Sample records for l1 lagrange point

  1. Investigating Trojan Asteroids at the L4/L5 Sun-Earth Lagrange Points

    NASA Technical Reports Server (NTRS)

    John, K. K.; Graham, L. D.; Abell, P. A.

    2015-01-01

    Investigations of Earth's Trojan asteroids will have benefits for science, exploration, and resource utilization. By sending a small spacecraft to the Sun-Earth L4 or L5 Lagrange points to investigate near-Earth objects, Earth's Trojan population can be better understood. This could lead to future missions for larger precursor spacecraft as well as human missions. The presence of objects in the Sun-Earth L4 and L5 Lagrange points has long been suspected, and in 2010 NASA's Wide-field Infrared Survey Explorer (WISE) detected a 300 m object. To investigate these Earth Trojan asteroid objects, it is both essential and feasible to send spacecraft to these regions. By exploring a wide field area, a small spacecraft equipped with an IR camera could hunt for Trojan asteroids and other Earth co-orbiting objects at the L4 or L5 Lagrange points in the near-term. By surveying the region, a zeroth-order approximation of the number of objects could be obtained with some rough constraints on their diameters, which may lead to the identification of potential candidates for further study. This would serve as a precursor for additional future robotic and human exploration targets. Depending on the inclination of these potential objects, they could be used as proving areas for future missions in the sense that the delta-V's to get to these targets are relatively low as compared to other rendezvous missions. They can serve as platforms for extended operations in deep space while interacting with a natural object in microgravity. Theoretically, such low inclination Earth Trojan asteroids exist. By sending a spacecraft to L4 or L5, these likely and potentially accessible targets could be identified.

  2. The Lagrange Points

    ERIC Educational Resources Information Center

    Lovell, M.S.

    2007-01-01

    This paper presents a derivation of all five Lagrange points by methods accessible to sixth-form students, and provides a further opportunity to match Newtonian gravity with centripetal force. The predictive powers of good scientific theories are also discussed with regard to the philosophy of science. Methods for calculating the positions of the…

  3. Modeling the Global Coronal Field with Simulated Synoptic Magnetograms from Earth and the Lagrange Points L3, L4, and L5

    NASA Astrophysics Data System (ADS)

    Petrie, Gordon; Pevtsov, Alexei; Schwarz, Andrew; DeRosa, Marc

    2018-06-01

    The solar photospheric magnetic flux distribution is key to structuring the global solar corona and heliosphere. Regular full-disk photospheric magnetogram data are therefore essential to our ability to model and forecast heliospheric phenomena such as space weather. However, our spatio-temporal coverage of the photospheric field is currently limited by our single vantage point at/near Earth. In particular, the polar fields play a leading role in structuring the large-scale corona and heliosphere, but each pole is unobservable for {>} 6 months per year. Here we model the possible effect of full-disk magnetogram data from the Lagrange points L4 and L5, each extending longitude coverage by 60°. Adding data also from the more distant point L3 extends the longitudinal coverage much further. The additional vantage points also improve the visibility of the globally influential polar fields. Using a flux-transport model for the solar photospheric field, we model full-disk observations from Earth/L1, L3, L4, and L5 over a solar cycle, construct synoptic maps using a novel weighting scheme adapted for merging magnetogram data from multiple viewpoints, and compute potential-field models for the global coronal field. Each additional viewpoint brings the maps and models into closer agreement with the reference field from the flux-transport simulation, with particular improvement at polar latitudes, the main source of the fast solar wind.

  4. Feasibility of cooling the Earth with a cloud of small spacecraft near the inner Lagrange point (L1).

    PubMed

    Angel, Roger

    2006-11-14

    If it were to become apparent that dangerous changes in global climate were inevitable, despite greenhouse gas controls, active methods to cool the Earth on an emergency basis might be desirable. The concept considered here is to block 1.8% of the solar flux with a space sunshade orbited near the inner Lagrange point (L1), in-line between the Earth and sun. Following the work of J. Early [Early, JT (1989) J Br Interplanet Soc 42:567-569], transparent material would be used to deflect the sunlight, rather than to absorb it, to minimize the shift in balance out from L1 caused by radiation pressure. Three advances aimed at practical implementation are presented. First is an optical design for a very thin refractive screen with low reflectivity, leading to a total sunshade mass of approximately 20 million tons. Second is a concept aimed at reducing transportation cost to 50 dollars/kg by using electromagnetic acceleration to escape Earth's gravity, followed by ion propulsion. Third is an implementation of the sunshade as a cloud of many spacecraft, autonomously stabilized by modulating solar radiation pressure. These meter-sized "flyers" would be assembled completely before launch, avoiding any need for construction or unfolding in space. They would weigh a gram each, be launched in stacks of 800,000, and remain for a projected lifetime of 50 years within a 100,000-km-long cloud. The concept builds on existing technologies. It seems feasible that it could be developed and deployed in approximately 25 years at a cost of a few trillion dollars, <0.5% of world gross domestic product (GDP) over that time.

  5. Feasibility of cooling the Earth with a cloud of small spacecraft near the inner Lagrange point (L1)

    PubMed Central

    Angel, Roger

    2006-01-01

    If it were to become apparent that dangerous changes in global climate were inevitable, despite greenhouse gas controls, active methods to cool the Earth on an emergency basis might be desirable. The concept considered here is to block 1.8% of the solar flux with a space sunshade orbited near the inner Lagrange point (L1), in-line between the Earth and sun. Following the work of J. Early [Early, JT (1989) J Br Interplanet Soc 42:567–569], transparent material would be used to deflect the sunlight, rather than to absorb it, to minimize the shift in balance out from L1 caused by radiation pressure. Three advances aimed at practical implementation are presented. First is an optical design for a very thin refractive screen with low reflectivity, leading to a total sunshade mass of ≈20 million tons. Second is a concept aimed at reducing transportation cost to $50/kg by using electromagnetic acceleration to escape Earth's gravity, followed by ion propulsion. Third is an implementation of the sunshade as a cloud of many spacecraft, autonomously stabilized by modulating solar radiation pressure. These meter-sized “flyers” would be assembled completely before launch, avoiding any need for construction or unfolding in space. They would weigh a gram each, be launched in stacks of 800,000, and remain for a projected lifetime of 50 years within a 100,000-km-long cloud. The concept builds on existing technologies. It seems feasible that it could be developed and deployed in ≈25 years at a cost of a few trillion dollars, <0.5% of world gross domestic product (GDP) over that time. PMID:17085589

  6. What Did We Think Could Be Learned About Earth From Lagrange Point Observations?

    NASA Technical Reports Server (NTRS)

    Wiscombe, Warren

    2011-01-01

    The scientific excitement surrounding the NASA Lagrange point mission Triana, now called DSCOVR, tended to be forgotten in the brouhaha over other aspects of the mission. Yet a small band of scientists in 1998 got very excited about the possibilities offered by the Lagrange-point perspective on our planet. As one of the original co-investigators on the Triana mission, I witnessed that scientific excitement firsthand. I will bring to life the early period, circa 1998 to 2000, and share the reasons that we thought the Lagrange-point perspective on Earth would be scientifically revolutionary.

  7. The Lagrange Points in a Binary Black Hole System: Applications to Electromagnetic Signatures

    NASA Technical Reports Server (NTRS)

    Schnittman, Jeremy

    2010-01-01

    We study the stability and evolution of the Lagrange points L_4 and L-5 in a black hole (BH) binary system, including gravitational radiation. We find that gas and stars can be shepherded in with the BH system until the final moments before merger, providing the fuel for a bright electromagnetic counterpart to a gravitational wave signal. Other astrophysical signatures include the ejection of hyper-velocity stars, gravitational collapse of globular clusters, and the periodic shift of narrow emission lines in AGN.

  8. How to use the Sun-Earth Lagrange points for fundamental physics and navigation

    NASA Astrophysics Data System (ADS)

    Tartaglia, A.; Lorenzini, E. C.; Lucchesi, D.; Pucacco, G.; Ruggiero, M. L.; Valko, P.

    2018-01-01

    We illustrate the proposal, nicknamed LAGRANGE, to use spacecraft, located at the Sun-Earth Lagrange points, as a physical reference frame. Performing time of flight measurements of electromagnetic signals traveling on closed paths between the points, we show that it would be possible: (a) to refine gravitational time delay knowledge due both to the Sun and the Earth; (b) to detect the gravito-magnetic frame dragging of the Sun, so deducing information about the interior of the star; (c) to check the possible existence of a galactic gravitomagnetic field, which would imply a revision of the properties of a dark matter halo; (d) to set up a relativistic positioning and navigation system at the scale of the inner solar system. The paper presents estimated values for the relevant quantities and discusses the feasibility of the project analyzing the behavior of the space devices close to the Lagrange points.

  9. Lagrange Point Missions: the Key to Next-Generation Integrated Earth Observations. DSCOVR Innovation

    NASA Astrophysics Data System (ADS)

    Valero, F. P. J.

    2016-12-01

    From L-1 DSCOVR is capable of new, unique observations potentially conducive to a deeper scientific understanding of the Earth sciences. At L-1 and L-2 the net gravitational pull of the Earth and Sun equals the centripetal force required to orbit the Sun with the same period as the Earth. Satellites at or near L-1 and L-2 keep the same position relative to the Sun and the Earth. DSCOVR does not orbit the Earth but the Sun in synchronism with Earth, acts like a planetoid (orbits the Sun in the ecliptic plane) while acquiring integrated plus spatially and time resolved scientific data as Earth rotates around its axis. Because of the planet's axial tilt relative to the ecliptic plane, the Polar Regions are visible during local summer from L-1 and local winter from L-2 (Fig. 1). DSCOVR's synoptic and continuous observations solve most of the temporal and spatial limitations associated with low Earth (LEO) and Geostationary (GEO) orbits. Two observatories, one at L-1 (daytime) and one at L-2 (nighttime), would acquire minute-by-minute climate quality data for essentially every point on Earth. The integration of L-1, L-2, LEO, and GEO satellites plus the Moon offers new scientific tools and enriched data sets for Earth sciences. Lagrange points observatories are key to next-generation integrated Earth observations. For example, DSCOVR at L-1 views the Earth plus the Moon (a reference) and simultaneously, at one time or another, all LEO and GEO satellites. The L-1 and L-2 satellites would be the link between the Moon, LEO and GEO satellites while providing the data needed to build an integrated Earth observational system. The above properties are the bases for DSCOVR's innovation and scientific approach that systematically observes climate drivers (radiation, aerosols, ozone, clouds, water vapor, vegetation) from L-1 in a way not possible but synergistic with other satellites. Next step: more capable L-1 plus L-2 satellites. The way of the future.

  10. Transit detection of a `starshade' at the inner lagrange point of an exoplanet

    NASA Astrophysics Data System (ADS)

    Gaidos, E.

    2017-08-01

    All water-covered rocky planets in the inner habitable zones of solar-type stars will inevitably experience a catastrophic runaway climate due to increasing stellar luminosity and limits to outgoing infrared radiation from wet greenhouse atmospheres. Reflectors or scatterers placed near Earth's inner Lagrange point (L_1) have been proposed as a "geoengineering' solution to anthropogenic climate change and an advanced version of this could modulate incident irradiation over many Gyr or `rescue' a planet from the interior of the habitable zone. The distance of the starshade from the planet that minimizes its mass is 1.6 times the Earth-L_1 distance. Such a starshade would have to be similar in size to the planet and the mutual occultations during planetary transits could produce a characteristic maximum at mid-transit in the light curve. Because of a fortuitous ratio of densities, Earth-size planets around G dwarf stars present the best opportunity to detect such an artefact. The signal would be persistent and is potentially detectable by a future space photometry mission to characterize transiting planets. The signal could be distinguished from natural phenomenon, I.e. starspots or cometary dust clouds, by its shape, persistence and transmission spectrum.

  11. Spacecraft Formation Flying near Sun-Earth L2 Lagrange Point: Trajectory Generation and Adaptive Full-State Feedback Control

    NASA Technical Reports Server (NTRS)

    Wong, Hong; Kapila, Vikram

    2004-01-01

    In this paper, we present a method for trajectory generation and adaptive full-state feedback control to facilitate spacecraft formation flying near the Sun-Earth L2 Lagrange point. Specifically, the dynamics of a spacecraft in the neighborhood of a Halo orbit reveals that there exist quasi-periodic orbits surrounding the Halo orbit. Thus, a spacecraft formation is created by placing a leader spacecraft on a desired Halo orbit and placing follower spacecraft on desired quasi-periodic orbits. To produce a formation maintenance controller, we first develop the nonlinear dynamics of a follower spacecraft relative to the leader spacecraft. We assume that the leader spacecraft is on a desired Halo orbit trajectory and the follower spacecraft is to track a desired quasi-periodic orbit surrounding the Halo orbit. Then, we design an adaptive, full-state feedback position tracking controller for the follower spacecraft providing an adaptive compensation for the unknown mass of the follower spacecraft. The proposed control law is simulated for the case of the leader and follower spacecraft pair and is shown to yield global, asymptotic convergence of the relative position tracking errors.

  12. Remote sensing optical instrumentation for enhanced space weather monitoring from the L1 and L5 Lagrange points

    NASA Astrophysics Data System (ADS)

    Kraft, S.; Puschmann, K. G.; Luntama, J. P.

    2017-09-01

    As part of the Space Situational Awareness Programme (SSA), ESA has initiated the assessment of two missions currently foreseen to be implemented to enable enhanced space weather monitoring. These missions utilize the positioning of satellites at the Lagrangian L1 and L5 points. These Phase 0 or Pre-Phase A mission studies are about to be completed and will thereby have soon passed the Mission Definition Review. Phase A studies are planned to start in 2017. The space weather monitoring system currently considers four remote sensing optical instruments and several in-situ instruments to analyse the Sun and the solar wind conditions, in order to provide early warnings of increased solar activity and to identify and mitigate potential threats to society and ground, airborne and space based infrastructure. The suggested optical instruments take heritage from ESA and NASA science missions like SOHO, STEREO and Solar Orbiter, but the instruments are foreseen to be optimized for operational space weather monitoring purposes with high reliability and robustness demands. The instruments are required to provide high quality measurements particularly during severe space weather events. The program intends to utilize the results of the on-going ESA instrument prototyping and technology development activities, and to initiate pre-developments of the operational space weather instruments to ensure the required maturity before the mission implementation.

  13. Science Enabled by the Ares V: A Large Monolithic Telescope Placed at the Second Sun-Earth Lagrange Point

    NASA Technical Reports Server (NTRS)

    Hopkins, Randall C.; Stahl, H. Philip

    2007-01-01

    The payload mass and volume capabilities of the planned Ares V launch vehicle provide the science community with unprecedented opportunities to place large science payloads into low earth orbit and beyond. One example, the outcome of a recent study conducted at the NASA Marshall Space Flight Center, is a large, monolithic telescope with a primary mirror diameter of 6.2 meters placed into a halo orbit about the second Sun-Earth Lagrange point, or L2, approximately 1.5 million kin beyond Earth's orbit. Operating in the visible and ultraviolet regions of the electromagnetic spectrum, such a large telescope would allow astronomers to detect bio-signatures and characterize the atmospheres of transiting exoplanets, provide high resolution imaging three or more times better than the Hubble Space Telescope and the James Webb Space Telescope, and observe the ultraviolet light from warm baryonic matter.

  14. A suggested trajectory for a Venus-sun, earth-sun Lagrange points mission, Vela

    NASA Technical Reports Server (NTRS)

    Bender, D. F.

    1979-01-01

    The possibility is suggested of investigating the existence of small, as-yet undiscovered, asteroids orbiting in the solar system near the earth-sun or Venus-sun stable Lagrange points by means of a spacecraft which traverses these regions. The type of trajectory suggested lies in the ecliptic plane and has a period of 5/6 years and a perihelion at the Venus orbital distance. The regions in which stable orbits associated with the earth and with Venus may lie are estimated to be a thin and tadpole-shaped area extending from 35 deg to 100 deg from the planet. Crossings of the regions by the trajectory are described, and the requirements for detecting the presence of 1 km sized asteroids are presented and shown to be attainable.

  15. DSCOVR_EPIC_L1A

    Atmospheric Science Data Center

    2018-05-07

    ... Level:  L1 Platform:  DEEP SPACE CLIMATE OBSERVATORY Instrument:  CCD IMAGER Spatial ... L1B LAGRANGE Legacy:  Retired data product , click here for a newer version. For more information or ...

  16. DSCOVR_EPIC_L1B

    Atmospheric Science Data Center

    2018-05-05

    ... Level:  L1 Platform:  DEEP SPACE CLIMATE OBSERVATORY Instrument:  CCD IMAGER Spatial ... L1B LAGRANGE Legacy:  Retired data product , click here for a newer version. For more information or ...

  17. Deep Space Transportation System Using the Sun-Earth L2 Point

    NASA Technical Reports Server (NTRS)

    Matsumoto, Michihiro

    2007-01-01

    Recently, various kinds of planetary explorations have become more feasible, taking the advantage of low thrust propulsion means such as ion engines that have come into practical use. The field of space activity has now been expanded even to the rim of the outer solar system. In this context, the Japan Aerospace Exploration Agency (JAXA) has started investigating a Deep Space Port built at the L2 Lagrange point in the Sun-Earth system. For the purpose of making the deep space port practically useful, there is a need to establish a method to making spaceship depart and return from/to the port. This paper first discusses the escape maneuvers originating from the L2 point under the restricted three-body problem. Impulsive maneuvers from the L2 point are extensively studied here, and using the results, optimal low-thrust escape strategies are synthesized. Furthermore, this paper proposes the optimal escape and acceleration maneuvers schemes using Electric Delta-V Earth Gravity Assist (EDVEGA) technique.

  18. Optimal Sunshade Configurations for Space-Based Geoengineering near the Sun-Earth L1 Point.

    PubMed

    Sánchez, Joan-Pau; McInnes, Colin R

    2015-01-01

    Within the context of anthropogenic climate change, but also considering the Earth's natural climate variability, this paper explores the speculative possibility of large-scale active control of the Earth's radiative forcing. In particular, the paper revisits the concept of deploying a large sunshade or occulting disk at a static position near the Sun-Earth L1 Lagrange equilibrium point. Among the solar radiation management methods that have been proposed thus far, space-based concepts are generally seen as the least timely, albeit also as one of the most efficient. Large occulting structures could potentially offset all of the global mean temperature increase due to greenhouse gas emissions. This paper investigates optimal configurations of orbiting occulting disks that not only offset a global temperature increase, but also mitigate regional differences such as latitudinal and seasonal difference of monthly mean temperature. A globally resolved energy balance model is used to provide insights into the coupling between the motion of the occulting disks and the Earth's climate. This allows us to revise previous studies, but also, for the first time, to search for families of orbits that improve the efficiency of occulting disks at offsetting climate change on both global and regional scales. Although natural orbits exist near the L1 equilibrium point, their period does not match that required for geoengineering purposes, thus forced orbits were designed that require small changes to the disk attitude in order to control its motion. Finally, configurations of two occulting disks are presented which provide the same shading area as previously published studies, but achieve reductions of residual latitudinal and seasonal temperature changes.

  19. Optimal Sunshade Configurations for Space-Based Geoengineering near the Sun-Earth L1 Point

    PubMed Central

    Sánchez, Joan-Pau; McInnes, Colin R.

    2015-01-01

    Within the context of anthropogenic climate change, but also considering the Earth’s natural climate variability, this paper explores the speculative possibility of large-scale active control of the Earth’s radiative forcing. In particular, the paper revisits the concept of deploying a large sunshade or occulting disk at a static position near the Sun-Earth L1 Lagrange equilibrium point. Among the solar radiation management methods that have been proposed thus far, space-based concepts are generally seen as the least timely, albeit also as one of the most efficient. Large occulting structures could potentially offset all of the global mean temperature increase due to greenhouse gas emissions. This paper investigates optimal configurations of orbiting occulting disks that not only offset a global temperature increase, but also mitigate regional differences such as latitudinal and seasonal difference of monthly mean temperature. A globally resolved energy balance model is used to provide insights into the coupling between the motion of the occulting disks and the Earth’s climate. This allows us to revise previous studies, but also, for the first time, to search for families of orbits that improve the efficiency of occulting disks at offsetting climate change on both global and regional scales. Although natural orbits exist near the L1 equilibrium point, their period does not match that required for geoengineering purposes, thus forced orbits were designed that require small changes to the disk attitude in order to control its motion. Finally, configurations of two occulting disks are presented which provide the same shading area as previously published studies, but achieve reductions of residual latitudinal and seasonal temperature changes. PMID:26309047

  20. Revisiting the Tale of Hercules: How Stars Orbiting the Lagrange Points Visit the Sun

    NASA Astrophysics Data System (ADS)

    Pérez-Villegas, Angeles; Portail, Matthieu; Wegg, Christopher; Gerhard, Ortwin

    2017-05-01

    We propose a novel explanation for the Hercules stream consistent with recent measurements of the extent and pattern speed of the Galactic bar. We have adapted a made-to-measure dynamical model tailored for the Milky Way to investigate the kinematics of the solar neighborhood (SNd). The model matches the 3D density of the red clump giant stars (RCGs) in the bulge and bar as well as stellar kinematics in the inner Galaxy, with a pattern speed of 39 km s-1 kpc-1. Cross-matching this model with the Gaia DR1 TGAS data combined with RAVE and LAMOST radial velocities, we find that the model naturally predicts a bimodality in the U-V-velocity distribution for nearby stars which is in good agreement with the Hercules stream. In the model, the Hercules stream is made of stars orbiting the Lagrange points of the bar which move outward from the bar’s corotation radius to visit the SNd. While the model is not yet a quantitative fit of the velocity distribution, the new picture naturally predicts that the Hercules stream is more prominent inward from the Sun and nearly absent only a few 100 pc outward of the Sun, and plausibly explains that Hercules is prominent in old and metal-rich stars.

  1. L1 libration point manned space habitat

    NASA Technical Reports Server (NTRS)

    Luttges, Marvin; Johnson, Steve; Banks, Gary; Johnson, Richard; Meyer, Christian; Pepin, Scott; Macelroy, Robert

    1989-01-01

    Second generation stations or Manned Space Habitats (MSHs) are discussed for an Earth-Moon libration point and in lunar orbit. The conceptual design of such a station is outlined. Systems and subsystems described reflect anticipation of moderate technology growth. The evolution of the L1 environments is discussed, several selected subsystems are outlined, and how the L1 MSH will complete some of its activities is described.

  2. Variational Integrators for Interconnected Lagrange-Dirac Systems

    NASA Astrophysics Data System (ADS)

    Parks, Helen; Leok, Melvin

    2017-10-01

    Interconnected systems are an important class of mathematical models, as they allow for the construction of complex, hierarchical, multiphysics, and multiscale models by the interconnection of simpler subsystems. Lagrange-Dirac mechanical systems provide a broad category of mathematical models that are closed under interconnection, and in this paper, we develop a framework for the interconnection of discrete Lagrange-Dirac mechanical systems, with a view toward constructing geometric structure-preserving discretizations of interconnected systems. This work builds on previous work on the interconnection of continuous Lagrange-Dirac systems (Jacobs and Yoshimura in J Geom Mech 6(1):67-98, 2014) and discrete Dirac variational integrators (Leok and Ohsawa in Found Comput Math 11(5), 529-562, 2011). We test our results by simulating some of the continuous examples given in Jacobs and Yoshimura (2014).

  3. A Lagrange multiplier and Hopfield-type barrier function method for the traveling salesman problem.

    PubMed

    Dang, Chuangyin; Xu, Lei

    2002-02-01

    A Lagrange multiplier and Hopfield-type barrier function method is proposed for approximating a solution of the traveling salesman problem. The method is derived from applications of Lagrange multipliers and a Hopfield-type barrier function and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the method searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that lower and upper bounds on variables are always satisfied automatically if the step length is a number between zero and one. At each iteration, the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the method converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the method seems more effective and efficient than the softassign algorithm.

  4. A globally convergent Lagrange and barrier function iterative algorithm for the traveling salesman problem.

    PubMed

    Dang, C; Xu, L

    2001-03-01

    In this paper a globally convergent Lagrange and barrier function iterative algorithm is proposed for approximating a solution of the traveling salesman problem. The algorithm employs an entropy-type barrier function to deal with nonnegativity constraints and Lagrange multipliers to handle linear equality constraints, and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the algorithm searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that the nonnegativity constraints are always satisfied automatically if the step length is a number between zero and one. At each iteration the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the algorithm converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the algorithm seems more effective and efficient than the softassign algorithm.

  5. Initial Results of a Survey of Earth's L4 Point for Possible Earth Trojan Asteroids

    NASA Astrophysics Data System (ADS)

    Connors, M.; Veillet, C.; Wiegert, P.; Innanen, K.; Mikkola, S.

    2000-10-01

    Using the Canada-France-Hawaii 3.6 m telescope and the new CFH12k wide-field CCD imager, a survey of the region near Earth's L4 (morning) Lagrange Point was conducted in May and July/August 2000, in hopes of finding asteroids at or near this point. This survey was motivated by the dynamical interest of a possible Earth Trojan asteroid (ETA) population and by the fact that they would be the easiest asteroids to access from Earth. Recent calculations (Wiegert, Innanen and Mikkola, 2000, Icarus v. 145, 33-43) indicate stability of objects in ETA orbits over a million year timescale and that their on-sky density would be greatest roughly five degrees sunward of the L4 position. An optimized search technique was used, with tracking at the anticipated rate of the target bodies, near real-time scanning of images, and duplication of fields to aid in detection and permit followup. Limited time is available on any given night to search near the Lagrange points, and operations must be conducted at large air mass. Approximately 9 square degrees were efficiently searched and two interesting asteroids were found, NEA 2000 PM8 and our provisionally named CFZ001. CFZ001 cannot be excluded from being an Earth Trojan although that is not the optimal solution for the short arc we observed. This object, of R magnitude 22, was easily detected, suggesting that our search technique worked well. This survey supports the earlier conclusion of Whitely and Tholen (1998, Icarus v. 136, 154-167) that a large population of several hundred meter diameter ETAs does not exist. However, our effective search technique and the discovery of two interesting asteroids suggest the value of completing the survey with approximately 10 more square degrees to be searched near L4 and a comparable search to be done at L5. Funding from Canada's NSERC and HIA and the Academic Research Fund of Athabasca University is gratefully acknowledged.

  6. Effect of Finite Particle Size on Convergence of Point Particle Models in Euler-Lagrange Multiphase Dispersed Flow

    NASA Astrophysics Data System (ADS)

    Nili, Samaun; Park, Chanyoung; Haftka, Raphael T.; Kim, Nam H.; Balachandar, S.

    2017-11-01

    Point particle methods are extensively used in simulating Euler-Lagrange multiphase dispersed flow. When particles are much smaller than the Eulerian grid the point particle model is on firm theoretical ground. However, this standard approach of evaluating the gas-particle coupling at the particle center fails to converge as the Eulerian grid is reduced below particle size. We present an approach to model the interaction between particles and fluid for finite size particles that permits convergence. We use the generalized Faxen form to compute the force on a particle and compare the results against traditional point particle method. We apportion the different force components on the particle to fluid cells based on the fraction of particle volume or surface in the cell. The application is to a one-dimensional model of shock propagation through a particle-laden field at moderate volume fraction, where the convergence is achieved for a well-formulated force model and back coupling for finite size particles. Comparison with 3D direct fully resolved numerical simulations will be used to check if the approach also improves accuracy compared to the point particle model. Work supported by the U.S. Department of Energy, National Nuclear Security Administration, Advanced Simulation and Computing Program, as a Cooperative Agreement under the Predictive Science Academic Alliance Program, under Contract No. DE-NA0002378.

  7. Earth to Moon Transfer: Direct vs Via Libration Points (L1, L2)

    NASA Technical Reports Server (NTRS)

    Condon, Gerald L.; Wilson, Samuel W.

    2004-01-01

    For some three decades, the Apollo-style mission has served as a proven baseline technique for transporting flight crews to the Moon and back with expendable hardware. This approach provides an optimal design for expeditionary missions, emphasizing operational flexibility in terms of safely returning the crew in the event of a hardware failure. However, its application is limited essentially to low-latitude lunar sites, and it leaves much to be desired as a model for exploratory and evolutionary programs that employ reusable space-based hardware. This study compares the performance requirements for a lunar orbit rendezvous mission type with one using the cislunar libration point (L1) as a stopover and staging point for access to arbitrary sites on the lunar surface. For selected constraints and mission objectives, it contrasts the relative uniformity of performance cost when the L1 staging point is used with the wide variation of cost for the Apollo-style lunar orbit rendezvous.

  8. Predicting the safe load on backpacker's arm using Lagrange multipliers method

    NASA Astrophysics Data System (ADS)

    Abdalla, Faisal Saleh; Rambely, Azmin Sham

    2014-09-01

    In this study, a technique has been suggested to reduce a backpack load by transmitting determined loads to the children arm. The purpose of this paper is to estimate school children arm muscles while load carriage as well as to determine the safe load can be carried at wrist while walking with backpack. A mathematical model, as three DOFs model, was investigated in the sagittal plane and Lagrange multipliers method (LMM) was utilized to minimize a quadratic objective function of muscle forces. The muscle forces were minimized with three different load conditions which are termed as 0-L=0 N, 1-L=21.95 N, and 2-L=43.9 N. The investigated muscles were estimated and compared to their maximum forces throughout the load conditions. Flexor and extensor muscles were estimated and the results showed that flexor muscles were active while extensor muscles showed inactivity. The estimated muscle forces were didn't exceed their maximum forces with 0-L and 1-L conditions whereas biceps and FCR muscles exceeded their maximum forces with 2-L condition. Consequently, 1-L condition is quiet safe to be carried by hand whereas 2-L condition is not. Thus to reduce the load in the backpack the transmitted load shouldn't exceed 1-L condition.

  9. The Impact of Discontinuity Front Orientation on the Accuracy of L1 Space Weather Forecasting

    NASA Astrophysics Data System (ADS)

    Szabo, A.

    2013-12-01

    Current space weather forecasting from the Sun-Earth first Lagrange (L1) point assumes that all observed solar wind discontinuity fronts (interplanetary shocks, ICME boundaries) are perpendicular to the Sun-Earth line and are propagating radially out from eh Sun. In reality, these weather fronts can have significantly tilted orientation. Combined ACE, Wind and Soho observations allow the quantification of this effect. With the launch of the DSCOVR spacecraft in early 2015, dual real-time solar wind measurements will become available (at least at some time). Algorithms and their impact exploiting this unique scenario will be discussed.

  10. Error estimates of Lagrange interpolation and orthonormal expansions for Freud weights

    NASA Astrophysics Data System (ADS)

    Kwon, K. H.; Lee, D. W.

    2001-08-01

    Let Sn[f] be the nth partial sum of the orthonormal polynomials expansion with respect to a Freud weight. Then we obtain sufficient conditions for the boundedness of Sn[f] and discuss the speed of the convergence of Sn[f] in weighted Lp space. We also find sufficient conditions for the boundedness of the Lagrange interpolation polynomial Ln[f], whose nodal points are the zeros of orthonormal polynomials with respect to a Freud weight. In particular, if W(x)=e-(1/2)x2 is the Hermite weight function, then we obtain sufficient conditions for the inequalities to hold:andwhere and k=0,1,2...,r.

  11. The motion near L{sub 4} equilibrium point under non-point mass primaries

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

    Huda, I. N., E-mail: ibnu.nurul@students.itb.ac.id; Utama, J. A.; Madley, D.

    2015-09-30

    The Circular Restricted Three-Body Problem (CRTBP) possesses five equilibrium points, that comprise three collinear (L{sub 1}, L{sub 2}, and L{sub 3}) and two triangular points (L{sub 4} and L{sub 5}). The classical study (with the primaries are point mass) suggests that the equilibrium points may cause the velocity of infinitesimal object relatively becomes zero and reveals the zero velocity curve. We study the motion of infinitesimal object near triangular equilibrium point (L{sub 4}) and determine its zero velocity curve. We extend the study by taking into account the effects of radiation of the bigger primary (q{sub 1} ≠ 1, q{submore » 2} = 1) and oblateness of the smaller primary (A{sub 1} = 0, A{sub 2} ≠ 0). The location of L{sub 4} is analytically derived then the stability of L{sub 4} and its zero velocity curves are studied numerically. Our study suggests that the oblateness and the radiation of primaries may affect the stability and zero velocity curve around L{sub 4}.« less

  12. End of Life Disposal for Three Libration Point Missions through Manipulation of the Jacobi Constant and Zero Velocity Curves

    NASA Technical Reports Server (NTRS)

    Petersen, Jeremy; Brown, Jonathan

    2015-01-01

    Flight Dynamics Facility (FDF) located at NASA Goddard Space Flight Center (GSFC) provides the flight dynamics expertise for three Sun-Earth Moon L1 missions. Advanced Composition Explorer (ACE) launched August 1997 Solar and Heliospheric Observatory (SOHO) launched December 1995 Global Geospace Science WIND satellite launched November 1994 entered Lagrange point orbit in 2004.

  13. 16QAM Blind Equalization via Maximum Entropy Density Approximation Technique and Nonlinear Lagrange Multipliers

    PubMed Central

    Mauda, R.; Pinchas, M.

    2014-01-01

    Recently a new blind equalization method was proposed for the 16QAM constellation input inspired by the maximum entropy density approximation technique with improved equalization performance compared to the maximum entropy approach, Godard's algorithm, and others. In addition, an approximated expression for the minimum mean square error (MSE) was obtained. The idea was to find those Lagrange multipliers that bring the approximated MSE to minimum. Since the derivation of the obtained MSE with respect to the Lagrange multipliers leads to a nonlinear equation for the Lagrange multipliers, the part in the MSE expression that caused the nonlinearity in the equation for the Lagrange multipliers was ignored. Thus, the obtained Lagrange multipliers were not those Lagrange multipliers that bring the approximated MSE to minimum. In this paper, we derive a new set of Lagrange multipliers based on the nonlinear expression for the Lagrange multipliers obtained from minimizing the approximated MSE with respect to the Lagrange multipliers. Simulation results indicate that for the high signal to noise ratio (SNR) case, a faster convergence rate is obtained for a channel causing a high initial intersymbol interference (ISI) while the same equalization performance is obtained for an easy channel (initial ISI low). PMID:24723813

  14. Getting to L1 the Hard Way: Triana's Launch Options

    NASA Technical Reports Server (NTRS)

    Houghton, Martin B.; Bauer, Frank H. (Technical Monitor)

    2002-01-01

    Over the past four years, NASA's Goddard Space Flight Center has built and tested the Triana observatory, which will be the first Earth observing science satellite to take advantage of the unique perspective offered by a Lissajous orbit about the first Earth-Sun Lagrange Point (L1). Triana was originally meant to fly on the U.S. Space Transportation System (a.k.a. the Space Shuttle but complications with the shuttle manifest have forced Triana into a 'wait and see' attitude. The observatory is currently being stored at NASA's Goddard Space Flight Center, where it waits for an appropriate launch opportunity to surface. To that end, several possible alternatives have been considered, including variations on the nominal shuttle deployment scenario, a high inclination Delta-type launch from Vandenberg Air Force Base, a Tsyklon class vehicle launched from Baikonur, Kazakhstan, and a ride on a French Ariane vehicle out of French Guiana into a somewhat arbitrary geostationary transfer orbit (GTO). This paper chronicles and outlines the pros and cons of how each of these opportunities could be used to send Triana on its way to L1.

  15. Getting to L1 the Hard Way: Triana's Launch Options

    NASA Technical Reports Server (NTRS)

    Houghton, Martin B.; Bauer, Frank H. (Technical Monitor)

    2002-01-01

    Over the past four years, NASA's Goddard Space Flight Center has built and tested the Triana observatory, which will be the first Earth observing science satellite to take advantage of the unique perspective offered by a Lissajous orbit about the first Earth-Sun Lagrange Point (L1). Triana was originally meant to fly on the U.S. Space Transportation System (a.k.a. the Space Shuttle), but complications with the shuttle manifest have forced Triana into a "wait and see" attitude. The observatory is currently being stored at NASA's Goddard Space Flight Center, where it waits for an appropriate launch opportunity to materialize. To that end, several possible alternatives have been considered, including variations on the nominal shuttle deployment scenario, a high inclination Delta-type launch from Vandenberg Air Force Base, a Tsyklon class vehicle launched from Baikonur, Kazakhstan, and a ride on a French Ariane vehicle out of French Guiana into a somewhat arbitrary geostationary transfer orbit (GTO). This paper chronicles and outlines the pros and cons of how each of these opportunities could be used to send Triana on its way to L1.

  16. Optimal trajectories from the Earth-Moon L1 and L3 points to deflect hazardous asteroids and comets.

    PubMed

    Maccone, Claudio

    2004-05-01

    Software code named asteroff was recently created by the author to simulate the deflection of hazardous asteroids off of their collision course with the Earth. This code was both copyrighted and patented to avoid unauthorized use of ideas that could possibly be vital to construct a planetary defense system in the vicinity of the Earth. Having so said, the basic ideas and equations underlying the asteroff simulation code are openly described in this paper. A system of two space bases housing missiles is proposed to achieve the planetary defense of the Earth against dangerous asteroids and comets, collectively called impactors herein. We show that the layout of the Earth-Moon system with the five relevant Lagrangian (or libration) points in space leads naturally to only one, unmistakable location of these two space bases within the sphere of influence of the Earth. These locations are at the two Lagrangian points L(1) (between the Earth and the Moon) and L(3) (in the direction opposite to the Moon from the Earth). We show that placing missile bases at L(1) and L(3) would enable those missiles to deflect the trajectory of impactors by hitting them orthogonally to their impact trajectory toward the Earth, so as to maximize their deflection. We show that confocal conics are the best class of trajectories fulfilling this orthogonal deflection requirement. One additional remark is that the theory developed in this paper is just a beginning for a wider set of future research. In fact, we only develop the Keplerian analytical theory for the optimal planetary defense achievable from the Earth-Moon Lagrangian points L(1) and L(3). Much more sophisticated analytical refinements would be needed to: (1) take into account many perturbation forces of all kinds acting on both the impactors and missiles shot from L(1) and L(3); (2) add more (non-optimal) trajectories of missiles shot from either the Lagrangian points L(4) and L(5) of the Earth-Moon System or from the surface of the

  17. The Sun-Earth saddle point: characterization and opportunities to test general relativity

    NASA Astrophysics Data System (ADS)

    Topputo, Francesco; Dei Tos, Diogene A.; Rasotto, Mirco; Nakamiya, Masaki

    2018-04-01

    The saddle points are locations where the net gravitational accelerations balance. These regions are gathering more attention within the astrophysics community. Regions about the saddle points present clean, close-to-zero background acceleration environments where possible deviations from General Relativity can be tested and quantified. Their location suggests that flying through a saddle point can be accomplished by leveraging highly nonlinear orbits. In this paper, the geometrical and dynamical properties of the Sun-Earth saddle point are characterized. A systematic approach is devised to find ballistic orbits that experience one or multiple passages through this point. A parametric analysis is performed to consider spacecraft initially on L_{1,2} Lagrange point orbits. Sun-Earth saddle point ballistic fly-through trajectories are evaluated and classified for potential use. Results indicate an abundance of short-duration, regular solutions with a variety of characteristics.

  18. Accuracy of Lagrange-sinc functions as a basis set for electronic structure calculations of atoms and molecules

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

    Choi, Sunghwan; Hong, Kwangwoo; Kim, Jaewook

    2015-03-07

    We developed a self-consistent field program based on Kohn-Sham density functional theory using Lagrange-sinc functions as a basis set and examined its numerical accuracy for atoms and molecules through comparison with the results of Gaussian basis sets. The result of the Kohn-Sham inversion formula from the Lagrange-sinc basis set manifests that the pseudopotential method is essential for cost-effective calculations. The Lagrange-sinc basis set shows faster convergence of the kinetic and correlation energies of benzene as its size increases than the finite difference method does, though both share the same uniform grid. Using a scaling factor smaller than or equal tomore » 0.226 bohr and pseudopotentials with nonlinear core correction, its accuracy for the atomization energies of the G2-1 set is comparable to all-electron complete basis set limits (mean absolute deviation ≤1 kcal/mol). The same basis set also shows small mean absolute deviations in the ionization energies, electron affinities, and static polarizabilities of atoms in the G2-1 set. In particular, the Lagrange-sinc basis set shows high accuracy with rapid convergence in describing density or orbital changes by an external electric field. Moreover, the Lagrange-sinc basis set can readily improve its accuracy toward a complete basis set limit by simply decreasing the scaling factor regardless of systems.« less

  19. Lunar and Lagrangian Point L1 L2 CubeSat Communication and Navigation Considerations

    NASA Technical Reports Server (NTRS)

    Schaire, Scott; Wong, Yen F.; Altunc, Serhat; Bussey, George; Shelton, Marta; Folta, Dave; Gramling, Cheryl; Celeste, Peter; Anderson, Mile; Perrotto, Trish; hide

    2017-01-01

    CubeSats have grown in sophistication to the point that relatively low-cost mission solutions could be undertaken for planetary exploration. There are unique considerations for lunar and L1/L2 CubeSat communication and navigation compared with low earth orbit CubeSats. This paper explores those considerations as they relate to the Lunar IceCube Mission. The Lunar IceCube is a CubeSat mission led by Morehead State University with participation from NASA Goddard Space Flight Center, Jet Propulsion Laboratory, the Busek Company and Vermont Tech. It will search for surface water ice and other resources from a high inclination lunar orbit. Lunar IceCube is one of a select group of CubeSats designed to explore beyond low-earth orbit that will fly on NASA’s Space Launch System (SLS) as secondary payloads for Exploration Mission (EM) 1. Lunar IceCube and the EM-1 CubeSats will lay the groundwork for future lunar and L1/L2 CubeSat missions. This paper discusses communication and navigation needs for the Lunar IceCube mission and navigation and radiation tolerance requirements related to lunar and L1/L2 orbits. Potential CubeSat radios and antennas for such missions are investigated and compared. Ground station coverage, link analysis, and ground station solutions are also discussed. This paper will describe modifications in process for the Morehead ground station, as well as further enhancements of the Morehead ground station and NASA Near Earth Network (NEN) that are being considered. The potential NEN enhancements include upgrading current NEN Cortex receiver with Forward Error Correction (FEC) Turbo Code, providing X-band uplink capability, and adding ranging options. The benefits of ground station enhancements for CubeSats flown on NASA Exploration Missions (EM) are presented. This paper also describes how the NEN may support lunar and L1/L2 CubeSats without any enhancements. In addition, NEN is studying other initiatives to better support the CubeSat community

  20. Projection-based stabilization of interface Lagrange multipliers in immersogeometric fluid-thin structure interaction analysis, with application to heart valve modeling.

    PubMed

    Kamensky, David; Evans, John A; Hsu, Ming-Chen; Bazilevs, Yuri

    2017-11-01

    This paper discusses a method of stabilizing Lagrange multiplier fields used to couple thin immersed shell structures and surrounding fluids. The method retains essential conservation properties by stabilizing only the portion of the constraint orthogonal to a coarse multiplier space. This stabilization can easily be applied within iterative methods or semi-implicit time integrators that avoid directly solving a saddle point problem for the Lagrange multiplier field. Heart valve simulations demonstrate applicability of the proposed method to 3D unsteady simulations. An appendix sketches the relation between the proposed method and a high-order-accurate approach for simpler model problems.

  1. Lunar and Lagrangian Point L1 L2 CubeSat Communication and Navigation Considerations

    NASA Technical Reports Server (NTRS)

    Schaire, Scott; Wong, Yen F.; Altunc, Serhat; Bussey, George D.; Shelton, Marta; Folta, Dave; Gramling, Cheryl; Celeste, Peter; Anderson, Mike; Perrotto, Trish; hide

    2017-01-01

    CubeSats have grown in sophistication to the point that relatively low-cost mission solutions could be undertaken for planetary exploration. There are unique considerations for Lunar and L1L2 CubeSat communication and navigation compared with low earth orbit CubeSats. This paper explores those considerations as they relate to the MoreheadGSFC Lunar IceCube Mission. The Lunar IceCube is a CubeSat mission led by Morehead State University with participation from NASA Goddard Space Flight Center, JPL, the Busek Company and Vermont Tech. It will search for surface water ice and other resources from a high inclination lunar orbit. Lunar IceCube is one of a select group of CubeSats designed to explore beyond low-earth orbit that will fly on NASAs Space Launch System (SLS) as secondary payloads for Exploration Mission (EM) 1. Lunar IceCube and the EM-1 CubeSats will lay the groundwork for future lunar and L1L2 CubeSat missions. This paper discusses communication and navigation needs for the Lunar IceCube mission and navigation and radiation tolerance requirements related to lunar and L1L2 orbits. Potential CubeSat radio and antennas for such missions are investigated and compared. Ground station coverage, link analysis, and ground station solutions are also discussed. There are currently modifications in process for the Morehead ground station. Further enhancement of the Morehead ground station and the NASA Near Earth Network (NEN) are being examined. This paper describes how the NEN may support Lunar and L1L2 CubeSats without any enhancements and potential expansion of NEN to better support such missions in the future. The potential NEN enhancements include upgrading current NEN Cortex receiver with Forward Error Correction (FEC) Turbo Code, providing X-band Uplink capability, and adding ranging options. The benefits of ground station enhancements for CubeSats flown on NASA Exploration Missions (EM) are presented. The paper also discusses other initiatives that the NEN is

  2. LAGRANGE: LAser GRavitational-wave ANtenna in GEodetic Orbit

    NASA Astrophysics Data System (ADS)

    Buchman, S.; Conklin, J. W.; Balakrishnan, K.; Aguero, V.; Alfauwaz, A.; Aljadaan, A.; Almajed, M.; Altwaijry, H.; Saud, T. A.; Byer, R. L.; Bower, K.; Costello, B.; Cutler, G. D.; DeBra, D. B.; Faied, D. M.; Foster, C.; Genova, A. L.; Hanson, J.; Hooper, K.; Hultgren, E.; Klavins, A.; Lantz, B.; Lipa, J. A.; Palmer, A.; Plante, B.; Sanchez, H. S.; Saraf, S.; Schaechter, D.; Shu, K.; Smith, E.; Tenerelli, D.; Vanbezooijen, R.; Vasudevan, G.; Williams, S. D.; Worden, S. P.; Zhou, J.; Zoellner, A.

    2013-01-01

    We describe a new space gravitational wave observatory design called LAG-RANGE that maintains all important LISA science at about half the cost and with reduced technical risk. It consists of three drag-free spacecraft in a geocentric formation. Fixed antennas allow continuous contact with the Earth, solving the problem of communications bandwidth and latency. A 70 mm diameter sphere with a 35 mm gap to its enclosure serves as the single inertial reference per spacecraft, operating in “true” drag-free mode (no test mass forcing). Other advantages are: a simple caging design based on the DISCOS 1972 drag-free mission, an all optical read-out with pm fine and nm coarse sensors, and the extensive technology heritage from the Honeywell gyroscopes, and the DISCOS and Gravity Probe B drag-free sensors. An Interferometric Measurement System, designed with reflective optics and a highly stabilized frequency standard, performs the ranging between test masses and requires a single optical bench with one laser per spacecraft. Two 20 cm diameter telescopes per spacecraft, each with infield pointing, incorporate novel technology developed for advanced optical systems by Lockheed Martin, who also designed the spacecraft based on a multi-flight proven bus structure. Additional technological advancements include updated drag-free propulsion, thermal control, charge management systems, and materials. LAGRANGE subsystems are designed to be scalable and modular, making them interchangeable with those of LISA or other gravitational science missions. We plan to space qualify critical technologies on small and nano satellite flights, with the first launch (UV-LED Sat) in 2013.

  3. Lagrange constraint neural network for audio varying BSS

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.; Hsu, Charles C.

    2002-03-01

    Lagrange Constraint Neural Network (LCNN) is a statistical-mechanical ab-initio model without assuming the artificial neural network (ANN) model at all but derived it from the first principle of Hamilton and Lagrange Methodology: H(S,A)= f(S)- (lambda) C(s,A(x,t)) that incorporates measurement constraint C(S,A(x,t))= (lambda) ([A]S-X)+((lambda) 0-1)((Sigma) isi -1) using the vector Lagrange multiplier-(lambda) and a- priori Shannon Entropy f(S) = -(Sigma) i si log si as the Contrast function of unknown number of independent sources si. Szu et al. have first solved in 1997 the general Blind Source Separation (BSS) problem for spatial-temporal varying mixing matrix for the real world remote sensing where a large pixel footprint implies the mixing matrix [A(x,t)] necessarily fill with diurnal and seasonal variations. Because the ground truth is difficult to be ascertained in the remote sensing, we have thus illustrated in this paper, each step of the LCNN algorithm for the simulated spatial-temporal varying BSS in speech, music audio mixing. We review and compare LCNN with other popular a-posteriori Maximum Entropy methodologies defined by ANN weight matrix-[W] sigmoid-(sigma) post processing H(Y=(sigma) ([W]X)) by Bell-Sejnowski, Amari and Oja (BSAO) called Independent Component Analysis (ICA). Both are mirror symmetric of the MaxEnt methodologies and work for a constant unknown mixing matrix [A], but the major difference is whether the ensemble average is taken at neighborhood pixel data X's in BASO or at the a priori sources S variables in LCNN that dictates which method works for spatial-temporal varying [A(x,t)] that would not allow the neighborhood pixel average. We expected the success of sharper de-mixing by the LCNN method in terms of a controlled ground truth experiment in the simulation of variant mixture of two music of similar Kurtosis (15 seconds composed of Saint-Saens Swan and Rachmaninov cello concerto).

  4. Pointwise convergence of derivatives of Lagrange interpolation polynomials for exponential weights

    NASA Astrophysics Data System (ADS)

    Damelin, S. B.; Jung, H. S.

    2005-01-01

    For a general class of exponential weights on the line and on (-1,1), we study pointwise convergence of the derivatives of Lagrange interpolation. Our weights include even weights of smooth polynomial decay near +/-[infinity] (Freud weights), even weights of faster than smooth polynomial decay near +/-[infinity] (Erdos weights) and even weights which vanish strongly near +/-1, for example Pollaczek type weights.

  5. DSCOVR/EPIC Images and Science: A New Way to View the Entire Sunlit Earth From A Sun-Earth Lagrange-1 Orbit

    NASA Astrophysics Data System (ADS)

    Herman, J. R.; Marshak, A.; Szabo, A.

    2015-12-01

    The DSCOVR mission was launched into a Sun-Earth Lagrange-1 orbit 1.5 million kilometers from earth in February 2015 onboard a SpaceX Falcon-9 rocket. The solar wind and earth science instruments were tested during the 4.5 month journey to L-1. The first data were obtained during the June-July commissioning phase, which included the first moderate resolution (10 km) color images of the entire sunlit earth, color images of the Moon, and scientific data from 10 narrow band filters (317.5, 325, 340, 388, 443, 551, 680, 687.75, 764, and 779.5 nm). Three of these filters were used to construct the color images (443, 551, 680 nm) based on the average eye response histogram of the sunlit earth. This talk will discuss some of the issues involved in deriving science quality data for global ozone, the aerosol index (dust, smoke, and volcanic ash), cloud amounts and reflectivity, and cloud height (measured from the O2 A- and B-bands). As with most new satellites, the science data are preliminary.

  6. Necessary conditions for weighted mean convergence of Lagrange interpolation for exponential weights

    NASA Astrophysics Data System (ADS)

    Damelin, S. B.; Jung, H. S.; Kwon, K. H.

    2001-07-01

    Given a continuous real-valued function f which vanishes outside a fixed finite interval, we establish necessary conditions for weighted mean convergence of Lagrange interpolation for a general class of even weights w which are of exponential decay on the real line or at the endpoints of (-1,1).

  7. Point-spread function reconstruction in ground-based astronomy by l(1)-l(p) model.

    PubMed

    Chan, Raymond H; Yuan, Xiaoming; Zhang, Wenxing

    2012-11-01

    In ground-based astronomy, images of objects in outer space are acquired via ground-based telescopes. However, the imaging system is generally interfered by atmospheric turbulence, and hence images so acquired are blurred with unknown point-spread function (PSF). To restore the observed images, the wavefront of light at the telescope's aperture is utilized to derive the PSF. A model with the Tikhonov regularization has been proposed to find the high-resolution phase gradients by solving a least-squares system. Here we propose the l(1)-l(p) (p=1, 2) model for reconstructing the phase gradients. This model can provide sharper edges in the gradients while removing noise. The minimization models can easily be solved by the Douglas-Rachford alternating direction method of a multiplier, and the convergence rate is readily established. Numerical results are given to illustrate that the model can give better phase gradients and hence a more accurate PSF. As a result, the restored images are much more accurate when compared to the traditional Tikhonov regularization model.

  8. Long Term Missions at the Sun-Earth Libration Point L1: ACE, SOHO, and WIND

    NASA Technical Reports Server (NTRS)

    Roberts, Craig E.

    2011-01-01

    Three heliophysics missions - the Solar Heliospheric Observatory (SOHO), the Advanced Composition Explorer (ACE), and the Global Geoscience WIND - have been orbiting the Sun-Earth interior libration point L1 continuously since 1996, 1997, and 2004, respectively. ACE and WIND (both NASA missions) and SOHO (an ESA-NASA joint mission) are all operated from the NASA Goddard Space Flight Center Flight Dynamics Facility. While ACE and SOHO have been dedicated libration point orbiters since their launches, WIND prior to 2004 flew a remarkable 10-year deep-space trajectory that featured 38 targeted lunar flybys. The L1 orbits and the mission histories of the three spacecraft are briefly reviewed, and the station-keeping techniques and orbit maneuver experience are discussed.

  9. Zeros of Schrödinger's Radial Function Rnl(r) and Kummer's Function 1F1(-a c; z) and Their ``Angle'' Distributions

    NASA Astrophysics Data System (ADS)

    Tarasov, V. F.

    In the present paper exact formulae for the calculation of zeros of Rnl(r) and 1F1(-a c; z), where z = 2 λ r, a = n - l - 1 >= 0 and c = 2l + 2 >= 2 are presented. For a <= 4 the method due to Tartallia and Cardono, and that due to L. Ferrai, L. Euler and J. L. Lagrange are used. In other cases (a > 4) numerical methods are employed to obtain the results (to within 10-15). For greater geometrical obviousness of the irregulary distribution (as a > 3) of zeros xk = zk - (c + a - 1) on the axis y = 0, the circular diagrams with the radius Ra = (a - 1) √ {c + a - 1} are presented for the first time. It is possible to notice some singularities of distribution of these zeros and their images - the points Tk - on the circle. For a = 3 and 4 their exact ``angle'' asymptotics (as c --> ∞) are obtained. It is shown that in the basis of the L. Ferrari, L. Euler and J.-L. Lagrange methods, using for solving the equation 1F1(-4 c; z) = 0, one Common for all these methods. equation is obtained viz., the cubic resolvent equation of FEL-type. Calculating of zeros xk of the Rnl(r) and 1F1(z) functions enable us to show the ``singular'' cases (a, c) = (4, 6), (6, 4), (8, 14), ...

  10. [MPLW515L point mutation in patients with myeloproliferative disease].

    PubMed

    Xia, Jun; Xu, Wei; Zhang, Su-Jiang; Fan, Lei; Qiao, Chun; Li, Jian-Yong

    2008-12-01

    In order to investigate the frequency of MPLW515L and JAK2V617F point mutations of the patients with myeloproliferative disease (MPD) in Nanjing area, MPLW515L and JAK2V617F point mutations were simultaneously detected by alleles specific polymerase chain reaction (AS-PCR) and sequencing in 190 MPD patients. The results showed that MPLW515L point mutation was detected in 1 out of 102 essential thrombocythemia (ET) patients (1.0%) and was not detected in 32 polycythemia vera (PV) patients, 13 idiopathic myelofibrosis (IMF) patients, 43 chronic myelogenous leukemia (CML) patients. JAK2V617F point mutation was detected in 20 out of 32 PV patients (62.5%), 43 out of 102 ET patients (42.2%), 5 out of 13 IMF patients (38.5%), and was not detected in 43 CML patients. It is concluded that MPLW515L point mutation exists in ET patient, but is not found in PV, IMF and CML. JAK2V617F point mutation exists in PV, ET and IMF, but not in CML.

  11. Minimum Propellant Low-Thrust Maneuvers near the Libration Points

    NASA Astrophysics Data System (ADS)

    Marinescu, A.; Dumitrache, M.

    The impulse technique certainly can bring the vehicle on orbits around the libration points or close to them. The question that aries is, by what means can the vehicle arrive in such cases at the libration points? A first investigation carried out in this paper can give an answer: the use of the technique of low-thrust, which, in addition, can bring the vehicle from the libration points near to or into orbits around these points. This aspect is considered in this present paper where for the applications we have considered the transfer for orbits of the equidistant point L4 and of the collinear point L2, from Earth-moon system. This transfer maneuver can be used to insertion one satellite on libration points orbits. In Earth- moon system the points L 4 and L 5 because an vehicle in on of the equidistant points in quite stable and remains in its vicinity of perturbed, have potential interest for the establishment of transporder satellite for interplanetary tracking. In contrast an vehicle in one of the collinear points is quite instable and it will oscillate along the Earth-moon-axis at increasing amplitude and gradually escape from the libration point. Let use assume that a space vehicle equipped with a low-thrust propulsion is near a libration point L. We consider the planar motion in the restricted frame of the three bodies in the rotating system L, where the Earth-moon distance D=l. The unit of time T is period of the moon's orbit divided by 2 and multiplied by the square root of the quantity one plus the moon/Earth mass ratio, and the unit of mass is the Earth's mass. With these predictions the motion equatios of the vehicle equiped with a low-thrust propulsion installation in the linear approximation near the libration point, have been established. The parameters of the motion at the beginning and the end of these maneuvers are known, the variational problem has been formulated as a Lagrange type problem with fixed extremities. On established the differential

  12. Integración automatizada de las ecuaciones de Lagrange en el movimiento orbital.

    NASA Astrophysics Data System (ADS)

    Abad, A.; San Juan, J. F.

    The new techniques of algebraic manipulation, especially the Poisson Series Processor, permit the analytical integration of the more and more complex problems of celestial mechanics. The authors are developing a new Poisson Series Processor, PSPC, and they use it to solve the Lagrange equation of the orbital motion. They integrate the Lagrange equation by using the stroboscopic method, and apply it to the main problem of the artificial satellite theory.

  13. 78 FR 21491 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662, 02/02-0661] DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that DeltaPoint Capital IV, L.P. and DeltaPoint...

  14. Centrifuge Rotor Models: A Comparison of the Euler-Lagrange and the Bond Graph Modeling Approach

    NASA Technical Reports Server (NTRS)

    Granda, Jose J.; Ramakrishnan, Jayant; Nguyen, Louis H.

    2006-01-01

    A viewgraph presentation on centrifuge rotor models with a comparison using Euler-Lagrange and bond graph methods is shown. The topics include: 1) Objectives; 2) MOdeling Approach Comparisons; 3) Model Structures; and 4) Application.

  15. The Relation Among the Likelihood Ratio-, Wald-, and Lagrange Multiplier Tests and Their Applicability to Small Samples,

    DTIC Science & Technology

    1982-04-01

    S. (1979), "Conflict Among Criteria for Testing Hypothesis: Extension and Comments," Econometrica, 47, 203-207 Breusch , T. S. and Pagan , A. R. (1980...Savin, N. E. (1977), "Conflict Among Criteria for Testing Hypothesis in the Multivariate Linear Regression Model," Econometrica, 45, 1263-1278 Breusch , T...VNCLASSIFIED RAND//-6756NL U l~ I- THE RELATION AMONG THE LIKELIHOOD RATIO-, WALD-, AND LAGRANGE MULTIPLIER TESTS AND THEIR APPLICABILITY TO SMALL SAMPLES

  16. Lagrange multiplier for perishable inventory model considering warehouse capacity planning

    NASA Astrophysics Data System (ADS)

    Amran, Tiena Gustina; Fatima, Zenny

    2017-06-01

    This paper presented Lagrange Muktiplier approach for solving perishable raw material inventory planning considering warehouse capacity. A food company faced an issue of managing perishable raw materials and marinades which have limited shelf life. Another constraint to be considered was the capacity of the warehouse. Therefore, an inventory model considering shelf life and raw material warehouse capacity are needed in order to minimize the company's inventory cost. The inventory model implemented in this study was the adapted economic order quantity (EOQ) model which is optimized using Lagrange multiplier. The model and solution approach were applied to solve a case industry in a food manufacturer. The result showed that the total inventory cost decreased 2.42% after applying the proposed approach.

  17. Using Solar Radiation Pressure to Control L2 Orbits

    NASA Technical Reports Server (NTRS)

    Tene, Noam; Richon, Karen; Folta, David

    1998-01-01

    The main perturbations at the Sun-Earth Lagrange points L1 and L2 are from solar radiation pressure (SRP), the Moon and the planets. Traditional approaches to trajectory design for Lagrange-point orbits use maneuvers every few months to correct for these perturbations. The gravitational effects of the Moon and the planets are small and periodic. However, they cannot be neglected because small perturbations in the direction of the unstable eigenvector are enough to cause exponential growth within a few months. The main effect of a constant SRP is to shift the center of the orbit by a small distance. For spacecraft with large sun-shields like the Microwave Anisotropy Probe (MAP) and the Next Generation Space Telescope (NGST), the SRP effect is larger than all other perturbations and depends mostly on spacecraft attitude. Small variations in the spacecraft attitude are large enough to excite or control the exponential eigenvector. A closed-loop linear controller based on the SRP variations would eliminate one of the largest errors to the orbit and provide a continuous acceleration for use in controlling other disturbances. It is possible to design reference trajectories that account for the periodic lunar and planetary perturbations and still satisfy mission requirements. When such trajectories are used the acceleration required to control the unstable eigenvector is well within the capabilities of a continuous linear controller. Initial estimates show that by using attitude control it should be possible to minimize and even eliminate thruster maneuvers for station keeping.

  18. DSCOVR: A New Perspective for Earth Observations from Space. Synergism and Complementarity with Existing Platforms

    NASA Astrophysics Data System (ADS)

    Valero, F. P.

    2011-12-01

    The Sun-Earth Lagrange points L-1 and L-2 mark positions where the gravitational pull of the Earth and Sun precisely equals the centripetal force required to rotate with the Earth about the Sun with the same orbital period as the Earth. Therefore, a satellite maintained at one of these Lagrange points would keep the same relative position to the Sun and the Earth and be able to observe most points on the planet as the Earth rotates during the day. L-1 and L-2 are of particular interest because a satellite at either location can easily be maintained near the Sun-Earth line and views the entire daytime hemisphere from L-1 and the entire nighttime hemisphere from L-2. Since L-1 and L-2 are in the ecliptic plane, synoptic, high temporal-resolution observations would be obtained as every point on the planet, including both polar regions, transits from sunrise to sunset (L-1) or from sunset to sunrise (L-2). In summary, a pair of deep-space observatories, one at L-1 (daytime) and one at L-2 (nighttime), could acquire minute by minute climate quality data for essentially every point on Earth, all observations simultaneously for the whole planet. Such unique attributes are incorporated in the Deep Space Climate Observatory (DSCOVR) that will systematically observe climate drivers (radiation, aerosols, ozone, clouds, oxygen A-band) from L-1 in ways not possible but synergistically complementary with platforms in Low Earth Orbit (LEO) or Geostationary Earth Orbit (GEO). The combination of Solar Lagrange Points (located in the ecliptic plane) GEO (located in the equatorial plane) and LEO platforms would certainly provide a powerful observational tool as well as enriched data sets for Earth sciences. Such synergism is greatly enhanced when one considers the potential of utilizing LEO, GEO, and Lagrange point satellites as components of an integrated observational system. For example, satellites at L-1 and L-2 will view the Earth plus the Moon while simultaneously having in

  19. Long Term Missions at the Sun-Earth Libration Point L1: ACE, SOHO, and WIND

    NASA Technical Reports Server (NTRS)

    Roberts, Craig E.

    2011-01-01

    Three heliophysics missions -- the Advanced Composition Explorer (ACE), Solar Heliospheric Observatory (SOHO), and the Global Geoscience WIND -- have been orbiting the Sun-Earth interior libration point L1 continuously since 1997, 1996, and 2004, respectively. ACE and WIND (both NASA missions) and SOHO (an ESA-NASA joint mission) are all operated from the NASA Goddard Space Flight Center (GSFC). While ACE and SOHO have been dedicated libration point orbiters since their launches, WIND has had also a remarkable 10-year career flying a deep-space, multiple lunar-flyby trajectory prior to 2004. That era featured 36 targeted lunar flybys with excursions to both L1 and L2 before its final insertion in L1 orbit. A figure depicts the orbits of the three spacecraft, showing projections of the orbits onto the orthographic planes of a solar rotating ecliptic frame of reference. The SOHO orbit is a quasi-periodic halo orbit, where the frequencies of the in-plane and out-of-plane motions are practically equal. Such an orbit is seen to repeat itself with a period of approximately 178 days. For ACE and WIND, the frequencies of the in-plane and out-of-plane motions are unequal, giving rise to the characteristic Lissajous motion. ACE's orbit is of moderately small amplitude, whereas WIND's orbit is a large-amplitude Lissajous of dimensions close to those of the SOHO halo orbit. As motion about the collinear points is inherently unstable, stationkeeping maneuvers are necessary to prevent orbital decay and eventual escape from the L1 region. Though the three spacecraft are dissimilar (SOHO is a 3-axis stabilized Sun pointer, WIND is a spin-stabilized ecliptic pole pointer, and ACE is also spin-stabilized with its spin axis maintained between 4 and 20 degrees of the Sun), the stationkeeping technique for the three is fundamentally the same. The technique consists of correcting the energy of the orbit via a delta-V directed parallel or anti-parallel to the Spacecraft-to-Sun line. SOHO

  20. First observations of volcanic eruption clouds from L1 by DSCOVR/EPIC

    NASA Astrophysics Data System (ADS)

    Carn, S. A.; Krotkov, N. A.; Taylor, S.; Fisher, B. L.; Li, C.; Hughes, E. J.; Bhartia, P. K.; Prata, F.

    2016-12-01

    Volcanic emissions of sulfur dioxide (SO2) and ash have been measured by ultraviolet (UV) sensors on US and European polar-orbiting satellites since the late 1970s. Although successful, the main limitation of these UV observations from low-Earth orbit has been poor temporal resolution. Timeliness can be crucial when detecting hazardous volcanic eruption clouds that threaten aviation, and most operational geostationary satellites cannot detect SO2, a key tracer of volcanic plumes. In 2015, the launch of the Earth Polychromatic Imaging Camera (EPIC) aboard the Deep Space Climate Observatory (DSCOVR) provided the first opportunity to observe volcanic clouds from the L1 Lagrange point. EPIC is a 10-band spectroradiometer spanning UV to near-IR wavelengths with two UV channels sensitive to SO2, and a ground resolution of 25 km. The unique L1 vantage point provides continuous observations of the sunlit Earth disk, potentially offering multiple daily observations of volcanic SO2 and ash clouds in the EPIC field of view. When coupled with complementary retrievals from polar-orbiting UV and infrared (IR) sensors such as the Ozone Monitoring Instrument (OMI), the Ozone Mapping and Profiler Suite (OMPS), and the Atmospheric Infrared Sounder (AIRS), the increased observation frequency afforded by DSCOVR/EPIC will permit more timely volcanic eruption detection, improved trajectory modeling, and novel analyses of the temporal evolution of volcanic clouds. We demonstrate the sensitivity of EPIC UV radiances to volcanic clouds using examples from the first year of EPIC observations including the December 2015 paroxysmal eruption of Etna volcano (Italy). When combined with OMI and OMPS measurements, the EPIC SO2 data permit hourly tracking of the Etna eruption cloud as it drifts away from the volcano. We also describe ongoing efforts to adapt existing UV backscatter (BUV) algorithms to produce operational EPIC SO2 and Ash Index (AI) products.

  1. Orbit Determination (OD) Error Analysis Results for the Triana Sun-Earth L1 Libration Point Mission and for the Fourier Kelvin Stellar Interferometer (FKSI) Sun-Earth L2 Libration Point Mission Concept

    NASA Technical Reports Server (NTRS)

    Marr, Greg C.

    2003-01-01

    The Triana spacecraft was designed to be launched by the Space Shuttle. The nominal Triana mission orbit will be a Sun-Earth L1 libration point orbit. Using the NASA Goddard Space Flight Center's Orbit Determination Error Analysis System (ODEAS), orbit determination (OD) error analysis results are presented for all phases of the Triana mission from the first correction maneuver through approximately launch plus 6 months. Results are also presented for the science data collection phase of the Fourier Kelvin Stellar Interferometer Sun-Earth L2 libration point mission concept with momentum unloading thrust perturbations during the tracking arc. The Triana analysis includes extensive analysis of an initial short arc orbit determination solution and results using both Deep Space Network (DSN) and commercial Universal Space Network (USN) statistics. These results could be utilized in support of future Sun-Earth libration point missions.

  2. Technique to eliminate computational instability in multibody simulations employing the Lagrange multiplier

    NASA Technical Reports Server (NTRS)

    Watts, G.

    1992-01-01

    A programming technique to eliminate computational instability in multibody simulations that use the Lagrange multiplier is presented. The computational instability occurs when the attached bodies drift apart and violate the constraints. The programming technique uses the constraint equation, instead of integration, to determine the coordinates that are not independent. Although the equations of motion are unchanged, a complete derivation of the incorporation of the Lagrange multiplier into the equation of motion for two bodies is presented. A listing of a digital computer program which uses the programming technique to eliminate computational instability is also presented. The computer program simulates a solid rocket booster and parachute connected by a frictionless swivel.

  3. Visualizing and Understanding the Components of Lagrange and Newton Interpolation

    ERIC Educational Resources Information Center

    Yang, Yajun; Gordon, Sheldon P.

    2016-01-01

    This article takes a close look at Lagrange and Newton interpolation by graphically examining the component functions of each of these formulas. Although interpolation methods are often considered simply to be computational procedures, we demonstrate how the components of the polynomial terms in these formulas provide insight into where these…

  4. Scale-Limited Lagrange Stability and Finite-Time Synchronization for Memristive Recurrent Neural Networks on Time Scales.

    PubMed

    Xiao, Qiang; Zeng, Zhigang

    2017-10-01

    The existed results of Lagrange stability and finite-time synchronization for memristive recurrent neural networks (MRNNs) are scale-free on time evolvement, and some restrictions appear naturally. In this paper, two novel scale-limited comparison principles are established by means of inequality techniques and induction principle on time scales. Then the results concerning Lagrange stability and global finite-time synchronization of MRNNs on time scales are obtained. Scaled-limited Lagrange stability criteria are derived, in detail, via nonsmooth analysis and theory of time scales. Moreover, novel criteria for achieving the global finite-time synchronization are acquired. In addition, the derived method can also be used to study global finite-time stabilization. The proposed results extend or improve the existed ones in the literatures. Two numerical examples are chosen to show the effectiveness of the obtained results.

  5. Modified Lagrange invariants and their role in determining transverse and axial imaging resolutions of self-interference incoherent holographic systems.

    PubMed

    Rosen, Joseph; Kelner, Roy

    2014-11-17

    The Lagrange invariant is a well-known law for optical imaging systems formulated in the frame of ray optics. In this study, we reformulate this law in terms of wave optics and relate it to the resolution limits of various imaging systems. Furthermore, this modified Lagrange invariant is generalized for imaging along the z axis, resulting with the axial Lagrange invariant which can be used to analyze the axial resolution of various imaging systems. To demonstrate the effectiveness of the theory, analysis of the lateral and the axial imaging resolutions is provided for Fresnel incoherent correlation holography (FINCH) systems.

  6. 78 FR 21491 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ... Small Business Investment Act of 1958, as amended (``the Act''), in connection with the financing of a... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662, 02/02-0661] DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption Under Section 312 of the Small Business...

  7. Transfer to the Collinear Libration Point L3 in the Sun-Earth+Moon System

    NASA Technical Reports Server (NTRS)

    Hou, Xi-yun; Tang, Jing-shi; Liu, Lin

    2007-01-01

    The collinear libration point L3 of the sun-earth+moon system is an ideal place for some space missions. Although there has been a great amount of work concerning the applications of the other two collinear libration points L1 and L2, little work has been done about the point L3. In this paper, the dynamics of the libration points was briefly introduced first. Then a way to transfer the spacecraft to the collinear libration point L3 via the invariant manifolds of the other two collinear libration points was proposed. Theoretical works under the model of circular restricted three-body problem were done. For the sun-earth+moon system, this model is a good approximation. The results obtained are useful when a transfer trajectory under the real solar system is designed.

  8. THE POSSIBLE IMPACT OF L5 MAGNETOGRAMS ON NON-POTENTIAL SOLAR CORONAL MAGNETIC FIELD SIMULATIONS

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

    Weinzierl, Marion; Yeates, Anthony R.; Mackay, Duncan H.

    The proposed Carrington-L5 mission would bring instruments to the L5 Lagrange point to provide us with crucial data for space weather prediction. To assess the importance of including a magnetograph, we consider the possible differences in non-potential solar coronal magnetic field simulations when magnetograph observations are available from the L5 point, compared with an L1-based field of view (FOV). A timeseries of synoptic radial magnetic field maps is constructed to capture the emergence of two active regions from the L5 FOV. These regions are initially absent in the L1 magnetic field maps, but are included once they rotate into themore » L1 FOV. Non-potential simulations for these two sets of input data are compared in detail. Within the bipolar active regions themselves, differences in the magnetic field structure can exist between the two simulations once the active regions are included in both. These differences tend to reduce within 5 days of the active region being included in L1. The delayed emergence in L1 can, however, lead to significant persistent differences in long-range connectivity between the active regions and the surrounding fields, and also in the global magnetic energy. In particular, the open magnetic flux and the location of open magnetic footpoints, are sensitive to capturing the real-time of emergence. These results suggest that a magnetograph at L5 could significantly improve predictions of the non-potential corona, the interplanetary magnetic field, and of solar wind source regions on the Sun.« less

  9. L-fuzzy fixed points theorems for L-fuzzy mappings via βℱL-admissible pair.

    PubMed

    Rashid, Maliha; Azam, Akbar; Mehmood, Nayyar

    2014-01-01

    We define the concept of βℱL-admissible for a pair of L-fuzzy mappings and establish the existence of common L-fuzzy fixed point theorem. Our result generalizes some useful results in the literature. We provide an example to support our result.

  10. The research of the coupled orbital-attitude controlled motion of celestial body in the neighborhood of the collinear libration point L1

    NASA Astrophysics Data System (ADS)

    Shmyrov, A.; Shmyrov, V.; Shymanchuk, D.

    2017-10-01

    This article considers the motion of a celestial body within the restricted three-body problem of the Sun-Earth system. The equations of controlled coupled attitude-orbit motion in the neighborhood of collinear libration point L1 are investigated. The translational orbital motion of a celestial body is described using Hill's equations of circular restricted three-body problem of the Sun-Earth system. Rotational orbital motion is described using Euler's dynamic equations and quaternion kinematic equation. We investigate the problem of stability of celestial body rotational orbital motion in relative equilibrium positions and stabilization of celestial body rotational orbital motion with proposed control laws in the neighborhood of collinear libration point L1. To study stabilization problem, Lyapunov function is constructed in the form of the sum of the kinetic energy and special "kinematic function" of the Rodriguez-Hamiltonian parameters. Numerical modeling of the controlled rotational motion of a celestial body at libration point L1 is carried out. The numerical characteristics of the control parameters and rotational motion are given.

  11. Euler-Lagrange formulas for pseudo-Kähler manifolds

    NASA Astrophysics Data System (ADS)

    Park, JeongHyeong

    2016-01-01

    Let c be a characteristic form of degree k which is defined on a Kähler manifold of real dimension m > 2 k. Taking the inner product with the Kähler form Ωk gives a scalar invariant which can be considered as a generalized Lovelock functional. The associated Euler-Lagrange equations are a generalized Einstein-Gauss-Bonnet gravity theory; this theory restricts to the canonical formalism if c =c2 is the second Chern form. We extend previous work studying these equations from the Kähler to the pseudo-Kähler setting.

  12. Comparison of PD-L1 mRNA Expression Measured with the CheckPoint Typer® Assay with PD-L1 Protein Expression Assessed with Immunohistochemistry in Non-small Cell Lung Cancer.

    PubMed

    Erber, Ramona; Stöhr, Robert; Herlein, Stefanie; Giedl, Claudia; Rieker, Ralf Joachim; Fuchs, Florian; Ficker, Joachim H; Hartmann, Arndt; Veltrup, Elke; Wirtz, Ralph M; Brueckl, Wolfgang M

    2017-12-01

    Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has become important since the development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut-offs have been used in different trials to predict response to these drugs, thus comparison of those studies is difficult. We compared PD-L1 mRNA expression measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we investigated the impact of different tumour tissue acquisition methods on the reliability of PD-L1 measurement techniques. NSCLC cases (N=22), including n=9 mediastinal lymph node biopsies acquired by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and n=5 metastases, were evaluated prospectively for PD-L1 protein on tumor cells (TC) and immune cells (IC) using E1L3N and 28-8 antibodies and PD-L1 mRNA using the CheckPoint TYPER® assay. In primary NSCLC tissues, agreement between PD-L1 mRNA and TC staining using the 28-8 antibody was excellent (ĸ=0.85, p=0.0002). Comparing both PD-L1 antibodies against each other showed a kappa value of 0.58 (p=0.0106). In EBUS-TBNA, PD-L1 mRNA correlated perfectly with the 28-8 antibody (ĸ=1.0, p=0.0023). PD-L1 mRNA levels significantly differed when comparing 28-8 TC staining of tumours >49% with 1-49% and 0% (p=0.0040; p=0.0081, respectively). In metastatic lesions, differences between PD-L1 mRNA and IHC became apparent (ĸ=0.2, p=0.2525). Testing of PD-L1 mRNA and 28-8 IHC showed an excellent agreement in NSCLC samples including mediastinal lymph node biopsies. Since PD-L1 expression in >50% TC detected by 28-8 IHC can be reliably detected by RT-qPCR, quantitative PD-L1 mRNA determination should be considered as an alternative to IHC as there is no interobserver variability in RNA results. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. L-Fuzzy Fixed Points Theorems for L-Fuzzy Mappings via β ℱL-Admissible Pair

    PubMed Central

    Rashid, Maliha; Azam, Akbar

    2014-01-01

    We define the concept of β ℱL-admissible for a pair of L-fuzzy mappings and establish the existence of common L-fuzzy fixed point theorem. Our result generalizes some useful results in the literature. We provide an example to support our result. PMID:24688441

  14. The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex*

    PubMed Central

    Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E.; Jaspers, Nicolaas G. J.; Kaptein, Robert; Hoeijmakers, Jan H. J.; Boelens, Rolf

    2015-01-01

    The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe231, Leu231 lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation. PMID:26085086

  15. The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex.

    PubMed

    Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E; Jaspers, Nicolaas G J; Kaptein, Robert; Hoeijmakers, Jan H J; Boelens, Rolf

    2015-08-14

    The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe(231), Leu(231) lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Augmented Lagrange Hopfield network for solving economic dispatch problem in competitive environment

    NASA Astrophysics Data System (ADS)

    Vo, Dieu Ngoc; Ongsakul, Weerakorn; Nguyen, Khai Phuc

    2012-11-01

    This paper proposes an augmented Lagrange Hopfield network (ALHN) for solving economic dispatch (ED) problem in the competitive environment. The proposed ALHN is a continuous Hopfield network with its energy function based on augmented Lagrange function for efficiently dealing with constrained optimization problems. The ALHN method can overcome the drawbacks of the conventional Hopfield network such as local optimum, long computational time, and linear constraints. The proposed method is used for solving the ED problem with two revenue models of revenue based on payment for power delivered and payment for reserve allocated. The proposed ALHN has been tested on two systems of 3 units and 10 units for the two considered revenue models. The obtained results from the proposed methods are compared to those from differential evolution (DE) and particle swarm optimization (PSO) methods. The result comparison has indicated that the proposed method is very efficient for solving the problem. Therefore, the proposed ALHN could be a favorable tool for ED problem in the competitive environment.

  17. Alternative Transfer to the Earth-Moon Lagrangian Points L4 and L5 Using Lunar Gravity assist

    NASA Astrophysics Data System (ADS)

    Salazar, Francisco; Winter, Othon; Macau, Elbert; Bertachini de Almeida Prado, Antonio Fernando

    2012-07-01

    Lagrangian points L4 and L5 lie at 60 degrees ahead of and behind Moon in its orbit with respect to the Earth. Each one of them is a third point of an equilateral triangle with the base of the line defined by those two bodies. These Lagrangian points are stable for the Earth-Moon mass ratio. Because of their distance electromagnetic radiations from the Earth arrive on them substantially attenuated. As so, these Lagrangian points represent remarkable positions to host astronomical observatories. However, this same distance characteristic may be a challenge for periodic servicing mission. This paper studies transfer orbits in the planar restricted three-body problem. To avoid solving a two-boundary problem, the patched-conic approximation is used to find initial conditions to transfer a spacecraft between an Earth circular parking orbit and the Lagrangian points L4, L5 (in the Earth-Moon system), such that a swing-by maneuver is applied using the lunar gravity. We also found orbits that can be used to make a tour to the Lagrangian points L4, L5 based on the theorem of image trajectories. Keywords: Stable Lagrangian points, L4, L5, Three-Body problem, Patched Conic, Swing-by

  18. Parallel processing a three-dimensional free-lagrange code

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

    Mandell, D.A.; Trease, H.E.

    1989-01-01

    A three-dimensional, time-dependent free-Lagrange hydrodynamics code has been multitasked and autotasked on a CRAY X-MP/416. The multitasking was done by using the Los Alamos Multitasking Control Library, which is a superset of the CRAY multitasking library. Autotasking is done by using constructs which are only comment cards if the source code is not run through a preprocessor. The three-dimensional algorithm has presented a number of problems that simpler algorithms, such as those for one-dimensional hydrodynamics, did not exhibit. Problems in converting the serial code, originally written for a CRAY-1, to a multitasking code are discussed. Autotasking of a rewritten versionmore » of the code is discussed. Timing results for subroutines and hot spots in the serial code are presented and suggestions for additional tools and debugging aids are given. Theoretical speedup results obtained from Amdahl's law and actual speedup results obtained on a dedicated machine are presented. Suggestions for designing large parallel codes are given.« less

  19. On the commutator of C^{\\infty}} -symmetries and the reduction of Euler-Lagrange equations

    NASA Astrophysics Data System (ADS)

    Ruiz, A.; Muriel, C.; Olver, P. J.

    2018-04-01

    A novel procedure to reduce by four the order of Euler-Lagrange equations associated to nth order variational problems involving single variable integrals is presented. In preparation, a new formula for the commutator of two \

  20. Smoot Cosmology Group

    Science.gov Websites

    orbit around L2, the second Lagrange point of the Earth-Sun system, which is about 1.5 million orbits L2, it makes one rotation about the Sun per year. The spacecraft spin axis has to be rotated at the same rate in order to remain Sun pointed. This is achieved by making regular manoeuvres that will

  1. Free-Lagrange methods for compressible hydrodynamics in two space dimensions

    NASA Astrophysics Data System (ADS)

    Crowley, W. E.

    1985-03-01

    Since 1970 a research and development program in Free-Lagrange methods has been active at Livermore. The initial steps were taken with incompressible flows for simplicity. Since then the effort has been concentrated on compressible flows with shocks in two space dimensions and time. In general, the line integral method has been used to evaluate derivatives and the artificial viscosity method has been used to deal with shocks. Basically, two Free-Lagrange formulations for compressible flows in two space dimensions and time have been tested and both will be described. In method one, all prognostic quantities were node centered and staggered in time. The artificial viscosity was zone centered. One mesh reconnection philosphy was that the mesh should be optimized so that nearest neighbors were connected together. Another was that vertex angles should tend toward equality. In method one, all mesh elements were triangles. In method two, both quadrilateral and triangular mesh elements are permitted. The mesh variables are staggered in space and time as suggested originally by Richtmyer and von Neumann. The mesh reconnection strategy is entirely different in method two. In contrast to the global strategy of nearest neighbors, we now have a more local strategy that reconnects in order to keep the integration time step above a user chosen threshold. An additional strategy reconnects in the vicinity of large relative fluid motions. Mesh reconnection consists of two parts: (1) the tools that permits nodes to be merged and quads to be split into triangles etc. and; (2) the strategy that dictates how and when to use the tools. Both tools and strategies change with time in a continuing effort to expand the capabilities of the method. New ideas are continually being tried and evaluated.

  2. A composite experimental dynamic substructuring method based on partitioned algorithms and localized Lagrange multipliers

    NASA Astrophysics Data System (ADS)

    Abbiati, Giuseppe; La Salandra, Vincenzo; Bursi, Oreste S.; Caracoglia, Luca

    2018-02-01

    Successful online hybrid (numerical/physical) dynamic substructuring simulations have shown their potential in enabling realistic dynamic analysis of almost any type of non-linear structural system (e.g., an as-built/isolated viaduct, a petrochemical piping system subjected to non-stationary seismic loading, etc.). Moreover, owing to faster and more accurate testing equipment, a number of different offline experimental substructuring methods, operating both in time (e.g. the impulse-based substructuring) and frequency domains (i.e. the Lagrange multiplier frequency-based substructuring), have been employed in mechanical engineering to examine dynamic substructure coupling. Numerous studies have dealt with the above-mentioned methods and with consequent uncertainty propagation issues, either associated with experimental errors or modelling assumptions. Nonetheless, a limited number of publications have systematically cross-examined the performance of the various Experimental Dynamic Substructuring (EDS) methods and the possibility of their exploitation in a complementary way to expedite a hybrid experiment/numerical simulation. From this perspective, this paper performs a comparative uncertainty propagation analysis of three EDS algorithms for coupling physical and numerical subdomains with a dual assembly approach based on localized Lagrange multipliers. The main results and comparisons are based on a series of Monte Carlo simulations carried out on a five-DoF linear/non-linear chain-like systems that include typical aleatoric uncertainties emerging from measurement errors and excitation loads. In addition, we propose a new Composite-EDS (C-EDS) method to fuse both online and offline algorithms into a unique simulator. Capitalizing from the results of a more complex case study composed of a coupled isolated tank-piping system, we provide a feasible way to employ the C-EDS method when nonlinearities and multi-point constraints are present in the emulated system.

  3. Preliminary Design Considerations for Access and Operations in Earth-Moon L1/L2 Orbits

    NASA Technical Reports Server (NTRS)

    Folta, David C.; Pavlak, Thomas A.; Haapala, Amanda F.; Howell, Kathleen C.

    2013-01-01

    Within the context of manned spaceflight activities, Earth-Moon libration point orbits could support lunar surface operations and serve as staging areas for future missions to near-Earth asteroids and Mars. This investigation examines preliminary design considerations including Earth-Moon L1/L2 libration point orbit selection, transfers, and stationkeeping costs associated with maintaining a spacecraft in the vicinity of L1 or L2 for a specified duration. Existing tools in multi-body trajectory design, dynamical systems theory, and orbit maintenance are leveraged in this analysis to explore end-to-end concepts for manned missions to Earth-Moon libration points.

  4. Carbon Dioxide Compensation Points of Flowering Plants 1

    PubMed Central

    Krenzer, Eugene G.; Moss, Dale N.; Crookston, R. Kent

    1975-01-01

    Carbon dioxide compensation points of several hundred species of monocotyledons and dicotyledons have been measured during the course of various experiments in our laboratory over a period of several years. These have been classified into two groups: high, compensation points of 40 μl/l or greater; and low, compensation points of 10 μl/l or less. They are listed alphabetically both by families and species for monocotyledons and dicotyledons. Only two species did not unequivocally fit into the above established groups. These were Moricandia arvensis (L.) DC., which had an average compensation point of 26 μl/l and Panicum milioides Nees ex Trin., which was variable, but most often equilibrated between 12 to 20 μl/l CO2. PMID:16659272

  5. 78 FR 32294 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P., License No. 02/02-0662,02/02...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... Small Business Investment Act of 1958, as amended (``the Act''), in connection with the financing of a... SMALL BUSINESS ADMINISTRATION DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P., License No. 02/02-0662,02/02-0661; Notice Seeking Exemption Under Section 312 of the Small Business...

  6. Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response.

    PubMed

    Holmström, Morten Orebo; Riley, Caroline Hasselbalch; Skov, Vibe; Svane, Inge Marie; Hasselbalch, Hans Carl; Andersen, Mads Hald

    2018-01-01

    The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4 + T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.

  7. A Fluid Structure Algorithm with Lagrange Multipliers to Model Free Swimming

    NASA Astrophysics Data System (ADS)

    Sahin, Mehmet; Dilek, Ezgi

    2017-11-01

    A new monolithic approach is prosed to solve the fluid-structure interaction (FSI) problem with Lagrange multipliers in order to model free swimming/flying. In the present approach, the fluid domain is modeled by the incompressible Navier-Stokes equations and discretized using an Arbitrary Lagrangian-Eulerian (ALE) formulation based on the stable side-centered unstructured finite volume method. The solid domain is modeled by the constitutive laws for the nonlinear Saint Venant-Kirchhoff material and the classical Galerkin finite element method is used to discretize the governing equations in a Lagrangian frame. In order to impose the body motion/deformation, the distance between the constraint pair nodes is imposed using the Lagrange multipliers, which is independent from the frame of reference. The resulting algebraic linear equations are solved in a fully coupled manner using a dual approach (null space method). The present numerical algorithm is initially validated for the classical FSI benchmark problems and then applied to the free swimming of three linked ellipses. The authors are grateful for the use of the computing resources provided by the National Center for High Performance Computing (UYBHM) under Grant Number 10752009 and the computing facilities at TUBITAK-ULAKBIM, High Performance and Grid Computing Center.

  8. Synoptic ozone, cloud reflectivity, and erythemal irradiance from sunrise to sunset for the whole earth as viewed by the DSCOVR spacecraft from the earth-sun Lagrange 1 orbit

    NASA Astrophysics Data System (ADS)

    Herman, Jay; Huang, Liang; McPeters, Richard; Ziemke, Jerry; Cede, Alexander; Blank, Karin

    2018-01-01

    EPIC (Earth Polychromatic Imaging Camera) on board the DSCOVR (Deep Space Climate Observatory) spacecraft is the first earth science instrument located near the earth-sun gravitational plus centrifugal force balance point, Lagrange 1. EPIC measures earth-reflected radiances in 10 wavelength channels ranging from 317.5 to 779.5 nm. Of these channels, four are in the UV range 317.5, 325, 340, and 388 nm, which are used to retrieve O3, 388 nm scene reflectivity (LER: Lambert equivalent reflectivity), SO2, and aerosol properties. These new synoptic quantities are retrieved for the entire sunlit globe from sunrise to sunset multiple times per day as the earth rotates in EPIC's field of view. Retrieved ozone amounts agree with ground-based measurements and satellite data to within 3 %. The ozone amounts and LER are combined to derive the erythemal irradiance for the earth's entire sunlit surface at a nadir resolution of 18 × 18 km2 using a computationally efficient approximation to a radiative transfer calculation of irradiance. The results show very high summertime values of the UV index (UVI) in the Andes and Himalayas (greater than 18), and high values of UVI near the Equator at equinox.

  9. PID position regulation in one-degree-of-freedom Euler-Lagrange systems actuated by a PMSM

    NASA Astrophysics Data System (ADS)

    Verastegui-Galván, J.; Hernández-Guzmán, V. M.; Orrante-Sakanassi, J.

    2018-02-01

    This paper is concerned with position regulation in one-degree-of-freedom Euler-Lagrange Systems. We consider that the mechanical subsystem is actuated by a permanent magnet synchronous motor (PMSM). Our proposal consists of a Proportional-Integral-Derivative (PID) controller for the mechanical subsystem and a slight variation of field oriented control for the PMSM. We take into account the motor electric dynamics during the stability analysis. We present, for the first time, a global asymptotic stability proof for such a control scheme without requiring the mechanical subsystem to naturally possess viscous friction. Finally, as a corollary of our main result we prove global asymptotic stability for output feedback PID regulation of one-degree-of-freedom Euler-Lagrange systems when generated torque is considered as the system input, i.e. when the electric dynamics of PMSM's is not taken into account.

  10. Distributed Fault-Tolerant Control of Networked Uncertain Euler-Lagrange Systems Under Actuator Faults.

    PubMed

    Chen, Gang; Song, Yongduan; Lewis, Frank L

    2016-05-03

    This paper investigates the distributed fault-tolerant control problem of networked Euler-Lagrange systems with actuator and communication link faults. An adaptive fault-tolerant cooperative control scheme is proposed to achieve the coordinated tracking control of networked uncertain Lagrange systems on a general directed communication topology, which contains a spanning tree with the root node being the active target system. The proposed algorithm is capable of compensating for the actuator bias fault, the partial loss of effectiveness actuation fault, the communication link fault, the model uncertainty, and the external disturbance simultaneously. The control scheme does not use any fault detection and isolation mechanism to detect, separate, and identify the actuator faults online, which largely reduces the online computation and expedites the responsiveness of the controller. To validate the effectiveness of the proposed method, a test-bed of multiple robot-arm cooperative control system is developed for real-time verification. Experiments on the networked robot-arms are conduced and the results confirm the benefits and the effectiveness of the proposed distributed fault-tolerant control algorithms.

  11. Early Mission Maneuver Operations for the Deep Space Climate Observatory Sun-Earth L1 Libration Point Mission

    NASA Technical Reports Server (NTRS)

    Roberts, Craig; Case, Sara; Reagoso, John; Webster, Cassandra

    2015-01-01

    The Deep Space Climate Observatory mission launched on February 11, 2015, and inserted onto a transfer trajectory toward a Lissajous orbit around the Sun-Earth L1 libration point. This paper presents an overview of the baseline transfer orbit and early mission maneuver operations leading up to the start of nominal science orbit operations. In particular, the analysis and performance of the spacecraft insertion, mid-course correction maneuvers, and the deep-space Lissajous orbit insertion maneuvers are discussed, com-paring the baseline orbit with actual mission results and highlighting mission and operations constraints..

  12. Alternative transfer to the Earth-Moon Lagrangian points L4 and L5 using lunar gravity assist

    NASA Astrophysics Data System (ADS)

    Salazar, F. J. T.; Macau, E. E. N.; Winter, O. C.

    2014-02-01

    Lagrangian points L4 and L5 lie at 60° ahead of and behind the Moon in its orbit with respect to the Earth. Each one of them is a third point of an equilateral triangle with the base of the line defined by those two bodies. These Lagrangian points are stable for the Earth-Moon mass ratio. As so, these Lagrangian points represent remarkable positions to host astronomical observatories or space stations. However, this same distance characteristic may be a challenge for periodic servicing mission. This paper studies elliptic trajectories from an Earth circular parking orbit to reach the Moon's sphere of influence and apply a swing-by maneuver in order to re-direct the path of a spacecraft to a vicinity of the Lagrangian points L4 and L5. Once the geocentric transfer orbit and the initial impulsive thrust have been determined, the goal is to establish the angle at which the geocentric trajectory crosses the lunar sphere of influence in such a way that when the spacecraft leaves the Moon's gravitational field, its trajectory and velocity with respect to the Earth change in order to the spacecraft arrives at L4 and L5. In this work, the planar Circular Restricted Three Body Problem approximation is used and in order to avoid solving a two boundary problem, the patched-conic approximation is considered.

  13. Imaging Near-Earth Electron Densities Using Thomson Scattering

    DTIC Science & Technology

    2009-01-15

    geocentric solar magnetospheric (GSM) coordinates1. TECs were initially computed from a viewing loca- tion at the Sun-Earth L1 Lagrange point2 for both...further find that an elliptical Earth orbit (apogee ~30 RE) is a suitable lower- cost option for a demonstration mission. 5. SIMULATED OBSERVATIONS We

  14. Comparing L1 and L2 Texts and Writers in First-Year Composition

    ERIC Educational Resources Information Center

    Eckstein, Grant; Ferris, Dana

    2018-01-01

    Scholars have at various points discussed the needs of second language (L2) writers enrolled in "mainstream" composition courses where they are mixed with native (L1) English speakers. Other researchers have investigated the experiences of L2 writers in mainstream classes and the perceptions of their instructors about their abilities and…

  15. Spacecraft Maneuvering at the Sun/Earth-Moon L2 Libration Point

    NASA Astrophysics Data System (ADS)

    Shahid, Kamran

    of the proposed control techniques for spacecraft maneuvering using solar radiation pressure at the L2 libration point. Stationkeeping accuracies of 50m and formation maintenance accuracies of less than 1m are possible using solar radiation pressure at a sub-L2 libration point. The benefits of these control techniques include increasing libration point mission lifetimes and doubling payload mass fractions as compared to conventional propulsion methods.

  16. Point mutations in acetylcholinesterase 1 associated with chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens Stål.

    PubMed

    Zhang, Y; Yang, B; Li, J; Liu, M; Liu, Z

    2017-08-01

    Insecticide resistance frequently results from target-site insensitivity, such as point mutations in acetylcholinesterases (AChEs) for resistance to organophosphates and carbamates. From a field-originated population of Nilaparvata lugens, a major rice pest, a resistant population (R9) was obtained by nine-generation continuous selection with chlorpyrifos. From the same field population, a relatively susceptible population (S9) was also constructed through rearing without any insecticides. Compared to the susceptible strain, Sus [medium lethal dose (LC 50 ) = 0.012 mg/l], R9 had a resistance ratio (RR) of 253.08-fold, whereas the RR of S9 was only 2.25-fold. Piperonyl butoxide and triphenyl phosphate synergized chlorpyrifos in R9 less than three-fold, indicating other important mechanisms for high resistance. The target-site insensitivity was supported by the key property differences of crude AChEs between R9 and S9. Compared to S9, three mutations (G119S, F331C and I332L) were detected in NlAChE1 from individuals of the R9 and field populations, but no mutation was detected in NlAChE2. G119S and F331C could decreased insecticide sensitivities in recombinant NlAChE1, whereas I332L took effect through increasing the influence of F331C on target insensitivity. F331C might be deleterious because of its influence on the catalytic efficiency of NlAChE1, whereas I332L would decrease these adverse effects and maintain the normal functions of AChEs. © 2017 The Royal Entomological Society.

  17. Stress-Induced Acoustic Variation in L2 and L1 Spanish Vowels.

    PubMed

    Romanelli, Sofía; Menegotto, Andrea; Smyth, Ron

    2018-05-28

    We assessed the effect of lexical stress on the duration and quality of Spanish word-final vowels /a, e, o/ produced by American English late intermediate learners of L2 Spanish, as compared to those of native L1 Argentine Spanish speakers. Participants read 54 real words ending in /a, e, o/, with either final or penultimate lexical stress, embedded in a text and a word list. We measured vowel duration and both F1 and F2 frequencies at 3 temporal points. stressed vowels were longer than unstressed vowels, in Spanish L1 and L2. L1 and L2 Spanish stressed /a/ and /e/ had higher F1 values than their unstressed counterparts. Only the L2 speakers showed evidence of rising offglides for /e/ and /o/. The L2 and L1 Spanish vowel space was compressed in the absence of stress. Lexical stress affected the vowel quality of L1 and L2 Spanish vowels. We provide an up-to-date account of the formant trajectories of Argentine River Plate Spanish word-final /a, e, o/ and offer experimental support to the claim that stress affects the quality of Spanish vowels in word-final contexts. © 2018 S. Karger AG, Basel.

  18. Conceptual Design of a Synoptic Interplanetary Monitor Platform at L sub 1 (SIMPL).

    DTIC Science & Technology

    1985-11-01

    solar events. -159- . . . .. . 105 II1II" -I .5 year mission at Earth-Sun- libration point plus transfer orbit eDashed line is approximate true dose as...Design .. ...................................... 27 4.1 The L Libration Point .......................... 27 4.2 L Orbit Options...34) to provide power, attitude control, communications, and other support to maintain the instruments in a halo orbit around the L libration point ; 4. a

  19. 78 FR 69516 - DeltaPoint Capital IV, L.P.; License No. 02/02-0662; Notice Seeking Exemption Under the Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... 107.730). DeltaPoint Capital IV, L.P. provided financing to BioMaxx, Inc., 1 Fishers Road, Suite 160...., an Associate of DeltaPoint Capital IV, L.P., owns more than ten percent of BioMaxx, Inc. Therefore...

  20. Modeling of Mixing Behavior in a Combined Blowing Steelmaking Converter with a Filter-Based Euler-Lagrange Model

    NASA Astrophysics Data System (ADS)

    Li, Mingming; Li, Lin; Li, Qiang; Zou, Zongshu

    2018-05-01

    A filter-based Euler-Lagrange multiphase flow model is used to study the mixing behavior in a combined blowing steelmaking converter. The Euler-based volume of fluid approach is employed to simulate the top blowing, while the Lagrange-based discrete phase model that embeds the local volume change of rising bubbles for the bottom blowing. A filter-based turbulence method based on the local meshing resolution is proposed aiming to improve the modeling of turbulent eddy viscosities. The model validity is verified through comparison with physical experiments in terms of mixing curves and mixing times. The effects of the bottom gas flow rate on bath flow and mixing behavior are investigated and the inherent reasons for the mixing result are clarified in terms of the characteristics of bottom-blowing plumes, the interaction between plumes and top-blowing jets, and the change of bath flow structure.

  1. Particle Swarm Optimization of Low-Thrust, Geocentric-to-Halo-Orbit Transfers

    NASA Astrophysics Data System (ADS)

    Abraham, Andrew J.

    Missions to Lagrange points are becoming increasingly popular amongst spacecraft mission planners. Lagrange points are locations in space where the gravity force from two bodies, and the centrifugal force acting on a third body, cancel. To date, all spacecraft that have visited a Lagrange point have done so using high-thrust, chemical propulsion. Due to the increasing availability of low-thrust (high efficiency) propulsive devices, and their increasing capability in terms of fuel efficiency and instantaneous thrust, it has now become possible for a spacecraft to reach a Lagrange point orbit without the aid of chemical propellant. While at any given time there are many paths for a low-thrust trajectory to take, only one is optimal. The traditional approach to spacecraft trajectory optimization utilizes some form of gradient-based algorithm. While these algorithms offer numerous advantages, they also have a few significant shortcomings. The three most significant shortcomings are: (1) the fact that an initial guess solution is required to initialize the algorithm, (2) the radius of convergence can be quite small and can allow the algorithm to become trapped in local minima, and (3) gradient information is not always assessable nor always trustworthy for a given problem. To avoid these problems, this dissertation is focused on optimizing a low-thrust transfer trajectory from a geocentric orbit to an Earth-Moon, L1, Lagrange point orbit using the method of Particle Swarm Optimization (PSO). The PSO method is an evolutionary heuristic that was originally written to model birds swarming to locate hidden food sources. This PSO method will enable the exploration of the invariant stable manifold of the target Lagrange point orbit in an effort to optimize the spacecraft's low-thrust trajectory. Examples of these optimized trajectories are presented and contrasted with those found using traditional, gradient-based approaches. In summary, the results of this dissertation find

  2. North American CO2 fluxes for 2007-2015 from NOAA's CarbonTracker-Lagrange Regional Inverse Modeling Framework

    NASA Astrophysics Data System (ADS)

    Andrews, A. E.; Hu, L.; Thoning, K. W.; Nehrkorn, T.; Mountain, M. E.; Jacobson, A. R.; Michalak, A.; Dlugokencky, E. J.; Sweeney, C.; Worthy, D. E. J.; Miller, J. B.; Fischer, M. L.; Biraud, S.; van der Velde, I. R.; Basu, S.; Tans, P. P.

    2017-12-01

    CarbonTracker-Lagrange (CT-L) is a new high-resolution regional inverse modeling system for improved estimation of North American CO2 fluxes. CT-L uses footprints from the Stochastic Time-Inverted Lagrangian Transport (STILT) model driven by high-resolution (10 to 30 km) meteorological fields from the Weather Research and Forecasting (WRF) model. We performed a suite of synthetic-data experiments to evaluate a variety of inversion configurations, including (1) solving for scaling factors to an a priori flux versus additive corrections, (2) solving for fluxes at 3-hrly resolution versus at coarser temporal resolution, (3) solving for fluxes at 1o × 1o resolution versus at large eco-regional scales. Our framework explicitly and objectively solves for the optimal solution with a full error covariance matrix with maximum likelihood estimation, thereby enabling rigorous uncertainty estimates for the derived fluxes. In the synthetic-data inversions, we find that solving for weekly scaling factors of a priori Net Ecosystem Exchange (NEE) at 1o × 1o resolution with optimization of diurnal cycles of CO2 fluxes yields faithful retrieval of the specified "true" fluxes as those solved at 3-hrly resolution. In contrast, a scheme that does not allow for optimization of diurnal cycles of CO2 fluxes suffered from larger aggregation errors. We then applied the optimal inversion setup to estimate North American fluxes for 2007-2015 using real atmospheric CO2 observations, multiple prior estimates of NEE, and multiple boundary values estimated from the NOAA's global Eulerian CarbonTracker (CarbonTracker) and from an empirical approach. Our derived North American land CO2 fluxes show larger seasonal amplitude than those estimated from the CarbonTracker, removing seasonal biases in the CarbonTracker's simulated CO2 mole fractions. Independent evaluations using in-situ CO2 eddy covariance flux measurements and independent aircraft profiles also suggest an improved estimation on North

  3. Voidage correction algorithm for unresolved Euler-Lagrange simulations

    NASA Astrophysics Data System (ADS)

    Askarishahi, Maryam; Salehi, Mohammad-Sadegh; Radl, Stefan

    2018-04-01

    The effect of grid coarsening on the predicted total drag force and heat exchange rate in dense gas-particle flows is investigated using Euler-Lagrange (EL) approach. We demonstrate that grid coarsening may reduce the predicted total drag force and exchange rate. Surprisingly, exchange coefficients predicted by the EL approach deviate more significantly from the exact value compared to results of Euler-Euler (EE)-based calculations. The voidage gradient is identified as the root cause of this peculiar behavior. Consequently, we propose a correction algorithm based on a sigmoidal function to predict the voidage experienced by individual particles. Our correction algorithm can significantly improve the prediction of exchange coefficients in EL models, which is tested for simulations involving Euler grid cell sizes between 2d_p and 12d_p . It is most relevant in simulations of dense polydisperse particle suspensions featuring steep voidage profiles. For these suspensions, classical approaches may result in an error of the total exchange rate of up to 30%.

  4. Direct observations of L-I-H and H-I-L transitions with the X-point reciprocating probe in ASDEX Upgrade

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

    Müller, S. H.; Conway, G. D.; Birkenmeier, G.

    A reciprocating Langmuir probe was used to directly measure the behavior of turbulence and flows in the X-point region during transitions between low-(L) and high-confinement (H) mode in ASDEX Upgrade. The probe traverses the divertor horizontally in 140 ms, typically 2–5 cm below the X-point. Toroidal Mach number, density, floating potential (ϕ{sub f}), and electron temperature (T{sub e}) are measured. In the regime accessible to the probe (P{sub inj}<1.5 MW, line-integrated core density <4×10{sup 19} m{sup −2}), the L-H transition features an intermediate phase (I-phase), characterized by limit-cycle oscillations at 0.5–3 kHz [Conway et al., Phys. Rev. Lett. 106, 065001 (2011)]. The probe measurements revealmore » that this pulsing affects both the density and the toroidal Mach number. It is present in both the low-(LFS) and high-field sides (HFS) of the scrape-off layer, while high-amplitude broadband turbulence usually dominates the private-flux region. Profile comparisons between L-mode and I-phase show lower density in pulsing regions and small shifts in T{sub e}, directed oppositely on LFS and HFS, which are compensated by shifts in ϕ{sub f} to yield a surprisingly unchanged plasma potential profile. Directly observed L-I-phase transitions reveal that the onset of the pulsing is preceded by a fast 50% density drop in the HFS X-point region. Back transitions to L-mode occur essentially symmetrically, with the pulsing stopping first, followed by a fast recovery to L-mode density levels in the divertor.« less

  5. Lagrange formula for differential operators on a tree-graph and the resolvents of well-posed restrictions of operator

    NASA Astrophysics Data System (ADS)

    Koshkarbayev, Nurbol; Kanguzhin, Baltabek

    2017-09-01

    In this paper we study the question on the full description of well-posed restrictions of given maximal differential operator on a tree-graph. Lagrange formula for differential operator on a tree with Kirchhoff conditions at its internal vertices is presented.

  6. Domain decomposition methods for nonconforming finite element spaces of Lagrange-type

    NASA Technical Reports Server (NTRS)

    Cowsar, Lawrence C.

    1993-01-01

    In this article, we consider the application of three popular domain decomposition methods to Lagrange-type nonconforming finite element discretizations of scalar, self-adjoint, second order elliptic equations. The additive Schwarz method of Dryja and Widlund, the vertex space method of Smith, and the balancing method of Mandel applied to nonconforming elements are shown to converge at a rate no worse than their applications to the standard conforming piecewise linear Galerkin discretization. Essentially, the theory for the nonconforming elements is inherited from the existing theory for the conforming elements with only modest modification by constructing an isomorphism between the nonconforming finite element space and a space of continuous piecewise linear functions.

  7. Generalized Lagrange Jacobi Gauss-Lobatto (GLJGL) Collocation Method for Solving Linear and Nonlinear Fokker-Planck Equations

    NASA Astrophysics Data System (ADS)

    Parand, K.; Latifi, S.; Moayeri, M. M.; Delkhosh, M.

    2018-05-01

    In this study, we have constructed a new numerical approach for solving the time-dependent linear and nonlinear Fokker-Planck equations. In fact, we have discretized the time variable with Crank-Nicolson method and for the space variable, a numerical method based on Generalized Lagrange Jacobi Gauss-Lobatto (GLJGL) collocation method is applied. It leads to in solving the equation in a series of time steps and at each time step, the problem is reduced to a problem consisting of a system of algebraic equations that greatly simplifies the problem. One can observe that the proposed method is simple and accurate. Indeed, one of its merits is that it is derivative-free and by proposing a formula for derivative matrices, the difficulty aroused in calculation is overcome, along with that it does not need to calculate the General Lagrange basis and matrices; they have Kronecker property. Linear and nonlinear Fokker-Planck equations are given as examples and the results amply demonstrate that the presented method is very valid, effective, reliable and does not require any restrictive assumptions for nonlinear terms.

  8. Prediction of a Densely Loaded Particle-Laden Jet using a Euler-Lagrange Dense Spray Model

    NASA Astrophysics Data System (ADS)

    Pakseresht, Pedram; Apte, Sourabh V.

    2017-11-01

    Modeling of a dense spray regime using an Euler-Lagrange discrete-element approach is challenging because of local high volume loading. A subgrid cluster of droplets can lead to locally high void fractions for the disperse phase. Under these conditions, spatio-temporal changes in the carrier phase volume fractions, which are commonly neglected in spray simulations in an Euler-Lagrange two-way coupling model, could become important. Accounting for the carrier phase volume fraction variations, leads to zero-Mach number, variable density governing equations. Using pressure-based solvers, this gives rise to a source term in the pressure Poisson equation and a non-divergence free velocity field. To test the validity and predictive capability of such an approach, a round jet laden with solid particles is investigated using Direct Numerical Simulation and compared with available experimental data for different loadings. Various volume fractions spanning from dilute to dense regimes are investigated with and without taking into account the volume displacement effects. The predictions of the two approaches are compared and analyzed to investigate the effectiveness of the dense spray model. Financial support was provided by National Aeronautics and Space Administration (NASA).

  9. Synthesis of a controller for stabilizing the motion of a rigid body about a fixed point

    NASA Astrophysics Data System (ADS)

    Zabolotnov, Yu. M.; Lobanov, A. A.

    2017-05-01

    A method for the approximate design of an optimal controller for stabilizing the motion of a rigid body about a fixed point is considered. It is assumed that rigid body motion is nearly the motion in the classical Lagrange case. The method is based on the common use of the Bellman dynamic programming principle and the averagingmethod. The latter is used to solve theHamilton-Jacobi-Bellman equation approximately, which permits synthesizing the controller. The proposed method for controller design can be used in many problems close to the problem of motion of the Lagrange top (the motion of a rigid body in the atmosphere, the motion of a rigid body fastened to a cable in deployment of the orbital cable system, etc.).

  10. [L-THIA-based management design for controlling urban non-point source pollution].

    PubMed

    Guo, Qing-Hai; Yang, Liu; Ke-Ming, Ma

    2007-11-01

    L-THIA Model was used to simulate the amounts of NPS pollutants in 2 catchments of Sanjiao watershed (Sj1, Sj2) in Hanyang district, and the total simulated amount of NPS loads in Sj1 and Sj2 were 1.82 x 10(4) kg, 1.38 x 10(5) kg, respectively. Based on the theory of resource-sink" and interaction of pattern with process, a series of BMPs, including green roof, grassland, porous pavement, infiltration trench, vegetative filter strip and wet pond, were optimized, and effects of BMPs were simulated along the surface runoff pathway. The results show that total pollutants outputs entering Sj1 and Sj2 account for 14.65% and 6.57%, respectively. Combining L-THIA model and BMPs in series is a proper measure for non-point source pollution control and urban development planning at watershed or region scale.

  11. Observing Coronal Mass Ejections from the Sun-Earth L5 Point

    NASA Astrophysics Data System (ADS)

    Gopalswamy, N.; Davila, J. M.; St Cyr, O. C.

    2013-12-01

    Coronal mass ejections (CMEs) are the most energetic phenomenon in the heliosphere and are known to be responsible for severe space weather. Most of the current knowledge on CMEs accumulated over the past few decades has been derived from observations made from the Sun-Earth line, which is not the ideal vantage point to observe Earth-affecting CMEs (Gopalswamy et al., 2011a,b). The STEREO mission viewed CMEs from points away from the Sun-Earth line and demonstrated the importance of such observations in understanding the three-dimensional structure of CMEs and their true kinematics. In this paper, we show that it is advantageous to observe CMEs from the Sun-Earth L5 point in studying CMEs that affect Earth. In particular, these observations are important in identifying that part of the CME that is likely to arrive at Earth. L5 observations are critical for several aspects of CME studies such as: (i) they can also provide near-Sun space speed of CMEs, which is an important input for modeling Earth-arriving CMEs, (ii) backside and frontside CMEs can be readily distinguished even without inner coronal imagers, and (iii) preceding CMEs in the path of Earth-affecting CMEs can be identified for a better estimate of the travel time, which may not be possible from the Sun-Earth line. We also discuss how the L5 vantage point compares with the Sun-Earth L4 point for observing Earth-affecting CMEs. References Gopalswamy, N., Davila, J. M., St. Cyr, O. C., Sittler, E. C., Auchère, F., Duvall, T. L., Hoeksema, J. T., Maksimovic, M., MacDowall, R. J., Szabo, A., Collier, M. R. (2011a), Earth-Affecting Solar Causes Observatory (EASCO): A potential International Living with a Star Mission from Sun-Earth L5 JASTP 73, 658-663, DOI: 10.1016/j.jastp.2011.01.013 Gopalswamy, N., Davila, J. M., Auchère, F., Schou, J., Korendyke, C. M. Shih, A., Johnston, J. C., MacDowall, R. J., Maksimovic, M., Sittler, E., et al. (2011b), Earth-Affecting Solar Causes Observatory (EASCO): a mission at

  12. Three dimensional elements with Lagrange multipliers for the modified couple stress theory

    NASA Astrophysics Data System (ADS)

    Kwon, Young-Rok; Lee, Byung-Chai

    2018-07-01

    Three dimensional mixed elements for the modified couple stress theory are proposed. The C1 continuity for the displacement field, which is required because of the curvature term in the variational form of the theory, is satisfied weakly by introducing a supplementary rotation as an independent variable and constraining the relation between the rotation and the displacement with a Lagrange multiplier vector. An additional constraint about the deviatoric curvature is also considered for three dimensional problems. Weak forms with one constraint and two constraints are derived, and four elements satisfying convergence criteria are developed by applying different approximations to each field of independent variables. The elements pass a [InlineEquation not available: see fulltext.] patch test for three dimensional problems. Numerical examples show that the additional constraint could be considered essential for the three dimensional elements, and one of the elements is recommended for practical applications via the comparison of the performances of the elements. In addition, all the proposed elements can represent the size effect well.

  13. Two-point correlation function for Dirichlet L-functions

    NASA Astrophysics Data System (ADS)

    Bogomolny, E.; Keating, J. P.

    2013-03-01

    The two-point correlation function for the zeros of Dirichlet L-functions at a height E on the critical line is calculated heuristically using a generalization of the Hardy-Littlewood conjecture for pairs of primes in arithmetic progression. The result matches the conjectured random-matrix form in the limit as E → ∞ and, importantly, includes finite-E corrections. These finite-E corrections differ from those in the case of the Riemann zeta-function, obtained in Bogomolny and Keating (1996 Phys. Rev. Lett. 77 1472), by certain finite products of primes which divide the modulus of the primitive character used to construct the L-function in question.

  14. Identifying fMRI Model Violations with Lagrange Multiplier Tests

    PubMed Central

    Cassidy, Ben; Long, Christopher J; Rae, Caroline; Solo, Victor

    2013-01-01

    The standard modeling framework in Functional Magnetic Resonance Imaging (fMRI) is predicated on assumptions of linearity, time invariance and stationarity. These assumptions are rarely checked because doing so requires specialised software, although failure to do so can lead to bias and mistaken inference. Identifying model violations is an essential but largely neglected step in standard fMRI data analysis. Using Lagrange Multiplier testing methods we have developed simple and efficient procedures for detecting model violations such as non-linearity, non-stationarity and validity of the common Double Gamma specification for hemodynamic response. These procedures are computationally cheap and can easily be added to a conventional analysis. The test statistic is calculated at each voxel and displayed as a spatial anomaly map which shows regions where a model is violated. The methodology is illustrated with a large number of real data examples. PMID:22542665

  15. Blow-up solutions for L 2 supercritical gKdV equations with exactly k blow-up points

    NASA Astrophysics Data System (ADS)

    Lan, Yang

    2017-08-01

    In this paper we consider the slightly L 2-supercritical gKdV equations \\partialt u+(uxx+u\\vert u\\vert p-1)_x=0 , with the nonlinearity 5 and 0<\\varepsilon\\ll 1 . In the previous work of the author, we know that there exists a stable self-similar blow-up dynamics for slightly L 2-supercritical gKdV equations. Such solutions can be viewed as solutions with a single blow-up point. In this paper we will prove the existence of solutions with multiple blow-up points, and give a description of the formation of the singularity near the blow-up time.

  16. On a Lagrange-Hamilton formalism describing position and momentum uncertainties

    NASA Technical Reports Server (NTRS)

    Schuch, Dieter

    1993-01-01

    According to Heisenberg's uncertainty relation, in quantum mechanics it is not possible to determine, simultaneously, exact values for the position and the momentum of a material system. Calculating the mean value of the Hamiltonian operator with the aid of exact analytic Gaussian wave packet solutions, these uncertainties cause an energy contribution additional to the classical energy of the system. For the harmonic oscillator, e.g., this nonclassical energy represents the ground state energy. It will be shown that this additional energy contribution can be considered as a Hamiltonian function, if it is written in appropriate variables. With the help of the usual Lagrange-Hamilton formalism known from classical particle mechanics, but now considering this new Hamiltonian function, it is possible to obtain the equations of motion for position and momentum uncertainties.

  17. Design of the stabilizing control of the orbital motion in the vicinity of the collinear libration point L1 using the analytical representation of the invariant manifold

    NASA Astrophysics Data System (ADS)

    Maliavkin, G. P.; Shmyrov, A. S.; Shmyrov, V. A.

    2018-05-01

    Vicinities of collinear libration points of the Sun-Earth system are currently quite attractive for the space navigation. Today, various projects on placing of spacecrafts observing the Sun in the L1 libration point and telescopes in L2 have been implemented (e.g. spacecrafts "WIND", "SOHO", "Herschel", "Planck"). Collinear libration points being unstable leads to the problem of stabilization of a spacecraft's motion. Laws of stabilizing motion control in vicinity of L1 point can be constructed using the analytical representation of a stable invariant manifold. Efficiency of these control laws depends on the precision of the representation. Within the model of Hill's approximation of the circular restricted three-body problem in the rotating geocentric coordinate system one can obtain the analytical representation of an invariant manifold filled with bounded trajectories in a form of series in terms of powers of the phase variables. Approximate representations of the orders from the first to the fourth inclusive can be used to construct four laws of stabilizing feedback motion control under which trajectories approach the manifold. By virtue of numerical simulation the comparison can be made: how the precision of the representation of the invariant manifold influences the efficiency of the control, expressed by energy consumptions (characteristic velocity). It shows that using approximations of higher orders in constructing the control laws can significantly reduce the energy consumptions on implementing the control compared to the linear approximation.

  18. Immune Checkpoint PD-1/PD-L1: Is There Life Beyond Antibodies?

    PubMed

    Konstantinidou, Markella; Zarganes-Tzitzikas, Tryfon; Magiera-Mularz, Katarzyna; Holak, Tad A; Dömling, Alexander

    2018-04-23

    The PD-1/PD-L1 interaction has emerged as a significant target in cancer immunotherapy. Current medications include monoclonal antibodies, which have shown impressive clinical results in the treatment of several types of tumors. The cocrystal structure of human PD-1 and PD-L1 is expected to be a valuable starting point for the design of novel inhibitors, along with the recent crystal structures with monoclonal antibodies, small molecules, and macrocycles. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Gene Expression Data to Mouse Atlas Registration Using a Nonlinear Elasticity Smoother and Landmark Points Constraints

    PubMed Central

    Lin, Tungyou; Guyader, Carole Le; Dinov, Ivo; Thompson, Paul; Toga, Arthur; Vese, Luminita

    2013-01-01

    This paper proposes a numerical algorithm for image registration using energy minimization and nonlinear elasticity regularization. Application to the registration of gene expression data to a neuroanatomical mouse atlas in two dimensions is shown. We apply a nonlinear elasticity regularization to allow larger and smoother deformations, and further enforce optimality constraints on the landmark points distance for better feature matching. To overcome the difficulty of minimizing the nonlinear elasticity functional due to the nonlinearity in the derivatives of the displacement vector field, we introduce a matrix variable to approximate the Jacobian matrix and solve for the simplified Euler-Lagrange equations. By comparison with image registration using linear regularization, experimental results show that the proposed nonlinear elasticity model also needs fewer numerical corrections such as regridding steps for binary image registration, it renders better ground truth, and produces larger mutual information; most importantly, the landmark points distance and L2 dissimilarity measure between the gene expression data and corresponding mouse atlas are smaller compared with the registration model with biharmonic regularization. PMID:24273381

  20. PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile.

    PubMed

    Pizarro, Carolina; García-Díaz, Diego F; Codner, Ethel; Salas-Pérez, Francisca; Carrasco, Elena; Pérez-Bravo, Francisco

    2014-11-01

    Type 1 diabetes (T1D) has a complex etiology in which genetic and environmental factors are involved, whose interactions have not yet been completely clarified. In this context, the role in PD-1 pathway and its ligands 1 and 2 (PD-L1 and PD-L2) have been proposed as candidates in several autoimmune diseases. The aim of this work was to determine the allele and haplotype frequency of six gene polymorphisms of PD-ligands (PD-L1 and PD-L2) in Chilean T1D patients and their effect on serum levels of PD-L1 and autoantibody profile (GAD65 and IA2). This study cohort comprised 205 T1D patients and 205 normal children. We performed genotypic analysis of PD-L1 and PD-L2 genes by TaqMan method. Determination of anti-GAD65 and anti-IA-2 autoantibodies was performed by ELISA. The PD-L1 serum levels were measured. The allelic distribution of PD-L1 variants (rs2297137 and rs4143815) showed differences between T1D patients and controls (p = 0.035 and p = 0.022, respectively). No differences were detected among the PD-L2 polymorphisms, and only the rs16923189 showed genetic variation. T1D patients showed decreased serum levels of PD-L1 compared to controls: 1.42 [0.23-7.45] ng/mL versus 3.35 [0.49-5.89] ng/mL (p < 0.025). In addition, the CGG haplotype in PD-L1 associated with T1D (constructed from rs822342, rs2297137 and rs4143815 polymorphisms) showed an OR = 1.44 [1.08 to 1.93]. Finally, no association of these genetic variants was observed with serum concentrations of PD ligands or auto-antibody profile, although a correlation between PD-L1 ligand serum concentration and the age at disease onset was detected. Two polymorphism of PD-L1 are presented in different allelic variants between T1D and healthy subjects, also PDL-1 serum levels are significantly lowered in diabetics patients. Moreover, the age of onset of the disease determine differences between serum ligand levels in diabetics, being lower in younger. These results points to a possible establishment of

  1. Water production in comets C/2011 L4 (PanSTARRS) and C/2012 F6 (Lemmon) from observations with Soho/Swan

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

    Combi, M. R.; Aptekar, G.; Bertaux, J.-L.

    2014-06-01

    Comets C/2011 L4 (PanSTARRS) and C/2012 F6 (Lemmon) were observed throughout their 2012-2013 apparitions with the Solar Wind Anisotropies (SWAN) all-sky hydrogen Lyα camera on board the Solar and Heliosphere Observatory (SOHO) satellite. SOHO has been in a halo orbit around the L1 Earth-Sun Lagrange point since early 1996 and has been observing the interplanetary medium and comets beginning with C/1996 B2 (Hyakutake). The global water production from these comets was determined from an analysis of the SWAN Lyα camera observations. Comet C/2011 L4 (PanSTARRS), which reached its perihelion distance of 0.302 AU on 2013 March 10.17, was observed onmore » 50 days between 2013 January 29 and April 30. Comet C/2012 F6 (Lemmon), which reached its perihelion distance of 0.731 AU on 2013 March 24.51, was observed on 109 days between 2012 November 29 and 2013 June 31. The maximum water production rates were ∼1 × 10{sup 30} molecules s{sup –1} for both comets. The activities of both comets were asymmetric about perihelion. C/2011 L4 (PanSTARRS) was more active before perihelion than after, but C/2012 F6 (Lemmon) was more active after perihelion than before.« less

  2. Vocabulary Development in Norwegian L1 and L2 Learners in the Kindergarten-School Transition

    ERIC Educational Resources Information Center

    Karlsen, Jannicke; Lyster, Solveig-Alma Halaas; Lervåg, Arne

    2017-01-01

    This study examined the vocabulary development of Norwegian second language (L2) learners with Urdu/Punjabi as their first language (L1) at two time-points from kindergarten to primary school, and compared it to the vocabulary development of monolingual Norwegian children. Using path models, the associations between number of picture books in the…

  3. Observation of two new L4 Neptune Trojans in the Dark Energy Survey supernova fields

    DOE PAGES

    Gerdes, D. W.

    2016-01-28

    We report the discovery of the eighth and ninth known Trojans in stable orbits around Neptune's leading Lagrange point, L4. The objects 2014 QO 441 and 2014 QP 441 were detected in data obtained during the 2013-14 and 2014-15 observing seasons by the Dark Energy Survey, using the Dark Energy Camera (DECam) on the 4-meter Blanco telescope at Cerro Tololo Inter- American Observatory. Both are in high-inclination orbits (18.8° and 19.4° respectively). Furthermore, with an eccentricity of 0.104, 2014 QO 441 has the most eccentric orbit of the eleven known stable Neptune Trojans. We describe the search procedure and investigatemore » the objects' long-term dynamical stability and physical properties.« less

  4. Polestitters: Using Solar Sails for Constant Real-time Sensing of Earth's Polar Regions

    NASA Astrophysics Data System (ADS)

    Mulligan, P.; Diedrich, B. L.; Barnes, N.; Derbes, B.

    2012-12-01

    NASA has funded the Sunjammer mission - a near term demonstration of solar sail technology (2014/15). Sunjammer has the potential to demonstrate stationkeeping out of Earth's orbital plane. This is a first step in achieving "polesitter" orbits with year-round, real-time visibility of Earth's polar regions. Potential applications for such missions are illustrated. Solar sails have long been a concept for spacecraft propulsion that works by exchanging momentum with sunlight reflected by large, lightweight, mirrored sails. In addition to enabling propellantless propulsion throughout the solar system and beyond, their continuous thrust enables artificial Lagrange orbits (ALOs), some of which can be called "polesitter" orbits, with 24-hour, year-round visibility of Earth's polar regions. Several potential Earth remote sensing applications have been identified that address the limited temporal and spatial coverage from traditional polar and geostationary satellites. The Galileo spacecraft during its 1990 Earth flyby acquired imagery and radiometer data similar to the view from a polesitter. The Galileo imagery was used to derive aerosols and cloud variations used in atmospheric motion vector (AMV) derivations. Composites of satellite imagery over the South Pole is routinely used to derive atmospheric motion vectors like those performed regularly from geostationary satellites. The JAXA IKAROS mission flew a 14x14m solar sail past Venus in 2010. Sunjammer will demonstrate a state of the art 38x38m solar sail from Earth to an artificial Lagrange orbit located sunward and north of the sun-Earth L1 point. Traditional spacecraft can orbit naturally occurring Lagrange equilibrium points between the sun and Earth. The low, continuous thrust of solar sails can change where these points occur, creating new orbits with a variety of potential applications including polar remote sensing, space weather monitoring, and polar communications. This figure illustrates a selection of

  5. Perturbed Equations of Motion for Formation Flight Near the Sun-Earth L2 Point

    NASA Technical Reports Server (NTRS)

    Segerman, Alan M.; Zedd, Michael F.

    2005-01-01

    This Memorandum Report consists of a compilation of three individual reports, of increasing complexity, describing investigations of formation flight of spacecraft in the vicinity of the L2 Sun-Earth 1ibration point. The individual reports form the following parts of this compilation: - Introduction to the relative motion of spacecraft about the Sun-Earth L2 Point - Linear and quadratic modelling and solution of the relative motion - Modelling the Perturbations - Elliptical Earth Orbit, Lunar Gravity, Solar Radiation Pressure, Thrusters. The three parts are self-contained, with somewhat, varying notation and terminology. After fair1y significant literature searches: this new work (of Parts 2 and 3) is deemed to be unique because it describes the primary perturbations to the description of relative motion between nearby spacecraft. The effect of the elliptical motion of the Earth about the Sun was verified to be the dominant perturbation to the circular restricted three body problem. Contributions due to lunar gravity and solar radiation pressure are seen to have much smaller effect.

  6. Application of parallel distributed Lagrange multiplier technique to simulate coupled Fluid-Granular flows in pipes with varying Cross-Sectional area

    DOE PAGES

    Kanarska, Yuliya; Walton, Otis

    2015-11-30

    Fluid-granular flows are common phenomena in nature and industry. Here, an efficient computational technique based on the distributed Lagrange multiplier method is utilized to simulate complex fluid-granular flows. Each particle is explicitly resolved on an Eulerian grid as a separate domain, using solid volume fractions. The fluid equations are solved through the entire computational domain, however, Lagrange multiplier constrains are applied inside the particle domain such that the fluid within any volume associated with a solid particle moves as an incompressible rigid body. The particle–particle interactions are implemented using explicit force-displacement interactions for frictional inelastic particles similar to the DEMmore » method with some modifications using the volume of an overlapping region as an input to the contact forces. Here, a parallel implementation of the method is based on the SAMRAI (Structured Adaptive Mesh Refinement Application Infrastructure) library.« less

  7. Robust adaptive uniform exact tracking control for uncertain Euler-Lagrange system

    NASA Astrophysics Data System (ADS)

    Yang, Yana; Hua, Changchun; Li, Junpeng; Guan, Xinping

    2017-12-01

    This paper offers a solution to the robust adaptive uniform exact tracking control for uncertain nonlinear Euler-Lagrange (EL) system. An adaptive finite-time tracking control algorithm is designed by proposing a novel nonsingular integral terminal sliding-mode surface. Moreover, a new adaptive parameter tuning law is also developed by making good use of the system tracking errors and the adaptive parameter estimation errors. Thus, both the trajectory tracking and the parameter estimation can be achieved in a guaranteed time adjusted arbitrarily based on practical demands, simultaneously. Additionally, the control result for the EL system proposed in this paper can be extended to high-order nonlinear systems easily. Finally, a test-bed 2-DOF robot arm is set-up to demonstrate the performance of the new control algorithm.

  8. Inflection-point inflation in a hyper-charge oriented U ( 1 ) X model

    DOE PAGES

    Okada, Nobuchika; Okada, Satomi; Raut, Digesh

    2017-03-31

    Inflection-point inflation is an interesting possibility to realize a successful slow-roll inflation when inflation is driven by a single scalar field with its value during inflation below the Planck mass (ΦI≲M Pl). In order for a renormalization group (RG) improved effective λΦ 4 potential to develop an inflection-point, the running quartic coupling λ(Φ) must exhibit a minimum with an almost vanishing value in its RG evolution, namely λ(Φ I)≃0 and β λ(ΦI)≃0, where β λ is the beta-function of the quartic coupling. Here in this paper, we consider the inflection-point inflation in the context of the minimal gauged U(1) Xmore » extended Standard Model (SM), which is a generalization of the minimal U(1) B$-$L model, and is constructed as a linear combination of the SM U(1) Y and U(1) B$-$L gauge symmetries. We identify the U(1) X Higgs field with the inflaton field. For a successful inflection-point inflation to be consistent with the current cosmological observations, the mass ratios among the U(1) X gauge boson, the right-handed neutrinos and the U(1) X Higgs boson are fixed. Focusing on the case that the extra U(1) X gauge symmetry is mostly aligned along the SM U(1) Y direction, we investigate a consistency between the inflationary predictions and the latest LHC Run-2 results on the search for a narrow resonance with the di-lepton final state.« less

  9. Inflection-point inflation in a hyper-charge oriented U ( 1 ) X model

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

    Okada, Nobuchika; Okada, Satomi; Raut, Digesh

    Inflection-point inflation is an interesting possibility to realize a successful slow-roll inflation when inflation is driven by a single scalar field with its value during inflation below the Planck mass (ΦI≲M Pl). In order for a renormalization group (RG) improved effective λΦ 4 potential to develop an inflection-point, the running quartic coupling λ(Φ) must exhibit a minimum with an almost vanishing value in its RG evolution, namely λ(Φ I)≃0 and β λ(ΦI)≃0, where β λ is the beta-function of the quartic coupling. Here in this paper, we consider the inflection-point inflation in the context of the minimal gauged U(1) Xmore » extended Standard Model (SM), which is a generalization of the minimal U(1) B$-$L model, and is constructed as a linear combination of the SM U(1) Y and U(1) B$-$L gauge symmetries. We identify the U(1) X Higgs field with the inflaton field. For a successful inflection-point inflation to be consistent with the current cosmological observations, the mass ratios among the U(1) X gauge boson, the right-handed neutrinos and the U(1) X Higgs boson are fixed. Focusing on the case that the extra U(1) X gauge symmetry is mostly aligned along the SM U(1) Y direction, we investigate a consistency between the inflationary predictions and the latest LHC Run-2 results on the search for a narrow resonance with the di-lepton final state.« less

  10. CarbonTracker-Lagrange: A Framework for Greenhouse Gas Flux Estimation at Regional to Continental Scales

    NASA Astrophysics Data System (ADS)

    Andrews, A. E.

    2016-12-01

    CarbonTracker-Lagrange (CT-L) is a flexible modeling framework developed to take advantage of newly available atmospheric data for CO2 and other long-lived gases such as CH4 and N2O. The North American atmospheric CO2 measurement network has grown from three sites in 2004 to >100 sites in 2015. The US network includes tall tower, mountaintop, surface, and aircraft sites in the NOAA Global Greenhouse Gas Reference Network along with sites maintained by university, government and private sector researchers. The Canadian network is operated by Environment and Climate Change Canada. This unprecedented dataset can provide spatially and temporally resolved CO2 emissions and uptake flux estimates and quantitative information about drivers of variability, such as drought and temperature. CT-L is a platform for systematic comparison of data assimilation techniques and evaluation of assumed prior, model and observation errors. A novel feature of CT-L is the optimization of boundary values along with surface fluxes, leveraging vertically resolved data available from NOAA's aircraft sampling program. CT-L uses observation footprints (influence functions) from the Weather Research and Forecasting/Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) modeling system to relate atmospheric measurements to upwind fluxes and boundary values. Footprints are pre-computed and the optimization algorithms are efficient, so many variants of the calculation can be performed. Fluxes are adjusted using Bayesian or Geostatistical methods to provide optimal agreement with observations. Satellite measurements of CO2 and CH4 from GOSAT are available starting in July 2009 and from OCO-2 since September 2014. With support from the NASA Carbon Monitoring System, we are developing flux estimation strategies that use remote sensing and in situ data together, including geostatistical inversions using satellite retrievals of solar-induced chlorophyll fluorescence. CT-L enables quantitative

  11. Relative Critical Points

    NASA Astrophysics Data System (ADS)

    Lewis, Debra

    2013-05-01

    Relative equilibria of Lagrangian and Hamiltonian systems with symmetry are critical points of appropriate scalar functions parametrized by the Lie algebra (or its dual) of the symmetry group. Setting aside the structures - symplectic, Poisson, or variational - generating dynamical systems from such functions highlights the common features of their construction and analysis, and supports the construction of analogous functions in non-Hamiltonian settings. If the symmetry group is nonabelian, the functions are invariant only with respect to the isotropy subgroup of the given parameter value. Replacing the parametrized family of functions with a single function on the product manifold and extending the action using the (co)adjoint action on the algebra or its dual yields a fully invariant function. An invariant map can be used to reverse the usual perspective: rather than selecting a parametrized family of functions and finding their critical points, conditions under which functions will be critical on specific orbits, typically distinguished by isotropy class, can be derived. This strategy is illustrated using several well-known mechanical systems - the Lagrange top, the double spherical pendulum, the free rigid body, and the Riemann ellipsoids - and generalizations of these systems.

  12. Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.

    PubMed

    Springuel, Lorraine; Losdyck, Elisabeth; Saussoy, Pascale; Turcq, Béatrice; Mahon, François-Xavier; Knoops, Laurent; Renauld, Jean-Christophe

    2016-12-01

    Genomic instability drives cancer progression by promoting genetic abnormalities that allow for the multi-step clonal selection of cells with growth advantages. We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect in mutation avoidance mechanisms. In the first part of this paper, we discovered that the gene encoding mutL homolog-1 (MLH1), a key component of the DNA mismatch repair system, is silenced by promoter methylation in TS1 cells. By means of stable ectopic expression and RNA interference methods, we showed that the high frequencies of growth factor-independent and inhibitor-resistant cells with activating JAK mutations can be attributed to the absence of MLH1 expression. In the second part of this paper, we confirm the clinical relevance of our findings by showing that chronic myeloid leukemia relapses upon ABL-targeted therapy correlated with a lower expression of MLH1 messenger RNA. Interestingly, the mutational profile observed in our TS1 model, characterized by a strong predominance of T:A>C:G transitions, was identical to the one described in the literature for primitive cells derived from chronic myeloid leukemia patients. Taken together, our observations demonstrate for the first time a causal relationship between MLH1-deficiency and incidence of oncogenic point mutations in tyrosine kinases driving cell transformation and acquired resistance to kinase-targeted cancer therapies.

  13. On the effects of L2 perception and of individual differences in L1 production on L2 pronunciation

    PubMed Central

    Kartushina, Natalia; Frauenfelder, Ulrich H.

    2014-01-01

    The speech of late second language (L2) learners is generally marked by an accent. The dominant theoretical perspective attributes accents to deficient L2 perception arising from a transfer of L1 phonology, which is thought to influence L2 perception and production. In this study we evaluate the explanatory role of L2 perception in L2 production and explore alternative explanations arising from the L1 phonological system, such as for example, the role of L1 production. Specifically we examine the role of an individual’s L1 productions in the production of L2 vowel contrasts. Fourteen Spanish adolescents studying French at school were assessed on their perception and production of the mid-close/mid-open contrasts, /ø-œ/ and /e-ε/, which are, respectively, acoustically distinct from Spanish sounds, or similar to them. The participants’ native productions were explored to assess (1) the variability in the production of native vowels (i.e., the compactness of vowel categories in F1/F2 acoustic space), and (2) the position of the vowels in the acoustic space. The results revealed that although poorly perceived contrasts were generally produced poorly, there was no correlation between individual performance in perception and production, and no effect of L2 perception on L2 production in mixed-effects regression analyses. This result is consistent with a growing body of psycholinguistic and neuroimaging research that suggest partial dissociations between L2 perception and production. In contrast, individual differences in the compactness and position of native vowels predicted L2 production accuracy. These results point to existence of surface transfer of individual L1 phonetic realizations to L2 space and demonstrate that pre-existing features of the native space in production partly determine how new sounds can be accommodated in that space. PMID:25414678

  14. Augmented Lagrange Programming Neural Network for Localization Using Time-Difference-of-Arrival Measurements.

    PubMed

    Han, Zifa; Leung, Chi Sing; So, Hing Cheung; Constantinides, Anthony George

    2017-08-15

    A commonly used measurement model for locating a mobile source is time-difference-of-arrival (TDOA). As each TDOA measurement defines a hyperbola, it is not straightforward to compute the mobile source position due to the nonlinear relationship in the measurements. This brief exploits the Lagrange programming neural network (LPNN), which provides a general framework to solve nonlinear constrained optimization problems, for the TDOA-based localization. The local stability of the proposed LPNN solution is also analyzed. Simulation results are included to evaluate the localization accuracy of the LPNN scheme by comparing with the state-of-the-art methods and the optimality benchmark of Cramér-Rao lower bound.

  15. Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

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

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510; Yoshizaki, Takayuki

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. Black-Right-Pointing-Pointer Adipose lipin-1 expression is reduced in obesity. Black-Right-Pointing-Pointer Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. Black-Right-Pointing-Pointer Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytesmore » by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-{kappa}B activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.« less

  16. 17. View to west. Detail, connection point L2 (see plans), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. View to west. Detail, connection point L2 (see plans), from below deck. (135mm lens) - South Fork Trinity River Bridge, State Highway 299 spanning South Fork Trinity River, Salyer, Trinity County, CA

  17. Future of anti-PD-1/PD-L1 applications: Combinations with other therapeutic regimens.

    PubMed

    Song, Mengjia; Chen, Xinfeng; Wang, Liping; Zhang, Yi

    2018-04-01

    Programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) blockade has shown promising effects in cancer immunotherapy. Removing the so-called " brakes" on T cell immune responses by blocking the PD-1/PD-L1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients. However, 30%-60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site, immunosuppressive factors in the tumor microenvironment (TME), and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.

  18. Orbit Determination Error Analysis Results for the Triana Sun-Earth L2 Libration Point Mission

    NASA Technical Reports Server (NTRS)

    Marr, G.

    2003-01-01

    Using the NASA Goddard Space Flight Center's Orbit Determination Error Analysis System (ODEAS), orbit determination error analysis results are presented for all phases of the Triana Sun-Earth L1 libration point mission and for the science data collection phase of a future Sun-Earth L2 libration point mission. The Triana spacecraft was nominally to be released by the Space Shuttle in a low Earth orbit, and this analysis focuses on that scenario. From the release orbit a transfer trajectory insertion (TTI) maneuver performed using a solid stage would increase the velocity be approximately 3.1 km/sec sending Triana on a direct trajectory to its mission orbit. The Triana mission orbit is a Sun-Earth L1 Lissajous orbit with a Sun-Earth-vehicle (SEV) angle between 4.0 and 15.0 degrees, which would be achieved after a Lissajous orbit insertion (LOI) maneuver at approximately launch plus 6 months. Because Triana was to be launched by the Space Shuttle, TTI could potentially occur over a 16 orbit range from low Earth orbit. This analysis was performed assuming TTI was performed from a low Earth orbit with an inclination of 28.5 degrees and assuming support from a combination of three Deep Space Network (DSN) stations, Goldstone, Canberra, and Madrid and four commercial Universal Space Network (USN) stations, Alaska, Hawaii, Perth, and Santiago. These ground stations would provide coherent two-way range and range rate tracking data usable for orbit determination. Larger range and range rate errors were assumed for the USN stations. Nominally, DSN support would end at TTI+144 hours assuming there were no USN problems. Post-TTI coverage for a range of TTI longitudes for a given nominal trajectory case were analyzed. The orbit determination error analysis after the first correction maneuver would be generally applicable to any libration point mission utilizing a direct trajectory.

  19. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.

    PubMed

    Cartier, Anna E; Djakovic, Stevan N; Salehi, Afshin; Wilson, Scott M; Masliah, Eliezer; Patrick, Gentry N

    2009-06-17

    Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

  20. The utility of polarized heliospheric imaging for space weather monitoring.

    PubMed

    DeForest, C E; Howard, T A; Webb, D F; Davies, J A

    2016-01-01

    A polarizing heliospheric imager is a critical next generation tool for space weather monitoring and prediction. Heliospheric imagers can track coronal mass ejections (CMEs) as they cross the solar system, using sunlight scattered by electrons in the CME. This tracking has been demonstrated to improve the forecasting of impact probability and arrival time for Earth-directed CMEs. Polarized imaging allows locating CMEs in three dimensions from a single vantage point. Recent advances in heliospheric imaging have demonstrated that a polarized imager is feasible with current component technology.Developing this technology to a high technology readiness level is critical for space weather relevant imaging from either a near-Earth or deep-space mission. In this primarily technical review, we developpreliminary hardware requirements for a space weather polarizing heliospheric imager system and outline possible ways to flight qualify and ultimately deploy the technology operationally on upcoming specific missions. We consider deployment as an instrument on NOAA's Deep Space Climate Observatory follow-on near the Sun-Earth L1 Lagrange point, as a stand-alone constellation of smallsats in low Earth orbit, or as an instrument located at the Sun-Earth L5 Lagrange point. The critical first step is the demonstration of the technology, in either a science or prototype operational mission context.

  1. Guidance of a Solar Sail Spacecraft to the Sun - L(2) Point.

    NASA Astrophysics Data System (ADS)

    Hur, Sun Hae

    The guidance of a solar sail spacecraft along a minimum-time path from an Earth orbit to a region near the Sun-Earth L_2 libration point is investigated. Possible missions to this point include a spacecraft "listening" for possible extra-terrestrial electromagnetic signals and a science payload to study the geomagnetic tail. A key advantage of the solar sail is that it requires no fuel. The control variables are the sail angles relative to the Sun-Earth line. The thrust is very small, on the order of 1 mm/s^2, and its magnitude and direction are highly coupled. Despite this limited controllability, the "free" thrust can be used for a wide variety of terminal conditions including halo orbits. If the Moon's mass is lumped with the Earth, there are quasi-equilibrium points near L_2. However, they are unstable so that some form of station keeping is required, and the sail can provide this without any fuel usage. In the two-dimensional case, regulating about a nominal orbit is shown to require less control and result in smaller amplitude error response than regulating about a quasi-equilibrium point. In the three-dimensional halo orbit case, station keeping using periodically varying gains is demonstrated. To compute the minimum-time path, the trajectory is divided into two segments: the spiral segment and the transition segment. The spiral segment is computed using a control law that maximizes the rate of energy increase at each time. The transition segment is computed as the solution of the time-optimal control problem from the endpoint of the spiral to the terminal point. It is shown that the path resulting from this approximate strategy is very close to the exact optimal path. For the guidance problem, the approximate strategy in the spiral segment already gives a nonlinear full-state feedback law. However, for large perturbations, follower guidance using an auxiliary propulsion is used for part of the spiral. In the transition segment, neighboring extremal feedback

  2. Variational tricomplex of a local gauge system, Lagrange structure and weak Poisson bracket

    NASA Astrophysics Data System (ADS)

    Sharapov, A. A.

    2015-09-01

    We introduce the concept of a variational tricomplex, which is applicable both to variational and nonvariational gauge systems. Assigning this tricomplex with an appropriate symplectic structure and a Cauchy foliation, we establish a general correspondence between the Lagrangian and Hamiltonian pictures of one and the same (not necessarily variational) dynamics. In practical terms, this correspondence allows one to construct the generating functional of a weak Poisson structure starting from that of a Lagrange structure. As a byproduct, a covariant procedure is proposed for deriving the classical BRST charge of the BFV formalism by a given BV master action. The general approach is illustrated by the examples of Maxwell’s electrodynamics and chiral bosons in two dimensions.

  3. PD-L1 expression according to the EGFR status in primary lung adenocarcinoma.

    PubMed

    Takada, Kazuki; Toyokawa, Gouji; Tagawa, Tetsuzo; Kohashi, Kenichi; Shimokawa, Mototsugu; Akamine, Takaki; Takamori, Shinkichi; Hirai, Fumihiko; Shoji, Fumihiro; Okamoto, Tatsuro; Oda, Yoshinao; Maehara, Yoshihiko

    2018-02-01

    It was reported that programmed cell death-ligand 1 (PD-L1) expression is associated with smoking and wild-type epidermal growth factor receptor (EGFR) in lung adenocarcinoma. However, the association between PD-L1 expression and EGFR mutation site in EGFR mutation-positive lung adenocarcinoma is unclear. We retrospectively examined the relationship between PD-L1 expression and EGFR status in 441 surgically resected primary lung adenocarcinomas. Membrane PD-L1 expression on tumor cells was evaluated by immunohistochemical analysis using a PD-L1 antibody (clone SP142) and defined by tumor proportion scores (TPSs) of 0%, 1-4%, 5-49%, and ≥50%, respectively. Two hundred and eighteen (49.4%) patients had wild-type EGFR, and 223 (50.6%) had mutant EGFR-98 (44.0%) with exon 19 deletion, 116 (52.0%) with exon 21 L858R point mutation, and nine (4.0%) with another EGFR mutation. Overall, Fisher's exact test showed that PD-L1 positivity was associated with wild-type EGFR, and there was only one case with PD-L1 TPS ≥50% among the cases with mutant EGFR. The analysis of cases with mutant EGFR indicated no significant association between EGFR mutation site and PD-L1 expression. However, the prevalence of PD-L1 TPS 5-49% was higher among patients with EGFR exon 19 deletion than with EGFR exon 21 L858R point mutation. PD-L1 expression was significantly associated with wild-type EGFR, and PD-L1 TPS ≥50% seldom overlaps with presence of driver oncogene EGFR. There was no significant difference in PD-L1 expression among the EGFR mutation sites. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Relationships among L1 Print Exposure and Early L1 Literacy Skills, L2 Aptitude, and L2 Proficiency

    ERIC Educational Resources Information Center

    Sparks, Richard L.; Patton, Jon; Ganschow, Leonore; Humbach, Nancy

    2012-01-01

    Authors examined the relationship between individual differences in L1 print exposure and differences in early L1 skills and later L2 aptitude, L2 proficiency, and L2 classroom achievement. Participants were administered measures of L1 word decoding, spelling, phonemic awareness, reading comprehension, receptive vocabulary, and listening…

  5. Erratum: ``The Luminosity Function of IRAS Point Source Catalog Redshift Survey Galaxies'' (ApJ, 587, L89 [2003])

    NASA Astrophysics Data System (ADS)

    Takeuchi, Tsutomu T.; Yoshikawa, Kohji; Ishii, Takako T.

    2004-05-01

    We have mentioned that we normalized the parameters for the luminosity function by the Hubble constant H0=100 km s-1 Mpc-1 however, for the characteristic luminosity L* we erroneously normalized it by H0=70 km s-1 Mpc-1. As a result, we have proposed wrong numerical factors for L*. In addition, there is a typographic error in the exponent of equation (6) of the published manuscript. Correct values are as follows: L*=(4.34+/-0.86)×108 h-2 [Lsolar] for equation (4), and L*=(2.50+/-0.44)×109 h-2 [Lsolar] and L*=(9.55+/-0.20)×108 h-2 [Lsolar] for equations (5) and (6), respectively. All the other parameters are correct. The errors have occurred only in the final conversion, and they do not affect our discussions and conclusions at all. We thank P. Ranalli for pointing out the errors.

  6. Analysis of complex elastic structures by a Rayleigh-Ritz component modes method using Lagrange multipliers. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Klein, L. R.

    1974-01-01

    The free vibrations of elastic structures of arbitrary complexity were analyzed in terms of their component modes. The method was based upon the use of the normal unconstrained modes of the components in a Rayleigh-Ritz analysis. The continuity conditions were enforced by means of Lagrange Multipliers. Examples of the structures considered are: (1) beams with nonuniform properties; (2) airplane structures with high or low aspect ratio lifting surface components; (3) the oblique wing airplane; and (4) plate structures. The method was also applied to the analysis of modal damping of linear elastic structures. Convergence of the method versus the number of modes per component and/or the number of components is discussed and compared to more conventional approaches, ad-hoc methods, and experimental results.

  7. Science objectives of the magnetic field experiment onboard Aditya-L1 spacecraft

    NASA Astrophysics Data System (ADS)

    Yadav, Vipin K.; Srivastava, Nandita; Ghosh, S. S.; Srikar, P. T.; Subhalakshmi, Krishnamoorthy

    2018-01-01

    The Aditya-L1 is first Indian solar mission scheduled to be placed in a halo orbit around the first Lagrangian point (L1) of Sun-Earth system in the year 2018-19. The approved scientific payloads onboard Aditya-L1 spacecraft includes a Fluxgate Digital Magnetometer (FGM) to measure the local magnetic field which is necessary to supplement the outcome of other scientific experiments onboard. The in-situ vector magnetic field data at L1 is essential for better understanding of the data provided by the particle and plasma analysis experiments, onboard Aditya-L1 mission. Also, the dynamics of Coronal Mass Ejections (CMEs) can be better understood with the help of in-situ magnetic field data at the L1 point region. This data will also serve as crucial input for the short lead-time space weather forecasting models. The proposed FGM is a dual range magnetic sensor on a 6 m long boom mounted on the Sun viewing panel deck and configured to deploy along the negative roll direction of the spacecraft. Two sets of sensors (tri-axial each) are proposed to be mounted, one at the tip of boom (6 m from the spacecraft) and other, midway (3 m from the spacecraft). The main science objective of this experiment is to measure the magnitude and nature of the interplanetary magnetic field (IMF) locally and to study the disturbed magnetic conditions and extreme solar events by detecting the CME from Sun as a transient event. The proposed secondary science objectives are to study the impact of interplanetary structures and shock solar wind interaction on geo-space environment and to detect low frequency plasma waves emanating from the solar corona at L1 point. This will provide a better understanding on how the Sun affects interplanetary space. In this paper, we shall give the main scientific objectives of the magnetic field experiment and brief technical details of the FGM onboard Aditya-1 spacecraft.

  8. James Webb Space Telescope - L2 Communications for Science Data Processing

    NASA Technical Reports Server (NTRS)

    Johns, Alan; Seaton, Bonita; Gal-Edd, Jonathan; Jones, Ronald; Fatig, Curtis; Wasiak, Francis

    2008-01-01

    JWST is the first NASA mission at the second Lagrange point (L2) to identify the need for data rates higher than 10 megabits per second (Mbps). JWST will produce approximately 235 Gigabits of science data every day that will be downlinked to the Deep Space Network (DSN). To get the data rates desired required moving away from X-band frequencies to Ka-band frequencies. To accomplish this transition, the DSN is upgrading its infrastructure. This new range of frequencies are becoming the new standard for high data rate science missions at L2. With the new frequency range, the issues of alternatives antenna deployment, off nominal scenarios, NASA implementation of the Ka-band 26 GHz, and navigation requirements will be discussed in this paper. JWST is also using Consultative Committee for Space Data Systems (CCSDS) standard process for reliable file transfer using CCSDS File Delivery Protocol (CFDP). For JWST the use of the CFDP protocol provides level zero processing at the DSN site. This paper will address NASA implementations of Ground Stations in support of Ka-band 26 GHz and lesson learned from implementing a file base (CFDP) protocol operational system.

  9. 1. EXTERIOR VIEW OF 209 WARE STREET LOOKING SOUTH. THIS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. EXTERIOR VIEW OF 209 WARE STREET LOOKING SOUTH. THIS STRUCTURE WAS ONE OF APPROXIMATELY SEVENTEEN DUPLEXES BUILT AS THE ORIGINAL WORKER HOUSING FOR THE LaGRANGE COTTON MILLS, LATER KNOWN AS CALUMET MILL. LaGRANGE MILLS (1888-89) WAS THE FIRST COTTON MILL IN LaGRANGE. NOTE THE GABLE-ON-HIP ROOF FORM AND TWO IDENTICAL STRUCTURES VISIBLE TO THE LEFT. - 209 Ware Street (House), 209 Ware Street, La Grange, Troup County, GA

  10. Characterization of the NPC1L1 gene and proteome from an exceptional responder to ezetimibe.

    PubMed

    Schweitzer, Morris; Makhoul, Sandra; Paliouras, Miltiadis; Beitel, Lenore K; Gottlieb, Bruce; Trifiro, Mark; Chowdhury, Shafinaz F; Zaman, Naif M; Wang, Edwin; Davis, Harry; Chalifour, Lorraine E

    2016-03-01

    Strategies to reduce LDL-cholesterol involve reductions in cholesterol synthesis or absorption. We identified a familial hypercholesterolemia patient with an exceptional response to the cholesterol absorption inhibitor, ezetimibe. Niemann-Pick C 1-like 1 (NPC1L1) is the molecular target of ezetimibe. Sequencing identified nucleotide changes predicted to change amino acids 52 (L52P), 300 (I300T) and 489 (S489G) in exceptional NPC1L1. In silico analyses identified increased stability and cholesterol binding affinity in L52P-NPC1L1 versus WT-NPC1L1. HEK293 cells overexpressing WT-NPC1L1 or NPC1L1 harboring amino acid changes singly or in combination (Comb-NPC1L1) had reduced cholesterol uptake in Comb-NPC1L1 when ezetimibe was present. Cholesterol uptake was reduced by ezetimibe in L52P-NPC1L1, I300T-NPC1L1, but increased in S489G-NPC1L1 overexpressing cells. Immunolocalization studies found preferential plasma membrane localization of mutant NPC1L1 independent of ezetimibe. Flotillin 1 and 2 expression was reduced and binding to Comb-NPC1L1 was reduced independent of ezetimibe exposure. Proteomic analyses identified increased association with proteins that modulate intermediate filament proteins in Comb-NPC1L1 versus WT-NPC1L1 treated with ezetimibe. This is the first detailed analysis of the role of NPC1L1 mutations in an exceptional responder to ezetimibe. The results point to a complex set of events in which the combined mutations were shown to affect cholesterol uptake in the presence of ezetimibe. Proteomic analysis suggests that the exceptional response may also lie in the nature of interactions with cytosolic proteins. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Orbit Determination of Spacecraft in Earth-Moon L1 and L2 Libration Point Orbits

    NASA Technical Reports Server (NTRS)

    Woodard, Mark; Cosgrove, Daniel; Morinelli, Patrick; Marchese, Jeff; Owens, Brandon; Folta, David

    2011-01-01

    The ARTEMIS mission, part of the THEMIS extended mission, is the first to fly spacecraft in the Earth-Moon Lissajous regions. In 2009, two of the five THEMIS spacecraft were redeployed from Earth-centered orbits to arrive in Earth-Moon Lissajous orbits in late 2010. Starting in August 2010, the ARTEMIS P1 spacecraft executed numerous stationkeeping maneuvers, initially maintaining a lunar L2 Lissajous orbit before transitioning into a lunar L1 orbit. The ARTEMIS P2 spacecraft entered a L1 Lissajous orbit in October 2010. In April 2011, both ARTEMIS spacecraft will suspend Lissajous stationkeeping and will be maneuvered into lunar orbits. The success of the ARTEMIS mission has allowed the science team to gather unprecedented magnetospheric measurements in the lunar Lissajous regions. In order to effectively perform lunar Lissajous stationkeeping maneuvers, the ARTEMIS operations team has provided orbit determination solutions with typical accuracies on the order of 0.1 km in position and 0.1 cm/s in velocity. The ARTEMIS team utilizes the Goddard Trajectory Determination System (GTDS), using a batch least squares method, to process range and Doppler tracking measurements from the NASA Deep Space Network (DSN), Berkeley Ground Station (BGS), Merritt Island (MILA) station, and United Space Network (USN). The team has also investigated processing of the same tracking data measurements using the Orbit Determination Tool Kit (ODTK) software, which uses an extended Kalman filter and recursive smoother to estimate the orbit. The orbit determination results from each of these methods will be presented and we will discuss the advantages and disadvantages associated with using each method in the lunar Lissajous regions. Orbit determination accuracy is dependent on both the quality and quantity of tracking measurements, fidelity of the orbit force models, and the estimation techniques used. Prior to Lissajous operations, the team determined the appropriate quantity of tracking

  12. Space Instrument Optimization by Implementing of Generic Three Bodies Circular Restricted Problem

    NASA Astrophysics Data System (ADS)

    Nejat, Cyrus

    2011-01-01

    In this study, the main discussion emphasizes on the spacecraft operation with a concentration on stationary points in space. To achieve these objectives, the circular restricted problem was solved for selected approaches. The equations of motion of three body restricted problem was demonstrated to apply in cases other than Lagrange's (1736-1813 A.D.) achievements, by means of the purposed CN (Cyrus Nejat) theorem along with appropriate comments. In addition to five Lagrange, two other points, CN1 and CN2 were found to be in unstable equilibrium points in a very large distance respect to Lagrange points, but stable at infinity. A very interesting simulation of Milky Way Galaxy and Andromeda Galaxy were created to find the Lagrange points, CN points (Cyrus Nejat Points), and CN lines (Cyrus Nejat Lines). The equations of motion were rearranged such a way that the transfer trajectory would be conical, by means of decoupling concept. The main objective was to make a halo orbit transfer about CN lines. The author purposes therefore that all of the corresponding sizing design that they must be developed by optimization techniques would be considered in future approaches. The optimization techniques are sufficient procedures to search for the most ideal response of a system.

  13. The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies and perspective.

    PubMed

    Guirgis, Helmy M

    2018-02-20

    The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). Previously reported median overall survival (OS) and prices posted by parent company were utilized. The OS gains over controls in days were graded (gr) from A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year. Adverse events treatment costs (AEsTC) were reported separately. The cost/life-year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days × 360 days. The relative value of the ICPI were expressed as $100,000/C/LYG. Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr ¾ > 20%, AEsTC $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr ¾ were < 20% at average costs of $1480. In non-squamous NSCLC, Nivo demonstrated OS/g 84/C and C/LYG $558,326 as compared with 264/A and $177,645 in PD-L1 > 10%. Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to 162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g 57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1 enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and Pembro from 0.15 to 0.53. Simplified methodology to grade OS and weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC, value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and enhanced value at seemingly justifiable costs.

  14. The impact of language co-activation on L1 and L2 speech fluency.

    PubMed

    Bergmann, Christopher; Sprenger, Simone A; Schmid, Monika S

    2015-10-01

    Fluent speech depends on the availability of well-established linguistic knowledge and routines for speech planning and articulation. A lack of speech fluency in late second-language (L2) learners may point to a deficiency of these representations, due to incomplete acquisition. Experiments on bilingual language processing have shown, however, that there are strong reasons to believe that multilingual speakers experience co-activation of the languages they speak. We have studied to what degree language co-activation affects fluency in the speech of bilinguals, comparing a monolingual German control group with two bilingual groups: 1) first-language (L1) attriters, who have fully acquired German before emigrating to an L2 English environment, and 2) immersed L2 learners of German (L1: English). We have analysed the temporal fluency and the incidence of disfluency markers (pauses, repetitions and self-corrections) in spontaneous film retellings. Our findings show that learners to speak more slowly than controls and attriters. Also, on each count, the speech of at least one of the bilingual groups contains more disfluency markers than the retellings of the control group. Generally speaking, both bilingual groups-learners and attriters-are equally (dis)fluent and significantly more disfluent than the monolingual speakers. Given that the L1 attriters are unaffected by incomplete acquisition, we interpret these findings as evidence for language competition during speech production. Copyright © 2015. Published by Elsevier B.V.

  15. 1. STREETSCAPE VIEW OF 208 VINE STREET (FIRST HOUSE ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. STREETSCAPE VIEW OF 208 VINE STREET (FIRST HOUSE ON RIGHT) LOOKING WEST. THIS STRUCTURE WAS ONE OF APPROXIMATELY SEVENTEEN DUPLEXES BUILT AS THE ORIGINAL WORKER HOUSING FOR THE LaGRANGE COTTON MILLS, LATER KNOWN AS CALUMET MILL. LaGRANGE MILLS (1888-89) WAS THE FIRST COTTON MILL IN LaGRANGE. NOTE THE GABLE-ON-HIP ROOF FORM AND IDENTICAL STRUCTURES FACING EACH OTHER ALONG BOTH SIDES OF THE NARROW STREET. - 208 Vine Street (House), 208 Vine Street, La Grange, Troup County, GA

  16. Magnitudes, nature, and effects of point and nonpoint discharges in the Chattahoochee River Basin, Atlanta to West Point Dam, Georgia

    USGS Publications Warehouse

    Stamer, J.K.; Cherry, Rodney N.; Faye, R.E.; Kleckner, R.L.

    1979-01-01

    During the period April 1975 to June 1978, the U.S. Geological Survey conducted a river-quality assessment of the Upper Chattahoochee River basin in Georgia. One objective of the study was to assess the magnitudes, nature, and effects of point and non-point discharges in the Chattahoochee River basin from Atlanta to the West Point Dam. On an average annual basis and during the storm period of March 1215, 1976, non-point-source loads for most constituents analyzed were larger than point-source loads at the Whitesburg station, located on the Chattahoochee River about 40 river miles downstream of Atlanta. Most of the non-point-source constituent loads in the Atlanta-to-Whitesburg reach were from urban areas. Average annual point-source discharges accounted for about 50 percent of the dissolved nitrogen, total nitrogen, and total phosphorus loads, and about 70 percent of the dissolved phosphorus loads at Whitesburg. During weekends, power generation at the upstream Buford Dam hydroelectric facility is minimal. Streamflow at the Atlanta station during dry-weather weekends is estimated to be about 1,200 ft3/s (cubic feet per second). Average daily dissolved-oxygen concentrations of less than 5.0 mg/L (milligrams per liter) occurred often in the river, about 20 river miles downstream from Atlanta during these periods from May to November. During a low-flow period, June 1-2, 1977, five municipal point sources contributed 63 percent of the ultimate biochemical oxygen demand, 97 percent of the ammonium nitrogen, 78 percent of the total nitrogen, and 90 percent of the total phosphorus loads at the Franklin station, at the upstream end of West Point Lake. Average daily concentrations of 13 mg/L of ultimate biochemical oxygen demand and 1.8 mg/L of ammonium nitrogen were observed about 2 river miles downstream from two of the municipal point sources. Carbonaceous and nitrogenous oxygen demands caused dissolved-oxygen concentrations between 4.1 and 5.0 mg/L to occur in a 22-mile

  17. Optical transmission for the James Webb Space Telescope

    NASA Astrophysics Data System (ADS)

    Lightsey, Paul A.; Gallagher, Benjamin B.; Nickles, Neal; Copp, Tracy

    2012-09-01

    The fabrication and coating of the mirrors for the James Webb Space Telescope has been completed. The spectral reflectivity of the protected gold coated beryllium mirrors has been measured. The predicted end-of-life transmission through the telescope builds from these values. The additional phenomena that have been analyzed are contamination effects and effects of the environment for the JWST operation about the Earth-Sun L2 Lagrange libration point. The L2 environment analysis has been based on radiation testing of mirror samples and hypervelocity testing to assess the micrometeoroid impact effects. The mirror showed no change in reflectance over the VIS-SWIR wavelengths after exposure to 6-9 Grad (Si) that simulated 6 years orbiting the L2 Lagrange point. The effects of hypervelocity particle impacts on the mirrors from test data has been extrapolated to the to the anticipated flux characteristics for micrometeoroids at the L2 environment. The results show that the micrometeoroid effects are orders of magnitude below the particulate contamination effects. The final end-of-life transmission for the mirrors including all of these phenomena will meet the performance requirements for JWST.

  18. Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

    PubMed

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2018-04-01

    Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

  19. GhL1L1 affects cell fate specification by regulating GhPIN1-mediated auxin distribution.

    PubMed

    Xu, Jiao; Yang, Xiyan; Li, Baoqi; Chen, Lin; Min, Ling; Zhang, Xianlong

    2018-05-13

    Auxin is as an efficient initiator and regulator of cell fate during somatic embryogenesis (SE), but the molecular mechanisms and regulating networks of this process are not well understood. In this report, we analysed SE process induced by Leafy cotyledon1-like 1 (GhL1L1), a NF-YB subfamily gene specifically expressed in embryonic tissues in cotton. We also identified the target gene of GhL1L1, and its role in auxin distribution and cell fate specification during embryonic development was analysed. Overexpression of GhL1L1 accelerated embryonic cell formation, associated with an increased concentration of IAA in embryogenic calluses (ECs) and in the shoot apical meristem (SAM), corresponding to altered expression of the auxin transport gene GhPIN1. By contrast, GhL1L1-deficient explants showed retarded embryonic cell formation, and the concentration of IAA was decreased in GhL1L1-deficient ECs. Disruption of auxin distribution accelerated the specification of embryonic cell fate together with regulation of GhPIN1. Furthermore, we showed that PHOSPHATASE 2AA2 (GhPP2AA2) was activated by GhL1L1 through targeting the G-box of its promoter, hence regulating the activity of GhPIN1 protein. Our results indicate that GhL1L1 functions as a key regulator in auxin distribution to regulate cell fate specification in cotton and contribute to the understanding of the complex process of SE in plant species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Cosmological constraints from the convergence 1-point probability distribution

    NASA Astrophysics Data System (ADS)

    Patton, Kenneth; Blazek, Jonathan; Honscheid, Klaus; Huff, Eric; Melchior, Peter; Ross, Ashley J.; Suchyta, Eric

    2017-11-01

    We examine the cosmological information available from the 1-point probability density function (PDF) of the weak-lensing convergence field, utilizing fast L-PICOLA simulations and a Fisher analysis. We find competitive constraints in the Ωm-σ8 plane from the convergence PDF with 188 arcmin2 pixels compared to the cosmic shear power spectrum with an equivalent number of modes (ℓ < 886). The convergence PDF also partially breaks the degeneracy cosmic shear exhibits in that parameter space. A joint analysis of the convergence PDF and shear 2-point function also reduces the impact of shape measurement systematics, to which the PDF is less susceptible, and improves the total figure of merit by a factor of 2-3, depending on the level of systematics. Finally, we present a correction factor necessary for calculating the unbiased Fisher information from finite differences using a limited number of cosmological simulations.

  1. Formation Flying Satellite Control Around the L2 Sun-Earth Libration Point

    NASA Technical Reports Server (NTRS)

    Hamilton, Nicholas H.; Folta, David; Carpenter, Russell; Bauer, Frank (Technical Monitor)

    2002-01-01

    This paper discusses the development of a linear control algorithm for formations in the vicinity of the L2 sun-Earth libration point. The development of a simplified extended Kalman filter is included as well. Simulations are created for the analysis of the stationkeeping and various formation maneuvers of the Stellar Imager mission. The simulations provide tracking error, estimation error, and control effort results. For formation maneuvering, the formation spacecraft track to within 4 meters of their desired position and within 1.5 millimeters per second of their desired zero velocity. The filter, with few exceptions, keeps the estimation errors within their three-sigma values. Without noise, the controller performs extremely well, with the formation spacecraft tracking to within several micrometers. Each spacecraft uses around 1 to 2 grams of propellant per maneuver, depending on the circumstances.

  2. The James Webb Space Telescope

    NASA Technical Reports Server (NTRS)

    Mather, John

    2003-01-01

    The James Webb Space Telescope (JWST) will extend the discoveries of the Hubble Space Telescope by deploying a large cooled infrared telescope at the Sun-Earth Lagrange point L2. It will have a 6 m aperture and three instruments covering the wavelength range from 0.6 to 28 microns.

  3. The generation and accumulation of interstitial atoms and vacancies in alloys with L1{sub 2} superstructure

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

    Pantyukhova, Olga, E-mail: Pantyukhova@list.ru; Starenchenko, Vladimir, E-mail: star@tsuab.ru; Starenchenko, Svetlana, E-mail: sve-starenchenko@yandex.ru

    2016-01-15

    The dependences of the point defect concentration (interstitial atoms and vacancies) on the deformation degree were calculated for the L1{sub 2} alloys with the high and low antiphase boundaries (APB) energy in terms of the mathematical model of the work and thermal strengthening of the alloys with the L1{sub 2} structure; the concentration of the point defects generated and annihilated in the process of deformation was estimated. It was found that the main part of the point defects generating during plastic deformation annihilates, the residual density of the deformation point defects does not exceed 10{sup −5}.

  4. Regulation of Synaptic Structure by the Ubiquitin C-terminal Hydrolase UCH-L1

    PubMed Central

    Cartier, Anna E.; Djakovic, Stevan N.; Salehi, Afshin; Wilson, Scott M.; Masliah, Eliezer; Patrick, Gentry N.

    2009-01-01

    UCH-L1 is a de-ubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We have found that UCH-L1 activity is rapidly up-regulated by NMDA receptor activation which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of pre and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1 inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner. PMID:19535597

  5. 78 FR 45592 - DeltaPoint Capital IV, LP;

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-29

    ... Regulations (13 CFR 107.730). DeltaPoint Capital IV, L.P. provided financing to BioMaxx, Inc., 1 Fishers Road... York), L.P., an Associate of DeltaPoint Capital IV, L.P., owns more than ten percent of BioMaxx, Inc...

  6. Spectral L2/L1 norm: A new perspective for spectral kurtosis for characterizing non-stationary signals

    NASA Astrophysics Data System (ADS)

    Wang, Dong

    2018-05-01

    Thanks to the great efforts made by Antoni (2006), spectral kurtosis has been recognized as a milestone for characterizing non-stationary signals, especially bearing fault signals. The main idea of spectral kurtosis is to use the fourth standardized moment, namely kurtosis, as a function of spectral frequency so as to indicate how repetitive transients caused by a bearing defect vary with frequency. Moreover, spectral kurtosis is defined based on an analytic bearing fault signal constructed from either a complex filter or Hilbert transform. On the other hand, another attractive work was reported by Borghesani et al. (2014) to mathematically reveal the relationship between the kurtosis of an analytical bearing fault signal and the square of the squared envelope spectrum of the analytical bearing fault signal for explaining spectral correlation for quantification of bearing fault signals. More interestingly, it was discovered that the sum of peaks at cyclic frequencies in the square of the squared envelope spectrum corresponds to the raw 4th order moment. Inspired by the aforementioned works, in this paper, we mathematically show that: (1) spectral kurtosis can be decomposed into squared envelope and squared L2/L1 norm so that spectral kurtosis can be explained as spectral squared L2/L1 norm; (2) spectral L2/L1 norm is formally defined for characterizing bearing fault signals and its two geometrical explanations are made; (3) spectral L2/L1 norm is proportional to the square root of the sum of peaks at cyclic frequencies in the square of the squared envelope spectrum; (4) some extensions of spectral L2/L1 norm for characterizing bearing fault signals are pointed out.

  7. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.

    PubMed

    Lee, Hyun Tae; Lee, Ju Yeon; Lim, Heejin; Lee, Sang Hyung; Moon, Yu Jeong; Pyo, Hyo Jeong; Ryu, Seong Eon; Shin, Woori; Heo, Yong-Seok

    2017-07-17

    In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

  8. [PD-L1 expression and PD-1/PD-L1 inhibitors in breast cancer].

    PubMed

    Monneur, Audrey; Gonçalves, Anthony; Bertucci, François

    2018-03-01

    The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing). Its prognostic value remains controversial when assessed with immunohistochemistry, whereas it seems favorable in triple-negative cancers when assessed at the mRNA level. Early clinical trials with PD-1/PD-L1 inhibitors in breast cancer have shown efficacy in terms of tumor response and/or disease control in refractory metastatic breast cancers, notably in the triple-negative subtype. Many trials are currently underway, both in the metastatic and neo-adjuvant setting. A crucial issue is identification of biomarkers predictive of response to PD-1/PD-L1 inhibitors. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  9. Sparse Recovery via l1 and L1 Optimization

    DTIC Science & Technology

    2014-11-01

    problem, with t being the descent direc- tion, obtaining ut = uxx + f − 1 µ p(u) (6) as an evolution equation. We can hope that these L1 regularized (or...implementation. He considered a wide class of second–order elliptic equations and, with Friedman [14], an extension to parabolic equa- tions. In [15, 16...obtaining an elliptic PDE, or by gradi- ent descent to obtain a parabolic PDE. Addition- ally, some PDEs can be rewritten using the L1 subgradient such as the

  10. Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2.

    PubMed

    Knops, Noël B B; Bos, Krista K; Kerstjens, Mieke; van Dael, Karin; Vos, Yvonne J

    2008-07-15

    We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment with a vasopressin analogue, which pointed to nephrogenic diabetes insipidus (NDI). L1 syndrome and X-linked NDI are distinct clinical disorders caused by mutations in the L1CAM and AVPR2 genes, respectively, located in adjacent positions in Xq28. In this boy we found a deletion of 61,577 basepairs encompassing the entire L1CAM and AVPR2 genes and extending into intron 7 of the ARHGAP4 gene. To our knowledge this is the first description of a patient with a deletion of these three genes. He is the second patient to be described with L1 syndrome and NDI. During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism. 2008 Wiley-Liss, Inc.

  11. The Next Generation Space Telescope

    NASA Technical Reports Server (NTRS)

    Mather, John C.; Seery, Bernard (Technical Monitor)

    2001-01-01

    The Next Generation Space Telescope NGST is an 6-7 m class radiatively cooled telescope, planned for launch to the Lagrange point L2 in 2009, to be built by a partnership of NASA, ESA, and CSA. The NGST science program calls for three core instruments: 1) Near IR camera, 0.6 - 5 micrometer; 2) Near IR multiobject spectrometer, 1 - 5 micrometer, and 3) Mid IR camera and spectrometer, 5 - 28 micrometers. I will report on the scientific goals, project status, and the recent reduction in aperture from the target of 8 m.

  12. Cosmological constraints from the convergence 1-point probability distribution

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

    Patton, Kenneth; Blazek, Jonathan; Honscheid, Klaus

    2017-06-29

    Here, we examine the cosmological information available from the 1-point probability density function (PDF) of the weak-lensing convergence field, utilizing fast l-picola simulations and a Fisher analysis. We find competitive constraints in the Ωm–σ8 plane from the convergence PDF with 188 arcmin 2 pixels compared to the cosmic shear power spectrum with an equivalent number of modes (ℓ < 886). The convergence PDF also partially breaks the degeneracy cosmic shear exhibits in that parameter space. A joint analysis of the convergence PDF and shear 2-point function also reduces the impact of shape measurement systematics, to which the PDF is lessmore » susceptible, and improves the total figure of merit by a factor of 2–3, depending on the level of systematics. Finally, we present a correction factor necessary for calculating the unbiased Fisher information from finite differences using a limited number of cosmological simulations.« less

  13. Simulation of Shallow Water Jets with a Unified Element-based Continuous/Discontinuous Galerkin Model with Grid Flexibility on the Sphere

    DTIC Science & Technology

    2013-01-01

    is the derivative of the N th-order Legendre polynomial . Given these definitions, the one-dimensional Lagrange polynomials hi(ξ) are hi(ξ) = − 1 N(N...2. Detail of one interface patch in the northern hemisphere. The high-order Legendre -Gauss-Lobatto (LGL) points are added to the linear grid by...smaller ones by a Lagrange polynomial of order nI . The number of quadrilateral elements and grid points of the final grid are then given by Np = 6(N

  14. Orbital Maneuvers for Spacecrafts Travelling to/from the Lagrangian Points

    NASA Astrophysics Data System (ADS)

    Bertachini, A.

    The well-known Lagrangian points that appear in the planar restricted three-body problem (Szebehely, 1967) are very important for astronautical applications. They are five points of equilibrium in the equations of motion, what means that a particle located at one of those points with zero velocity will remain there indefinitely. The collinear points (L1, L2 and L3) are always unstable and the triangular points (L4 and L5) are stable in the present case studied (Sun-Earth system). They are all very good points to locate a space-station, since they require a small amount of V (and fuel), the control to be used for station-keeping. The triangular points are specially good for this purpose, since they are stable equilibrium points. In this paper, the planar restricted three-body problem is regularized (using Lemaître regularization) and combined with numerical integration and gradient methods to solve the two point boundary value problem (the Lambert's three-body problem). This combination is applied to the search of families of transfer orbits between the Lagrangian points and the Earth, in the Sun-Earth system, with the minimum possible cost of the control used. So, the final goal of this paper is to find the magnitude and direction of the two impulses to be applied in the spacecraft to complete the transfer: the first one when leaving/arriving at the Lagrangian point and the second one when arriving/living at the Earth. This paper is a continuation of two previous papers that studied transfers in the Earth-Moon system: Broucke (1979), that studied transfer orbits between the Lagrangian points and the Moon and Prado (1996), that studied transfer orbits between the Lagrangian points and the Earth. So, the equations of motion are: whereis the pseudo-potential given by: To solve the TPBVP in the regularized variables the following steps are used: i) Guess a initial velocity Vi, so together with the initial prescribed position ri the complete initial state is known; ii

  15. Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination.

    PubMed

    Gong, Jun; Le, Thang Q; Massarelli, Erminia; Hendifar, Andrew E; Tuli, Richard

    2018-06-04

    Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.

  16. NPC1L1 and Cholesterol Transport

    PubMed Central

    Betters, Jenna L.; Yu, Liqing

    2010-01-01

    The polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1), is enriched in the apical membrane of small intestine absorptive enterocytes where it mediates extracellular sterol transport across the brush border membrane. It is essential for intestinal sterol absorption and is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that lowers blood cholesterol in humans. NPC1L1 is also highly expressed in human liver. The hepatic function of NPC1L1 may be to limit excessive biliary cholesterol loss. NPC1L1-dependent sterol uptake seems to be a clathrin-mediated endocytic process and is regulated by cellular cholesterol content. Recently, NPC1L1 inhibition has been shown to have beneficial effects on components of the metabolic syndrome, such as obesity, insulin resistance, fatty liver, in addition to atherosclerosis. PMID:20307540

  17. Integrating Meaning and Structure in L1-L2 and L2-L1 Translations

    ERIC Educational Resources Information Center

    Lim, Jung Hyun; Christianson, Kiel

    2013-01-01

    This article examined the integration of semantic and morphosyntactic information by Korean learners of English as a second language (L2). In Experiment 1, L2 learners listened to English active or passive sentences that were either plausible or implausible and translated them into Korean. A significant number of Korean translations maintained the…

  18. L1 and L2 Distance Effects in Learning L3 Dutch

    ERIC Educational Resources Information Center

    Schepens, Job J.; der Slik, Frans; Hout, Roeland

    2016-01-01

    Many people speak more than two languages. How do languages acquired earlier affect the learnability of additional languages? We show that linguistic distances between speakers' first (L1) and second (L2) languages and their third (L3) language play a role. Larger distances from the L1 to the L3 and from the L2 to the L3 correlate with lower…

  19. Processing of English Focal Stress by L1-English and L1-Mandarin/L2-English Speakers

    ERIC Educational Resources Information Center

    Guigelaar, Ellen R.

    2017-01-01

    Late second language (L2) learners often struggle with L2 prosody, both in perception and production. This may result from first language (L1) interference or some property of how a second language functions in a late learner independent of what their L1 might be. Here we investigate prosody's role in determining information structure through…

  20. Cloning and Expression Analysis of Genes Encoding Lytic Endopeptidases L1 and L5 from Lysobacter sp. Strain XL1

    PubMed Central

    Lapteva, Y. S.; Zolova, O. E.; Shlyapnikov, M. G.; Tsfasman, I. M.; Muranova, T. A.; Stepnaya, O. A.; Kulaev, I. S.

    2012-01-01

    Lytic enzymes are the group of hydrolases that break down structural polymers of the cell walls of various microorganisms. In this work, we determined the nucleotide sequences of the Lysobacter sp. strain XL1 alpA and alpB genes, which code for, respectively, secreted lytic endopeptidases L1 (AlpA) and L5 (AlpB). In silico analysis of their amino acid sequences showed these endopeptidases to be homologous proteins synthesized as precursors similar in structural organization: the mature enzyme sequence is preceded by an N-terminal signal peptide and a pro region. On the basis of phylogenetic analysis, endopeptidases AlpA and AlpB were assigned to the S1E family [clan PA(S)] of serine peptidases. Expression of the alpA and alpB open reading frames (ORFs) in Escherichia coli confirmed that they code for functionally active lytic enzymes. Each ORF was predicted to have the Shine-Dalgarno sequence located at a canonical distance from the start codon and a potential Rho-independent transcription terminator immediately after the stop codon. The alpA and alpB mRNAs were experimentally found to be monocistronic; transcription start points were determined for both mRNAs. The synthesis of the alpA and alpB mRNAs was shown to occur predominantly in the late logarithmic growth phase. The amount of alpA mRNA in cells of Lysobacter sp. strain XL1 was much higher, which correlates with greater production of endopeptidase L1 than of L5. PMID:22865082

  1. Cloning and expression analysis of genes encoding lytic endopeptidases L1 and L5 from Lysobacter sp. strain XL1.

    PubMed

    Lapteva, Y S; Zolova, O E; Shlyapnikov, M G; Tsfasman, I M; Muranova, T A; Stepnaya, O A; Kulaev, I S; Granovsky, I E

    2012-10-01

    Lytic enzymes are the group of hydrolases that break down structural polymers of the cell walls of various microorganisms. In this work, we determined the nucleotide sequences of the Lysobacter sp. strain XL1 alpA and alpB genes, which code for, respectively, secreted lytic endopeptidases L1 (AlpA) and L5 (AlpB). In silico analysis of their amino acid sequences showed these endopeptidases to be homologous proteins synthesized as precursors similar in structural organization: the mature enzyme sequence is preceded by an N-terminal signal peptide and a pro region. On the basis of phylogenetic analysis, endopeptidases AlpA and AlpB were assigned to the S1E family [clan PA(S)] of serine peptidases. Expression of the alpA and alpB open reading frames (ORFs) in Escherichia coli confirmed that they code for functionally active lytic enzymes. Each ORF was predicted to have the Shine-Dalgarno sequence located at a canonical distance from the start codon and a potential Rho-independent transcription terminator immediately after the stop codon. The alpA and alpB mRNAs were experimentally found to be monocistronic; transcription start points were determined for both mRNAs. The synthesis of the alpA and alpB mRNAs was shown to occur predominantly in the late logarithmic growth phase. The amount of alpA mRNA in cells of Lysobacter sp. strain XL1 was much higher, which correlates with greater production of endopeptidase L1 than of L5.

  2. Cooperatively surrounding control for multiple Euler-Lagrange systems subjected to uncertain dynamics and input constraints

    NASA Astrophysics Data System (ADS)

    Chen, Liang-Ming; Lv, Yue-Yong; Li, Chuan-Jiang; Ma, Guang-Fu

    2016-12-01

    In this paper, we investigate cooperatively surrounding control (CSC) of multi-agent systems modeled by Euler-Lagrange (EL) equations under a directed graph. With the consideration of the uncertain dynamics in an EL system, a backstepping CSC algorithm combined with neural-networks is proposed first such that the agents can move cooperatively to surround the stationary target. Then, a command filtered backstepping CSC algorithm is further proposed to deal with the constraints on control input and the absence of neighbors’ velocity information. Numerical examples of eight satellites surrounding one space target illustrate the effectiveness of the theoretical results. Project supported by the National Basic Research Program of China (Grant No. 2012CB720000) and the National Natural Science Foundation of China (Grant Nos. 61304005 and 61403103).

  3. Coherence Analysis of the Solar Wind Between l1 and the Lunar Orbit

    NASA Astrophysics Data System (ADS)

    Crane, S. O.; Fuqua, H.; Poppe, A. R.; Harada, Y.; Fatemi, S.; Delory, G. T.

    2016-12-01

    A cross correlation analysis of the lunar and solar wind interaction was performed to understand coherence length scales. This is mandatory for conducting tests in electromagnetic sounding of the moon with two measurement probes. Signal processing and data analysis methods encompass the study of the lunar electromagnetic plasma environment with properties of the solar wind at key positions outside of Earth's magnetosphere. Variations in solar activity detected by ACE, WIND, Kaguya and Lunar Prospector can be informative regarding how well correlated the magnetic properties of the solar wind are between the 1st Lagrange point (ACE & WIND orbits) and the lunar orbit (Kaguya & Lunar Prospector investigations). The analysis objective is to use cross correlation to understand the solar wind coherence between these positions. This requires mastering concrete analysis tools to filter and use data that yields high (>0.80) or intermediate (0.70-0.80) coherence values, while demonstrating an analysis of up to one month of data, and archiving poor (<0.50) cross correlation coefficients for effects of orbit position and downstream distance. We also consider the impact of high energy events such as Coronal Mass Ejections, Solar Flares, and shocks that may be recorded by `ACE's List of Disturbances and Transients' to the effect that, at the current level of analysis, various expected coefficients between 0.55 and 0.85 have been generated for up to 3 months of data, 2008-02-01 through 2008-05-03.

  4. Searching for life with the Terrestrial Planet Finder: Lagrange point options for a formation flying interferometer

    NASA Technical Reports Server (NTRS)

    Beichman, C.; Gomez, G.; Lo, M.; Masdemont, J.; Romans, L.

    2002-01-01

    In this paper, we describe the mission design for TPF assuming a distributed spacecraft concept using formation flight around both a halo orbit around L2 as well as a heliocentric orbit. Although the mission architecture is still under study, the next two years will include study of four design cncepts and a downselect to two concepts around 2005.

  5. PD-1/PD-L1 in disease.

    PubMed

    Kuol, Nyanbol; Stojanovska, Lily; Nurgali, Kulmira; Apostolopoulos, Vasso

    2018-02-01

    Expression of PD-1 on T/B cells regulates peripheral tolerance and autoimmunity. Binding of PD-1 to its ligand, PD-L1, leads to protection against self-reactivity. In contrary, tumor cells have evolved immune escape mechanisms whereby overexpression of PD-L1 induces anergy and/or apoptosis of PD-1 positive T cells by interfering with T cell receptor signal transduction. PD-L1 and PD-1 blockade using antibodies are in human clinical trials as an alternative cancer treatment modality. Areas covered: We describe the role of PD-1/PD-L1 in disease in the context of autoimmunity, neurological disorders, stroke and cancer. For immunotherapy/vaccines to be successful, the expression of PD-L1/PD-1 on immune cells should be considered, and the combination of checkpoint inhibitors and vaccines may pave the way for successful outcomes to disease.

  6. Exploratory study of serum ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein for outcome prognostication after pediatric cardiac arrest.

    PubMed

    Fink, Ericka L; Berger, Rachel P; Clark, Robert S B; Watson, R Scott; Angus, Derek C; Panigrahy, Ashok; Richichi, Rudolph; Callaway, Clifton W; Bell, Michael J; Mondello, Stefania; Hayes, Ronald L; Kochanek, Patrick M

    2016-04-01

    Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest. Single center prospective study. Serum biomarkers were measured at 2 time points during the initial 72 h in children after cardiac arrest (n=19) and once in healthy children (controls, n=43). We recorded demographics and details of the cardiac arrest and resuscitation. We determined the associations between serum biomarker concentrations and Pediatric Cerebral Performance Category (PCPC) at 6 months (favorable (PCPC 1-3) or unfavorable (PCPC 4-6)). The initial assessment (time point 1) occurred at a median (IQR) of 10.5 (5.5-17.0)h and the second assessment (time point 2) at 59.0 (54.5-65.0)h post-cardiac arrest. Serum UCH-L1 was higher among children following cardiac arrest than among controls at both time points (p<0.05). Serum GFAP in subjects with unfavorable outcome was higher at time point 2 than in controls (p<0.05). Serum UCH-L1 at time point 1 (AUC 0.782) and both UCH-L1 and GFAP at time point 2 had good classification accuracy for outcome (AUC 0.822 and 0.796), p<0.05 for all. Preliminary data suggest that serum UCH-L1 and GFAP may be of use to prognosticate outcome after pediatric cardiac arrest at clinically-relevant time points and should be validated prospectively. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Exploratory Study of Serum Ubiquitin Carboxyl-Terminal Esterase L1 and Glial Fibrillary Acidic Protein for Outcome Prognostication after Pediatric Cardiac Arrest

    PubMed Central

    Fink, Ericka L; Berger, Rachel P; Clark, Robert SB; Watson, R. Scott; Angus, Derek C; Panigrahy, Ashok; Richichi, Rudolph; Callaway, Clifton W; Bell, Michael J; Mondello, Stefania; Hayes, Ronald L.; Kochanek, Patrick M

    2016-01-01

    Introduction Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest. Methods Single center prospective study. Serum biomarkers were measured at 2 time points during the initial 72 h in children after cardiac arrest (n=19) and once in healthy children (controls, n=43). We recorded demographics and details of the cardiac arrest and resuscitation. We determined the associations between serum biomarker concentrations and Pediatric Cerebral Performance Category (PCPC) at 6 months (favorable (PCPC 1–3) or unfavorable (PCPC 4–6)). Results The initial assessment (time point 1) occurred at a median (IQR) of 10.5 (5.5–17.0) h and the second assessment (time point 2) at 59.0 (54.5–65.0) h post-cardiac arrest. Serum UCH-L1 was higher among children following cardiac arrest than among controls at both time points (p<0.05). Serum GFAP in subjects with unfavorable outcome was higher at time point 2 than in controls (p<0.05). Serum UCH-L1 at time point 1 (AUC 0.782) and both UCH-L1 and GFAP at time point 2 had good classification accuracy for outcome (AUC 0.822 and 0.796), p<0.05 for all. Conclusion Preliminary data suggest that serum UCH-L1 and GFAP may be of use to prognosticate outcome after pediatric cardiac arrest at clinically-relevant time points and should be validated prospectively. PMID:26855294

  8. Use of libration-point orbits for space observatories

    NASA Technical Reports Server (NTRS)

    Farquhar, Robert W.; Dunham, David W.

    1990-01-01

    The sun-earth libration points, L1 and L2, are located 1.5 million kilometers from the earth toward and away from the sun. Halo orbits about these points have significant advantages for space observatories in terms of viewing geometry, thermal and radiation environment, and delta-V expediture.

  9. Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

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

    An, Lei, E-mail: anleim@yahoo.com.cn; Pang, Yun-Wei, E-mail: yunweipang@126.com; Gao, Hong-Mei, E-mail: Gaohongmei_123@yahoo.cn

    Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlledmore » experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.« less

  10. Distributed-Lagrange-Multiplier-based computational method for particulate flow with collisions

    NASA Astrophysics Data System (ADS)

    Ardekani, Arezoo; Rangel, Roger

    2006-11-01

    A Distributed-Lagrange-Multiplier-based computational method is developed for colliding particles in a solid-fluid system. A numerical simulation is conducted in two dimensions using the finite volume method. The entire domain is treated as a fluid but the fluid in the particle domains satisfies a rigidity constraint. We present an efficient method for predicting the collision between particles. In earlier methods, a repulsive force was applied to the particles when their distance was less than a critical value. In this method, an impulsive force is computed. During the frictionless collision process between two particles, linear momentum is conserved while the tangential forces are zero. Thus, instead of satisfying a condition of rigid body motion for each particle separately, as done when particles are not in contact, both particles are rigidified together along their line of centers. Particles separate from each other when the impulsive force is less than zero and after this time, a rigidity constraint is satisfied for each particle separately. Grid independency is implemented to ensure the accuracy of the numerical simulation. A comparison between this method and previous collision strategies is presented and discussed.

  11. Dynamics of tethered satellites in the vicinity of the Lagrangian point L2 of the Earth-Moon system

    NASA Astrophysics Data System (ADS)

    Baião, M. F.; Stuchi, T. J.

    2017-08-01

    This paper analyzes the dynamical evolution of satellites formed by two masses connected by a cable— tethered satellites. We derive the Lagrangian equations of motion in the neighborhood of the collinear equilibrium points, especially for the L2 , of the restricted problem of three bodies. The rigid body configuration is expanded in Legendre polynomials up to fourth degree. We present some numerical simulations of the influence of the parameters such as cable length, mass ratio and initial conditions in the behavior of the tethered satellites. The equation for the collinear equilibrium point is derived and numerically solved. The evolution of the equilibria with the variation of the cable length as a parameter is studied. We also present a discussion of the linear stability around these equilibria. Based on this analysis calculate some unstable Lyapunov orbits associated to these equilibrium points. We found periodic orbits in which the tether travels parallel to itself without involving the angular motion. The numerical applications are focused on the Earth-Moon system. However, the general character of the equations allows applications to the L1 equilibrium and obviously to systems other than the Earth-Moon.

  12. Testing of Lagrange multiplier damped least-squares control algorithm for woofer-tweeter adaptive optics

    PubMed Central

    Zou, Weiyao; Burns, Stephen A.

    2012-01-01

    A Lagrange multiplier-based damped least-squares control algorithm for woofer-tweeter (W-T) dual deformable-mirror (DM) adaptive optics (AO) is tested with a breadboard system. We show that the algorithm can complementarily command the two DMs to correct wavefront aberrations within a single optimization process: the woofer DM correcting the high-stroke, low-order aberrations, and the tweeter DM correcting the low-stroke, high-order aberrations. The optimal damping factor for a DM is found to be the median of the eigenvalue spectrum of the influence matrix of that DM. Wavefront control accuracy is maximized with the optimized control parameters. For the breadboard system, the residual wavefront error can be controlled to the precision of 0.03 μm in root mean square. The W-T dual-DM AO has applications in both ophthalmology and astronomy. PMID:22441462

  13. Passive remote sensing of altitude and optical depth of dust plumes using the oxygen A and B bands: First results from EPIC/DSCOVR at Lagrange-1 point

    NASA Astrophysics Data System (ADS)

    Xu, Xiaoguang; Wang, Jun; Wang, Yi; Zeng, Jing; Torres, Omar; Yang, Yuekui; Marshak, Alexander; Reid, Jeffrey; Miller, Steve

    2017-07-01

    We presented an algorithm for inferring aerosol layer height (ALH) and optical depth (AOD) over ocean surface from radiances in oxygen A and B bands measured by the Earth Polychromatic Imaging Camera (EPIC) on the Deep Space Climate Observatory (DSCOVR) orbiting at Lagrangian-1 point. The algorithm was applied to EPIC imagery of a 2 day dust outbreak over the North Atlantic Ocean. Retrieved ALHs and AODs were evaluated against counterparts observed by Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP), Moderate Resolution Imaging Spectroradiometer, and Aerosol Robotic Network. The comparisons showed 71.5% of EPIC-retrieved ALHs were within ±0.5 km of those determined from CALIOP and 74.4% of EPIC AOD retrievals fell within a ± (0.1 + 10%) envelope of MODIS retrievals. This study demonstrates the potential of EPIC measurements for retrieving global aerosol height multiple times daily, which are essential for evaluating aerosol profile simulated in climate models and for better estimating aerosol radiative effects.

  14. Implicit Prosody and Cue-based Retrieval: L1 and L2 Agreement and Comprehension during Reading

    PubMed Central

    Pratt, Elizabeth; Fernández, Eva M.

    2016-01-01

    This project focuses on structural and prosodic effects during reading, examining their influence on agreement processing and comprehension in native English (L1) and Spanish–English bilingual (L2) speakers. We consolidate research from several distinct areas of inquiry—cognitive processing, reading fluency, and L1/L2 processing—in order to support the integration of prosody with a cue-based retrieval mechanism for subject-verb agreement. To explore this proposal, the experimental design manipulated text presentation to influence implicit prosody, using sentences designed to induce subject-verb agreement attraction errors. Materials included simple and complex relative clauses with head nouns and verbs that were either matched or mismatched for number. Participants read items in one of three presentation formats (whole sentence, word-by-word, or phrase-by-phrase), rated each item for grammaticality, and responded to a comprehension probe. Results indicated that while overall, message comprehension was prioritized over subject-verb agreement computation, presentation format differentially affected both measures in the L1 and L2 groups. For the L1 participants, facilitating the projection of phrasal prosody onto text (phrase-by-phrase presentation) enhanced performance in agreement processing, while disrupting prosodic projection via word-by-word presentation decreased comprehension accuracy. For the L2 participants, however, phrase-by-phrase presentation was not significantly beneficial for agreement processing, and additionally resulted in lower comprehension accuracy. These differences point to a significant role of prosodic phrasing during agreement processing in both L1 and L2 speakers, additionally suggesting that it may contribute to a cue-based retrieval agreement model, either acting as a cue directly, or otherwise scaffolding the retrieval process. The discussion and results presented provide support both for a cue-based retrieval mechanism in

  15. Implicit Prosody and Cue-based Retrieval: L1 and L2 Agreement and Comprehension during Reading.

    PubMed

    Pratt, Elizabeth; Fernández, Eva M

    2016-01-01

    This project focuses on structural and prosodic effects during reading, examining their influence on agreement processing and comprehension in native English (L1) and Spanish-English bilingual (L2) speakers. We consolidate research from several distinct areas of inquiry-cognitive processing, reading fluency, and L1/L2 processing-in order to support the integration of prosody with a cue-based retrieval mechanism for subject-verb agreement. To explore this proposal, the experimental design manipulated text presentation to influence implicit prosody, using sentences designed to induce subject-verb agreement attraction errors. Materials included simple and complex relative clauses with head nouns and verbs that were either matched or mismatched for number. Participants read items in one of three presentation formats (whole sentence, word-by-word, or phrase-by-phrase), rated each item for grammaticality, and responded to a comprehension probe. Results indicated that while overall, message comprehension was prioritized over subject-verb agreement computation, presentation format differentially affected both measures in the L1 and L2 groups. For the L1 participants, facilitating the projection of phrasal prosody onto text (phrase-by-phrase presentation) enhanced performance in agreement processing, while disrupting prosodic projection via word-by-word presentation decreased comprehension accuracy. For the L2 participants, however, phrase-by-phrase presentation was not significantly beneficial for agreement processing, and additionally resulted in lower comprehension accuracy. These differences point to a significant role of prosodic phrasing during agreement processing in both L1 and L2 speakers, additionally suggesting that it may contribute to a cue-based retrieval agreement model, either acting as a cue directly, or otherwise scaffolding the retrieval process. The discussion and results presented provide support both for a cue-based retrieval mechanism in agreement

  16. Advances in Highly Constrained Multi-Phase Trajectory Generation using the General Pseudospectral Optimization Software (GPOPS)

    DTIC Science & Technology

    2013-08-01

    release; distribution unlimited. PA Number 412-TW-PA-13395 f generic function g acceleration due to gravity h altitude L aerodynamic lift force L Lagrange...cost m vehicle mass M Mach number n number of coefficients in polynomial regression p highest order of polynomial regression Q dynamic pressure R...Method (RPM); the collocation points are defined by the roots of Legendre -Gauss- Radau (LGR) functions.9 GPOPS also automatically refines the “mesh” by

  17. Active and Passive Sensing from Geosynchronous and Libration Orbits

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark; Raymond, Carol; Hildebrand, Peter

    2003-01-01

    The development of the LEO (EOS) missions has led the way to new technologies and new science discoveries. However, LEO measurements alone cannot cost effectively produce high time resolution measurements needed to move the science to the next level. Both GEO and the Lagrange points, L1 and L2, provide vantage points that will allow higher time resolution measurements. GEO is currently being exploited by weather satellites, but the sensors currently operating at GEO do not provide the spatial or spectral resolution needed for atmospheric trace gas, ocean or land surface measurements. It is also may be possible to place active sensors in geostationary orbit. It seems clear, that the next era in earth observation and discovery will be opened by sensor systems operating beyond near earth orbit.

  18. Do L2 Writing Courses Affect the Improvement of L1 Writing Skills via Skills Transfer from L2 to L1?

    ERIC Educational Resources Information Center

    Gonca, Altmisdort

    2016-01-01

    This study investigates the relationship of second language (L2) writing skills proficiency with the first language (L1) writing skills, in light of the language transfer. The study aims to analyze the positive effects of L2 writing proficiency on L1 writing proficiency. Forty native Turkish-speaking university students participated in the study.…

  19. Development and Evaluation of a Hydrostatic Dynamical Core Using the Spectral Element/Discontinuous Galerkin Methods

    DTIC Science & Technology

    2014-04-01

    The CG and DG horizontal discretization employs high-order nodal basis functions associated with Lagrange polynomials based on Gauss-Lobatto- Legendre ...and DG horizontal discretization employs high-order nodal basis functions 29 associated with Lagrange polynomials based on Gauss-Lobatto- Legendre ...Inside 235 each element we build ( 1)N + Gauss-Lobatto- Legendre (GLL) quadrature points, where N 236 indicate the polynomial order of the basis

  20. Testing of Lagrange multiplier damped least-squares control algorithm for woofer-tweeter adaptive optics.

    PubMed

    Zou, Weiyao; Burns, Stephen A

    2012-03-20

    A Lagrange multiplier-based damped least-squares control algorithm for woofer-tweeter (W-T) dual deformable-mirror (DM) adaptive optics (AO) is tested with a breadboard system. We show that the algorithm can complementarily command the two DMs to correct wavefront aberrations within a single optimization process: the woofer DM correcting the high-stroke, low-order aberrations, and the tweeter DM correcting the low-stroke, high-order aberrations. The optimal damping factor for a DM is found to be the median of the eigenvalue spectrum of the influence matrix of that DM. Wavefront control accuracy is maximized with the optimized control parameters. For the breadboard system, the residual wavefront error can be controlled to the precision of 0.03 μm in root mean square. The W-T dual-DM AO has applications in both ophthalmology and astronomy. © 2012 Optical Society of America

  1. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis.

    PubMed

    Carter, Laura L; Leach, Michael W; Azoitei, Mihai L; Cui, Junqing; Pelker, Jeffrey W; Jussif, Jason; Benoit, Steve; Ireland, Gretchen; Luxenberg, Deborah; Askew, G Roger; Milarski, Kim L; Groves, Christopher; Brown, Tom; Carito, Brenda A; Percival, Karen; Carreno, Beatriz M; Collins, Mary; Marusic, Suzana

    2007-01-01

    Interactions between PD-1 and its two differentially expressed ligands, PD-L1 and PD-L2, attenuate T cell activation and effector function. To determine the role of these molecules in autoimmune disease of the CNS, PD-1-/-, PD-L1-/- and PD-L2-/- mice were generated and immunized to induce experimental autoimmune encephalomyelitis (EAE). PD-1-/- and PD-L1-/- mice developed more severe EAE than wild type and PD-L2-/- mice. Consistent with this, PD-1-/- and PD-L1-/- cells produced elevated levels of the pro-inflammatory cytokines IFN-gamma, TNF, IL-6 and IL-17. These results demonstrate that interactions between PD-1/PD-L1, but not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE.

  2. Does reading in shallow L1 orthography slow attrition of language-specific morphological structures?

    PubMed

    Zaretsky, Elena; Bar-Shalom, Eva G

    2010-01-01

    This study looks at the relationship between L1 (Russian) attrition and L1 reading ability in Russian-English-speaking bilingual children. Ten Russian-English bilingual children and 10 adults participated in this study. Nine out of 10 children participants were born in the US and used L1 as their primary language of interaction within the family, but the intensity and the length of uninterrupted L1 exposure differed for each child. All participants were tested on perception (grammaticality judgement) and production (narrative) tasks to assess their sensitivity to and retention of the morphosyntactic structure of L1. All children showed some attrition of grammatical morphemes, specifically in the Russian systems of declension and conjugation; however, the degree of attrition correlated with reading ability in L1, i.e. children with L1 reading skills showed a lesser degree of attrition for some language-specific morphosyntactic structures. This finding shows interdependence of oral and reading skills and points to the role reading in language with shallow orthography may play in preservation of L1 grammatical structures in oral language. The implications for the clinical applications are also discussed.

  3. Promises and Obstacles of L1 Use in Language Classrooms: A State-of-the-Art Review

    ERIC Educational Resources Information Center

    Ghobadi, Mehdi; Ghasemi, Hadi

    2015-01-01

    Translation and language teaching techniques which take language learners' first language (L1) as point of reference for teaching the second language (L2) have been long discouraged on the ground that these teaching techniques would end in the fossilization of L2 structure forms in the learner's Interlanguage system. However, in recent years, the…

  4. Cloud Point and Liquid-Liquid Equilibrium Behavior of Thermosensitive Polymer L61 and Salt Aqueous Two-Phase System.

    PubMed

    Rao, Wenwei; Wang, Yun; Han, Juan; Wang, Lei; Chen, Tong; Liu, Yan; Ni, Liang

    2015-06-25

    The cloud point of thermosensitive triblock polymer L61, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO), was determined in the presence of various electrolytes (K2HPO4, (NH4)3C6H5O7, and K3C6H5O7). The cloud point of L61 was lowered by the addition of electrolytes, and the cloud point of L61 decreased linearly with increasing electrolyte concentration. The efficacy of electrolytes on reducing cloud point followed the order: K3C6H5O7 > (NH4)3C6H5O7 > K2HPO4. With the increase in salt concentration, aqueous two-phase systems exhibited a phase inversion. In addition, increasing the temperature reduced the concentration of salt needed that could promote phase inversion. The phase diagrams and liquid-liquid equilibrium data of the L61-K2HPO4/(NH4)3C6H5O7/K3C6H5O7 aqueous two-phase systems (before the phase inversion but also after phase inversion) were determined at T = (25, 30, and 35) °C. Phase diagrams of aqueous two-phase systems were fitted to a four-parameter empirical nonlinear expression. Moreover, the slopes of the tie-lines and the area of two-phase region in the diagram have a tendency to rise with increasing temperature. The capacity of different salts to induce aqueous two-phase system formation was the same order as the ability of salts to reduce the cloud point.

  5. Do L1 Reading Achievement and L1 Print Exposure Contribute to the Prediction of L2 Proficiency?

    ERIC Educational Resources Information Center

    Sparks, Richard L.; Patton, Jon; Ganschow, Leonore; Humbach, Nancy

    2012-01-01

    The study examined whether individual differences in high school first language (L1) reading achievement and print exposure would account for unique variance in second language (L2) written (word decoding, spelling, writing, reading comprehension) and oral (listening/speaking) proficiency after adjusting for the effects of early L1 literacy and…

  6. Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes.

    PubMed

    Nandy, Suman Kumar; Seal, Alpana

    2016-01-01

    Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases.

  7. Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes

    PubMed Central

    Nandy, Suman Kumar; Seal, Alpana

    2016-01-01

    Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases. PMID:27764212

  8. L1 to Teach L2: Complexities and Contradictions

    ERIC Educational Resources Information Center

    Copland, Fiona; Neokleous, Georgios

    2011-01-01

    This article uncovers the complexities and contradictions inherent in making decisions about L1 use in the English language classroom. Through an analysis of data from classrooms in a Cypriot context and from interviews with Cypriot teachers, a number of functions for L1 use are identified, as are the teachers' rationales for using L1 for…

  9. Novel roles for LIX1L in promoting cancer cell proliferation through ROS1-mediated LIX1L phosphorylation

    PubMed Central

    Nakamura, Satoki; Kahyo, Tomoaki; Tao, Hong; Shibata, Kiyoshi; Kurabe, Nobuya; Yamada, Hidetaka; Shinmura, Kazuya; Ohnishi, Kazunori; Sugimura, Haruhiko

    2015-01-01

    Herein, we report the characterization of Limb expression 1-like, (LIX1L), a putative RNA-binding protein (RBP) containing a double-stranded RNA binding motif, which is highly expressed in various cancer tissues. Analysis of MALDI-TOF/TOF mass spectrometry and RNA immunoprecipitation-sequencing of interacting proteins and the microRNAs (miRNAs) bound to LIX1L revealed that LIX1L interacts with proteins (RIOK1, nucleolin and PABPC4) and miRNAs (has-miRNA-520a-5p, −300, −216b, −326, −190a, −548b-3p, −7–5p and −1296) in HEK-293 cells. Moreover, the reduction of phosphorylated Tyr136 (pTyr136) in LIX1L through the homeodomain peptide, PY136, inhibited LIX1L-induced cell proliferation in vitro, and PY136 inhibited MKN45 cell proliferation in vivo. We also determined the miRNA-targeted genes and showed that was apoptosis induced through the reduction of pTyr136. Moreover, ROS1, HCK, ABL1, ABL2, JAK3, LCK and TYR03 were identified as candidate kinases responsible for the phosphorylation of Tyr136 of LIX1L. These data provide novel insights into the biological significance of LIX1L, suggesting that this protein might be an RBP, with implications for therapeutic approaches for targeting LIX1L in LIX1L-expressing cancer cells. PMID:26310847

  10. L1-CAM in cancerous tissues.

    PubMed

    Gavert, Nancy; Ben-Shmuel, Amir; Raveh, Shani; Ben-Ze'ev, Avri

    2008-11-01

    L1-cell adhesion molecule (L1-CAM) is a cell adhesion receptor of the immunoglobulin superfamily, known for its roles in nerve cell function. While originally believed to be present only in brain cells, in recent years L1-CAM has been detected in other tissues, and in a variety of cancer cells, including some common types of human cancer. We review the prevalence of L1-CAM in human cancer, the possible mechanisms involved in L1-CAM-mediated tumorigenesis, and cancer therapies based upon L1-CAM antibody treatment. In colon cancer cells, the L1-CAM gene was identified as a target of the Wnt/beta-catenin-TCF signaling pathway, and L1-CAM was exclusively detected at the invasive front of colon and ovarian cancer tissue. The expression of L1-CAM in normal and cancer cells enhanced tumorigenesis and conferred metastasis in colon cancer cells. Antibodies against the L1-CAM ectodomain severely inhibited the proliferation of a variety of cancer cells in culture and reduced tumor burden when injected into mice harboring cancer cells expressing L1-CAM. These results, in addition to the presence of L1-CAM on the cell surface and its restricted distribution in normal tissues, make it an ideal target for tumor therapy.

  11. Pairwise-interaction extended point-particle model for particle-laden flows

    NASA Astrophysics Data System (ADS)

    Akiki, G.; Moore, W. C.; Balachandar, S.

    2017-12-01

    In this work we consider the pairwise interaction extended point-particle (PIEP) model for Euler-Lagrange simulations of particle-laden flows. By accounting for the precise location of neighbors the PIEP model goes beyond local particle volume fraction, and distinguishes the influence of upstream, downstream and laterally located neighbors. The two main ingredients of the PIEP model are (i) the undisturbed flow at any particle is evaluated as a superposition of the macroscale flow and a microscale flow that is approximated as a pairwise superposition of perturbation fields induced by each of the neighboring particles, and (ii) the forces and torque on the particle are then calculated from the undisturbed flow using the Faxén form of the force relation. The computational efficiency of the standard Euler-Lagrange approach is retained, since the microscale perturbation fields induced by a neighbor are pre-computed and stored as PIEP maps. Here we extend the PIEP force model of Akiki et al. [3] with a corresponding torque model to systematically include the effect of perturbation fields induced by the neighbors in evaluating the net torque. Also, we use DNS results from a uniform flow over two stationary spheres to further improve the PIEP force and torque models. We then test the PIEP model in three different sedimentation problems and compare the results against corresponding DNS to assess the accuracy of the PIEP model and improvement over the standard point-particle approach. In the case of two sedimenting spheres in a quiescent ambient the PIEP model is shown to capture the drafting-kissing-tumbling process. In cases of 5 and 80 sedimenting spheres a good agreement is obtained between the PIEP simulation and the DNS. For all three simulations, the DEM-PIEP was able to recreate, to a good extent, the results from the DNS, while requiring only a negligible fraction of the numerical resources required by the fully-resolved DNS.

  12. Pairwise Interaction Extended Point-Particle (PIEP) model for multiphase jets and sedimenting particles

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Balachandar, S.

    2017-11-01

    We perform a series of Euler-Lagrange direct numerical simulations (DNS) for multiphase jets and sedimenting particles. The forces the flow exerts on the particles in these two-way coupled simulations are computed using the Basset-Bousinesq-Oseen (BBO) equations. These forces do not explicitly account for particle-particle interactions, even though such pairwise interactions induced by the perturbations from neighboring particles may be important especially when the particle volume fraction is high. Such effects have been largely unaddressed in the literature. Here, we implement the Pairwise Interaction Extended Point-Particle (PIEP) model to simulate the effect of neighboring particle pairs. A simple collision model is also applied to avoid unphysical overlapping of solid spherical particles. The simulation results indicate that the PIEP model provides a more elaborative and complicated movement of the dispersed phase (droplets and particles). Office of Naval Research (ONR) Multidisciplinary University Research Initiative (MURI) project N00014-16-1-2617.

  13. Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy?

    PubMed

    Tang, Fei; Zheng, Pan

    2018-01-01

    Antibody blockade of the PD-1/PD-L1 pathway has elicited durable antitumor responses in the therapy of a broad spectrum of cancers. PD-L1 is constitutively expressed in certain tumors and host immune cells, and its expression can be induced or maintained by many factors. The expression of PD-L1 on tumor tissues has been reported to be positively correlated with the efficacy of anti-PD-1/PD-L1 therapy in patients. However, multiple clinical trials indicate that patients with PD-L1-negative tumors also respond to this blockade therapy, which suggests the potential contribution of PD-L1 from host immune cells. Recently, six articles independently evaluated and verified the contributions of PD-L1 from tumor versus non-tumor cells in various mouse tumor models. These studies confirmed that PD-L1 on either tumor cells or host immune cells contributes to tumor escape, and the relative contributions of PD-L1 on these cells seem to be context-dependent. While both tumor- and host-derived PD-L1 can play critical roles in immune suppression, differences in tumor immunogenicity appear to underlie their relative importance. Notably, these reports highlight the essential roles of PD-L1 from host myeloid cells in negatively regulating T cell activation and limiting T cell trafficking. Therefore, comprehensive evaluating the global PD-L1 expression, rather than monitoring PD-L1 expression on tumor cells alone, should be a more accurate way for predicting responses in PD-1/PD-L1 blockade therapy in cancer patients.

  14. Relativistic semiempirical-core-potential calculations in Ca+,Sr+ , and Ba+ ions on Lagrange meshes

    NASA Astrophysics Data System (ADS)

    Filippin, Livio; Schiffmann, Sacha; Dohet-Eraly, Jérémy; Baye, Daniel; Godefroid, Michel

    2018-01-01

    Relativistic atomic structure calculations are carried out in alkaline-earth-metal ions using a semiempirical-core-potential approach. The systems are partitioned into frozen-core electrons and an active valence electron. The core orbitals are defined by a Dirac-Hartree-Fock calculation using the grasp2k package. The valence electron is described by a Dirac-like Hamiltonian involving a core-polarization potential to simulate the core-valence electron correlation. The associated equation is solved with the Lagrange-mesh method, which is an approximate variational approach having the form of a mesh calculation because of the use of a Gauss quadrature to calculate matrix elements. Properties involving the low-lying metastable D 3 /2 ,5 /2 2 states of Ca+, Sr+, and Ba+ are studied, such as polarizabilities, one- and two-photon decay rates, and lifetimes. Good agreement is found with other theory and observation, which is promising for further applications in alkalilike systems.

  15. L1-norm locally linear representation regularization multi-source adaptation learning.

    PubMed

    Tao, Jianwen; Wen, Shiting; Hu, Wenjun

    2015-09-01

    In most supervised domain adaptation learning (DAL) tasks, one has access only to a small number of labeled examples from target domain. Therefore the success of supervised DAL in this "small sample" regime needs the effective utilization of the large amounts of unlabeled data to extract information that is useful for generalization. Toward this end, we here use the geometric intuition of manifold assumption to extend the established frameworks in existing model-based DAL methods for function learning by incorporating additional information about the target geometric structure of the marginal distribution. We would like to ensure that the solution is smooth with respect to both the ambient space and the target marginal distribution. In doing this, we propose a novel L1-norm locally linear representation regularization multi-source adaptation learning framework which exploits the geometry of the probability distribution, which has two techniques. Firstly, an L1-norm locally linear representation method is presented for robust graph construction by replacing the L2-norm reconstruction measure in LLE with L1-norm one, which is termed as L1-LLR for short. Secondly, considering the robust graph regularization, we replace traditional graph Laplacian regularization with our new L1-LLR graph Laplacian regularization and therefore construct new graph-based semi-supervised learning framework with multi-source adaptation constraint, which is coined as L1-MSAL method. Moreover, to deal with the nonlinear learning problem, we also generalize the L1-MSAL method by mapping the input data points from the input space to a high-dimensional reproducing kernel Hilbert space (RKHS) via a nonlinear mapping. Promising experimental results have been obtained on several real-world datasets such as face, visual video and object. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm.

    PubMed

    Zou, Weiyao; Qi, Xiaofeng; Burns, Stephen A

    2011-07-01

    We implemented a Lagrange-multiplier (LM)-based damped least-squares (DLS) control algorithm in a woofer-tweeter dual deformable-mirror (DM) adaptive optics scanning laser ophthalmoscope (AOSLO). The algorithm uses data from a single Shack-Hartmann wavefront sensor to simultaneously correct large-amplitude low-order aberrations by a woofer DM and small-amplitude higher-order aberrations by a tweeter DM. We measured the in vivo performance of high resolution retinal imaging with the dual DM AOSLO. We compared the simultaneous LM-based DLS dual DM controller with both single DM controller, and a successive dual DM controller. We evaluated performance using both wavefront (RMS) and image quality metrics including brightness and power spectrum. The simultaneous LM-based dual DM AO can consistently provide near diffraction-limited in vivo routine imaging of human retina.

  17. Lagrange constraint neural networks for massive pixel parallel image demixing

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.; Hsu, Charles C.

    2002-03-01

    We have shown that the remote sensing optical imaging to achieve detailed sub-pixel decomposition is a unique application of blind source separation (BSS) that is truly linear of far away weak signal, instantaneous speed of light without delay, and along the line of sight without multiple paths. In early papers, we have presented a direct application of statistical mechanical de-mixing method called Lagrange Constraint Neural Network (LCNN). While the BSAO algorithm (using a posteriori MaxEnt ANN and neighborhood pixel average) is not acceptable for remote sensing, a mirror symmetric LCNN approach is all right assuming a priori MaxEnt for unknown sources to be averaged over the source statistics (not neighborhood pixel data) in a pixel-by-pixel independent fashion. LCNN reduces the computation complexity, save a great number of memory devices, and cut the cost of implementation. The Landsat system is designed to measure the radiation to deduce surface conditions and materials. For any given material, the amount of emitted and reflected radiation varies by the wavelength. In practice, a single pixel of a Landsat image has seven channels receiving 0.1 to 12 microns of radiation from the ground within a 20x20 meter footprint containing a variety of radiation materials. A-priori LCNN algorithm provides the spatial-temporal variation of mixture that is hardly de-mixable by other a-posteriori BSS or ICA methods. We have already compared the Landsat remote sensing using both methods in WCCI 2002 Hawaii. Unfortunately the absolute benchmark is not possible because of lacking of the ground truth. We will arbitrarily mix two incoherent sampled images as the ground truth. However, the constant total probability of co-located sources within the pixel footprint is necessary for the remote sensing constraint (since on a clear day the total reflecting energy is constant in neighborhood receiving pixel sensors), we have to normalized two image pixel-by-pixel as well. Then, the

  18. Effectiveness of anti-PD-1/PD-L1 antibodies in urothelial carcinoma patients with different PD-L1 expression levels: a meta-analysis.

    PubMed

    Liu, Junqi; Zhang, Chuanfeng; Hu, Jiegang; Tian, Qing; Wang, Xin; Gu, Hao; Zhang, Song; Zhao, Di; Fan, Ruitai

    2018-02-23

    Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD-1)/programmed death-ligand1 (PD-L1) inhibitors. We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD-1/PD-L1 antibodies in patients with different PD-L1 expression levels. We divided patients into three groups according to the percentages of PD-L1-positive cells, namely the low- PD-L1 (PD-L1 < 1%), the medium-PD-L1 (PD-L11 and < 5%) and the high-PD-L1 (PD-L1 ≥ 5%) groups. We found that the high-PD-L1 group responded significantly better than other groups (P = 0.0003, ORs = 0.45, 95%CI: 0.29-071; P = 0.0009, ORs = 0.43, 95%CI: 0.25-0.73, for low-PD-L1 and medium-PD-L1 groups, respectively), while the latter two groups responded similarly (P = 0.90, ORs = 1.06, 95%CI: 0.62-1.83) to both PD-1 and PD-L1 inhibitors. Furthermore, we found that the medium-PD-L1 and high-PD-L1 groups responded similarly to PD-1/ PD-L1 inhibitors (P = 0.65, ORs = 1.11, 95%CI: 0.69-1.77), while the low-PD-L1 group responded better to PD-1 inhibitors than PD-L1 inhibitors (P = 0.046, ORs = 1.92, 95%CI: 0.98-3.89). Our results suggest that PD-L1 positive patients should be defined as those with ≥ 5% or greaterPD-L1-positive cells. PD-1 antibodies performed better only in the low-group patients, likely because they could block the interactions of PD-1 with both PD-L1 and PD-L2.

  19. Minimum Error Bounded Efficient L1 Tracker with Occlusion Detection (PREPRINT)

    DTIC Science & Technology

    2011-01-01

    Minimum Error Bounded Efficient `1 Tracker with Occlusion Detection Xue Mei\\ ∗ Haibin Ling† Yi Wu†[ Erik Blasch‡ Li Bai] \\Assembly Test Technology...proposed BPR-L1 tracker is tested on several challenging benchmark sequences involving chal- lenges such as occlusion and illumination changes. In all...point method de - pends on the value of the regularization parameter λ. In the experiments, we found that the total number of PCG is a few hundred. The

  20. L1 French Learning of L2 Spanish Past Tenses: L1 Transfer versus Aspect and Interface Issues

    ERIC Educational Resources Information Center

    Amenós-Pons, José; Ahern, Aoife; Gujarro-Fuentes, Pedro

    2017-01-01

    This paper examines the process of acquiring L2s that are closely related to the L1 through data on how adult French speakers learning L2 Spanish in a formal setting develop knowledge and use of past tenses in this L2. We consider the role of transfer and simplification in acquiring mental representations of the L2 grammar, specifically in the…

  1. Stability of Dalteparin 1,000 Unit/mL in 0.9% Sodium Chloride for Injection in Polypropylene Syringes.

    PubMed

    Kirkham, Kylian; Munson, Jessica M; McCluskey, Susan V; Graner, Kevin K

    2017-01-01

    The stability of dalteparin 1,000 units/mL in 0.9% sodium chloride for injection stored in polypropylene syringes under refrigeration was examined. Dalteparin 1,000-units/mL syringes were prepared by adding 9 mL of 0.9% sodium chloride for injection to 1 mL of dalteparin sodium 10,000 unit/mL from commercial single-use syringes. Compounded solutions in 0.5-mL aliquots were transferred to 1-mL polypropylene syringes and sealed with a Luer lock tip cap and stored at refrigerated temperatures (2°C to 8°C) with ambient fluorescent light exposure. Syringes from three batches of dalteparin 1,000 units/mL were potency tested in duplicate by a stability-indicating high-performance liquid chromatography assay using a 0.5-mL sample at specified intervals. Visual and pH testing were performed on each batch. Samples were visually inspected for container integrity, color, and clarity. Samples for pH testing were prepared using a 1:1 dilution of dalteparin 1,000 units/mL in sterile water for injection and underwent duplicate analysis at each time point. High-performance liquid chromatography analyses showed a remaining percent of the initial dalteparin content at day 30 of 94.88% ± 2.11%. Samples remained colorless and clear with no signs of container compromise and no visual particulate matter at each time point. Throughout the 30-day study period, pH values remained within 0.3-pH units from the initial value of 5.84. Dalteparin 1,000 unit/mL in 0.9% sodium chloride for injection, packaged in 1-mL polypropylene syringes was stable for at least 30 days while stored at refrigerated conditions with ambient fluorescent light exposure. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  2. MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

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

    Schwartz, C.E.; Wang, Y.; Schroer, R.J.

    1994-09-01

    The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have anmore » altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.« less

  3. Adapting the Euler-Lagrange equation to study one-dimensional motions under the action of a constant force

    NASA Astrophysics Data System (ADS)

    Dias, Clenilda F.; Araújo, Maria A. S.; Carvalho-Santos, Vagson L.

    2018-01-01

    The Euler-Lagrange equations (ELE) are very important in the theoretical description of several physical systems. In this work we have used a simplified form of ELE to study one-dimensional motions under the action of a constant force. From the use of the definition of partial derivative, we have proposed two operators, here called mean delta operators, which may be used to solve the ELE in a simplest way. We have applied this simplification to solve three simple mechanical problems in which the particle is under the action of the gravitational field: a free fall body, the Atwood’s machine and the inclined plan. The proposed simplification can be used to introduce the lagrangian formalism in teaching classical mechanics in introductory physics courses.

  4. High-affinity PD-1 molecules deliver improved interaction with PD-L1 and PD-L2.

    PubMed

    Li, Yanyan; Liang, Zhaoduan; Tian, Ye; Cai, Wenxuan; Weng, Zhiming; Chen, Lin; Zhang, Huanling; Bao, Yifeng; Zheng, Hongjun; Zeng, Sihai; Bei, Chunhua; Li, Yi

    2018-06-11

    The inhibitory checkpoint molecule programmed death (PD)-1 plays a vital role in maintaining immune homeostasis upon binding to its ligands, PD-L1 and PD-L2. Several recent studies have demonstrated that soluble PD-1 (sPD-1) can block the interaction between membrane PD-1 and PD-L1 to enhance the anti-tumor capability of T cells. However, the affinity of natural sPD-1 binding to PD-L1 is too low to permit therapeutic applications. Here a PD-1 variant with ~3,000-fold and ~70-fold affinity increase to bind PD-L1 and PD-L2, respectively, was generated through directed molecular evolution and phage display technology. Structural analysis showed that mutations at amino acid positions 124 and 132 of PD-1 played major roles in enhancing the affinity of PD-1 binding to its ligands. The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells or dendritic cells (DCs), and it could enhance the proliferation and IFN-γ release of activated lymphocytes. These features potentially qualify the high-affinity PD-1 variant as a unique candidate for the development of a new class of PD-1 immune checkpoint blockade therapeutics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Trajectory Design Strategies for the NGST L2 Libration Point Mission

    NASA Technical Reports Server (NTRS)

    Folta, David; Cooley, Steven; Howell, Kathleen; Bauer, Frank H.

    2001-01-01

    The Origins' Next Generation Space Telescope (NGST) trajectory design is addressed in light of improved methods for attaining constrained orbit parameters and their control at the exterior collinear libration point, L2. The use of a dynamical systems approach, state-space equations for initial libration orbit control, and optimization to achieve constrained orbit parameters are emphasized. The NGST trajectory design encompasses a direct transfer and orbit maintenance under a constant acceleration. A dynamical systems approach can be used to provide a biased orbit and stationkeeping maintenance method that incorporates the constraint of a single axis correction scheme.

  6. Montgomery Point Lock and Dam, White River, Arkansas

    DTIC Science & Technology

    2016-01-01

    ER D C/ CH L TR -1 6- 1 Monitoring Completed Navigation Projects (MCNP) Program Montgomery Point Lock and Dam, White River, Arkansas Co...Navigation Projects (MCNP) Program ERDC/CHL TR-16-1 January 2016 Montgomery Point Lock and Dam, White River, Arkansas Allen Hammack, Michael Winkler, and...20314-1000 Under MCNP Work Unit: Montgomery Point Lock and Dam, White River, Arkansas ERDC/CHL TR-16-1 ii Abstract Montgomery Point Lock and

  7. L1 Korean and L1 Mandarin L2 English Learners' Acquisition of the Count/Mass Distinction in English

    ERIC Educational Resources Information Center

    Choi, Sea Hee; Ionin, Tania; Zhu, Yeqiu

    2018-01-01

    This study investigates the second language (L2) acquisition of the English count/mass distinction by speakers of Korean and Mandarin Chinese, with a focus on the semantics of atomicity. It is hypothesized that L1-Korean and L1-Mandarin L2-English learners are influenced by atomicity in the use of the count/mass morphosyntax in English. This…

  8. 1. Occident Terminal Elevator and annex, (l)1930/workhouse and annex 1925 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Occident Terminal Elevator and annex, (l)-1930/workhouse and annex 1925 with train shed Peavey Duluth Terminal Annex on left 1930-workhouse 1908 (white silos). - Occident Terminal Elevator & Storage Annex, South side of second slip, north from outer end of Rice's Point, east of Garfield Avenue, Duluth, St. Louis County, MN

  9. MAP Attitude Control System Design and Analysis

    NASA Technical Reports Server (NTRS)

    Andrews, S. F.; Campbell, C. E.; Ericsson-Jackson, A. J.; Markley, F. L.; ODonnell, J. R., Jr.

    1997-01-01

    The Microwave Anisotropy Probe (MAP) is a follow-on to the Differential Microwave Radiometer (DMR) instrument on the Cosmic Background Explorer (COBE) spacecraft. The MAP spacecraft will perform its mission in a Lissajous orbit around the Earth-Sun L(sub 2) Lagrange point to suppress potential instrument disturbances. To make a full-sky map of cosmic microwave background fluctuations, a combination fast spin and slow precession motion will be used. MAP requires a propulsion system to reach L(sub 2), to unload system momentum, and to perform stationkeeping maneuvers once at L(sub 2). A minimum hardware, power and thermal safe control mode must also be provided. Sufficient attitude knowledge must be provided to yield instrument pointing to a standard deviation of 1.8 arc-minutes. The short development time and tight budgets require a new way of designing, simulating, and analyzing the Attitude Control System (ACS). This paper presents the design and analysis of the control system to meet these requirements.

  10. L1CAM in human cancer.

    PubMed

    Altevogt, Peter; Doberstein, Kai; Fogel, Mina

    2016-04-01

    L1 cell adhesion molecule (L1CAM) is one of the first neural adhesion molecules described with important functions in the development of the nervous system. Subsequent work discovered that L1CAM is expressed in many human cancers and is often associated with bad prognosis. This is most likely due to the motility and invasion promoting function of L1CAM. Here, we describe the path L1CAM has taken from a neural adhesion molecule to a recognized tumor antigen. We summarize the literature on L1CAM expression in cancers and pre-cancerous lesions. We focus on the genetic elements required for its re-expression and highlight preclinical studies for targeted therapy. The data suggest that L1CAM is a valuable diagnostic/prognostic marker and an attractive target for the therapy of several human cancers. © 2015 UICC.

  11. L2 Effects on L1 Event Conceptualization

    ERIC Educational Resources Information Center

    Bylund, Emanuel; Jarvis, Scott

    2011-01-01

    The finding that speakers of aspect languages encode event endpoints to a lesser extent than do speakers of non-aspect languages has led to the hypothesis that there is a relationship between grammatical aspect and event conceptualization (e.g., von Stutterheim and Nuse, 2003). The present study concerns L1 event conceptualization in 40 L1

  12. Graph cuts via l1 norm minimization.

    PubMed

    Bhusnurmath, Arvind; Taylor, Camillo J

    2008-10-01

    Graph cuts have become an increasingly important tool for solving a number of energy minimization problems in computer vision and other fields. In this paper, the graph cut problem is reformulated as an unconstrained l1 norm minimization that can be solved effectively using interior point methods. This reformulation exposes connections between the graph cuts and other related continuous optimization problems. Eventually the problem is reduced to solving a sequence of sparse linear systems involving the Laplacian of the underlying graph. The proposed procedure exploits the structure of these linear systems in a manner that is easily amenable to parallel implementations. Experimental results obtained by applying the procedure to graphs derived from image processing problems are provided.

  13. [Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures].

    PubMed

    Peters, I; Tezval, H; Kramer, M W; Wolters, M; Grünwald, V; Kuczyk, M A; Serth, J

    2015-11-01

    The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein

  14. Mechanism for the decrease in the FIP1L1-PDGFRalpha protein level in EoL-1 cells by histone deacetylase inhibitors.

    PubMed

    Ishihara, Kenji; Kaneko, Motoko; Kitamura, Hajime; Takahashi, Aki; Hong, Jang Ja; Seyama, Toshio; Iida, Koji; Wada, Hiroshi; Hirasawa, Noriyasu; Ohuchi, Kazuo

    2008-01-01

    Acetylation and deacetylation of proteins occur in cells in response to various stimuli, and are reversibly catalyzed by histone acetyltransferase and histone deacetylase (HDAC), respectively. EoL-1 cells have an FIP1L1-PDGFRA fusion gene that causes transformation of eosinophilic precursor cells into leukemia cells. The HDAC inhibitors apicidin and n-butyrate suppress the proliferation of EoL-1 cells and induce differentiation into eosinophils by a decrease in the protein level of FIP1L1-PDGFRalpha without affecting the mRNA level for FIP1L1-PDGFRA. In this study, we analyzed the mechanism by which the protein level of FIP1L1-PDGFRalpha is decreased by apicidin and n-butyrate. EoL-1 cells were incubated in the presence of the HDAC inhibitors apicidin, trichostatin A or n-butyrate. The protein levels of FIP1L1-PDGFRalpha and phosphorylated eIF-2alpha were determined by Western blotting. Actinomycin D and cycloheximide were used to block RNA synthesis and protein synthesis, respectively, in the chasing experiment of the amount of FIP1L1-PDGFRalpha protein. When apicidin- and n-butyrate-treated EoL-1 cells were incubated in the presence of actinomycin D, the decrease in the protein level of FIP1L1-PDGFRalpha was significantly enhanced when compared with controls. In contrast, the protein levels were not changed by cycloheximide among these groups. Apicidin and n-butyrate induced the continuous phosphorylation of eIF-2alpha for up to 8 days. The decrease in the level of FIP1L1-PDGFRalpha protein by continuous inhibition of HDAC may be due to the decrease in the translation rate of FIP1L1-PDGFRA. Copyright 2008 S. Karger AG, Basel.

  15. Quantifying the Quality Difference between L1 and L2 Essays: A Rating Procedure with Bilingual Raters and L1 and L2 Benchmark Essays

    ERIC Educational Resources Information Center

    Tillema, Marion; van den Bergh, Huub; Rijlaarsdam, Gert; Sanders, Ted

    2013-01-01

    It is the consensus that, as a result of the extra constraints placed on working memory, texts written in a second language (L2) are usually of lower quality than texts written in the first language (L1) by the same writer. However, no method is currently available for quantifying the quality difference between L1 and L2 texts. In the present…

  16. An Euler-Lagrange method considering bubble radial dynamics for modeling sonochemical reactors.

    PubMed

    Jamshidi, Rashid; Brenner, Gunther

    2014-01-01

    Unsteady numerical computations are performed to investigate the flow field, wave propagation and the structure of bubbles in sonochemical reactors. The turbulent flow field is simulated using a two-equation Reynolds-Averaged Navier-Stokes (RANS) model. The distribution of the acoustic pressure is solved based on the Helmholtz equation using a finite volume method (FVM). The radial dynamics of a single bubble are considered by applying the Keller-Miksis equation to consider the compressibility of the liquid to the first order of acoustical Mach number. To investigate the structure of bubbles, a one-way coupling Euler-Lagrange approach is used to simulate the bulk medium and the bubbles as the dispersed phase. Drag, gravity, buoyancy, added mass, volume change and first Bjerknes forces are considered and their orders of magnitude are compared. To verify the implemented numerical algorithms, results for one- and two-dimensional simplified test cases are compared with analytical solutions. The results show good agreement with experimental results for the relationship between the acoustic pressure amplitude and the volume fraction of the bubbles. The two-dimensional axi-symmetric results are in good agreement with experimentally observed structure of bubbles close to sonotrode. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Threshold to Transfer Writing Skills from L1 to L2

    ERIC Educational Resources Information Center

    Ito, Fumihiko

    2009-01-01

    Background: It has been hypothesized that L2 (second language) readers are not able to draw on their L1 (first language) reading skills for the successful development of L2 reading skills until they develop a certain proficiency in L2 because a lack of proficiency blocks transfer of L1 reading skills to the reading of L2 texts. This minimum degree…

  18. Three cases with L1 syndrome and two novel mutations in the L1CAM gene.

    PubMed

    Marín, Rosario; Ley-Martos, Miriam; Gutiérrez, Gema; Rodríguez-Sánchez, Felicidad; Arroyo, Diego; Mora-López, Francisco

    2015-11-01

    Mutations in the L1CAM gene have been identified in the following various X-linked neurological disorders: congenital hydrocephalus; mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; spastic paraplegia; and agenesis of the corpus callosum. These conditions are currently considered different phenotypes of a single entity known as L1 syndrome. We present three families with L1 syndrome. Sequencing of the L1CAM gene allowed the identification of the following mutations involved: a known splicing mutation (c.3531-12G>A) and two novel ones: a missense mutation (c.1754A>C; p.Asp585Ala) and a nonsense mutation (c.3478C>T; p.Gln1160Stop). The number of affected males and carrier females identified in a relatively small population suggests that L1 syndrome may be under-diagnosed. L1 syndrome should be considered in the differential diagnosis of intellectual disability or mental retardation in children, especially when other signs such as hydrocephalus or adducted thumbs are present.

  19. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

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

    Kusunoki, Chisato, E-mail: yosizaki@belle.shiga-med.ac.jp; Yang, Liu; Yoshizaki, Takeshi

    Highlights: Black-Right-Pointing-Pointer Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. Black-Right-Pointing-Pointer EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. Black-Right-Pointing-Pointer Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid ({omega}3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of {omega}3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treatedmore » with {omega}3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). {omega}3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with {omega}3-PUFA prevented H{sub 2}O{sub 2}-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.« less

  20. Distributed adaptive asymptotically consensus tracking control of uncertain Euler-Lagrange systems under directed graph condition.

    PubMed

    Wang, Wei; Wen, Changyun; Huang, Jiangshuai; Fan, Huijin

    2017-11-01

    In this paper, a backstepping based distributed adaptive control scheme is proposed for multiple uncertain Euler-Lagrange systems under directed graph condition. The common desired trajectory is allowed totally unknown by part of the subsystems and the linearly parameterized trajectory model assumed in currently available results is no longer needed. To compensate the effects due to unknown trajectory information, a smooth function of consensus errors and certain positive integrable functions are introduced in designing virtual control inputs. Besides, to overcome the difficulty of completely counteracting the coupling terms of distributed consensus errors and parameter estimation errors in the presence of asymmetric Laplacian matrix, extra information transmission of local parameter estimates are introduced among linked subsystem and adaptive gain technique is adopted to generate distributed torque inputs. It is shown that with the proposed distributed adaptive control scheme, global uniform boundedness of all the closed-loop signals and asymptotically output consensus tracking can be achieved. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  1. The Relationship between L1 Fluency and L2 Fluency Development

    ERIC Educational Resources Information Center

    Derwing, Tracey M.; Munro, Murray J.; Thomson, Ronald I.; Rossiter, Marian J.

    2009-01-01

    A fundamental question in the study of second language (L2) fluency is the extent to which temporal characteristics of speakers' first language (L1) productions predict the same characteristics in the L2. A close relationship between a speaker's L1 and L2 temporal characteristics would suggest that fluency is governed by an underlying trait. This…

  2. Generalized concurrence measure for faithful quantification of multiparticle pure state entanglement using Lagrange's identity and wedge product

    NASA Astrophysics Data System (ADS)

    Bhaskara, Vineeth S.; Panigrahi, Prasanta K.

    2017-05-01

    Concurrence, introduced by Hill and Wootters (Phys Rev Lett 78:5022, 1997), provides an important measure of entanglement for a general pair of qubits that is faithful: strictly positive for entangled states and vanishing for all separable states. Such a measure captures the entire content of entanglement, providing necessary and sufficient conditions for separability. We present an extension of concurrence to multiparticle pure states in arbitrary dimensions by a new framework using the Lagrange's identity and wedge product representation of separability conditions, which coincides with the "I-concurrence" of Rungta et al. (Phys Rev A 64:042315, 2001) who proposed by extending Wootters's spin-flip operator to a so-called universal inverter superoperator. Our framework exposes an inherent geometry of entanglement and may be useful for the further extensions to mixed and continuous variable states.

  3. Design and Comparison of Cascaded H-Bridge, Modular Multilevel Converter, and 5-L Active Neutral Point Clamped Topologies for Motor Drive Applications

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

    Marzoughi, Alinaghi; Burgos, Rolando; Boroyevich, Dushan

    This paper presents the design procedure and comparison of converters currently used in medium-voltage high-power motor drive applications. For this purpose, the cascaded H-bridge (CHB), modular multilevel converter (MMC), and five-level active neutral point clamped (5-L ANPC) topologies are targeted. The design is performed using 1.7-kV insulated gate bipolar transistors (IGBTs) for CHB and MMC converters, and utilizing 3.3- and 4.5-kV IGBTs for 5-L ANPC topology as normally done in industry. The comparison is done between the designed converter topologies at three different voltage levels (4.16, 6.9, and 13.8 kV, with only the first two voltage levels in case ofmore » the 5-L ANPC) and two different power levels (3 and 5 MVA), in order to elucidate the dependence of different parameters on voltage and power rating. Finally, the comparison is done from several points of view such as efficiency, capacitive energy storage, semiconductor utilization, parts count (for measure of reliability), and power density.« less

  4. [Construction and application of prokaryotic expression system of Leptospira interrogans lipL32/1-lipL41/1 fusion gene].

    PubMed

    Luo, Dong-jiao; Yan, Jie; Mao, Ya-fei; Li, Shu-ping; Luo, Yi-hui; Li, Li-wei

    2005-01-01

    To construct lipL32/1-lipL41/1 fusion gene and its prokaryotic expression system and to determine frequencies of carrying and expression of lipL32 and lipL41 genes in L.interrogans wild strains and specific antibody levels in sera from leptospirosis patients. lipL32/1-lipL41/1 fusion gene was constructed using linking primer PCR method and the prokaryotic expression system of the fusion gene done with routine techniques. SDS-PAGE was used to examine expression of the target recombinant protein rLipL32/1-rLipL41/1. Immunogenicity of rLipL32/1-rLipL41/1 was identified by Western blot. PCR and MAT were performed to detect carrying and expression of lipL32 and lipL41 genes in 97 wild L.interrogans strains. Antibodies against products of lipL32 and lipL41 genes in serum samples from 228 leptospirosis patients were detected by ELISA method. The homogeneity of nucleotide and putative amino acid sequence of lipL32/1-lipL41/1 fusion gene were 99.9 % and 99.8 % in comparison with the reported sequences. Expression output of the target recombinant protein rLipL32/1-rLipL41/1, mainly present in inclusion body, accounted for 10 % of the total bacterial proteins. Both the rabbit antisera against rLipL32/1 and rLipL41/1 could combine to rLipL32/1-rLipL41/1. 97.9 % and 87.6 % of the L.interrogans wild strains had lipL32 and lipL41 genes, respectively. 95.9 % and 84.5 % of the wild strains were positive for MAT with titers of 1:4 - 1:128 using rabbit anti-rLipL32s or anti-rLipL41s sera, respectively. 94.7 % - 97.4 % of the patients'serum samples were positive for rLipL32s antibodies, while 78.5 % - 84.6 % of them were rLipL41s antibodies detectable. lipL32/1-jlipL41/1 fusion gene and its prokaryotic expression system were successfully constructed. The expressed fusion protein had qualified immunogenicity. Both the lipL32 and lipL41 genes are extensively carried and frequently expressed by different serogroups of L.interrogans, and their expression products exhibit cross-antigenicity.

  5. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway.

    PubMed

    Tremblay-LeMay, Rosemarie; Rastgoo, Nasrin; Chang, Hong

    2018-03-27

    Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combinations with other drugs used in the treatment of multiple myeloma seemed promising, and clinical trials are ongoing. However, there have recently been concerns about the safety of PD-1 and PD-L1 inhibitors combined with immunomodulators in the treatment of multiple myeloma, and several trials have been suspended. There is therefore a need for alternative combinations of drugs or different approaches to target this pathway. Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has been associated with intrinsic aggressive features independent of immune evasion mechanisms, thereby providing a rationale for the adoption of new strategies directly targeting PD-L1 protein expression. Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators. This review will focus on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that have been shown to modulate this expression.

  6. L1 literacy affects L2 pronunciation intake and text vocalization

    NASA Astrophysics Data System (ADS)

    Walton, Martin

    2005-04-01

    For both deaf and hearing learners, L1 acquisition calls on auditive, gestural and visual modes in progressive processes over longer stages imposed in strictly anatomical and social order from the earliest pre-lexical phase [Jusczyk (1993), Kuhl & Meltzoff (1996)] to ultimate literacy. By contrast, L2 learning will call on accelerating procedures but with restricted input, arbitrated by L1 literacy as can be traced in the English of French-speaking learners, whether observed in spontaneous speech or in text vocalization modes. An inventory of their predictable omissions, intrusions and substitutions at suprasegmental and syllabic levels, many of which they can actually hear while unable to vocalize in real-time, suggests that a photogenic segmentation of continuous speech into alphabetical units has eclipsed the indispensable earlier phonogenic module, filtering L2 intake and output. This competing mode analysis hypothesizes a critical effect on L2 pronunciation of L1 graphemic procedures acquired usually before puberty, informing data for any Critical Period Hypothesis or amounts of L1 activation influencing L2 accent [Flege (1997, 1998)] or any psychoacoustic French deafness with regard to English stress-timing [Dupoux (1997)]. A metaphonic model [Howell & Dean (1991)] adapted for French learners may remedially distance L1 from L2 vocalization procedures.

  7. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

    PubMed

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-03-01

    Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

  8. L1 Explicit Instruction Can Improve L2 Online and Offline Performance

    ERIC Educational Resources Information Center

    McManus, Kevin; Marsden, Emma

    2017-01-01

    This study investigated the effectiveness of providing L1 explicit information (EI) with practice for making more accurate and faster interpretations of L2 French "Imparfait" (IMP). Two treatments were investigated: (a) "L2-only," providing EI about the L2 with L2 interpretation practice, and (b) "L2+L1," providing…

  9. A Node Localization Algorithm Based on Multi-Granularity Regional Division and the Lagrange Multiplier Method in Wireless Sensor Networks.

    PubMed

    Shang, Fengjun; Jiang, Yi; Xiong, Anping; Su, Wen; He, Li

    2016-11-18

    With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed. When the unknown node is inside positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is outside positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.

  10. Evaluation of a transient, simultaneous, arbitrary Lagrange-Euler based multi-physics method for simulating the mitral heart valve.

    PubMed

    Espino, Daniel M; Shepherd, Duncan E T; Hukins, David W L

    2014-01-01

    A transient multi-physics model of the mitral heart valve has been developed, which allows simultaneous calculation of fluid flow and structural deformation. A recently developed contact method has been applied to enable simulation of systole (the stage when blood pressure is elevated within the heart to pump blood to the body). The geometry was simplified to represent the mitral valve within the heart walls in two dimensions. Only the mitral valve undergoes deformation. A moving arbitrary Lagrange-Euler mesh is used to allow true fluid-structure interaction (FSI). The FSI model requires blood flow to induce valve closure by inducing strains in the region of 10-20%. Model predictions were found to be consistent with existing literature and will undergo further development.

  11. Recombination Creates Novel L1 (Line-1) Elements in Rattus Norvegicus

    PubMed Central

    Hayward, B. E.; Zavanelli, M.; Furano, A. V.

    1997-01-01

    Mammalian L1 (long interspersed repeated DNA, LINE-1) retrotransposons consist of a 5' untranslated region (UTR) with regulatory properties, two protein encoding regions (ORF I, ORF II, which encodes a reverse transcriptase) and a 3' UTR. L1 elements have been evolving in mammals for >100 million years and this process continues to generate novel L1 subfamilies in modern species. Here we characterized the youngest known subfamily in Rattus norvegicus, L1(mlvi2), and unexpectedly found that this element has a dual ancestry. While its 3' UTR shares the same lineage as its nearest chronologically antecedent subfamilies, L1(3) and L1(4), its ORF I sequence does not. The L1(mlvi2) ORF I was derived from an ancestral ORF I sequence that was the evolutionary precursor of the L1(3) and L1(4) ORF I. We suggest that an ancestral ORF I sequence was recruited into the modern L1(mlvi2) subfamily by recombination that possibly could have resulted from template strand switching by the reverse transcriptase during L1 replication. This mechanism could also account for some of the structural features of rodent L1 5' UTR and ORF I sequences including one of the more dramatic features of L1 evolution in mammals, namely the repeated acquisition of novel 5' UTRs. PMID:9178013

  12. Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes

    PubMed Central

    Ikebuchi, Ryoyo; Konnai, Satoru; Okagawa, Tomohiro; Yokoyama, Kazumasa; Nakajima, Chie; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2014-01-01

    Programmed death-ligand 1 (PD-L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death-1 (PD-1). However, the mechanism of PD-L1-mediated inhibitory signalling after PD-L1 cross-linking by anti-PD-L1 monoclonal antibody (mAb) or PD-1–immunogloblin fusion protein (PD-1-Ig) is still unknown, although it may induce cell death of PD-L1+ cells required for regular immune reactions. In this study, PD-1-Ig or anti-PD-L1 mAb treatment was tested in cell lines that expressed PD-L1 and bovine lymphocytes to investigate whether the treatment induces immune reactivation or PD-L1-mediated cell death. PD-L1 cross-linking by PD-1-Ig or anti-PD-L1 mAb primarily increased the number of dead cells in PD-L1high cells, but not in PD-L1low cells; these cells were prepared from Cos-7 cells in which bovine PD-L1 expression was induced by transfection. The PD-L1-mediated cell death also occurred in Cos-7 and HeLa cells transfected with vectors only encoding the extracellular region of PD-L1. In bovine lymphocytes, the anti-PD-L1 mAb treatment up-regulated interferon-γ (IFN-γ) production, whereas PD-1-Ig treatment decreased this cytokine production and cell proliferation. The IFN-γ production in B-cell-depleted peripheral blood mononuclear cells was not reduced by PD-1-Ig treatment and the percentages of dead cells in PD-L1+ B cells were increased by PD-1-Ig treatment, indicating that PD-1-Ig-induced immunosuppression in bovine lymphocytes could be caused by PD-L1-mediated B-cell death. This study provides novel information for the understanding of signalling through PD-L1. PMID:24405267

  13. Libration Point Navigation Concepts Supporting Exploration Vision

    NASA Technical Reports Server (NTRS)

    Carpenter, J. Russell; Folta, David C.; Moreau, Michael C.; Gramling, Cheryl J.

    2004-01-01

    Farquhar described several libration point navigation concepts that would appear to support NASA s current exploration vision. One concept is a Lunar Relay Satellite operating in the vicinity of Earth-Moon L2, providing Earth-to-lunar far-side and long- range surface-to-surface navigation and communications capability. Reference [ 1] lists several advantages of such a system in comparison to a lunar orbiting relay satellite constellation. Among these are one or two vs. many satellites for coverage, simplified acquisition and tracking due to very low relative motion, much longer contact times, and simpler antenna pointing. An obvious additional advantage of such a system is that uninterrupted links to Earth avoid performing critical maneuvers "in the blind." Another concept described is the use of Earth-Moon L1 for lunar orbit rendezvous, rather than low lunar orbit as was done for Apollo. This rendezvous technique would avoid large plane change and high fuel cost associated with high latitude landing sites and long stay times. Earth-Moon L1 also offers unconstrained launch windows from the lunar surface. Farquhar claims this technique requires only slightly higher fuel cost than low lunar orbit rendezvous for short-stay equatorial landings. Farquhar also describes an Interplanetary Transportation System that would use libration points as terminals for an interplanetary shuttle. This approach would offer increased operational flexibility in terms of launch windows, rendezvous, aborts, etc. in comparison to elliptical orbit transfers. More recently, other works including Folta[3] and Howell[4] have shown that patching together unstable trajectories departing Earth-Moon libration points with stable trajectories approaching planetary libration points may also offer lower overall fuel costs than elliptical orbit transfers. Another concept Farquhar described was a Deep Space Relay at Earth-Moon IA and/or L5 that would serve as a high data rate optical navigation and

  14. Influence of a weak gravitational wave on a bound system of two point-masses. [of binary stars

    NASA Technical Reports Server (NTRS)

    Turner, M. S.

    1979-01-01

    The problem of a weak gravitational wave impinging upon a nonrelativistic bound system of two point masses is considered. The geodesic equation for each mass is expanded in terms of two small parameters, v/c and dimensionless wave amplitude, in a manner similar to the post-Newtonian expansion; the geodesic equations are resolved into orbital and center-of-mass equations of motion. The effect of the wave on the orbit is determined by using Lagrange's planetary equations to calculate the time evolution of the orbital elements. The gauge properties of the solutions and, in particular, the gauge invariance of the secular effects are discussed.

  15. NSDC Policy Points. Volume 1, Number 4

    ERIC Educational Resources Information Center

    National Staff Development Council, 2009

    2009-01-01

    "NSDC Policy Points" is a newsletter published by the National Staff Development Council (NSDC). This issue of "NSDC Policy Points" discusses why collaborative learning is critical to professional development. Included in this newsletter is an article about team learning in Cedar Rapids, Iowa. [For Volume 1, Number 3 of…

  16. L1 English/L2 Spanish: Orthography-Phonology Activation without Contrasts

    ERIC Educational Resources Information Center

    Shea, Christine

    2017-01-01

    We consider how orthography activates sounds that are in a noncontrastive relationship in the second language (L2) and for which only one variant exists in the first language (L1). Participants were L1 English / L2 Spanish and native Spanish listeners. Intervocalically, Spanish graphemes "b d g" correspond phonetically to stops and…

  17. L1 Use in L2 Vocabulary Learning: Facilitator or Barrier

    ERIC Educational Resources Information Center

    Liu, Jing

    2008-01-01

    Based on empirical research and qualitative analysis, this paper aims to explore the effects of L1 use on L2 vocabulary teaching. The results show that, during L2 vocabulary teaching process, the proper application of L1 can effectively facilitate the memorization of new words, and the bilingual method (both English explanation and Chinese…

  18. Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions

    NASA Astrophysics Data System (ADS)

    Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele

    2013-10-01

    The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

  19. Power transmission by laser beam from lunar-synchronous satellite

    NASA Technical Reports Server (NTRS)

    Williams, M. D.; Deyoung, R. J.; Schuster, G. L.; Choi, S. H.; Dagle, J. E.; Coomes, E. P.; Antoniak, Z. I.; Bamberger, J. A.; Bates, J. M.; Chiu, M. A.

    1993-01-01

    The possibility of beaming power from synchronous lunar orbits (the L1 and L2 Lagrange points) to a manned long-range lunar rover is addressed. The rover and two versions of a satellite system (one powered by a nuclear reactor, the other by photovoltaics) are described in terms of their masses, geometries, power needs, missions, and technological capabilities. Laser beam power is generated by a laser diode array in the satellite and converted to 30 kW of electrical power at the rover. Present technological capabilities, with some extrapolation to near future capabilities, are used in the descriptions. The advantages of the two satellite/rover systems over other such systems and over rovers with onboard power are discussed along with the possibility of enabling other missions.

  20. Flights between a neighborhoods of unstable libration points of Sun-Earth system

    NASA Astrophysics Data System (ADS)

    Surkova, Valerya; Shmyrov, Vasily

    2018-05-01

    In this paper we study the problem of constructing impulse flights between neighborhoods of unstable collinear libration points of the Sun-Earth system [1]. Such maneuvering in near-Earth space may prove to be in demand in modern space navigation. For example, such a maneuvering was done by the space vehicle GENESIS. Three test points are chosen for the implementation of the impulse control, in order to move to a neighborhood of the libration point L2. It is shown that the earlier on the exit from the vicinity of the libration point L1 impulse control was realized, the sooner the neighborhood L2 was achieved. Separated from this problem, the problem of optimal control in the neighborhood of L2 was considered and a form of stabilizing control is presented.

  1. Reading Attitudes in L1 and L2, and Their Influence on L2 Extensive Reading

    ERIC Educational Resources Information Center

    Yamashita, Junko

    2004-01-01

    This study examines the relationship between both first language (L1) and second language (L2) reading attitudes, and learners' performance in L2 extensive reading. Four reading attitude variables were identified (Comfort, Anxiety, Value, Self-perception), both in L1 and L2, according to learners' responses to a questionnaire. Results of analyses…

  2. Preliminary Planar Formation: Flight Dynamics Near Sun-Earth L2 Point

    NASA Technical Reports Server (NTRS)

    Segerman, Alan M.; Zedd, Michael F.

    2003-01-01

    NASA's Goddard Space Flight Center is planning a series of missions in the vicinity of the Sun-Earth L2 libration point. Some of these projects will involve a distributed space system of telescope spacecraft acting together as a single telescope for high-resolution. The individual telescopes will be configured in a plane, surrounding a hub, where the telescope plane can be aimed toward various astronomical targets of interest. In preparation for these missions, it is necessary to develop an improved understanding of the dynamical behavior of objects in a planar configuration near L2. The classical circular restricted three body problem is taken as the basis for the analysis. At first order, the motion of such a telescope relative to the hub is described by a system of linear second order differential equations. These equations are identical to the circular restricted problem's linear equations describing the hub motion about L2. Therefore, the fundamental frequencies, both parallel to and normal to the ecliptic plane, are the same for the relative telescope motion as for the hub motion. To maintain the telescope plane for the duration necessary for the planned observations, a halo-type orbit of the telescopes about the hub is investigated. By using a halo orbit, the individual telescopes remain in approximately the same plane over the observation duration. For such an orbit, the fundamental periods parallel to and normal to the ecliptic plane are forced to be the same by careful selection of the initial conditions in order to adjust the higher order forces. The relative amplitudes of the resulting oscillations are associated with the orientation of the telescope plane relative to the ecliptic. As in the circular restricted problem, initial conditions for the linearized equations must be selected so as not to excite the convergent or divergent linear modes. In a higher order analysis, the telescope relative motion equations include the effects of the position of the

  3. Shot noise in systems with semi-Dirac points

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

    Zhai, Feng; Wang, Juan

    2014-08-14

    We calculate the ballistic conductance and shot noise of electrons through a two-dimensional stripe system (width W ≫ length L) with semi-Dirac band-touching points. We find that the ratio between zero-temperature noise power and mean current (the Fano factor) is highly anisotropic. When the transport is along the linear-dispersion direction and the Fermi energy is fixed at the semi-Dirac point, the Fano factor has a universal value F = 0.179 while a minimum conductivity exists and scales with L{sup 1∕2}. Along the parabolic dispersion direction, the Fano factor at the semi-Dirac point has a contact-independent limit exceeding 0.9, which varies weakly withmore » L due to the common-path interference of evanescent waves. Our findings suggest a way to discern the type of band-touching points.« less

  4. How Does L1 and L2 Exposure Impact L1 Performance in Bilingual Children? Evidence from Polish-English Migrants to the United Kingdom

    PubMed Central

    Haman, Ewa; Wodniecka, Zofia; Marecka, Marta; Szewczyk, Jakub; Białecka-Pikul, Marta; Otwinowska, Agnieszka; Mieszkowska, Karolina; Łuniewska, Magdalena; Kołak, Joanna; Miękisz, Aneta; Kacprzak, Agnieszka; Banasik, Natalia; Foryś-Nogala, Małgorzata

    2017-01-01

    Most studies on bilingual language development focus on children’s second language (L2). Here, we investigated first language (L1) development of Polish-English early migrant bilinguals in four domains: vocabulary, grammar, phonological processing, and discourse. We first compared Polish language skills between bilinguals and their Polish non-migrant monolingual peers, and then investigated the influence of the cumulative exposure to L1 and L2 on bilinguals’ performance. We then examined whether high exposure to L1 could possibly minimize the gap between monolinguals and bilinguals. We analyzed data from 233 typically developing children (88 bilingual and 145 monolingual) aged 4;0 to 7;5 (years;months) on six language measures in Polish: receptive vocabulary, productive vocabulary, receptive grammar, productive grammar (sentence repetition), phonological processing (non-word repetition), and discourse abilities (narration). Information about language exposure was obtained via parental questionnaires. For each language task, we analyzed the data from the subsample of bilinguals who had completed all the tasks in question and from monolinguals matched one-on-one to the bilingual group on age, SES (measured by years of mother’s education), gender, non-verbal IQ, and short-term memory. The bilingual children scored lower than monolinguals in all language domains, except discourse. The group differences were more pronounced on the productive tasks (vocabulary, grammar, and phonological processing) and moderate on the receptive tasks (vocabulary and grammar). L1 exposure correlated positively with the vocabulary size and phonological processing. Grammar scores were not related to the levels of L1 exposure, but were predicted by general cognitive abilities. L2 exposure negatively influenced productive grammar in L1, suggesting possible L2 transfer effects on L1 grammatical performance. Children’s narrative skills benefitted from exposure to two languages: both L1

  5. L1 and L2 Word Recognotion in Finnish. Examining L1 Effects on L2 Processing of Morphological Complexity and Morphophonological Transparency

    ERIC Educational Resources Information Center

    Vainio, Seppo; Anneli, Pajunen; Hyona, Jukka

    2014-01-01

    This study investigated the effect of the first language (L1) on the visual word recognition of inflected nouns in second language (L2) Finnish by native Russian and Chinese speakers. Case inflection is common in Russian and in Finnish but nonexistent in Chinese. Several models have been posited to describe L2 morphological processing. The unified…

  6. Orbit Determination Accuracy for Comets on Earth-Impacting Trajectories

    NASA Technical Reports Server (NTRS)

    Kay-Bunnell, Linda

    2004-01-01

    The results presented show the level of orbit determination accuracy obtainable for long-period comets discovered approximately one year before collision with Earth. Preliminary orbits are determined from simulated observations using Gauss' method. Additional measurements are incorporated to improve the solution through the use of a Kalman filter, and include non-gravitational perturbations due to outgassing. Comparisons between observatories in several different circular heliocentric orbits show that observatories in orbits with radii less than 1 AU result in increased orbit determination accuracy for short tracking durations due to increased parallax per unit time. However, an observatory at 1 AU will perform similarly if the tracking duration is increased, and accuracy is significantly improved if additional observatories are positioned at the Sun-Earth Lagrange points L3, L4, or L5. A single observatory at 1 AU capable of both optical and range measurements yields the highest orbit determination accuracy in the shortest amount of time when compared to other systems of observatories.

  7. On the Effects of L2 on Iranian Bilinguals' L1 Writing Ability

    ERIC Educational Resources Information Center

    Agheshteh, Hessam

    2015-01-01

    While the effects of L1 on L2 have been extensively investigated, the effects of L2 on L1 have been largely ignored. The present study attempted to address this issue by investigating the effects of L2 English on Iranian Bilinguals' L1 writing ability. For this end, 61 participants, 30 bilinguals and 31 monolinguals, were assessed on an…

  8. [Eukaryotic expression of Leptospira interrogans lipL32/1-ompL1/1 fusion gene encoding genus-specific protein antigens and the immunoreactivity of expression products].

    PubMed

    Yan, Jie; Zhao, Shou-feng; Mao, Ya-fei; Ruan, Ping; Luo, Yi-hui; Li, Shu-ping; Li, Li-wei

    2005-01-01

    To construct the eukaryotic expression system of L.interrogans lipL32/1-ompL1/1 fusion gene and to identify the immunoreactivity of expression products. PCR with linking primer was used to construct the fusion gene lipL32/1-ompL1/1. The P.pastoris eukaryotic expression system of the fusion gene, pPIC9K-lipL32/1-ompL1/1-P. pastorisGS115, was constructed after the fusion gene was cloned and sequenced. Colony with phenotype His(+)Mut(+) was isolated by using MD and MM plates and His(+) Mut(+) transformant with high resistance to G418 was screened out by using YPD plate. Using lysate of His(+) Mut(+) colony with high copies of the target gene digested with yeast lyase as the template and 5'AOX1 and 3'AOX1 as the primers, the target fusion gene in chromosome DNA of the constructed P. pastoris engineering strain was detected by PCR. Methanol in BMMY medium was used to induce the target recombinant protein rLipL32/1-rOmpL1/1 expression. rLipL32/1-rOmpL1/1 in the medium supernatant was extracted by using ammonium sulfate precipitation and Ni-NTA affinity chromatography. Output and immunoreactivity of rLipL32/1-rOmpL1/1 were measured by SDS-PAGE and Western blot methods, respectively. Amplification fragments of the obtained fusion gene lipL32/1-ompL1/1 was 1794 bp in size. The homogeneity of nucleotide and putative amino acid sequences of the fusion gene were as high as 99.94 % and 100 %, respectively, compared with the sequences of original lipL32/1 and ompL1/1 genotypes. The constructed eukaryotic expression system was able to secrete rLipL32/1-rOmpL1/1 with an output of 10 % of the total proteins in the supernatant, which located the expected position after SDS-PAGE. The rabbit anti-rLipL32/1 and anti-rOmpL1/1 sera could combine the expressed rLipL32/1-rOmpL1/1. An eukaryotic expression system with high efficiency in P.pastoris of L.interrogans lipL32/1-ompL1/1 fusion gene was successfully constructed in this study. The expressed fusion protein shows specific

  9. A low diffusive Lagrange-remap scheme for the simulation of violent air-water free-surface flows

    NASA Astrophysics Data System (ADS)

    Bernard-Champmartin, Aude; De Vuyst, Florian

    2014-10-01

    In 2002, Després and Lagoutière [17] proposed a low-diffusive advection scheme for pure transport equation problems, which is particularly accurate for step-shaped solutions, and thus suited for interface tracking procedure by a color function. This has been extended by Kokh and Lagoutière [28] in the context of compressible multifluid flows using a five-equation model. In this paper, we explore a simplified variant approach for gas-liquid three-equation models. The Eulerian numerical scheme has two ingredients: a robust remapped Lagrange solver for the solution of the volume-averaged equations, and a low diffusive compressive scheme for the advection of the gas mass fraction. Numerical experiments show the performance of the computational approach on various flow reference problems: dam break, sloshing of a tank filled with water, water-water impact and finally a case of Rayleigh-Taylor instability. One of the advantages of the present interface capturing solver is its natural implementation on parallel processors or computers.

  10. Eddy interaction model for turbulent suspension in Reynolds-averaged Euler-Lagrange simulations of steady sheet flow

    NASA Astrophysics Data System (ADS)

    Cheng, Zhen; Chauchat, Julien; Hsu, Tian-Jian; Calantoni, Joseph

    2018-01-01

    A Reynolds-averaged Euler-Lagrange sediment transport model (CFDEM-EIM) was developed for steady sheet flow, where the inter-granular interactions were resolved and the flow turbulence was modeled with a low Reynolds number corrected k - ω turbulence closure modified for two-phase flows. To model the effect of turbulence on the sediment suspension, the interaction between the turbulent eddies and particles was simulated with an eddy interaction model (EIM). The EIM was first calibrated with measurements from dilute suspension experiments. We demonstrated that the eddy-interaction model was able to reproduce the well-known Rouse profile for suspended sediment concentration. The model results were found to be sensitive to the choice of the coefficient, C0, associated with the turbulence-sediment interaction time. A value C0 = 3 was suggested to match the measured concentration in the dilute suspension. The calibrated CFDEM-EIM was used to model a steady sheet flow experiment of lightweight coarse particles and yielded reasonable agreements with measured velocity, concentration and turbulence kinetic energy profiles. Further numerical experiments for sheet flow suggested that when C0 was decreased to C0 < 3, the simulation under-predicted the amount of suspended sediment in the dilute region and the Schmidt number is over-predicted (Sc > 1.0). Additional simulations for a range of Shields parameters between 0.3 and 1.2 confirmed that CFDEM-EIM was capable of predicting sediment transport rates similar to empirical formulations. Based on the analysis of sediment transport rate and transport layer thickness, the EIM and the resulting suspended load were shown to be important when the fall parameter is less than 1.25.

  11. Shear-wave seismic reflection imaging and impedance inversion for a near-surface point-bar

    NASA Astrophysics Data System (ADS)

    Benton, N. W.; Morrison, M.; Lorenzo, J. M.; Odom, B.; Clift, P. D.; Olson, E.; Gostic, A.

    2017-12-01

    Imaging and inversion of SH-waves are useful to detect, map, and quantitatively characterize near-surface point-bar strata. We conduct a horizontally-polarized (SH) reflection survey across and along a near-surface (9 - 40 m) downstream point-bar. We invert for shear-impedance profiles and correlate our interpretation to electrical conductivity (EC) logs in adjacent wells to study the internal architecture and lithology of point-bars. We acquire two common-midpoint (CMP) SH-wave seismic reflection lines at False River (Point Coupee Parish, Louisiana). A 104 m long seismic line (L1) is oriented orthogonal (NW - SE) to point-bar strike. A second line (L2) is 48 m long and set parallel to point-bar strike (NE - SW). Two EC wells lie 33 m apart. Both wells are parallel with respect to the L1 survey and offset from it by 15 m. EC log measurements range from 1 - 25 m depth. Interference of Love-waves prevents seismic imaging at depths less than 9 m. The L1 and L2 data sets are inverted for shear-impedance using a model-based band-limited impedance (BLIMP) algorithm that incorporates a low-frequency velocity model. This model is also used for the depthing processing. The L1 cross-section shows coherent dipping reflection events ( 4 - 7º) from 0.15 - 0.35 s (10 - 40 m). The corresponding shear-impedance profile also reveals coherent and dipping impedance contrasts that grow in magnitude with increasing depth. The L2 cross-section shows comparatively less dip ( 1º) as well as sharper and shallower continuity of reflection events (0.1 - 0.28 s TWT or 9 - 25 m). Depth-converted (TVD) seismic amplitudes and impedance values correlate to near-surface point-bar geology via superposition of log data. The first well (W5) shows distinct EC local maxima (+50 - 70 mS/m) at 14.5 and 15.5 m depth that correlate well with the seismic amplitudes and impedance values from both L1 and L2 data sets. The second well (W7) shows comparatively lower local maxima (+40 - 60 mS/m) but at greater

  12. Phosphorylation of ORF1p is required for L1 retrotransposition.

    PubMed

    Cook, Pamela R; Jones, Charles E; Furano, Anthony V

    2015-04-07

    Although members of the L1 (LINE-1) clade of non-LTR retrotransposons can be deleterious, the L1 clade has remained active in most mammals for ∼100 million years and generated almost 40% of the human genome. The details of L1-host interaction are largely unknown, however. Here we report that L1 activity requires phosphorylation of the protein encoded by the L1 ORF1 (ORF1p). Critical phospho-acceptor residues (two serines and two threonines) reside in four conserved proline-directed protein kinase (PDPK) target sites. The PDPK family includes mitogen-activated protein kinases and cyclin-dependent kinases. Mutation of any PDPK phospho-acceptor inhibits L1 retrotransposition. The phosphomimetic aspartic acid can restore activity at the two serine sites, but not at either threonine site, where it is strongly inhibitory. ORF1p also contains conserved PDPK docking sites, which promote specific interaction of PDPKs with their targets. As expected, mutations in these sites also inhibit L1 activity. PDPK mutations in ORF1p that inactivate L1 have no significant effect on the ability of ORF1p to anneal RNA in vitro, an important biochemical property of the protein. We show that phosphorylated PDPK sites in ORF1p are required for an interaction with the peptidyl prolyl isomerase 1 (Pin1), a critical component of PDPK-mediated regulation. Pin1 acts via isomerization of proline side chains at phosphorylated PDPK motifs, thereby affecting substrate conformation and activity. Our demonstration that L1 activity is dependent on and integrated with cellular phosphorylation regulatory cascades significantly increases our understanding of interactions between L1 and its host.

  13. Monitoring solar irradiance from L2 with Gaia

    NASA Astrophysics Data System (ADS)

    Serpell, E.

    2017-09-01

    Gaia is the European Space Agency's cornerstone astrometry mission to measure the positions of a billion stars in the Milky Way with unprecedented accuracy. Since early 2014 Gaia has been operating in a halo orbit around the second Sun-Earth Lagrange point that provides the stable thermal environment, without Earth eclipses, needed for the payload to function accurately. The spacecraft is equipped with a number of thermally isolated, sun-facing thermistors that provide a continuous measurement of the local equilibrium temperature. As a consequence of the spacecraft design and operational conditions these temperature measurements have been used to infer the solar output over a broad wavelength range. In this paper we present an analysis of temperature measurements made of the Gaia solar panels at frequencies of up to 1 Hz for the first 35 months of routine operations. We show that the Gaia solar panel temperature measurements are capable of precisely determining short term changes to the solar output at a level of better than 0.04% with time constants of a few minutes.

  14. A Study of Relationships between L1 Pragmatic Transfer and L2 Proficiency

    ERIC Educational Resources Information Center

    Bu, Jiemin

    2012-01-01

    Studies in interlanguage pragmatics have shown that L2 learners' proficiency has an influence on the occurrences of L1 pragmatic transfer. However, questions remain whether the relationship between L1 pragmatic transfer and L2 proficiency is positive or negative. This paper is designed to study L1 pragmatic transfer in requests made by Chinese…

  15. 1. PARKING LOT AT GLACIER POINT. HALF DOME AT CENTER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. PARKING LOT AT GLACIER POINT. HALF DOME AT CENTER REAR. LOOKING NE. GIS: N-36 43 45.8 / W-119 34 14.1 - Glacier Point Road, Between Chinquapin Flat & Glacier Point, Yosemite Village, Mariposa County, CA

  16. A note on libration point orbits, temporary capture and low-energy transfers

    NASA Astrophysics Data System (ADS)

    Fantino, E.; Gómez, G.; Masdemont, J. J.; Ren, Y.

    2010-11-01

    In the circular restricted three-body problem (CR3BP) the weak stability boundary (WSB) is defined as a boundary set in the phase space between stable and unstable motion relative to the second primary. At a given energy level, the boundaries of such region are provided by the stable manifolds of the central objects of the L1 and L2 libration points, i.e., the two planar Lyapunov orbits. Besides, the unstable manifolds of libration point orbits (LPOs) around L1 and L2 have been identified as responsible for the weak or temporary capture around the second primary of the system. These two issues suggest the existence of natural dynamical channels between the Earth's vicinity and the Sun-Earth libration points L1 and L2. Furthermore, it has been shown that the Sun-Earth L2 central unstable manifolds can be linked, through an heteroclinic connection, to the central stable manifolds of the L2 point in the Earth-Moon three-body problem. This concept has been applied to the design of low energy transfers (LETs) from the Earth to the Moon. In this contribution we consider all the above three issues, i.e., weak stability boundaries, temporary capture and low energy transfers, and we discuss the role played by the invariant manifolds of LPOs in each of them. The study is made in the planar approximation.

  17. Bilingual Lexical Access during L1 Sentence Reading: The Effects of L2 Knowledge, Semantic Constraint, and L1-L2 Intermixing

    ERIC Educational Resources Information Center

    Titone, Debra; Libben, Maya; Mercier, Julie; Whitford, Veronica; Pivneva, Irina

    2011-01-01

    Libben and Titone (2009) recently observed that cognate facilitation and interlingual homograph interference were attenuated by increased semantic constraint during bilingual second language (L2) reading, using eye movement measures. We now investigate whether cross-language activation also occurs during first language (L1) reading as a function…

  18. Reliability of the Lactate Scout point-of-care instrument for the determination of blood L-lactate concentration in sheep.

    PubMed

    Kaynar, Ozgur; Karapinar, Tolga; Hayirli, Armagan; Baydar, Ersoy

    2015-12-01

    Data on accuracy and precision of the Lactate Scout point-of-care (POC) analyzer in ovine medicine are lacking. The purpose of the study was to assess the reliability of the Lactate Scout in sheep. Fifty-seven sheep at varying ages with various diseases were included. Blood lactate concentration in samples collected from the jugular vein was measured immediately on the Lactate Scout. Plasma L-lactate concentration was measured by the Cobas autoanalyzer as the reference method. Data were subjected to Student's t-test, Passing-Bablok regression, and Bland-Altman plot analyses for comparison and assessment of accuracy, precision, and reliability. Plasma l-lactate concentration was consistently lower than blood L-lactate concentration (3.06 ± 0.24 vs 3.3 ± 0.3 mmol/L, P < .0001). There was a positive correlation between plasma and blood L-lactate concentrations (r = .98, P < .0001). The Lactate Scout had 99% accuracy and 98% precision with the reference method. Blood (Y) and plasma (X) L-lactate concentrations were fitted to Y = 0.28 + 1.00 · X, with a residual standard deviation of 0.31 and a negligible deviation from the identity line (P = .93). The bias was fitted to Y = 0.10 + 0.05 · X, with Sy.x of 0.44 (P < .07). The Lactate Scout has high accuracy and precision, with a negligible bias. It is a reliable POC analyzer to assess L-lactate concentration in ovine medicine. © 2015 American Society for Veterinary Clinical Pathology.

  19. The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/- -SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels.

    PubMed

    Leckngam, Prapapun; Limweeraprajak, Ektong; Kiewkarnkha, Tiemjan; Tatu, Thanusak

    2017-01-01

    Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- - SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - - SEA and -α 3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- - SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

  20. Multilingual Acquisition of Vowels in L1 Polish, L2 Danish and L3 English

    ERIC Educational Resources Information Center

    Sypianska, Jolanta

    2016-01-01

    The aim of this paper is to determine whether all languages in the linguistic repertoire of a multilingual speaker manifest cross-linguistic influence (CLI) and establish the directions of CLI on the basis of chosen vowels from the linguistic repertoire of two groups: the Bilingual group (L1 Polish/L2 Danish) and the Multilingual group (L1

  1. The Effects of L1 and L2 Group Discussions on L2 Reading Comprehension

    ERIC Educational Resources Information Center

    Turnbull, Blake; Evans, Moyra Sweetnam

    2017-01-01

    The aim of this study was to explore the effects of post-reading group discussions in both first (L1) and second (L2) languages on L2 reading comprehension. The participants were fifteen Japanese university students of intermediate-level English. Three cohorts read four English texts and produced individual written recalls. Group 1 (the control…

  2. Experimental/clinical evaluation of EIT image reconstruction with l1 data and image norms

    NASA Astrophysics Data System (ADS)

    Mamatjan, Yasin; Borsic, Andrea; Gürsoy, Doga; Adler, Andy

    2013-04-01

    Electrical impedance tomography (EIT) image reconstruction is ill-posed, and the spatial resolution of reconstructed images is low due to the diffuse propagation of current and limited number of independent measurements. Generally, image reconstruction is formulated using a regularized scheme in which l2 norms are preferred for both the data misfit and image prior terms due to computational convenience which result in smooth solutions. However, recent work on a Primal Dual-Interior Point Method (PDIPM) framework showed its effectiveness in dealing with the minimization problem. l1 norms on data and regularization terms in EIT image reconstruction address both problems of reconstruction with sharp edges and dealing with measurement errors. We aim for a clinical and experimental evaluation of the PDIPM method by selecting scenarios (human lung and dog breathing) with known electrode errors, which require a rigorous regularization and cause the failure of reconstructions with l2 norm. Results demonstrate the applicability of PDIPM algorithms, especially l1 data and regularization norms for clinical applications of EIT showing that l1 solution is not only more robust to measurement errors in clinical setting, but also provides high contrast resolution on organ boundaries.

  3. L1C signal design options

    USGS Publications Warehouse

    Betz, J.W.; Cahn, C.R.; Dafesh, P.A.; Hegarty, C.J.; Hudnut, K.W.; Jones, A.J.; Keegan, R.; Kovach, K.; Lenahan, L.S.; Ma, H.H.; Rushanan, J.J.; Stansell, T.A.; Wang, C.C.; Yi, S.K.

    2006-01-01

    Design activities for a new civil signal centered at 1575.42 MHz, called L1C, began in 2003, and the Phase 1 effort was completed in 2004. The L1C signal design has evolved and matured during a Phase 2 design activity that began in 2005. Phase 2 has built on the initial design activity, guided by responses to international user surveys conducted during Phase 1. A common core of signal characteristics has been developed to provide advances in robustness and performance. The Phase 2 activity produced five design options, all drawing upon the core signal characteristics, while representing different blends of characteristics and capabilities. A second round of international user surveys was completed to solicit advice concerning these design options. This paper provides an update of the L1C design process, and describes the current L1C design options. Initial performance estimates are presented for each design option, displaying trades between signal tracking robustness, the speed and robustness of clock and ephemeris data, and the rate and robustness of other data message contents. Planned remaining activities are summarized, leading to optimization of the L1C design.

  4. Revisiting Fluctuations in L2 Article Choice in L1-Korean L2-English Learners.

    PubMed

    Sarker, Bijon K; Baek, Seunghyun

    2017-04-01

    The current study investigated the distinction of L2 (second language) English article choice sensitivity in fifty-three L1-Korean L2-English learners in semantic contexts. In the context of English as a foreign language, the participants were divided into two groups based on grammatical ability as determined by their performance on a cloze test. In addition, a forced-choice elicitation test and a writing production test were administered to assess, respectively, the participants' receptive and productive article choice abilities. Regardless of grammatical ability, the results disclosed the overuse of the indefinite a in the [[Formula: see text]definite, -specific] context and the definite the in the [-definite, [Formula: see text]specific] context on the forced-choice elicitation test. In the [[Formula: see text]definite, [Formula: see text]specific] and [-definite, -specific] contexts, however, the overuse of either the indefinite a or the definite the, respectively, was less likely. Furthermore, it was revealed on the writing test that the participants more accurately used the definite the than the indefinite a, and they were also found to unreasonably omit more articles than to add or substitute articles on the writing production test. The findings across the two tests indicate that L1-Korean L2-English learners are more likely to have intrinsic difficulties transferring their L1 noun phrase (NP) knowledge to L2 NP knowledge owing to structural discrepancies and complex interfaces between L1 NPs and L2 NPs with respect to syntactic, semantic and pragmatic/discourse language subsystems.

  5. PD-L1 expression in extrahepatic cholangiocarcinoma.

    PubMed

    Walter, Dirk; Herrmann, Eva; Schnitzbauer, Andreas A; Zeuzem, Stefan; Hansmann, Martin Leo; Peveling-Oberhag, Jan; Hartmann, Sylvia

    2017-09-01

    To investigate the expression of the programmed cell death 1 (PD-1) receptor-programmed cell death ligand 1 (PD-L1) pathway and the clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). Tissue samples from patients with eCCA [n = 69; perihilar cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression, and correlations with clinicopathological characteristics, including survival data, were determined. PD-L1 was found on both tumour cells of eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant correlations of PD-L1 expression on cancer cells with venous invasion (P = 0.031) and poor differentiation of the tumour (P = 0.048) were observed. In 19 of 69 (27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas infiltration with CD3-positive and CD163-positive cells was found in 63 of 69 (91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five CD3-positive cells per high-power field was significantly correlated with poorer differentiation (P = 0.015) and venous invasion (P < 0.001) of CCA. PD-L1 expression was not correlated with patient survival, but PD-L1 expression on tumour cells combined with low infiltration of CD3-positive TILs was associated with an unfavourable outcome (P = 0.027). Only a small number of eCCA patients are PD-L1-positive, which might be important for future application of PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more invasive growth and worse overall survival. © 2017 John Wiley & Sons Ltd.

  6. Mapping the cosmos

    NASA Astrophysics Data System (ADS)

    Clery, Daniel

    2009-04-01

    For the last seven years, NASA's Wilkinson Microwave Anisotropy Probe (WMAP) has kept a lonely vigil in an area in space some 1.5 million kilometres further out from the Sun beyond the Earth. Known as Lagrange point L2, it is where a space probe can usefully hover, little disturbed by stray signals from home and without having to use much fuel to keep it in position. But WMAP will soon have company: two groundbreaking missions from the European Space Agency (ESA), due to be launched on the same Ariane-5 rocket later this month, will take up their positions next to NASA's craft.

  7. Motions about a fixed point by hypergeometric functions: new non-complex analytical solutions and integration of the herpolhode

    NASA Astrophysics Data System (ADS)

    Mingari Scarpello, Giovanni; Ritelli, Daniele

    2018-06-01

    The present study highlights the dynamics of a body moving about a fixed point and provides analytical closed form solutions. Firstly, for the symmetrical heavy body, that is the Lagrange-Poisson case, we compute the second (precession, ψ ) and third (spin, φ) Euler angles in explicit and real form by means of multiple hypergeometric (Lauricella) functions. Secondly, releasing the weight assumption but adding the complication of the asymmetry, by means of elliptic integrals of third kind, we provide the precession angle ψ completing the treatment of the Euler-Poinsot case. Thirdly, by integrating the relevant differential equation, we reach the finite polar equation of a special motion trajectory named the herpolhode. Finally, we keep the symmetry of the first problem, but without weight, and take into account a viscous dissipation. The use of motion first integrals—adopted for the first two problems—is no longer practicable in this situation; therefore, the Euler equations, faced directly, are driving to particular occurrences of Bessel functions of order - 1/2.

  8. L-rhamnose induces browning in 3T3-L1 white adipocytes and activates HIB1B brown adipocytes.

    PubMed

    Choi, Minji; Mukherjee, Sulagna; Kang, Nam Hyeon; Barkat, Jameel Lone; Parray, Hilal Ahmad; Yun, Jong Won

    2018-06-01

    Induction of the brown adipocyte-like phenotype in white adipocytes (browning) is considered as a novel strategy to fight obesity due to the ability of brown adipocytes to increase energy expenditure. Here, we report that L-rhamnose induced browning by elevating expression levels of beige-specific marker genes, including Cd137, Cited1, Tbx1, Prdm16, Tmem26, and Ucp1, in 3T3-L1 adipocytes. Moreover, L-rhamnose markedly elevated expression levels of proteins involved in thermogenesis both in 3T3-L1 white and HIB1B brown adipocytes. L-rhamnose treatment in 3T3-L1 adipocytes also significantly elevated protein levels of p-HSL, p-AMPK, ACOX, and CPT1 as well as reduced levels of ACC, FAS, C/EBPα, and PPARγ, suggesting its possible role in enhancement of lipolysis and lipid catabolism as well as reduced adipogenesis and lipogenesis, respectively. The quick technique of efficient molecular docking provided insight into the strong binding of L-rhamnose to the fat-digesting glycine residue of β 3 -adrenergic receptor (AR), indicating strong involvement of L-rhamnose in fat metabolism. Further examination of the molecular mechanism of L-rhamnose revealed that it induced browning of 3T3-L1 adipocytes via coordination of multiple signaling pathways through β 3 -AR, SIRT1, PKA, and p-38. To the best of our knowledge, this is the first study to demonstrate that L-rhamnose plays multiple modulatory roles in the induction of white fat browning, activation of brown adipocytes, as well as promotion of lipid metabolism, thereby demonstrating its therapeutic potential for treatment of obesity. © 2018 IUBMB Life, 70(6):563-573, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  9. Metacognitive Online Reading Strategy Use: Readers' Perceptions in L1 and L2

    ERIC Educational Resources Information Center

    Taki, Saeed

    2016-01-01

    This study aimed to explore whether first-language (L1) readers of different language backgrounds would employ similar metacognitive online reading strategies and whether reading online in a second language (L2) could be influenced by L1 reading strategies. To this end, 52 Canadian college students as English L1 readers and 38 Iranian university…

  10. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

    PubMed

    Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

    2018-02-01

    Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy. Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This

  11. Point-point and point-line moving-window correlation spectroscopy and its applications

    NASA Astrophysics Data System (ADS)

    Zhou, Qun; Sun, Suqin; Zhan, Daqi; Yu, Zhiwu

    2008-07-01

    In this paper, we present a new extension of generalized two-dimensional (2D) correlation spectroscopy. Two new algorithms, namely point-point (P-P) correlation and point-line (P-L) correlation, have been introduced to do the moving-window 2D correlation (MW2D) analysis. The new method has been applied to a spectral model consisting of two different processes. The results indicate that P-P correlation spectroscopy can unveil the details and re-constitute the entire process, whilst the P-L can provide general feature of the concerned processes. Phase transition behavior of dimyristoylphosphotidylethanolamine (DMPE) has been studied using MW2D correlation spectroscopy. The newly proposed method verifies that the phase transition temperature is 56 °C, same as the result got from a differential scanning calorimeter. To illustrate the new method further, a lysine and lactose mixture has been studied under thermo perturbation. Using the P-P MW2D, the Maillard reaction of the mixture was clearly monitored, which has been very difficult using conventional display of FTIR spectra.

  12. Genetics Home Reference: L1 syndrome

    MedlinePlus

    ... X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases. Acta Neuropathol. 2013 Sep; ... F. Three cases with L1 syndrome and two novel mutations in the L1CAM gene. Eur J Pediatr. ...

  13. L1 Epithelioid Hemangioma.

    PubMed

    Davis, Joel D; Koppenhaver, Shane

    2017-05-01

    A 24-year-old male soldier on limited-duty status was referred to physical therapy by his primary care physician for a 2-year history of insidious-onset and slowly progressive low back pain. Lumbar radiographs were noncontributory. Shortly after initiating rehabilitation, the patient underwent magnetic resonance imaging that was previously ordered by his primary care physician. Radiology identified a complex mass and cortical fracturing within the L1 vertebral body, and subsequent computed tomography imaging demonstrated mixed sclerotic and lytic foci at L1. Biopsy later confirmed an epithelioid hemangioma. J Orthop Sports Phys Ther 2017;47(5):367. doi:10.2519/jospt.2017.6689.

  14. Transition from the mechanics of material points to the mechanics of structured particles

    NASA Astrophysics Data System (ADS)

    Somsikov, V. M.

    2016-01-01

    In this paper, necessity of creation of mechanics of structured particles is discussed. The way to create this mechanics within the laws of classical mechanics with the use of energy equation is shown. The occurrence of breaking of time symmetry within the mechanics of structured particles is shown, as well as the introduction of concept of entropy in the framework of classical mechanics. The way to create the mechanics of non-equilibrium systems in the thermodynamic approach is shown. It is also shown that the use of hypothesis of holonomic constraints while deriving the canonical Lagrange equation made it impossible to describe irreversible dynamics. The difference between the mechanics of structured particles and the mechanics of material points is discussed. It is also shown that the matter is infinitely divisible according to the laws of classical mechanics.

  15. The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

    PubMed Central

    Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

    2013-01-01

    Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

  16. L1 and L2 Spoken Word Processing: Evidence from Divided Attention Paradigm.

    PubMed

    Shafiee Nahrkhalaji, Saeedeh; Lotfi, Ahmad Reza; Koosha, Mansour

    2016-10-01

    The present study aims to reveal some facts concerning first language (L 1 ) and second language (L 2 ) spoken-word processing in unbalanced proficient bilinguals using behavioral measures. The intention here is to examine the effects of auditory repetition word priming and semantic priming in first and second languages of these bilinguals. The other goal is to explore the effects of attention manipulation on implicit retrieval of perceptual and conceptual properties of spoken L 1 and L 2 words. In so doing, the participants performed auditory word priming and semantic priming as memory tests in their L 1 and L 2 . In a half of the trials of each experiment, they carried out the memory test while simultaneously performing a secondary task in visual modality. The results revealed that effects of auditory word priming and semantic priming were present when participants processed L 1 and L 2 words in full attention condition. Attention manipulation could reduce priming magnitude in both experiments in L 2 . Moreover, L 2 word retrieval increases the reaction times and reduces accuracy on the simultaneous secondary task to protect its own accuracy and speed.

  17. Town Hall Meeting Presentation

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2002-01-01

    The James Webb Space Telescope (JWST), formerly known as the Next Generation Space Telescope (NGST), will be the successor to the Hubble Space Telescope. It will carry 3 instruments to a deep space orbit around the Sun-Earth Lagrange point L2, and will cover the wavelength range from 0.6 to 28 microns. The design concepts and current status of the project will be summarized, including the telescope and observatory contract proposed by the new prime contractor, TRW.

  18. 1. SOUTH FRONT OF TURBINE BUILDING BUILDING L1 (LEFT) AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. SOUTH FRONT OF TURBINE BUILDING BUILDING L1 (LEFT) AND OF L.P. BOILER ROOM BUILDING L2 (RIGHT) - Portland General Electric Company, Turbine Building, 1841 Southeast Water Street, Portland, Multnomah County, OR

  19. Numerical and In Vitro Experimental Investigation of the Hemolytic Performance at the Off-Design Point of an Axial Ventricular Assist Pump.

    PubMed

    Liu, Guang-Mao; Jin, Dong-Hai; Jiang, Xi-Hang; Zhou, Jian-Ye; Zhang, Yan; Chen, Hai-Bo; Hu, Sheng-Shou; Gui, Xing-Min

    The ventricular assist pumps do not always function at the design point; instead, these pumps may operate at unfavorable off-design points. For example, the axial ventricular assist pump FW-2, in which the design point is 5 L/min flow rate against 100 mm Hg pressure increase at 8,000 rpm, sometimes works at off-design flow rates of 1 to 4 L/min. The hemolytic performance of the FW-2 at both the design point and at off-design points was estimated numerically and tested in vitro. Flow characteristics in the pump were numerically simulated and analyzed with special attention paid to the scalar sheer stress and exposure time. An in vitro hemolysis test was conducted to verify the numerical results. The simulation results showed that the scalar shear stress in the rotor region at the 1 L/min off-design point was 70% greater than at the 5 L/min design point. The hemolysis index at the 1 L/min off-design point was 3.6 times greater than at the 5 L/min design point. The in vitro results showed that the normalized index of hemolysis increased from 0.017 g/100 L at the 5 L/min design point to 0.162 g/100 L at the 1 L/min off-design point. The hemolysis comparison between the different blood pump flow rates will be helpful for future pump design point selection and will guide the usage of ventricular assist pumps. The hemolytic performance of the blood pump at the working point in the clinic should receive more focus.

  20. The Influence of Schema and Cultural Difference on L1 and L2 Reading

    ERIC Educational Resources Information Center

    Yang, Shi-sheng

    2010-01-01

    Reading in L1 shares numerous basic elements with reading in L2, and the processes also differ greatly. Intriguing questions involve whether there are two parallel cognitive processes at work, or whether there are processing strategies that accommodate both L1 and L2. This paper examines how reading in L1 is different from and similar to reading…

  1. Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

    PubMed

    Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

    2018-03-27

    Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

  2. L1 Use in the L2 Classroom: One Teacher's Self-Evaluation

    ERIC Educational Resources Information Center

    Edstrom, Anne

    2006-01-01

    Predominant, if not exclusive, use of the target language has long been considered an important principle of second language (L2) instruction. Previous research has attempted to quantify the amount of the first language (L1) used in the classroom and has explored the purposes or functions of teachers' "lapses" into their students' L1. The present…

  3. A Small Mission Concept to the Sun-Earth Lagrangian L5 Point for Innovative Solar, Heliospheric and Space Weather Science

    NASA Technical Reports Server (NTRS)

    Lavraud, B.; Liu, Y.; Segura, K.; He, J.; Qin, G.; Temmer, M.; Vial, J.-C.; Xiong, M.; Davies, J. A.; Rouillard, A. P.; hide

    2016-01-01

    We present a concept for a small mission to the Sun-Earth Lagrangian L5 point for innovative solar, heliospheric and space weather science. The proposed INvestigation of Solar-Terrestrial Activity aNd Transients (INSTANT) mission is designed to identify how solar coronal magnetic fields drive eruptions, mass transport and particle acceleration that impact the Earth and the heliosphere. INSTANT is the first mission designed to (1) obtain measurements of coronal magnetic fields from space and (2) determine coronal mass ejection (CME) kinematics with unparalleled accuracy. Thanks to innovative instrumentation at a vantage point that provides the most suitable perspective view of the Sun-Earth system, INSTANT would uniquely track the whole chain of fundamental processes driving space weather at Earth. We present the science requirements, payload and mission profile that fulfill ambitious science objectives within small mission programmatic boundary conditions.

  4. A small mission concept to the Sun-Earth Lagrangian L5 point for innovative solar, heliospheric and space weather science

    NASA Astrophysics Data System (ADS)

    Lavraud, B.; Liu, Y.; Segura, K.; He, J.; Qin, G.; Temmer, M.; Vial, J.-C.; Xiong, M.; Davies, J. A.; Rouillard, A. P.; Pinto, R.; Auchère, F.; Harrison, R. A.; Eyles, C.; Gan, W.; Lamy, P.; Xia, L.; Eastwood, J. P.; Kong, L.; Wang, J.; Wimmer-Schweingruber, R. F.; Zhang, S.; Zong, Q.; Soucek, J.; An, J.; Prech, L.; Zhang, A.; Rochus, P.; Bothmer, V.; Janvier, M.; Maksimovic, M.; Escoubet, C. P.; Kilpua, E. K. J.; Tappin, J.; Vainio, R.; Poedts, S.; Dunlop, M. W.; Savani, N.; Gopalswamy, N.; Bale, S. D.; Li, G.; Howard, T.; DeForest, C.; Webb, D.; Lugaz, N.; Fuselier, S. A.; Dalmasse, K.; Tallineau, J.; Vranken, D.; Fernández, J. G.

    2016-08-01

    We present a concept for a small mission to the Sun-Earth Lagrangian L5 point for innovative solar, heliospheric and space weather science. The proposed INvestigation of Solar-Terrestrial Activity aNd Transients (INSTANT) mission is designed to identify how solar coronal magnetic fields drive eruptions, mass transport and particle acceleration that impact the Earth and the heliosphere. INSTANT is the first mission designed to (1) obtain measurements of coronal magnetic fields from space and (2) determine coronal mass ejection (CME) kinematics with unparalleled accuracy. Thanks to innovative instrumentation at a vantage point that provides the most suitable perspective view of the Sun-Earth system, INSTANT would uniquely track the whole chain of fundamental processes driving space weather at Earth. We present the science requirements, payload and mission profile that fulfill ambitious science objectives within small mission programmatic boundary conditions.

  5. Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules.

    PubMed

    Holm, J; Hillenbrand, R; Steuber, V; Bartsch, U; Moos, M; Lübbert, H; Montag, D; Schachner, M

    1996-08-01

    We have identified a close homologue of L1 (CHL1) in the mouse. CHL1 comprises an N-terminal signal sequence, six immunoglobulin (Ig)-like domains, 4.5 fibronectin type III (FN)-like repeats, a transmembrane domain and a C-terminal, most likely intracellular domain of approximately 100 amino acids. CHL1 is most similar in its extracellular domain to chicken Ng-CAM (approximately 40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr-CAM, Drosophila neuroglian and zebrafish L1.1 (37-28% amino acid identity), and mouse F3, rat TAG-1 and rat BIG-1 (approximately 27% amino acid identity). The similarity with other members of the Ig superfamily [e.g. neural cell adhesion molecule (N-CAM), DCC, HLAR, rse] is 16-11%. The intracellular domain is most similar to mouse and chicken Nr-CAM, mouse and rat neurofascin (approximately 60% amino acid identity) followed by chicken neurofascin and Ng-CAM, Drosophila neuroglian and zebrafish L1.1 and L1.2 (approximately 40% amino acid identity). Besides the high overall homology and conserved modular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng-CAM; chicken/mouse Nr-CAM; Drosophila neuroglian; zebrafish L1.1 and L1.2; chicken/mouse neurofascin/rat ankyrin-binding glycoprotein), criteria characteristic of L1 were identified with regard to the number of amino acids between positions of conserved amino acid residues defining distances within and between two adjacent Ig-like domains and FN-like repeats. These show a collinearity in the six Ig-like domains and four adjacent FN-like repeats that is remarkably conserved between L1 and molecules containing these modules (designated the L1 family cassette), including the GPI-linked forms of the F3 subgroup (mouse F3/chicken F11/human CNTN1; rat BIG-1/mouse PANG; rat TAG-1/mouse TAX-1/chicken axonin-1). The colorectal cancer molecule (DCC), previously introduced as an N-CAM-like molecule, conforms to the L1 family

  6. L-glutamine is a key parameter in the immunosuppression phenomenon

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

    Hammami, Ines; Chen, Jingkui; Bronte, Vincenzo

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer The absence of L-Gln inhibited iNOS activity, but not ARG1 one. Black-Right-Pointing-Pointer MSC-1 cells were able to inhibit Jurkat cell growth, but not their viability. Black-Right-Pointing-Pointer Absence of L-Gln down-regulated central carbon metabolism and L-Arg recycling. Black-Right-Pointing-Pointer Absence of L-Gln deteriorated cell bioenergetic status. Black-Right-Pointing-Pointer L-Gln is crucial for iNOS-mediated immunosuppression activity. -- Abstract: Suppression of tumour-specific T-cell functions by myeloid-derived suppressor cells (MDSCs) is a dominant mechanism of tumour escape. MDSCs express two enzymes, i.e. inducible nitric oxide synthase (iNOS) and arginase (ARG1), which metabolize the semi-essential amino acid L-arginine (L-Arg) whose bioavailability is crucial for T-cellmore » proliferation and functions. Recently, we showed that glutaminolysis supports MDSC maturation process by ensuring the supply of intermediates and energy. In this work, we used an immortalized cell line derived from mouse MDSCs (MSC-1 cell line) to further investigate the role of L-glutamine (L-Gln) in the maintenance of MDSC immunosuppressive activity. Culturing MSC-1 cells in L-Gln-limited medium inhibited iNOS activity, while ARG1 was not affected. MSC-1 cells inhibited Jukat cell growth without any noticeable effect on their viability. The characterization of MSC-1 cell metabolic profile revealed that L-Gln is an important precursor of lactate production via the NADP{sup +}-dependent malic enzyme, which co-produces NADPH. Moreover, the TCA cycle activity was down-regulated in the absence of L-Gln and the cell bioenergetic status was deteriorated accordingly. This strongly suggests that iNOS activity, but not that of ARG1, is related to an enhanced central carbon metabolism and a high bioenergetic status. Taken altogether, our results suggest that the control of glutaminolysis fluxes may represent a valuable target for

  7. THE INTERACTION BETWEEN L1-TYPE PROTEINS AND ANKYRINS - A MASTER SWITCH FOR L1-TYPE CAM FUNCTION #

    PubMed Central

    HORTSCH, MICHAEL; NAGARAJ, KAKANAHALLI; GODENSCHWEGE, TANJA A.

    2008-01-01

    L1-type cell adhesion molecules (CAMs) are important mediators of neural differentiation, including axonal outgrowth and pathfinding and also of synapse formation and maintenance. In addition, their interactions with cytoskeletal components are highly conserved and regulated. How these different aspects of CAM functionality relate to each other is not well understood. Based on results from our and other laboratories we propose that Ankyrin-binding to L1-type CAMs provides a master switch. The interaction with Ankyrins directs L1-type adhesive proteins into different functional contexts, either Ankyrin-independent functions, such as neurite outgrowth and axonal pathfinding or into Ankyrin-dependent functions, such as L1’s role at axon initial segments (AIS), paranodal regions, synapses and in dendrites. PMID:18839070

  8. Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB.

    PubMed

    Guo, Yun-Yun; Lu, Yi; Zheng, Yuan; Chen, Xiao-Rong; Dong, Jun-Lu; Yuan, Rong-Rong; Huang, Shu-Hong; Yu, Hui; Wang, Yue; Chen, Zhe-Yu; Su, Bo

    2017-06-21

    Multiple studies have established that brain-derived neurotrophic factor (BDNF) plays a critical role in the regulation of synaptic plasticity via its receptor, TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological functions remain poorly understood. In this study, we demonstrate that ubiquitin C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning learning and memory via the regulation of ubiquitination of TrkB. We provide evidence that UCH-L1 can deubiquitinate TrkB directly. K460 in the juxtamembane domain of TrkB is the primary ubiquitination site and is regulated by UCH-L1. By using a peptide that competitively inhibits the association between UCH-L1 and TrkB, we show that the blockade of UCH-L1-regulated TrkB deubiquitination leads to increased BDNF-induced TrkB internalization and consequently directs the internalized TrkB to the degradation pathway, resulting in increased degradation of surface TrkB and attenuation of TrkB activation and its downstream signaling pathways. Moreover, injection of the peptide into the DG region of mice impairs hippocampus-dependent memory. Together, our results suggest that the ubiquitination of TrkB is a mechanism that controls its downstream signaling pathways via the regulation of its endocytosis and postendocytic trafficking and that UCH-L1 mediates the deubiquitination of TrkB and could be a potential target for the modulation of hippocampus-dependent memory. SIGNIFICANCE STATEMENT Ubiquitin C-terminal hydrolase L1 (UCH-L1) has been demonstrated to play important roles in the regulation of synaptic plasticity and learning and memory. TrkB, the receptor for brain-derived neurotrophic factor, has also been shown to be a potent regulator of synaptic plasticity. In this study, we demonstrate that UCH-L1 functions as a deubiquitinase for TrkB. The blockage of UCH-L1-regulated deubiquitination of Trk

  9. Do Low Serum UCH-L1 and TDP-43 Levels Indicate Disturbed Ubiquitin-Proteosome System in Autism Spectrum Disorder?

    PubMed Central

    ÇETİN, İhsan; TEZDİĞ, İhsan; TARAKÇIOĞLU, Mahmut Cem; KADAK, Muhammed Tayyib; DEMİREL, Ömer Faruk; ÖZER, Ömer Faruk; ERDOĞAN, Fırat; DOĞANGÜN, Burak

    2017-01-01

    Introduction The mechanism of ubiquitination-related abnormalities causing neural development problems is still unclear. We examined the association between autism and serum transactive response DNA-binding protein-43 (TDP-43) and ubiquitin c-terminal hydrolase-L1 (UCH-L1) levels, both of which are members of the ubiquitin-proteosome system. Methods We measured serum levels of TDP-43 and UCH-L1 in 24 children with autism and 24 healthy children. Childhood Autism Rating Scale (CARS) was used to assess symptom severity at admission. Results The mean serum TDP-43 and UCH-L1 levels in children with autism spectrum disorder (ASD) were found to decrease compared to healthy controls (p<0.001, 506.21±780.97 ng/L and 1245.80±996.76 ng/L, respectively; 3.08±5.44 ng/mL and 8.64±6.67 ng/mL, respectively). A positive correlation between serum TDP-43 levels and UCH-L1 levels was found in the ASD group (r=0.947, n=24, p<0.001). The CARS score of children with ASD was 48.91 points (standard deviation [SD]: 5.82). Conclusion Low serum levels of UCH-L1 and TDP-43 may reflect disturbed ubiquitination in autism. PMID:29033641

  10. Lexical statistics of competition in L2 versus L1 listening

    NASA Astrophysics Data System (ADS)

    Cutler, Anne

    2005-09-01

    Spoken-word recognition involves multiple activation of alternative word candidates and competition between these alternatives. Phonemic confusions in L2 listening increase the number of potentially active words, thus slowing word recognition by adding competitors. This study used a 70,000-word English lexicon backed by frequency statistics from a 17,900,000-word corpus to assess the competition increase resulting from two representative phonemic confusions, one vocalic (ae/E) and one consonantal (r/l), in L2 versus L1 listening. The first analysis involved word embedding. Embedded words (cat in cattle, rib in ribbon) cause competition, which phonemic confusion can increase (cat in kettle, rib in liberty). The average increase in number of embedded words was 59.6 and 48.3 temporary ambiguity. Even when no embeddings are present, multiple alternatives are possible: para- can become parrot, paradise, etc., but also pallet, palace given /r/-/l/ confusion. Phoneme confusions (vowel or consonant) in first or second position in the word approximately doubled the number of activated candidates; confusions later in the word increased activation by on average 53 third, 42 confusions significantly increase competition for L2 compared with L1 listeners.

  11. L1 and L2 Strategy Use in Reading Comprehension of Chinese EFL Readers

    ERIC Educational Resources Information Center

    Tsai, Yea-Ru; Ernst, Cheryl; Talley, Paul C.

    2010-01-01

    This study revealed the relationship between L1 (Mandarin Chinese) and L2 (English) strategy use in L2 reading comprehension by focusing on the correlation of L1 reading ability, L2 proficiency and employed reading strategies. The participants, 222 undergraduates learning English as a foreign language (EFL), were classified into skilled and…

  12. Modelling of Dynamics of a Wheeled Mobile Robot with Mecanum Wheels with the use of Lagrange Equations of the Second Kind

    NASA Astrophysics Data System (ADS)

    Hendzel, Z.; Rykała, Ł.

    2017-02-01

    The work presents the dynamic equations of motion of a wheeled mobile robot with mecanum wheels derived with the use of Lagrange equations of the second kind. Mecanum wheels are a new type of wheels used in wheeled mobile robots and they consist of freely rotating rollers attached to the circumference of the wheels. In order to derive dynamic equations of motion of a wheeled mobile robot, the kinetic energy of the system is determined, as well as the generalised forces affecting the system. The resulting mathematical model of a wheeled mobile robot was generated with the use of Maple V software. The results of a solution of inverse and forward problems of dynamics of the discussed object are also published.

  13. PD-1/PD-L1 pathway inhibitors in advanced prostate cancer.

    PubMed

    Isaacsson Velho, Pedro; Antonarakis, Emmanuel S

    2018-05-01

    Pharmacological inhibition of immune checkpoint receptors or their ligands represents a transformative breakthrough in the management of multiple cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for the management of metastatic prostate cancer (PCa), the commonest non-cutaneous malignancy in men. Areas covered: We review our current understanding of the PD-1/PD-L1 pathway in cancer, the use of anti-PD-1/PD-L1 therapeutics in PCa, and potential subgroups of PCa patients who may derive the greatest benefit from these agents (such as men with tumors that have expression of PD-L1 and/or high mutational load). We also review the prior and current clinical trials evaluating the blockade of PD-1/PD-L1 in PCa, highlighting some of the key ongoing studies of greatest relevance to the field. Expert commentary: Clinical trials investigating PD-1/PD-L1 inhibitors should be encouraged in patients with PCa. While it is unlikely that immune checkpoint monotherapies will produce long-lasting responses in a substantial proportion of patients, there is early evidence of activity in some patient subsets. These subgroups may include those with high PD-L1 expression, those with hypermutated or microsatellite-unstable tumors, and those enriched for germline and/or somatic DNA-repair gene mutations (e.g. intraductal/ductal histology, primary Gleason pattern 5, and perhaps AR-V7-positive tumors).

  14. Per-point and per-field contextual classification of multipolarization and multiple incidence angle aircraft L-band radar data

    NASA Technical Reports Server (NTRS)

    Hoffer, Roger M.; Hussin, Yousif Ali

    1989-01-01

    Multipolarized aircraft L-band radar data are classified using two different image classification algorithms: (1) a per-point classifier, and (2) a contextual, or per-field, classifier. Due to the distinct variations in radar backscatter as a function of incidence angle, the data are stratified into three incidence-angle groupings, and training and test data are defined for each stratum. A low-pass digital mean filter with varied window size (i.e., 3x3, 5x5, and 7x7 pixels) is applied to the data prior to the classification. A predominately forested area in northern Florida was the study site. The results obtained by using these image classifiers are then presented and discussed.

  15. The Exact Solution to Rank-1 L1-Norm TUCKER2 Decomposition

    NASA Astrophysics Data System (ADS)

    Markopoulos, Panos P.; Chachlakis, Dimitris G.; Papalexakis, Evangelos E.

    2018-04-01

    We study rank-1 {L1-norm-based TUCKER2} (L1-TUCKER2) decomposition of 3-way tensors, treated as a collection of $N$ $D \\times M$ matrices that are to be jointly decomposed. Our contributions are as follows. i) We prove that the problem is equivalent to combinatorial optimization over $N$ antipodal-binary variables. ii) We derive the first two algorithms in the literature for its exact solution. The first algorithm has cost exponential in $N$; the second one has cost polynomial in $N$ (under a mild assumption). Our algorithms are accompanied by formal complexity analysis. iii) We conduct numerical studies to compare the performance of exact L1-TUCKER2 (proposed) with standard HOSVD, HOOI, GLRAM, PCA, L1-PCA, and TPCA-L1. Our studies show that L1-TUCKER2 outperforms (in tensor approximation) all the above counterparts when the processed data are outlier corrupted.

  16. Robust L1-norm two-dimensional linear discriminant analysis.

    PubMed

    Li, Chun-Na; Shao, Yuan-Hai; Deng, Nai-Yang

    2015-05-01

    In this paper, we propose an L1-norm two-dimensional linear discriminant analysis (L1-2DLDA) with robust performance. Different from the conventional two-dimensional linear discriminant analysis with L2-norm (L2-2DLDA), where the optimization problem is transferred to a generalized eigenvalue problem, the optimization problem in our L1-2DLDA is solved by a simple justifiable iterative technique, and its convergence is guaranteed. Compared with L2-2DLDA, our L1-2DLDA is more robust to outliers and noises since the L1-norm is used. This is supported by our preliminary experiments on toy example and face datasets, which show the improvement of our L1-2DLDA over L2-2DLDA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The Effects of L2 Reading Skills on L1 Reading Skills through Transfer

    ERIC Educational Resources Information Center

    Altmisdort, Gonca

    2016-01-01

    This study investigated whether transfer from L2 to L1 in reading occurs, and if so, which reading sub-skills are transferred into L1 reading. The aim is to identify the role of second language reading skills in L1 reading skills by means of transfer. In addition, the positive effects of the second language transfer to the first language in the…

  18. Revisiting Fluctuations in L2 Article Choice in L1-Korean L2-English Learners

    ERIC Educational Resources Information Center

    Sarker, Bijon K.; Baek, Seunghyun

    2017-01-01

    The current study investigated the distinction of L2 (second language) English article choice sensitivity in fifty-three L1-Korean L2-English learners in semantic contexts. In the context of English as a foreign language, the participants were divided into two groups based on grammatical ability as determined by their performance on a cloze test.…

  19. Ezetimibe-sensitive cholesterol uptake by NPC1L1 protein does not require endocytosis

    PubMed Central

    Johnson, Tory A.; Pfeffer, Suzanne R.

    2016-01-01

    Human NPC1L1 protein mediates cholesterol absorption in the intestine and liver and is the target of the drug ezetimibe, which is used to treat hypercholesterolemia. Previous studies concluded that NPC1L1-GFP protein trafficking is regulated by cholesterol binding and that ezetimibe blocks NPC1L1-GFP function by inhibiting its endocytosis. We used cell surface biotinylation to monitor NPC1L1-GFP endocytosis and show that ezetimibe does not alter the rate of NPC1L1-GFP endocytosis in cultured rat hepatocytes grown under normal growth conditions. As expected, NPC1L1-GFP endocytosis depends in part on C-terminal, cytoplasmically oriented sequences, but endocytosis does not require cholesterol binding to NPC1L1’s N-terminal domain. In addition, two small- molecule inhibitors of general (and NPC1L1-GFP) endocytosis failed to inhibit the ezetimibe-sensitive uptake of [3H]cholesterol from taurocholate micelles. These experiments demonstrate that cholesterol uptake by NPC1L1 does not require endocytosis; moreover, ezetimibe interferes with NPC1L1’s cholesterol adsorption activity without blocking NPC1L1 internalization in RH7777 cells. PMID:27075173

  20. PD-L1 expression and prognostic impact in glioblastoma

    PubMed Central

    Nduom, Edjah K.; Wei, Jun; Yaghi, Nasser K.; Huang, Neal; Kong, Ling-Yuan; Gabrusiewicz, Konrad; Ling, Xiaoyang; Zhou, Shouhao; Ivan, Cristina; Chen, Jie Qing; Burks, Jared K.; Fuller, Greg N.; Calin, George A.; Conrad, Charles A.; Creasy, Caitlin; Ritthipichai, Krit; Radvanyi, Laszlo; Heimberger, Amy B.

    2016-01-01

    Background Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. Methods Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. Results The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%–86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. Conclusions The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome. PMID:26323609

  1. Raising Learners' Awareness through L1-L2 Teacher Collaboration

    ERIC Educational Resources Information Center

    Gunning, Pamela; White, Joanna; Busque, Christine

    2016-01-01

    There is considerable interest in teacher collaboration across mother tongue and second language curricula. However, cross-curricular collaboration in reading strategy instruction has seldom been investigated. We report a two-year study involving collaboration between the French first language (L1) and English second language (L2) teachers in an…

  2. Characterization of the L4-L5-S1 motion segment using the stepwise reduction method.

    PubMed

    Jaramillo, Héctor Enrique; Puttlitz, Christian M; McGilvray, Kirk; García, José J

    2016-05-03

    The two aims of this study were to generate data for a more accurate calibration of finite element models including the L5-S1 segment, and to find mechanical differences between the L4-L5 and L5-S1 segments. Then, the range of motion (ROM) and facet forces for the L4-S1 segment were measured using the stepwise reduction method. This consists of sequentially testing and reducing each segment in nine stages by cutting the ligaments, facet capsules, and removing the nucleus. Five L4-S1 human segments (median: 65 years, range: 53-84 years, SD=11.0 years) were loaded under a maximum pure moment of 8Nm. The ROM was measured using stereo-photogrammetry via tracking of three markers and the facet contact forces (CF) were measured using a Tekscan system. The ROM for the L4-L5 segment and all stages showed good agreement with published data. The major differences in ROM between the L4-L5 and L5-S1 segments were found for lateral bending and all stages, for which the L4-L5 ROM was about 1.5-3 times higher than that of the L5-S1 segment, consistent with L5-S1 facet CF about 1.3 to 4 times higher than those measured for the L4-L5 segment. For the other movements and few stages, the L4-L5 ROM was significantly lower that of the L5-S1 segment. ROM and CF provide important baseline data for more accurate calibration of FE models and to understand the role that their structures play in lower lumbar spine mechanics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Keeping a Spacecraft on the Sun-Earth Line

    NASA Technical Reports Server (NTRS)

    Roithmayr, Carlos M.; Kay-Bunnell, Linda

    2005-01-01

    Measurements of Earth's atmosphere as it occults sunlight can be obtained advantageously from a spacecraft placed in the proximity of the Sun-Earth Lagrange point L2. Maintaining the condition of continuous solar occultation by all parts of the atmospheric disk requires that the displacement of the spacecraft perpendicular to the Sun-Earth line remains less than 200 km. However, the gravitational force exerted by the Earth s moon must be negated by propulsion in order to meet this rather tight constraint. We provide an estimate of propulsive force needed to keep the spacecraft coincident with L2, as well as estimates of velocity increments needed to maintain various trajectories in the close vicinity of L2.

  4. Infinite-disorder critical points of models with stretched exponential interactions

    NASA Astrophysics Data System (ADS)

    Juhász, Róbert

    2014-09-01

    We show that an interaction decaying as a stretched exponential function of distance, J(l)˜ e-cl^a , is able to alter the universality class of short-range systems having an infinite-disorder critical point. To do so, we study the low-energy properties of the random transverse-field Ising chain with the above form of interaction by a strong-disorder renormalization group (SDRG) approach. We find that the critical behavior of the model is controlled by infinite-disorder fixed points different from those of the short-range model if 0 < a < 1/2. In this range, the critical exponents calculated analytically by a simplified SDRG scheme are found to vary with a, while, for a > 1/2, the model belongs to the same universality class as its short-range variant. The entanglement entropy of a block of size L increases logarithmically with L at the critical point but, unlike the short-range model, the prefactor is dependent on disorder in the range 0 < a < 1/2. Numerical results obtained by an improved SDRG scheme are found to be in agreement with the analytical predictions. The same fixed points are expected to describe the critical behavior of, among others, the random contact process with stretched exponentially decaying activation rates.

  5. Perturbed Equations of Motion for Formation Flight Near the Sun-Earth L2 Point

    NASA Technical Reports Server (NTRS)

    Luquette, Richard; Segerman, A. M.; Zedd, M. F.

    2005-01-01

    NASA is planning missions to the vicinity of the Sun-Earth L(sub 2) point, some involving a distributed system of telescope spacecraft, configured in a plane about a hub. Several sets of differential equations are written for the formation flight of such telescopes relative to the hub, with varying levels of fidelity. Effects are cast as additive perturbations to the circular restricted three-body problem, expanded in terms of the system distanced, to an accuracy of 10-20 m. These include Earth's orbital eccentricity, lunar motion, solar radiation pressure, and small thrusting forces. Simulations validating the expanded differential equations are presented.

  6. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    PubMed

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-12-01

    Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution.

    PubMed

    Nguyen, Thu H M; Carreira, Patricia E; Sanchez-Luque, Francisco J; Schauer, Stephanie N; Fagg, Allister C; Richardson, Sandra R; Davies, Claire M; Jesuadian, J Samuel; Kempen, Marie-Jeanne H C; Troskie, Robin-Lee; James, Cini; Beaven, Elizabeth A; Wallis, Tristan P; Coward, Jermaine I G; Chetty, Naven P; Crandon, Alexander J; Venter, Deon J; Armes, Jane E; Perrin, Lewis C; Hooper, John D; Ewing, Adam D; Upton, Kyle R; Faulkner, Geoffrey J

    2018-06-26

    LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Discourse Connectives in L1 and L2 Argumentative Writing

    ERIC Educational Resources Information Center

    Hu, Chunyu; Li, Yuanyuan

    2015-01-01

    Discourse connectives (DCs) are multi-functional devices used to connect discourse segments and fulfill interpersonal levels of discourse. This study investigates the use of selected 80 DCs within 11 categories in the argumentative essays produced by L1 and L2 university students. The analysis is based on the International Corpus Network of Asian…

  9. Access to Mars from Earth-Moon Libration Point Orbits:. [Manifold and Direct Options

    NASA Technical Reports Server (NTRS)

    Kakoi, Masaki; Howell, Kathleen C.; Folta, David

    2014-01-01

    This investigation is focused specifically on transfers from Earth-Moon L(sub 1)/L(sub 2) libration point orbits to Mars. Initially, the analysis is based in the circular restricted three-body problem to utilize the framework of the invariant manifolds. Various departure scenarios are compared, including arcs that leverage manifolds associated with the Sun-Earth L(sub 2) orbits as well as non-manifold trajectories. For the manifold options, ballistic transfers from Earth-Moon L(sub 2) libration point orbits to Sun-Earth L(sub 1)/L(sub 2) halo orbits are first computed. This autonomous procedure applies to both departure and arrival between the Earth-Moon and Sun-Earth systems. Departure times in the lunar cycle, amplitudes and types of libration point orbits, manifold selection, and the orientation/location of the surface of section all contribute to produce a variety of options. As the destination planet, the ephemeris position for Mars is employed throughout the analysis. The complete transfer is transitioned to the ephemeris model after the initial design phase. Results for multiple departure/arrival scenarios are compared.

  10. BCoR-L1 variation and breast cancer.

    PubMed

    Lose, Felicity; Arnold, Jeremy; Young, David B; Brown, Carolyn J; Mann, Graham J; Pupo, Gulietta M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Spurdle, Amanda B

    2007-01-01

    BRCA1 is involved in numerous essential processes in the cell, and the effects of BRCA1 dysfunction in breast cancer carcinogenesis are well described. Many of the breast cancer susceptibility genes such as BRCA2, p53, ATM, CHEK2, and BRIP1 encode proteins that interact with BRCA1. BCL6 corepressor-like 1 (BCoR-L1) is a newly described BRCA1-interacting protein that displays high homology to several proteins known to be involved in the fundamental processes of DNA damage repair and transcription regulation. BCoR-L1 has been shown to play a role in transcription corepression, and expression of the X-linked BCoR-L1 gene has been reported to be dysregulated in breast cancer subjects. BCoR-L1 is located on the X chromosome and is subject to X inactivation. We performed mutation analysis of 38 BRCA1/2 mutation-negative breast cancer families with male breast cancer, prostate cancer, and/or haplotype sharing around BCoR-L1 to determine whether there is a role for BCoR-L1 as a high-risk breast cancer predisposition gene. In addition, we conducted quantitative real-time PCR (qRT-PCR) on lymphoblastoid cell lines (LCLs) from the index cases from these families and a number of cancer cell lines to assess the role of BCoR-L1 dysregulation in cancer and cancer families. Very little variation was detected in the coding region, and qRT-PCR analysis revealed that BCoR-L1 expression is highly variable in cancer-free subjects, high-risk breast cancer patients, and cancer cell lines. We also report the investigation of a new expression control, DIDO1 (death inducer-obliterator 1), that is superior to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and UBC (ubiquitin C) for analysis of expression in LCLs. Our results suggest that BCoR-L1 expression does not play a large role in predisposition to familial breast cancer.

  11. L2 Word Recognition: Influence of L1 Orthography on Multi-Syllabic Word Recognition

    ERIC Educational Resources Information Center

    Hamada, Megumi

    2017-01-01

    L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on…

  12. [PD1/PD-L1 immunohistochemistry in thoracic oncology: Where are we?

    PubMed

    Hofman, Paul; Ilié, Marius; Lassalle, Sandra; Long, Elodie; Bence, Coraline; Butori, Catherine; Hofman, Véronique

    2017-02-01

    The assays for the assessment of the PD-L1 status by immunohistochemistry are available in clinical studies in thoracic oncology to predict response to immunotherapies targeting the PD-1/PD-L1 pathway. With the arrival of this new class of molecules in second line and very soon in first line of treatment for patients with advanced or metastatic non-small cell lung cancer, these tests will certainly be required in routine once these new drugs will be granted marketing authorization. The rapid introduction of these "companion" or "complementary" tests seems essential to select patients to benefit from these effective but also expensive and sometimes toxic therapies. Although challenged by some oncologists (as some patients not expressing PD-L1 may sometimes respond to PD-1/PD-L1 blockade), the anti-PD-L1 immunohistochemically approach seems inevitable in 2017. This new activity developed in the pathology laboratories raises several questions: which anti-PD-L1 clone should be used? On which device? What threshold of positivity should be considered? Should PD-L1 expression be assessed on tumor cells as well as on the immune cells? What controls should be used? Comparative studies are underway or have been already implemented in order to answer some of these questions. This review addresses the different evaluation criteria for immunohistochemistry using the main anti-PD-L1 antibodies used to date as well the recently published studies using these antibodies in thoracic oncology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Use of L1 in L2 Reading Comprehension among Tertiary ESL Learners

    ERIC Educational Resources Information Center

    Seng, Goh Hock; Hashim, Fatimah

    2006-01-01

    This study is an attempt to provide insights into the extent of first language (L1) use while reading second language (L2) texts in a collaborative situation among tertiary ESL learners. Through the identification of reading strategies utilized by the subjects, the study is also aimed at discovering possible reasons for the use of L1 while…

  14. Processing Focus Structure in L1 and L2 French: L2 Proficiency Effects on ERPs

    ERIC Educational Resources Information Center

    Reichle, Robert V.; Birdsong, David

    2014-01-01

    This study examined the event-related potentials (ERPs) elicited by focus processing among first language (L1) speakers and second language (L2) learners of French. Participants read wh-questions containing explicit focus marking, followed by responses instantiating contrastive and informational focus. We hypothesized that L2 proficiency would…

  15. Evaluation of the Consistency among In Situ and Remote Sensing Measurements of CO2 over North America using the CarbonTracker-Lagrange Regional Inverse Modeling Framework

    NASA Astrophysics Data System (ADS)

    Andrews, A. E.; Trudeau, M.; Hu, L.; Thoning, K. W.; Shiga, Y. P.; Michalak, A. M.; Benmergui, J. S.; Mountain, M. E.; Nehrkorn, T.; O'Dell, C.; Jacobson, A. R.; Miller, J.; Sweeney, C.; Chen, H.; Ploeger, F.; Tans, P. P.

    2017-12-01

    CarbonTracker-Lagrange (CT-L) is a regional inverse modeling system for estimating CO2 fluxes with rigorous uncertainty quantification. CT-L uses footprints from the Stochastic Time-Inverted Lagrangian Transport (STILT) model driven by high-resolution (10 to 30 km) meteorological fields from the Weather Research and Forecasting (WRF) model. We have computed a library of footprints corresponding to in situ and remote sensing measurements of CO2 over North America for 2007-2015. GOSAT and OCO-2 XCO2 retrievals are simulated using a suite of CT-L terrestrial ecosystem flux estimates that have been optimized with respect to in situ atmospheric CO2 measurements along with fossil fuel fluxes from emissions inventories. A vertical profile of STILT-WRF footprints was constructed corresponding to each simulated satellite retrieval, and CO2 profiles are generated by convolving the footprints with fluxes and attaching initial values advected from the domain boundaries. The stratospheric contribution to XCO2 has been estimated using 4-dimensional CO2 fields from the NOAA CarbonTracker model (version CT2016) and from the Chemical Lagrangian Model of the Stratosphere (CLaMS), after scaling the model fields to match data from the NOAA AirCore surface-to-stratosphere air sampling system. Tropospheric lateral boundary conditions are from CT2016 and from an empirical boundary value product derived from aircraft and marine boundary layer data. The averaging kernel and a priori CO2 profile are taken into account for direct comparisons with retrievals. We have focused on North America due to the relatively dense in situ measurements available with the aim of developing strategies for combined assimilation of in situ and remote sensing data. We will consider the extent to which interannual variability in terrestrial fluxes is manifest in the real and simulated satellite retrievals, and we will investigate possible systematic biases in the satellite retrievals and in the model.

  16. Dynamical evolution of a fictitious population of binary Neptune Trojans

    NASA Astrophysics Data System (ADS)

    Brunini, Adrián

    2018-03-01

    We present numerical simulations of the evolution of a synthetic population of Binary Neptune Trojans, under the influence of the solar perturbations and tidal friction (the so-called Kozai cycles and tidal friction evolution). Our model includes the dynamical influence of the four giant planets on the heliocentric orbit of the binary centre of mass. In this paper, we explore the evolution of initially tight binaries around the Neptune L4 Lagrange point. We found that the variation of the heliocentric orbital elements due to the libration around the Lagrange point introduces significant changes in the orbital evolution of the binaries. Collisional processes would not play a significant role in the dynamical evolution of Neptune Trojans. After 4.5 × 109 yr of evolution, ˜50 per cent of the synthetic systems end up separated as single objects, most of them with slow diurnal rotation rate. The final orbital distribution of the surviving binary systems is statistically similar to the one found for Kuiper Belt Binaries when collisional evolution is not included in the model. Systems composed by a primary and a small satellite are more fragile than the ones composed by components of similar sizes.

  17. ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.

    PubMed

    Taiwo, Babafemi O; Zheng, Lu; Stefanescu, Andrei; Nyaku, Amesika; Bezins, Baiba; Wallis, Carole L; Godfrey, Catherine; Sax, Paul E; Acosta, Edward; Haas, David; Smith, Kimberly Y; Sha, Beverly; Van Dam, Cornelius; Gulick, Roy M

    2018-05-17

    Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine. A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA ≥1000 and <500000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA <50 copies/mL (FDA [US Food and Drug Administration] Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20 or >200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF. One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA >100000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm3. Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the >100000 copies/mL and ≤100000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at ≥1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events. Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500000 copies/mL in this pilot trial, but a participant developed resistance mutations. NCT02582684.

  18. Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer.

    PubMed

    Vecchio, Giancarlo; Parascandolo, Alessia; Allocca, Chiara; Ugolini, Clara; Basolo, Fulvio; Moracci, Marco; Strazzulli, Andrea; Cobucci-Ponzano, Beatrice; Laukkanen, Mikko O; Castellone, Maria Domenica; Tsuchida, Nobuo

    2017-04-18

    Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.

  19. Ezetimibe-sensitive cholesterol uptake by NPC1L1 protein does not require endocytosis.

    PubMed

    Johnson, Tory A; Pfeffer, Suzanne R

    2016-06-01

    Human NPC1L1 protein mediates cholesterol absorption in the intestine and liver and is the target of the drug ezetimibe, which is used to treat hypercholesterolemia. Previous studies concluded that NPC1L1-GFP protein trafficking is regulated by cholesterol binding and that ezetimibe blocks NPC1L1-GFP function by inhibiting its endocytosis. We used cell surface biotinylation to monitor NPC1L1-GFP endocytosis and show that ezetimibe does not alter the rate of NPC1L1-GFP endocytosis in cultured rat hepatocytes grown under normal growth conditions. As expected, NPC1L1-GFP endocytosis depends in part on C-terminal, cytoplasmically oriented sequences, but endocytosis does not require cholesterol binding to NPC1L1's N-terminal domain. In addition, two small- molecule inhibitors of general (and NPC1L1-GFP) endocytosis failed to inhibit the ezetimibe-sensitive uptake of [(3)H]cholesterol from taurocholate micelles. These experiments demonstrate that cholesterol uptake by NPC1L1 does not require endocytosis; moreover, ezetimibe interferes with NPC1L1's cholesterol adsorption activity without blocking NPC1L1 internalization in RH7777 cells. © 2016 Johnson and Pfeffer. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  20. A Lunar L2-Farside Exploration and Science Mission Concept with the ORion Multi-Purpose Crew Vehicle and a Teleoperated Lander/Rover

    NASA Technical Reports Server (NTRS)

    Burns, Jack O.; Kring, David; Norris, Scott; Hopkins, Josh; Lazio, Joseph; Kasper, Justin

    2012-01-01

    A novel concept is presented in this paper for a human mission to the lunar L2 (Lagrange) point that would be a proving ground for future exploration missions to deep space while also overseeing scientifically important investigations. In an L2 halo orbit above the lunar farside, the astronauts would travel 15% farther from Earth than did the Apollo astronauts and spend almost three times longer in deep space. Such missions would validate the Orion MPCV's life support systems, would demonstrate the high-speed re-entry capability needed for return from deep space, and would measure astronauts' radiation dose from cosmic rays and solar flares to verify that Orion would provide sufficient protection, as it is designed to do. On this proposed mission, the astronauts would teleoperate landers and rovers on the unexplored lunar farside, which would obtain samples from the geologically interesting farside and deploy a low radio frequency telescope. Sampling the South Pole-Aitkin basin (one of the oldest impact basins in the solar system) is a key science objective of the 2011 Planetary Science Decadal Survey. Observations of the Universe's first stars/galaxies at low radio frequencies are a priority of the 2010 Astronomy & Astrophysics Decadal Survey. Such telerobotic oversight would also demonstrate capability for human and robotic cooperation on future, more complex deep space missions.

  1. CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.

    PubMed

    Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

    2016-03-15

    Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis.

  2. CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

    PubMed Central

    Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

    2016-01-01

    Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis. PMID:26918453

  3. Point-of-Care Hemoglobin A1c Testing: An Evidence-Based Analysis

    PubMed Central

    2014-01-01

    Background The increasing prevalence of diabetes in Ontario means that there will be growing demand for hemoglobin A1c (HbA1c) testing to monitor glycemic control for the management of this chronic disease. Testing HbA1c where patients receive their diabetes care may improve system efficiency if the results from point-of-care HbA1c testing are comparable to those from laboratory HbA1c measurements. Objectives To review the correlation between point-of-care HbA1c testing and laboratory HbA1c measurement in patients with diabetes in clinical settings. Data Sources The literature search included studies published between January 2003 and June 2013. Search terms included glycohemoglobin, hemoglobin A1c, point of care, and diabetes. Review Methods Studies were included if participants had diabetes; if they compared point-of-care HbA1c devices (licensed by Health Canada and available in Canada) with laboratory HbA1c measurement (reference method); if they performed point-of-care HbA1c testing using capillary blood samples (finger pricks) and laboratory HbA1c measurement using venous blood samples within 7 days; and if they reported a correlation coefficient between point-of-care HbA1c and laboratory HbA1c results. Results Three point-of-care HbA1c devices were reviewed in this analysis: Bayer's A1cNow+, Bio-Rad's In2it, and Siemens’ DCA Vantage. Five observational studies met the inclusion criteria. The pooled results showed a positive correlation between point-of-care HbA1c testing and laboratory HbA1c measurement (correlation coefficient, 0.967; 95% confidence interval, 0.960–0.973). Limitations Outcomes were limited to the correlation coefficient, as this was a commonly reported measure of analytical performance in the literature. Results should be interpreted with caution due to risk of bias related to selection of participants, reference standards, and the multiple steps involved in POC HbA1c testing. Conclusions Moderate quality evidence showed a positive

  4. Description of the L1C signal

    USGS Publications Warehouse

    Betz, J.W.; Blanco, M.A.; Cahn, C.R.; Dafesh, P.A.; Hegarty, C.J.; Hudnut, K.W.; Kasemsri, V.; Keegan, R.; Kovach, K.; Lenahan, L.S.; Ma, H.H.; Rushanan, J.J.; Sklar, D.; Stansell, T.A.; Wang, C.C.; Yi, S.K.

    2006-01-01

    Detailed design of the modernized LI civil signal (L1C) signal has been completed, and the resulting draft Interface Specification IS-GPS-800 was released in Spring 2006. The novel characteristics of the optimized L1C signal design provide advanced capabilities while offering to receiver designers considerable flexibility in how to use these capabilities. L1C provides a number of advanced features, including: 75% of power in a pilot component for enhanced signal tracking, advanced Weilbased spreading codes, an overlay code on the pilot that provides data message synchronization, support for improved reading of clock and ephemeris by combining message symbols across messages, advanced forward error control coding, and data symbol interleaving to combat fading. The resulting design offers receiver designers the opportunity to obtain unmatched performance in many ways. This paper describes the design of L1C. A summary of LIC's background and history is provided. The signal description then proceeds with the overall signal structure consisting of a pilot component and a carrier component. The new L1C spreading code family is described, along with the logic used for generating these spreading codes. Overlay codes on the pilot channel are also described, as is the logic used for generating the overlay codes. Spreading modulation characteristics are summarized. The data message structure is also presented, showing the format for providing time, ephemeris, and system data to users, along with features that enable receivers to perform code combining. Encoding of rapidly changing time bits is described, as are the Low Density Parity Check codes used for forward error control of slowly changing time bits, clock, ephemeris, and system data. The structure of the interleaver is also presented. A summary of L 1C's unique features and their benefits is provided, along with a discussion of the plan for L1C implementation.

  5. Bayesian model of categorical effects in L1 and L2 speech perception

    NASA Astrophysics Data System (ADS)

    Kronrod, Yakov

    In this dissertation I present a model that captures categorical effects in both first language (L1) and second language (L2) speech perception. In L1 perception, categorical effects range between extremely strong for consonants to nearly continuous perception of vowels. I treat the problem of speech perception as a statistical inference problem and by quantifying categoricity I obtain a unified model of both strong and weak categorical effects. In this optimal inference mechanism, the listener uses their knowledge of categories and the acoustics of the signal to infer the intended productions of the speaker. The model splits up speech variability into meaningful category variance and perceptual noise variance. The ratio of these two variances, which I call Tau, directly correlates with the degree of categorical effects for a given phoneme or continuum. By fitting the model to behavioral data from different phonemes, I show how a single parametric quantitative variation can lead to the different degrees of categorical effects seen in perception experiments with different phonemes. In L2 perception, L1 categories have been shown to exert an effect on how L2 sounds are identified and how well the listener is able to discriminate them. Various models have been developed to relate the state of L1 categories with both the initial and eventual ability to process the L2. These models largely lacked a formalized metric to measure perceptual distance, a means of making a-priori predictions of behavior for a new contrast, and a way of describing non-discrete gradient effects. In the second part of my dissertation, I apply the same computational model that I used to unify L1 categorical effects to examining L2 perception. I show that we can use the model to make the same type of predictions as other SLA models, but also provide a quantitative framework while formalizing all measures of similarity and bias. Further, I show how using this model to consider L2 learners at

  6. l-Asparaginase from Proteus vulgaris1

    PubMed Central

    Tosa, Tetsuya; Sano, Ryujiro; Yamamoto, Kozo; Nakamura, Masatoshi; Ando, Katsuko; Chibata, Ichiro

    1971-01-01

    To produce an immunologically and enzymologically new type of l-asparaginase, 108 strains of bacteria were screened for enzyme production. As a result, 13 bacteria belonging to the genera Alcaligenes, Bacterium, and Proteus were found to produce l-asparaginases in high levels. Among these l-asparaginases, partially purified l-asparaginases from B. cadaveris and P. vulgaris showed antitumor activity. A partially purified l-asparaginase preparation of P. vulgaris did not react with the antibody of Escherichia colil-asparaginase on the Ouchterlony agar plate. Culture conditions for the production of l-asparaginase by P. vulgaris were investigated in detail. The enzyme was produced in high yields when cells were grown aerobically in a medium containing sodium fumarate and corn steep liquor. The addition of glucose or ammonium ion to the medium, however, resulted in depressed production of l-asparaginase. Under the optimum conditions, 3,700 international units of l-asparaginase was obtained from 1 liter of culture medium. Images PMID:5000866

  7. PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma.

    PubMed

    Fontugne, Jacqueline; Augustin, Jérémy; Pujals, Anaïs; Compagnon, Philippe; Rousseau, Benoit; Luciani, Alain; Tournigand, Christophe; Cherqui, Daniel; Azoulay, Daniel; Pawlotsky, Jean-Michel; Calderaro, Julien

    2017-04-11

    Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression.A series of 58 iCCAs and 41 pCCAs was included in the study. PD-L1, PD-1 and CD3 expression was investigated using immunohistochemistry. Density of TILs was evaluated by immunohistochemistry using a quantitative score of CD3-stained intratumoral lymphocytes.PD-L1 expression by neoplastic cells was observed in 9 cases (9%, 5 iCCAs and 4 pCCAs). PD-L1 positive inflammatory cell aggregates were identified in 46% (n = 46) of the cases (31 iCCAs and 15 pCCAs). PD-L1 expression by either neoplastic or inflammatory cells was associated to high density of CD3-positive TILs (p = 0.01 and p = 0.005, respectively). The number of PD-L1 positive inflammatory cell aggregates was higher in tumors with high PD-1 expression (p < 0.0001).Altogether, PD-L1 in iCCA and pCCA is mainly expressed in tumors with high density of TILs. Our results suggest that CCAs with dense intratumoral lymphocytic infiltration might represent good candidates for PD-L1/PD-1 blocking agents.

  8. 17 CFR 1.34 - Monthly record, “point balance”.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Recordkeeping § 1.34 Monthly record, “point balance”. (a) Each... statement commonly known as a “point balance,” which accrues or brings to the official closing price, or... contracts long and short in the customers' accounts are in balance with those in the carrying futures...

  9. 17 CFR 1.34 - Monthly record, “point balance”.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Recordkeeping § 1.34 Monthly record, “point balance”. (a) Each... statement commonly known as a “point balance,” which accrues or brings to the official closing price, or... contracts long and short in the customers' accounts are in balance with those in the carrying futures...

  10. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

    PubMed Central

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-01-01

    INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

  11. Children's Use of Requests in Chinese (L1) and English (L2): A Case Study in Taiwan

    ERIC Educational Resources Information Center

    Kuo, Li-feng

    2010-01-01

    Much research on requests has been carried out among L1 Chinese adults, L1 Chinese children, L1 children, L2 adults, and L2 children, but no studies to date have simultaneously examined Chinese children's requests in Chinese (L1) and English (L2). The aim of this study is to investigate how Taiwanese elementary school children vary requests…

  12. L1 Differences and L2 Similarities: Teaching Verb Tenses in English

    ERIC Educational Resources Information Center

    Collins, Laura

    2007-01-01

    In making decisions regarding the focus for grammar teaching, ESL instructors may take into consideration errors that appear to result from the influence of their students' first language(s) (L1). There is also evidence from language acquisition research suggesting that for some grammatical features, learners of different L1 backgrounds may face…

  13. Effect of ethylene and 1-methylcyclopropene on the postharvest behavior of cape gooseberry fruits (Physalis peruviana L.).

    PubMed

    Balaguera-López, Helber E; Espinal-Ruiz, Mauricio; Zacarías, Lorenzo; Herrera, Aníbal O

    2017-01-01

    Cape gooseberry (Physalis peruviana L.) fruits are highly perishable berries that exhibit a climacteric respiratory behavior. The objective of this study was to evaluate the effect of ethylene and the ethylene action inhibitor 1-methylcyclopropene on the postharvest behavior of cape gooseberry fruits (ecotype Colombia). Fruits were treated with ethylene, in an ethephon application (1000 µL L -1 ), and pretreated with 1-methylcyclopropene (1 µL L -1 ), 1-methylcyclopropene+ethylene, and results compared with a control without application. Subsequently, the fruits were maintained at room temperature (20 ℃, 75% RH) for up to 11 days. The pretreatment of the cape gooseberry fruits with 1-methylcyclopropene delayed most of the ripening-associated parameters, with a reduction in the respiration rate and ethylene production, skin color development, total soluble solids, total carotenoid content, loss of firmness, loss of total titratable acidity and emission of volatile compounds such as ethyl octanoate, ethyl butanoate, ethyl decanoate, and hexyl decanoate. Conversely, application of ethephon accelerated most of these physiological changes and also overcame most of the effects prevented by the ethylene action inhibitor. Altogether, the results supported the idea of a climacteric-like behavior for cape gooseberry fruits and pointing out that the pretreatment with 1-methylcyclopropene may be a promising and efficient postharvest treatment to delay maturity and extend the postharvest period. © The Author(s) 2016.

  14. Site Selection and Deployment Scenarios for Servicing of Deep-Space Observatories

    NASA Technical Reports Server (NTRS)

    Willenberg, Harvey J.; Fruhwirth, Michael A.; Potter, Seth D.; Leete, Stephen J.; Moe, Rud V.

    2001-01-01

    The deep-space environment and relative transportation accessibility of the Weak Stability Boundary (WSB) region connecting the Earth-Moon and Sun-Earth libration points makes the Sun-Earth L2 an attractive operating location for future observatories. A summary is presented of key characteristics of future observatories designed to operate in this region. The ability to service observatories that operate within the region around the Lagrange points may greatly enhance their reliability, lifetime, and scientific return. The range of servicing missions might begin with initial deployment, assembly, test, and checkout. Post-assembly servicing missions might also include maintenance and repair, critical fluids resupply, and instrument upgrades. We define the range of servicing missions that can be performed with extravehicular activity, with teleoperated robots, and with autonomous robots. We then describe deployment scenarios that affect payload design. A trade study is summarized of the benefits and risks of alternative servicing sites, including at the International Space Station, at other low-Earth-orbit locations, at the Earth-Moon L1 location, and on-site at the Sun-Earth L2 location. Required technology trades and development issues for observatory servicing at each site, and with each level of autonomy, are summarized.

  15. A Small Spacecraft Swarm Deployment and Stationkeeping Strategy for Sun-Earth L1 Halo Orbits

    NASA Technical Reports Server (NTRS)

    Conn, Tracie R.; Bookbinder, Jay

    2018-01-01

    Spacecraft orbits about the Sun-Earth librarian point L1 have been of interest since the 1950s. An L1 halo orbit was first achieved with the International Sun-Earth Explorer-3 (ISEE-3) mission, and similar orbits around Sun-Earth L1 were achieved in the Solar and Heliospheric Observatory (SOHO), Advanced Composition Explorer (ACE), Genesis, and Deep Space Climate Observatory (DSCOVR) missions. With recent advancements in CubeSat technology, we envision that it will soon be feasible to deploy CubeSats at L1. As opposed to these prior missions where one large satellite orbited alone, a swarm of CubeSats at L1 would enable novel science data return, providing a topology for intersatellite measurements of heliophysics phenomena both spatially and temporally, at varying spatial scales.The purpose of this iPoster is to present a flight dynamics strategy for a swarm of numerous CubeSats orbiting Sun-Earth L1. The presented method is a coupled, two-part solution. First, we present a deployment strategy for the CubeSats that is optimized to produce prescribed, time-varying intersatellite baselines for the purposes of collecting magnetometer data as well as radiometric measurements from cross-links. Second, we employ a loose control strategy that was successfully applied to SOHO and ACE for minimized stationkeeping fuel expenditure. We emphasize that the presented solution is practical within the current state-of-the-art and heritage CubeSat technology, citing capabilities of CubeSat designs that will launch on the upcoming Exploration Mission 1 (EM-1) to lunar orbits and beyond. Within this iPoster, we present animations of the simulated deployment strategy and resulting spacecraft trajectories. Mission design parameters such as total delta-v required for long-term station keeping and minimummaximummean spacecraft separation distances are also presented.

  16. A Small Spacecraft Swarm Deployment and Stationkeeping Strategy for Sun-Earth L1 Halo Orbits

    NASA Astrophysics Data System (ADS)

    Renea Conn, Tracie; Bookbinder, Jay

    2018-01-01

    Spacecraft orbits about the Sun-Earth librarian point L1 have been of interest since the 1950s. An L1 halo orbit was first achieved with the International Sun-Earth Explorer-3 (ISEE-3) mission, and similar orbits around Sun-Earth L1 were achieved in the Solar and Heliospheric Observatory (SOHO), Advanced Composition Explorer (ACE), Genesis, and Deep Space Climate Observatory (DSCOVR) missions. With recent advancements in CubeSat technology, we envision that it will soon be feasible to deploy CubeSats at L1. As opposed to these prior missions where one large satellite orbited alone, a swarm of CubeSats at L1 would enable novel science data return, providing a topology for intersatellite measurements of heliophysics phenomena both spatially and temporally, at varying spatial scales.The purpose of this iPoster is to present a flight dynamics strategy for a swarm of numerous CubeSats orbiting Sun-Earth L1. The presented method is a coupled, two-part solution. First, we present a deployment strategy for the CubeSats that is optimized to produce prescribed, time-varying intersatellite baselines for the purposes of collecting magnetometer data as well as radiometric measurements from cross-links. Second, we employ a loose control strategy that was successfully applied to SOHO and ACE for minimized stationkeeping propellant expenditure. We emphasize that the presented solution is practical within the current state-of-the-art and heritage CubeSat technology, citing capabilities of CubeSat designs that will launch on the upcoming Exploration Mission 1 (EM-1) to lunar orbits and beyond. Within this iPoster, we present animations of the simulated deployment strategy and resulting spacecraft trajectories. Mission design parameters such as total Δv required for long-term station keeping and minimum/maximum/mean spacecraft separation distances are also presented.

  17. Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1.

    PubMed

    Nemoto, Yuki; Shosu, Kazuha; Okuda, Masaru; Noguchi, Shunsuke; Mizuno, Takuya

    2018-04-01

    Recent research has focused on immunotherapy, particularly with regard to cancer treatment. Programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) pathway blockade is a central topic of the promising immunotherapy field. In veterinary medicine, observations of the PD-1/PD-L1 pathway, including the relationship between immune cells and diseases, have increased. In this study, monoclonal antibodies specific to canine PD-1 and PD-L1 were developed, and the antibodies against PD-1 and PD-L1 bind to PD-1 and PD-L1 overexpressing cells, respectively. Additionally, each antibody interfered with the interaction between PD-1 and PD-L1. The expression of PD-1 and PD-L1 was detected on activated T cells from canine peripheral blood mononuclear cells (PBMC), and, remarkably, was the first recorded instance of PD-L1 expression on canine immature dendritic cells. Production of IFN-γ by activated T cells increased significantly when incubated with anti-PD-1 antibody alone and with both anti-PD-1 and anti-PD-L1 antibodies, revealing the functional effects of the antibodies. The antibodies will be useful for research on immune systems and may be the first passive immunotherapy approach in canine cancer patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Investigations on bending-torsional vibrations of rotor during rotor-stator rub using Lagrange multiplier method

    NASA Astrophysics Data System (ADS)

    Mokhtar, Md Asjad; Kamalakar Darpe, Ashish; Gupta, Kshitij

    2017-08-01

    The ever-increasing need of highly efficient rotating machinery causes reduction in the clearance between rotating and non-rotating parts and increase in the chances of interaction between these parts. The rotor-stator contact, known as rub, has always been recognized as one of the potential causes of rotor system malfunctions and a source of secondary failures. It is one of few causes that influence both lateral and torsional vibrations. In this paper, the rotor stator interaction phenomenon is investigated in the finite element framework using Lagrange multiplier based contact mechanics approach. The stator is modelled as a beam that can respond to axial penetration and lateral friction force during the contact with the rotor. It ensures dynamic stator contact boundary and more realistic contact conditions in contrast to most of the earlier approaches. The rotor bending-torsional mode coupling during contact is considered and the vibration response in bending and torsion are analysed. The effect of parameters such as clearance, friction coefficient and stator stiffness are studied at various operating speeds and it has been found that certain parameter values generate peculiar rub related features. Presence of sub-harmonics in the lateral vibration frequency spectra are prominently observed when the rotor operates near the integer multiple of its lateral critical speed. The spectrum cascade of torsional vibration shows the presence of bending critical speed along with the larger amplitudes of frequencies close to torsional natural frequency of the rotor. When m × 1/n X frequency component of rotational frequency comes closer to the torsional natural frequency, stronger torsional vibration amplitude is noticed in the spectrum cascade. The combined information from the stator vibration and rotor lateral-torsional vibration spectral features is proposed for robust rub identification.

  19. 26 CFR 1.412(l)(7)-1 - Mortality tables used to determine current liability.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... liability. 1.412(l)(7)-1 Section 1.412(l)(7)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.412(l)(7)-1 Mortality tables used to determine current liability. (a) In general. The... under section 412(l)(7) for participants and beneficiaries (other than disabled participants) for plan...

  20. Characterization of monocarboxylate transporter 1 (MCT1) binding affinity for Basigin gene products and L1cam.

    PubMed

    Howard, John; Finch, Nicole A; Ochrietor, Judith D

    2010-07-01

    The purpose of this study was to determine the binding affinities of Basigin gene products and neural cell adhesion molecule L1cam for monocarboxylate transporter-1 (MCT1). ELISA binding assays were performed in which recombinant proteins of the transmembrane domains of Basigin gene products and L1cam were incubated with MCT1 captured from mouse brain. It was determined that Basigin gene products bind MCT1 with moderate affinity, but L1cam does not bind MCT1. Despite a high degree of sequence conservation between Basigin gene products and L1cam, the sequences are different enough to prevent L1cam from interacting with MCT1.

  1. On the error propagation of semi-Lagrange and Fourier methods for advection problems☆

    PubMed Central

    Einkemmer, Lukas; Ostermann, Alexander

    2015-01-01

    In this paper we study the error propagation of numerical schemes for the advection equation in the case where high precision is desired. The numerical methods considered are based on the fast Fourier transform, polynomial interpolation (semi-Lagrangian methods using a Lagrange or spline interpolation), and a discontinuous Galerkin semi-Lagrangian approach (which is conservative and has to store more than a single value per cell). We demonstrate, by carrying out numerical experiments, that the worst case error estimates given in the literature provide a good explanation for the error propagation of the interpolation-based semi-Lagrangian methods. For the discontinuous Galerkin semi-Lagrangian method, however, we find that the characteristic property of semi-Lagrangian error estimates (namely the fact that the error increases proportionally to the number of time steps) is not observed. We provide an explanation for this behavior and conduct numerical simulations that corroborate the different qualitative features of the error in the two respective types of semi-Lagrangian methods. The method based on the fast Fourier transform is exact but, due to round-off errors, susceptible to a linear increase of the error in the number of time steps. We show how to modify the Cooley–Tukey algorithm in order to obtain an error growth that is proportional to the square root of the number of time steps. Finally, we show, for a simple model, that our conclusions hold true if the advection solver is used as part of a splitting scheme. PMID:25844018

  2. The Role of Multiword Building Blocks in Explaining L1-L2 Differences.

    PubMed

    Arnon, Inbal; Christiansen, Morten H

    2017-07-01

    Why are children better language learners than adults despite being worse at a range of other cognitive tasks? Here, we explore the role of multiword sequences in explaining L1-L2 differences in learning. In particular, we propose that children and adults differ in their reliance on such multiword units (MWUs) in learning, and that this difference affects learning strategies and outcomes, and leads to difficulty in learning certain grammatical relations. In the first part, we review recent findings that suggest that MWUs play a facilitative role in learning. We then discuss the implications of these findings for L1-L2 differences: We hypothesize that adults are both less likely to extract MWUs and less capable of benefiting from them in the process of learning. In the next section, we draw on psycholinguistic, developmental, and computational findings to support these predictions. We end with a discussion of the relation between this proposal and other accounts of L1-L2 difficulty. Copyright © 2017 Cognitive Science Society, Inc.

  3. [Establishment and validation of normal human L1-L5 lumbar three-dimensional finite element model].

    PubMed

    Zhu, Zhenqi; Liu, Chenjun; Wang, Jiefu; Wang, Kaifeng; Huang, Zhixin; Wang, Weida; Liu, Haiying

    2014-10-14

    To create and validate a L1-L5 lumbar three-dimensional finite element model. The L1-L5 lumbar spines of a male healthy volunteer were scanned with computed tomography (CT). And a L1-L5 lumbar three-dimensional finite element model was created with the aid of software packages of Mimics, Geomagic and Ansys. Then border conditions were set, unit type was determined, finite element mesh was divided and a model was established for loading and calculating. Average model stiffness under the conditions of flexion, extension, lateral bending and axial rotation was calculated and compared with the outcomes of former articles for validation. A normal human L1-L5 lumbar three-dimensional finite element model was established to include 459 340 elements and 661 938 nodes. After constraining the inferior endplate of L5 vertebral body, 500 kg × m × s⁻² compressive loading was imposed averagely on the superior endplate of L1 vertebral body. Then 10 kg × m² × s⁻² moment simulating flexion, extension, lateral bending and axial rotation were imposed on the superior endplate of L1 vertebral body. Eventually the average stiffness of all directions was calculated and it was similar to the outcomes of former articles. The L1-L5 lumbar three-dimensional finite element model is validated so that it may used with biomechanical simulation and analysis of normal or surgical models.

  4. PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer

    PubMed Central

    Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L.; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

    2013-01-01

    Background Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. Methods/Results RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). Conclusions PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression. PMID

  5. PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.

    PubMed

    Song, Minmin; Chen, Defeng; Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

    2013-01-01

    Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression.

  6. L1-L2 Convergence in Clausal Packaging in Japanese and English

    ERIC Educational Resources Information Center

    Brown, Amanda; Gullberg, Marianne

    2013-01-01

    This study investigates L1-L2 convergence among bilinguals at an intermediate (CEFR-B2) level of L2 proficiency, focusing on the clausal packaging of Manner and Path of motion. Previous research has shown cross-linguistic differences between English and Japanese in this domain (Allen et al., 2003; Kita & Ozyurek, 2003, though note Brown &…

  7. Evolutionally dynamic L1 regulation in embryonic stem cells

    PubMed Central

    Castro-Diaz, Nathaly; Ecco, Gabriela; Coluccio, Andrea; Kapopoulou, Adamandia; Yazdanpanah, Benyamin; Friedli, Marc; Duc, Julien; Jang, Suk Min; Turelli, Priscilla; Trono, Didier

    2014-01-01

    Mobile elements are important evolutionary forces that challenge genomic integrity. Long interspersed element-1 (L1, also known as LINE-1) is the only autonomous transposon still active in the human genome. It displays an unusual pattern of evolution, with, at any given time, a single active L1 lineage amplifying to thousands of copies before getting replaced by a new lineage, likely under pressure of host restriction factors, which act notably by silencing L1 expression during early embryogenesis. Here, we demonstrate that in human embryonic stem (hES) cells, KAP1 (KRAB [Krüppel-associated box domain]-associated protein 1), the master cofactor of KRAB-containing zinc finger proteins (KRAB-ZFPs) previously implicated in the restriction of endogenous retroviruses, represses a discrete subset of L1 lineages predicted to have entered the ancestral genome between 26.8 million and 7.6 million years ago. In mice, we documented a similar chronologically conditioned pattern, albeit with a much contracted time scale. We could further identify an L1-binding KRAB-ZFP, suggesting that this rapidly evolving protein family is more globally responsible for L1 recognition. KAP1 knockdown in hES cells induced the expression of KAP1-bound L1 elements, but their younger, human-specific counterparts (L1Hs) were unaffected. Instead, they were stimulated by depleting DNA methyltransferases, consistent with recent evidence demonstrating that the PIWI–piRNA (PIWI-interacting RNA) pathway regulates L1Hs in hES cells. Altogether, these data indicate that the early embryonic control of L1 is an evolutionarily dynamic process and support a model in which newly emerged lineages are first suppressed by DNA methylation-inducing small RNA-based mechanisms before KAP1-recruiting protein repressors are selected. PMID:24939876

  8. Small-molecule inhibitors of FGFR, integrins and FAK selectively decrease L1CAM-stimulated glioblastoma cell motility and proliferation.

    PubMed

    Anderson, Hannah J; Galileo, Deni S

    2016-06-01

    The cell adhesion/recognition protein L1CAM (L1; CD171) has previously been shown to act through integrin, focal adhesion kinase (FAK) and fibroblast growth factor receptor (FGFR) signaling pathways to increase the motility and proliferation of glioblastoma cells in an autocrine/paracrine manner. Here, we investigated the effects of clinically relevant small-molecule inhibitors of the integrin, FAK and FGFR signaling pathways on glioblastoma-derived cells to determine their effectiveness and selectivity for diminishing L1-mediated stimulation. The effects of the FGFR inhibitor PD173074, the FAK inhibitors PF431396 and Y15 and the αvβ3/αvβ5 integrin inhibitor cilengitide were assessed in L1-positive and L1-negative variants of the human glioblastoma-derived cell lines T98G and U-118 MG. Their motility and proliferation were quantified using time-lapse microscopy and DNA content/cell cycle analyses, respectively. The application of all four inhibitors resulted in reductions in L1-mediated motility and proliferation rates of L1-positive glioblastoma-derived cells, down to the level of L1-negative cells when used at nanomolar concentrations, whereas no or much smaller reductions in these rates were obtained in L1-negative cells. In addition, we found that single inhibitor treatment resulted in maximum effects (i.e., combinations of FAK or integrin inhibitors with the FGFR inhibitor were rarely more effective). These results suggest that FAK may act as a point of convergence between the integrin and FGFR signaling pathways stimulated by L1 in these cells. We here show for the first time that small-molecule inhibitors of FGFR, integrins and FAK effectively and selectively abolish L1-stimulated migration and proliferation of glioblastoma-derived cells. Our results suggest that these inhibitors have the potential to reduce the aggressiveness of high-grade gliomas expressing L1.

  9. Determinants of BH3 binding specificity for Mcl-1 vs. Bcl-xL

    PubMed Central

    Dutta, Sanjib; Gullá, Stefano; Chen, T. Scott; Fire, Emiko; Grant, Robert A.; Keating, Amy E.

    2010-01-01

    Interactions among Bcl-2 family proteins are important for regulating apoptosis. Pro-survival members of the family interact with pro-apoptotic BH3-only members, inhibiting execution of cell death through the mitochondrial pathway. Structurally, this interaction is mediated by binding of the alpha-helical BH3 region of the pro-apoptotic proteins to a conserved hydrophobic groove on the pro-survival proteins. Native BH3-only proteins exhibit selectivity in binding pro-survival members, as do small molecules that block these interactions. Understanding the sequence and structural basis of interaction specificity in this family is important, as it may allow the prediction of new Bcl-2 family associations and/or the design of new classes of selective inhibitors to serve as reagents or therapeutics. In this work we used two complementary techniques, yeast surface display screening from combinatorial peptide libraries and SPOT peptide array analysis, to elucidate specificity determinants for binding to Bcl-xL vs. Mcl-1, two prominent pro-survival proteins. We screened a randomized library and identified BH3 peptides that bound to either Mcl-1 or Bcl-xL selectively, or to both with high affinity. The peptides competed with native ligands for binding into the conserved hydrophobic groove, as illustrated in detail by a crystal structure of a specific peptide bound to Mcl-1. Mcl-1 selective peptides from the screen were highly specific for binding Mcl-1 in preference to Bcl-xL, Bcl-2, Bcl-w and Bfl-1, whereas Bcl-xL selective peptides showed some cross-interaction with related proteins Bcl-2 and Bcl-w. Mutational analyses using SPOT arrays revealed the effects of 170 point mutations made in the background of a peptide derived from the BH3 region of Bim, and a simple predictive model constructed using these data explained much of the specificity observed in our Mcl-1 vs. Bcl-xL binders. PMID:20363230

  10. Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-kappa B response element

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

    Nagasaki, Haruka; Yoshimura, Takeshi; Aoki, Naohito, E-mail: n-aoki@bio.mie-u.ac.jp

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Inflammation status in adipocytes can be monitored by the new assay system. Black-Right-Pointing-Pointer Only an aliquot of conditioned medium is required without cell lysis. Black-Right-Pointing-Pointer Inflammation-attenuating compounds can be screened more conveniently. -- Abstract: We have established 3T3-L1 cells possessing a secretory Gaussia luciferase (GLuc) gene under the control of nuclear factor-kappa B (NF-{kappa}B) response element. The 3T3-L1 cells named 3T3-L1-NF-{kappa}B-RE-GLuc could differentiate into adipocyte as comparably as parental 3T3-L1 cells. Inflammatory cytokines such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-1{beta} induced GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes in a concentration- and time-dependent manner. GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLucmore » adipocytes was also induced when cultured with RAW264.7 macrophages and was dramatically enhanced by lipopolysaccharide (LPS)-activated macrophages. An NF-{kappa}B activation inhibitor BAY-11-7085 and an antioxidant N-acetyl cysteine significantly suppressed GLuc secretion induced by macrophages. Finally, we found that rosemary-derived carnosic acid strongly suppressed GLuc secretion induced by macrophages and on the contrary up-regulated adiponectin secretion. Collectively, by using 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes, inflammation status can be monitored in real time and inflammation-attenuating compounds can be screened more conveniently.« less

  11. Expression of PD-L1 on Canine Tumor Cells and Enhancement of IFN-γ Production from Tumor-Infiltrating Cells by PD-L1 Blockade

    PubMed Central

    Maekawa, Naoya; Konnai, Satoru; Ikebuchi, Ryoyo; Okagawa, Tomohiro; Adachi, Mami; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2014-01-01

    Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the “exhausted” status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1–expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed. PMID:24915569

  12. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

    PubMed

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-11-01

    The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

  13. Representation and Embodiment of Meaning in L2 Communication: Motion Events in the Speech and Gesture of Advanced L2 Korean and L2 English Speakers

    ERIC Educational Resources Information Center

    Choi, Soojung; Lantolf, James P.

    2008-01-01

    This study investigates the interface between speech and gesture in second language (L2) narration within Slobin's (2003) thinking-for-speaking (TFS) framework as well as with respect to McNeill's (1992, 2005) growth point (GP) hypothesis. Specifically, our interest is in whether speakers shift from a first language (L1) to a L2 TFS pattern as…

  14. Localization and role of NPC1L1 in cholesterol absorption in human intestine.

    PubMed

    Sané, Alain Théophile; Sinnett, Daniel; Delvin, Edgard; Bendayan, Moise; Marcil, Valérie; Ménard, Daniel; Beaulieu, Jean-François; Levy, Emile

    2006-10-01

    Recent studies have documented the presence of Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine and its capacity to transport cholesterol in mice and rats. The current investigation was undertaken to explore the localization and function of NPC1L1 in human enterocytes. Cell fractionation experiments revealed an NPC1L1 association with apical membrane of the enterocyte in human jejunum. Signal was also detected in lysosomes, endosomes, and mitochondria. Confirmation of cellular NPC1L1 distribution was obtained by immunocytochemistry. Knockdown of NPC1L1 caused a decline in the ability of Caco-2 cells to capture micellar [(14)C]free cholesterol. Furthermore, this NPC1L1 suppression resulted in increased and decreased mRNA levels and activity of HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and of ACAT, the key enzyme in cholesterol esterification, respectively. An increase was also noted in the transcriptional factor sterol-regulatory element binding protein that modulates cholesterol homeostasis. Efforts were devoted to define the impact of NPC1L1 knockdown on other mediators of cholesterol uptake. RT-PCR evidence is presented to show the significant decrease in the levels of scavenger receptor class B type I (SR-BI) with no changes in ABCA1, ABCG5, and cluster determinant 36 in NPC1L1-deficient Caco-2 cells. Together, our data suggest that NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans.

  15. A Network Meta-analysis Comparing the Efficacy and Safety of Anti-PD-1 with Anti-PD-L1 in Non-small Cell Lung Cancer.

    PubMed

    You, Wei; Liu, Mei; Miao, Ji-Dong; Liao, Yu-Qian; Song, Yi-Bing; Cai, Dian-Kun; Gao, Yang; Peng, Hao

    2018-01-01

    Background : This network meta-analysis aimed at comparing anti-programmed death 1 (anti-PD-1) with anti-programmed death ligand 1(anti-PD-L1) immunotherapy in patients with metastatic, previously treated non-small cell lung cancer (NSCLC) who failed first-line treatment. Methods : We searched electronic databases to identify all eligible clinical trials. End-points included overall survival (OS), progression-free survival (PFS) and objective response. Hazard ratios (HRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted. Network meta-analysis was performed using the frequentist approach for multiple treatment comparisons. Results : In total, 3024 patients were randomly assigned: 1117 received anti-PD-1 therapy (nivolumab + pembrolizumab), 569 received anti-PD-L1 (atezolizumab) and 1338 received docetaxel. Anti-PD-1 (HR, 0.56; 95% CI, 0.48-0.66) and anti-PD-L1 (HR, 0.64; 95% CI, 0.51-0.79) achieved better OS than docetaxel, and anti-PD-1 was superior to docetaxel in terms of PFS (HR, 0.75; 95% CI, 0.62-0.89). Moreover, anti-PD-1 achieved the highest effect on OS and PFS, with a P-score of 91.2% and 95.5%, respectively. With regard to tumor response, anti-PD-1 group had a higher rate of responders than that in anti-PD-L1 (HR, 0.35; 95% CI, 0.19-0.65) and docetaxel (HR, 0.36; 95% CI, 0.25-0.52) groups. Undoubtedly, anti-PD-1 and anti-PD-L1 obtained less toxicity profile than docetaxel, and no significant difference was observed between anti-PD-1 and anti-PD-L1 groups. Conclusions : Anti-PD-1 may be a better choice for patients with metastatic and previously treated NSCLC who failed first-line treatment in terms of the treatment ranking.

  16. A Prerequisite to L1 Homophone Effects in L2 Spoken-Word Recognition

    ERIC Educational Resources Information Center

    Nakai, Satsuki; Lindsay, Shane; Ota, Mitsuhiko

    2015-01-01

    When both members of a phonemic contrast in L2 (second language) are perceptually mapped to a single phoneme in one's L1 (first language), L2 words containing a member of that contrast can spuriously activate L2 words in spoken-word recognition. For example, upon hearing cattle, Dutch speakers of English are reported to experience activation…

  17. Cognitive Style and Reading Comprehension in L1 and L2.

    ERIC Educational Resources Information Center

    Vivaldo-Lima, Javier

    This paper presents the results of a research study carried out with Mexican college students to analyze the relationship between readers' cognitive styles (field dependent/independent) and their performance at different levels of written discourse processing in Spanish (L1) and English (L2). The sample for the study included 452 undergraduate…

  18. KCNQ1 p.L353L affects splicing and modifies the phenotype in a founder population with long QT syndrome type 1

    PubMed Central

    Kapplinger, Jamie D; Erickson, Anders; Asuri, Sirisha; Tester, David J; McIntosh, Sarah; Kerr, Charles R; Morrison, Julie; Tang, Anthony; Sanatani, Shubhayan; Arbour, Laura; Ackerman, Michael J

    2017-01-01

    Background Variable expressivity and incomplete penetrance between individuals with identical long QT syndrome (LQTS) causative mutations largely remain unexplained. Founder populations provide a unique opportunity to explore modifying genetic effects. We examined the role of a novel synonymous KCNQ1 p.L353L variant on the splicing of exon 8 and on heart rate corrected QT interval (QTc) in a population known to have a pathogenic LQTS type 1 (LQTS1) causative mutation, p.V205M, in KCNQ1-encoded Kv7.1. Methods 419 adults were genotyped for p.V205M, p.L353L and a previously described QTc modifier (KCNH2-p.K897T). Adjusted linear regression determined the effect of each variant on QTc, alone and in combination. In addition, peripheral blood RNA was extracted from three controls and three p.L353L-positive individuals. The mutant transcript levels were assessed via qPCR and normalised to overall KCNQ1 transcript levels to assess the effect on splicing. Results For women and men, respectively, p.L353L alone conferred a 10.0 (p=0.064) ms and 14.0 (p=0.014) ms increase in QTc and in men only a significant interaction effect in combination with the p.V205M (34.6 ms, p=0.003) resulting in a QTc of ∼500 ms. The mechanism of p.L353L's effect was attributed to approximately threefold increase in exon 8 exclusion resulting in ∼25% mutant transcripts of the total KCNQ1 transcript levels. Conclusions Our results provide the first evidence that synonymous variants outside the canonical splice sites in KCNQ1 can alter splicing and clinically impact phenotype. Through this mechanism, we identified that p.L353L can precipitate QT prolongation by itself and produce a clinically relevant interactive effect in conjunction with other LQTS variants. PMID:28264985

  19. Exploring a New Technique for Comparing Bilinguals' L1 and L2 Reading Speed

    ERIC Educational Resources Information Center

    Gauvin, Hanna S.; Hulstijn, Jan H.

    2010-01-01

    Is it possible to tell whether bilinguals are able to read simple text in their two languages equally fluently? Is it thus possible to distinguish balanced bilinguals from unbalanced bilinguals with respect to reading fluency in their first language (L1) and second language (L2)? In this study, we avoided making direct comparisons between L1 and…

  20. Method for Grey Scale Mapping of Underground Obstacles Using Video Pulse Radar Return

    DTIC Science & Technology

    1978-12-01

    the botton of Figure 3 is apparent. However, Figure 4 exhibits the one observed weakness of the Lagrange (or any polynomial) method. Large...t. . .. MWISS.S*4SW. - . W. . . SSV*V~t~fl~d*W*.StS . W ..... *W... *sn AW ~oo .*IB.Se.ve SWWZ.WWT...W. . . WVW.S* . *SS~SUA*.. ........ 0.305 mi stilf...5533 .. ... tel +lllt~llllllllllllllllll~l~ll............. . : .......lI~lI I llll~~ll .---I e~ ---- ..... lot I s 1 1i ....... IEr .5C

  1. Real-time Kp predictions from ACE real time solar wind

    NASA Astrophysics Data System (ADS)

    Detman, Thomas; Joselyn, Joann

    1999-06-01

    The Advanced Composition Explorer (ACE) spacecraft provides nearly continuous monitoring of solar wind plasma, magnetic fields, and energetic particles from the Sun-Earth L1 Lagrange point upstream of Earth in the solar wind. The Space Environment Center (SEC) in Boulder receives ACE telemetry from a group of international network of tracking stations. One-minute, and 1-hour averages of solar wind speed, density, temperature, and magnetic field components are posted on SEC's World Wide Web page within 3 to 5 minutes after they are measured. The ACE Real Time Solar Wind (RTSW) can be used to provide real-time warnings and short term forecasts of geomagnetic storms based on the (traditional) Kp index. Here, we use historical data to evaluate the performance of the first real-time Kp prediction algorithm to become operational.

  2. Determination of L1 retrotransposition kinetics in cultured cells

    PubMed Central

    Ostertag, Eric M.; Luning Prak, Eline T.; DeBerardinis, Ralph J.; Moran, John V.; Kazazian, Haig H.

    2000-01-01

    L1 retrotransposons are autonomous retroelements that are active in the human and mouse genomes. Previously, we developed a cultured cell assay that uses a neomycin phosphotransferase (neo) retrotransposition cassette to determine relative retrotransposition frequencies among various L1 elements. Here, we describe a new retrotransposition assay that uses an enhanced green fluorescent protein (EGFP) retrotransposition cassette to determine retrotransposition kinetics in cultured cells. We show that retrotransposition is not detected in cultured cells during the first 48 h post-transfection, but then proceeds at a continuous high rate for at least 16 days. We also determine the relative retrotransposition rates of two similar human L1 retrotransposons, L1RP and L1.3. L1RP retrotransposed in the EGFP assay at a rate of ~0.5% of transfected cells/day, ~3-fold higher than the rate measured for L1.3. We conclude that the new assay detects near real time retrotransposition in a single cell and is sufficiently sensitive to differentiate retrotransposition rates among similar L1 elements. The EGFP assay exhibits improved speed and accuracy compared to the previous assay when used to determine relative retrotransposition frequencies. Furthermore, the EGFP cassette has an expanded range of experimental applications. PMID:10684937

  3. DSCOVR_NISTAR_L1A

    Atmospheric Science Data Center

    2018-05-05

    ... Raw and calibrated radiometer science and engineering data. Project Title:  DSCOVR Discipline:  ... Level:  L1 Platform:  DEEP SPACE CLIMATE OBSERVATORY Instrument:  PHOTODIODE RADIOMETER ...

  4. The ORF1 Protein Encoded by LINE-1: Structure and Function During L1 Retrotransposition

    PubMed Central

    Martin, Sandra L.

    2006-01-01

    LINE-1, or L1 is an autonomous non-LTR retrotransposon in mammals. Retrotransposition requires the function of the two, L1-encoded polypeptides, ORF1p and ORF2p. Early recognition of regions of homology between the predicted amino acid sequence of ORF2 and known endonuclease and reverse transcriptase enzymes led to testable hypotheses regarding the function of ORF2p in retrotransposition. As predicted, ORF2p has been demonstrated to have both endonuclease and reverse transcriptase activities. In contrast, no homologs of known function have contributed to our understanding of the function of ORF1p during retrotransposition. Nevertheless, significant advances have been made such that we now know that ORF1p is a high affinity RNA binding protein that forms a ribonucleoprotein particle together with L1 RNA. Furthermore, ORF1p is a nucleic acid chaperone and this nucleic acid chaperone activity is required for L1 retrotransposition. PMID:16877816

  5. Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.

    PubMed

    De Rocker, Nina; Vergult, Sarah; Koolen, David; Jacobs, Eva; Hoischen, Alexander; Zeesman, Susan; Bang, Birgitte; Béna, Frédérique; Bockaert, Nele; Bongers, Ernie M; de Ravel, Thomy; Devriendt, Koenraad; Giglio, Sabrina; Faivre, Laurence; Joss, Shelagh; Maas, Saskia; Marle, Nathalie; Novara, Francesca; Nowaczyk, Malgorzata J M; Peeters, Hilde; Polstra, Abeltje; Roelens, Filip; Rosenberg, Carla; Thevenon, Julien; Tümer, Zeynep; Vanhauwaert, Suzanne; Varvagiannis, Konstantinos; Willaert, Andy; Willemsen, Marjolein; Willems, Marjolaine; Zuffardi, Orsetta; Coucke, Paul; Speleman, Frank; Eichler, Evan E; Kleefstra, Tjitske; Menten, Björn

    2015-06-01

    Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. In this study we evaluated a cohort of 22 patients (15 sporadic patients and two families) with a 2p25.3 aberration to further refine the clinical phenotype and to delineate the role of MYT1L in intellectual disability and obesity. In addition, myt1l spatiotemporal expression in zebrafish embryos was analyzed by quantitative polymerase chain reaction and whole-mount in situ hybridization. Complete MYT1L deletion, intragenic deletion, or duplication was observed in all sporadic patients, in addition to two patients with a de novo point mutation in MYT1L. The familial cases comprise a 6-Mb deletion in a father and his three children and a 5' MYT1L overlapping duplication in a father and his two children. Expression analysis in zebrafish embryos shows specific myt1l expression in the developing brain. Our data strongly strengthen the hypothesis that MYT1L is the causal gene for the observed syndromal intellectual disability. Moreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.Genet Med 17 6, 460-466.

  6. Multiplexed Immunofluorescence Reveals Potential PD-1/PD-L1 Pathway Vulnerabilities in Craniopharyngioma.

    PubMed

    Coy, Shannon; Rashid, Rumana; Lin, Jia-Ren; Du, Ziming; Donson, Andrew M; Hankinson, Todd C; Foreman, Nicholas K; Manley, Peter E; Kieran, Mark W; Reardon, David A; Sorger, Peter K; Santagata, Sandro

    2018-03-02

    Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous (ACP) and papillary (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible to BRAF/MEK inhibitors, but effective targeted therapies are needed for ACP. We explored the feasibility of targeting the PD-1/PD-L1 immune checkpoint pathway in ACP and PCP. We mapped and quantified PD-L1 and PD-1 expression in ACP and PCP resections using immunohistochemistry, immunofluorescence, and RNA in situ hybridization. We used tissue-based cyclic immunofluorescence (t-CyCIF) to map the spatial distribution of immune cells and characterize cell cycle and signaling pathways in ACP tumor cells which intrinsically express PD-1. All ACP (15±14% of cells, n=23, average±S.D.) and PCP (35±22% of cells, n=18) resections expressed PD-L1. In ACP, PD-L1 was predominantly expressed by tumor cells comprising the cyst-lining. In PCP, PD-L1 was highly-expressed by tumor cells surrounding the stromal fibrovascular cores. ACP also exhibited tumor cell-intrinsic PD-1 expression in whorled epithelial cells with nuclear-localized beta-catenin. These cells exhibited evidence of elevated mTOR and MAPK signaling. Profiling of immune populations in ACP and PCP showed a modest density of CD8+ T-cells. ACP exhibit PD-L1 expression in the tumor cyst-lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.

  7. Integrated Flight/Structural Mode Control for Very Flexible Aircraft Using L1 Adaptive Output Feedback Controller

    NASA Technical Reports Server (NTRS)

    Che, Jiaxing; Cao, Chengyu; Gregory, Irene M.

    2012-01-01

    This paper explores application of adaptive control architecture to a light, high-aspect ratio, flexible aircraft configuration that exhibits strong rigid body/flexible mode coupling. Specifically, an L(sub 1) adaptive output feedback controller is developed for a semi-span wind tunnel model capable of motion. The wind tunnel mount allows the semi-span model to translate vertically and pitch at the wing root, resulting in better simulation of an aircraft s rigid body motion. The control objective is to design a pitch control with altitude hold while suppressing body freedom flutter. The controller is an output feedback nominal controller (LQG) augmented by an L(sub 1) adaptive loop. A modification to the L(sub 1) output feedback is proposed to make it more suitable for flexible structures. The new control law relaxes the required bounds on the unmatched uncertainty and allows dependence on the state as well as time, i.e. a more general unmatched nonlinearity. The paper presents controller development and simulated performance responses. Simulation is conducted by using full state flexible wing models derived from test data at 10 different dynamic pressure conditions. An L(sub 1) adaptive output feedback controller is designed for a single test point and is then applied to all the test cases. The simulation results show that the L(sub 1) augmented controller can stabilize and meet the performance requirements for all 10 test conditions ranging from 30 psf to 130 psf dynamic pressure.

  8. L1/L2 Differences in the Acquisition of Form-Meaning Pairings in a Second Language

    ERIC Educational Resources Information Center

    McManus, Kevin

    2015-01-01

    This paper examines the impact of L1/L2 form-meaning differences in the domain of aspect to investigate whether L2 learners are able to acquire properties of the L2 that are different from the L1. Oral data were collected from English- and German-speaking university learners of French L2 (n = 75) at two different levels of proficiency. The results…

  9. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... determines that such recharacterization is appropriate to prevent avoidance of any tax imposed by title 26 of...) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.7701(l)-1 Conduit financing...

  10. Unusual Water Production Activity of Comet C/2012 S1 (ISON): Outbursts and Continuous Fragmentation

    NASA Astrophysics Data System (ADS)

    Combi, M. R.; Fougere, N.; Mäkinen, J. T. T.; Bertaux, J.-L.; Quémerais, E.; Ferron, S.

    2014-06-01

    The Solar Wind ANisotropies (SWAN) all-sky hydrogen Lyα camera on the SOlar and Heliospheric Observer (SOHO) satellite observed the hydrogen coma of comet C/2012 S1 (ISON) for most of the last month of its activity from 2013 October 24 to November 24, ending just 4 days before perihelion and its final disruption. The water production rate of the comet was determined from these observations. SOHO has been operating in a halo orbit around the Earth-Sun L1 Lagrange point since its launch in late 1995. Most water vapor produced by comets is ultimately photodissociated into two H atoms and one O atom producing a huge hydrogen coma that is routinely observed in the daily SWAN images in comets of sufficient brightness. Water production rates were calculated from 22 images over most of the last month of the pre-perihelion apparition. The water production rate increased very slowly on average from October 24.9 until November 12.9, staying between 1.8 and 3.4 × 1028 s-1, after which it increased dramatically, reaching 1.6 to 2 × 1030 s-1 from November 21.6 to 23.6. It was not detected after perihelion on December 3.7 when it should have been visible. We examine the active surface area necessary to explain the water production rate and its variation and are able to place constraints on the physical size of the original nucleus necessary to account for the large amount of activity from November 12.9 and until just before perihelion.

  11. Instability study for LOFT for L2-1, L2-2, and L2-3 pretest steady-state operating conditions

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

    Eide, S.A.

    The results are presented of a thermal-hydrodynamic flow instability study of the LOFT reactor for the L2-1, L2-2, and L2-3 pretest steady-state operating conditions. Comparison is made between the LOFT reactor and a typical PWR, and the effects on stability of differences in operating parameters and geometry are discussed. Results indicate that the LOFT reactor will be thermal-hydrodynamically stable for nominal and worst case operating conditions. The study supports the LOFT Experimental Safety Analyses for the L2-1, L2-2, and L2-3 tests.

  12. Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections.

    PubMed

    Bergenstal, Richard M; Bailey, Timothy S; Rodbard, David; Ziemen, Monika; Guo, Hailing; Muehlen-Bartmer, Isabel; Ahmann, Andrew J

    2017-04-01

    The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events. The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5]; P = 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (<54 mg/dL by SMPG) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]). Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100. © 2017 by the American Diabetes Association.

  13. KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

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

    Bentz, Gretchen L.; Bheda-Malge, Anjali; Wang, Ling

    Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressedmore » in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies. - Highlights: • Infection of endothelial cells with KSHV induced UCH-L1 expression. • KSHV LANA is sufficient for the induction of uch-l1. • Co-infection with KSHV and EBV (observed in some PELs) results in the additive induction of uch-l1. • EBV LMP1 also induced UCH-L1 expression. • LANA- and LMP1-mediated activation of the uch-l1 promoter is in part through RBP-Jκ.« less

  14. Determination of the Minimum Delta V Transfer Trajectory from a Low Earth Orbit to a Stable Orbit Around the Lagrangian Point L4 in a Restricted Four-Body System.

    DTIC Science & Technology

    1979-12-01

    the Moon revolves around the Earth. T. A . Heppenheimer (Ref 5) and his colleagues B. O’Leary and D. Kaplan (Ref 7) have also examined the pro- blem of...colony location and transfer trajectories. Heppenheimer found a 2/1 resonant orbit around the Earth 2S that could be reached from L2 by a Hohmann...would not allow a catcher near either of these points. In their work together, O’Leary, Kaplan and Heppenheimer found a transfer trajectory from L2

  15. The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.

    PubMed

    Sato, Yasunori; Kinoshita, Masahiko; Takemura, Shigekazu; Tanaka, Shogo; Hamano, Genya; Nakamori, Shoji; Fujikawa, Masahiro; Sugawara, Yasuhiko; Yamamoto, Takatsugu; Arimoto, Akira; Yamamura, Minako; Sasaki, Motoko; Harada, Kenichi; Nakanuma, Yasuni; Kubo, Shoji

    2017-03-01

    An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  16. The cell adhesion molecule L1 regulates the expression of choline acetyltransferase and the development of septal cholinergic neurons

    PubMed Central

    Cui, Xuezhi; Weng, Ying-Qi; Frappé, Isabelle; Burgess, Alison; Girão da Cruz, M Teresa; Schachner, Melitta; Aubert, Isabelle

    2011-01-01

    Mutations in the L1 gene cause severe brain malformations and mental retardation. We investigated the potential roles of L1 in the regulation of choline acetyltransferase (ChAT) and in the development of septal cholinergic neurons, which are known to project to the hippocampus and play key roles in cognitive functions. Using stereological approaches, we detected significantly fewer ChAT-positive cholinergic neurons in the medial septum and vertical limb of the diagonal band of Broca (MS/VDB) of 2-week-old L1-deficient mice compared to wild-type littermates (1644 ± 137 vs. 2051 ± 165, P = 0.038). ChAT protein levels in the septum were 53% lower in 2-week-old L1-deficient mice compared to wild-type littermates. ChAT activity in the septum was significantly reduced in L1-deficient mice compared to wild-type littermates at 1 (34%) and 2 (40%) weeks of age. In vitro, increasing doses of L1-Fc induced ChAT activity in septal neurons with a significant linear trend (*P = 0.0065). At 4 weeks of age in the septum and at all time points investigated in the caudate-putamen (CPu), the number of ChAT-positive neurons and the levels of ChAT activity were not statistically different between L1-deficient mice and wild-type littermates. The total number of cells positive for the neuronal nuclear antigen (NeuN) in the MS/VDB and CPu was not statistically different in L1-deficient mice compared to wild-type littermates, and comparable expression of the cell cycle marker Ki67 was observed. Our results indicate that L1 is required for the timely maturation of septal cholinergic neurons and that L1 promotes the expression and activity of ChAT in septal neurons. PMID:22399087

  17. Comparative Genomic Sequencing and Pathogenic Properties of Equine Herpesvirus 1 KyA and RacL11

    PubMed Central

    Shakya, Akhalesh K.; O’Callaghan, Dennis J.; Kim, Seong K.

    2017-01-01

    Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 Kentucky A (KyA) is attenuated in the mouse and equine, whereas wild-type pathogenic strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb. The complete DNA sequencing of the KyA genome revealed that genes UL17 (ORF17), US6 (ORF73; gI), US7 (ORF74; gE), and US8 (ORF75; 10 K) are deleted as compared to the RacL11 and Ab4 genomes. In-frame deletions in the US1 (ORF68), US4 (ORF71; gp2), and UL63 (ORF63; EICP0) genes and point mutations in 14 different open reading frames (ORFs) were detected in the KyA genome. Interestingly, UL1 (ORF1) and UL2 (ORF2) were deleted in both KyA and RacL11. Our previous studies showed that EHV-1 glycoproteins gI, gE, and full-length gp2 contribute to the pathogenesis of the RacL11 strain. The confirmation of these gene deletions in KyA suggests their contribution to the attenuation of this virus. The growth kinetics results revealed that KyA replicates to high titers in cell culture as compared to RacL11 and Ab4, indicating that the above genomic deletions and mutations in KyA do not have an inhibitory effect on KyA replication in cells of mouse, rabbit, equine, or human origin. Studies of EHV-1 pathogenesis in CBA mice showed that KyA is attenuated whereas mice infected with RacL11 succumbed by 3–6 days post-infection, which is consistent with our previous results. PMID:29312962

  18. Restricted L1 Estimators and Their Covariances,

    DTIC Science & Technology

    1980-06-01

    CD22 w =e 1-.< l’ -- I -M Ce -=, -2 C 22 CD -. 00 CD LJ L":v, wD .-C >-C CD U., -D -a 22J CD: CD. Vt. U.1 . CD* 31- a UOC CD I" -J zI == CŖ - 1- InCC.J...C 22 CC:.: 2 15Cb In0’C C 4 t’ 3 CD.2-cm I- I.- iC2 CD-3SJ U. cc CDam CC 22 0.-J~ I- iD C Me CC .JJ . A.2 Dt-2C. 2. D ~ 2 CD, Z-i- C -J 2Cn LI CD22 ...22 "I.- bII CD 0.-..CW I -- k- -o. CDCD-c =DDCCC-ce CDI- 22eCCDC.C I-L- 5 2wI-CDUct. I4.CDgCD Ci L., 2=9 E Mm t,2 cm CD22 ,,- D.-.2RCC Ce:CD .Cc n 9

  19. L1CAM in the Early Enteric and Urogenital System

    PubMed Central

    Pechriggl, Elisabeth Judith; Concin, Nicole; Blumer, Michael J.; Bitsche, Mario; Zwierzina, Marit; Dudas, Jozsef; Koziel, Katarzyna; Altevogt, Peter; Zeimet, Alain-Gustave; Fritsch, Helga

    2016-01-01

    L1 cell adhesion molecule (L1CAM) is a transmembrane molecule belonging to the L1 protein family. It has shown to be a key player in axonal guidance in the course of neuronal development. Furthermore, L1CAM is also crucial for the establishment of the enteric and urogenital organs and is aberrantly expressed in cancer originating in these organs. Carcinogenesis and embryogenesis follow a lot of similar molecular pathways, but unfortunately, comprehensive data on L1CAM expression and localization in human developing organs are lacking so far. In the present study we, therefore, examined the spatiotemporal distribution of L1CAM in the early human fetal period (weeks 8–12 of gestation) by means of immunohistochemistry and in situ hybridization (ISH). In the epithelia of the gastrointestinal organs, L1CAM localization cannot be observed in the examined stages most likely due to their advanced polarization and differentiation. Despite these results, our ISH data indicate weak L1CAM expression, but only in few epithelial cells. The genital tracts, however, are distinctly L1CAM positive throughout the entire fetal period. We, therefore, conclude that in embryogenesis L1CAM is crucial for further differentiation of epithelia. PMID:28026654

  20. Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated, advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

    PubMed

    Zhuansun, Yongxun; Huang, Fengting; Du, Yumo; Lin, Lin; Chen, Rui; Li, Jianguo

    2017-03-01

    The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients. Only randomized controlled trials (RCTs) comparing anti-PD-1/PD-L1 antibody with conventional chemotherapy in NSCLC were included. Overall survival (OS) in the intention-to-treat population was the primary outcome. The secondary outcomes were: progression-free survival (PFS) in the intention-to-treat population, objective response rate (ORR), the incidence of adverse events, OS and PFS in different PD-L1 expression subgroups. Four trials with a total of 2,174 patients were included. Anti-PD-1/PD-L1 antibody showed a significant benefit to OS in the intention-to-treat population [combined hazard ratio (HR) 0.67; 95% CI: 0.61-0.75, P<0.00001], a 33% reduction in the relative risk of death. PFS also favored anti-PD-1/PD-L1 antibody (HR 0.81, 95% CI: 0.70-0.95, P=0.009). The ORR was significantly higher with anti-PD-1/PD-L1 antibody than those with chemotherapy (RR of nonresponse, 0.92; 95% CI: 0.89-0.95, P<0.00001). Anti-PD-1/PD-L1 antibody was associated with greater efficacy than chemotherapy across the end points of OS and PFS when tumor PD-L1 expression scored ≥1%, ≥5%, and ≥50%, except for tumor PD-L1 expression scored <1%. The group receiving anti-PD-1/PD-L1 antibody had lower rates of treatment-related adverse events of any grade (RR 0.77; 95% CI: 0.73-0.81, P<0.00001) and treatment-related adverse events of grade 3-5 (RR 0.24; 95% CI: 0.14-0.41, P<0.00001). Anti

  1. Multistage ordering and critical singularities in C o1 -xZ nxA l2O4(0 ≤x ≤1 ) : Dilution and pressure effects in a magnetically frustrated system

    NASA Astrophysics Data System (ADS)

    Naka, Takashi; Sato, Koichi; Matsushita, Yoshitaka; Terada, Noriki; Ishii, Satoshi; Nakane, Takayuki; Taguchi, Minori; Nakayama, Minako; Hashishin, Takeshi; Ohara, Satoshi; Takami, Seiichi; Matsushita, Akiyuki

    2015-06-01

    We report comprehensive studies of the crystallographic, magnetic, and thermal properties of a spinel-type magnetically frustrated compound, CoA l2O4 , and a magnetically diluted system, C o1- xZ nxA l2O4 . These studies revealed the effects of dilution and disorder when the tetrahedral magnetic Co ion was replaced by the nonmagnetic Zn ion. Low-temperature anomalies were observed in magnetic susceptibility at x <0.6 . A multicritical point was apparent at T =3.4 K and x =0.12 , where the antiferromagnetic, spin-glass-like, and paramagnetic phases met. At that point, the quenched ferromagnetic component induced by a magnetic field during cooling was sharply enhanced and was observable below x =0.6 . At x ˜0.6 , magnetic susceptibility and specific heat were described by temperature power laws, χ ˜C /T ˜T-δ , in accord with the site percolation threshold of the diamond lattice. This behavior is reminiscent of a quantum critical singularity. We propose an x -temperature phase diagram in the range 0 ≤x ≤1 for C o1- xZ nxA l2O4 . The transition temperature of CoA l2O4 determined from magnetic susceptibility measured under hydrostatic pressure increased with increasing pressure.

  2. On l(1): Optimal decentralized performance

    NASA Technical Reports Server (NTRS)

    Sourlas, Dennis; Manousiouthakis, Vasilios

    1993-01-01

    In this paper, the Manousiouthakis parametrization of all decentralized stabilizing controllers is employed in mathematically formulating the l(sup 1) optimal decentralized controller synthesis problem. The resulting optimization problem is infinite dimensional and therefore not directly amenable to computations. It is shown that finite dimensional optimization problems that have value arbitrarily close to the infinite dimensional one can be constructed. Based on this result, an algorithm that solves the l(sup 1) decentralized performance problems is presented. A global optimization approach to the solution of the infinite dimensional approximating problems is also discussed.

  3. Materials trade study for lunar/gateway missions.

    PubMed

    Tripathi, R K; Wilson, J W; Cucinotta, F A; Anderson, B M; Simonsen, L C

    2003-01-01

    The National Aeronautics and Space Administration (NASA) administrator has identified protection from radiation hazards as one of the two biggest problems of the agency with respect to human deep space missions. The intensity and strength of cosmic radiation in deep space makes this a 'must solve' problem for space missions. The Moon and two Earth-Moon Lagrange points near Moon are being proposed as hubs for deep space missions. The focus of this study is to identify approaches to protecting astronauts and habitats from adverse effects from space radiation both for single missions and multiple missions for career astronauts to these destinations. As the great cost of added radiation shielding is a potential limiting factor in deep space missions, reduction of mass, without compromising safety, is of paramount importance. The choice of material and selection of the crew profile play major roles in design and mission operations. Material trade studies in shield design over multi-segmented missions involving multiple work and living areas in the transport and duty phase of space mission's to two Earth-Moon co-linear Lagrange points (L1) between Earth and the Moon and (L2) on back side of the moon as seen from Earth, and to the Moon have been studied. It is found that, for single missions, current state-of-the-art knowledge of material provides adequate shielding. On the other hand, the choice of shield material is absolutely critical for career astronauts and revolutionary materials need to be developed for these missions. This study also provides a guide to the effectiveness of multifunctional materials in preparation for more detailed geometry studies in progress. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  4. 75 FR 14206 - FPL Energy Point Beach, LLC; Point Beach Nuclear Plant, Units 1 and 2; Environmental Assessment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-266 And 50-301; NRC-2010-0123 FPL Energy Point Beach, LLC; Point Beach Nuclear Plant, Units 1 and 2; Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory Commission (NRC) is considering issuance of an Exemption, pursuant to...

  5. Bovine papillomavirus type 4 L1 gene transfection in a Drosophila S2 cell expression system: absence of L1 protein expression

    PubMed Central

    Góes, Luiz Gustavo Bentim; de Freitas, Antonio Carlos; Ferraz, Oilita Pereira; Rieger, Tania Tassinari; dos Santos, José Ferreira; Pereira, Alexandre; Beçak, Willy; Lindsey, Charles J.; de Cassia Stocco, Rita

    2008-01-01

    The development of a bovine papillomavirus (BPV) vaccine is an outstanding challenge. BPV protein L1 gene transfection in the Drosophila melanogaster S2 cell expression system failed to produce L1 protein notwithstanding correct L1 gene insertion. Severe genetic inbalance in the host cell line, including cytogenetic alterations, may account for the lack of protein expression. PMID:24031166

  6. Elevated levels of neural recognition molecule L1 in the cerebrospinal fluid of patients with Alzheimer disease and other dementia syndromes.

    PubMed

    Strekalova, Helen; Buhmann, Carsten; Kleene, Ralf; Eggers, Christian; Saffell, Jane; Hemperly, John; Weiller, Cornelius; Müller-Thomsen, Tomas; Schachner, Melitta

    2006-01-01

    In this study we surveyed a total of 218 cerebrospinal fluid (CSF) samples from patients with different neurological diseases including Alzheimer disease, non-Alzheimer forms of dementia, other neurodegenerative diseases without dementia and normal controls to quantitate by capture ELISA the concentrations of the immunoglobulin superfamily adhesion molecules L1 and NCAM, and characterized by immunoblot analysis the molecular forms of L1 and NCAM. We found a significant increase of L1 and a strong tendency for increase of the soluble fragments of NCAM in the CSF of Alzheimer patients compared to the normal control group. The proteolytic fragments of L1, but not NCAM were also elevated in patients with vascular dementia and dementia of mixed type. Higher L1 concentrations were observed irrespective of age and gender. NCAM concentrations were independent of gender, but positively correlated with age and, surprisingly, also with incidence of multiple sclerosis. Thus, there was an influence of Alzheimer and non-Alzheimer dementias and neurodegeneration on L1, whereas age and neurodegeneration influenced NCAM concentrations. These observations point to an abnormal processing and/or shedding of L1 and NCAM in dementia-related neurodegeneration and age, respectively, reflecting changes in adhesion molecule-related cell interactions.

  7. Searching for artificial equilibrium points to place satellites "above and below" L3 in the Sun-Earth system

    NASA Astrophysics Data System (ADS)

    de Almeida, A. K., Jr.; Prado, A. F. B. A.; Sanchez, D. M.; Yokoyama, T.

    2017-10-01

    Regarding practical applications of L3 of the Sun-Earth system, there are few studies with the goal of placing a spacecraft at this point, or in orbit around it. One of the main problems in placing a spacecraft near this equilibrium point is the fact that it is located behind the Sun with respect to the Earth. The Sun would be blocking direct communication between the spacecraft and the Earth. The present research gives several options to solve this problem by using a solar sail to place one or two spacecraft above and/or below the Ecliptic plane. This sail could also be used for the mission itself, to collect energy or particles. By using an adequate size, location and attitude of the solar sail, the equilibrium point can be moved from its original location to allow communications between the spacecraft and the Earth. A preliminary study of a solar sail that uses this strategy is shown here.

  8. Characterization of high order spatial discretizations and lumping techniques for discontinuous finite element SN transport

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

    Maginot, P. G.; Ragusa, J. C.; Morel, J. E.

    2013-07-01

    We examine several possible methods of mass matrix lumping for discontinuous finite element discrete ordinates transport using a Lagrange interpolatory polynomial trial space. Though positive outflow angular flux is guaranteed with traditional mass matrix lumping in a purely absorbing 1-D slab cell for the linear discontinuous approximation, we show that when used with higher degree interpolatory polynomial trial spaces, traditional lumping does yield strictly positive outflows and does not increase in accuracy with an increase in trial space polynomial degree. As an alternative, we examine methods which are 'self-lumping'. Self-lumping methods yield diagonal mass matrices by using numerical quadrature restrictedmore » to the Lagrange interpolatory points. Using equally-spaced interpolatory points, self-lumping is achieved through the use of closed Newton-Cotes formulas, resulting in strictly positive outflows in pure absorbers for odd power polynomials in 1-D slab geometry. By changing interpolatory points from the traditional equally-spaced points to the quadrature points of the Gauss-Legendre or Lobatto-Gauss-Legendre quadratures, it is possible to generate solution representations with a diagonal mass matrix and a strictly positive outflow for any degree polynomial solution representation in a pure absorber medium in 1-D slab geometry. Further, there is no inherent limit to local truncation error order of accuracy when using interpolatory points that correspond to the quadrature points of high order accuracy numerical quadrature schemes. (authors)« less

  9. Line defect Schur indices, Verlinde algebras and U(1) r fixed points

    NASA Astrophysics Data System (ADS)

    Neitzke, Andrew; Yan, Fei

    2017-11-01

    Given an N=2 superconformal field theory, we reconsider the Schur index ℐ L ( q) in the presence of a half line defect L. Recently Cordova-Gaiotto-Shao found that ℐ L ( q) admits an expansion in terms of characters of the chiral algebra A introduced by Beem et al., with simple coefficients υ L, β ( q). We report a puzzling new feature of this expansion: the q → 1 limit of the coefficients υ L, β ( q) is linearly related to the vacuum expectation values 〈 L〉 in U(1) r -invariant vacua of the theory compactified on S 1. This relation can be expressed algebraically as a commutative diagram involving three algebras: the algebra generated by line defects, the algebra of functions on U(1) r -invariant vacua, and a Verlindelike algebra associated to A . Our evidence is experimental, by direct computation in the Argyres-Douglas theories of type ( A 1, A 2), ( A 1, A 4), ( A 1, A 6), ( A 1, D 3) and ( A 1, D 5). In the latter two theories, which have flavor symmetries, the Verlinde-like algebra which appears is a new deformation of algebras previously considered.

  10. The Amount, Purpose, and Reasons for Using L1 in L2 Classrooms

    ERIC Educational Resources Information Center

    de la Campa, Juliane C.; Nassaji, Hossein

    2009-01-01

    This study examined the amount, the purposes, and the reasons why L1 is used in L2 classrooms. Data consist of video and audio recording of samples of two instructors' L2 classes over the course of a 12-week semester in two second-year German conversation university courses, instructor interviews, and stimulated recall sessions. Results revealed…

  11. L1 retrotransposons and somatic mosaicism in the brain.

    PubMed

    Richardson, Sandra R; Morell, Santiago; Faulkner, Geoffrey J

    2014-01-01

    Long interspersed element 1 (LINE-1 or L1) retrotransposons have generated one-third of the human genome, and their ongoing mobility is a source of inter- and intraindividual genetic diversity. Although retrotransposition in metazoans has long been considered a germline phenomenon, recent experiments using cultured cells, animal models, and human tissues have revealed extensive L1 mobilization in rodent and human neurons, as well as mobile element activity in the Drosophila brain. In this review, we evaluate the available evidence for L1 retrotransposition in the brain and discuss mechanisms that may regulate neuronal retrotransposition in vivo. We compare experimental strategies used to map de novo somatic retrotransposition events and present the optimal criteria to identify a somatic L1 insertion. Finally, we discuss the unresolved impact of L1-mediated somatic mosaicism upon normal neurobiology, as well as its potential to drive neurological disease.

  12. Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

    PubMed

    Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

    2017-01-01

    Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

  13. A proximity algorithm accelerated by Gauss-Seidel iterations for L1/TV denoising models

    NASA Astrophysics Data System (ADS)

    Li, Qia; Micchelli, Charles A.; Shen, Lixin; Xu, Yuesheng

    2012-09-01

    Our goal in this paper is to improve the computational performance of the proximity algorithms for the L1/TV denoising model. This leads us to a new characterization of all solutions to the L1/TV model via fixed-point equations expressed in terms of the proximity operators. Based upon this observation we develop an algorithm for solving the model and establish its convergence. Furthermore, we demonstrate that the proposed algorithm can be accelerated through the use of the componentwise Gauss-Seidel iteration so that the CPU time consumed is significantly reduced. Numerical experiments using the proposed algorithm for impulsive noise removal are included, with a comparison to three recently developed algorithms. The numerical results show that while the proposed algorithm enjoys a high quality of the restored images, as the other three known algorithms do, it performs significantly better in terms of computational efficiency measured in the CPU time consumed.

  14. 1. GENERAL VIEW OF WEST FACE OF ENTRY CONTROL POINT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. GENERAL VIEW OF WEST FACE OF ENTRY CONTROL POINT (BLDG. 768) SHOWING RELATIVE POSITION TO TECHNICAL SUPPORT BUILDING (BLDG. 762/762A) AND SLC-3 AIR FORCE BUILDING (BLDG. 761) - Vandenberg Air Force Base, Space Launch Complex 3, Entry Control Point, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  15. Renorming c0 and closed, bounded, convex sets with fixed point property for affine nonexpansive mappings

    NASA Astrophysics Data System (ADS)

    Nezir, Veysel; Mustafa, Nizami

    2017-04-01

    In 2008, P.K. Lin provided the first example of a nonreflexive space that can be renormed to have fixed point property for nonexpansive mappings. This space was the Banach space of absolutely summable sequences l1 and researchers aim to generalize this to c0, Banach space of null sequences. Before P.K. Lin's intriguing result, in 1979, Goebel and Kuczumow showed that there is a large class of non-weak* compact closed, bounded, convex subsets of l1 with fixed point property for nonexpansive mappings. Then, P.K. Lin inspired by Goebel and Kuczumow's ideas to give his result. Similarly to P.K. Lin's study, Hernández-Linares worked on L1 and in his Ph.D. thesis, supervisored under Maria Japón, showed that L1 can be renormed to have fixed point property for affine nonexpansive mappings. Then, related questions for c0 have been considered by researchers. Recently, Nezir constructed several equivalent norms on c0 and showed that there are non-weakly compact closed, bounded, convex subsets of c0 with fixed point property for affine nonexpansive mappings. In this study, we construct a family of equivalent norms containing those developed by Nezir as well and show that there exists a large class of non-weakly compact closed, bounded, convex subsets of c0 with fixed point property for affine nonexpansive mappings.

  16. PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.

    PubMed

    Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing

    2018-02-12

    The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer. The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors. Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors. Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Are Alphabetic Language-Derived Models of L2 Reading Relevant to L1 Logographic Background Readers?

    ERIC Educational Resources Information Center

    Ehrich, John Fitzgerald; Zhang, Lawrence Jun; Mu, Jon Congjun; Ehrich, Lisa Catherine

    2013-01-01

    In this paper, we argue that second language (L2) reading research, which has been informed by studies involving first language (L1) alphabetic English reading, may be less relevant to L2 readers with non-alphabetic reading backgrounds, such as Chinese readers with an L1 logographic (Chinese character) learning history. We provide both…

  18. Determinants of BH3 Binding Specificity for Mcl-1 versus Bcl-x[subscript L

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

    Dutta, Sanjib; Gullá, Stefano; Chen, T. Scott

    2010-06-25

    Interactions among Bcl-2 family proteins are important for regulating apoptosis. Prosurvival members of the family interact with proapoptotic BH3 (Bcl-2-homology-3)-only members, inhibiting execution of cell death through the mitochondrial pathway. Structurally, this interaction is mediated by binding of the {alpha}-helical BH3 region of the proapoptotic proteins to a conserved hydrophobic groove on the prosurvival proteins. Native BH3-only proteins exhibit selectivity in binding prosurvival members, as do small molecules that block these interactions. Understanding the sequence and structural basis of interaction specificity in this family is important, as it may allow the prediction of new Bcl-2 family associations and/or the designmore » of new classes of selective inhibitors to serve as reagents or therapeutics. In this work, we used two complementary techniques - yeast surface display screening from combinatorial peptide libraries and SPOT peptide array analysis - to elucidate specificity determinants for binding to Bcl-x{sub L} versus Mcl-1, two prominent prosurvival proteins. We screened a randomized library and identified BH3 peptides that bound to either Mcl-1 or Bcl-x{sub L} selectively or to both with high affinity. The peptides competed with native ligands for binding into the conserved hydrophobic groove, as illustrated in detail by a crystal structure of a specific peptide bound to Mcl-1. Mcl-1-selective peptides from the screen were highly specific for binding Mcl-1 in preference to Bcl-x{sub L}, Bcl-2, Bcl-w, and Bfl-1, whereas Bcl-x{sub L}-selective peptides showed some cross-interaction with related proteins Bcl-2 and Bcl-w. Mutational analyses using SPOT arrays revealed the effects of 170 point mutations made in the background of a peptide derived from the BH3 region of Bim, and a simple predictive model constructed using these data explained much of the specificity observed in our Mcl-1 versus Bcl-x{sub L} binders.« less

  19. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  20. Plasmonic Roche lobe in metal-dielectric-metal structure

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

    Shiu, Ruei-Cheng; Lan, Yung-Chiang

    2013-07-15

    This study investigates a plasmonic Roche lobe that is based on a metal-dielectric-metal (MDM) structure using finite-difference time-domain simulations and theoretical analyses. The effective refractive index of the MDM structure has two centers and is inversely proportional to the distance from the position of interest to the centers, in a manner that is analogous to the gravitational potential in a two-star system. The motion of surface plasmons (SPs) strongly depends on the ratio of permittivities at the two centers. The Lagrange point is an unstable equilibrium point for SPs that propagate in the system. After the SPs have passed throughmore » the Lagrange point, their spread drastically increases.« less

  1. Toward Independent L2 Readers: Effects of Text Adjuncts, Subject Knowledge, L1 Reading, and L2 Proficiency

    ERIC Educational Resources Information Center

    Brantmeier, Cindy; Hammadou Sullivan, JoAnn; Strube, Michael

    2014-01-01

    With 97 learners in an advanced Spanish course, the study examines the effects of textual enhancement adjuncts, prior subject knowledge, first language (L1) reading ability, and second language (L2) Spanish proficiency on L2 comprehension of scientific passages. Readings included two texts with two types of embedded questions: a pause or written…

  2. PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1

    PubMed Central

    Chen, Gang; Kim, Yong Ho; Li, Hui; Luo, Hao; Liu, Da-Lu; Zhang, Zhi-Jun; Lay, Mark; Chang, Wonseok; Zhang, Yu-Qiu; Ji, Ru-Rong

    2018-01-01

    Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through PD-1 receptor expressed on T cells. However, the role of PD-L1/PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglia (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evokes analgesia in naïve mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induces mechanical allodynia. Mice lacking Pd1 exhibit thermal and mechanical hypersensitivity. PD-1 activation in DRG nociceptive neurons by PD-L1 induces SHP-1 phosphorylation, inhibits sodium channels, and causes hyperpolarization through activation of TREK2 K+ channels. PD-L1 also potently suppresses nociceptive neuron excitability of human DRGs. Remarkably, blocking PD-L1 or PD-1 elicits spontaneous pain and allodynia in melanoma-bearing mice. Our findings identify a previously unrecognized role of PD-L1 as an endogenous pain inhibitor and a neuromodulator. PMID:28530662

  3. Interactions between EGFR and PD-1/PD-L1 pathway: Implications for treatment of NSCLC.

    PubMed

    Li, Xue; Lian, Zhen; Wang, Shuai; Xing, Ligang; Yu, Jinming

    2018-04-01

    Immune checkpoint inhibitors targeting the programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway displayed striking and durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, it is still undefined about the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with EGFR activating mutations. Preclinical studies indicate the immune modulatory effect of EGFR signaling by regulating expression of MHC I/II and PD-L1 on tumor cells and activity of lymphocytes. Thus, it might be practicable for the use of PD-1/PD-L1 inhibitors as monotherapy or combined with EGFR-TKIs in patients with EGFR activating mutations. In this review, we discussed the regulation effect of EGFR signaling on PD-1/PD-L1 pathway and the potential mechanisms behind combing EGFR-TKIs with PD-1/PD-L1 inhibitors. We also reviewed current available data on PD-1/PD-L1 inhibitors as monotherapy or combined with EGFR-TKIs in NSCLC with EGFR activating mutations, and explored possible factors influence its efficacy, which would be important considerations for future clinical trial designs. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Reviving the Dead: History and Reactivation of an Extinct L1

    PubMed Central

    Yang, Lei; Brunsfeld, John; Scott, LuAnn; Wichman, Holly

    2014-01-01

    Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accommodated two or more simultaneously active L1 families throughout their evolutionary history, and major peaks of L1 deposition into the genome always involved multiple families. We compared the consensus sequences of the two major megabat L1 families at the time of their extinction to consensus L1s of a variety of mammalian species. Megabat L1s are comparable to the other mammalian L1s in terms of adenosine content and conserved amino acids in the open reading frames (ORFs). However, the intergenic region (IGR) of the reconstructed element from the more active family is dramatically longer than the IGR of well-characterized human and mouse L1s. We synthesized the reconstructed element from this L1 family and tested the ability of its components to support retrotransposition in a tissue culture assay. Both ORFs are capable of supporting retrotransposition, while the IGR is inhibitory to retrotransposition, especially when combined with either of the reconstructed ORFs. We dissected the inhibitory effect of the IGR by testing truncated and shuffled versions and found that length is a key factor, but not the only one affecting inhibition of retrotransposition. Although the IGR is inhibitory to retrotransposition, this inhibition does not account for the extinction of L1s in megabats. Overall, the evolution of the L1 sequence or the quiescence of L1 is unlikely the reason of L1 extinction. PMID:24968166

  5. Reviving the dead: history and reactivation of an extinct l1.

    PubMed

    Yang, Lei; Brunsfeld, John; Scott, LuAnn; Wichman, Holly

    2014-06-01

    Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accommodated two or more simultaneously active L1 families throughout their evolutionary history, and major peaks of L1 deposition into the genome always involved multiple families. We compared the consensus sequences of the two major megabat L1 families at the time of their extinction to consensus L1s of a variety of mammalian species. Megabat L1s are comparable to the other mammalian L1s in terms of adenosine content and conserved amino acids in the open reading frames (ORFs). However, the intergenic region (IGR) of the reconstructed element from the more active family is dramatically longer than the IGR of well-characterized human and mouse L1s. We synthesized the reconstructed element from this L1 family and tested the ability of its components to support retrotransposition in a tissue culture assay. Both ORFs are capable of supporting retrotransposition, while the IGR is inhibitory to retrotransposition, especially when combined with either of the reconstructed ORFs. We dissected the inhibitory effect of the IGR by testing truncated and shuffled versions and found that length is a key factor, but not the only one affecting inhibition of retrotransposition. Although the IGR is inhibitory to retrotransposition, this inhibition does not account for the extinction of L1s in megabats. Overall, the evolution of the L1 sequence or the quiescence of L1 is unlikely the reason of L1 extinction.

  6. Human LINE-1 retrotransposition requires a metastable coiled coil and a positively charged N-terminus in L1ORF1p

    PubMed Central

    Khazina, Elena

    2018-01-01

    LINE-1 (L1) is an autonomous retrotransposon, which acted throughout mammalian evolution and keeps contributing to human genotypic diversity, genetic disease and cancer. L1 encodes two essential proteins: L1ORF1p, a unique RNA-binding protein, and L1ORF2p, an endonuclease and reverse transcriptase. L1ORF1p contains an essential, but rapidly evolving N-terminal portion, homo-trimerizes via a coiled coil and packages L1RNA into large assemblies. Here, we determined crystal structures of the entire coiled coil domain of human L1ORF1p. We show that retrotransposition requires a non-ideal and metastable coiled coil structure, and a strongly basic L1ORF1p amino terminus. Human L1ORF1p therefore emerges as a highly calibrated molecular machine, sensitive to mutation but functional in different hosts. Our analysis rationalizes the locally rapid L1ORF1p sequence evolution and reveals striking mechanistic parallels to coiled coil-containing membrane fusion proteins. It also suggests how trimeric L1ORF1p could form larger meshworks and indicates critical novel steps in L1 retrotransposition. PMID:29565245

  7. Regularized Filters for L1-Norm-Based Common Spatial Patterns.

    PubMed

    Wang, Haixian; Li, Xiaomeng

    2016-02-01

    The l1 -norm-based common spatial patterns (CSP-L1) approach is a recently developed technique for optimizing spatial filters in the field of electroencephalogram (EEG)-based brain computer interfaces. The l1 -norm-based expression of dispersion in CSP-L1 alleviates the negative impact of outliers. In this paper, we further improve the robustness of CSP-L1 by taking into account noise which does not necessarily have as large a deviation as with outliers. The noise modelling is formulated by using the waveform length of the EEG time course. With the noise modelling, we then regularize the objective function of CSP-L1, in which the l1-norm is used in two folds: one is the dispersion and the other is the waveform length. An iterative algorithm is designed to resolve the optimization problem of the regularized objective function. A toy illustration and the experiments of classification on real EEG data sets show the effectiveness of the proposed method.

  8. Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis.

    PubMed

    Kurano, Makoto; Hara, Masumi; Satoh, Hiroaki; Tsukamoto, Kazuhisa

    2015-05-01

    Inhibition of intestinal NPC1L1 by ezetimibe has been demonstrated to improve glucose metabolism in rodent models; however, the role of hepatic NPC1L1 in glucose metabolism has not been elucidated. In this study, we analyzed the effects of hepatic NPC1L1 on glucose metabolism. We overexpressed NPC1L1 in the livers of lean wild type mice, diet-induced obesity mice and db/db mice with adenoviral gene transfer. We found that in all three mouse models, hepatic NPC1L1 overexpression lowered fasting blood glucose levels as well as blood glucose levels on ad libitum; in db/db mice, hepatic NPC1L1 overexpression improved blood glucose levels to almost the same as those found in lean wild type mice. A pyruvate tolerance test revealed that gluconeogenesis was suppressed by hepatic NPC1L1 overexpression. Further analyses revealed that hepatic NPC1L1 overexpression decreased the expression of FoxO1, resulting in the reduced expression of G6Pase and PEPCK, key enzymes in gluconeogenesis. These results indicate that hepatic NPC1L1 might have distinct properties of suppressing gluconeogenesis via inhibition of FoxO1 pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Generation and evaluation of Cryosat-2 SARIn L1b Interferometric elevation

    NASA Astrophysics Data System (ADS)

    DONG, Y.; Zhang, K.; Liu, Q.; MA, J.; WANG, J.

    2016-12-01

    CryoSat-2 radar altimeter data have successfully used in mapping surface elevations of ice caps and ice sheets, finding the change of surface height in polar area. The SARIn mode of Synthetic Aperture Interferometric Altimeter (SIRAL), which working similar with the traditional Interferometric Synthetic Aperture Radar (IFSAR) method, can improve the across- and along-track resolution by IFSAR processing algorithm. In this study, three L1b Baseline-C SARIn tracks over the Filchner ice shelf are used to generate the location and height of ground points in sloping glacial terrain. The elevation data is mapped and validated with IceBridge Airborne Topographic Mapper (ATM) data acquired at Nov. 2, 2012. The comparison with ATM data shows a mean difference of -1.91 m with a stand deviation of 4.04 m.

  10. Assimilation of L2 vowels to L1 phonemes governs L2 learning in adulthood: a behavioral and ERP study

    PubMed Central

    Grimaldi, Mirko; Sisinni, Bianca; Gili Fivela, Barbara; Invitto, Sara; Resta, Donatella; Alku, Paavo; Brattico, Elvira

    2014-01-01

    According to the Perceptual Assimilation Model (PAM), articulatory similarity/dissimilarity between sounds of the second language (L2) and the native language (L1) governs L2 learnability in adulthood and predicts L2 sound perception by naïve listeners. We performed behavioral and neurophysiological experiments on two groups of university students at the first and fifth years of the English language curriculum and on a group of naïve listeners. Categorization and discrimination tests, as well as the mismatch negativity (MMN) brain response to L2 sound changes, showed that the discriminatory capabilities of the students did not significantly differ from those of the naïve subjects. In line with the PAM model, we extend the findings of previous behavioral studies showing that, at the neural level, classroom instruction in adulthood relies on assimilation of L2 vowels to L1 phoneme categories and does not trigger improvement in L2 phonetic discrimination. Implications for L2 classroom teaching practices are discussed. PMID:24860470

  11. Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated, advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

    PubMed Central

    Zhuansun, Yongxun; Huang, Fengting; Du, Yumo; Lin, Lin

    2017-01-01

    Background The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. Methods PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients. Only randomized controlled trials (RCTs) comparing anti-PD-1/PD-L1 antibody with conventional chemotherapy in NSCLC were included. Overall survival (OS) in the intention-to-treat population was the primary outcome. The secondary outcomes were: progression-free survival (PFS) in the intention-to-treat population, objective response rate (ORR), the incidence of adverse events, OS and PFS in different PD-L1 expression subgroups. Results Four trials with a total of 2,174 patients were included. Anti-PD-1/PD-L1 antibody showed a significant benefit to OS in the intention-to-treat population [combined hazard ratio (HR) 0.67; 95% CI: 0.61–0.75, P<0.00001], a 33% reduction in the relative risk of death. PFS also favored anti-PD-1/PD-L1 antibody (HR 0.81, 95% CI: 0.70–0.95, P=0.009). The ORR was significantly higher with anti-PD-1/PD-L1 antibody than those with chemotherapy (RR of nonresponse, 0.92; 95% CI: 0.89–0.95, P<0.00001). Anti-PD-1/PD-L1 antibody was associated with greater efficacy than chemotherapy across the end points of OS and PFS when tumor PD-L1 expression scored ≥1%, ≥5%, and ≥50%, except for tumor PD-L1 expression scored <1%. The group receiving anti-PD-1/PD-L1 antibody had lower rates of treatment-related adverse events of any grade (RR 0.77; 95% CI: 0.73–0.81, P<0.00001) and treatment-related adverse events of grade 3–5 (RR 0

  12. Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

    PubMed

    Chung, Jee-Eun; Lee, Kyung Eun; Chang, Byung Chul; Gwak, Hye Sun

    2018-01-30

    The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. Copyright © 2017. Published by Elsevier B.V.

  13. Rendezvous missions with minimoons from L1

    NASA Astrophysics Data System (ADS)

    Chyba, M.; Haberkorn, T.; Patterson, G.

    2014-07-01

    We propose to present asteroid capture missions with the so-called minimoons. Minimoons are small asteroids that are temporarily captured objects on orbits in the Earth-Moon system. It has been suggested that, despite their small capture probability, at any time there are one or two meter diameter minimoons, and progressively greater numbers at smaller diameters. The minimoons orbits differ significantly from elliptical orbits which renders a rendezvous mission more challenging, however they offer many advantages for such missions that overcome this fact. First, they are already on geocentric orbits which results in short duration missions with low Delta-v, this translates in cost efficiency and low-risk targets. Second, beside their close proximity to Earth, an advantage is their small size since it provides us with the luxury to retrieve the entire asteroid and not only a sample of material. Accessing the interior structure of a near-Earth satellite in its morphological context is crucial to an in-depth analysis of the structure of the asteroid. Historically, 2006 RH120 is the only minimoon that has been detected but work is ongoing to determine which modifications to current observation facilities is necessary to provide detection algorithm capabilities. In the event that detection is successful, an efficient algorithm to produce a space mission to rendezvous with the detected minimoon is highly desirable to take advantage of this opportunity. This is the main focus of our work. For the design of the mission we propose the following. The spacecraft is first placed in hibernation on a Lissajoux orbit around the liberation point L1 of the Earth-Moon system. We focus on eight-shaped Lissajoux orbits to take advantage of the stability properties of their invariant manifolds for our transfers since the cost to minimize is the spacecraft fuel consumption. Once a minimoon has been detected we must choose a point on its orbit to rendezvous (in position and velocities

  14. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation.

    PubMed

    Hartmann, Bianca; Wai, Timothy; Hu, Hao; MacVicar, Thomas; Musante, Luciana; Fischer-Zirnsak, Björn; Stenzel, Werner; Gräf, Ralph; van den Heuvel, Lambert; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Langer, Thomas; Kaindl, Angela M

    2016-08-06

    Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans.

  15. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation

    PubMed Central

    Hartmann, Bianca; Wai, Timothy; Hu, Hao; MacVicar, Thomas; Musante, Luciana; Fischer-Zirnsak, Björn; Stenzel, Werner; Gräf, Ralph; van den Heuvel, Lambert; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Langer, Thomas; Kaindl, Angela M

    2016-01-01

    Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans. DOI: http://dx.doi.org/10.7554/eLife.16078.001 PMID:27495975

  16. Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.

    PubMed

    Reinecke, James B; Katafiasz, Dawn; Naslavsky, Naava; Caplan, Steve

    2015-01-01

    During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms.

    PubMed

    Ilie, Marius; Khambata-Ford, Shirin; Copie-Bergman, Christiane; Huang, Lingkang; Juco, Jonathan; Hofman, Veronique; Hofman, Paul

    2017-01-01

    For non-small cell lung cancer (NSCLC), treatment with pembrolizumab is limited to patients with tumours expressing PD-L1 assessed by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx (Dako, Inc.) companion diagnostic test, on the Dako Autostainer Link 48 (ASL48) platform. Optimised protocols are urgently needed for use of the 22C3 antibody concentrate to test PD-L1 expression on more widely available IHC autostainers. We evaluated PD-L1 expression using the 22C3 antibody concentrate in the three main commercially available autostainers Dako ASL48, BenchMark ULTRA (Ventana Medical Systems, Inc.), and Bond-III (Leica Biosystems) and compared the staining results with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Several technical conditions for laboratory-developed tests (LDTs) were evaluated in tonsil specimens and a training set of three NSCLC samples. Optimised protocols were then validated in 120 NSCLC specimens. Optimised protocols were obtained on both the VENTANA BenchMark ULTRA and Dako ASL48 platforms. Significant expression of PD-L1 was obtained on tissue controls with the Leica Bond-III autostainer when high concentrations of the 22C3 antibody were used. It therefore was not tested on the 120 NSCLC specimens. An almost 100% concordance rate for dichotomized tumour proportion score (TPS) results was observed between TPS ratings using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Interpathologist agreement was high on both LDTs and the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Availability of standardized protocols for determining PD-L1 expression using the 22C3 antibody concentrate on the widely available Dako ASL48 and VENTANA BenchMark ULTRA IHC platforms will expand the number of laboratories able to determine eligibility of patients with NSCLC for treatment with pembrolizumab in a reliable and concordant

  18. f( R, L m ) gravity

    NASA Astrophysics Data System (ADS)

    Harko, Tiberiu; Lobo, Francisco S. N.

    2010-11-01

    We generalize the f( R) type gravity models by assuming that the gravitational Lagrangian is given by an arbitrary function of the Ricci scalar R and of the matter Lagrangian L m . We obtain the gravitational field equations in the metric formalism, as well as the equations of motion for test particles, which follow from the covariant divergence of the energy-momentum tensor. The equations of motion for test particles can also be derived from a variational principle in the particular case in which the Lagrangian density of the matter is an arbitrary function of the energy density of the matter only. Generally, the motion is non-geodesic, and it takes place in the presence of an extra force orthogonal to the four-velocity. The Newtonian limit of the equation of motion is also considered, and a procedure for obtaining the energy-momentum tensor of the matter is presented. The gravitational field equations and the equations of motion for a particular model in which the action of the gravitational field has an exponential dependence on the standard general relativistic Hilbert-Einstein Lagrange density are also derived.

  19. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

    PubMed Central

    Xu-Monette, Zijun Y.; Zhang, Mingzhi; Li, Jianyong; Young, Ken H.

    2017-01-01

    PD-1–PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1–PD-L1 axis is affected by the complex immunologic regulation network, and some CD8+ T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer. PMID:29255458

  20. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

    PubMed

    Xu-Monette, Zijun Y; Zhang, Mingzhi; Li, Jianyong; Young, Ken H

    2017-01-01

    PD-1-PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1-PD-L1 axis is affected by the complex immunologic regulation network, and some CD8 + T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer.

  1. Reading in L2 (English) and L1 (Persian): An Investigation into Reverse Transfer of Reading Strategies

    ERIC Educational Resources Information Center

    Talebi, Seyed Hassan

    2012-01-01

    This study investigates the effect of reading strategies instruction in L2 (English) on raising reading strategies awareness and use and reading ability of Iranian EFL learners in L2 (English) and L1 (Persian) as a result of transfer of reading strategies from L2 to L1. To this purpose, 120 students of intermediate and advanced English proficiency…

  2. PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas.

    PubMed

    Wang, Yi; Wu, Ling; Tian, Chen; Zhang, Yizhuo

    2018-02-01

    Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas. In this review, we outline the rationale for investigation of PD-1-PD-L1 immune-checkpoint blockade in lymphomas and discuss their prospect of applications in clinical treatment.

  3. Morphometric MRI Imaging Study of the Corridor for the Oblique Lumbar Interbody Fusion Technique at L1-L5.

    PubMed

    Julian Li, Jia Xi; Mobbs, Ralph J; Phan, Kevin

    2018-03-01

    Anterior lumbar interbody fusion and lateral lumbar interbody fusion are associated with approach-related disadvantages. Oblique lumbar interbody fusion (OLIF) is the proposed solution, especially for upper lumbar levels. We analyzed the size and regional anatomy of the corridor used in the OLIF technique between levels L1 and L5. This is a morphometric study of 200 randomly selected magnetic resonance imaging (MRI) studies with features of lumbar degenerative disease. On MRI, the oblique corridor was defined as the smallest distance between the psoas major muscle and aorta or inferior vena cava (or common iliac artery) and measured at the L1/L2, L2/L3, L3/L4, and L4/L5 disc levels on both the left and right on the axial images at the mid-disc level. Mean distances of the oblique corridor on the left side were L1/L2 = 18.90 mm, L2/L3 = 15.50 mm; L3/L4 = 12.75 mm, and L4/L5 = 8.92 mm; on the right side, they were L1/L2 = 14.80 mm, L2/L3 = 5.50 mm, L3/L4 = 3.00 mm, and L4/L5 = 1.46 mm. For both sides, the corridor size was not significantly affected by sex, and it increased with age and decreased at the inferior lumbar disc levels. The L1/L2 and L2/L3 levels may be obstructed by the ipsilateral kidney and renal vasculature on both sides and the liver on the right side. A left-sided OLIF approach is viable for both sexes. Oblique access to the L1/L2 and L2/L3 disc levels is feasible regardless of age, whereas the L3/L4 and L4/L5 levels may be more suitable in older patients, especially for male patients. The right-sided approach is less likely to be performed effectively. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Solar and Heliospheric Data Requirements: Going Further Than L1

    NASA Technical Reports Server (NTRS)

    Szabo, A.

    2011-01-01

    Current operational space weather forecasting relies on solar wind observations made by the ACE spacecraft located at the L1 point providing 30-40 minutes warning time. Some use is also made of SOHO and STEREO solar imaging that potentially can give multiple days of warning time. However, our understanding of the propagation and evolution of solar wind transients is still limited resulting in a typical timing uncertainty of approximately 10 hours. In order to improve this critical understanding, a number of NASA missions are being planned. Specifically the Solar Probe Plus and Solar Orbiter missions will investigate the inner Heliospheric evolution of coronal mass ejections and the acceleration and propagation of solar energetic particles. In addition, a number of multi-spacecraft concepts have been studied that have the potential to significantly improve the accuracy of long-term space weather forecasts.

  5. Grid Effect on Spherical Shallow Water Jets Using Continuous and Discontinuous Galerkin Methods

    DTIC Science & Technology

    2013-01-01

    The high-order Legendre -Gauss-Lobatto (LGL) points are added to the linear grid by projecting the linear elements onto the auxiliary gnomonic space...mapping, the triangles are subdivided into smaller ones by a Lagrange polynomial of order nI . The number of quadrilateral elements and grid points of...of the acceleration of gravity and the vertical height of the fluid), ν∇2 is the artificial viscosity term of viscous coefficient ν = 1× 105 m2 s−1

  6. The structure of the regulatory region of the rat L1 (L1Rn, long interspersed repeated) DNA family of transposable elements.

    PubMed Central

    Furano, A V; Robb, S M; Robb, F T

    1988-01-01

    Here we report the DNA structure of the left 1.5 kb of two newly isolated full length members of the rat L1 DNA family (L1Rn, long interspersed repeated DNA). In contrast to earlier isolated rat L1 members, both of these contain promoter-like regions that are most likely full length. In addition, the promoter-like region of both members has undergone a partial tandem duplication. A second internal region of the left end of one of the reported members is also tandemly duplicated. The propensity of the left end of rat L1 elements to undergo this form of genetic rearrangement, as well as other structural features revealed by the present work, is discussed in light of the fact that during evolution the otherwise conserved mammalian L1 DNA families have each acquired completely different promoter-like regions. In an accompanying paper [Nur, I., Pascale, E., and Furano, A. V. (1988) Nucleic Acids Res. 16, submitted], we report that one of the rat promoter-like regions can function as a promoter in rat cells when fused to the Escherichia coli chloramphenicol acyltransferase gene. PMID:2845369

  7. The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients

    PubMed Central

    Han, Weidong; Wang, Xian; Fang, Yong; Li, Da; Pan, Hongming; Zhang, Li

    2015-01-01

    The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T cells and B cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. The cancer patients harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential new anticancer strategy is attracting more and more attention in cancer treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported to enhance anticancer immune responses and induce tumor cell death. Nonetheless, the precise molecular mechanisms by which PD-1 affects various cancers remain elusive. Moreover, this therapy is not effective for all the cancer patients and only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1, indicating these antibodies may only works in a subset of certain cancers. Thus, understanding the novel function of PD-1 and genetic determinants of response to anti-PD-1 therapy will allow us to develop a more effective and individualized immunotherapeutic strategy for cancer. PMID:26305724

  8. L-Asparaginase Production by Erwinia aroideae1

    PubMed Central

    Peterson, R. E.; Ciegler, A.

    1969-01-01

    Maximum yields of 1,250 IU (international unit)/g (dry weight of cells) of L-asparaginase were obtained in 8 hr from Erwinia aroideae NRRL B-138. Partial purification and concentration of the extracted L-asparaginase yielded a preparation with an activity of 275 IU/ml. Only one L-asparaginase was present as determined by electrophoresis, and the enzyme exhibited a pH optimum of 7.5 and a Km of 3 × 10-3 M. PMID:5803630

  9. VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites

    PubMed Central

    Czogalla, Katrin J.; Liphardt, Kerstin; Höning, Klara; Hornung, Veit; Biswas, Arijit; Watzka, Matthias

    2018-01-01

    Vitamin K reduction is catalyzed by 2 enzymes in vitro: the vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) and its isozyme VKORC1-like1 (VKORC1L1). In vivo, VKORC1 reduces vitamin K to sustain γ-carboxylation of vitamin K-dependent proteins, including coagulation factors. Inhibition of VKORC1 by oral anticoagulants (OACs) is clinically used in therapy and in prevention of thrombosis. However, OACs also inhibit VKORC1L1, which was previously shown to play a role in intracellular redox homeostasis in vitro. Here, we report data for the first time on specific inhibition of both VKOR enzymes for various OACs and rodenticides examined in a cell-based assay. Effects on endogenous VKORC1 and VKORC1L1 were independently investigated in genetically engineered HEK 293T cells that were knocked out for the respective genes by CRISPR/Cas9 technology. In general, dose-responses for 4-hydroxycoumarins and 1,3-indandiones were enzyme-dependent, with lower susceptibility for VKORC1L1 compared with VKORC1. In contrast, rodenticides exhibited nearly identical dose-responses for both enzymes. To explain the distinct inhibition pattern, we performed in silico modeling suggesting different warfarin binding sites for VKORC1 and VKORC1L1. We identified arginine residues at positions 38, 42, and 68 in the endoplasmatic reticulum luminal loop of VKORC1L1 responsible for charge-stabilized warfarin binding, resulting in a binding pocket that is diametrically opposite to that of VKORC1. In conclusion, our findings provide insight into structural and molecular drug binding on VKORC1, and especially on VKORC1L1. PMID:29581108

  10. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the 'L-arginine paradox'

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

    Shin, Soyoung; Mohan, Srinidi; Fung, Ho-Leung, E-mail: hlfung@buffalo.edu

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Our findings provide a possible solution to the 'L-arginine paradox'. Black-Right-Pointing-Pointer Extracellular L-arginine concentration is the major determinant of NO production. Black-Right-Pointing-Pointer Cellular L-arginine action is limited by cellular ARG transport, not the K{sub m} of NOS. Black-Right-Pointing-Pointer We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of {sup 15}N{sub 4}-ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h.more » To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, {sup 15}N{sub 4}-ARG, dimethylarginines, and L-citrulline by an LC-MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by{sup 15}N-nitrite or estimated {sup 15}N{sub 3}-citrulline concentrations when {sup 15}N{sub 4}-ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced {sup 15}N{sub 4}-ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by {sup 15}N-nitrite, total nitrite and {sup 15}N{sub 3}-citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside

  11. Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab.

    PubMed

    Zhang, Fei; Qi, Xiaoqiang; Wang, Xiaoxiao; Wei, Diyang; Wu, Jiawei; Feng, Lingling; Cai, Haiyan; Wang, Yugang; Zeng, Naiyan; Xu, Ting; Zhou, Aiwu; Zheng, Ying

    2017-10-27

    Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain. The binding involves extensive hydrogen-bonding and hydrophobic interactions. Notably there are multiple aromatic residues from the CDR loops forming Pi-Pi stacking or cation-Pi interactions within the center of the binding interface and the buried surface area is more than 2000 Å 2 , which is the largest amongst all the known PD-L1/antibody structures. Mutagenesis study revealed that two hot-spot residues (E58, R113) of PD-L1 contribute significantly to the binding of atezolizumab. The structure also shows that atezolizumab binds PD-L1 with a distinct heavy and light chain orientation and it blocks PD-1/PD-L1 interaction through competing with PD-1 for the same PD-L1 surface area. Taken together, the complex structure of PD-L1/atezolizumab solved here revealed the molecular mechanism of atezolizumab in immunotherapy and provides basis for future monoclonal antibody optimization and rational design of small chemical compounds targeting PD-L1 surface.

  12. Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab

    PubMed Central

    Wei, Diyang; Wu, Jiawei; Feng, Lingling; Cai, Haiyan; Wang, Yugang; Zeng, Naiyan; Xu, Ting; Zhou, Aiwu; Zheng, Ying

    2017-01-01

    Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain. The binding involves extensive hydrogen-bonding and hydrophobic interactions. Notably there are multiple aromatic residues from the CDR loops forming Pi-Pi stacking or cation-Pi interactions within the center of the binding interface and the buried surface area is more than 2000 Å2, which is the largest amongst all the known PD-L1/antibody structures. Mutagenesis study revealed that two hot-spot residues (E58, R113) of PD-L1 contribute significantly to the binding of atezolizumab. The structure also shows that atezolizumab binds PD-L1 with a distinct heavy and light chain orientation and it blocks PD-1/PD-L1 interaction through competing with PD-1 for the same PD-L1 surface area. Taken together, the complex structure of PD-L1/atezolizumab solved here revealed the molecular mechanism of atezolizumab in immunotherapy and provides basis for future monoclonal antibody optimization and rational design of small chemical compounds targeting PD-L1 surface. PMID:29163822

  13. Tridimensional morphology and kinetics of etch pit on the {l_brace}0 0 0 1{r_brace} plane of sapphire crystal

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

    Zhang Lunyong; Sun Jianfei, E-mail: jfsun_hit@263.net; Zuo Hongbo

    2012-08-15

    The tridimensional morphology and etching kinetics of the etch pit on the C-{l_brace}0 0 0 1{r_brace} plane of sapphire crystal ({alpha}-Al{sub 2}O{sub 3}) in molten KOH were studied experimentally. It was shown that the etch pit takes on tridimensional morphologies with triangular symmetry same as the symmetric property of the sapphire crystal. Pits like centric and eccentric triangular pyramid as well as hexagonal pyramid were observed, but the latter is less in density. In-depth analyses show the side walls of the etch pits belong to the {l_brace}1 1{sup Macron} 0 2{sup Macron }{r_brace} family, and the triangular pit contains edgesmore » full composed by Al{sup 3+} ions on the etching surface so it is more stable than the hexagonal pit since its edges on the etching surface contains Al{sup 2+} ions. The etch pits developed in a manner of kinematic wave by the step moving with constant speed, which is controlled by the chemical reaction with activation energy of 96.6 kJ/mol between Al{sub 2}O{sub 3} and KOH. - Graphical abstract: Schematic showing the atomic configuration of the predicted side walls of regular triangular pyramid shaped etch pit on the C-{l_brace}0 0 0 1{r_brace} plane of sapphire crystal. Highlights: Black-Right-Pointing-Pointer Observed the tridimensional morphology of etch pits. Black-Right-Pointing-Pointer Figured out the atomic configuration origin of the etch pits. Black-Right-Pointing-Pointer Quantitatively determined the etch rates of the etch pits.« less

  14. 1. EXTERIOR VIEW OF 1103 TROUP STREET FROM WEST/NORTHWEST. THIS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. EXTERIOR VIEW OF 1103 TROUP STREET FROM WEST/NORTHWEST. THIS STRUCTURE WAS BUILT AS WORKER HOUSING FOR THE HILLSIDE COTTON MILL BUILT BY CALLAWAY MILLS IN SOUTHWEST LaGRANGE, 1914-15. - 1103 Troup Street (House), 1103 Troup Street, La Grange, Troup County, GA

  15. N-Terminal Truncated UCH-L1 Prevents Parkinson's Disease Associated Damage

    PubMed Central

    Kim, Hee-Jung; Kim, Hyun Jung; Jeong, Jae-Eun; Baek, Jeong Yeob; Jeong, Jaeho; Kim, Sun; Kim, Young-Mee; Kim, Youhwa; Nam, Jin Han; Huh, Sue Hee; Seo, Jawon; Jin, Byung Kwan; Lee, Kong-Joo

    2014-01-01

    Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD. PMID:24959670

  16. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN P...

  17. A simulation of the instrument pointing system for the Astro-1 mission

    NASA Technical Reports Server (NTRS)

    Whorton, M.; West, M.; Rakoczy, J.

    1991-01-01

    NASA has recently completed a shuttle-borne stellar ultraviolet astronomy mission known as Astro-1. A three axis instrument pointing system (IPS) was employed to accurately point the science instruments. In order to analyze the pointing control system and verify pointing performance, a simulation of the IPS was developed using the multibody dynamics software TREETOPS. The TREETOPS IPS simulation is capable of accurately modeling the multibody IPS system undergoing large angle, nonlinear motion. The simulation is documented and example cases are presented demonstrating disturbance rejection, fine pointing operations, and multiple target pointing and slewing of the IPS.

  18. TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin

    PubMed Central

    Aldasoro Arguinano, Alex-Ander; Dadé, Sébastien; Stathopoulou, Maria; Derive, Marc; Coumba Ndiaye, Ndeye; Xie, Ting; Masson, Christine; Gibot, Sébastien

    2017-01-01

    High levels of TREM-1 are associated with cardiovascular and inflammatory diseases risks and the most recent studies have showed that TREM-1 deletion or blockade is associated with up to 60% reduction of the development of atherosclerosis. So far, it is unknown whether the levels of TREM-1 protein are genetically regulated. Moreover, TREM family receptors have been suggested to regulate the cellular adhesion process. The goal of this study was to investigate whether polymorphisms within TREM-1 are regulating the variants of serum TREM-1 levels and the expression levels of their mRNA. Furthermore, we aimed to point out associations between polymorphisms on TREM-1 and blood levels of selectins. Among the 10 SNPs studied, the minor allele T of rs2234246, was associated with increased sTREM-1 in the discovery population (p-value = 0.003), explaining 33% of its variance, and with increased levels of mRNA (p-value = 0.007). The same allele was associated with increased soluble L-selectin levels (p-value = 0.011). The higher levels of sTREM-1 and L-selectin were confirmed in the replication population (p-value = 0.0007 and p-value = 0.018 respectively). We demonstrated for the first time one SNP on TREM-1, affecting its expression levels. These novel results, support the hypothesis that TREM-1 affects monocytes extravasation and accumulation processes leading to atherogenesis and atherosclerotic plaque progression, possibly through increased inflammation and subsequent higher expression of sL-selectin. PMID:28771614

  19. Influence of time point of calibration on accuracy of continuous glucose monitoring in individuals with type 1 diabetes.

    PubMed

    Zueger, Thomas; Diem, Peter; Mougiakakou, Stavroula; Stettler, Christoph

    2012-07-01

    Data on the influence of calibration on accuracy of continuous glucose monitoring (CGM) are scarce. The aim of the present study was to investigate whether the time point of calibration has an influence on sensor accuracy and whether this effect differs according to glycemic level. Two CGM sensors were inserted simultaneously in the abdomen on either side of 20 individuals with type 1 diabetes. One sensor was calibrated predominantly using preprandial glucose (calibration(PRE)). The other sensor was calibrated predominantly using postprandial glucose (calibration(POST)). At minimum three additional glucose values per day were obtained for analysis of accuracy. Sensor readings were divided into four categories according to the glycemic range of the reference values (low, ≤4 mmol/L; euglycemic, 4.1-7 mmol/L; hyperglycemic I, 7.1-14 mmol/L; and hyperglycemic II, >14 mmol/L). The overall mean±SEM absolute relative difference (MARD) between capillary reference values and sensor readings was 18.3±0.8% for calibration(PRE) and 21.9±1.2% for calibration(POST) (P<0.001). MARD according to glycemic range was 47.4±6.5% (low), 17.4±1.3% (euglycemic), 15.0±0.8% (hyperglycemic I), and 17.7±1.9% (hyperglycemic II) for calibration(PRE) and 67.5±9.5% (low), 24.2±1.8% (euglycemic), 15.5±0.9% (hyperglycemic I), and 15.3±1.9% (hyperglycemic II) for calibration(POST). In the low and euglycemic ranges MARD was significantly lower in calibration(PRE) compared with calibration(POST) (P=0.007 and P<0.001, respectively). Sensor calibration predominantly based on preprandial glucose resulted in a significantly higher overall sensor accuracy compared with a predominantly postprandial calibration. The difference was most pronounced in the hypo- and euglycemic reference range, whereas both calibration patterns were comparable in the hyperglycemic range.

  20. L2-L1 Translation Priming Effects in a Lexical Decision Task: Evidence From Low Proficient Korean-English Bilinguals

    PubMed Central

    Lee, Yoonhyoung; Jang, Euna; Choi, Wonil

    2018-01-01

    One of the key issues in bilingual lexical representation is whether L1 processing is facilitated by L2 words. In this study, we conducted two experiments using the masked priming paradigm to examine how L2-L1 translation priming effects emerge when unbalanced, low proficiency, Korean-English bilinguals performed a lexical decision task. In Experiment 1, we used a 150 ms SOA (50 ms prime duration followed by a blank interval of 100 ms) and found a significant L2-L1 translation priming effect. In contrast, in Experiment 2, we used a 60 ms SOA (50 ms prime duration followed by a blank interval of 10 ms) and found a null effect of L2-L1 translation priming. This finding is the first demonstration of a significant L2-L1 translation priming effect with unbalanced Korean-English bilinguals. Implications of this work are discussed with regard to bilingual word recognition models. PMID:29599733

  1. Significance of specific force models in two applications: Solar sails to sun-earth L4/L5 and grail data analysis suggesting lava tubes and buried craters on the moon

    NASA Astrophysics Data System (ADS)

    Sood, Rohan

    In the trajectory design process, gravitational interaction between the bodies of interest plays a key role in developing the over-arching force model. However, non-gravitational forces, such as solar radiation pressure (SRP), can significantly influence the motion of a spacecraft. Incorporating SRP within the dynamical model can assist in estimating the trajectory of a spacecraft with greater precision, in particular, for a spacecraft with a large area-to-mass ratio, i.e., solar sails. Subsequently, in the trajectory design process, solar radiation pressure can be leveraged to maneuver the sail-based spacecraft. First, to construct low energy transfers, the invariant manifolds are explored that form an important tool in the computation and design of complex trajectories. The focus is the investigation of trajectory design options, incorporating solar sail dynamics, from the Earth parking orbit to the vicinity of triangular Lagrange points. Thereafter, an optimization scheme assisted in investigating the ?V requirement to depart from the Earth parking orbit. Harnessing the solar radiation pressure, the spacecraft is delivered to the vicinity of the displaced Lagrange point and maintains a trajectory close to the artificial libration point with the help of the solar sail. However, these trajectories are converged in a model formulated as a three-body problem with additional acceleration from solar radiation pressure. Thus, the trajectories are transitioned to higher fidelity ephemeris model to account for additional perturbing accelerations that may dominate the sail-craft dynamics and improve upon the trajectory design process. Alternatively, precise knowledge of the motion of a spacecraft about a central body and the contribution of the SRP can assist in deriving a highly accurate gravity field model. The high resolution gravity data can potentially assist in exploring the surface and subsurface properties of a particular body. With the goal of expanding human

  2. 26 CFR 36.3121(l)(5)-1 - Effect of termination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Effect of termination. 36.3121(l)(5)-1 Section 36.3121(l)(5)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SUBSIDIARIES § 36.3121(l)(5)-1 Effect of termination. (a) Termination of entire agreement. (1) If the effective...

  3. 26 CFR 36.3121(l)(1)-3 - Effect of agreement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Effect of agreement. 36.3121(l)(1)-3 Section 36.3121(l)(1)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SUBSIDIARIES § 36.3121(l)(1)-3 Effect of agreement. (a) Liability for amounts equivalent to tax—(1) In general...

  4. Asymmetric light transmission based on coupling between photonic crystal waveguides and L1/L3 cavity

    NASA Astrophysics Data System (ADS)

    Zhang, Jinqiannan; Chai, Hongyu; Yu, Zhongyuan; Cheng, Xiang; Ye, Han; Liu, Yumin

    2017-09-01

    A compact design of all-optical diode with mode conversion function based on a two-dimensional photonic crystal waveguide and an L1 or L3 cavity is theoretically investigated. The proposed photonic crystal structures comprise a triangular arrangement of air holes embedded in a silicon substrate. Asymmetric light propagation is achieved via the spatial mode match/mismatch in the coupling region. The simulations show that at each cavity's resonance frequency, the transmission efficiency of the structure with the L1 and L3 cavities reach 79% and 73%, while the corresponding unidirectionalities are 46 and 37 dB, respectively. The functional frequency can be controlled by simply adjusting the radii of specific air holes in the L1 and L3 cavities. The proposed structure can be used as a frequency filter, a beam splitter and has potential applications in all-optical integrated circuits.

  5. Ultra-thin L1{sub 0}-FePt for perpendicular anisotropy L1{sub 0}-FePt/Ag/[Co/Pd]{sub 30} pseudo spin valves

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

    Ho, Pin; Chow, Gan Moog; Chen, Jing-Sheng, E-mail: msecj@nus.edu.sg

    2014-05-07

    Perpendicular anisotropy L1{sub 0}-FePt/Ag/[Co/Pd]{sub 30} pseudo spin valves (PSVs) with ultra-thin L1{sub 0}-FePt alloy free layer possessing high anisotropy and thermal stability have been fabricated and studied. The thickness of the L1{sub 0}-FePt layer was varied between 2 and 4 nm. The PSV became increasingly decoupled with reduced L1{sub 0}-FePt thickness due to the larger difference between the coercivity of the L1{sub 0}-FePt and [Co/Pd]{sub 30} films. The PSV with an ultra-thin L1{sub 0}-FePt free layer of 2 nm displayed a high K{sub u} of 2.21 × 10{sup 7} ergs/cm{sup 3}, high thermal stability of 84 and a largest giant magnetoresistance of 0.54%.

  6. L2 Word Recognition: Influence of L1 Orthography on Multi-syllabic Word Recognition.

    PubMed

    Hamada, Megumi

    2017-10-01

    L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on the position of an embedded word. The participants were Arabic ESL learners, Chinese ESL learners, and native speakers of English. The task was a word search task, in which the participants identified a target word embedded in a pseudoword at the initial, middle, or final position. The search accuracy and speed indicated that all groups showed a strong preference for the initial position. The accuracy data further indicated group differences. The Arabic group showed higher accuracy in the final than middle, while the Chinese group showed the opposite and the native speakers showed no difference between the two positions. The findings suggest that L2 multi-syllabic word recognition involves unique processes.

  7. An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia.

    PubMed

    Martín, B; Solanas-Barca, M; García-Otín, A-L; Pampín, S; Cofán, M; Ros, E; Rodríguez-Rey, J-C; Pocoví, M; Civeira, F

    2010-05-01

    A substantial number of subjects with autosomal dominant hypercholesterolemia (ADH) do not have LDL receptor (LDLR) or apolipoprotein B (APOB) mutations. Some ADH subjects appear to hyperabsorb sterols from the intestine, thus we hypothesized that they could have variants of the Niemann-Pick C1-Like 1 gene (NPC1L1). NPC1L1 encodes a crucial protein involved in intestinal sterol absorption. Four NPC1L1 variants (-133A>G, -18C>A, 1679C>G, 28650A>G) were analyzed in 271 (155 women and 116 men) ADH bearers without mutations in LDLR or APOB aged 30-70years and 274 (180 women and 94 men) control subjects aged 25-65years. The AC haplotype determined by the -133A>G and -18C>A variants was underrepresented in ADH subjects compared to controls (p=0.01). In the ADH group, cholesterol absorption/synthesis markers were significantly lower in AC homozygotes that in all others haplotypes. Electrophoretic mobility shift assay (EMSA) results revealed that the -133A-specific oligonucleotide produced a retarded band stronger than the -133G allele. Luciferase activity with NPC1L1 -133G variant was 2.5-fold higher than with the -133A variant. The -133A>G polymorphism exerts a significant effect on NPC1L1 promoter activity. NPC1L1 promoter variants might explain in part the hypercholesterolemic phenotype of some subjects with nonLDLR/nonAPOB ADH. Copyright 2009 Elsevier B.V. All rights reserved.

  8. Functional effects of CCL3L1 copy number.

    PubMed

    Carpenter, D; McIntosh, R S; Pleass, R J; Armour, J A L

    2012-07-01

    Copy number variation (CNV) is becoming increasingly important as a feature of human variation in disease susceptibility studies. However, the consequences of CNV are not so well understood. Here, we present data exploring the functional consequences of CNV of CCL3L1 in 55 independent UK samples with no known clinical phenotypes. The copy number of CCL3L1 was determined by the paralogue ratio test, and expression levels of macrophage inflammatory protein-1α (MIP-1α) and mRNA from stimulated monocytes were measured and analysed. The data show no statistically significant association of MIP-1α protein levels with copy number. However, there was a significant correlation between copy number and CCL3L1:CCL3 mRNA ratio. The data also provide evidence that expression of CCL3 predominates in both protein and mRNA, and therefore the observed variation of CCL3 is potentially more important biologically than that of CNV of CCL3L1.

  9. Collocational Links in the L2 Mental Lexicon and the Influence of L1 Intralexical Knowledge

    ERIC Educational Resources Information Center

    Wolter, Brent; Gyllstad, Henrik

    2011-01-01

    This article assesses the influence of L1 intralexical knowledge on the formation of L2 intralexical collocations. Two tests, a primed lexical decision task (LDT) and a test of receptive collocational knowledge, were administered to a group of non-native speakers (NNSs) (L1 Swedish), with native speakers (NSs) of English serving as controls on the…

  10. The Nucleotide Excision Repair Pathway Limits L1 Retrotransposition

    PubMed Central

    Servant, Geraldine; Streva, Vincent A.; Derbes, Rebecca S.; Wijetunge, Madushani I.; Neeland, Marc; White, Travis B.; Belancio, Victoria P.; Roy-Engel, Astrid M.; Deininger, Prescott L.

    2017-01-01

    Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a “copy-and-paste” mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3′ DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway. To determine if the NER pathway prevents the insertion of retroelements in the genome, we monitored the retrotransposition efficiencies of engineered L1 elements in NER-deficient cells and in their complemented versions. Core proteins of the NER pathway, XPD and XPA, and the lesion binding protein, XPC, are involved in limiting L1 retrotransposition. In addition, sequence analysis of recovered de novo L1 inserts and their genomic locations in NER-deficient cells demonstrated the presence of abnormally large duplications at the site of insertion, suggesting that NER proteins may also play a role in the normal L1 insertion process. Here, we propose new functions for the NER pathway in the maintenance of genome integrity: limitation of insertional mutations caused by retrotransposons and the prevention of potentially mutagenic large genomic duplications at the site of retrotransposon insertion events. PMID:28049704

  11. Histone methyltransferase Ash1L mediates activity-dependent repression of neurexin-1α

    PubMed Central

    Zhu, Τao; Liang, Chen; Li, Dongdong; Tian, Miaomiao; Liu, Sanxiong; Gao, Guanjun; Guan, Ji-Song

    2016-01-01

    Activity-dependent transcription is critical for the regulation of long-term synaptic plasticity and plastic rewiring in the brain. Here, we report that the transcription of neurexin1α (nrxn1α), a presynaptic adhesion molecule for synaptic formation, is regulated by transient neuronal activation. We showed that 10 minutes of firing at 50 Hz in neurons repressed the expression of nrxn1α for 24 hours in a primary cortical neuron culture through a transcriptional repression mechanism. By performing a screening assay using a synthetic zinc finger protein (ZFP) to pull down the proteins enriched near the nrxn1α promoter region in vivo, we identified that Ash1L, a histone methyltransferase, is enriched in the nrxn1α promoter. Neuronal activity triggered binding of Ash1L to the promoter and enriched the histone marker H3K36me2 at the nrxn1α promoter region. Knockout of Ash1L in mice completely abolished the activity-dependent repression of nrxn1α. Taken together, our results reveal that a novel process of activity-dependent transcriptional repression exists in neurons and that Ash1L mediates the long-term repression of nrxn1α, thus implicating an important role for epigenetic modification in brain functioning. PMID:27229316

  12. Cloning, expression, and characterization of bacterial L-arabinose 1-dehydrogenase involved in an alternative pathway of L-arabinose metabolism.

    PubMed

    Watanabe, Seiya; Kodaki, Tsutomu; Kodak, Tsutomu; Makino, Keisuke

    2006-02-03

    Azospirillum brasiliense converts L-arabinose to alpha-ketoglutarate via five hypothetical enzymatic steps. We purified and characterized L-arabinose 1-dehydrogenase (EC 1.1.1.46), catalyzing the conversion of L-arabinose to L-arabino-gamma-lactone as an enzyme responsible for the first step of this alternative pathway of L-arabinose metabolism. The purified enzyme preferred NADP+ to NAD+ as a coenzyme. Kinetic analysis revealed that the enzyme had high catalytic efficiency for both L-arabinose and D-galactose. The gene encoding L-arabinose 1-dehydrogenase was cloned using a partial peptide sequence of the purified enzyme and was overexpressed in Escherichia coli as a fully active enzyme. The enzyme consists of 308 amino acids and has a calculated molecular mass of 33,663.92 Da. The deduced amino acid sequence had some similarity to glucose-fructose oxidoreductase, D-xylose 1-dehydrogenase, and D-galactose 1-dehydrogenase. Site-directed mutagenesis revealed that the enzyme possesses unique catalytic amino acid residues. Northern blot analysis showed that this gene was induced by L-arabinose but not by D-galactose. Furthermore, a disruptant of the L-arabinose 1-dehydrogenase gene did not grow on L-arabinose but grew on D-galactose at the same growth rate as the wild-type strain. There was a partial gene for L-arabinose transport in the flanking region of the L-arabinose 1-dehydrogenase gene. These results indicated that the enzyme is involved in the metabolism of L-arabinose but not D-galactose. This is the first identification of a gene involved in an alternative pathway of L-arabinose metabolism in bacterium.

  13. Contrastive Analysis of English and Japanese Demonstratives from the Perspective of L1 and L2 Acquisition.

    ERIC Educational Resources Information Center

    Niimura, Tomomi; Hayashi, Brenda

    1996-01-01

    Presents a contrastive analysis of English and Japanese demonstratives based on the first- (L1) and second-language (L2) data of an earlier study. First, the traditional explanations and their alternative models for English and Japanese are presented, then, all models are tested with the L1 and L2 data, which leads to a discussion of the different…

  14. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study.

    PubMed

    van der Putten, Louis Jm; Visser, Nicole Cm; van de Vijver, Koen; Santacana, Maria; Bronsert, Peter; Bulten, Johan; Hirschfeld, Marc; Colas, Eva; Gil-Moreno, Antonio; Garcia, Angel; Mancebo, Gemma; Alameda, Fransesc; Trovik, Jone; Kopperud, Reidun K; Huvila, Jutta; Schrauwen, Stefanie; Koskas, Martin; Walker, Francine; Weinberger, Vit; Minar, Lubos; Jandakova, Eva; Snijders, Marc Plm; van den Berg-van Erp, Saskia; Matias-Guiu, Xavier; Salvesen, Helga B; Amant, Frederic; Massuger, Leon Fag; Pijnenborg, Johanna Ma

    2016-09-06

    Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.

  15. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

    PubMed Central

    van der Putten, Louis JM; Visser, Nicole CM; van de Vijver, Koen; Santacana, Maria; Bronsert, Peter; Bulten, Johan; Hirschfeld, Marc; Colas, Eva; Gil-Moreno, Antonio; Garcia, Angel; Mancebo, Gemma; Alameda, Fransesc; Trovik, Jone; Kopperud, Reidun K; Huvila, Jutta; Schrauwen, Stefanie; Koskas, Martin; Walker, Francine; Weinberger, Vit; Minar, Lubos; Jandakova, Eva; Snijders, Marc PLM; van den Berg-van Erp, Saskia; Matias-Guiu, Xavier; Salvesen, Helga B; Amant, Frederic; Massuger, Leon FAG; Pijnenborg, Johanna MA

    2016-01-01

    Background: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. Methods: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. Results: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. Conclusions: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied. PMID:27505134

  16. Frontline Science: Defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1

    PubMed Central

    Patera, Andriani C.; Drewry, Anne M.; Chang, Katherine; Beiter, Evan R.; Osborne, Dale; Hotchkiss, Richard S.

    2016-01-01

    Sepsis is a heterogeneous syndrome comprising a highly diverse and dynamic mixture of hyperinflammatory and compensatory anti-inflammatory immune responses. This immune phenotypic diversity highlights the importance of proper patient selection for treatment with the immunomodulatory drugs that are entering clinical trials. To better understand the serial changes in immunity of critically ill patients and to evaluate the potential efficacy of blocking key inhibitory pathways in sepsis, we undertook a broad phenotypic and functional analysis of innate and acquired immunity in the same aliquot of blood from septic, critically ill nonseptic, and healthy donors. We also tested the ability of blocking the checkpoint inhibitors programmed death receptor-1 (PD-1) and its ligand (PD-L1) to restore the function of innate and acquired immune cells. Neutrophil and monocyte function (phagocytosis, CD163, cytokine expression) were progressively diminished as sepsis persisted. An increasing frequency in PD-L1+-suppressor phenotype neutrophils [low-density neutrophils (LDNs)] was also noted. PD-L1+ LDNs and defective neutrophil function correlated with disease severity, consistent with the potential importance of suppressive neutrophil populations in sepsis. Reduced neutrophil and monocyte function correlated both with their own PD-L1 expression and with PD-1 expression on CD8+ T cells and NK cells. Conversely, reduced CD8+ T cell and NK cell functions (IFN-γ production, granzyme B, and CD107a expression) correlated with elevated PD-L1+ LDNs. Importantly, addition of antibodies against PD-1 or PD-L1 restored function in neutrophil, monocyte, T cells, and NK cells, underlining the impact of the PD-1:PD-L1 axis in sepsis-immune suppression and the ability to treat multiple deficits with a single immunomodulatory agent. PMID:27671246

  17. Does right lateral decubitus position change retroperitoneal oblique corridor? A radiographic evaluation from L1 to L5.

    PubMed

    Zhang, Fan; Xu, Haocheng; Yin, Bo; Tao, Hongyue; Yang, Shuo; Sun, Chi; Wang, Yitao; Yin, Jun; Shao, Minghao; Wang, Hongli; Xia, Xinlei; Ma, Xiaosheng; Lu, Feizhou; Jiang, Jianyuan

    2017-03-01

    To determine if the retroperitoneal oblique corridor will be affected by right lateral decubitus position. Forty volunteers were randomly enrolled and MRI scan was performed from L1 to L5 in supine and right lateral decubitus positions, respectively. In images across the center of each disc, O was defined as the center of a disc and A (supine) or A' (right lateral decubitus) was located in left lateral border of the aorta or the iliac artery; B (supine) or B' (right lateral decubitus) was on the anterior medial border of the psoas. The distance of AB and A'B' (Recorded as A-Ps and A-Pr, respectively) at each level was recorded and compared to each other. The relationships between A-Pr, sex, BMI and relative psoas cross-sectional area (PCSA) at each level were also evaluated. A-Pr was significantly smaller than A-Ps at L1/2, L2/3 and L3/4 (All p < 0.05); there was no significantly difference of A-Pr between all levels (p = 0.105), but L1/2 seemed to be larger than L3/4, followed by L2/3 and L4/5; A-Pr at each level was not affected by sex (All p > 0.05); linear relationships were found between A-Pr, BMI and PCSA at L1/2 and L3/4. ROC at L1/2, L2/3 and L3/4 will significantly decrease from supine to right lateral decubitus position and the reason may be due to the relaxed psoas deformation. Using MRI images in supine position for pre-operatively ROC evaluation is not accurate. Spine surgeon should also be more cautious when OLIF is performed at L4/5 where ROC is the smallest. Patients from Asia and those with strong psoas major at L1/2 and L3/4 are also associated with relatively narrow ROC.

  18. L2 Acquisition of Prosodic Properties of Speech Rhythm: Evidence from L1 Mandarin and German Learners of English

    ERIC Educational Resources Information Center

    Li, Aike; Post, Brechtje

    2014-01-01

    This study examines the development of speech rhythm in second language (L2) learners of typologically different first languages (L1s) at different levels of proficiency. An empirical investigation of durational variation in L2 English productions by L1 Mandarin learners and L1 German learners compared to native control values in English and the…

  19. A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer.

    PubMed

    Tao, Li-Hua; Zhou, Xin-Ru; Li, Fu-Chao; Chen, Qi; Meng, Fan-Yi; Mao, Yong; Li, Rui; Hua, Dong; Zhang, Hong-Jian; Wang, Wei-Peng; Chen, Wei-Chang

    2017-03-01

    PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3'-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility.

  20. Functional effects of CCL3L1 copy number

    PubMed Central

    Carpenter, Danielle; McIntosh, Richard S; Pleass, Richard J; Armour, John AL

    2012-01-01

    Copy number variation (CNV) is becoming increasingly important as a feature of human variation in disease susceptibility studies. However, the consequences of copy number variation are not so well understood. Here we present data exploring the functional consequences of copy number variation of CCL3L1 in 55 independent UK samples with no known clinical phenotypes. Copy number of CCL3L1 was determined by the paralogue ratio test (PRT), and expression levels of MIP-1α and mRNA from stimulated monocytes were measured and analysed. The data show no statistically significant association of MIP-1α protein levels with copy number. However, there was a significant correlation between copy number and CCL3L1:CCL3 mRNA ratio. The data also provide evidence that expression of CCL3 predominates in both protein and mRNA, and therefore the observed variation of CCL3 is potentially more important biologically than that of copy number variation of CCL3L1. PMID:22476153

  1. STIM1L traps and gates Orai1 channels without remodeling the cortical ER

    PubMed Central

    Saüc, Sophie; Bulla, Monica; Nunes, Paula; Orci, Lelio; Marchetti, Anna; Antigny, Fabrice; Bernheim, Laurent; Cosson, Pierre; Frieden, Maud; Demaurex, Nicolas

    2015-01-01

    STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca2+ entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca2+ influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca2+ imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1−/−/Stim2−/− fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca2+ elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides. PMID:25736291

  2. Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC)

    PubMed Central

    Vecchiarelli, Silvia; Passiglia, Francesco; D’Incecco, Armida; Gallo, Marianna; De Luca, Antonella; Rossi, Elisa; D’Incà, Federica; Minuti, Gabriele; Landi, Lorenza; Bennati, Chiara; Spreafico, Michela; D’Arcangelo, Manolo; Mazza, Valentina; Normanno, Nicola; Cappuzzo, Federico

    2018-01-01

    Background This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome. Methods Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p-value. Results Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort (p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months (p = 0.062) and 8.8 vs 9.3 months (p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant (p = 0.063). Conclusions This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations. PMID:29707129

  3. SMOS L1C and L2 Validation in Australia

    NASA Technical Reports Server (NTRS)

    Rudiger, Christoph; Walker, Jeffrey P.; Kerr, Yann H.; Mialon, Arnaud; Merlin, Olivier; Kim, Edward J.

    2012-01-01

    Extensive airborne field campaigns (Australian Airborne Cal/val Experiments for SMOS - AACES) were undertaken during the 2010 summer and winter seasons of the southern hemisphere. The purpose of those campaigns was the validation of the Level 1c (brightness temperature) and Level 2 (soil moisture) products of the ESA-led Soil Moisture and Ocean Salinity (SMOS) mission. As SMOS is the first satellite to globally map L-band (1.4GHz) emissions from the Earth?s surface, and the first 2-dimensional interferometric microwave radiometer used for Earth observation, large scale and long-term validation campaigns have been conducted world-wide, of which AACES is the most extensive. AACES combined large scale medium-resolution airborne L-band and spectral observations, along with high-resolution in-situ measurements of soil moisture across a 50,000km2 area of the Murrumbidgee River catchment, located in south-eastern Australia. This paper presents a qualitative assessment of the SMOS brightness temperature and soil moisture products.

  4. Perceptual Processing of Mandarin Nasals by L1 and L2 Mandarin Speakers

    ERIC Educational Resources Information Center

    Lai, Yi-hsiu

    2012-01-01

    Nasals are cross-linguistically susceptible to change, especially in the syllable final position. Acoustic reports on Mandarin nasal production have recently shown that the syllable-final distinction is frequently dropped. Few studies, however, have addressed the issue of perceptual processing in Mandarin nasals for L1 and L2 speakers of Mandarin…

  5. Genome-wide linkage mapping of QTL for black point reaction in bread wheat (Triticum aestivum L.).

    PubMed

    Liu, Jindong; He, Zhonghu; Wu, Ling; Bai, Bin; Wen, Weie; Xie, Chaojie; Xia, Xianchun

    2016-11-01

    Nine QTL for black point resistance in wheat were identified using a RIL population derived from a Linmai 2/Zhong 892 cross and 90K SNP assay. Black point, discoloration of the embryo end of the grain, downgrades wheat grain quality leading to significant economic losses to the wheat industry. The availability of molecular markers will accelerate improvement of black point resistance in wheat breeding. The aims of this study were to identify quantitative trait loci (QTL) for black point resistance and tightly linked molecular markers, and to search for candidate genes using a high-density genetic linkage map of wheat. A recombinant inbred line (RIL) population derived from the cross Linmai 2/Zhong 892 was evaluated for black point reaction during the 2011-2012, 2012-2013 and 2013-2014 cropping seasons, providing data for seven environments. A high-density linkage map was constructed by genotyping the RILs with the wheat 90K single nucleotide polymorphism (SNP) chip. Composite interval mapping detected nine QTL on chromosomes 2AL, 2BL, 3AL, 3BL, 5AS, 6A, 7AL (2) and 7BS, designated as QBp.caas-2AL, QBp.caas-2BL, QBp.caas-3AL, QBp.caas-3BL, QBp.caas-5AS, QBp.caas-6A, QBp.caas-7AL.1, QBp.caas-7AL.2 and QBp.caas-7BS, respectively. All resistance alleles, except for QBp.caas-7AL.1 from Linmai 2, were contributed by Zhong 892. QBp.caas-3BL, QBp.caas-5AS, QBp.caas-7AL.1, QBp.caas-7AL.2 and QBp.caas-7BS probably represent new loci for black point resistance. Sequences of tightly linked SNPs were used to survey wheat and related cereal genomes identifying three candidate genes for black point resistance. The tightly linked SNP markers can be used in marker-assisted breeding in combination with the kompetitive allele specific PCR technique to improve black point resistance.

  6. A Free-Return Earth-Moon Cycler Orbit for an Interplanetary Cruise Ship

    NASA Technical Reports Server (NTRS)

    Genova, Anthony L.; Aldrin, Buzz

    2015-01-01

    A periodic circumlunar orbit is presented that can be used by an interplanetary cruise ship for regular travel between Earth and the Moon. This Earth-Moon cycler orbit was revealed by introducing solar gravity and modest phasing maneuvers (average of 39 m/s per month) which yields close-Earth encounters every 7 or 10 days. Lunar encounters occur every 26 days and offer the chance for a smaller craft to depart the cycler and enter lunar orbit, or head for a Lagrange point (e.g., EM-L2 halo orbit), distant retrograde orbit (DRO), or interplanetary destination such as a near-Earth object (NEO) or Mars. Additionally, return-to-Earth abort options are available from many points along the cycling trajectory.

  7. 26 CFR 36.3121(l)(1)-2 - Amendment of agreement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Amendment of agreement. 36.3121(l)(1)-2 Section 36.3121(l)(1)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SUBSIDIARIES § 36.3121(l)(1)-2 Amendment of agreement. (a) An agreement entered into by a domestic corporation...

  8. Optimization of L: -methionine feeding strategy for improving S-adenosyl-L: -methionine production by methionine adenosyltransferase overexpressed Pichia pastoris.

    PubMed

    Hu, Hui; Qian, Jiangchao; Chu, Ju; Wang, Yonghong; Zhuang, Yingping; Zhang, Siliang

    2009-07-01

    The recombinant Pichia pastoris harboring an improved methionine adenosyltransferase (MAT) shuffled gene was employed to biosynthesize S-adenosyl-L: -methionine (SAM). Two L: -methionine (L: -Met) addition strategies were used to supply the precursor: the batch addition strategy (L: -Met was added separately at three time points) and the continuous feeding strategies (L: -Met was fed continuously at the rate of 0.1, 0.2, and 0.5 g l(-1) h(-1), respectively). SAM accumulation, L: -Met conversion rate, and SAM productivity with the continuous feeding strategies were all improved over the batch addition strategy, which reached 8.46 +/- 0.31 g l(-1), 41.7 +/- 1.4%, and 0.18 +/- 0.01 g l(-1) h(-1) with the best continuous feeding strategy (0.2 g l(-1) h(-1)), respectively. The bottleneck for SAM production with the low L: -Met feeding rate (0.1 g L(-1) h(-1)) was the insufficient L: -Met supply. The analysis of the key enzyme activities indicated that the tricarboxylic acid cycle and glycolytic pathway were reduced with the increasing L: -Met feeding rate, which decreased the adenosine triphosphate (ATP) synthesis. The MAT activity also decreased as the L: -Met feeding rate rose. The reduced ATP synthesis and MAT activity were probably the reason for the low SAM accumulation when the L: -Met feeding rate reached 0.5 g l(-1) h(-1).

  9. BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer.

    PubMed

    Wieser, Verena; Gaugg, Inge; Fleischer, Martina; Shivalingaiah, Giridhar; Wenzel, Soeren; Sprung, Susanne; Lax, Sigurd F; Zeimet, Alain G; Fiegl, Heidelinde; Marth, Christian

    2018-04-03

    Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status. TP53 -mutated OC strongly expressed PD-L1 compared to TP53 wild-type OC ( p = 0.028) and BRCA1/2 -mutated OC increasingly expressed PD-1 ( p = 0.024) and PD-L1 ( p = 0.012) compared to BRCA1/2 wild-type OC. For the first time in human, we noted a strong correlation between tumoral IFNG and PD-1 or PD-L1 mRNA-expression, respectively ( p < 0.001). OC tissue increasingly expressed PD-1 compared to healthy controls (vs. ovaries: p < 0.001; vs. tubes: p = 0.018). PD-1 and PD-L1 mRNA-expression increased with higher tumor grade ( p = 0.008 and p = 0.027, respectively) and younger age (< median age, p = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high PD-1 and PD-L1 mRNA-expression was associated with reduced progression-free ( p = 0.024) and overall survival ( p = 0.049) but only in the univariate analysis. Our study suggests that in OC PD-1 / PD-L1 mRNA-expression is controlled by IFNγ and affected by TP53 and BRCA1/2 mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- PD1 / PD-L1 immunotherapy.

  10. PD-L1 inhibitors in the pipeline: Promise and progress.

    PubMed

    Vanella, Vito; Festino, Lucia; Strudel, Martina; Simeone, Ester; Grimaldi, Antonio M; Ascierto, Paolo A

    2017-01-01

    Checkpoint inhibitors have improved survival for patients with melanoma, non-small-cell lung cancer (NSCLC), bladder, head and neck and other cancers. Antibodies against PD-L1, including atezolizumab, avelumab and durvalumab, are also being developed and have been approved for various cancers. Compared with anti-CTLA-4 drugs, studies with anti-PD-1/PD-L1 agents have suggested higher response rates and improved survival. Targeting PD-L1 rather than PD-1 may also theoretically offer further benefit, with the potential for improved efficacy and reduced toxicity, although this has not been clearly shown by clinical experience to date. Anti-PD-L1 agents have shown good efficacy and manageable toxicity in several tumor types.

  11. PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.

    PubMed

    Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying

    2018-04-01

    The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined. We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls. Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-γ-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. International Space Station Centrifuge Rotor Models A Comparison of the Euler-Lagrange and the Bond Graph Modeling Approach

    NASA Technical Reports Server (NTRS)

    Nguyen, Louis H.; Ramakrishnan, Jayant; Granda, Jose J.

    2006-01-01

    The assembly and operation of the International Space Station (ISS) require extensive testing and engineering analysis to verify that the Space Station system of systems would work together without any adverse interactions. Since the dynamic behavior of an entire Space Station cannot be tested on earth, math models of the Space Station structures and mechanical systems have to be built and integrated in computer simulations and analysis tools to analyze and predict what will happen in space. The ISS Centrifuge Rotor (CR) is one of many mechanical systems that need to be modeled and analyzed to verify the ISS integrated system performance on-orbit. This study investigates using Bond Graph modeling techniques as quick and simplified ways to generate models of the ISS Centrifuge Rotor. This paper outlines the steps used to generate simple and more complex models of the CR using Bond Graph Computer Aided Modeling Program with Graphical Input (CAMP-G). Comparisons of the Bond Graph CR models with those derived from Euler-Lagrange equations in MATLAB and those developed using multibody dynamic simulation at the National Aeronautics and Space Administration (NASA) Johnson Space Center (JSC) are presented to demonstrate the usefulness of the Bond Graph modeling approach for aeronautics and space applications.

  13. Diffuse interface simulation of bubble rising process: a comparison of adaptive mesh refinement and arbitrary lagrange-euler methods

    NASA Astrophysics Data System (ADS)

    Wang, Ye; Cai, Jiejin; Li, Qiong; Yin, Huaqiang; Yang, Xingtuan

    2018-06-01

    Gas-liquid two phase flow exists in several industrial processes and light-water reactors (LWRs). A diffuse interface based finite element method with two different mesh generation methods namely, the Adaptive Mesh Refinement (AMR) and the Arbitrary Lagrange Euler (ALE) methods is used to model the shape and velocity changes in a rising bubble. Moreover, the calculating speed and mesh generation strategies of AMR and ALE are contrasted. The simulation results agree with the Bhagat's experiments, indicating that both mesh generation methods can simulate the characteristics of bubble accurately. We concluded that: the small bubble rises as elliptical with oscillation, whereas a larger bubble (11 mm > d > 7 mm) rises with a morphology between the elliptical and cap type with a larger oscillation. When the bubble is large (d > 11 mm), it rises up as a cap type, and the amplitude becomes smaller. Moreover, it takes longer to achieve the stable shape from the ellipsoid to the spherical cap type with the increase of the bubble diameter. The results also show that for smaller diameter case, the ALE method uses fewer grids and has a faster calculation speed, but the AMR method can solve the case of a large geometry deformation efficiently.

  14. GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain.

    PubMed

    Huang, Hung-Hsiang; Hassinen, Antti; Sundaram, Subha; Spiess, Andrej-Nikolai; Kellokumpu, Sakari; Stanley, Pamela

    2015-09-15

    Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP-L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis.

  15. Apolipoprotein L1 Variant Associated with Increased Susceptibility to Trypanosome Infection

    PubMed Central

    Cuypers, Bart; Lecordier, Laurence; Meehan, Conor J.; Van den Broeck, Frederik; Imamura, Hideo; Büscher, Philippe; Dujardin, Jean-Claude; Laukens, Kris; Schnaufer, Achim; Dewar, Caroline; Lewis, Michael; Balmer, Oliver; Azurago, Thomas; Kyei-Faried, Sardick; Ohene, Sally-Ann; Duah, Boateng; Homiah, Prince; Mensah, Ebenezer Kofi; Anleah, Francis; Franco, Jose Ramon; Pays, Etienne

    2016-01-01

    ABSTRACT African trypanosomes, except Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause human African trypanosomiasis, are lysed by the human serum protein apolipoprotein L1 (ApoL1). These two subspecies can resist human ApoL1 because they express the serum resistance proteins T. b. gambiense glycoprotein (TgsGP) and serum resistance-associated protein (SRA), respectively. Whereas in T. b. rhodesiense, SRA is necessary and sufficient to inhibit ApoL1, in T. b. gambiense, TgsGP cannot protect against high ApoL1 uptake, so different additional mechanisms contribute to limit this uptake. Here we report a complex interplay between trypanosomes and an ApoL1 variant, revealing important insights into innate human immunity against these parasites. Using whole-genome sequencing, we characterized an atypical T. b. gambiense infection in a patient in Ghana. We show that the infecting trypanosome has diverged from the classical T. b. gambiense strains and lacks the TgsGP defense mechanism against human serum. By sequencing the ApoL1 gene of the patient and subsequent in vitro mutagenesis experiments, we demonstrate that a homozygous missense substitution (N264K) in the membrane-addressing domain of this ApoL1 variant knocks down the trypanolytic activity, allowing the trypanosome to avoid ApoL1-mediated immunity. PMID:27073096

  16. Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells

    PubMed Central

    Coufal, Nicole G.; Garcia-Perez, Josè Luis; Peng, Grace E.; Marchetto, Maria C. N.; Muotri, Alysson R.; Mu, Yangling; Carson, Christian T.; Macia, Angela; Moran, John V.; Gage, Fred H.

    2011-01-01

    Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition. PMID:22159035

  17. PD-L1 is an activation-independent marker of brown adipocytes.

    PubMed

    Ingram, Jessica R; Dougan, Michael; Rashidian, Mohammad; Knoll, Marko; Keliher, Edmund J; Garrett, Sarah; Garforth, Scott; Blomberg, Olga S; Espinosa, Camilo; Bhan, Atul; Almo, Steven C; Weissleder, Ralph; Lodish, Harvey; Dougan, Stephanie K; Ploegh, Hidde L

    2017-09-21

    Programmed death ligand 1 (PD-L1) is expressed on a number of immune and cancer cells, where it can downregulate antitumor immune responses. Its expression has been linked to metabolic changes in these cells. Here we develop a radiolabeled camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emission tomography (PET). PET-CT imaging shows a robust and specific PD-L1 signal in brown adipose tissue (BAT). We confirm expression of PD-L1 on brown adipocytes and demonstrate that signal intensity does not change in response to cold exposure or β-adrenergic activation. This is the first robust method of visualizing murine brown fat independent of its activation state.Current approaches to visualise brown adipose tissue (BAT) rely primarily on markers that reflect its metabolic activity. Here, the authors show that PD-L1 is expressed on brown adipocytes, does not change upon BAT activation, and that BAT volume in mice can be measured by PET-CT with a radiolabeled anti-PD-L1 antibody.

  18. Material Assessment of L97A1/L96A1 Grenades by Fourier Transform Infrared Spectroscopy and Thermogravimetric Analysis

    DTIC Science & Technology

    2010-12-01

    infrared (FTIR) spectroscopy Differential scanning calorimetry ( DSC ) L97A1/L96A1 grenades Thermogravimetric analysis (TGA) 16. SECURITY CLASSIFICATION OF...Spectroscopy The FTIR scan (fig. 3) shows two baseline materials • The blue spectra represent the Nylon 6 sample • The black spectra represent Nylon 6...The black spectra represent a sample taken from the body of the older grenade body • The relative size and location of all the peaks are identical

  19. PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma.

    PubMed

    Mitteldorf, Christina; Berisha, Arbeneshe; Tronnier, Michael; Pfaltz, Monique C; Kempf, Werner

    2017-09-01

    Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(-) samples were mostly PD-L1 negative. Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The Effect of Syntactic Complexity on Fluency: Comparing Actives and Passives in L1 and L2 Speech

    ERIC Educational Resources Information Center

    Sadri Mirdamadi, Farhad; De Jong, Nivja H.

    2015-01-01

    This study investigates how syntactic complexity affects speaking performance in first (L1) and second language (L2) in terms of speaking fluency. Participants (30 Dutch native speakers with an average to advanced level of English) performed two speaking experiments, one in Dutch (L1) and one in English (L2). Syntactic complexity was…