats, and more slowly in those from hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation increases in atrophying muscles, and these hormone- and cytokine-dependent responses are in large part due to activation of the N-end rule pathway.

  1. Making large class basic histology lectures more interactive: The use of draw-along mapping techniques and associated educational activities.

    PubMed

    Kotzé, Sanet Henriët; Mole, Calvin Gerald

    2015-01-01

    At Stellenbosch University, South Africa, basic histology is taught to a combination class of almost 400 first-year medical, physiotherapy, and dietetic students. Many students often find the amount of work in basic histology lectures overwhelming and consequently loose interest. The aim was to determine if a draw-along mapping activity would focus students during large class lectures. After each lecture on three basic histology tissues, a guided draw-along mapping session covering the work from the lecture was introduced in the form of a click-advance PowerPoint presentation which was used to demonstrate the unfolding of an "ideal" map. The lecturer simultaneously drew a similar map using an overhead projector allowing the students to draw their own maps on blank sheets of paper along with the lecturer. Students remained attentive during the activity and many participated in answering informal questions posed by the lecturer as the map-making session progressed. After the last session, students completed an anonymous, voluntary questionnaire (response rate of 78%). The majority of students found the draw-along maps useful (94%) and believed that its use should be continued in the future (93%). A significant increase (P < 0.001) was found in the test results of student cohorts who were given the current intervention compared to cohorts from previous years who were given mind maps as handouts only or had no intervention. The use of the draw-along mapping sessions were successful in focusing students during large class lectures while also providing them with a useful tool for their studies.

  2. Delivering Science to Large Audiences: Experiments in Active Learning and Public Lectures at the University of Michigan

    NASA Astrophysics Data System (ADS)

    McKay, T.

    1999-12-01

    The problem of disseminating scientific knowledge to the broader community in an effective and efficient way is always with us. At the University of Michigan we have been addressing this problem in several ways. Every year we teach introductory physics to about 3000 students. We believe that, in addition to a pedagogical responsibility, this is an important opportunity for outreach. We report on a variety of approaches to active learning in large lecture classes which are aimed at aiding student comprehension of conceptual material. These have the side affect of improving their general impression of science. In addition to the traditional classroom, we have also engaged in a broader outreach program through the Saturday Morning Physics lecture series, which through a combination of programming and advertising draws audiences of 250 a week to 15 weeks of lectures on topics of current research. We conclude with some general observations about the relation between the success of these public lectures and our large lecture classes. This work is supported by a CAREER award from the National Science Foundation, the University of Michigan, and the Ted Annis Foundation.

  3. A Fiber-Optic Aircraft Lightning Current Measurement Sensor

    NASA Technical Reports Server (NTRS)

    Nguyen, Truong X.; Ely, Jay J.; Szatkowski, George N.

    2013-01-01

    A fiber-optic current sensor based on the Faraday Effect is developed for aircraft installations. It can measure total lightning current amplitudes and waveforms, including continuing current. Additional benefits include being small, lightweight, non-conducting, safe from electromagnetic interference, and free of hysteresis and saturation. The Faraday Effect causes light polarization to rotate in presence of magnetic field in the direction of light propagation. Measuring the total induced light polarization change yields the total current enclosed. The system operates at 1310nm laser wavelength and can measure approximately 300 A - 300 kA, a 60 dB range. A reflective polarimetric scheme is used, where the light polarization change is measured after a round-trip propagation through the fiber. A two-detector setup measures the two orthogonal polarizations for noise subtraction and improved dynamic range. The current response curve is non-linear and requires a simple spline-fit correction. Effects of high current were achieved in laboratory using combinations of multiple fiber and wire loops. Good result comparisons against reference sensors were achieved up to 300 kA. Accurate measurements on a simulated aircraft fuselage and an internal structure illustrate capabilities that maybe difficult with traditional sensors. Also tested at a commercial lightning test facility from 20 kA to 200 kA, accuracy within 3-10% was achieved even with non-optimum setups.

  4. Testing of a Fiber Optic Wear, Erosion and Regression Sensor

    NASA Technical Reports Server (NTRS)

    Korman, Valentin; Polzin, Kurt A.

    2011-01-01

    The nature of the physical processes and harsh environments associated with erosion and wear in propulsion environments makes their measurement and real-time rate quantification difficult. A fiber optic sensor capable of determining the wear (regression, erosion, ablation) associated with these environments has been developed and tested in a number of different applications to validate the technique. The sensor consists of two fiber optics that have differing attenuation coefficients and transmit light to detectors. The ratio of the two measured intensities can be correlated to the lengths of the fiber optic lines, and if the fibers and the host parent material in which they are embedded wear at the same rate the remaining length of fiber provides a real-time measure of the wear process. Testing in several disparate situations has been performed, with the data exhibiting excellent qualitative agreement with the theoretical description of the process and when a separate calibrated regression measurement is available good quantitative agreement is obtained as well. The light collected by the fibers can also be used to optically obtain the spectra and measure the internal temperature of the wear layer.

  5. Electroretinography in dogs using a fiber electrode prototype

    PubMed Central

    Pereira, A.L.; Montiani-Ferreira, F.; Santos, V.R.; Salomão, S.R.; Souza, C.; Berezovsky, A.

    2013-01-01

    We compared two electroretinography (ERG) electrodes in dogs using ERG standards of the International Society for Clinical Electrophysiology of Vision (ISCEV). Ten healthy Yorkshire terrier dogs (mean age, 2.80 ± 1.42 years; 6 females) weighing 5.20 ± 1.56 kg were evaluated using an ERG system for veterinary use. Dark- and light-adapted ERG responses were recorded using an ERG-Jet electrode and a fiber electrode prototype. The examinations were performed during 2 visits, 3 weeks apart. Both electrodes (ERG-Jet or fiber prototype) were used on each animal and the first eye to be recorded (OD × OS) was selected randomly. Three weeks later the examination was repeated on the same animal switching the type of electrode to be used that day and the first eye to be examined. The magnitude and waveform quality obtained with the two electrode types were similar for all ERG responses. ERG amplitudes and implicit times obtained from dogs using the fiber electrode prototype were comparable to those obtained with the ERG-Jet electrode for rod, maximal rod-cone summed, cone, and 30-Hz flicker responses. The fiber electrode prototype is a low-cost device, available as an alternative instrument for clinical veterinary ERG recording for retinal function assessment. PMID:23558860

  6. Structural response of a fiber composite compressor fan blade airfoil

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Minich, M. D.

    1975-01-01

    A theoretical investigation was performed to determine the structural response of a fiber composite airfoil typical of those encountered in high-tip speed compressor fan blades when subjected to load conditions anticipated in such applications. The analysis method consisted of composite mechanics embedded in pre- and post-processors coupled with NASTRAN. The load conditions examined include thermal due to aerodynamic heating, pressure due to aerodynamic forces, and centrifugal. Root reactions due to various load conditions, average composite and ply stresses, ply delaminations, and the fundamental modes and the corresponding reactions were investigated. The results show that the thermal and pressure stresses are negligible compared to those caused by the centrifugal forces. The core-shell concept for composite blades is an inefficient design and is sensitive to interply delaminations. The results are presented in graphical and tabular forms to illustrate the types and amount of data required for the analysis, and to provide quantitative data associated with the various responses which can be helpful in designing composite blades.

  7. A fiber optic wind vane: A conceptual view

    SciTech Connect

    Parker, M.J.; Heaverly, M.

    1996-07-01

    The use of tall towers for the normal operation of meteorological instrumentation is ideal for ensuring that representative measurements are obtained relative to the nearby terrain. Tall towers also expose instrumentation to unwanted environmental side-effects such as lightning surges. The proximity of many industrial observation sites for meteorological towers also introduces unwanted problems including radio frequency interference (RFI) from radio, television, or microwave transmitters, explosive environments, and electrical power cabling. Typical meteorological instrumentation systems incorporate protective mechanisms such as grounding networks, surge protectors and electrical shielding to combat electrical problems. Still, even with elaborate protective systems, damages to instrumentation and a loss of valid data can occur which often results in extended outages. The use of fiber optic technology in meteorological instrumentation holds great promise to eliminate many of the problems associated with monitoring on tall towers. A fiber optic sensor would be impervious to lightning surges and all forms of RFI. The sensor would provide a high signal to noise ratio output since little or no electrical interference would be involved in data transmission. A longer field life for mechanical devices such as a wind vane would be realized since all physical contact points, such as those found in a potentiometer, would be eliminated. Therefore, the precision, resolution, linearity, starting threshold and accuracy could be dramatically improved without the hindrance of moving parts.

  8. Development of GoSlo-SR-5-69, a potent activator of large conductance Ca2+-activated K+ (BK) channels.

    PubMed

    Roy, Subhrangsu; Large, Roddy J; Akande, Adebola Morayo; Kshatri, Aravind; Webb, Tim I; Domene, Carmen; Sergeant, Gerard P; McHale, Noel G; Thornbury, Keith D; Hollywood, Mark A

    2014-03-21

    We have designed, synthesised and characterised the effects of a number of novel anthraquinone derivatives and assessed their effects on large conductance, Ca(2+) activated K(+) (BK) channels recorded from rabbit bladder smooth muscle cells using the excised, inside/out configuration of the patch clamp technique. These compounds are members of the GoSlo-SR family of compounds, which potently open BK channels and shift the voltage required for half maximal activation (V1/2) negatively. The efficacy of the anilinoanthraquinone derivatives was enhanced when the size of ring D was increased, since the cyclopentane and cyclohexane derivatives shifted the V1/2, by -24 ± 6 mV and -54 ± 8 mV, respectively, whereas the cycloheptane and cyclooctane derivatives shifted the V1/2 by -61 ± 6 mV and -106 ± 6 mV. To examine if a combination of hydrophobicity and steric bulking of this region further enhanced their ability to open BK channels, we synthesised a number of naphthalene and tetrahydro-naphthalene derivatives. The tetrahydro-2-naphthalene derivative GoSlo-SR-5-69 was the most potent and efficacious of the series since it was able to shift the activation V1/2 by greater than -100 mV when applied at a concentration of 1 μM and had an EC50 of 251 nM, making it one of the most potent and efficacious BK channel openers synthesised to date.

  9. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma.

    PubMed

    Milhollen, Michael A; Traore, Tary; Adams-Duffy, Jennifer; Thomas, Michael P; Berger, Allison J; Dang, Lenny; Dick, Lawrence R; Garnsey, James J; Koenig, Erik; Langston, Steven P; Manfredi, Mark; Narayanan, Usha; Rolfe, Mark; Staudt, Louis M; Soucy, Teresa A; Yu, Jie; Zhang, Julie; Bolen, Joseph B; Smith, Peter G

    2010-09-02

    MLN4924 is a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor. In most cancer cells tested, inhibition of NAE leads to induction of DNA rereplication, resulting in DNA damage and cell death. However, in preclinical models of activated B cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), we show that MLN4924 induces an alternative mechanism of action. Treatment of ABC DLBCL cells with MLN4924 resulted in rapid accumulation of pIkappaBalpha, decrease in nuclear p65 content, reduction of nuclear factor-kappaB (NF-kappaB) transcriptional activity, and G(1) arrest, ultimately resulting in apoptosis induction, events consistent with potent NF-kappaB pathway inhibition. Treatment of germinal-center B cell-like (GCB) DLBCL cells resulted in an increase in cellular Cdt-1 and accumulation of cells in S-phase, consistent with cells undergoing DNA rereplication. In vivo administration of MLN4924 to mice bearing human xenograft tumors of ABC- and GCB-DLBCL blocked NAE pathway biomarkers and resulted in complete tumor growth inhibition. In primary human tumor models of ABC-DLBCL, MLN4924 treatment resulted in NF-kappaB pathway inhibition accompanied by tumor regressions. This work describes a novel mechanism of targeted NF-kappaB pathway modulation in DLBCL and provides strong rationale for clinical development of MLN4924 against NF-kappaB-dependent lymphomas.

  10. Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca(2+)-Activated K(+) Channels In Vitro.

    PubMed

    Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

    2017-02-01

    Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca(2+)-activated K(+) channel (BKCa) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca(2+) levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BKCa channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BKCa channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca(2+) and preventing neuronal apoptosis, and this is mediated by BKCa channel activation.

  11. Juvenile hormone-dopamine systems for the promotion of flight activity in males of the large carpenter bee Xylocopa appendiculata.

    PubMed

    Sasaki, Ken; Nagao, Takashi

    2013-12-01

    The reproductive roles of dopamine and dopamine regulation systems are known in social hymenopterans, but the knowledge on the regulation systems in solitary species is still needed. To test the possibility that juvenile hormone (JH) and brain dopamine interact to trigger territorial flight behavior in males of a solitary bee species, the effects on biogenic amines of JH analog treatments and behavioral assays with dopamine injections in males of the large carpenter bee Xylocopa appendiculata were quantified. Brain dopamine levels were significantly higher in methoprene-treated males than in control males 4 days after treatment, but were not significantly different after 7 days. Brain octopamine and serotonin levels did not differ between methoprene-treated and control males at 4 and 7 days after treatment. Injection of dopamine caused significantly higher locomotor activities and a shorter duration for flight initiation in experimental versus control males. These results suggest that brain dopamine can be regulated by JH and enhances flight activities in males. The JH-dopamine system in males of this solitary bee species is similar to that of males of the highly eusocial honeybee Apis mellifera.

  12. Experiment on large scale plume interaction with a stratified gas environment resembling the thermal activity of a autocatalytic recombiner

    SciTech Connect

    Mignot, G.; Kapulla, R.; Paladino, D.; Zboray, R.

    2012-07-01

    Computational Fluid Dynamics codes (CFD) are increasingly being used to simulate containment conditions after various transient accident scenarios. Consequently, the reliability of such codes must be tested against experimental data. Such validation experiments related to gas mixing and hydrogen transport within containment compartments addressing the effect of heat source are presented in this paper. The experiments were conducted in the large-scale thermal-hydraulics PANDA facility located at the Paul-Scherrer-Inst. (PSI) in Switzerland, in the frame of the OECD/SETH-2 project. A 10 kW electric heater simulating the thermal activity of the autocatalytic recombiner was activated at full power in a containment vessel at the top of which a thick helium layer is initially present. The hot plume interacts with the bottom of the helium layer which is slowly eroded until complete break up at 1350 s. After final erosion of the layer a strong temperature and concentration gradient is maintained in the vessel below the heater inlet as well as in the adjacent vessel below the interconnecting pipe. A detailed characterization of the operating heater suggests the presence of cold gas ingress at the outlet that affects the flow in the chimney. This can be of concern if present in a real PAR unit. (authors)

  13. Juvenile hormone-dopamine systems for the promotion of flight activity in males of the large carpenter bee Xylocopa appendiculata

    NASA Astrophysics Data System (ADS)

    Sasaki, Ken; Nagao, Takashi

    2013-12-01

    The reproductive roles of dopamine and dopamine regulation systems are known in social hymenopterans, but the knowledge on the regulation systems in solitary species is still needed. To test the possibility that juvenile hormone (JH) and brain dopamine interact to trigger territorial flight behavior in males of a solitary bee species, the effects on biogenic amines of JH analog treatments and behavioral assays with dopamine injections in males of the large carpenter bee Xylocopa appendiculata were quantified. Brain dopamine levels were significantly higher in methoprene-treated males than in control males 4 days after treatment, but were not significantly different after 7 days. Brain octopamine and serotonin levels did not differ between methoprene-treated and control males at 4 and 7 days after treatment. Injection of dopamine caused significantly higher locomotor activities and a shorter duration for flight initiation in experimental versus control males. These results suggest that brain dopamine can be regulated by JH and enhances flight activities in males. The JH-dopamine system in males of this solitary bee species is similar to that of males of the highly eusocial honeybee Apis mellifera.

  14. Acute stress induces down-regulation of large-conductance Ca2+-activated potassium channels in the lateral amygdala

    PubMed Central

    Guo, Yan-yan; Liu, Shui-bing; Cui, Guang-Bin; Ma, Lan; Feng, Bin; Xing, Jiang-hao; Yang, Qi; Li, Xiao-qiang; Wu, Yu-mei; Xiong, Li-ze; Zhang, Weiqi; Zhao, Ming-gao

    2012-01-01

    Large-conductance Ca2+-activated potassium channels (BKCa) are highly expressed in the lateral amygdala (LA), which is closely involved in assigning stress disorders, but data on their role in the neuronal circuits of stress disorders are limited. In the present study, a significant reduction in BKCa channel expression in the amygdala of mice accompanied anxiety-like behaviour induced by acute stress. Whole-cell patch-clamp recordings from LA neurons of the anxious animals revealed a pronounced reduction in the fast after-hyperpolarization (fAHP) of action potentials mediated by BKCa channels that led to hyperexcitability of the LA neurons. Activation of BKCa channels in the LA reversed stress-induced anxiety-like behaviour after stress. Furthermore, down-regulated BKCa channels notably increased the evoked NMDA receptor-mediated excitatory postsynaptic potentials at the thalamo-LA synapses. These data demonstrate, for the first time, that restraint stress-induced anxiety-like behaviour could at least partly be explained by alterations in the functional BKCa channels in the LA. PMID:22199169

  15. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    PubMed

    Berdyyeva, Tamara; Otte, Stephani; Aluisio, Leah; Ziv, Yaniv; Burns, Laurie D; Dugovic, Christine; Yun, Sujin; Ghosh, Kunal K; Schnitzer, Mark J; Lovenberg, Timothy; Bonaventure, Pascal

    2014-01-01

    Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  16. TWO EPOCHS OF VERY LARGE ARRAY OBSERVATIONS OF WATER MASER EMISSION IN THE ACTIVE GALAXY NGC 6240

    SciTech Connect

    Hagiwara, Yoshiaki

    2010-12-15

    Studies of 22 GHz H{sub 2}O maser emission from the merging galaxy NGC 6240 with double nuclei are presented. Two epochs of Very Large Array (VLA) observations in the A-configuration in spectral-line mode were carried out at 0.1 arcsec resolution by covering the redshifted velocity range of {approx}300 km s{sup -1} with respect to the systemic velocity of the galaxy. The purpose of these new observations is twofold: to detect an H{sub 2}O maser that an earlier VLA observation pinpointed in the southern nucleus in the northern nucleus as well to clarify the kinematics of the double nuclei, and to understand the origin of the maser in the galaxy. In the second epoch, one velocity feature peaking at V{sub LSR} = 7491.1 km s{sup -1}, redshifted by {approx}200 km s{sup -1} relative to the systemic velocity, was detected only toward the southern nucleus. The detection of an H{sub 2}O maser feature at or near this velocity had never been reported in earlier observations. However, including the known velocity features at redshifted velocities, no other velocity features were observed toward either nuclei throughout these epochs. The maser remains unresolved at an angular resolution of {approx}0.''1, corresponding to a linear size of less than about 45 pc. The two epochs of VLA observations show that the maser intensity is variable on timescales of at least three months, while the correlation between the maser intensity and the radio continuum intensity is not certain from our data. It is plausible that the maser in NGC 6240 is associated with the activity of an active galactic nucleus in the southern nucleus. Alternatively, the maser can be explained by star-forming activity at the site of massive star formation in the galaxy.

  17. Large-conductance calcium-activated potassium channels in purkinje cell plasma membranes are clustered at sites of hypolemmal microdomains.

    PubMed

    Kaufmann, Walter A; Ferraguti, Francesco; Fukazawa, Yugo; Kasugai, Yu; Shigemoto, Ryuichi; Laake, Petter; Sexton, Joseph A; Ruth, Peter; Wietzorrek, Georg; Knaus, Hans-Günther; Storm, Johan F; Ottersen, Ole Petter

    2009-07-10

    Calcium-activated potassium channels have been shown to be critically involved in neuronal function, but an elucidation of their detailed roles awaits identification of the microdomains where they are located. This study was undertaken to unravel the precise subcellular distribution of the large-conductance calcium-activated potassium channels (called BK, KCa1.1, or Slo1) in the somatodendritic compartment of cerebellar Purkinje cells by means of postembedding immunogold cytochemistry and SDS-digested freeze-fracture replica labeling (SDS-FRL). We found BK channels to be unevenly distributed over the Purkinje cell plasma membrane. At distal dendritic compartments, BK channels were scattered over the plasma membrane of dendritic shafts and spines but absent from postsynaptic densities. At the soma and proximal dendrites, BK channels formed two distinct pools. One pool was scattered over the plasma membrane, whereas the other pool was clustered in plasma membrane domains overlying subsurface cisterns. The labeling density ratio of clustered to scattered channels was about 60:1, established in SDS-FRL. Subsurface cisterns, also called hypolemmal cisterns, are subcompartments of the endoplasmic reticulum likely representing calciosomes that unload and refill Ca2+ independently. Purkinje cell subsurface cisterns are enriched in inositol 1,4,5-triphosphate receptors that mediate the effects of several neurotransmitters, hormones, and growth factors by releasing Ca2+ into the cytosol, generating local Ca2+ sparks. Such increases in cytosolic [Ca2+] may be sufficient for BK channel activation. Clustered BK channels in the plasma membrane may thus participate in building a functional unit (plasmerosome) with the underlying calciosome that contributes significantly to local signaling in Purkinje cells.

  18. Rat supraoptic magnocellular neurones show distinct large conductance, Ca2+-activated K+ channel subtypes in cell bodies versus nerve endings

    PubMed Central

    Dopico, Alejandro M; Widmer, Hélène; Wang, Gang; Lemos, José R; Treistman, Steven N

    1999-01-01

    Large conductance, Ca2+-activated K+ (BK) channels were identified in freshly dissociated rat supraoptic neurones using patch clamp techniques. The single channel conductance of cell body BK channels, recorded from inside-out patches in symmetric 145 mM K+, was 246.1 pS, compared with 213 pS in nerve ending BK channels (P < 0.01). At low open probability (Po), the reciprocal of the slope in the ln(NPo)-voltage relationship (N, number of available channels in the patch) for cell body and nerve ending channels were similar: 11 vs. 14 mVper e-fold change in NPo, respectively. At 40 mV, the [Ca2+]i producing half-maximal activation was 273 nM, as opposed to > 1.53 μM for the neurohypophysial channel, indicating the higher Ca2+ sensitivity of the cell body isochannel. Cell body BK channels showed fast kinetics (open time constant, 8.5 ms; fast closed time constant, 1.6 and slow closed time constant, 12.7 ms), identifying them as ‘type I’ isochannels, as opposed to the slow gating (type II) of neurohypophysial BK channels. Cell body BK activity was reduced by 10 nM charybdotoxin (NPo, 37 % of control), or 10 nM iberiotoxin (NPo, 5 % of control), whereas neurohypophysial BK channels are insensitive to charybdotoxin at concentrations as high as 360 nM. Whilst blockade of nerve ending BK channels markedly slowed the repolarization of evoked single spikes, blockade of cell body channels was without effect on repolarization of evoked single spikes. Ethanol reversibly increased neurohypophysial BK channel activity (EC50, 22 mM; maximal effect, 100 mM). In contrast, ethanol (up to 100 mM) failed to increase cell body BK channel activity. In conclusion, we have characterized BK channels in supraoptic neuronal cell bodies, and demonstrated that they display different electrophysiological and pharmacological properties from their counterparts in the nerve endings. PMID:10432342

  19. Self-sustaining non-repetitive activity in a large scale neuronal-level model of the hippocampal circuit

    PubMed Central

    Scorcioni, Ruggero; Hamilton, David J.; Ascoli, Giorgio A.

    2008-01-01

    fail to reproduce the full behavioral complexity of the large-scale model. Thus network size, cell class diversity, and connectivity details may all be critical to generate self-sustained non-repetitive activity patterns. PMID:18595658

  20. Self-sustaining non-repetitive activity in a large scale neuronal-level model of the hippocampal circuit.

    PubMed

    Scorcioni, Ruggero; Hamilton, David J; Ascoli, Giorgio A

    2008-10-01

    to reproduce the full behavioral complexity of the large-scale model. Thus network size, cell class diversity, and connectivity details may all be critical to generate self-sustained non-repetitive activity patterns.

  1. Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance a2+-activated K+ channels

    PubMed Central

    Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

    2015-01-01

    Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). Key Results At a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by Nω-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. Conclusions and Implications The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels. PMID:25652142

  2. Adaptive ultrasonic sensor using a fiber ring laser with tandem fiber Bragg gratings.

    PubMed

    Liu, Tongqing; Hu, Lingling; Han, Ming

    2014-08-01

    We propose and demonstrate an intensity-demodulated fiber-optic ultrasonic sensor system that can be self-adaptive to large quasi-static background strain perturbations. The sensor system is based on a fiber ring laser (FRL) whose laser cavity includes a pair of fiber Bragg gratings (FBGs). Self-adaptive ultrasonic detection is achieved by a tandem design where the two FBGs are engineered to have differential spectral responses to ultrasonic waves and are installed side-by-side at the same location on a structure. As a result, ultrasonic waves lead to relative spectral shifts of the FBGs and modulations to the cold-cavity loss of the FRL. Ultrasonic waves can then be detected directly from the laser intensity variations in response to the cold-cavity loss modulation. The sensor system is insensitive to quasi-static background strains because they lead to identical responses of the tandem FBGs. Based on the principle, a FRL sensor system was demonstrated and tested for adaptive ultrasonic detection when large static strains as well as dynamic sinusoidal vibrations were applied to the sensor.

  3. Reframing Perceptions of the Lecture from Challenges to Opportunities: Embedding Active Learning and Formative Assessment into the Teaching of Large Classes

    ERIC Educational Resources Information Center

    Winstone, Naomi; Millward, Lynne

    2012-01-01

    Teaching and assessing large classes can be reframed from focusing on overcoming difficulties with large classes, to seeking the unique educational opportunities provided by such learning environments. We discuss data and examples illustrating how active learning and formative assessment can be successfully embedded into the teaching of large…

  4. pH-activated size reduction of large compound nanoparticles for in vivo nucleus-targeted drug delivery.

    PubMed

    Fan, Yanbin; Li, Chunyan; Li, Fuyou; Chen, Daoyong

    2016-04-01

    Nucleus-targeted drug delivery is a promising strategy for anticancer therapy, but in vivo nucleus-targeted drug delivery has been challenging. Limited by the channel size of the nucleopore, vehicles that enter the nucleus via the nucleopore actively should be small and decorated with nuclear localization signal (NLS). However, the small vehicle size may promote leakage of vehicles into normal tissues, and the positively-charged NLS can lead to strong non-specific interactions in vivo. In the present study, we demonstrate an in vivo nucleus-targeted drug delivery using large compound nanoparticles with detachable PEG shell. The nanoparticles are composed of PEG-benzoic imine-oligo-l-lysine/iridium(III) metallodrug complex and formed in a kinetically-controlled fashion. Under physiological conditions (pH 7.4), the nanoparticles are large (ca. 150 nm) and protected by an inert PEG shell. When internalized into intracellular acidic endo/lysosomes of cancer cells, the nanoparticles dissociate into smaller ones (ca. 40 nm) and the PEG chains detach due to the cleavage of the benzoic imine bond at low pH. The small nanoparticles, with exposure of the oligo-l-lysine after the detachment of the PEG shield, then translocate into the nucleus via the nucleopore due to the small size and nuclear localization ability of the oligo-l-lysine. Importantly, the small particles could significantly release the contained drug into the nucleus, leading to ca. 20-fold higher cytotoxicity compared to the native drug in vitro. Further in vivo application of the nucleus-targeting nano-system in a nude-mice model showed significant tumor inhibition and remarkable life-span elongation.

  5. Palmitoylation of the β4-Subunit Regulates Surface Expression of Large Conductance Calcium-activated Potassium Channel Splice Variants*

    PubMed Central

    Chen, Lie; Bi, Danlei; Tian, Lijun; McClafferty, Heather; Steeb, Franziska; Ruth, Peter; Knaus, Hans Guenther; Shipston, Michael J.

    2013-01-01

    Regulatory β-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on β-subunit function is largely unknown. Here we demonstrate that the human β4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory β-subunit. β4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the β4-subunit alone. Importantly, palmitoylated β4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas β4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and β4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, β4-subunits. Our data reveal a novel mechanism by which palmitoylated β4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels. PMID:23504458

  6. Development of a fiber optic pavement subgrade strain measurement system

    NASA Astrophysics Data System (ADS)

    Miller, Craig Emerson

    2000-11-01

    This dissertation describes the development of a fiber optic sensing system to measure strains within the soil subgrade of highway pavements resulting from traffic loads. The motivation to develop such a device include improvements to: (1)all phases of pavement design, (2)theoretical models used to predict pavement performance, and (3)pavement rehabilitation. The design of the sensing system encompasses selecting an appropriate transducer design as well as the development of optimal optical and demodulation systems. The first is spring based, which attempts to match its spring stiffness to that of the soil-data indicate it is not an optimal transducer design. The second transducer implements anchoring plates attached to two telescoping tubes which allows the soil to be compacted to a desired density between the plates to dictate the transducer's behavior. Both transducers include an extrinsic Fabry- Perot cavity to impose the soil strains onto a phase change of the optical signal propagating through the cavity. The optical system includes a low coherence source and allows phase modulation via path length stretching by adding a second interferometer in series with the transducer, resulting in a path matched differential interferometer. A digitally implemented synthetic heterodyne demodulator based on a four step phase stepping algorithm is used to obtain unambiguous soil strain information from the displacement of the Fabry-Perot cavity. The demodulator is calibrated and characterized by illuminating the transducer with a second long coherence source of different wavelength. The transducer using anchoring plates is embedded within cylindrical soil specimens of varying soil types and soil moisture contents. Loads are applied to the specimen and resulting strains are measured using the embedded fiber optic gage and LVDTs attached to the surface of the specimen. This experimental verification is substantiated using a finite element analysis to predict any differences

  7. Diabetes downregulates large-conductance Ca2+-activated potassium beta 1 channel subunit in retinal arteriolar smooth muscle.

    PubMed

    McGahon, Mary K; Dash, Durga P; Arora, Aruna; Wall, Noreen; Dawicki, Jennine; Simpson, David A; Scholfield, C Norman; McGeown, J Graham; Curtis, Tim M

    2007-03-16

    Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca(2+) release events (Ca(2+)-sparks), trigger the activation of large-conductance Ca(2+)-activated K(+)(BK)-channels which hyperpolarize and relax vascular smooth muscle cells, thereby causing vasodilatation. In the present study, we examined BK channel function in retinal vascular smooth muscle cells from streptozotocin-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted nondiabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca(2+)](i) release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca(2+)-sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BKalpha subunit was unchanged. The Ca(2+)-sensitivity of single BK channels from diabetic retinal vascular smooth muscle cells was markedly reduced. The BKbeta1 subunit confers Ca(2+)-sensitivity to BK channel complexes and both transcript and protein levels for BKbeta1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BKbeta1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.

  8. RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma

    PubMed Central

    Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexandar; Wang, Jing; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; Han van Krieken, J.; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Jeffrey Medeiros, L.; Pham, Lan V.; Young, Ken H.

    2016-01-01

    It has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-κB subunits and involved in the classical NF-κB pathway. However, the prognostic and biological significance of RelA/p65 is equivocal in the field. In this study, we assessed RelA/p65 nuclear expression by immunohistochemistry in 487 patients with de novo diffuse large B-cell lymphoma (DLBCL), and studied the effects of molecular and pharmacological inhibition of NF-κB on cell viability. We found RelA/p65 nuclear expression, without associations with other apparent genetic or phenotypic abnormalities, had unfavorable prognostic impact in patients with stage I/II DLBCL. Gene expressionprofiling analysis suggested immune dysregulation and antiapoptosis may be relevant for the poorer prognosis associated with p65 hyperactivation in germinal center B-cell–like (GCB) DLBCL and in activated B-cell–like (ABC) DLBCL, respectively. We knocked down individual NF-κB subunits in representative DLBCL cells in vitro, and found targeting p65 was more effective than targeting other NF-κB subunits in inhibiting cell growth and survival. In summary, RelA/p65 nuclear overexpression correlates with significant poor survival in early-stage DLBCL patients, and therapeutic targeting RelA/p65 is effective in inhibiting proliferation and survival of DLBCL with NF-κB hyperactivation. PMID:27941215

  9. Giant stellar arcs in the Large Magellanic Cloud: a possible link with past activity of the Milky Way nucleus

    NASA Astrophysics Data System (ADS)

    Efremov, Yuri N.

    2013-02-01

    The origin of the giant stellar arcs in the Large Magellanic Cloud (LMC) remains a controversial issue, one that has been discussed since 1966. No other star/cluster arc is so perfect a segment of a circle; moreover, there is another similar arc nearby. Many hypotheses were advanced to explain these arcs and all but one of these was disproved. It was proposed in 2004 that the origin of these arcs was a bow shock from the jet that is intermittently fired by the Milky Way nucleus; during its last episode of activity the jet was pointed toward the LMC. Quite recently, evidence for such a jet indeed appeared. We suggest that it was once energetic enough to trigger star formation in the LMC, and if the jet opening angle was about 2° then it could push out H i gas from a region of about 2 kpc in size, forming a cavity LMC4, but also squeeze two dense clouds that occurred in the same area, causing the formation of stars along their surfaces facing the core of the Milky Way. As a result, spherical segments of stellar shells might arise, visible now as the arcs named the Quadrant and Sextant, the apexes of which point towards the centre of the Milky Way. The orientation of both arcs could be the key to unlocking their origin. Here we give data that confirm the above hypothesis, amongst which are the radial velocities of stars inside and outside the larger of the LMC arcs. The probability is low that a jet from an active galactic nucleus (AGN) points towards a nearby galaxy and triggers star formation there, but a few other examples are now known or suspected.

  10. Energetic ion losses caused by magnetohydrodynamic activity resonant and non-resonant with energetic ions in Large Helical Device

    NASA Astrophysics Data System (ADS)

    Ogawa, Kunihiro; Isobe, Mitsutaka; Toi, Kazuo; Shimizu, Akihiro; Spong, Donald A.; Osakabe, Masaki; Yamamoto, Satoshi; the LHD Experiment Group

    2014-09-01

    Experiments to reveal energetic ion dynamics associated with magnetohydrodynamic activity are ongoing in the Large Helical Device (LHD). Interactions between beam-driven toroidal Alfvén eigenmodes (TAEs) and energetic ions have been investigated. Energetic ion losses induced by beam-driven burst TAEs have been observed using a scintillator-based lost fast-ion probe (SLIP) in neutral beam-heated high β plasmas. The loss flux of co-going beam ions increases as the TAE amplitude increases. In addition to this, the expulsion of beam ions associated with edge-localized modes (ELMs) has been also recognized in LHD. The SLIP has indicated that beam ions having co-going and barely co-going orbits are affected by ELMs. The relation between ELM amplitude and ELM-induced loss has a dispersed structure. To understand the energetic ion loss process, a numerical simulation based on an orbit-following model, DELTA5D, that incorporates magnetic fluctuations is performed. The calculation result shows that energetic ions confined in the interior region are lost due to TAE instability, with a diffusive process characterizing their loss. For the ELM, energetic ions existing near the confinement/loss boundary are lost through a convective process. We found that the ELM-induced loss flux measured by SLIP changes with the ELM phase. This relation between the ELM amplitude and measured ELM-induced loss results in a more dispersed loss structure.

  11. Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline.

    PubMed

    Pulvino, Mary; Chen, Luojing; Oleksyn, David; Li, Jing; Compitello, George; Rossi, Randy; Spence, Stephen; Balakrishnan, Vijaya; Jordan, Craig; Poligone, Brian; Casulo, Carla; Burack, Richard; Shapiro, Joel L; Bernstein, Steven; Friedberg, Jonathan W; Deshaies, Raymond J; Land, Hartmut; Zhao, Jiyong

    2015-06-20

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes.

  12. Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline

    PubMed Central

    Pulvino, Mary; Chen, Luojing; Oleksyn, David; Li, Jing; Compitello, George; Rossi, Randy; Spence, Stephen; Balakrishnan, Vijaya; Jordan, Craig; Poligone, Brian; Casulo, Carla; Burack, Richard; Shapiro, Joel L.; Bernstein, Steven; Friedberg, Jonathan W.; Deshaies, Raymond J.; Land, Hartmut; Zhao, Jiyong

    2015-01-01

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes. PMID:26142707

  13. Improvements on GPS Location Cluster Analysis for the Prediction of Large Carnivore Feeding Activities: Ground-Truth Detection Probability and Inclusion of Activity Sensor Measures

    PubMed Central

    Blecha, Kevin A.; Alldredge, Mat W.

    2015-01-01

    Animal space use studies using GPS collar technology are increasingly incorporating behavior based analysis of spatio-temporal data in order to expand inferences of resource use. GPS location cluster analysis is one such technique applied to large carnivores to identify the timing and location of feeding events. For logistical and financial reasons, researchers often implement predictive models for identifying these events. We present two separate improvements for predictive models that future practitioners can implement. Thus far, feeding prediction models have incorporated a small range of covariates, usually limited to spatio-temporal characteristics of the GPS data. Using GPS collared cougar (Puma concolor) we include activity sensor data as an additional covariate to increase prediction performance of feeding presence/absence. Integral to the predictive modeling of feeding events is a ground-truthing component, in which GPS location clusters are visited by human observers to confirm the presence or absence of feeding remains. Failing to account for sources of ground-truthing false-absences can bias the number of predicted feeding events to be low. Thus we account for some ground-truthing error sources directly in the model with covariates and when applying model predictions. Accounting for these errors resulted in a 10% increase in the number of clusters predicted to be feeding events. Using a double-observer design, we show that the ground-truthing false-absence rate is relatively low (4%) using a search delay of 2–60 days. Overall, we provide two separate improvements to the GPS cluster analysis techniques that can be expanded upon and implemented in future studies interested in identifying feeding behaviors of large carnivores. PMID:26398546

  14. Improvements on GPS Location Cluster Analysis for the Prediction of Large Carnivore Feeding Activities: Ground-Truth Detection Probability and Inclusion of Activity Sensor Measures.

    PubMed

    Blecha, Kevin A; Alldredge, Mat W

    2015-01-01

    Animal space use studies using GPS collar technology are increasingly incorporating behavior based analysis of spatio-temporal data in order to expand inferences of resource use. GPS location cluster analysis is one such technique applied to large carnivores to identify the timing and location of feeding events. For logistical and financial reasons, researchers often implement predictive models for identifying these events. We present two separate improvements for predictive models that future practitioners can implement. Thus far, feeding prediction models have incorporated a small range of covariates, usually limited to spatio-temporal characteristics of the GPS data. Using GPS collared cougar (Puma concolor) we include activity sensor data as an additional covariate to increase prediction performance of feeding presence/absence. Integral to the predictive modeling of feeding events is a ground-truthing component, in which GPS location clusters are visited by human observers to confirm the presence or absence of feeding remains. Failing to account for sources of ground-truthing false-absences can bias the number of predicted feeding events to be low. Thus we account for some ground-truthing error sources directly in the model with covariates and when applying model predictions. Accounting for these errors resulted in a 10% increase in the number of clusters predicted to be feeding events. Using a double-observer design, we show that the ground-truthing false-absence rate is relatively low (4%) using a search delay of 2-60 days. Overall, we provide two separate improvements to the GPS cluster analysis techniques that can be expanded upon and implemented in future studies interested in identifying feeding behaviors of large carnivores.

  15. Provenance of a large Lower Cretaceous turbidite submarine fan complex on the active Laurasian margin: Central Pontides, northern Turkey

    NASA Astrophysics Data System (ADS)

    Akdoğan, Remziye; Okay, Aral I.; Sunal, Gürsel; Tari, Gabor; Meinhold, Guido; Kylander-Clark, Andrew R. C.

    2017-02-01

    The Pontides formed the southern active margin of Laurasia during the Mesozoic. They became separated from mainland Laurasia during the Late Cretaceous, with the opening of the Black Sea as an oceanic back-arc basin. During the Early Cretaceous, a large submarine turbidite fan complex developed in the Central Pontides. The turbidites cover an area of 400 km by 90 km with a thickness of more than 2 km. We have investigated the provenance of these turbidites-the Çağlayan Formation-using paleocurrent measurements, U-Pb detrital zircon ages, REE abundances of dated zircons and geochemistry of detrital rutile grains. 1924 paleocurrent measurements from 96 outcrop stations indicate flow direction from northwest to southeast in the eastern part of the Çağlayan Basin and from north-northeast to west-southwest in the western part. 1194 detrital zircon ages from 13 Lower Cretaceous sandstone samples show different patterns in the eastern, central and western parts of the basin. The majority of the U-Pb detrital zircon ages in the eastern part of the basin are Archean and Paleoproterozoic (61% of all zircon ages, 337 grains); rocks of these ages are absent in the Pontides and present in the Ukrainian Shield, which indicates a source north of the Black Sea. In the western part of the basin the majority of the zircons are Carboniferous and Neoproterozoic (68%, 246 grains) implying more local sources within the Pontides. The detrital zircons from the central part show an age spectrum as mixture of zircons from western and eastern parts. Significantly, Jurassic and Early Cretaceous zircons make up less than 2% of the total zircon population, which implies lack of a coeval magmatic arc in the region. This is compatible with the absence of the Lower Cretaceous granites in the Pontides. Thus, although the Çağlayan Basin occupied a fore-arc position above the subduction zone, the arc was missing, probably due to flat subduction, and the basin was largely fed from the Ukrainian

  16. Chandra, Extreme Ultraviolet Explorer, and Very Large Array Observations of the Active Binary System σ2 Coronae Borealis

    NASA Astrophysics Data System (ADS)

    Osten, Rachel A.; Ayres, Thomas R.; Brown, Alexander; Linsky, Jeffrey L.; Krishnamurthi, Anita

    2003-01-01

    We present the results of a coordinated observing campaign on the short-period RS CVn binary σ2 Coronae Borealis (F6V+G0V Porb=1.14 days) with the Very Large Array, the Extreme Ultraviolet Explorer, and the Chandra X-Ray Observatory High-Energy Transmission Grating Spectrometer. The radio emission is consistent with previously determined quiescent gyrosynchrotron properties. Multiple flares were seen with Extreme Ultraviolet Explorer, five occurring within two consecutive orbital periods. The first of these flares was observed with Chandra. The Chandra observations of σ2 CrB showed no systematic variations of line fluxes, widths, or Doppler shifts with orbital phase, nor any response in line width or offset due to the flare. This is consistent with both stars being equally active coronal emitters. We have developed a self-consistent method of spectral analysis to derive information from the line and continuum emissions concerning the distribution of plasma with temperature and elemental abundances. A bimodal temperature distribution is appropriate for both quiescent and flare intervals, with a stable peak at 6-8 MK and another variable enhancement at higher temperatures, with evidence for significant contribution from temperatures up to 50 MK during the flare, compared to 30 MK during quiescence. The iron abundance is subsolar during quiescence but is enriched by about a factor of 2 during a large flare seen with Chandra. The noble gas elements neon and argon show elevated abundances with respect to iron, but there is no clear evidence for any first ionization potential-based abundance pattern during quiescence or the flare. We have determined coronal electron densities from the helium-like ions O VII, Ne IX, Mg XI, and Si XIII, which imply densities >=1010 cm-3. There is a small enhancement in the electron densities derived for the flare, but it is not statistically significant. We call attention to electron temperature constraints provided by the ratios of 1s2

  17. A novel large-conductance Ca(2+)-activated potassium channel and current in nerve terminals of the rat neurohypophysis.

    PubMed Central

    Wang, G; Thorn, P; Lemos, J R

    1992-01-01

    corresponds most closely to a Ca(2+)-activated K+ current (IK(Ca)) and not to a delayed rectifier or IA-like current. It also has properties different from that of the Ca(2+)-dependent outward current described in the magnocellular neuronal cell bodies of the hypothalamus. 8. A large conductance channel is often observed in isolated rat neurohypophysial nerve terminals. The channel had a unit conductance of 231 pS in symmetrical 150 mM K+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1284313

  18. Continuous, Large-Scale Processing of Seismic Archives for High-Resolution Monitoring of Seismic Activity and Seismogenic Properties

    NASA Astrophysics Data System (ADS)

    Waldhauser, F.; Schaff, D. P.

    2012-12-01

    Archives of digital seismic data recorded by seismometer networks around the world have grown tremendously over the last several decades helped by the deployment of seismic stations and their continued operation within the framework of monitoring earthquake activity and verification of the Nuclear Test-Ban Treaty. We show results from our continuing effort in developing efficient waveform cross-correlation and double-difference analysis methods for the large-scale processing of regional and global seismic archives to improve existing earthquake parameter estimates, detect seismic events with magnitudes below current detection thresholds, and improve real-time monitoring procedures. We demonstrate the performance of these algorithms as applied to the 28-year long seismic archive of the Northern California Seismic Network. The tools enable the computation of periodic updates of a high-resolution earthquake catalog of currently over 500,000 earthquakes using simultaneous double-difference inversions, achieving up to three orders of magnitude resolution improvement over existing hypocenter locations. This catalog, together with associated metadata, form the underlying relational database for a real-time double-difference scheme, DDRT, which rapidly computes high-precision correlation times and hypocenter locations of new events with respect to the background archive (http://ddrt.ldeo.columbia.edu). The DDRT system facilitates near-real-time seismicity analysis, including the ability to search at an unprecedented resolution for spatio-temporal changes in seismogenic properties. In areas with continuously recording stations, we show that a detector built around a scaled cross-correlation function can lower the detection threshold by one magnitude unit compared to the STA/LTA based detector employed at the network. This leads to increased event density, which in turn pushes the resolution capability of our location algorithms. On a global scale, we are currently building

  19. An integrated approach for monitoring efficiency and investments of activated sludge-based wastewater treatment plants at large spatial scale.

    PubMed

    De Gisi, Sabino; Sabia, Gianpaolo; Casella, Patrizia; Farina, Roberto

    2015-08-01

    WISE, the Water Information System for Europe, is the web-portal of the European Commission (EU) that disseminates the quality state of the receiving water bodies and the efficiency of the municipal wastewater treatment plants (WWTPs) in order to monitor advances in the application of both the Water Framework Directive (WFD) as well as the Urban Wastewater Treatment Directive (UWWTD). With the intention to develop WISE applications, the aim of the work was to define and apply an integrated approach capable of monitoring the efficiency and investments of activated sludge-based WWTPs located in a large spatial area, providing the following outcomes useful to the decision-makers: (i) the identification of critical facilities and their critical processes by means of a Performance Assessment System (PAS), (ii) the choice of the most suitable upgrading actions, through a scenario analysis. (iii) the assessment of the investment costs to upgrade the critical WWTPs and (iv) the prioritization of the critical facilities by means of a multi-criteria approach which includes the stakeholders involvement, along with the integration of some technical, environmental, economic and health aspects. The implementation of the proposed approach to a high number of municipal WWTPs highlighted how the PAS developed was able to identify critical processes with a particular effectiveness in identifying the critical nutrient removal ones. In addition, a simplified approach that considers the cost related to a basic-configuration and those for the WWTP integration, allowed to link the critical processes identified and the investment costs. Finally, the questionnaire for the acquisition of data such as that provided by the Italian Institute of Statistics, the PAS defined and the database on the costs, if properly adapted, may allow for the extension of the integrated approach on an EU-scale by providing useful information to water utilities as well as institutions.

  20. Rectifying conductance substates in a large conductance Ca(2+)- activated K+ channel: evidence for a fluctuating barrier mechanism

    PubMed Central

    1996-01-01

    In this study, we investigated the mechanism underlying the production of inwardly rectifying subconductance states induced in large conductance Ca(2+)-activated K+ channels (maxi K(Ca) channels) by the small, homologous proteins, bovine pancreatic trypsin inhibitor (BPTI) and dendrotoxin-I (DTX). Low-resolution bilayer recordings of BPTI- induced substates display excess noise that is well described by a beta- distribution characteristic of a filtered, two-state process. High- resolution patch recordings of maxi K(Ca) channels from vascular smooth muscle cells confirm that the BPTI-induced substate is actually comprised of rapid, voltage-dependent transitions between the open state and a nearly closed state. Patch recordings of DTX-induced substates also exhibit excess noise consistent with a similar two-state fluctuation process that occurs at rates faster than those measured for the BPTI-induced substate. The results indicate that these examples of ligand-induced substates originate by a fluctuating barrier mechanism that is similar to one class of models proposed by Dani, J.A., and J.A. Fox (1991. J. Theor. Biol. 153: 401-423) to explain subconductance behavior of ion channels. To assess the general impact of such rapid fluctuations on the practical measurement of unitary currents by amplitude histograms, we simulated single-channel records for a linear, three-state scheme of C (closed)-O(open)-S(substate). This simulation defines a range of transition rates relative to filter frequency where rapid fluctuations can lead to serious underestimation of actual unitary current levels. On the basis of these experiments and simulations, we conclude that fluctuating barrier processes and open channel noise may play an important physiological role in the modulation of ion permeation. PMID:8741730

  1. Ca2+-dependent gating mechanisms for dSlo, a large-conductance Ca2+-activated K+ (BK) channel.

    PubMed Central

    Moss, B L; Silberberg, S D; Nimigean, C M; Magleby, K L

    1999-01-01

    The Ca2+-dependent gating mechanism of cloned BK channels from Drosophila (dSlo) was studied. Both a natural variant (A1/C2/E1/G3/IO) and a mutant (S942A) were expressed in Xenopus oocytes, and single-channel currents were recorded from excised patches of membrane. Stability plots were used to define stable segments of data. Unlike native BK channels from rat skeletal muscle in which increasing internal Ca2+ concentration (Cai2+) in the range of 5 to 30 microM increases mean open time, increasing Cai2+ in this range for dSlo had little effect on mean open time. However, further increases in Cai2+ to 300 or 3000 microM then typically increased dSlo mean open time. Kinetic schemes for the observed Ca2+-dependent gating kinetics of dSlo were evaluated by fitting two-dimensional dwell-time distributions using maximum likelihood techniques and by comparing observed dependency plots with those predicted by the models. Previously described kinetic schemes that largely account for the Ca2+-dependent kinetics of native BK channels from rat skeletal muscle did not adequately describe the Ca2+ dependence of dSlo. An expanded version of these schemes which, in addition to the Ca2+-activation steps, permitted a Ca2+-facilitated transition from each open state to a closed state, could approximate the Ca2+-dependent kinetics of dSlo, suggesting that Ca2+ may exert dual effects on gating. PMID:10354435

  2. Increased Expression of the Large Conductance, Calcium-Activated K+ (BK) Channel in Adult-Onset Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Donnelier, Julien; Braun, Samuel T.; Dolzhanskaya, Natalia; Ahrendt, Eva; Braun, Andrew P.; Velinov, Milen; Braun, Janice E. A.

    2015-01-01

    Cysteine string protein (CSPα) is a presynaptic J protein co-chaperone that opposes neurodegeneration. Mutations in CSPα (i.e., Leu115 to Arg substitution or deletion (Δ) of Leu116) cause adult neuronal ceroid lipofuscinosis (ANCL), a dominantly inherited neurodegenerative disease. We have previously demonstrated that CSPα limits the expression of large conductance, calcium-activated K+ (BK) channels in neurons, which may impact synaptic excitability and neurotransmission. Here we show by western blot analysis that expression of the pore-forming BKα subunit is elevated ~2.5 fold in the post-mortem cortex of a 36-year-old patient with the Leu116∆ CSPα mutation. Moreover, we find that the increase in BKα subunit level is selective for ANCL and not a general feature of neurodegenerative conditions. While reduced levels of CSPα are found in some postmortem cortex specimens from Alzheimer’s disease patients, we find no concomitant increase in BKα subunit expression in Alzheimer’s specimens. Both CSPα monomer and oligomer expression are reduced in synaptosomes prepared from ANCL cortex compared with control. In a cultured neuronal cell model, CSPα oligomers are short lived. The results of this study indicate that the Leu116∆ mutation leads to elevated BKα subunit levels in human cortex and extend our initial work in rodent models demonstrating the modulation of BKα subunit levels by the same CSPα mutation. While the precise sequence of pathogenic events still remains to be elucidated, our findings suggest that dysregulation of BK channels may contribute to neurodegeneration in ANCL. PMID:25905915

  3. Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization

    SciTech Connect

    Zhao, Chumin; Kanicki, Jerzy; Konstantinidis, Anastasios C.; Patel, Tushita

    2015-11-15

    Purpose: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50–300 e{sup −}) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). Methods: In this study, imaging performance of a large area (29 × 23 cm{sup 2}) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165–400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. Results: The LFW mode shows better DQE at low air kerma (K{sub a} < 10 μGy) and should be used for DBT. At current DBT applications, air kerma (K{sub a} ∼ 10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165–400 μm in size can be resolved using a MGD range of 0.3–1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at

  4. Equol increases cerebral blood flow in rats via activation of large-conductance Ca(2+)-activated K(+) channels in vascular smooth muscle cells.

    PubMed

    Yu, Wei; Wang, Yan; Song, Zheng; Zhao, Li-Mei; Li, Gui-Rong; Deng, Xiu-Ling

    2016-05-01

    The present study was designed to investigate the effect of equol on cerebral blood flow and the underlying molecular mechanisms. The regional cerebral blood flow in parietal lobe of rats was measured by using a laser Doppler flowmetry. Isolated cerebral basilar artery and mesenteric artery rings from rats were used for vascular reactivity measurement with a multi wire myography system. Outward K(+) current in smooth muscle cells of cerebral basilar artery, large-conductance Ca(2+)-activated K(+) (BK) channel current in BK-HEK 293 cells stably expressing both human α (hSlo)- and β1-subunits, and hSlo channel current in hSlo-HEK 293 cells expressing only the α-subunit of BK channels were recorded with whole cell patch-clamp technique. The results showed that equol significantly increased regional cerebral blood flow in rats, and produced a concentration-dependent but endothelium-independent relaxation in rat cerebral basilar arteries. Both paxilline and iberiotoxin, two selective BK channel blockers, significantly inhibited equol-induced vasodilation in cerebral arteries. Outward K(+) currents in smooth muscle cells of cerebral basilar artery were increased by equol and fully reversed by washout or blockade of BK channels with iberiotoxin. Equol remarkably enhanced human BK current in BK-HEK 293 cells, but not hSlo current in hSlo-HEK 293 cells, and the increase was completely abolished by co-application of paxilline. Our findings provide the first information that equol selectively stimulates BK channel current by acting on its β1 subunit, which may in turn contribute to the equol-mediated vasodilation and cerebral blood flow increase.

  5. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

    PubMed

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  6. Time evolution of damage due to environmentally assisted aging in a fiber bundle model

    NASA Astrophysics Data System (ADS)

    Lennartz-Sassinek, S.; Main, I. G.; Danku, Z.; Kun, F.

    2013-09-01

    Damage growth in composite materials is a complex process which is of interest in many fields of science and engineering. We consider this problem in a fiber bundle model where fibers undergo an aging process due to the accumulation of damage driven by the locally acting stress in a chemically active environment. By subjecting the bundle to a constant external load, fibers fail either when the load on them exceeds their individual intrinsic strength or when the accumulated internal damage exceeds a random threshold. We analyze the time evolution of the breaking process under low external loads where aging of fibers dominates. In the mean field limit, we show analytically that the aging system continuously accelerates in a way which can be characterized by an inverse power law of the event rate with a singularity that defines a failure time. The exponent is not universal; it depends on the details of the aging process. For localized load sharing, a more complex damage process emerges which is dominated by distinct spatial regions of the system with different degrees of stress concentration. Analytical calculations revealed that the final acceleration to global failure is preceded by a stationary accumulation of damage. When the disorder is strong, the accelerating phase has the same functional behavior as in the mean field limit. The analytical results are verified by computer simulations.

  7. Process for preparing multilayer enzyme coating on a fiber

    DOEpatents

    Kim, Jungbae; Kwak, Ja Hun; Grate, Jay W.

    2009-11-03

    A process for preparing high stability, high activity biocatalytic materials is disclosed and processes for using the same. The process involves coating of a material or fiber with enzymes and enzyme aggregate providing a material or fiber with high biocatalytic activity and stability useful in heterogeneous environments. In one illustrative approach, enzyme "seeds" are covalently attached to polymer nanofibers followed by treatment with a reagent that crosslinks additional enzyme molecules to the seed enzymes forming enzyme aggregates thereby improving biocatalytic activity due to increased enzyme loading and enzyme stability. This approach creates a useful new biocatalytic immobilized enzyme system with potential applications in bioconversion, bioremediation, biosensors, and biofuel cells.

  8. Fall Chinook Salmon Spawning Activity Versus Daylight and Flow in the Tailrace of a Large Hydroelectric Dam

    SciTech Connect

    McMichael, Geoffrey A.; McKinstry, Craig A.; Vucelick, Jessica A.; Lukas, Joe

    2005-05-01

    We deployed an acoustic system during the fall Chinook salmon (Oncorhynchus tshawytscha) spawning season in 2001 to determine whether fall Chinook salmon spawning activity in a hydroelectric dam tailrace area was affected by daylight or river flow dynamics. The system was deployed following a randomized study design to record fall Chinook salmon spawning activity during day and night periods in two index areas downstream of Wanapum Dam on the Columbia River in Washington, USA. One index area was a deepwater spawning area located (river kilometer (rkm) 663) in 9 to 11 m of water. The other index site was a moderate depth mid-channel bar, where water depths ranged from 2.5 to 6 m. The acoustic system was used to collect spawning activity data during free-drifts in a boat through the index areas. Spawning activity was defined as digs per minute from underwater sound recordings. Fall Chinook salmon spawning activity in the Wanapum Dam tailrace was influenced by daylight and river discharge. Results showed there was a substantial amount of spawning activity occurring during both daylight and darkness. However, there was significantly more spawning activity during daylight than at night in both index areas. Spawning activity was also affected by flow. Project discharge had a pronounced non-linear effect on spawning activity. Spawning activity was generally highest at project discharges between 1,700 and 2266 m3 sec-1 in both spawning areas, with reduced activity as discharge increased to between 3,400 and 4,250 m3 sec-1. We concluded that fall Chinook salmon spawning activity in highly variable environments was affected more by flow (and velocity) than by daylight.

  9. Remote-controlled delivery of CO via photoactive CO-releasing materials on a fiber optical device.

    PubMed

    Gläser, Steve; Mede, Ralf; Görls, Helmar; Seupel, Susanne; Bohlender, Carmen; Wyrwa, Ralf; Schirmer, Sina; Dochow, Sebastian; Reddy, Gandra Upendar; Popp, Jürgen; Westerhausen, Matthias; Schiller, Alexander

    2016-08-16

    Although carbon monoxide (CO) delivery materials (CORMAs) have been generated, remote-controlled delivery with light-activated CORMAs at a local site has not been achieved. In this work, a fiber optic-based CO delivery system is described in which the photoactive and water insoluble CO releasing molecule (CORM) manganese(i) tricarbonyl [(OC)3Mn(μ3-SR)]4 (R = nPr, 1) has been non-covalently embedded into poly(l-lactide-co-d/l-lactide) and poly(methyl methacrylate) non-woven fabrics via the electrospinning technique. SEM images of the hybrid materials show a porous fiber morphology for both polymer supports. The polylactide non-woven fabric was attached to a fiber optical device. In combination with a laser irradiation source, remote-controlled and light-triggered CO release at 405 nm excitation wavelength was achieved. The device enabled a high flexibility of the spatially and timely defined application of CO with the biocompatible hybrid fabric in aqueous media. The rates of liberated CO were adjusted with the light intensity of the laser. CO release was confirmed via ATR-IR spectroscopy, a portable electrochemical CO sensor and a heterogeneous myoglobin assay.

  10. Assessing the Feasibility of Large-Scale Countercyclical Public Job-Creation. Final Report, Volume II. Activities Suitable for Public Job-Creation and Their Characteristics.

    ERIC Educational Resources Information Center

    Urban Inst., Washington, DC.

    This second of a three-volume report of a study done to assess the feasibility of large-scale, countercyclical public job creation contains chapter 2 of the report on the methods and findings with respect to job-creating activities, their job-creation potential, and related characteristics. (Volume 1, comprised of the report's first chapter,…

  11. Health-Related Fitness Knowledge and Its Relation to Student Physical Activity Patterns at a Large U.S. Southern State University

    ERIC Educational Resources Information Center

    Keating, Xiaofen D.; Castro-Pinero, Jose; Centeio, Erin; Harrison, Louis, Jr.; Ramirez, Tere; Chen, Li

    2010-01-01

    This study examined student health-related fitness (HRF) knowledge and its relationship to physical activity (PA). The participants were undergraduate students from a large U.S. state university. HRF knowledge was assessed using a test consisting of 150 multiple choice items. Differences in HRF knowledge scores by sex, ethnicity, and years in…

  12. Psychometric Evaluation of the Behavioral Inhibition/Behavioral Activation Scales in a Large Sample of Outpatients With Anxiety and Mood Disorders

    ERIC Educational Resources Information Center

    Campbell-Sills, Laura; Liverant, Gabrielle I.; Brown, Timothy A.

    2004-01-01

    The latent structure, reliability, and validity of the Behavioral Inhibition/Behavioral Activation Scales (BIS/BAS; C. L. Carver & T. L. White, 1994) were examined in a large sample of outpatients (N = 1,825) with anxiety and mood disorders. Four subsamples were used for exploratory and confirmatory factor analyses. In addition to generally…

  13. [The changes of the activity of NO-synthases and oxidative processes under conditions of 5-HT receptors activation in the stomach and large intestine in streptozocin-induced diabetes mellitus].

    PubMed

    Skliarov, O Ia; Detsyk, O I

    2012-01-01

    We investigated the activity of NO-synthases, lipoperoxidation processes, antioxidant defense enzymes in the muscular layers of stomach and large intestine. The L-arginine concentration in blood plasma was also monitored under conditions of 2-weeks activation of 5-HT4 receptors by mosaprid in streptozocin-induced diabetes mellitus. We showed that the onset of diabetes mellitus is accompanied by a 2.4-2.8-fold increase in the activity of inducible NO-synthase and a 23-40% increase in the SOD activity. The nitric oxide content and TBA products in the muscular layers of stomach and large intestine were increased, whereas the motor-evacuational function of the stomach and large intestine decreased. Activation of 5-HT4 receptors by mosaprid under conditions of diabetes mellitus decreased the activity of inducible NO-synthase, the lipoperoxidation processes, nitrite anion content and TBA products in muscular layers of stomach and large intestine by 23%. At the same time, we observed an increase in the motor-evacuational function of stomach and large intestine without affecting the blood sugar level.

  14. Construct Validity Evidence for Single-Response Items to Estimate Physical Activity Levels in Large Sample Studies

    ERIC Educational Resources Information Center

    Jackson, Allen W.; Morrow, James R., Jr.; Bowles, Heather R.; FitzGerald, Shannon J.; Blair, Steven N.

    2007-01-01

    Valid measurement of physical activity is important for studying the risks for morbidity and mortality. The purpose of this study was to examine evidence of construct validity of two similar single-response items assessing physical activity via self-report. Both items are based on the stages of change model. The sample was 687 participants (men =…

  15. Creating an Environment Conducive to Active and Collaborative Learning: Redesigning Introduction to Sociology at a Large Research University

    ERIC Educational Resources Information Center

    Lo, C. C.; Prohaska, A.

    2011-01-01

    In 2003 a Southeastern research university undertook the redesign of an introductory sociology course in order to improve student success by adding active and collaborative learning activities that gave students greater responsibility for learning. The new "hybrid" course provides most course materials online, requires electronic…

  16. Implementing Distance Teaching at a Large Scale in Medical Education: A Struggle between Dominant and Non-Dominant Teaching Activities

    ERIC Educational Resources Information Center

    Pettersson, Fanny; Olofsson, Anders D.

    2015-01-01

    This paper examines possibilities and challenges when implementing distance teaching of theoretical content in a regionalized medical program (RMP). It will be argued that Cultural-Historical Activity Theory (CHAT) and the concepts of dominant and non-dominant activities, including conflicts and transitional actions, can lead to an understanding…

  17. The large-leaved Kudingcha (Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng): a traditional Chinese tea with plentiful secondary metabolites and potential biological activities.

    PubMed

    Li, Li; Xu, Li J; Ma, Gui Z; Dong, Yin M; Peng, Yong; Xiao, Pei G

    2013-07-01

    In China, Kudingcha has been used for almost 2,000 years as a tea to quench thirst, remove phlegm, refresh the mind, and improve eyesight. The group of large-leaved Kudingcha is coveted for its potential effects on lipid metabolism, which are attributed to the presence of characteristic ingredients. This contribution reviews studies from the past few decades regarding the plant characteristics, ethnobotanical usages, chemical constituents, and related biological activities of the large-leaved Kudingcha (Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng). Triterpenoids, phenolic acids, flavonoids, and essential oils are the main metabolites in the large-leaved Kudingcha, and these ingredients protect the vascular system, regulate lipid metabolism, and have antioxidant, hypoglycemic, and anti-tumor effects. Moreover, large-leaved Kudingcha shares several properties with the popular green tea and the Yerba maté from South America.

  18. Examining the Content of Head Start Teachers' Literacy Instruction within Two Activity Contexts during Large-Group Circle Time

    ERIC Educational Resources Information Center

    Zhang, Chenyi; Diamond, Karen E.; Powell, Douglas R.

    2015-01-01

    Large-group circle time is an important component of many preschool classrooms' daily schedules. This study scrutinized the teaching content of Head Start teachers' literacy instruction (i.e., the types of literacy concept embedded within the instruction, lexical characteristics of teachers' talk, and elaborations on literacy knowledge) in two…

  19. Piloting a fiber optics and electronic theory curriculum with high school students

    NASA Astrophysics Data System (ADS)

    Gilchrist, Pamela O.; Carpenter, Eric D.; Gray-Battle, Asia

    2014-07-01

    Previous participants from a multi-year blended learning intervention focusing on science, technology, engineering and mathematics (STEM) content knowledge, technical, college, and career preparatory skills were recruited to pilot a new module designed by the project staff. Participants met for a total of 22 contact hours receiving lectures from staff and two guest speakers from industries relevant to photonics, fiber optics hands-on experimentation, and practice with documenting progress. Activities included constructing a fiber optics communication system, troubleshooting breadboard circuits and diagrammed circuits as well as hypothesis testing to discover various aspects of fiber optic cables. Participants documented their activities, wrote reflections on the content and learning endeavor and gave talks about their research experiences to staff, peers, and relatives during the last session. Overall, it was found that a significant gain in content knowledge occurred between the time of pre-testing (Mean=0.54) and post-testing time points for the fiber optics portion of the curriculum via the use of a paired samples t-test (Mean=0.71), t=-2.72, p<.05. Additionally, the electronic theory test results were not a normal distribution and for this reason non-parametric testing was used, specifically a Wilcoxon signed-ranks test. Results indicated a significant increase in content knowledge occurred over time between the pre- (Mdn=0.35) and post-testing time points (Mdn=0.80) z=-2.49, p<,05, r=-0.59 for the electronic theory portion of the curriculum. An equivalent control group was recruited from the remaining participant pool, allowing for comparison between groups. The program design, findings, and lessons learned will be reported in this paper.

  20. Effect of High N-Acetylcysteine Concentrations on Antibiotic Activity against a Large Collection of Respiratory Pathogens

    PubMed Central

    Landini, Giulia; Di Maggio, Tiziana; Sergio, Francesco; Docquier, Jean-Denis; Rossolini, Gian Maria

    2016-01-01

    The effect of high N-acetylcysteine (NAC) concentrations (10 and 50 mM) on antibiotic activity against 40 strains of respiratory pathogens was investigated. NAC compromised the activity of carbapenems (of mostly imipenem and, to lesser extents, meropenem and ertapenem) in a dose-dependent fashion. We demonstrated chemical instability of carbapenems in the presence of NAC. With other antibiotics, 10 mM NAC had no major effects, while 50 mM NAC sporadically decreased (ceftriaxone and aminoglycosides) or increased (penicillins) antibiotic activity. PMID:27736757

  1. Small-scale and large-scale testing of photo-electrochemically activated leaching technology in Aprelkovo and Delmachik Mines

    NASA Astrophysics Data System (ADS)

    Sekisov, AG; Lavrov, AYu; Rubtsov, YuI

    2017-02-01

    The paper gives a description of tests and trials of the technology of heap gold leaching from rebellious ore in Aprelkovo and Delmachik Mines. Efficiency of leaching flowsheets with the stage-wise use of activated solutions of different reagents, including active forms of oxygen, is evaluated. Carbonate–peroxide solutions are used at the first stage of leaching to oxidize sulfide and sulfide–arsenide ore minerals to recover iron and copper from them. The second stage leaching uses active cyanide solutions to leach encapsulated and disperse gold and silver.

  2. Isolated spinach ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit .sup..epsilon. N-methyltransferase and method of inactivating ribulose-1,5-bisphosphatase carboxylase/oxygenase large subunit .sup..epsilon. N-methyltransferase activity

    DOEpatents

    Houtz, Robert L.

    1999-01-01

    The gene sequence for ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS) .sup..epsilon. N-methyltransferase (protein methylase III or Rubisco LSMT) from a plant which has a des(methyl) lysyl residue in the LS is disclosed. In addition, the full-length cDNA clones for Rubisco LSMT are disclosed. Transgenic plants and methods of producing same which have the Rubisco LSMT gene inserted into the DNA are also provided. Further, methods of inactivating the enzymatic activity of Rubisco LSMT are also disclosed.

  3. Micromachining of a fiber-to-waveguide coupler using grayscale lithography and through-wafer etch

    NASA Astrophysics Data System (ADS)

    Dillon, Thomas; Zablocki, Mathew; Shi, Shouyan; Murakowski, Janusz; Prather, Dennis

    2008-02-01

    For some time, the micro-optics and photonics fields have relied on fabrication processes and technology borrowed from the well-established silicon integrated circuit industry. However, new fabrication methodologies must be developed for greater flexibility in the machining of micro-optic devices. To this end, we have explored grayscale lithography as an enabler for the realization of such devices. This process delivers the ability to sculpt materials arbitrarily in three dimensions, thus providing the flexibility to realize optical surfaces to shape, transform, and redirect the propagation of light efficiently. This has opened the door for new classes of optical devices. As such, we present a fiber-to-waveguide coupling structure utilizing a smoothly contoured lensing surface in the device layer of a silicon-on insulator (SOI) wafer, fabricated using grayscale lithography. The structure collects light incident normally to the wafer from a singlemode optical fiber plugged through the back surface and turns the light into the plane of the device layer, focusing it into a single-mode waveguide. The basis of operation is total internal reflection, and the device therefore has the potential advantages of providing a large bandwidth, low polarization sensitivity, high efficiency, and small footprint. The structure was optimized with a simulated annealing algorithm in conjunction with two-dimensional finite-difference time-domain (FDTD) simulation accelerated on the graphics processing unit (GPU), and achieves a theoretical efficiency of approximately seventy percent, including losses due to Fresnel reflection from the oxide/silicon interface. Initial fabrication results validate the principle of operation. We discuss the grayscale fabrication process as well as the through-wafer etch for mechanical stabilization and alignment of the optical fiber to the coupling structure. Refinement of the through-wafer etch process for high etch rate and appropriate sidewall taper are

  4. Characterisation of the large-scale production process of oyster mushroom (Pleurotus ostreatus) with the analysis of succession and spatial heterogeneity of lignocellulolytic enzyme activities.

    PubMed

    Bánfi, Renáta; Pohner, Zsuzsanna; Kovács, József; Luzics, Szabina; Nagy, Adrienn; Dudás, Melinda; Tanos, Péter; Márialigeti, Károly; Vajna, Balázs

    2015-12-01

    Oyster mushroom (Pleurotus ostreatus) lignocellulolytic enzyme activity pattern and variation was investigated in a large-scale facility from spawning until the end of the second flush. In the first cultivation cycle laccase production reached its peak during vegetative growth stage, while manganese-peroxidase showed the highest activity during fruiting body induction. Cellulose and hemicellulose degrading enzymes had maximal activity at the beginning of flush and harvest stage. The enzyme activities showed similar tendencies among five different mushroom substrate blocks representing a production house. The spatial variability analysis of enzyme activities pointed out the within substrate block heterogeneity as the main source if variation. This result was confirmed by Combined Cluster and Discriminant Analysis (CCDA) method showing minimal among block heterogeneity considering the whole investigation period; furthermore in the first cultivation cycle all blocks were grouped into one cluster.

  5. A Fiber-Optic Borehole Seismic Vector Sensor System for Geothermal Site Characterization and Monitoring

    SciTech Connect

    Paulsson, Bjorn N.P.; Thornburg, Jon A; He, Ruiqing

    2015-04-21

    Seismic techniques are the dominant geophysical techniques for the characterization of subsurface structures and stratigraphy. The seismic techniques also dominate the monitoring and mapping of reservoir injection and production processes. Borehole seismology, of all the seismic techniques, despite its current shortcomings, has been shown to provide the highest resolution characterization and most precise monitoring results because it generates higher signal to noise ratio and higher frequency data than surface seismic techniques. The operational environments for borehole seismic instruments are however much more demanding than for surface seismic instruments making both the instruments and the installation much more expensive. The current state-of-the-art borehole seismic instruments have not been robust enough for long term monitoring compounding the problems with expensive instruments and installations. Furthermore, they have also not been able to record the large bandwidth data available in boreholes or having the sensitivity allowing them to record small high frequency micro seismic events with high vector fidelity. To reliably achieve high resolution characterization and long term monitoring of Enhanced Geothermal Systems (EGS) sites a new generation of borehole seismic instruments must therefore be developed and deployed. To address the critical site characterization and monitoring needs for EGS programs, US Department of Energy (DOE) funded Paulsson, Inc. in 2010 to develop a fiber optic based ultra-large bandwidth clamped borehole seismic vector array capable of deploying up to one thousand 3C sensor pods suitable for deployment into ultra-high temperature and high pressure boreholes. Tests of the fiber optic seismic vector sensors developed on the DOE funding have shown that the new borehole seismic sensor technology is capable of generating outstanding high vector fidelity data with extremely large bandwidth: 0.01 – 6,000 Hz. Field tests have shown

  6. The large-scale magnetic field in the solar wind. [interplanetary magnetic fields/solar activity effects

    NASA Technical Reports Server (NTRS)

    Burlaga, L. F.; Ness, N. F.

    1975-01-01

    A large-scale, three dimensional magnetic field in the interplanetary medium with an expected classical spiral pattern to zeroth order is discussed. Systematic and random deviations which are expected are treated. The sector structure which should be evident at high latitudes is examined. Interplanetary streams are discussed as determining the patterns of magnetic field intensity. It was proposed that the large-scale spiral field can induce a meridional flow which might alter the field geometry somewhat. The nonuniformities caused by streams will probably significantly influence the motion of solar and galactic particles. It was concluded that knowledge of the 3-dimensional field and its dynamical effects can be obtained by in situ measurements by a probe which goes over the sun's poles. Diagrams of the magnetic fields are given.

  7. Matrix-dominated mechanical properties of a fiber composite lamina

    SciTech Connect

    Lyon, R.E.; Schumann, D.L.; DeTeresa, S.J.

    1992-05-18

    Matrix-dominated mechanical properties of unidirectional fiber composite laminae were determined from hoop-wound tube specimens and cylindrical rods fabricated from both wet-filament winding and prepreg material systems. Longitudinal shear modulus and strength as well as transverse Young's modulus, transverse tensile strength, and transverse compressive strength were obtained from a thin-walled tube specimen using a new fixturing design. Lamina properties are presented for several carbon fiber/epoxy composite materials. Longitudinal shear moduli were measured for both tubes and rods in torsion. Results obtained in the linear-elastic regimes above and below the glass transition temperature (Tg) of the matrix phase were compared with micromechanics predictions. Although agreement between predicted and measured shear moduli was reasonable below Tg, large discrepancies were observed when the matrix phase was elastomeric.

  8. Matrix-dominated mechanical properties of a fiber composite lamina

    SciTech Connect

    Lyon, R.E.; Schumann, D.L.; DeTeresa, S.J.

    1992-05-18

    Matrix-dominated mechanical properties of unidirectional fiber composite laminae were determined from hoop-wound tube specimens and cylindrical rods fabricated from both wet-filament winding and prepreg material systems. Longitudinal shear modulus and strength as well as transverse Young`s modulus, transverse tensile strength, and transverse compressive strength were obtained from a thin-walled tube specimen using a new fixturing design. Lamina properties are presented for several carbon fiber/epoxy composite materials. Longitudinal shear moduli were measured for both tubes and rods in torsion. Results obtained in the linear-elastic regimes above and below the glass transition temperature (Tg) of the matrix phase were compared with micromechanics predictions. Although agreement between predicted and measured shear moduli was reasonable below Tg, large discrepancies were observed when the matrix phase was elastomeric.

  9. Fiber optic liquid leak detection technique with an ultrasonic actuator and a fiber Bragg grating.

    PubMed

    Lee, Jung-Ryul; Tsuda, Hiroshi

    2005-12-15

    We present a technique for liquid leak detection in which ultrasonic and optical waves are introduced into a fiber simultaneously. The system is based on an ultrasonic technique using an ultrasonic actuator and a fiber Bragg grating receiver. A fiber-guided ultrasonic wave is utilized to stress the fiber Bragg grating, which is remote from the ultrasonic transmitter. When the traveling ultrasonic wave encounters a liquid, part of the wave will leak out from the fiber, which results in an ultrasonic strain decrease in the fiber Bragg grating. The ultrasonic wave and its attenuation are detected by the light variation of a narrowband laser source reflected and transmitted from the fiber Bragg grating, and the amplitude variation of the ultrasound can eventually be correlated with the fiber area coupled with the liquid.

  10. Uncertainty induced by chest wall thickness assessment methods on lung activity estimation for plutonium and americium: a large population-based study.

    PubMed

    Broggio, D; Lechaftois, X; Franck, D

    2015-03-01

    In vivo lung counting aims at assessing the retained activity in the lungs. The calibration factor relating the measured counts to the worker's specific retained lung activity can be obtained by several means and strongly depends on the chest wall thickness. Here we compare, for 374 male nuclear workers, the activity assessed with a reference protocol, where the material equivalent chest wall thickness is known from ultrasound measurements, with two other protocols. The counting system is an array of four germanium detectors.It is found that non site-specific equations for the assessment of the chest wall thickness induce large biases in the assessment of activity. For plutonium isotopes or (241)Am the proportion of workers for whom the retained activity is within ± 10% of the reference one is smaller than 10%.The use of site-specific equations raises this proportion to 20% and 58% for plutonium and (241)Am, respectively.Finally, for the studied population, when site-specific equations are used for the chest wall thickness, the standard uncertainties for the lung activity are 42% and 12.5%, for plutonium and (241)Am, respectively. Due to the relatively large size of the studied population, these values are a relatively robust estimate of the uncertainties due to the assessment of the chest wall thickness for the current practice at this site.

  11. Monolithic active quenching and picosecond timing circuit suitable for large-area single-photon avalanche diodes.

    PubMed

    Gallivanoni, A; Rech, I; Resnati, D; Ghioni, M; Cova, S

    2006-06-12

    A new integrated active quenching circuit (i-AQC) designed in a standard CMOS process is presented, capable of operating with any available single photon avalanche diode (SPAD) over wide temperature range. The circuit is suitable for attaining high photon timing resolution also with wide-area SPADs. The new i-AQC integrates the basic active-quenching loop, a patented low-side timing circuit comprising a fast pulse pick-up scheme that substantially improves time-jitter performance, and a novel active-load passive quenching mechanism (consisting of a current mirror rather than a traditional high-value resistor) greatly improves the maximum counting rate. The circuit is also suitable for portable instruments, miniaturized detector modules and SPAD-array detectors. The overall features of the circuit may open the way to new developments in diversified applications of time-correlated photon counting in life sciences and material sciences.

  12. Host range and cell cycle activation properties of polyomavirus large T-antigen mutants defective in pRB binding

    SciTech Connect

    Freund, R.; Bauer, P.H.; Benjamin, T.L.; Crissman, H.A.; Bradbury, E.M. |

    1994-11-01

    The authors have examined the growth properties of polyomavirus large T-antigen mutants that ar unable to bind pRB, the product of the retinoblastoma tumor suppressor gene. These mutants grow poorly on primary mouse cells yet grow well on NIH 3T3 and other established mouse cell lines. Preinfection of primary baby mouse kidney (BMK) epithelial cells with wild-type simian virus 40 renders these cells permissive to growth of pRB-binding polyomavirus mutants. Conversely, NIH 3T3 cells transfected by and expressing wild-type human pRB become nonpermissive. Primary fibroblasts for mouse embryos that carry a homozygous knockout of the RB gene are permissive, while those from normal littermates are nonpermissive. The host range of polyomavirus pRB-binding mutants is thus determined by expression or lack of expression of functional pRB by the host. These results demonstrate the importance of pRB binding by large T antigen for productive viral infection in primary cells. Failure of pRB-binding mutants to grow well in BMK cells correlates with their failure to induce progression from G{sub 0} or G{sub 1} through the S phase of the cell cycle. Time course studies show delayed synthesis and lower levels of accumulation of large T antigen, viral DNA, and VP1 in mutant compared with wild-type virus-infected BMK cells. These results support a model in which productive infection by polyomavirus in normal mouse cells is tightly coupled to the induction and progression of the cell cycle. 48 refs., 6 figs., 5 tabs.

  13. Design of a Fiber Optic Biosensor for Cholesterol Detection in Human Blood

    NASA Astrophysics Data System (ADS)

    Yunianto, M.; Permata, A. N.; Eka, D.; Ariningrum, D.; Wahyuningsih, S.; Marzuki, A.

    2017-02-01

    A fiber optic sensor is to detect the cholesterol content in blood serum-based biosensor using plastic optical fiber that has been designed. The fiber optic sensor designed with sensing area was a fiber optic grated by 5 scratches then given bending treatment by 5 cm. The first test was by UV-Vis spectrometer with linearity of 0.96. The second test was by light spectrometer with linearity in white LED of 0.94. Optical fiber sensors were made to work well on a range of blood serum concentration of 140 mg/dL to 250 mg/dL.

  14. A fiber optic buckle transducer for measurement of in vitro tendon strain

    NASA Astrophysics Data System (ADS)

    Roriz, Paulo; Ramos, António; Marques, Manuel B.; Simões, José A.; Frazão, Orlando

    2015-09-01

    The purpose of the present study is to present a prototype of a fiber optic based buckle transducer suitable for measuring strain caused by stretching of a tendon. The device has an E-shape and its central arm is instrumented with a fiber Bragg grating (FBG) sensor. The tendon adjusts to the E-form in a fashion that when it is stretched the central arm bends causing a shift of the Bragg's wavelength (λB) that is proportional to the amount of strain. This prototype is presented as an alternative to conventional strain gauge (SG) buckle transducers.

  15. Making Large Class Basic Histology Lectures More Interactive: The Use of Draw-Along Mapping Techniques and Associated Educational Activities

    ERIC Educational Resources Information Center

    Kotzé, Sanet Henriët; Mole, Calvin Gerald

    2015-01-01

    At Stellenbosch University, South Africa, basic histology is taught to a combination class of almost 400 first-year medical, physiotherapy, and dietetic students. Many students often find the amount of work in basic histology lectures overwhelming and consequently loose interest. The aim was to determine if a draw-along mapping activity would…

  16. A Novel Active-Learning Protein Purification Exercise for Large-Enrollment Introductory Biochemistry Courses Using the CHROM Web Applet

    ERIC Educational Resources Information Center

    Barrette-Ng, Isabelle H.; Usher, Ken C.

    2013-01-01

    The CHROM Web applet has been used to create a new active-learning exercise in which students design a purification scheme for a recombinant protein using ion-exchange chromatography (IEC). To successfully complete the exercise, students are challenged to apply elementary concepts from acid-base chemistry as well as protein and amino acid…

  17. Using Active Learning Strategies to Investigate Student Learning and Attitudes in a Large Enrollment, Introductory Geology Course

    ERIC Educational Resources Information Center

    Berry, Stacy Jane

    2013-01-01

    There has been an increased emphasis for college instruction to incorporate more active and collaborative involvement of students in the learning process. These views have been asserted by The Association of American Colleges (AAC), the National Science Foundation (NSF), and The National Research Counsel (NRC), which are advocating for the…

  18. Active Vibration Control of a Large Flexible Manipulator by Inertial Force and Joint Torque. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Lee, Soo Han

    1988-01-01

    The efficiency and positional accuracy of a lightweight flexible manipulator are limited by its flexural vibrations, which last after a gross motion is completed. The vibration delays subsequent operations. In the proposed work, the vibration is suppressed by inertial force of a small arm in addition to the joint actuators and passive damping treatment. The proposed approach is: (1) Dynamic modeling of a combined system, a large flexible manipulator and a small arm, (2) Determination of optimal sensor location and controller algorithm, and (3) Verification of the fitness of model and the performance of controller.

  19. A fiber positioner robot for the Gran Telescopio Canarias

    NASA Astrophysics Data System (ADS)

    Azzaro, M.; Becerril, S.; Vilar, C.; Arrillaga, X.; Sánchez, J.; Morales, I.; Carrera, M. A.; Prada, F.

    2010-07-01

    Fiber-fed spectrographs dedicated to observing massive portions of the sky are increasingly being more demanded within the astronomical community. For all the fiber-fed instruments, the primordial and common problem is the positioning of the fiber ends, which must match the position of the objects of a target field on the sky. Amongst the different approaches found in the state of the art, actuator arrays are one of the best. Indeed, an actuator array is able to position all the fiber heads simultaneously, thus making the reconfiguration time extremely short and the instrument efficiency high. The SIDE group* at the Instituto de Astrofisica de Andalucia, together with the industrial company AVS and the University of Barcelona, has been developing an actuator suitable for a large and scalable array. A real-scale prototype has been built and tested in order to validate its innovative design concept, as well as to verify the fulfillment of the mechanical requirements. The present article describes both the concept design and the test procedures and conditions. The main results are shown and a full justification of the validity of the proposed concept is provided.

  20. a Method to Achieve Large Volume, High Accuracy Photogrammetric Measurements Through the Use of AN Actively Deformable Sensor Mounting Platform

    NASA Astrophysics Data System (ADS)

    Sargeant, B.; Robson, S.; Szigeti, E.; Richardson, P.; El-Nounu, A.; Rafla, M.

    2016-06-01

    When using any optical measurement system one important factor to consider is the placement of the sensors in relation to the workpiece being measured. When making decisions on sensor placement compromises are necessary in selecting the best placement based on the shape and size of the object of interest and the desired resolution and accuracy. One such compromise is in the distance the sensors are placed from the measurement surface, where a smaller distance gives a higher spatial resolution and local accuracy and a greater distance reduces the number of measurements necessary to cover a large area reducing the build-up of errors between measurements and increasing global accuracy. This paper proposes a photogrammetric approach whereby a number of sensors on a continuously flexible mobile platform are used to obtain local measurements while the position of the sensors is determined by a 6DoF tracking solution and the results combined to give a single set of measurement data within a continuous global coordinate system. The ability of this approach to achieve both high accuracy measurement and give results over a large volume is then tested and areas of weakness to be improved upon are identified.

  1. Interferometric strain measurements with a fiber-optic probe

    NASA Astrophysics Data System (ADS)

    Burnham-Fay, E. D.; Jacobs-Perkins, D. W.; Ellis, J. D.

    2015-09-01

    Experience at the Laboratory for Laser Energetics has shown that broadband base vibrations make it difficult to position cryogenic inertial confinement fusion targets. These effects must be mitigated for National Ignition Facility-scale targets; to this end an active vibration stabilization system is proposed. A single-mode optical fiber strain probe and a novel fiber contained heterodyne interferometer have been developed as a position feedback sensor for the vibration control system. A resolution limit of 54.5 nƐ; is measured with the optical strain gauge, limited by the lock-in amplifier. Experimental measurements of the sensor that show good agreement with reference resistive strain gauge measurements are presented.

  2. Evidence for daily and weekly rhythmicity but not lunar or seasonal rhythmicity of physical activity in a large cohort of individuals from five different countries

    PubMed Central

    Refinetti, Roberto; Sani, Mamane; Jean-Louis, Girardin; Pandi-Perumal, Seithikurippu R.; Durazo-Arvizu, Ramon A.; Dugas, Lara R.; Kafensztok, Ruth; Bovet, Pascal; Forrester, Terrence E.; Lambert, Estelle V.; Plange-Rhule, Jacob; Luke, Amy

    2015-01-01

    Background Biological rhythmicity has been extensively studied in animals for many decades. Although temporal patterns of physical activity have been identified in humans, no large scale, multi-national study has been published, and no comparison has been attempted of the ubiquity of activity rhythms at different time scales (such as daily, weekly, monthly, and annual). Methods Using individually-worn actigraphy devices, physical activity of 2,328 individuals from five different countries (adults of African descent from Ghana, South Africa, Jamaica, Seychelles, and the United States) was measured for seven consecutive days at different times of the year. Results Analysis for rhythmic patterns identified daily rhythmicity of physical activity in all five of the represented nationalities. Weekly rhythmicity was found in some, but not all, of the nationalities. No significant evidence of lunar rhythmicity or seasonal rhythmicity was found in any of the groups. Conclusions These findings extend previous small-scale observations of daily rhythmicity to a large cohort of individuals from around the world. The findings also confirm the existence of modest weekly rhythmicity but not lunar or seasonal rhythmicity in human activity. These differences in rhythm strength have implications for the management of health hazards of rhythm misalignment. PMID:26402449

  3. STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

    PubMed

    Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

    2015-09-01

    Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

  4. The Kolumbo submarine volcano of Santorini island is a large pool of bacterial strains with antimicrobial activity.

    PubMed

    Bourbouli, Maria; Katsifas, Efstathios A; Papathanassiou, Evangelos; Karagouni, Amalia D

    2015-05-01

    Microbes in hydrothermal vents with their unique secondary metabolism may represent an untapped potential source of new natural products. In this study, samples were collected from the hydrothermal field of Kolumbo submarine volcano in the Aegean Sea, in order to isolate bacteria with antimicrobial activity. Eight hundred and thirty-two aerobic heterotrophic bacteria were isolated and then differentiated through BOX-PCR analysis at the strain level into 230 genomic fingerprints, which were screened against 13 different type strains (pathogenic and nonpathogenic) of Gram-positive, Gram-negative bacteria and fungi. Forty-two out of 176 bioactive-producing genotypes (76 %) exhibited antimicrobial activity against at least four different type strains and were selected for 16S rDNA sequencing and screening for nonribosomal peptide (NRPS) and polyketide (PKS) synthases genes. The isolates were assigned to genus Bacillus and Proteobacteria, and 20 strains harbored either NRPS, PKS type I or both genes. This is the first report on the diversity of culturable mesophilic bacteria associated with antimicrobial activity from Kolumbo area; the extremely high proportion of antimicrobial-producing strains suggested that this unique environment may represent a potential reservoir of novel bioactive compounds.

  5. The expression and activity of 5-LOX in the large intestine of horses harbouring encysted cyathostomin larvae.

    PubMed

    Giacominelli-Stuffler, Roberto; Frangipane di Regalbono, Antonio; Traversa, Donato; Geurden, Thomas; Marcer, Federica; Di Francesco, Andrea; Angelini, Chiara; di Cesare, Angela; Storelli, Maria Maddalena; Maccarrone, Mauro

    2014-06-16

    Leukotrienes are products of the arachidonic acid metabolism and act as potent inflammatory mediators modulating the immune response and various physiological processes. This study evaluated the expression and activity of 5-lipoxygenase (5-LOX), the enzyme that catalyzes the first two steps in the biosynthesis of leukotrienes, in horses infected by larval cyathostomins. Tissue samples from dorsal and ventral colon, and from the cecum were collected from 16 horses slaughtered for human consumption. Samples were analyzed to estimate the burdens of encysted cyathostomin larvae and adult luminal stages, and then processed for the evaluation of biochemical parameters. No significant differences were found in the protein expression and enzymatic activity of 5-LOX between animals harbouring only adult parasites and negative horses. The protein expression and enzyme activity of 5-LOX were significantly higher in horses harbouring encysted larvae in comparison with horses free of encysted larvae. Although preliminary, these results indicate that 5-LOX is an important mediator in the course of horse cyathostominosis and further studies are warranted to unveil the possible role this enzyme plays in the pathogenesis of horse cyathostominosis, and its potential as a diagnostic marker.

  6. Analysis and interpretation of CCD data on P/Halley and physical parameters and activity status of cometary nuclei at large heliocentric distance

    NASA Technical Reports Server (NTRS)

    Belton, Michael J. S.; Mueller, Beatrice

    1991-01-01

    The scientific objectives were as follows: (1) to construct a well sampled photometric time series of comet Halley extending to large heliocentric distances both post and pre-perihelion passage and derive a precise ephemeris for the nuclear spin so that the physical and chemical characteristics of individual regions of activity on the nucleus can be determined; and (2) to extend the techniques in the study of Comet Halley to the study of other cometary nuclei and to obtain new observational data.

  7. Optical and Radar Satellite Remote Sensing for Large Area Analysis of Landslide Activity in Southern Kyrgyzstan, Central Asia

    NASA Astrophysics Data System (ADS)

    Roessner, S.; Behling, R.; Teshebaeva, K. O.; Motagh, M.; Wetzel, H. U.

    2014-12-01

    The presented work has been investigating the potential of optical and radar satellite remote sensing for the spatio-temporal analysis of landslide activity at a regional scale along the eastern rim of the Fergana Basin representing the area of highest landslide activity in Kyrgyzstan. For this purpose a multi-temporal satellite remote sensing database has been established for a 12.000 km2 study area in Southern Kyrgyzstan containing a multitude of optical data acquired during the last 28 years as well as TerraSAR-X and ALOS-PALSAR acquired since 2007. The optical data have been mainly used for creating a multi-temporal inventory of backdated landslide activity. For this purpose an automated approach for object-oriented multi-temporal landslide detection has been developed which is based on the analysis of temporal NDVI-trajectories complemented by relief information to separate landslide-related surface changes from other land cover changes. Applying the approach to the whole study area using temporal high resolution RapidEye time series data has resulted in the automated detection of 612 landslide objects covering a total area of approx. 7.3 km². Currently, the approach is extended to the whole multi-sensor time-series database for systematic analysis of longer-term landslide occurrence at a regional scale. Radar remote sensing has been focussing on SAR Interferometry (InSAR) to detect landslide related surface deformation. InSAR data were processed by repeat-pass interferometry using the DORIS and SARScape software. To better assess ground deformation related to individual landslide objects, InSAR time-series analysis has been applied using the Small Baseline Subset (SBAS) method. Analysis of the results in combination with optical data and DEM information has revealed that most of the derived deformations are caused by slow movements in areas of already existing landslides indicating the reactivation of older slope failures. This way, InSAR analysis can

  8. [Post-marketing clinical safety assessment of Shenmai injection based on active monitoring and passive monitoring in large data background].

    PubMed

    Wang, Lian-xin; Xie, Yan-ming; Ai, Qing-hua; Song, Nian-bin

    2015-12-01

    This paper adopted a series of related analysis methods to comprehensively analyze post-marketing clinical safety data of Shenmai injection from 4,220 cases of SRS and 32,358 cases of multicenter, prospective, registered hospital centralized monitoring in large data background, calculated ADR incidence rate was 0.93 per 1,000, main symptoms of ADR includes chest pain, chills, skin itching, palpitations, fever, nausea, dizziness, vomiting, flushing, numbness, allergic reaction, cyanosis, rash, low back pain, and "breath", "anaphylactoid reaction" and "flush" were the safety warning signals of Shenmai injection. Primary disease for chronic pulmonary heart disease, thyroid disease, and combined with cerebral vascular disease, prior to the injection and continuous use of alprostadil, cyclic adenosine monophosphate, combined with quinolones, penicillins were suspicious influence factors of ADR of Shenmai injection, these promot the clinical safety.

  9. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

    PubMed

    Mahoney, J Matthew; Titiz, Ali S; Hernan, Amanda E; Scott, Rod C

    2016-01-01

    Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation.

  10. CERN-RD39 collaboration activities aimed at cryogenic silicon detector application in high-luminosity Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Li, Zheng; Eremin, Vladimir; Verbitskaya, Elena; Dehning, Bernd; Sapinski, Mariusz; Bartosik, Marcin R.; Alexopoulos, Andreas; Kurfürst, Christoph; Härkönen, Jaakko

    2016-07-01

    Beam Loss Monitors (BLM) made of silicon are new devices for monitoring of radiation environment in the vicinity of superconductive magnets of the Large Hadron Collider. The challenge of BLMs is extreme radiation hardness, up to 1016 protons/cm2 while placed in superfluid helium (temperature of 1.9 K). CERN BE-BI-BL group, together with CERN-RD39 collaboration, has developed prototypes of BLMs and investigated their device physics. An overview of this development-results of the in situ radiation tests of planar silicon detectors at 1.9 K, performed in 2012 and 2014-is presented. Our main finding is that silicon detectors survive under irradiation to 1×1016 p/cm2 at 1.9 K. In order to improve charge collection, current injection into the detector sensitive region (Current Injection Detector (CID)) was tested. The results indicate that the detector signal increases while operated in CID mode.

  11. Prediction of Large Joint Destruction in Patients With Rheumatoid Arthritis Using 18F-FDG PET/CT and Disease Activity Score.

    PubMed

    Suto, Takahito; Okamura, Koichi; Yonemoto, Yukio; Okura, Chisa; Tsushima, Yoshito; Takagishi, Kenji

    2016-02-01

    The assessments of joint damage in patients with rheumatoid arthritis (RA) are mainly restricted to small joints in the hands and feet. However, the development of arthritis in RA patients often involves the large joints, such as the shoulder, elbow, hip, knee, and ankle. Few studies have been reported regarding the degree of large joint destruction in RA patients. F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) visualizes the disease activity in large joints affected by RA. In this study, the associations between destruction of the large joints and the findings of FDG-PET/CT as well as laboratory parameters were investigated, and factors associated with large joint destruction after the administration of biological therapy were identified in RA patients. A total of 264 large joints in 23 RA patients (6 men and 17 women; mean age of 66.9 ± 7.9 years) were assessed in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The extent of FDG uptake in large joints (shoulder, elbow, wrist, hip, knee, and ankle) was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 12 large joints per patient obtained at baseline and after 2 years were assessed according to Larsen's method. A logistic regression analysis was performed to determine the factors most significantly contributing to the progression of joint destruction within 2 years. Radiographic progression of joint destruction was detected in 33 joints. The SUVmax at baseline and 6 months, and the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) at 6, 12, and 24 months were significantly higher in the group with progressive joint destruction. The SUVmax at baseline and DAS28-ESR at 6 months were found to be factors associated with joint destruction at 2 years (P < 0.05). The FDG uptake in the joints with destruction was higher than that observed in the joints

  12. Cocaine Enhances DC to T-cell HIV-1 Transmission by Activating DC-SIGN/LARG/LSP1 Complex and Facilitating Infectious Synapse Formation

    PubMed Central

    Prasad, Anil; Kulkarni, Rutuja; Jiang, Shuxian; Groopman, Jerome E.

    2017-01-01

    DC-SIGN is a dendritic cell surface structure which participates in binding and transmission of HIV-1. Here, for the first time we demonstrate that cocaine induces over expression of DC-SIGN and significantly enhances virus transfer from DCs to T-cells by increasing the binding and internalization of HIV-1 in DCs. We found that cocaine activates a DC-SIGN mediated ‘signalosome’ complex by enhancing its association with LARG and LSP1. Further, LARG was observed to participate in DC-SIGN mediated internalization of HIV-1 in DCs. Intracellular trafficking studies of HIV-1 in cocaine treated DCs revealed increased co-localization of HIV-1 with endosomal or multi vesicular body (MVB) markers such as CD81 and VPS4 and decreased co-localization with the phagolysomal marker LAMP1; this signified altered intracellular trafficking and decreased degradation of HIV-1 in cocaine treated DCs. Furthermore, we found that cocaine induced activation of LARG which in turn activated Rho A and the focal adhesion molecules FAK, Pyk2 and paxillin. This signaling cascade enhanced the formation of an infectious synapse between DCs and T-cells. Our study provides insight into the molecular mechanisms of cocaine’s contribution to key components in HIV pathogenesis and highlights novel targets for interrupting the virus life cycle in substance using hosts. PMID:28094782

  13. The 1.4 A crystal structure of the large and cold-active Vibrio sp. alkaline phosphatase.

    PubMed

    Helland, Ronny; Larsen, Renate Lie; Asgeirsson, Bjarni

    2009-02-01

    Alkaline phosphatase (AP) from the cold-adapted Vibrio strain G15-21 is among the AP variants with the highest known k(cat) value. Here the structure of the enzyme at 1.4 A resolution is reported and compared to APs from E. coli, human placenta, shrimp and the Antarctic bacterium strain TAB5. The Vibrio AP is a dimer although its monomers are without the long N-terminal helix that embraces the other subunit in many other APs. The long insertion loop, previously noted as a special feature of the Vibrio AP, serves a similar function. The surface does not have the high negative charge density as observed in shrimp AP, but a positively charged patch is observed around the active site that may be favourable for substrate binding. The dimer interface has a similar number of non-covalent interactions as other APs and the "crown"-domain is the largest observed in known APs. Part of it slopes over the catalytic site suggesting that the substrates may be small molecules. The catalytic serines are refined with multiple conformations in both monomers. One of the ligands to the catalytic zinc ion in binding site M1 is directly connected to the crown-domain and is closest to the dimer interface. Subtle movements in metal ligands may help in the release of the product and/or facilitate prior dephosphorylation of the covalent intermediate. Intersubunit interactions may be a major factor for promoting active site geometries that lead to the high catalytic activity of Vibrio AP at low temperatures.

  14. Understanding Faculty and Trainee Needs Related to Scholarly Activity in a Large, Nonuniversity Graduate Medical Education Program

    PubMed Central

    Becker, Davida; Garth, Hanna; Hollander, Rachel; Klein, Felice; Klau, Marc

    2017-01-01

    Context: Graduate medical education (GME) programs must develop curriculum to ensure scholarly activity among trainees and faculty to meet accreditation requirements and to support evidence-based medicine. Objective: Test whether research-related needs and interests varied across four groups: primary care trainees, specialty trainees, primary care faculty, and specialty faculty. Design: We surveyed a random sample of trainees and faculty in Kaiser Permanente Southern California’s GME programs. We investigated group differences in outcomes using Fisher exact and Kruskal-Wallis tests. Main Outcome Measures: Research experiences, skills, barriers, motivators, and interests in specific research skills development. Results: Participants included 47 trainees and 26 faculty (response rate = 30%). Among primary care faculty, 12 (71%) reported little or no research experience vs 1 (11%) for specialty faculty, 14 (41%) for primary care trainees, and 1 (8%) for specialty trainees (p < 0.001). Submission of research to the institutional review board, an abstract to a conference, or a manuscript for publication in the previous year varied across groups (p = 0.001, p = 0.003, and p < 0.001, respectively). Overall self-reported research skills also differed across groups (p < 0.001). Primary care faculty reported the lowest skill level. Research barriers that differed across groups included other work roles taking priority; desire for work-life balance; and lack of managerial support, research equipment, administrative support, and funding. Conclusion: Faculty and trainees in primary care and specialties have differing research-related needs that GME programs should consider when designing curricula to support scholarly activity. Developing research skills of primary care faculty is a priority to support trainees’ scholarly activity. PMID:28333607

  15. Bactericidal activity of cefoperazone with CP-45,899 against large inocula of beta-lactamase-producing Haemophilus influenzae.

    PubMed Central

    Yu, P K; Washington, J A

    1981-01-01

    Bactericidal activity of cefoperazone, alone and in combination with the beta-lactamase inhibitor CP-45,899, was tested against inocula of 10(7) colony-forming units of beta-lactamase-producing isolates of Haemophilus influenzae type b per ml. Of 19 strains tested, 10 required greater than or equal to 64 microgram of cefoperazone per ml for killing, whereas no strains were killed by less than 64 microgram of CP-45,899 per ml. Synergy occurred with the combination of 4 microgram of each agent per ml against 9 of the 10 cefoperazone-resistant strains. PMID:6269484

  16. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen.

    PubMed

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper; Arthur, Jonathan W; Graham, Mark E; Lavin, Martin

    2016-03-01

    Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

  17. Impaired non-specific suppressor-inducer T-cell activity in aged murine Peyer's patches, which can be corrected largely by IL-2 in vitro.

    PubMed Central

    Kawanishi, H; Kiely, J

    1989-01-01

    To shed further light on the mechanism of age-associated T-cell-mediated immunoregulatory alterations in gut non-specific mucosal immune responses, we studied in vitro the function of a variety of concanavalin A (Con A)-activated immunoregulatory T-cell subsets derived from aged murine Peyer's patches (PP) (BALB/c > 24 months old) in the production of class-specific immunoglobulins (Ig) by young (5-8 months old) lipopolysaccharide (LPS)-activated PP B cells. The in vitro induction of Con A-activated PP helper (Th) [L3T4+ Lyt-2- Vicia villosa non-adherent (VV-)], suppressor (Ts) L3T4- Lyt-2+ (VV-), and contrasuppresor (Tcs) (L3T4+ Lyt-2- VV+) T cells were compared for the two age groups. The activities of aged PP-derived Ts and Tcs cells were greatly impaired, in contrast to minor defects in activity of the aged Th cells. The induction of effector Tcs cells, however, depended on the presence of functionally effective Ts cells. Recombinant IL-2 (rIL-2) could largely correct this impaired generation of aged Ts and Tcs cells. Next, we determined the activities of Ts inducer (Tsi) (L3T4+ Lyt-2- VV-) T cells in aged PP in vitro. The cell activity was considerably diminished in aged mice. Then, we tested in vitro whether rIL-2 could reconstitute the impaired generation of the aged non-specific Tsi cell. The function of the latter cell was largely restored by rIL-2. Thus, the major functional (intrinsic) defect present in immunocompetent T lymphocytes of murine aged PP was confined to the Tsi cell. PMID:15493264

  18. Structure-activity relationships of a novel group of large-conductance Ca(2+)-activated K(+) (BK) channel modulators: the GoSlo-SR family.

    PubMed

    Roy, Subhrangsu; Morayo Akande, Adebola; Large, Roddy J; Webb, Tim I; Camarasu, Costin; Sergeant, Gerard P; McHale, Noel G; Thornbury, Keith D; Hollywood, Mark A

    2012-10-01

    Opening up ion channels: We synthesised a series of anthraquinone analogues, called the GoSlo-SR family. Their effects on bladder smooth muscle BK channels were examined and, as shown, shifted voltage dependent activation >-100 mV (at 10 μM). They were more efficacious than NS11021 and could provide a new scaffold for the design of efficacious BK openers.

  19. Prostaglandin F2a activates stress response signaling and induces expression of activating transcription factor 3 (ATF3) in bovine large luteal cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pulsatile uterine secretion of prostaglandin F2 alpha (PGF) triggers the regression of the corpus luteum (CL). Recent studies have explored global changes in gene expression in response to PGF that may contribute to structural and functional regression of the CL. Activating transcription facto...

  20. P/2008 CL94 (Lemmon) and P/2011 S1 (Gibbs): comet-like activity at large heliocentric distances

    NASA Astrophysics Data System (ADS)

    Kulyk, I.; Korsun, P.; Rousselot, P.; Afanasiev, V.; Ivanova, O.

    2016-06-01

    Based on spectroscopic and photometric observations we analyzed the dust environment of two minor distant objects, P/2008 CL94 (Lemmon) and P/2011 S1 (Gibbs). Both targets demonstrated the comet-like activity beyond the "zone of water-ice sublimation". Meanwhile the spectrum of P/2008 CL94 (Lemmon) did not reveal molecular emission features above reflected continuum in a spectral region of 4100-6800Å. Reddening of the continuum is linear along the dispersion with the mean normalized reflectivity gradient equals to 2.0% ± 0.4%. The normalized reflectivity of P/2011 S1 (Gibbs) derived from the V-R and R-I color indices equals 11% ± 9% and 26% ± 6% respectively. Both objects have likely small nuclei (about 2 and 4 km in the radii for P/2008 CL94 and P/2011 S1 respectively), which are consistent with nucleus sizes of 'Jupiter-family' comets. The level of physical activity of P/2008 CL94 and S/2011 S1 is characterized by R-Afρ quantity of 106 ± 3 cm and 76 ± 8 cm respectively. The Afρ values are resulted in dust production rates of about 1-2 kg/s, assuming the average geometric albedo of grains of 0.1 and the dust outflow velocities between 1 and 10 m/s.

  1. Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing

    PubMed Central

    Wongpalee, Somsakul Pop; Vashisht, Ajay; Sharma, Shalini; Chui, Darryl; Wohlschlegel, James A; Black, Douglas L

    2016-01-01

    Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition. The active early complex formed in the absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These results demonstrate that during early stages of splicing, exon RNP complexes are highly dynamic with many proteins failing to bind during PTBP1 arrest. DOI: http://dx.doi.org/10.7554/eLife.19743.001 PMID:27882870

  2. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry.

    PubMed

    Bartlett, Nancy L; Smith, Mitchell R; Siddiqi, Tanya; Advani, Ranjana H; O'Connor, Owen A; Sharman, Jeff P; Feldman, Tatyana; Savage, Kerry J; Shustov, Andrei R; Diefenbach, Catherine S; Oki, Yasuhiro; Palanca-Wessels, Maria Corinna; Uttarwar, Mayur; Li, Martha; Yang, Jing; Jacobsen, Eric D

    2017-07-01

    This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing DLBCL; after several patients with little to no CD30 achieved a complete remission (CR), the study evaluated treatment of DLBCL with undetectable CD30 (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL patients (31%) had an objective response (6 CRs [12%]). Median progression-free survival (PFS) was 1.4 months (range, 0.4-15.6) and median overall survival (OS) was 7.5 months (range, 0.7-18.6+). Subsequent CD30 expression quantitated by computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL responders had ≥1% CD30. Correlative analyses of CD30u and CD30-expressing DLBCL combined demonstrated that ≥1% CD30 expression by cIHC resulted in a trend toward a higher response rate and significantly longer median PFS and OS. A minimum CD30 expression threshold appears to be required for antitumor activity in DLBCL; however, other factors also likely contribute to activity. (NCT01421667).

  3. Comparison Of Several Methods Of Implementing A Fiber Optic IEEE 802.3 Ethernet

    NASA Astrophysics Data System (ADS)

    Thompson, Geoffrey O.

    1987-01-01

    Several different methods of implementing a fiber optic version of IEEE 802.3 10BASE LANs have been proposed as a candidate for standardization by IEEE. There have been extensive discussions as to the relative merits and features of the several systems. This paper will discuss the merits of each for this particular application on a comparative basis.

  4. Modeling root-reinforcement with a Fiber-Bundle Model and Monte Carlo simulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper uses sensitivity analysis and a Fiber-Bundle Model (FBM) to examine assumptions underpinning root-reinforcement models. First, different methods for apportioning load between intact roots were investigated. Second, a Monte Carlo approach was used to simulate plants with heartroot, platero...

  5. Spatial Gradients in Halogen Oxides Across the North Slope of Alaska Indicate That Halogen Activated Airmasses are Spatially Large

    NASA Astrophysics Data System (ADS)

    Simpson, W. R.; Hoenninger, G. S.; Platt, U.

    2005-12-01

    Reactive halogens are important oxidizers in the polar atmosphere during springtime. They deplete tropospheric ozone, oxidize hydrocarbons, and oxidize gas-phase mercury, causing it to deposit to the snow pack. We want to understand the mechanism by which halides in on snow/ice crystals and/or in aerosol particles are converted to reactive halogen species. This understanding can assist in prediction of mercury deposition and how that deposition depends on environmental variables like sea-ice extent and temperature. This mechanistic knowledge is particularly important in the context of a changing Arctic system. To study halogen activation, we are working in the Studies of the Northern Alaskan Coastal System (SNACS) project and here show results from 2005 including the LEADX experiment. A number of studies have implicated leads (cracks in the sea ice) as a source of halogen activation, but it is unclear if halogens are directly activated on ice surfaces at the lead (e.g. frost flowers) or if the lead is less directly involved. To address the role of leads in halogen activation, we measured bromine monoxide (BrO) using Multiple Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) at Barrow and Atqasuk, Alaska over a four-month period. The locations of these sites, either on the coast near a recurring lead in the case of Barrow, or 100km inland in the case of Atqasuk provides an ability to measure spatial gradients on the 100km length scale. In addition, the Barrow instrument was the first implementation of fully automated two dimensional MAX-DOAS where both elevation and azimuth were scanned. Because the MAX-DOAS method typically detects path-averaged BrO amounts between the instrument and a range of approximately 10km, differences in BrO between viewing azimuths allows us to determine short-length scale BrO gradients. From the 2-D MAX-DOAS observations at Barrow, we find that there are very small if any spatial gradients on the 10km length scale. From the

  6. Expression and large-scale production of the biochemically active human tissue-plasminogen activator in hairy roots of Oriental melon (Cucumis melo).

    PubMed

    Kim, Sung-Ryong; Sim, Joon-Soo; Ajjappala, Hemavathi; Kim, Yong-Hwan; Hahn, Bum-Soo

    2012-01-01

    Human tissue-plasminogen activator (t-PA) is a thrombolytic protein that plays an active role in dissolving fibrin clots by fibrinolysis and in activating plasminogen to plasmin in blood vessels. t-PA and synthetic t-PA (st-PA) genes were expressed as enzymatically active form in hairy roots of Oriental melon (Cucumis melo L. cv. Geumssaragi-euncheon) infected by Agrobacterium rhizogenes. The insertion of the t-PA genes in genomic DNA of transgenic hairy roots was verified by PCR. The presence and expression of t-PA-specific transcripts in the total RNAs of transgenic hairy roots were confirmed by RT-PCR. Western blot analysis of the transgenic hairy roots showed a single major band of 59-kDa recombinant t-PAs. ELISA demonstrated that the highest level of recombinant t-PA (798 ng mg⁻¹) was detected in hairy roots expressing t-PA. Similarly, the maximum fibrinolysis of recombinant t-PAs was observed in hairy roots transformed with t-PA. WPM medium was found to be more suitable for rapid growth of hairy roots among all the seven media types tested. The hairy root production was 5.8 times higher than that of White medium. The total yield of hairy roots grown on WPM medium was 621.8±8.7 g L⁻¹ at pH 7.0. These studies demonstrate that the hairy roots could be employed for the mass production of enzymatically active t-PA.

  7. Evolution of Early Cretaceous Paleotemperatures: A Balance Between Global Carbon Burial Rates and Large Igneous Provinces Activity

    NASA Astrophysics Data System (ADS)

    Bodin, S.; Meissner, P.; Janssen, N. M. M.; Steuber, T.; Mutterlose, J.

    2014-12-01

    The lack of a high-resolution, long-term Early Cretaceous paleotemperature record hampers a full-scale comprehension, as well as a more holistic approach, to Early Cretaceous climate changes. We present an extended compilation of belemnite-based oxygen, carbon and strontium isotope records covering the Berriasian to middle Albian from the Vocontian Basin (SE France). Integrated with paleontological and sedimentological evidences, this dataset clearly demonstrates that three intervals of cold climatic conditions have taken place during the Early Cretaceous greenhouse world. More specifically, these are taken place during (1) the late Valanginian-earliest Hauterivian, (2) the late early Aptian and (3) the latest Aptian - earliest Albian. Each of these intervals is associated with high amplitude sea-level fluctuations, pointing at transient installations of polar ice caps. As evidenced by carbon isotope positive excursions, each cold episode is associated with enhanced burial of organic matter on a global scale. Moreover, there is a very good match between the timing and size of large igneous provinces eruptions and the amplitude of Early Cretaceous warming episodes. Altogether, these observations confirm the instrumental role of atmospheric CO2 variations in the making of Mesozoic climate change. On a long-term perspective, during the Early Cretaceous, the coupling of global paleotemperature and seawater strontium isotopic ratio is best explained by temperature-controlled changes of continental crust weathering rates.

  8. Evolution of Early Cretaceous paleotemperatures: A balance between global carbon burial rates and large igneous provinces activity

    NASA Astrophysics Data System (ADS)

    Bodin, Stephane; Meissner, Philipp; Janssen, Nico; Steuber, Thomas; Mutterlose, Jörg

    2015-04-01

    The lack of a high-resolution, long-term Early Cretaceous paleotemperature record hampers a full-scale comprehension, as well as a more holistic approach, to Early Cretaceous climate changes. Here we present an extended compilation of belemnite-based oxygen, carbon and strontium isotope records covering the late Berriasian - middle Albian from the Vocontian Basin (SE France). Integrated with paleontological and sedimentological evidences, this dataset clearly demonstrates that three intervals of cold climatic conditions have taken place during the Early Cretaceous greenhouse world. More specifically, these have taken place during (1) the late Valanginian-earliest Hauterivian, (2) the late early Aptian and (3) the latest Aptian - earliest Albian. Each of these intervals is associated with high amplitude sea-level fluctuations, pointing at transient installations of polar ice caps. As evidenced by carbon isotope positive excursions, each cold episode is associated with enhanced burial of organic matter on a global scale. Moreover, there is a very good match between the timing and size of large igneous provinces eruptions and the amplitude of Early Cretaceous warming episodes. Altogether, these observations confirm the instrumental role of atmospheric CO2 variations in the making of Mesozoic climate change. On a long-term perspective, during the Early Cretaceous, the coupling of global paleotemperature and seawater strontium isotopic ratio is best explained by temperature-controlled changes of continental crust weathering rates.

  9. CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation.

    PubMed

    Miyagaki, Tomomitsu; Sugaya, Makoto; Murakami, Takashi; Asano, Yoshihide; Tada, Yayoi; Kadono, Takafumi; Okochi, Hitoshi; Tamaki, Kunihiko; Sato, Shinichi

    2011-03-15

    CCR3 is a specific marker of anaplastic large cell lymphoma (ALCL) cells. ALCL cells also express CCL11, a ligand for CCR3, leading to the hypothesis that CCL11 may play an autocrine role in ALCL progression. In this study, we investigated a role of CCL11 in cell survival and growth of human Ki-JK cells, established from an ALCL patient, and murine EL-4 lymphoma cells. Both Ki-JK and EL-4 cells expressed cell surface CCR3. CCL11 increased cell survival rates of Ki-JK cells in a dose-dependent manner, whereas it promoted EL-4 cell proliferation. Furthermore, CCL11 induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in both Ki-JK cells and EL-4 cells. Cell survival and tumor proliferation promoted by CCL11 was completely blocked by inhibition of ERK phosphorylation. CCL11 induced expression of antiapoptotic proteins, Bcl-xL and survivin, in Ki-JK cells. CCL11 also enhanced tumor growth of EL-4 and Ki-JK cells in vivo. Consistent with these results, tumor cells of cutaneous ALCL expressed CCR3 and increased levels of phosphorylated ERK1/2, Bcl-xL, and survivin in situ. Thus, our findings prompt a novel therapeutic approach to treat relapses of an aggressive form of lymphoma based on the discovery that a cell surface marker of disease functions as a critical autocrine growth receptor.

  10. Hierarchical chlorine-doped rutile TiO{sub 2} spherical clusters of nanorods: Large-scale synthesis and high photocatalytic activity

    SciTech Connect

    Xu Hua; Zheng Zhi; Zhang Lizhi Zhang Hailu; Deng Feng

    2008-09-15

    In this study, we report the synthesis of hierarchical chlorine-doped rutile TiO{sub 2} spherical clusters of nanorods photocatalyst on a large scale via a soft interface approach. This catalyst showed much higher photocatalytic activity than the famous commercial titania (Degussa P25) under visible light ({lambda}>420 nm). The resulting sample was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), nitrogen adsorption, X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy, {sup 1}H solid magic-angle spinning nuclear magnetic resonance (MAS-NMR) and photoluminescence spectroscopy. On the basis of characterization results, we found that the doping of chlorine resulted in red shift of absorption and higher surface acidity as well as crystal defects in the photocatalyst, which were the reasons for high photocatalytic activity of chlorine-doped TiO{sub 2} under visible light ({lambda}>420 nm). These hierarchical chlorine-doped rutile TiO{sub 2} spherical clusters of nanorods are very attractive in the fields of environmental pollutants removal and solar cell because of their easy separation and high activity. - Graphical abstract: Hierarchical chlorine-doped rutile TiO{sub 2} spherical clusters of nanorods photocatalyst were synthesized on a large scale via a soft interface approach. This catalyst showed much higher photocatalytic activity than the famous commercial titania (Degussa P25) under visible light ({lambda}>420 nm)

  11. Fully relativistic complete active space self-consistent field for large molecules: Quasi-second-order minimax optimization

    SciTech Connect

    Bates, Jefferson E.; Shiozaki, Toru

    2015-01-28

    We develop an efficient algorithm for four-component complete active space self-consistent field (CASSCF) methods on the basis of the Dirac equation that takes into account spin–orbit and other relativistic effects self-consistently. Orbitals are optimized using a trust-region quasi-Newton method with Hessian updates so that energies are minimized with respect to rotations among electronic orbitals and maximized with respect to rotations between electronic and positronic orbitals. Utilizing density fitting and parallel computation, we demonstrate that Dirac–Coulomb CASSCF calculations can be routinely performed on systems with 100 atoms and a few heavy-elements. The convergence behavior and wall times for octachloridodirhenate(III) and a tungsten methylidene complex are presented. In addition, the excitation energies of octachloridodirhenate(III) are reported using a state-averaged variant.

  12. Fully relativistic complete active space self-consistent field for large molecules: Quasi-second-order minimax optimization

    NASA Astrophysics Data System (ADS)

    Bates, Jefferson E.; Shiozaki, Toru

    2015-01-01

    We develop an efficient algorithm for four-component complete active space self-consistent field (CASSCF) methods on the basis of the Dirac equation that takes into account spin-orbit and other relativistic effects self-consistently. Orbitals are optimized using a trust-region quasi-Newton method with Hessian updates so that energies are minimized with respect to rotations among electronic orbitals and maximized with respect to rotations between electronic and positronic orbitals. Utilizing density fitting and parallel computation, we demonstrate that Dirac-Coulomb CASSCF calculations can be routinely performed on systems with 100 atoms and a few heavy-elements. The convergence behavior and wall times for octachloridodirhenate(III) and a tungsten methylidene complex are presented. In addition, the excitation energies of octachloridodirhenate(III) are reported using a state-averaged variant.

  13. Fully relativistic complete active space self-consistent field for large molecules: quasi-second-order minimax optimization.

    PubMed

    Bates, Jefferson E; Shiozaki, Toru

    2015-01-28

    We develop an efficient algorithm for four-component complete active space self-consistent field (CASSCF) methods on the basis of the Dirac equation that takes into account spin-orbit and other relativistic effects self-consistently. Orbitals are optimized using a trust-region quasi-Newton method with Hessian updates so that energies are minimized with respect to rotations among electronic orbitals and maximized with respect to rotations between electronic and positronic orbitals. Utilizing density fitting and parallel computation, we demonstrate that Dirac-Coulomb CASSCF calculations can be routinely performed on systems with 100 atoms and a few heavy-elements. The convergence behavior and wall times for octachloridodirhenate(III) and a tungsten methylidene complex are presented. In addition, the excitation energies of octachloridodirhenate(III) are reported using a state-averaged variant.

  14. NKT cell-TCR expression activates conventional T cells in vivo, but is largely dispensable for mature NKT cell biology.

    PubMed

    Vahl, J Christoph; Heger, Klaus; Knies, Nathalie; Hein, Marco Y; Boon, Louis; Yagita, Hideo; Polic, Bojan; Schmidt-Supprian, Marc

    2013-01-01

    Natural killer T (NKT) cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR.

  15. A ternary classification using machine learning methods of distinct estrogen receptor activities within a large collection of environmental chemicals.

    PubMed

    Zhang, Quan; Yan, Lu; Wu, Yan; Ji, Li; Chen, Yuanchen; Zhao, Meirong; Dong, Xiaowu

    2017-02-15

    Endocrine-disrupting chemicals (EDCs), which can threaten ecological safety and be harmful to human beings, have been cause for wide concern. There is a high demand for efficient methodologies for evaluating potential EDCs in the environment. Herein an evaluation platform was developed using novel and statistically robust ternary models via different machine learning models (i.e., linear discriminant analysis, classification and regression tree, and support vector machines). The platform is aimed at effectively classifying chemicals with agonistic, antagonistic, or no estrogen receptor (ER) activities. A total of 440 chemicals from the literature were selected to derive and optimize the three-class model. One hundred and nine new chemicals appeared on the 2014 EPA list for EDC screening, which were used to assess the predictive performances by comparing the E-screen results with the predicted results of the classification models. The best model was obtained using support vector machines (SVM) which recognized agonists and antagonists with accuracies of 76.6% and 75.0%, respectively, on the test set (with an overall predictive accuracy of 75.2%), and achieved a 10-fold cross-validation (CV) of 73.4%. The external predicted accuracy validated by the E-screen assay was 87.5%, which demonstrated the application value for a virtual alert for EDCs with ER agonistic or antagonistic activities. It was demonstrated that the ternary computational model could be used as a faster and less expensive method to identify EDCs that act through nuclear receptors, and to classify these chemicals into different mechanism groups.

  16. In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice.

    PubMed

    Chu, Man; Tam, Lai Shan; Zhu, Jing; Jiao, Delong; Liu, De Hua; Cai, Zhe; Dong, Jie; Kai Lam, Christopher Wei; Wong, Chun Kwok

    2017-03-01

    The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions. A remission of histopathology characteristics of skin and nephritis was also observed upon IL-38 treatment. Accordingly, IL-38 receptor was expressed on the cell surface of both CD4(+) Th and CD19(+) B lymphocytes. The splenic Th17 and DN T lymphocytes, the average mRNA level of epigenetically regulated gene expression of Th17 cells, and serum concentrations of IL-17 and IL-22 were significantly decreased upon the treatment of IL-38 (all p<0.05). The in vivo results suggest that IL-38 can ameliorate skin inflammation and nephritis in SLE mice probably via suppressing the formation of inflammatory cytokines such as IL-17 and IL-22, and pathogenic DN T cells. These findings may provide a biochemical basis for further investigation of the therapeutic mechanisms of IL-38 for the treatment of autoimmune-mediated inflammation.

  17. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    PubMed

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  18. Habitat Composition and Connectivity Predicts Bat Presence and Activity at Foraging Sites in a Large UK Conurbation

    PubMed Central

    Hale, James D.; Fairbrass, Alison J.; Matthews, Tom J.; Sadler, Jon P.

    2012-01-01

    Background Urbanization is characterized by high levels of sealed land-cover, and small, geometrically complex, fragmented land-use patches. The extent and density of urbanized land-use is increasing, with implications for habitat quality, connectivity and city ecology. Little is known about densification thresholds for urban ecosystem function, and the response of mammals, nocturnal and cryptic taxa are poorly studied in this respect. Bats (Chiroptera) are sensitive to changing urban form at a species, guild and community level, so are ideal model organisms for analyses of this nature. Methodology/Principal Findings We surveyed bats around urban ponds in the West Midlands conurbation, United Kingdom (UK). Sites were stratified between five urban land classes, representing a gradient of built land-cover at the 1 km2 scale. Models for bat presence and activity were developed using land-cover and land-use data from multiple radii around each pond. Structural connectivity of tree networks was used as an indicator of the functional connectivity between habitats. All species were sensitive to measures of urban density. Some were also sensitive to landscape composition and structural connectivity at different spatial scales. These results represent new findings for an urban area. The activity of Pipistrellus pipistrellus (Schreber 1774) exhibited a non-linear relationship with the area of built land-cover, being much reduced beyond the threshold of ∼60% built surface. The presence of tree networks appears to mitigate the negative effects of urbanization for this species. Conclusions/Significance Our results suggest that increasing urban density negatively impacts the study species. This has implications for infill development policy, built density targets and the compact city debate. Bats were also sensitive to the composition and structure of the urban form at a range of spatial scales, with implications for land-use planning and management. Protecting and

  19. Synthesis of large surface area nano-sized BiVO{sub 4} by an EDTA-modified hydrothermal process and its enhanced visible photocatalytic activity

    SciTech Connect

    Sun Wanting; Xie Mingzheng; Jing Liqiang; Luan Yunbo; Fu Honggang

    2011-11-15

    In this work, monoclinic scheelite-type BiVO{sub 4} nanoparticle with large surface area has been successfully synthesized, using Bi(NO{sub 3}){sub 3} and NH{sub 4}VO{sub 3} as raw materials, through a hydrothermal process in the presence of ethylene diamine tetraacetic acid (EDTA). It is demonstrated that the nanoparticle size of as-prepared BiVO{sub 4} becomes small by decreasing hydrothermal temperature, shortening hydrothermal reaction time and increasing EDTA amount used. The resulting BiVO{sub 4} nanoparticle with large surface area exhibits a good photocatalytic performance for degrading phenol solution as a model organic pollutant under visible illumination. The key of this method is the chelating role of EDTA group in the synthetic process that it can greatly control the concentration of Bi{sup 3+}, leading to the growth inhibition of BiVO{sub 4} crystallite. The work provides a route for the synthesis of Bi-containing nano-sized composite oxides with large surface area. - Graphical abstract: High visible active nano-sized BiVO{sub 4} photocatalyst with large surface area is successfully synthesized, which is attributed to the chelating role of EDTA group inhibiting the growth of BiVO{sub 4} crystallites. Highlights: > Monoclinic scheelite-type BiVO{sub 4} nanoparticle with large surface area has been synthesized by a hydrothermal process. > Key of this method is the chelating role of EDTA group inhibiting the growth of BiVO{sub 4} crystallites. > Resulting nano-sized BiVO{sub 4} exhibits a good photocatalytic activity for degrading phenol under visible illumination.

  20. Calycosin and Formononetin Induce Endothelium-Dependent Vasodilation by the Activation of Large-Conductance Ca2+-Activated K+ Channels (BKCa)

    PubMed Central

    Tseng, Hisa Hui Ling; Vong, Chi Teng; Leung, George Pak-Heng; Seto, Sai Wang; Lee, Simon Ming-Yuen

    2016-01-01

    Calycosin and formononetin are two structurally similar isoflavonoids that have been shown to induce vasodilation in aorta and conduit arteries, but study of their actions on endothelial functions is lacking. Here, we demonstrated that both isoflavonoids relaxed rat mesenteric resistance arteries in a concentration-dependent manner, which was reduced by endothelial disruption and nitric oxide synthase (NOS) inhibition, indicating the involvement of both endothelium and vascular smooth muscle. In addition, the endothelium-dependent vasodilation, but not the endothelium-independent vasodilation, was blocked by BKCa inhibitor iberiotoxin (IbTX). Using human umbilical vein endothelial cells (HUVECs) as a model, we showed calycosin and formononetin induced dose-dependent outwardly rectifying K+ currents using whole cell patch clamp. These currents were blocked by tetraethylammonium chloride (TEACl), charybdotoxin (ChTX), or IbTX, but not apamin. We further demonstrated that both isoflavonoids significantly increased nitric oxide (NO) production and upregulated the activities and expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS). These results suggested that calycosin and formononetin act as endothelial BKCa activators for mediating endothelium-dependent vasodilation through enhancing endothelium hyperpolarization and NO production. Since activation of BKCa plays a role in improving behavioral and cognitive disorders, we suggested that these two isoflavonoids could provide beneficial effects to cognitive disorders through vascular regulation. PMID:27994632

  1. Large-scale flank collapse events during the activity of Montagne Pelée, Martinique, Lesser Antilles

    NASA Astrophysics Data System (ADS)

    Le Friant, Anne; Boudon, Georges; Deplus, Christine; Villemant, Benoã®T.

    2003-01-01

    A horseshoe-shaped structure already identified on the southwestern flank of Montagne Pelée (Martinique, Lesser Antilles arc) was previously interpreted as resulting of a flank collapse event, but no debris avalanche deposits were observed at the time. New offshore high-resolution bathymetry and geophysical data (Aguadomar cruise; December 1998 to January 1999; R/V L'Atalante) lead us to identify three debris avalanche deposits on the submarine western flank of Montagne Pelée extending down to the Grenada Basin. They display morphological fronts and hummocky morphology on bathymetric data, speckled pattern on backscatter data and hyperbolic facies on 3.5 kHz and seismic profiles. New on-land geological studies lead us to identify two other horseshoe-shaped structures on the same flank of the volcano. The three submarine deposits have been traced back to the structures identified on land, which confirms the occurrence of repeated flank collapse events during the evolution of Montagne Pelée. The ages of the last two events are estimated at ˜9 ka and ˜25 ka on the basis of 14C and 238U/230Th dates. Every flank collapse produced debris avalanches which flowed down to the Caribbean Sea. We propose that the repeated instabilities are due to the large asymmetry of the island with western aerial and submarine slopes steeper than the eastern slopes. The asymmetry results from progressive loading by accumulation of volcanic products on the western slopes of the volcano and development of long-term gravitational instabilities. Meteoric and hydrothermal fluid circulation on the floor of the second flank collapse structure also creates a weakened hydrothermalized area, which favors the recurrence of flank collapses.

  2. Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-κB activation in diffuse large B-cell lymphoma.

    PubMed

    Qu, Changju; Liu, Yadong; Kunkalla, Kranthi; Singh, Rajesh R; Blonska, Marzenna; Lin, Xin; Agarwal, Nitin Kumar; Vega, Francisco

    2013-06-06

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Aberrant activation of Hedgehog (Hh) and nuclear factor (NF)-κB pathways is ubiquitously observed and known to mediate tumor growth, survival, and chemoresistance in DLBCL. Here, we find that activation of Hh signaling is positively correlated with NF-κB pathway in DLBCL tumors, and that smoothened (SMO), the signal transducer subunit of Hh pathway, contributes to NF-κB activation through recruiting G protein subunits Gαi and Gα12 to activate PKCβ/CARMA1/TRAF6/NEMO signaling axis followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO. Moreover, functional inhibition of SMO enhances the cytotoxic effects of NF-κB inhibitor. Altogether, our study reveals a noncanonical Hh signaling pathway in which SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-κB activation. This signaling cascade contributes to the survival of DLBCL and may serve as a potential target for combination therapies in DLBCL.

  3. Highly efficient graphene-based Cu(In, Ga)Se₂ solar cells with large active area.

    PubMed

    Yin, Ling; Zhang, Kang; Luo, Hailin; Cheng, Guanming; Ma, Xuhang; Xiong, Zhiyu; Xiao, Xudong

    2014-09-21

    Two-dimensional graphene has tremendous potential to be used as a transparent conducting electrode (TCE), owing to its high transparency and conductivity. To date graphene films have been applied to several kinds of solar cells except the Cu(In, Ga)Se₂ (CIGS) solar cell. In this work, we present a novel TCE structure consisting of a doped graphene film and a thin layer of poly(methyl methacrylate) (PMMA) to replace the ZnO:Al (AZO) electrode for CIGS. By optimizing the contact between graphene and intrinsic ZnO (i-ZnO), a high power conversion efficiency (PCE) of 13.5% has been achieved, which is among the highest efficiencies of graphene-based solar cells ever reported and approaching those of AZO-based solar cells. Besides, the active area of our solar cells reaches 45 mm(2), much larger than other highly efficient graphene-based solar cells (>10%) reported so far. Moreover, compared with AZO-based CIGS solar cells, the total reflectance of the graphene-based CIGS solar cells is decreased and the quantum efficiency of the graphene-based CIGS is enhanced in the near infrared region (NIR), which strongly support graphene as a competitive candidate material for the TCE in the CIGS solar cell. Furthermore, the graphene/PMMA film can protect the solar cell from moisture, making the graphene-based solar cells much more stable than the AZO-based solar cells.

  4. Targeting c-Myc-activated genes with a correlation method: Detection of global changes in large gene expression network dynamics

    PubMed Central

    Remondini, D.; O'Connell, B.; Intrator, N.; Sedivy, J. M.; Neretti, N.; Castellani, G. C.; Cooper, L. N.

    2005-01-01

    This work studies the dynamics of a gene expression time series network. The network, which is obtained from the correlation of gene expressions, exhibits global dynamic properties that emerge after a cell state perturbation. The main features of this network appear to be more robust when compared with those obtained with a network obtained from a linear Markov model. In particular, the network properties strongly depend on the exact time sequence relationships between genes and are destroyed by random temporal data shuffling. We discuss in detail the problem of finding targets of the c-myc protooncogene, which encodes a transcriptional regulator whose inappropriate expression has been correlated with a wide array of malignancies. The data used for network construction are a time series of gene expression, collected by microarray analysis of a rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein. We show that the correlation-based model can establish a clear relationship between network structure and the cascade of c-myc-activated genes. PMID:15867157

  5. Synthetic oligosaccharides as active pharmaceutical ingredients: lessons learned from the full synthesis of one heparin derivative on a large scale.

    PubMed

    Driguez, Pierre-Alexandre; Potier, Pierre; Trouilleux, Patrick

    2014-08-01

    Covering: up to November 2013. Heparin and heparan sulfate are natural polysaccharides with strong structural variations, which are responsible for their numerous specific biological properties. One key target of heparin, among others, is antithrombin, a serine protease inhibitor that, upon activation, mainly targets anticoagulation factors IIa and Xa. It is well documented that inhibition of the latter is due to a specific pentasaccharidic sequence, its synthetic analog being the registered drug fondaparinux. The replacement of hydroxyls by methoxy groups, N-sulfates by O-sulfonates and the modulation of the sulfation pattern gave rise to both idraparinux and its neutralizable form, idrabiotaparinux, two pentasaccharides with a significantly increased half-life compared to fondaparinux. Although numerous efforts have been devoted to improving the chemoenzymatic preparation of heparin fragments, enzymes are usually selective for their natural substrates, which limits the generation of some specific non-natural structures. Up to now, total synthesis has proved to be a valuable approach for the preparation of tailor-made and pure saccharides in the milligram to gram scale. This highlight will focus on the synthesis and the technical challenges associated with the development and the production of complex carbohydrates which will be exemplified with idrabiotaparinux. Particular attention will be paid to the process improvements needed in order to implement the production in a pilot plant, achieving batch generation on a multi-kilogram scale with a purity higher than 99.5%, and with no unknown impurity over 0.1%.

  6. On the variation of the ionospheric potential due to large-scale radioactivity enhancement and solar activity

    NASA Astrophysics Data System (ADS)

    Slyunyaev, Nikolay N.; Mareev, Evgeny A.; Zhidkov, Artem A.

    2015-08-01

    Sensitivity of the global electric circuit (GEC) to variations of atmospheric conductivity and current sources is analyzed and discussed. When the undisturbed exponential conductivity profile is assumed all over the Earth, the most substantial changes in the ionospheric potential (IP) are caused by conductivity perturbations inside thunderstorms; if, in addition, conductivity reduction inside thunderstorms and nonelectrified clouds is assumed, the IP becomes less sensitive to conductivity perturbations; besides, the IP is even more sensitive to source current variations than to conductivity. Current source and voltage source descriptions of GEC generators are compared; it is shown that the IP variation may critically depend on the chosen description. As an application, the IP variation due to nuclear weapons testing is studied; it is shown that neither local nor global increase of conductivity in the stratosphere could alone explain the observed 40% IP increase in the 1960s; at the same time this increase might be accounted for by a 40% increase in the source current density or a 46% reduction of the conductivity inside thunderstorms, provided that it was not reduced initially. The IP variation due to solar activity and, in particular, due to solar modulation of galactic cosmic ray flux is also discussed and modeled, which required an adequate parameterization of the rate of atmospheric ion pair production over the solar cycle. It is estimated that the maximum IP variation on the scale of the solar cycle does not exceed 5% of the mean value, unless source current perturbations are taken into account.

  7. Observing Dynamics in Large-Scale Birkeland Currents with the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE)

    NASA Astrophysics Data System (ADS)

    Anderson, B. J.; Korth, H.; Waters, C. L.; Barnes, R. J.; Olson, C.

    2015-12-01

    The Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) provides continuous global observations of the magnetic perturbations that predominantly reflect Birkeland currents. The data are acquired by avionics magnetometers of the Iridium satellites and allow measurements from 66 satellites in near-polar circular, low altitude orbits. The configuration of the Iridium satellite constellation determines the longitude sampling spacing of ~ 2 hours and the re-sampling cadence of the system which is 9 minutes. From 2008 to 2013 the AMPERE system was developed which included new flight software on the Iridium satellites to allow telemetry of higher rate data to the ground and the Science Data Center to derive Birkeland current perturbations from the data and invert these signals to derive the global distributions of the currents using data windows of ten minutes. There were many challenges in developing AMPERE including automating inter-calibration between satellites and the baseline determination and removals. The results of AMPERE provide stunning confirmation of many of the statistical estimates for the distribution of currents but more significantly open a new window to understand their instantaneous distribution and dynamics. Examples of new features of the currents and their dynamics revealed by AMPERE are presented. In addition, prospects for new data products and increased data quality anticipated from AMPERE-NEXT to be implemented on the Iridium-NEXT generation of satellites are discussed.

  8. A support vector machines approach for virtual screening of active compounds of single and multiple mechanisms from large libraries at an improved hit-rate and enrichment factor.

    PubMed

    Han, L Y; Ma, X H; Lin, H H; Jia, J; Zhu, F; Xue, Y; Li, Z R; Cao, Z W; Ji, Z L; Chen, Y Z

    2008-06-01

    Support vector machines (SVM) and other machine-learning (ML) methods have been explored as ligand-based virtual screening (VS) tools for facilitating lead discovery. While exhibiting good hit selection performance, in screening large compound libraries, these methods tend to produce lower hit-rate than those of the best performing VS tools, partly because their training-sets contain limited spectrum of inactive compounds. We tested whether the performance of SVM can be improved by using training-sets of diverse inactive compounds. In retrospective database screening of active compounds of single mechanism (HIV protease inhibitors, DHFR inhibitors, dopamine antagonists) and multiple mechanisms (CNS active agents) from large libraries of 2.986 million compounds, the yields, hit-rates, and enrichment factors of our SVM models are 52.4-78.0%, 4.7-73.8%, and 214-10,543, respectively, compared to those of 62-95%, 0.65-35%, and 20-1200 by structure-based VS and 55-81%, 0.2-0.7%, and 110-795 by other ligand-based VS tools in screening libraries of >or=1 million compounds. The hit-rates are comparable and the enrichment factors are substantially better than the best results of other VS tools. 24.3-87.6% of the predicted hits are outside the known hit families. SVM appears to be potentially useful for facilitating lead discovery in VS of large compound libraries.

  9. 16 CFR 303.40 - Use of terms in written advertisements that imply presence of a fiber.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... imply presence of a fiber. 303.40 Section 303.40 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.40 Use of terms in written advertisements that imply presence of a fiber. The use...

  10. Repeated large-magnitude earthquakes in a tectonically active, low-strain continental interior: The northern Tien Shan, Kyrgyzstan

    NASA Astrophysics Data System (ADS)

    Landgraf, A.; Dzhumabaeva, A.; Abdrakhmatov, K. E.; Strecker, M. R.; Macaulay, E. A.; Arrowsmith, Jr.; Sudhaus, H.; Preusser, F.; Rugel, G.; Merchel, S.

    2016-05-01

    The northern Tien Shan of Kyrgyzstan and Kazakhstan has been affected by a series of major earthquakes in the late 19th and early 20th centuries. To assess the significance of such a pulse of strain release in a continental interior, it is important to analyze and quantify strain release over multiple time scales. We have undertaken paleoseismological investigations at two geomorphically distinct sites (Panfilovkoe and Rot Front) near the Kyrgyz capital Bishkek. Although located near the historic epicenters, both sites were not affected by these earthquakes. Trenching was accompanied by dating stratigraphy and offset surfaces using luminescence, radiocarbon, and 10Be terrestrial cosmogenic nuclide methods. At Rot Front, trenching of a small scarp did not reveal evidence for surface rupture during the last 5000 years. The scarp rather resembles an extensive debris-flow lobe. At Panfilovkoe, we estimate a Late Pleistocene minimum slip rate of 0.2 ± 0.1 mm/a, averaged over at least two, probably three earthquake cycles. Dip-slip reverse motion along segmented, moderately steep faults resulted in hanging wall collapse scarps during different events. The most recent earthquake occurred around 3.6 ± 1.3 kyr ago (1σ), with dip-slip offsets between 1.2 and 1.4 m. We calculate a probabilistic paleomagnitude to be between 6.7 and 7.2, which is in agreement with regional data from the Kyrgyz range. The morphotectonic signals in the northern Tien Shan are a prime example of deformation in a tectonically active intracontinental mountain belt and as such can help understand the longer-term coevolution of topography and seismogenic processes in similar structural settings worldwide.

  11. Activated full-length myosin-X moves processively on filopodia with large steps toward diverse two-dimensional directions

    PubMed Central

    Sato, Osamu; Jung, Hyun Suk; Komatsu, Satoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M.; Homma, Kazuaki; Ikebe, Mitsuo

    2017-01-01

    Myosin-X, (Myo 10), is an unconventional myosin that transports the specific cargos to filopodial tips, and is associated with the mechanism underlying filopodia formation and extension. To clarify the innate motor characteristic, we studied the single molecule movement of a full-length myosin-X construct with leucine zipper at the C-terminal end of the tail (M10FullLZ) and the tail-truncated myosin-X without artificial dimerization motif (BAP-M101–979HMM). M10FullLZ localizes at the tip of filopodia like myosin-X full-length (M10Full). M10FullLZ moves on actin filaments in the presence of PI(3,4,5)P3, an activator of myosin-X. Single molecule motility analysis revealed that the step sizes of both M10FullLZ and BAP-M101–979HMM are widely distributed on single actin filaments that is consistent with electron microscopy observation. M10FullLZ moves on filopodial actin bundles of cells with a mean step size (~36 nm), similar to the step size on single actin filaments (~38 nm). Cartesian plot analysis revealed that M10FullLZ meandered on filopodial actin bundles to both x- and y- directions. These results suggest that the lever-arm of full-length myosin-X is flexible enough to processively steps on different actin filaments within the actin bundles of filopodia. This characteristic of myosin-X may facilitate actin filament convergence for filopodia production. PMID:28287133

  12. Large-conductance channel formation mediated by P2X7 receptor activation is regulated through distinct intracellular signaling pathways in peritoneal macrophages and 2BH4 cells.

    PubMed

    Faria, R X; Cascabulho, C M; Reis, R A M; Alves, Luiz Anastácio

    2010-07-01

    The P2X(7) receptor (P2X7R) is a ligand-gated ATP receptor that acts as a low- and large-conductance channel (pore) and is known to be coupled to several downstream effectors. Recently, we demonstrated that the formation of a large-conductance channel associated with the P2X(7) receptor is induced by increasing the intracellular Ca(2+) concentration (Faria et al., Am J Physiol Cell Physiol 297:C28-C42, 2005). Here, we investigated the intracellular signaling pathways associated with P2X(7) large-conductance channel formation using the patch clamp technique in conjunction with fluorescent imaging and flow cytometry assays in 2BH4 cells and peritoneal macrophages. Different antagonists were applied to investigate the following pathways: Ca(2+)-calmodulin, phospholipase A, phospholipase D, phospholipase C, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), MAPK/extracellular signal-regulated kinase, phosphoinositide 3-kinase (PI3K), and cytoskeletal proteins. Macroscopic ionic currents induced by 1 mM ATP were reduced by 85% in the presence of PKC antagonists. The addition of antagonists for MAPK, PI3K, and the cytoskeleton (actin, intermediary filament, and microtubule) blocked 92%, 83%, and 95% of the ionic currents induced by 1 mM ATP, respectively. Our results show that PKC, MAPK, PI3K, and cytoskeletal components are involved in P2X(7) receptor large-channel formation in 2BH4 cells and peritoneal macrophages.

  13. Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle.

    PubMed

    Hristov, Kiril L; Smith, Amy C; Parajuli, Shankar P; Malysz, John; Petkov, Georgi V

    2014-03-01

    Large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca(2+) imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca(2+) sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca(2+) levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca(2+)-dependent mechanism, thus increasing DSM contractility.

  14. Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

    PubMed

    Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

    2016-11-22

    Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm(2) V(-1) s(-1), on-off current ratio Ion/Ioff ∼ 10(4), and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

  15. Kinetic Structure of Large-Conductance Ca2+-activated K+ Channels Suggests that the Gating Includes Transitions through Intermediate or Secondary States

    PubMed Central

    Rothberg, Brad S.; Magleby, Karl L.

    1998-01-01

    Mechanisms for the Ca2+-dependent gating of single large-conductance Ca2+-activated K+ channels from cultured rat skeletal muscle were developed using two-dimensional analysis of single-channel currents recorded with the patch clamp technique. To extract and display the essential kinetic information, the kinetic structure, from the single channel currents, adjacent open and closed intervals were binned as pairs and plotted as two-dimensional dwell-time distributions, and the excesses and deficits of the interval pairs over that expected for independent pairing were plotted as dependency plots. The basic features of the kinetic structure were generally the same among single large-conductance Ca2+-activated K+ channels, but channel-specific differences were readily apparent, suggesting heterogeneities in the gating. Simple gating schemes drawn from the Monod- Wyman-Changeux (MWC) model for allosteric proteins could approximate the basic features of the Ca2+ dependence of the kinetic structure. However, consistent differences between the observed and predicted dependency plots suggested that additional brief lifetime closed states not included in MWC-type models were involved in the gating. Adding these additional brief closed states to the MWC-type models, either beyond the activation pathway (secondary closed states) or within the activation pathway (intermediate closed states), improved the description of the Ca2+ dependence of the kinetic structure. Secondary closed states are consistent with the closing of secondary gates or channel block. Intermediate closed states are consistent with mechanisms in which the channel activates by passing through a series of intermediate conformations between the more stable open and closed states. It is the added secondary or intermediate closed states that give rise to the majority of the brief closings (flickers) in the gating. PMID:9607935

  16. Perspective of detecting very high energy gamma-ray emission from active galactic nuclei with Large High Altitude Air Shower Observatory (LHAASO)

    NASA Astrophysics Data System (ADS)

    Zhao, Yi; Yuan, Qiang; Bi, Xiao-Jun; Zhu, Feng-Rong; Jia, Huan-Yu

    2016-10-01

    The detectability of active galactic nuclei (AGN), a major class of γ-ray emitters in the sky, by the newly planned Chinese project, Large High Altitude Air Shower Observatory (LHAASO), is investigated. The expectation is primarily based on the AGN catalog of Fermi Large Area Telescope (Fermi-LAT), with an extrapolation to the very high energy (VHE) range taking into account the absorption effect by the extragalactic background light (EBL). It is found that LHAASO may have the potential to detect more than several tens of the Fermi detected AGN, basically BL Lacertaes, with one-year sky survey. The capability of measuring the energy spectrum and light curve are also discussed.

  17. The large conductance Ca2+ -activated K+ (BKCa) channel regulates cell proliferation in SH-SY5Y neuroblastoma cells by activating the staurosporine-sensitive protein kinases

    PubMed Central

    Curci, Angela; Mele, Antonietta; Camerino, Giulia Maria; Dinardo, Maria Maddalena; Tricarico, Domenico

    2014-01-01

    Here we investigated on the role of the calcium activated K+-channels(BKCa) on the regulation of the neuronal viability. Recordings of the K+-channel current were performed using patch-clamp technique in human neuroblastoma cells (SH-SY5Y) in parallel with measurements of the cell viability in the absence or presence of the BKCa channel blockers iberiotoxin(IbTX) and tetraethylammonium (TEA) and the BKCa channel opener NS1619. Protein kinase C/A (PKC, PKA) activities in the cell lysate were investigated in the presence/absence of drugs. The whole-cell K+-current showed a slope conductance calculated at negative membrane potentials of 126.3 pS and 1.717 nS(n = 46) following depolarization. The intercept of the I/V curve was −33 mV. IbTX(10−8 – 4 × 10−7 M) reduced the K+-current at +30 mV with an IC50 of 1.85 × 10−7 M and an Imax of −46% (slope = 2.198) (n = 21). NS1619(10–100 × 10−6 M) enhanced the K+-current of +141% (n = 6), at −10 mV(Vm). TEA(10−5–10−3 M) reduced the K+-current with an IC50 of 3.54 × 10−5 M and an Imax of −90% (slope = 0.95) (n = 5). A concentration-dependent increase of cell proliferation was observed with TEA showing a maximal proliferative effect(MPE) of +38% (10−4 M). IbTX showed an MPE of +42% at 10−8 M concentration, reducing it at higher concentrations. The MPE of the NS1619(100 × 10−6 M) was +42%. The PKC inhibitor staurosporine (0.2–2 × 10−6 M) antagonized the proliferative actions of IbTX and TEA. IbTX (10 × 10−9 M), TEA (100 × 10−6 M), and the NS1619 significantly enhanced the PKC and PKA activities in the cell lysate with respect to the controls. These results suggest that BKCa channel regulates proliferation of the SH-SY5Y cells through PKC and PKA protein kinases. PMID:25538629

  18. The large conductance Ca(2+) -activated K(+) (BKCa) channel regulates cell proliferation in SH-SY5Y neuroblastoma cells by activating the staurosporine-sensitive protein kinases.

    PubMed

    Curci, Angela; Mele, Antonietta; Camerino, Giulia Maria; Dinardo, Maria Maddalena; Tricarico, Domenico

    2014-01-01

    Here we investigated on the role of the calcium activated K(+)-channels(BKCa) on the regulation of the neuronal viability. Recordings of the K(+)-channel current were performed using patch-clamp technique in human neuroblastoma cells (SH-SY5Y) in parallel with measurements of the cell viability in the absence or presence of the BKCa channel blockers iberiotoxin(IbTX) and tetraethylammonium (TEA) and the BKCa channel opener NS1619. Protein kinase C/A (PKC, PKA) activities in the cell lysate were investigated in the presence/absence of drugs. The whole-cell K(+)-current showed a slope conductance calculated at negative membrane potentials of 126.3 pS and 1.717 nS(n = 46) following depolarization. The intercept of the I/V curve was -33 mV. IbTX(10(-8) - 4 × 10(-7) M) reduced the K(+)-current at +30 mV with an IC50 of 1.85 × 10(-7) M and an Imax of -46% (slope = 2.198) (n = 21). NS1619(10-100 × 10(-6) M) enhanced the K(+)-current of +141% (n = 6), at -10 mV(Vm). TEA(10(-5)-10(-3) M) reduced the K(+)-current with an IC50 of 3.54 × 10(-5) M and an Imax of -90% (slope = 0.95) (n = 5). A concentration-dependent increase of cell proliferation was observed with TEA showing a maximal proliferative effect(MPE) of +38% (10(-4) M). IbTX showed an MPE of +42% at 10(-8) M concentration, reducing it at higher concentrations. The MPE of the NS1619(100 × 10(-6) M) was +42%. The PKC inhibitor staurosporine (0.2-2 × 10(-6) M) antagonized the proliferative actions of IbTX and TEA. IbTX (10 × 10(-9) M), TEA (100 × 10(-6) M), and the NS1619 significantly enhanced the PKC and PKA activities in the cell lysate with respect to the controls. These results suggest that BKCa channel regulates proliferation of the SH-SY5Y cells through PKC and PKA protein kinases.

  19. Diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression shows evidence of active B-cell receptor signaling by quantitative immunofluorescence

    PubMed Central

    Kovach, Alexandra E.; Le, Long P.; Feng, Derek; Baxter, Richard H. G.; Sohani, Aliyah R.

    2017-01-01

    B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics. High MYC and concurrent high MYC and BCL2 double-expression was positively correlated with individual markers of active BCR signaling and cases with MYC/BCL2 double-expression showed overall greater BCR activation compared to cases lacking double-expression. Our findings suggest that the BCR signaling pathway may be more active in MYC/BCL2 double-expressor DLBCL and may represent a rational therapeutic target in this aggressive DLBCL subgroup. PMID:28212447

  20. Animal-borne imaging reveals novel insights into the foraging behaviors and Diel activity of a large-bodied apex predator, the American alligator (Alligator mississippiensis).

    PubMed

    Nifong, James C; Nifong, Rachel L; Silliman, Brian R; Lowers, Russell H; Guillette, Louis J; Ferguson, Jake M; Welsh, Matthew; Abernathy, Kyler; Marshall, Greg

    2014-01-01

    Large-bodied, top- and apex predators (e.g., crocodilians, sharks, wolves, killer whales) can exert strong top-down effects within ecological communities through their interactions with prey. Due to inherent difficulties while studying the behavior of these often dangerous predatory species, relatively little is known regarding their feeding behaviors and activity patterns, information that is essential to understanding their role in regulating food web dynamics and ecological processes. Here we use animal-borne imaging systems (Crittercam) to study the foraging behavior and activity patterns of a cryptic, large-bodied predator, the American alligator (Alligator mississippiensis) in two estuaries of coastal Florida, USA. Using retrieved video data we examine the variation in foraging behaviors and activity patterns due to abiotic factors. We found the frequency of prey-attacks (mean = 0.49 prey attacks/hour) as well as the probability of prey-capture success (mean = 0.52 per attack) were significantly affected by time of day. Alligators attempted to capture prey most frequently during the night. Probability of prey-capture success per attack was highest during morning hours and sequentially lower during day, night, and sunset, respectively. Position in the water column also significantly affected prey-capture success, as individuals' experienced two-fold greater success when attacking prey while submerged. These estimates are the first for wild adult American alligators and one of the few examples for any crocodilian species worldwide. More broadly, these results reveal that our understandings of crocodilian foraging behaviors are biased due to previous studies containing limited observations of cryptic and nocturnal foraging interactions. Our results can be used to inform greater understanding regarding the top-down effects of American alligators in estuarine food webs. Additionally, our results highlight the importance and power of using animal-borne imaging when

  1. Animal-Borne Imaging Reveals Novel Insights into the Foraging Behaviors and Diel Activity of a Large-Bodied Apex Predator, the American Alligator (Alligator mississippiensis)

    PubMed Central

    Nifong, James C.; Nifong, Rachel L.; Silliman, Brian R.; Lowers, Russell H.; Guillette, Louis J.; Ferguson, Jake M.; Welsh, Matthew; Abernathy, Kyler; Marshall, Greg

    2014-01-01

    Large-bodied, top- and apex predators (e.g., crocodilians, sharks, wolves, killer whales) can exert strong top-down effects within ecological communities through their interactions with prey. Due to inherent difficulties while studying the behavior of these often dangerous predatory species, relatively little is known regarding their feeding behaviors and activity patterns, information that is essential to understanding their role in regulating food web dynamics and ecological processes. Here we use animal-borne imaging systems (Crittercam) to study the foraging behavior and activity patterns of a cryptic, large-bodied predator, the American alligator (Alligator mississippiensis) in two estuaries of coastal Florida, USA. Using retrieved video data we examine the variation in foraging behaviors and activity patterns due to abiotic factors. We found the frequency of prey-attacks (mean = 0.49 prey attacks/hour) as well as the probability of prey-capture success (mean = 0.52 per attack) were significantly affected by time of day. Alligators attempted to capture prey most frequently during the night. Probability of prey-capture success per attack was highest during morning hours and sequentially lower during day, night, and sunset, respectively. Position in the water column also significantly affected prey-capture success, as individuals’ experienced two-fold greater success when attacking prey while submerged. These estimates are the first for wild adult American alligators and one of the few examples for any crocodilian species worldwide. More broadly, these results reveal that our understandings of crocodilian foraging behaviors are biased due to previous studies containing limited observations of cryptic and nocturnal foraging interactions. Our results can be used to inform greater understanding regarding the top-down effects of American alligators in estuarine food webs. Additionally, our results highlight the importance and power of using animal

  2. A Physical Activity Intervention and Changes in Body Mass Index at a Middle School With a Large American Indian Population, Oklahoma, 2004–2009

    PubMed Central

    Folorunso, Olakunle A.; Moore, William E.

    2016-01-01

    School-based interventions can reach children and adolescents and aid in reducing the prevalence of childhood obesity. A physical education class that engaged middle school students in a daily 1-mile walk or run and other team sports was developed in a rural school in southwestern Oklahoma with a large American Indian population. Body mass index z scores decreased among boys and were stable among girls in the intervention group compared with students who did not participate in the intervention. A daily required walk or run may help to establish a physical activity habit with all of its associated benefits. PMID:27906646

  3. Activation of the STAT3 Signaling Pathway Is Associated With Poor Survival in Diffuse Large B-Cell Lymphoma Treated With R-CHOP

    PubMed Central

    Huang, Xin; Meng, Bin; Iqbal, Javeed; Ding, B. Belinda; Perry, Anamarija M.; Cao, Wenfeng; Smith, Lynette M.; Bi, Chengfeng; Jiang, Chunsun; Greiner, Timothy C.; Weisenburger, Dennis D.; Rimsza, Lisa; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M.; Gascoyne, Randy D.; Cook, James R.; Tubbs, Raymond R.; Jaffe, Elaine S.; Armitage, James O.; Vose, Julie M.; Staudt, Louis M.; McKeithan, Timothy W.; Chan, Wing C.; Ye, B. Hilda; Fu, Kai

    2013-01-01

    Purpose We previously reported that constitutive STAT3 activation is a prominent feature of the activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL). In this study, we investigated whether STAT3 activation can risk stratify patients with DLBCL. Patients and Methods By an immunohistochemical method, we investigated phosphotyrosine STAT3 (PY-STAT3) expression from 185 patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). Cell line-based siRNA experiments were also performed to generate an 11-gene, PY-STAT3 activation signature, which was used to study a previously published cohort of 222 patients with DLBCL. The STAT3 activation status determined by these two methods and by STAT3 mRNA levels were then correlated with survival. Results PY-STAT3 was detected in 37% of DLBCL and enriched in ABC-DLBCL cases (P = .03). PY-STAT3 positivity significantly correlated with poor overall survival (OS; P = .01) and event-free survival (EFS; P = .006). Similar observations were made for high levels of STAT3 mRNA. In multivariable analysis, PY-STAT3 status (P = .02), International Prognostic Index (P = .02), and BCL2 expression (P = .046) were independent prognosticators of OS in this cohort. Among the cell-of-origin subgroups, PY-STAT3 was associated with poor EFS among non–germinal center B-cell DLBCL cases only (P = .027). Similarly, the 11-gene STAT3 activation signature correlated with poor survival in the entire DLBCL cohort (OS, P < .001; EFS, P < .001) as well as the ABC-DLBCL subgroup (OS, P = .029; EFS, P = .025). Conclusion STAT3 activation correlated with poor survival in patients with DLBCL treated with R-CHOP, especially those with tumors of the ABC-DLBCL subtype. PMID:24220563

  4. N-terminal isoforms of the large-conductance Ca²⁺-activated K⁺ channel are differentially modulated by the auxiliary β1-subunit.

    PubMed

    Lorca, Ramón A; Stamnes, Susan J; Pillai, Meghan K; Hsiao, Jordy J; Wright, Michael E; England, Sarah K

    2014-04-04

    The large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel is essential for maintaining the membrane in a hyperpolarized state, thereby regulating neuronal excitability, smooth muscle contraction, and secretion. The BK(Ca) α-subunit has three predicted initiation codons that generate proteins with N-terminal ends starting with the amino acid sequences MANG, MSSN, or MDAL. Because the N-terminal region and first transmembrane domain of the α-subunit are required for modulation by auxiliary β1-subunits, we examined whether β1 differentially modulates the N-terminal BK(Ca) α-subunit isoforms. In the absence of β1, all isoforms had similar single-channel conductances and voltage-dependent activation. However, whereas β1 did not modulate the voltage-activation curve of MSSN, β1 induced a significant leftward shift of the voltage activation curves of both the MDAL and MANG isoforms. These shifts, of which the MDAL was larger, occurred at both 10 μM and 100 μM Ca(2+). The β1-subunit increased the open dwell times of all three isoforms and decreased the closed dwell times of MANG and MDAL but increased the closed dwell times of MSSN. The distinct modulation of voltage activation by the β1-subunit may be due to the differential effect of β1 on burst duration and interburst intervals observed among these isoforms. Additionally, we observed that the related β2-subunit induced comparable leftward shifts in the voltage-activation curves of all three isoforms, indicating that the differential modulation of these isoforms was specific to β1. These findings suggest that the relative expression of the N-terminal isoforms can fine-tune BK(Ca) channel activity in cells, highlighting a novel mechanism of BK(Ca) channel regulation.

  5. Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation.

    PubMed

    Higgins, Joseph J; Hao, Jin; Kosofsky, Barry E; Rajadhyaksha, Anjali M

    2008-07-01

    A nonsense mutation (R419X) in the human cereblon gene [mutation (mut) CRBN] causes a mild type of autosomal recessive nonsyndromal mental retardation (ARNSMR). CRBN, a cytosolic protein, regulates the assembly and neuronal surface expression of large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) in brain regions involved in memory and learning. Using the real-time quantitative polymerase chain reaction, we show that mut CRBN disturbs the development of adult brain BK(Ca) isoforms. These changes are predicted to result in BK(Ca) channels with a higher intracellular Ca(2+) sensitivity, faster activation, and slower deactivation kinetics. Such alterations may contribute to cognitive impairments in patients with mild ARNSMR.

  6. The power stability of a fiber amplifier based on a multifunction card and PID control program

    NASA Astrophysics Data System (ADS)

    Zhang, Linjie; Yang, Wenguang; Zhang, Hao; Zhao, JianMing; Jia, Suotang

    2016-06-01

    The power stability of a fiber amplifier was significantly improved by means of simultaneously controlling the current of a fiber amplifier and the diffraction efficiency of an acousto-optical modulator. The real-time fluctuation of laser power was recorded by a multifunction card and processed by a proportional-integral-derivative (PID) control program. The feedback loop voltage was introduced to the fiber laser amplifier and acoustic-optic modulator through the analog output of the multifunction card. The control method based on a multifunction card and PID program has good scalability, flexibility and reliability for the complex system on the condition in which the frequency and power of the laser need to be precisely stabilized.

  7. Analytical solution of magnetothermoelastic interaction in a fiber-reinforced anisotropic material

    NASA Astrophysics Data System (ADS)

    Hobiny, Aatef D.; Abbas, Ibrahim A.

    2016-12-01

    The present paper is concerned with the investigation of the analytical solution of a fiber-reinforced anisotropic material under generalized magnetothermoelastic theory using the eigenvalue approach. Based on the Lord-Shulman theory, the formulation is applied to generalized magnetothermoelasticity with one relaxation time. Based on eigenvalue approach, exponential Fourier transform and Laplace techniques, the analytical solutions has been obtained. The inverses of Fourier transforms are obtained analytically. Numerical computations for a fiber-reinforced-like material have been performed and the results are presented graphically. The results of the temperature, displacement components and stress components have been verified numerically and are represented graphically. Comparisons are made with the results predicted by the presence and absence of reinforcement.

  8. The Bacterial Tyrosine Kinase Activator TkmA Contributes to Biofilm Formation Largely Independently of the Cognate Kinase PtkA in Bacillus subtilis

    PubMed Central

    Gao, Tantan; Greenwich, Jennifer; Li, Yan

    2015-01-01

    ABSTRACT In Bacillus subtilis, biosynthesis of exopolysaccharide (EPS), a key biofilm matrix component, is regulated at the posttranslational level by the bacterial tyrosine kinase (BY-kinase) EpsB. EpsB, in turn, relies on the cognate kinase activator EpsA for activation. A concerted role of a second BY-kinase–kinase activator pair, PtkA and TkmA, respectively in biofilm formation was also indicated in previous studies. However, the exact functions of PtkA and TkmA in biofilm formation remain unclear. In this work, we show that the kinase activator TkmA contributes to biofilm formation largely independently of the cognate kinase, PtkA. We further show that the biofilm defect caused by a ΔtkmA mutation can be rescued by complementation by epsA, suggesting a functional overlap between TkmA and EpsA and providing a possible explanation for the role of TkmA in biofilm formation. We also show that the importance of TkmA in biofilm formation depends largely on medium conditions; the biofilm defect of ΔtkmA is very severe in the biofilm medium LBGM (lysogenic broth [LB] supplemented with 1% [vol/vol] glycerol and 100 μM MnSO4) but marginal in another commonly used biofilm medium, MSgg (5 mM potassium phosphate [pH 7.0], MOPS [100 mM morpholinepropanesulfonic acid] [pH 7.0], 2 mM MgCl2, 700 μM CaCl2, 50 μM MnCl2, 50 μM FeCl3, 1 μM ZnCl2, 2 μM thiamine, 0.5% glycerol, 0.5% glutamic acid, 50 μg/ml tryptophan, 50 μg/ml threonine, and 50 μg/ml phenylalanine). The molecular basis for the medium dependence is likely due to differential expression of tkmA and epsA in the two different media and complex regulation of these genes by both Spo0A and DegU. Our studies provide genetic evidence for possible cross talk between a BY-kinase activator (TkmA) and a noncognate kinase (EpsB) and an example of how environmental conditions may influence such cross talk in regulating biofilm formation in B. subtilis. IMPORTANCE In bacteria, biosynthesis of secreted polysaccharides

  9. A fiber-optical cable television system using a reflective semiconductor optical amplifier

    NASA Astrophysics Data System (ADS)

    Peng, P. C.; Shiu, K. C.; Liu, W. C.; Chen, K. J.; Lu, H. H.

    2013-02-01

    This investigation demonstrates a fiber-optical cable television system using a reflective semiconductor optical amplifier (RSOA) for uplink transmission. The downstream signal is cable television and the upstream signal is generated by remodulating the downstream signal via an RSOA with a radio-frequency signal. Favorable carrier-to-noise ratio, composite second-order, and composite triple beat are obtained for the downstream and the upstream signal is successfully transmitted over 60 km of single-mode fiber.

  10. Identification of budding yeast using a fiber-optic imaging bundle

    NASA Astrophysics Data System (ADS)

    Koschwanez, John; Holl, Mark; Marquardt, Brian; Dragavon, Joe; Burgess, Lloyd; Meldrum, Deirdre

    2004-05-01

    A successful imaging system has been designed and built for yeast pedigree analysis. The system uses a fiber-optic imaging bundle to recognize single yeast cells. Image processing software has been developed to accurately classify the cells as either budding or not budding a daughter cell. This system is intended to replace the body of a microscope for the detection of budding in a microfluidic system.

  11. Design of a fiber-optic transmitter for microwave analog transmission with high phase stability

    NASA Technical Reports Server (NTRS)

    Logan, R. T., Jr.; Lutes, G. F.; Primas, L. E.; Maleki, L.

    1990-01-01

    The principal considerations in the design of fiber-optic transmitters for highly phase-stable radio frequency and microwave analog transmission are discussed. Criteria for a fiber-optic transmitter design with improved amplitude and phase-noise performance are developed through consideration of factors affecting the phase noise, including low-frequency laser-bias supply noise, the magnitude and proximity of external reflections into the laser, and temperature excursions of the laser-transmitter package.

  12. A Fiber Optic Sensor Sensitive To Normal Pressure And Shear Stress

    NASA Astrophysics Data System (ADS)

    Cuomo, Frank W.; Kidwell, Robert S.; Hu, Andong

    1986-11-01

    A fiber optic lever sensing technique that can be used to measure normal pressure as well as shear stresses is discussed. This method uses three unequal fibers combining small size and good sensitivity. Static measurements appear to confirm the theoretical models predicted by geometrical optics and dynamic tests performed at frequencies up to 10 kHz indicate a flat response within this frequency range. These sensors are intended for use in a low speed wind tunnel environment.

  13. Toward endoscopes with no distal optics: video-rate scanning microscopy through a fiber bundle.

    PubMed

    Andresen, Esben Ravn; Bouwmans, Géraud; Monneret, Serge; Rigneault, Hervé

    2013-03-01

    We report a step toward scanning endomicroscopy without distal optics. The focusing of the beam at the distal end of a fiber bundle is achieved by imposing a parabolic phase profile across the exit face with the aid of a spatial light modulator. We achieve video-rate images by galvanometric scanning of the phase tilt at the proximal end. The approach is made possible by the bundle, designed to have very low coupling between cores.

  14. Activation of galanin receptor 2 stimulates large conductance Ca(2+)-dependent K(+) (BK) channels through the IP3 pathway in human embryonic kidney (HEK293) cells.

    PubMed

    Pan, Na Clara; Bai, Yun-Fei; Yang, Yutao; Hökfelt, Tomas; Xu, Zhi-Qing David

    2014-03-28

    The large conductance Ca(2+)-activated K(+) (BK) channels are widely distributed in the brain, and act as intracellular calcium sensors in neurons. They play an important feedback role in controlling Ca(2+) flux and Ca(2+)-dependent processes, including neurotransmitter release and cellular excitability. In this study, the effects of the neuropeptide galanin on BK channels were examined by determining the whole-cell currents and single-channel activities in human embryonic kidney (HEK293) cells co-expressing GalR2 and the BK alpha subunit. Galanin enhanced the currents of BK channels, in a concentration-dependent and PTX-independent manner, with an ED50 value of 71.8±16.9 nM. This activation was mediated by GalR2, since its agonist AR-M1896 mimicked the effect of galanin, and since galanin did not facilitate BK currents in cells co-expressing cDNAs of BK and GalR1 or GalR3. The galanin-induced BK current persisted after replacement with Ca(2+)-free solution, suggesting that extracellular Ca(2+) is not essential. Chelating intracellular Ca(2+) by either the slow Ca(2+) buffer EGTA or the fast Ca(2+) buffer BAPTA abolished galanin-mediated activation of BK channels, indicating the important role of intracellular Ca(2+). The role of Ca(2+) efflux from the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) was confirmed by application of thapsigargin, an irreversible inhibitor that depletes Ca(2+) from SR/ER. Moreover, the inositol-1,4,5-triphosphate receptor (IP3R) was identified as the mediator responsible for increased intracellular Ca(2+) activating BK channels. Taken together, activation of GalR2 leads to elevation of intracellular Ca(2+) is due to Ca(2+) efflux from ER through IP3R sequentially opening BK channels.

  15. CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas.

    PubMed

    Juilland, Mélanie; Gonzalez, Montserrat; Erdmann, Tabea; Banz, Yara; Jevnikar, Zala; Hailfinger, Stephan; Tzankov, Alexandar; Grau, Michael; Lenz, Georg; Novak, Urban; Thome, Margot

    2016-04-07

    A hallmark of the diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) type, a molecular subtype characterized by adverse outcome, is constitutive activation of the transcription factor nuclear factor-κB (NF-κB), which controls expression of genes promoting cellular survival and proliferation. Much less, however, is known about the role of the transcription factor activator protein-1 (AP-1) in ABC DLBCL. Here, we show that AP-1, like NF-κB, was controlled by constitutive activation of the B-cell receptor signaling component caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) and/or the Toll-like receptor signaling component myeloid differentiation primary response gene 88 (MyD88) in ABC DLBCL cell lines. In contrast to germinal center (GC) B-cell (GCB) DLBCL, ABC DLBCL cell lines expressed high levels of the AP-1 family members c-Jun, JunB, and JunD, which formed heterodimeric complexes with the AP-1 family members activating transcription factor (ATF) 2, ATF3, and ATF7. Inhibition of these complexes by a dominant-negative approach led to impaired growth of a majority of ABC DLBCL cell lines. Individual silencing of c-Jun, ATF2, or ATF3 decreased cellular survival and revealed c-Jun/ATF2-dependent control of ATF3 expression. As a consequence, ATF3 expression was much higher in ABC vs GCB DLBCL cell lines. Samples derived from DLBCL patients showed a clear trend toward high and nuclear ATF3 expression in nodal DLBCL of the non-GC or ABC subtype. These findings identify the activation of AP-1 complexes of the Jun/ATF-type as an important element controlling the growth of ABC DLBCL.

  16. CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas

    PubMed Central

    Juilland, Mélanie; Gonzalez, Montserrat; Erdmann, Tabea; Banz, Yara; Jevnikar, Zala; Hailfinger, Stephan; Tzankov, Alexandar; Grau, Michael; Lenz, Georg; Novak, Urban

    2016-01-01

    A hallmark of the diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) type, a molecular subtype characterized by adverse outcome, is constitutive activation of the transcription factor nuclear factor–κB (NF-κB), which controls expression of genes promoting cellular survival and proliferation. Much less, however, is known about the role of the transcription factor activator protein-1 (AP-1) in ABC DLBCL. Here, we show that AP-1, like NF-κB, was controlled by constitutive activation of the B-cell receptor signaling component caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) and/or the Toll-like receptor signaling component myeloid differentiation primary response gene 88 (MyD88) in ABC DLBCL cell lines. In contrast to germinal center (GC) B-cell (GCB) DLBCL, ABC DLBCL cell lines expressed high levels of the AP-1 family members c-Jun, JunB, and JunD, which formed heterodimeric complexes with the AP-1 family members activating transcription factor (ATF) 2, ATF3, and ATF7. Inhibition of these complexes by a dominant-negative approach led to impaired growth of a majority of ABC DLBCL cell lines. Individual silencing of c-Jun, ATF2, or ATF3 decreased cellular survival and revealed c-Jun/ATF2-dependent control of ATF3 expression. As a consequence, ATF3 expression was much higher in ABC vs GCB DLBCL cell lines. Samples derived from DLBCL patients showed a clear trend toward high and nuclear ATF3 expression in nodal DLBCL of the non-GC or ABC subtype. These findings identify the activation of AP-1 complexes of the Jun/ATF-type as an important element controlling the growth of ABC DLBCL. PMID:26747248

  17. Cosmological, large-scale simulations of BH growth: demographics, the AGN-host connection and the relevance of mergers in driving nuclear activity

    NASA Astrophysics Data System (ADS)

    Hirschmann, Michaela; Dolag, Klaus; Bachmann, Lisa

    2015-08-01

    We provide new insights into the cosmic evolution of black holes (BHs) and their host galaxies by employing large-scale cosmological, hydrodynamic simulations capturing a huge volume of (500 Mpc)3. They are shown to be successful in reproducing a number of observational, statistical constraints, e.g. the evolution of the AGN luminosity function (in the soft and hard X-ray band) together with the corresponding downsizing trend. This is mainly due to the evolution of the gas density in the vicinity of a BH and due to the correction for dust obscuration on a torus-level. We further demonstrate that only luminous AGN are preferentially triggered by merger events, while for the majority of moderately luminous AGN, additional driving mechanisms seem to be necessary. Exploring the AGN-host connection, we find that host SFRs and AGN luminosities are always correlated (albeit with a large scatter) when averaging over the AGN luminosities (but not when averaging over SFR) in reasonably good agreement with recent observations. Interestingly, for the most luminous AGN, a slightly tighter and steeper correlation between AGN luminosities and SFRs emerges, which may originate from the increasing relevance of mergers in driving their nuclear activity. Overall, the new generation AGN, BH and galaxy catalogues, provided by our simulation, are expected to significantly contribute to the interpretation of current and up-coming large-scale surveys (XMM, ATHENA, eRosita, Euclid) with respect to the evolution of BHs within the emerging cosmic structure.

  18. Estimated likelihood of observing a large earthquake on a continental low-angle normal fault and implications for low-angle normal fault activity

    NASA Astrophysics Data System (ADS)

    Styron, Richard H.; Hetland, Eric A.

    2014-04-01

    The lack of observed continental earthquakes that clearly occurred on low-angle normal faults (LANFs) may indicate that these structures are not seismically active or that these earthquakes are simply rare events. To address this, we compile all potentially active continental LANFs (24 in total) and calculate the likelihood of observing a significant earthquake on them over periods of 1-100 years. This probability depends on several factors including the frequency-magnitude distribution. For either a characteristic or Gutenberg-Richter distribution, we calculate a probability of about 0.5 that an earthquake greater than M6.5 (large enough to avoid ambiguity in dip angle) will be observed on any LANF in a period of 35 years, which is the current length of the global centroid moment tensor catalog. We then use Bayes' Theorem to illustrate how the absence of observed significant LANF seismicity over the catalog period moderately decreases the likelihood that the structures generate large earthquakes.

  19. Identification of One Novel Candidate Probiotic Lactobacillus plantarum Strain Active against Influenza Virus Infection in Mice by a Large-Scale Screening

    PubMed Central

    Kechaou, Noura; Chain, Florian; Gratadoux, Jean-Jacques; Blugeon, Sébastien; Bertho, Nicolas; Chevalier, Christophe; Le Goffic, Ronan; Courau, Stéphanie; Molimard, Pascal; Chatel, Jean Marc

    2013-01-01

    In this study, we developed a large-scale screening of bacterial strains in order to identify novel candidate probiotics with immunomodulatory properties. For this, 158 strains, including a majority of lactic acid bacteria (LAB), were screened by two different cellular models: tumor necrosis factor alpha (TNF-α)-activated HT-29 cells and peripheral blood mononuclear cells (PBMCs). Different strains responsive to both models (pro- and anti-inflammatory strains) were selected, and their protective effects were tested in vivo in a murine model of influenza virus infection. Daily intragastric administrations during 10 days before and 10 days after viral challenge (100 PFU of influenza virus H1N1 strain A Puerto Rico/8/1934 [A/PR8/34]/mouse) of Lactobacillus plantarum CNRZ1997, one potentially proinflammatory probiotic strain, led to a significant improvement in mouse health by reducing weight loss, alleviating clinical symptoms, and inhibiting significantly virus proliferation in lungs. In conclusion, in this study, we have combined two cellular models to allow the screening of a large number of LAB for their immunomodulatory properties. Moreover, we identified a novel candidate probiotic strain, L. plantarum CNRZ1997, active against influenza virus infection in mice. PMID:23263960

  20. Application of optimized large surface area date stone (Phoenix dactylifera ) activated carbon for rhodamin B removal from aqueous solution: Box-Behnken design approach.

    PubMed

    Danish, Mohammed; Khanday, Waheed Ahmad; Hashim, Rokiah; Sulaiman, Nurul Syuhada Binti; Akhtar, Mohammad Nishat; Nizami, Maniruddin

    2017-05-01

    Box-Behnken model of response surface methodology was used to study the effect of adsorption process parameters for Rhodamine B (RhB) removal from aqueous solution through optimized large surface area date stone activated carbon. The set experiments with three input parameters such as time (10-600min), adsorbent dosage (0.5-10g/L) and temperature (25-50°C) were considered for statistical significance. The adequate relation was found between the input variables and response (removal percentage of RhB) and Fisher values (F- values) along with P-values suggesting the significance of various term coefficients. At an optimum adsorbent dose of 0.53g/L, time 593min and temperature 46.20°C, the adsorption capacity of 210mg/g was attained with maximum desirability. The negative values of Gibb(')s free energy (ΔG) predicted spontaneity and feasibility of adsorption; whereas, positive Enthalpy change (ΔH) confirmed endothermic adsorption of RhB onto optimized large surface area date stone activated carbons (OLSADS-AC). The adsorption data were found to be the best fit on the Langmuir model supporting monolayer type of adsorption of RhB with maximum monolayer layer adsorption capacity of 196.08mg/g.

  1. Non-destructive elemental analysis of large meteorite samples by prompt gamma-ray neutron activation analysis with the internal mono-standard method.

    PubMed

    Latif, Sk A; Oura, Y; Ebihara, M; Nakahara, H

    2013-11-01

    Prompt gamma-ray neutron activation analysis (PGNAA) using the internal mono-standard method was tested for its applicability to analyzing large solid samples including irregularly shaped meteorite samples. For evaluating the accuracy and precision of the method, large quantities of the Geological Survey of Japan standardized rock powders (JB-1a, JG-1a, and JP-1) were analyzed and 12 elements (B, Na, Mg, Al, Cl, K, Ca, Ti, Mn, Fe, Sm, and Gd) were determined by using Si as an internal standard element. Analytical results were mostly in agreement with literature values within 10 %. The precision of the method was also shown to be within 10 % (1σ) for most of these elements. The analytical procedure was then applied to four stony meteorites (Allende, Kimble County, Leedey, Lake Labyrinth) and four iron meteorites (Canyon Diablo, Toluca (Mexico), Toluca (Xiquipilco), Squaw Creek) consisting of large chunks or single slabs. For stony meteorites, major elements (Mg, Al, Si, S, Ca, and Ni), minor elements (Na and Mn) and trace element (B, Cl, K, Ti, Co, and Sm) were determined with adequate accuracy. For iron meteorites, results for the Co and Ni mass fractions determined are all consistent with corresponding literature values. After the analysis, it was confirmed that the residual radioactivity remaining in the sample after PGNAA was very low and decreased down to the background level. This study shows that PGNAA with the internal mono-standard method is highly practical for determining the elemental composition of large, irregularly shaped solid samples including meteorites.

  2. Wanderlust kinetics and variable Ca(2+)-sensitivity of dSlo [correction of Drosophila], a large conductance CA(2+)-activated K+ channel, expressed in oocytes.

    PubMed Central

    Silberberg, S D; Lagrutta, A; Adelman, J P; Magleby, K L

    1996-01-01

    Cloned large conductance Ca2+-activated K+ channels (BK or maxi-K+ channels) from Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised membrane patches with the patch-clamp technique. Both a natural variant and a mutant that eliminated a putative cyclic AMP-dependent protein kinase phosphorylation site exhibited large, slow fluctuations in open probability with time. These fluctuations, termed "wanderlust kinetics," occurred with a time course of tens of seconds to minutes and had kinetic properties inconsistent with simple gating models. Wanderlust kinetics was still observed in the presence of 5mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the solution was increased by the addition of 5 mM HEDTA, suggesting that the wanderlust kinetics did not arise from Ca2+ release from caffeine and thapsigargin sensitive internal stores in the excised patch. The slow changes in kinetics associated with wanderlust kinetics could be generated with a discrete-state Markov model with transitions among three or more kinetic modes with different levels of open probability. To average out the wanderlust kinetics, large amounts of data were analyzed and demonstrated up to a threefold difference in the [Ca2+]i required for an open probability of 0.5 among channels expressed from the same injected mRNA. These findings indicate that cloned dSlo channels in excised patches from Xenopus oocytes can exhibit large variability in gating properties, both within a single channel and among channels. PMID:9643949

  3. Enhanced photocatalytic activity of hexagonal flake-like Bi2S3 / ZnS composites with a large percentage of reactive facets

    NASA Astrophysics Data System (ADS)

    Xiong, Dan-Ni; Huang, Gui-Fang; Zhou, Bing-Xin; Chang, Shengli; Wang, Fei; Huang, Wei-Qing

    2016-08-01

    Selectively exposing surfaces with high reactivity is an effective strategy to enhance the photocatalytic activity of semiconductor photocatalysts. We report the facile synthesis of hexagonal flake-like Bi2S3/ZnS composites with a large percentage of reactive exposed {2 2 1} facets by tuning only the molar ratios of Bi to Zn. The samples exhibit enhanced optical absorption and red shift of absorption edge. The Bi2S3/ZnS composites with hexagon morphology display superior photocatalytic degradation of methylene blue (MB), faster than that with pure Bi2S3 and pure ZnS by a factor of 7.1 and 3.6, respectively. The enhanced photocatalytic activity can be attributed to the highly reactive {2 2 1} exposed facets and the more efficient separation of photogenerated electron-hole pairs is due to the interface of the hetero-junction. Furthermore, a tentative mechanism for photodegradation of MB over Bi2S3/ZnS composites has been proposed involving the photogenerated holes and ṡOH radicals as the main active species, which is confirmed by using different scavengers. The novel constructed Bi2S3/ZnS composite is expected to be an attractive candidate as a photocatalyst for environmental purification and energy conversion.

  4. The novel kinesin spindle protein (KSP) inhibitor SB-743921 exhibits marked activity in in vivo and in vitro models of aggressive large B-cell lymphoma.

    PubMed

    Bongero, Danielle; Paoluzzi, Luca; Marchi, Enrica; Zullo, Kelly M; Neisa, Roberto; Mao, Yinghui; Escandon, Rafael; Wood, Ken; O'Connor, Owen A

    2015-01-01

    The kinesin spindle protein (KSP) is a mitotic protein essential for cell cycle control and motility. SB-743921 (hereafter SB-921) is an inhibitor that selectively targets the ATP-binding domain of the KSP. The preclinical activity of SB-921 was evaluated in models of diffuse large B-cell lymphoma (DLBCL). The cytotoxicity of SB-921 was evaluated in a series of germinal center (GC-DLBCL) and post-germinal center (ABC-DLBCL) DLBCL cell lines and a murine lymphoma xenograft model. GC-DLBCL lines generally demonstrated greater sensitivity to SB-921. IC50 values ranged between 1 nM and 900 nM for GC-DLBCL compared to 1 nM to 10 μM for ABC lines. SB-921 demonstrated marked activity in a xenograft model of Ly-1 (GC-DLBCL). While SB-921 was relatively more active in GC derived cell lines, ABC-derived lines still underwent apoptosis at higher concentrations. These results demonstrate that SB-921 inhibits proliferation and induces apoptosis in both GC-DLBCL and ABC-DLBCL.

  5. Large lateral movement of transmembrane helix S5 is not required for substrate access to the active site of rhomboid intramembrane protease.

    PubMed

    Xue, Yi; Ha, Ya

    2013-06-07

    Rhomboids represent an evolutionarily ancient protease family. Unlike most other proteases, they are polytopic membrane proteins and specialize in cleaving transmembrane protein substrates. The polar active site of rhomboid protease is embedded in the membrane and normally closed. For the bacterial rhomboid GlpG, it has been proposed that one of the transmembrane helices (S5) of the protease can rotate to open a lateral gate, enabling substrate to enter the protease from inside the membrane. Here, we studied the conformational change in GlpG by solving the cocrystal structure of the protease with a mechanism-based inhibitor. We also examined the lateral gating model by cross-linking S5 to a neighboring helix (S2). The crystal structure shows that inhibitor binding displaces a capping loop (L5) from the active site but causes only minor shifts in the transmembrane helices. Cross-linking S5 and S2, which not only restricts the lateral movement of S5 but also prevents substrate from passing between the two helices, does not hinder the ability of the protease to cleave a membrane protein substrate in detergent solution and in reconstituted membrane vesicles. Taken together, these data suggest that a large lateral movement of the S5 helix is not required for substrate access to the active site of rhomboid protease.

  6. [Diversity, relative abundance and activity patterns of medium and large mammals in a tropical deciduous forest in the Isthmus of Tehuantepec, Oaxaca, Mexico].

    PubMed

    Cortés-Marcial, Malinalli; Briones-Salas, Miguel

    2014-12-01

    The use of camera traps and mammal track search are complementary methods to monitoring species of which is not well documented their natural history, as in the case of medium and large mammals. To ensure its conservation and good management, it is necessary to generate information about the structure of the community and their populations. The objective of the present study was to estimate the diversity, relative abundance and activity patterns of medium and large mammals in a tropical deciduous forest located in the Isthmus of Tehuantepec, Oaxaca, Mexico. Samplings were conducted in three month intervals, from September 2011 to May 2013. We used photographic-sampling and track search, two complementary sampling methods. For photographic-sampling, 12 camera traps were placed covering an area of 60 km2, while for the tracks search a monthly tour of four line-transect surveys of three kilometers length each was undertaken. We obtained a total of 344 pictures with 5292 trap-days total sampling effort; in addition, 187 track records in a total of 144 km. With both methods we registered 21 species of mammals, in 13 families and seven orders, and five species resulted in new records to the area. The diversity index of Shannon-Wiener obtained with the method of tracks was H' = 2.41, while the most abundant species were Urocyon cinereoargen- teus (IAR = 0.23) and Pecari tajacu (IAR = 0.20). By the method of trap the most abundant species were P. tajacu (IAR = 2.62) and Nasua narica (IAR = 1.28). In terms of patterns of activity P. tajacu, N. narica and Odocoileus virginianus were primarily diurnal species; Canis latrans and Leopardus pardalis did not show preference for any schedule in particular, and Didelphis virginiana and Dasypus novemcinctus preferred to have nocturnal activity. This information can be of help to the creation of programs of management and conservation of mam- mals of medium and large in the Isthmus of Tehuantepec, Oaxaca, México.

  7. Computational efficiency of numerical approximations of tangent moduli for finite element implementation of a fiber-reinforced hyperelastic material model.

    PubMed

    Liu, Haofei; Sun, Wei

    2016-01-01

    In this study, we evaluated computational efficiency of finite element (FE) simulations when a numerical approximation method was used to obtain the tangent moduli. A fiber-reinforced hyperelastic material model for nearly incompressible soft tissues was implemented for 3D solid elements using both the approximation method and the closed-form analytical method, and validated by comparing the components of the tangent modulus tensor (also referred to as the material Jacobian) between the two methods. The computational efficiency of the approximation method was evaluated with different perturbation parameters and approximation schemes, and quantified by the number of iteration steps and CPU time required to complete these simulations. From the simulation results, it can be seen that the overall accuracy of the approximation method is improved by adopting the central difference approximation scheme compared to the forward Euler approximation scheme. For small-scale simulations with about 10,000 DOFs, the approximation schemes could reduce the CPU time substantially compared to the closed-form solution, due to the fact that fewer calculation steps are needed at each integration point. However, for a large-scale simulation with about 300,000 DOFs, the advantages of the approximation schemes diminish because the factorization of the stiffness matrix will dominate the solution time. Overall, as it is material model independent, the approximation method simplifies the FE implementation of a complex constitutive model with comparable accuracy and computational efficiency to the closed-form solution, which makes it attractive in FE simulations with complex material models.

  8. Single-channel biophysical and pharmacological characterizations of native human large-conductance calcium-activated potassium channels in freshly isolated detrusor smooth muscle cells.

    PubMed

    Malysz, John; Rovner, Eric S; Petkov, Georgi V

    2013-07-01

    Recent studies have demonstrated the importance of large-conductance Ca(2+)-activated K(+) (BK) channels in detrusor smooth muscle (DSM) function in vitro and in vivo. However, in-depth characterization of human native DSM single BK channels has not yet been provided. Here, we conducted single-channel recordings from excised patches from native human DSM cells. Inside-out and outside-out recordings in high K(+) symmetrical solution (containing 140 mM KCl and ~300 nM free Ca(2+)) showed single-channel conductance of 215-220 pS, half-maximum constant for activation of ~+75 to +80 mV, and low probability of opening (P o) at +20 mV that increased ~10-fold at +40 mV and ~60-fold at +60 mV. Using the inside-out configuration at +30 mV, reduction of intracellular [Ca(2+)] from ~300 nM to Ca(2+)-free decreased the P o by ~85 %, whereas elevation to ~800 nM increased P o by ~50-fold. The BK channel activator NS1619 (10 μM) enhanced the P o by ~10-fold at +30 mV; subsequent application of the selective BK channel inhibitor paxilline (500 nM) blocked the activity. Changes in intracellular [Ca(2+)] or the addition of NS1619 did not significantly alter the current amplitude or single-channel conductance. This is the first report to provide biophysical and pharmacological profiles of native human DSM single BK channels highlighting their importance in regulating human DSM excitability.

  9. Anticancer activity of SAHA, a potent histone deacetylase inhibitor, in NCI-H460 human large-cell lung carcinoma cells in vitro and in vivo.

    PubMed

    Zhao, Yanxia; Yu, Dandan; Wu, Hongge; Liu, Hongli; Zhou, Hongxia; Gu, Runxia; Zhang, Ruiguang; Zhang, Sheng; Wu, Gang

    2014-02-01

    Suberoylanilide hydroxamic acid (SAHA), a potent pan-histone deacetylase (HDAC) inhibitor, has been clinically approved for the treatment of cutaneous T-cell lymphoma (CTCL). SAHA has also been shown to exert a variety of anticancer activities in many other types of tumors, however, few studies have been reported in large-cell lung carcinoma (LCC). Our study aimed to investigate the potential antitumor effects of SAHA on LCC cells. Here, we report that SAHA was able to inhibit the proliferation of the LCC cell line NCI-H460 in a dose- and time-dependent manner, induced cell apoptosis and G2/M cell cycle arrest, decreased AKT and ERK phosphorylation, inhibited the expression of pro-angiogenic factors (VEGF, HIF-1α) in vitro, and suppressed tumor progression in an NCI-H460 cell nude mouse xenograft model in vivo. These results indicate that SAHA can exert its strong antitumor effects in LCC patient.

  10. Large-scale distribution and activity of prokaryotes in deep-sea surface sediments of the Mediterranean Sea and the adjacent Atlantic Ocean.

    PubMed

    Giovannelli, Donato; Molari, Massimiliano; d'Errico, Giuseppe; Baldrighi, Elisa; Pala, Claudia; Manini, Elena

    2013-01-01

    The deep-sea represents a substantial portion of the biosphere and has a major influence on carbon cycling and global biogeochemistry. Benthic deep-sea prokaryotes have crucial roles in this ecosystem, with their recycling of organic matter from the photic zone. Despite this, little is known about the large-scale distribution of prokaryotes in the surface deep-sea sediments. To assess the influence of environmental and trophic variables on the large-scale distribution of prokaryotes, we investigated the prokaryotic assemblage composition (Bacteria to Archaea and Euryarchaeota to Crenarchaeota ratio) and activity in the surface deep-sea sediments of the Mediterranean Sea and the adjacent North Atlantic Ocean. Prokaryotic abundance and biomass did not vary significantly across the Mediterranean Sea; however, there were depth-related trends in all areas. The abundance of prokaryotes was positively correlated with the sedimentary concentration of protein, an indicator of the quality and bioavailability of organic matter. Moving eastwards, the Bacteria contribution to the total prokaryotes decreased, which appears to be linked to the more oligotrophic conditions of the Eastern Mediterranean basins. Despite the increased importance of Archaea, the contributions of Crenarchaeota Marine Group I to the total pool was relatively constant across the investigated stations, with the exception of Matapan-Vavilov Deep, in which Euryarchaeota Marine Group II dominated. Overall, our data suggest that deeper areas of the Mediterranean Sea share more similar communities with each other than with shallower sites. Freshness and quality of sedimentary organic matter were identified through Generalized Additive Model analysis as the major factors for describing the variation in the prokaryotic community structure and activity in the surface deep-sea sediments. Longitude was also important in explaining the observed variability, which suggests that the overlying water masses might have a

  11. Film Excerpts Shown to Specifically Elicit Various Affects Lead to Overlapping Activation Foci in a Large Set of Symmetrical Brain Regions in Males

    PubMed Central

    Karama, Sherif; Armony, Jorge; Beauregard, Mario

    2011-01-01

    While the limbic system theory continues to be part of common scientific parlance, its validity has been questioned on multiple grounds. Nonetheless, the issue of whether or not there exists a set of brain areas preferentially dedicated to emotional processing remains central within affective neuroscience. Recently, a widespread neural reference space for emotion which includes limbic as well as other regions was characterized in a large meta-analysis. As methodologically heterogeneous studies go into such meta-analyses, showing in an individual study in which all parameters are kept constant, the involvement of overlapping areas for various emotion conditions in keeping with the neural reference space for emotion, would serve as valuable confirmatory evidence. Here, using fMRI, 20 young adult men were scanned while viewing validated neutral and effective emotion-eliciting short film excerpts shown to quickly and specifically elicit disgust, amusement, or sexual arousal. Each emotion-specific run included, in random order, multiple neutral and emotion condition blocks. A stringent conjunction analysis revealed a large overlap across emotion conditions that fit remarkably well with the neural reference space for emotion. This overlap included symmetrical bilateral activation of the medial prefrontal cortex, the anterior cingulate, the temporo-occipital junction, the basal ganglia, the brainstem, the amygdala, the hippocampus, the thalamus, the subthalamic nucleus, the posterior hypothalamus, the cerebellum, as well as the frontal operculum extending towards the anterior insula. This study clearly confirms for the visual modality, that processing emotional stimuli leads to widespread increases in activation that cluster within relatively confined areas, regardless of valence. PMID:21818311

  12. CD204 suppresses large heat shock protein-facilitated priming of tumor antigen gp100-specific T cells and chaperone vaccine activity against mouse melanoma.

    PubMed

    Qian, Jie; Yi, Huanfa; Guo, Chunqing; Yu, Xiaofei; Zuo, Daming; Chen, Xing; Kane, John M; Repasky, Elizabeth A; Subjeck, John R; Wang, Xiang-Yang

    2011-09-15

    We previously reported that scavenger receptor A (SRA/CD204), a binding structure on dendritic cells (DCs) for large stress/heat shock proteins (HSPs; e.g., hsp110 and grp170), attenuated an antitumor response elicited by large HSP-based vaccines. In this study, we show that SRA/CD204 interacts directly with exogenous hsp110, and lack of SRA/CD204 results in a reduction in the hsp110 binding and internalization by DCs. However, SRA(-/-) DCs pulsed with hsp110 or grp170-reconstituted gp100 chaperone complexes exhibit a profoundly increased capability of stimulating melanoma Ag gp100-specific naive T cells compared with wild-type (WT) DCs. Similar results were obtained when SRA/CD204 was silenced in DCs using short hairpin RNA-encoding lentiviruses. In addition, hsp110-stimulated SRA(-/-) DCs produced more inflammatory cytokines associated with increased NF-κB activation, implicating an immunosuppressive role for SRA/CD204. Immunization with the hsp110-gp100 vaccine resulted in a more robust gp100-specific CD8(+) T cell response in SRA(-/-) mice than in WT mice. Lastly, SRA/CD204 absence markedly improved the therapeutic efficacy of the hsp110-gp100 vaccine in mice established with B16 melanoma, which was accompanied by enhanced activation and tumor infiltration of CD8(+) T cells. Given the presence of multiple HSP-binding scavenger receptors on APCs, we propose that selective scavenger receptor interactions with HSPs may lead to highly distinct immunological consequences. Our findings provide new insights into the immune regulatory functions of SRA/CD204 and have important implications in the rational design of protein Ag-targeted recombinant chaperone vaccines for the treatment of cancer.

  13. An efficient top-down approach for the fabrication of large-aspect-ratio g-C3N4 nanosheets with enhanced photocatalytic activities.

    PubMed

    Tong, Jincheng; Zhang, Li; Li, Fei; Li, Mingming; Cao, Shaokui

    2015-09-28

    Graphitic carbon nitride (g-C3N4) nanosheets with large aspect ratios were fabricated from bulk g-C3N4 through an efficient top-down approach of moderate disintegration-exfoliation using diluted H2SO4 as an "efficient knife". By prior disintegration in a diluted H2SO4 solution, the exfoliation of bulk g-C3N4 was effectively accelerated. The as-prepared g-C3N4 nanosheets possess a two-dimensional (2D) thin-layer structure with seven-atom thickness, a large lateral size of about 1 μm, and a high specific surface area of 80 m(2) g(-1). Compared with the bulk precursor, the g-C3N4 nanosheets showed much higher efficiency of photogenerated charge transfer and separation, and consequently exhibited enhanced photocatalytic activity toward hydrogen evolution and pollutant decomposition under both full-sunlight and visible-light irradiation.

  14. The SpaceInn-SISMA Database: Characterization of a Large Sample of Variable and Active Stars by Means of Harps Spectra

    NASA Astrophysics Data System (ADS)

    Rainer, M.; Poretti, E.; Mistò, A.; Panzera, M. R.; Molinaro, M.; Cepparo, F.; Roth, M.; Michel, E.; Monteiro, M. J. P. F. G.

    2016-12-01

    We created a large database of physical parameters and variability indicators by fully reducing and analyzing the large number of spectra taken to complement the asteroseismic observations of the COnvection, ROtation and planetary Transits (CoRoT) satellite. 7103 spectra of 261 stars obtained with the ESO echelle spectrograph HARPS have been stored in the VO-compliant database Spectroscopic Indicators in a SeisMic Archive (SISMA), along with the CoRoT photometric data of the 72 CoRoT asteroseismic targets. The remaining stars belong to the same variable classes of the CoRoT targets and were observed to better characterize the properties of such classes. Several useful variability indicators (mean line profiles, indices of differential rotation, activity and emission lines) together with v\\sin i and radial-velocity measurements have been extracted from the spectra. The atmospheric parameters {T}{eff},{log}g, and [Fe/H] have been computed following a homogeneous procedure. As a result, we fully characterize a sample of new and known variable stars by computing several spectroscopic indicators, also providing some cases of simultaneous photometry and spectroscopy.