Sample records for l-1 day prelaunch

  1. JPSS-1 VIIRS Pre-Launch Radiometric Performance

    NASA Technical Reports Server (NTRS)

    Oudrari, Hassan; McIntire, Jeff; Xiong, Xiaoxiong; Butler, James; Efremova, Boryana; Ji, Jack; Lee, Shihyan; Schwarting, Tom

    2015-01-01

    The Visible Infrared Imaging Radiometer Suite (VIIRS) on-board the first Joint Polar Satellite System (JPSS) completed its sensor level testing on December 2014. The JPSS-1 (J1) mission is scheduled to launch in December 2016, and will be very similar to the Suomi-National Polar-orbiting Partnership (SNPP) mission. VIIRS instrument was designed to provide measurements of the globe twice daily. It is a wide-swath (3,040 kilometers) cross-track scanning radiometer with spatial resolutions of 370 and 740 meters at nadir for imaging and moderate bands, respectively. It covers the wavelength spectrum from reflective to long-wave infrared through 22 spectral bands [0.412 microns to 12.01 microns]. VIIRS observations are used to generate 22 environmental data products (EDRs). This paper will briefly describe J1 VIIRS characterization and calibration performance and methodologies executed during the pre-launch testing phases by the independent government team, to generate the at-launch baseline radiometric performance, and the metrics needed to populate the sensor data record (SDR) Look-Up-Tables (LUTs). This paper will also provide an assessment of the sensor pre-launch radiometric performance, such as the sensor signal to noise ratios (SNRs), dynamic range, reflective and emissive bands calibration performance, polarization sensitivity, bands spectral performance, response-vs-scan (RVS), near field and stray light responses. A set of performance metrics generated during the pre-launch testing program will be compared to the SNPP VIIRS pre-launch performance.

  2. JPSS-1 VIIRS Pre-Launch Radiometric Performance

    NASA Technical Reports Server (NTRS)

    Oudrari, Hassan; Mcintire, Jeffrey; Xiong, Xiaoxiong; Butler, James; Ji, Qiang; Schwarting, Tom; Zeng, Jinan

    2015-01-01

    The first Joint Polar Satellite System (JPSS-1 or J1) mission is scheduled to launch in January 2017, and will be very similar to the Suomi-National Polar-orbiting Partnership (SNPP) mission. The Visible Infrared Imaging Radiometer Suite (VIIRS) on board the J1 spacecraft completed its sensor level performance testing in December 2014. VIIRS instrument is expected to provide valuable information about the Earth environment and properties on a daily basis, using a wide-swath (3,040 km) cross-track scanning radiometer. The design covers the wavelength spectrum from reflective to long-wave infrared through 22 spectral bands, from 0.412 m to 12.01 m, and has spatial resolutions of 370 m and 740 m at nadir for imaging and moderate bands, respectively. This paper will provide an overview of pre-launch J1 VIIRS performance testing and methodologies, describing the at-launch baseline radiometric performance as well as the metrics needed to calibrate the instrument once on orbit. Key sensor performance metrics include the sensor signal to noise ratios (SNRs), dynamic range, reflective and emissive bands calibration performance, polarization sensitivity, bands spectral performance, response-vs-scan (RVS), near field response, and stray light rejection. A set of performance metrics generated during the pre-launch testing program will be compared to the sensor requirements and to SNPP VIIRS pre-launch performance.

  3. JPSS-1 Prelaunch News Conference

    NASA Image and Video Library

    2017-11-12

    JPSS-1 Prelaunch News Conference at Vandenberg Air Force Base hosted by Tori Mclendon, with Steve Volz, NOAA Satellite and Information Service, Greg Mandt, Director, NOAA Joint Polar Satellite Systems Program, Sandra Smalley, NASA Joint Agency Satellite Division, Omar Baez, Launch Manager, NASA Launch Services Program, Scott Messer, Program Manager for NASA Missions, United Launch Alliance, and Ross Malugani, Launch Weather Officer, VAFB 30th Space Wing.

  4. COOPER - PRELAUNCH (MA-9)

    NASA Image and Video Library

    1963-04-23

    S63-07521 (15 May 1963) --- Astronaut L. Gordon Cooper Jr., pilot of the Mercury-Atlas 9 (MA-9) Earth-orbital space mission, is assisted into his "Faith 7" Mercury spacecraft during the prelaunch countdown. MA-9 was launched on May 15, 1963, and the flight lasted for 34 hours and 20 minutes. Photo credit: NASA

  5. Design and Flight Performance of the Orion Pre-Launch Navigation System

    NASA Technical Reports Server (NTRS)

    Zanetti, Renato

    2016-01-01

    Launched in December 2014 atop a Delta IV Heavy from the Kennedy Space Center, the Orion vehicle's Exploration Flight Test-1 (EFT-1) successfully completed the objective to test the prelaunch and entry components of the system. Orion's pre-launch absolute navigation design is presented, together with its EFT-1 performance.

  6. STS-75 Flight Day 1

    NASA Technical Reports Server (NTRS)

    1996-01-01

    On this first day of the STS-75 mission, the flight crew, Cmdr. Andrew Allen, Pilot Scott Horowitz, Payload Cmdr. Franklin Chang-Diaz, Payload Specialist Umberto Guidoni (Italy), and Mission Specialists Jeffrey Hoffman, Maurizio Cheli (ESA) and Claude Nicollier (ESA), were shown performing pre-launch and launching activities. This international space mission's primary objective is the deployment of the Tethered Satellite System Reflight (TSS-1R) to a 12 mile length from the shuttle, a variety of experiments, and the satellite retrieval. These experiments include: Research on Orbital Plasma Electrodynamics (ROPE); TSS Deployer Core Equipment and Satellite Core Equipment (DCORE/SCORE); Research on Electrodynamic Tether Effects (RETE); Magnetic Field Experiments for TSS Missions (TEMAG); Shuttle Electrodynamic Tether Systems (SETS); Shuttle Potential and Return Electron Experiment (SPREE); Tether Optical Phenomena Experiment (TOP); and Observations at the Earth's Surface of Electromagnetic Emissions by TSS (OESSE). The mission's secondary objectives were those experiments found in the United States Microgravity Payload-3 (USMP-3), which include: Advanced Automated Directional Solidification Furnace (AADSF); Material pour l'Etude des Phenomenes Interessant la Solidification sur Terre et en Orbite (MEPHISTO); Space Acceleration Measurement System (SAMS); Orbital Acceleration Research Experiment (OARE); Critical Fluid Scattering Experiment (ZENO); and Isothermal Dendritic Growth Experiment (IDGE).

  7. STS-91 Flight Day 1 Highlights and Crew Activities Report

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first day of the STS-91 mission, the flight crew, Cmdr. Charles J. Precourt, Pilot Dominic L. Pudwill Gorie, and Mission Specialists Franklin R. Chang-Diaz, Janet Lynn Kavandi, Wendy B. Lawrence, Valery Victorovitch Ryumin and Andrew S. W. Thomas, can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  8. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    1st Lieutenant Kristina Williams, weather officer, 30th Space Wing, Vandenberg Air Force Base, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  9. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    1st Lieutenant Kristina Williams, weather officer, 30th Space Wing, Vandenberg Air Force Base, right, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  10. STS-113 Mission Highlights Resource Tape Flight Days 1-3. Tape: 1 of 4

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This video, part 1 of 4, shows the activities of the crew of Space Shuttle Endeavour during flight days 1-3 of STS-113. The crew consists of Commander Jim Wetherbee, Pilot Paul Lockhart, Mission Specialists Michael Lopez-Alegria and John Herrington. With them were the Expedition 6 crewmembers of the International Space Station (ISS), Ken Bowersox, Nikolai Budarin, and Don Pettit. Pre-launch procedures are shown, and the rain-delayed night launch is shown from several camera angles. On flight day 2 there was a check out of the Canadarm on Endeavour, and some intravehicular activity. Flight day 3 highlights the docking of Endeavour and the ISS, and preparation for an extravehicular activity (EVA) the following day. Earth views include the English Channel at night with a close-up of London, the coast of Ecuador, and some views of Endeavour with the Earth in the background.

  11. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Col. Michael Hough, Commander 30th Space Wing, Vandenberg Air Force Base, left, and 1st Lieutenant Kristina Williams, weather officer, 30th Space Wing, Vandenberg Air Force Base, discuss NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  12. Impact of shuttle environment on prelaunch handling of nickel-hydrogen batteries

    NASA Technical Reports Server (NTRS)

    Green, R. S.

    1986-01-01

    Deployment of the American Satellite Company 1 spacecraft for the Space Shuttle Discovery in August 1985 set a new milestone in nickel-hydrogen battery technology. This communications satellite is equipped with two 35 Ah nickel-hydrogen batteries and it is the first such satellite launched into orbit via the Space Shuttle. The prelaunch activities, combined with the environmental constraints onboard the Shuttle, led to the development of a new battery handling procedure. An outline of the prelaunch activities, with particular attention to battery charging, is presented.

  13. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    Scott Messer, program manager, NASA Missions, United Launch Alliance, speak to members of the news media during a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium in Florida.

  14. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    Sandra Smalley, director, Joint Agency Satellite Division, NASA Headquarters, speaks to members of the news media during a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium in Florida.

  15. STS-81 Flight Day 1

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This first day of the STS-81 mission begins with the flight crew, Cmdr. Michael A. Baker, Pilot Brent W. Jett, Mission Specialists, John M. Grunsfeld, Marsha S. Ivins, Peter J.K. Wisoff, and Jerry M. Linenger, performing pre-launch activities such as eating the traditional breakfast, being suited-up, and riding out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including the countdown, engine ignition, and launch. The film ends with the separation of the Solid Rocket Boosters (SRB) from the shuttle.

  16. PRELAUNCH ACTIVITY (GT-6) - ASTRONAUT THOMAS P. STAFFORD - MISC.

    NASA Image and Video Library

    1965-12-15

    S65-61806 (15 Dec. 1965) --- Astronaut Thomas P. Stafford, Gemini-6 prime crew pilot, is seen through spacecraft window as he awaits the remaining minutes of the Gemini-6 prelaunch countdown. A two-day mission in space was scheduled for astronauts Stafford and Walter M. Schirra Jr. (out of frame), command pilot. NASA successfully launched Gemini-6 from Pad 19 at 8:37 a.m. (EST) on Dec. 15, 1965. An attempt will be made to rendezvous Gemini-6 with Gemini-7. Photo credit: NASA or National Aeronautics and Space Administration

  17. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    Clay Flinn, launch weather officer, 4th Weather Squadron, Cape Canaveral Air Force Station, speaks to members of the news media during a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium in Florida.

  18. STS-83 Day 01

    NASA Technical Reports Server (NTRS)

    1997-01-01

    On this first day of the STS-83 mission, the flight crew, Cmdr. James D. Halsell Jr., Pilot Susan L. Still, Payload Cmdr. Janice E. Voss, Mission Specialists Michael L. Gernhardt and Donald A. Thomas, and Payload Specialists Gregory T. Linteris and Roger K. Crouch can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew can be seen being readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  19. The influence of black cumin seed oil therapy with dosage of 1.5 mL/day and 3 mL/day to interleukin-21 (IL-21) expression of the patients with metabolic syndrome risk

    NASA Astrophysics Data System (ADS)

    Fajar, D. R.; Akrom; Darmawan, E.

    2017-11-01

    Metabolic syndrome (MS) is a metabolic disorder caused by obesity and insulin resistance. In the state of obesity and insulin resistance occurs increased fat metabolism that causes production reactive oxygen species (ROS) and oxidative stress that makes dysregulation of adipose tissue that decreases antioxidant enzymes and immune system disorders. In diabetes mellitus there is pancreatic β cell damage caused by pro-inflammatory cytokines i.e interleukin-21 (IL-21). Black cumin seed oil (BCSO) contains antioxidants and immunomodulators but has not seen how it affects to IL-21. This study used cross over design to determine the effect of BCSO with dose of 1.5 mL/day and 3 mL/day dose of IL-21 in MS patients. The total subjects 66 of MS patients were divided into 2 groups. Group I was administered 1.5 mL/day and 3 mL/day of BCSO in dosage for 20 days and continued with washing out (BCSO discontinued) for 7 days. On the day 28, group I administrated 3 mL/day of BCSO and group II were given 1.5 mL/day of BCSO during 20 days. Statistical analysis showed that mean value expression of IL-21 were given by BCSO at dose 1.5 mL/day was 5.06±5.48 and BCSO at dose 3 mL/day 4.66±3.63 (p<0.05). The result showed that IL-21 expression in patient at risk of MS who received BCSO dose 3 mL/day were lower than those received adose of 1.5 mL/day for 20 days.

  20. Flight directors at JSC MCC Bldg 30 monitor STS-30 prelaunch activities

    NASA Image and Video Library

    1989-05-04

    Only moments away from ignition, Atlantis, Orbiter Vehicle (OV) 104, and its five member crew are the subjects of concern drawing serious countenance in this scene in the Flight Control Room (FCR) of JSC's Mission Control Center (MCC) Bldg 30. Ascent Flight Director Alan L. Briscoe, monitors the Kennedy Space Center pre-launch activity from the flight director (FD) console, along with Ronald D. Dittemore (center) and N. Wayne Hale, Jr.

  1. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    NASA Chief Scientist Jim Green discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  2. GRACE-FO Prelaunch Briefing

    NASA Image and Video Library

    2018-05-21

    NASA Headquarters Public Affairs Officer Steve Cole moderates a Gravity Recovery and Climate Experiment Follow-On (GRACE-FO) mission prelaunch media briefing, Monday, May 21, 2018, at Vandenberg Air Force Base in California. The twin GRACE-FO spacecraft will measure changes in how mass is redistributed within and among Earth's atmosphere, oceans, land and ice sheets, as well as within Earth itself. Photo Credit: (NASA/Bill Ingalls)

  3. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Tim Dunn, launch director, NASA’s Launch Services Program, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  4. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    A video showing NASA's InSight spacecraft separating from the Atlas V rocket is seen during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  5. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Stu Spath, InSight program manager, Lockheed Martin Space, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  6. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Andy Klesh, MarCO chief engineer, NASA JPL, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  7. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Tom Hoffman, InSight project manager, NASA JPL, right, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  8. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Tilman Spohn, HP3 investigation lead, Institute of Planetary Research (DLR), discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  9. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Annick Sylvestre-Baron, SEIS deputy project manager, CNES, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  10. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Scott Messer, United Launch Alliance program manager for NASA missions, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  11. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Bruce Banerdt, InSight principal investigator, NASA JPL, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  12. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Stephanie Smith, Digital & Social Media Supervisor, Jet Propulsion Laboratory moderates a prelaunch media briefing for the NASA InSight mission, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  13. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, Tim Dunn, NASA launch director at Kennedy, speaks to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  14. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, Tim Walsh, acting GOES-R System Program director for NOAA, speaks to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  15. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, Stephen Volz, director for Satellite and Information Services for NOAA, speaks to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  16. STS-85 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1997-01-01

    On this first day of the STS-85 mission, the flight crew, Cmdr. Curtis L. Brown, Jr., Pilot Kent V. Rominger, Payload Cmdr. N. Jan Davis (Ph.D.), Mission Specialists Robert L. Curbeam, Jr., and Stephen K. Robinson (Ph.D.), and Payload Specialist Bjarni V. Tryggvason can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew can be seen being readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  17. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    From left, Stephen Volz, assistant administrator for satellite and information services, National Oceanic and Atmospheric Administration (NOAA); and Greg Mandt, GOES-R system program director, NOAA, speak to members of the news media during a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium.

  18. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Jason Townsend, NASA's Deputy Social Media Manager, reads questions submitted by online social media followers during a prelaunch media briefing for NASA's InSight mission, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  19. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Social media guest listen as Bruce Banerdt, InSight principal investigator, NASA JPL, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  20. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Philippe Lognonné, SEIS investigation lead, Institut de Physique du Globe de Paris (IPGP) discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  1. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Col. Michael Hough, Commander 30th Space Wing, Vandenberg Air Force Base, discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  2. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    From left, Sandra Smalley, director, Joint Agency Satellite Division, NASA Headquarters; Omar Baez, launch director, NASA Kennedy; and Scott Messer, program manager, NASA Missions, United Launch Alliance, speak to members of the news media during a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium in Florida.

  3. GRACE-FO Prelaunch Briefing

    NASA Image and Video Library

    2018-05-21

    Phil Morton, NASA GRACE-FO project manager at JPL, second from right, discusses the Gravity Recovery and Climate Experiment Follow-On (GRACE-FO) mission during a prelaunch media briefing, Monday, May 21, 2018, at Vandenberg Air Force Base in California. The twin GRACE-FO spacecraft will measure changes in how mass is redistributed within and among Earth's atmosphere, oceans, land and ice sheets, as well as within Earth itself. Photo Credit: (NASA/Bill Ingalls)

  4. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Stu Spath, InSight program manager, Lockheed Martin Space, left, and Tom Hoffman, InSight project manager, NASA JPL, discuss NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  5. InSight Prelaunch Briefing

    NASA Image and Video Library

    2018-05-03

    Scott Messer, United Launch Alliance program manager for NASA missions, is seen on a monitor as he discusses NASA's InSight mission during a prelaunch media briefing, Thursday, May 3, 2018, at Vandenberg Air Force Base in California. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)

  6. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, and Kathy Winters, launch weather officer for the U.S. Air Force 45th Weather Squadron at Cape Canaveral Air Force Station, speaks to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  7. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, Tim Dunn, NASA launch director at Kennedy, left, and Scott Messer, manager of NASA Programs for United launch Alliance, speak to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  8. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, Sandra Smalley, director of the Joint Agency Satellite Division at NASA Headquarters in Washington D.C., speaks to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  9. STS-88 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first day of the STS-88 mission, the flight crew, Commander Robert D. Cabana, Pilot Frederick W. Sturckow, and Mission Specialists Nancy J. Currie, James H. Newman, Jerry L. Ross, and Sergei Krikalev can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the "white room" for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  10. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    From left, Stephen Volz, assistant administrator for satellite and information services, National Oceanic and Atmospheric Administration (NOAA); Greg Mandt, GOES-R system program director, NOAA; and Sandra Smalley, director, Joint Agency Satellite Division, NASA Headquarters, speak to members of the news media during a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium.

  11. Suomi NPP VIIRS Prelaunch and On-orbit Geometric Calibration and Characterization

    NASA Technical Reports Server (NTRS)

    Wolfe, Robert E.; Lin, Guoqing; Nishihama, Masahiro; Tewari, Krishna P.; Tilton, James C.; Isaacman, Alice R.

    2013-01-01

    The Visible Infrared Imager Radiometer Suite (VIIRS) sensor was launched 28 October 2011 on the Suomi National Polarorbiting Partnership (SNPP) satellite. VIIRS has 22 spectral bands covering the spectrum between 0.412 m and 12.01 m, including 16 moderate resolution bands (M-bands) with a spatial resolution of 750 m at nadir, 5 imaging resolution bands (I-bands) with a spatial resolution of 375 m at nadir, and 1 day-night band (DNB) with a near-constant 750 m spatial resolution throughout the scan. These bands are located in a visible and near infrared (VisNIR) focal plane assembly (FPA), a short- and mid-wave infrared (SWMWIR) FPA and a long-wave infrared (LWIR) FPA. All bands, except the DNB, are co-registered for proper environmental data records (EDRs) retrievals. Observations from VIIRS instrument provide long-term measurements of biogeophysical variables for climate research and polar satellite data stream for the operational communitys use in weather forecasting and disaster relief and other applications. Well Earth-located (geolocated) instrument data is important to retrieving accurate biogeophysical variables. This paper describes prelaunch pointing and alignment measurements, and the two sets of on-orbit correction of geolocation errors, the first of which corrected error from 1,300 m to within 75 m (20 I-band pixel size), and the second of which fine tuned scan angle dependent errors, bringing VIIRS geolocation products to high maturity in one and a half years of the SNPP VIIRS on-orbit operations. Prelaunch calibration and the on-orbit characterization of sensor spatial impulse responses and band-to-band co-registration (BBR) are also described.

  12. STS-99 Crew Activities Report/Flight Day 1 Highlights

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Live footage shows the crew, Commander Kevin R. Kregel, Pilot Dominic L. Pudwill Gorie, and Mission Specialists Janet L. Kavandi, Janice E. Voss, Mamoru Mohri and Gerhard P.J. Thiele, seated in the dining room with the traditional cake. The crew is seen performing various pre-launch activities including suit-up, walk out to the Astro-van, and strap-in into the vehicle. Also seen are the retractions of the orbiter access arm and the gaseous oxygen mint hood, main engine start, booster ignition, liftoff, and separation of the solid rocket boosters. The Red Team (first of the dual shift crew) includes Kregel, Kavandi, and Thiele, who are shown conducting jet thruster firings, activating radar instruments, and deploying the boom (mass).

  13. JPSS-1 VIIRS Pre-Launch Response Versus Scan Angle Testing and Performance

    NASA Technical Reports Server (NTRS)

    Moyer, David; McIntire, Jeff; Oudrari, Hassan; McCarthy, James; Xiong, Xiaoxiong; De Luccia, Frank

    2016-01-01

    The Visible Infrared Imaging Radiometer Suite (VIIRS) instruments on-board both the Suomi National Polar-orbiting Partnership (S-NPP) and the first Joint Polar Satellite System (JPSS-1) spacecraft, with launch dates of October 2011 and December 2016 respectively, are cross-track scanners with an angular swath of +/-56.06 deg. A four-mirror Rotating Telescope Assembly (RTA) is used for scanning combined with a Half Angle Mirror (HAM) that directs light exiting from the RTA into the aft-optics. It has 14 Reflective Solar Bands (RSBs), seven Thermal Emissive Bands (TEBs) and a panchromatic Day Night Band (DNB). There are three internal calibration targets, the Solar Diffuser, the BlackBody and the Space View, that have fixed scan angles within the internal cavity of VIIRS. VIIRS has calibration requirements of 2% on RSB reflectance and as tight as 0.4% on TEB radiance that requires the sensor's gain change across the scan or Response Versus Scan angle (RVS) to be well quantified. A flow down of the top level calibration requirements put constraints on the characterization of the RVS to 0.2%-0.3% but there are no specified limitations on the magnitude of response change across scan. The RVS change across scan angle can vary significantly between bands with the RSBs having smaller changes of approximately 2% and some TEBs having approximately 10% variation. Within aband, the RVS has both detector and HAM side dependencies that vary across scan. Errors in the RVS characterization will contribute to image banding and striping artifacts if their magnitudes are above the noise level of the detectors. The RVS was characterized pre-launch for both S-NPP and JPSS-1 VIIRS and a comparison of the RVS curves between these two sensors will be discussed.

  14. Suomi Npp and Jpss Pre-Launch Test Data Collection and Archive

    NASA Astrophysics Data System (ADS)

    Denning, M.; Ullman, R.; Guenther, B.; Kilcoyne, H.; Chandler, C.; Adameck, J.

    2012-12-01

    (GRAVITE), where they will reside for the life of the mission. As a result, data and documentation are available for query, analysis, and download by the cal/val community via the command-line GRAVITE Transfer Protocol (GTP) tool or via the NOAA-collaborative website "CasaNOSA". Instrument and spacecraft test data, telemetry, and ground support equipment information were collected and organized with detailed test procedures, logs, analyses, characterizations, and reports. This 45 Terabyte archive facilitates the comparison of on-orbit Suomi NPP operating characteristics with that observed prior to launch, and will serve as a resource to aid in the assessment of pre-launch JPSS-1 sensor performance. In summary, this paper will present the innovative pre-launch test data campaign infrastructures employed for Suomi NPP and planned for JPSS-1.

  15. STS-95 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first day of the STS-95 mission, the flight crew, Cmdr. Curtis L. Brown, Pilot Steven W. Lindsey, Mission Specialists Scott E. Parazynski, Stephen K. Robinson, and Pedro Duque, and Payload Specialists Chiaki Mukai and John H. Glenn, can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  16. InSight Prelaunch Overview

    NASA Image and Video Library

    2018-05-03

    Members of the media and social media participants attended the NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, or InSight, prelaunch briefing at Vandenberg Air Force Base in California. The presentation focused on InSight Mars lander. InSight is scheduled for liftoff May 5, 2018, atop a United Launch Alliance (ULA) Atlas V rocket from Space Launch Complex 3 at Vandenberg. The spacecraft will be the first mission to look deep beneath the Martian surface studying the planet's interior by measuring its heat output and listen for marsquakes.

  17. InSight Prelaunch Overview

    NASA Image and Video Library

    2018-05-03

    During a prelaunch briefing at Vandenberg Air Force Base in California, Stephanie Smith, NASA Communications, speaks to members of the media. The presentation focused on NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, or InSight, Mars lander. InSight is scheduled for liftoff May 5, 2018, atop a United Launch Alliance (ULA) Atlas V rocket from Space Launch Complex 3 at Vandenberg. The spacecraft will be the first mission to look deep beneath the Martian surface studying the planet's interior by measuring its heat output and listen for marsquakes.

  18. STS-105/Discovery/ISS 7A.1: Pre-Launch Activities, Launch, Orbit Activities and Landing

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The crew of Space Shuttle Discovery on STS-105 is introduced at their pre-launch meal and at suit-up. The crew members include Commander Scott Horowitz, Pilot Rick Sturckow, and Mission Specialists Patrick Forrester and Daniel Barry, together with the Expedition 3 crew of the International Space Station (ISS). The Expedition 3 crew includes Commander Frank Culbertson, Soyuz Commander Vladimir Dezhurov, and Flight Engineer Mikhail Tyurin. When the astronauts depart for the launch pad in the Astrovan, their convoy is shown from above. Upon reaching the launch pad, they conduct a walk around of the shuttle, display signs for family members while being inspected in the White Room, and are strapped into their seats onboard Disciovery. The video includes footage of Discovery in the Orbiter Processing Facility, and some of the pre-launch procedures at the Launch Control Center are shown. The angles of launch replays include: TV-1, Beach Tracker, VAB, Pad A, Tower 1, UCS-15, Grandstand, OTV-70, Onboard, IGOR, and UCS-23. The moment of docking between Discovery and the ISS is shown from inside Discovery's cabin. While in orbit, the crew conducted extravehicular activities (EVAs) to attach an experiments container, and install handrails on the Destiny module of the ISS. The video shows the docking and unloading of the Leonardo Multipurpose Logistics Module (MPLM) onto the ISS. The deployment of a satellite from Discovery with the coast of the Gulf of Mexico in the background is shown. Cape Canaveral is also shown from space. Landing replays include VAB, Tower 1, mid-field, South End SLF, North End SLF, Tower 2, Playalinda DOAMS, UCS-23, and Pilot Point of View (PPOV). NASA Administrator Dan Goldin meets the crew upon landing and participates in their walk around of Discovery. The video concludes with a short speech by commander Horowitz.

  19. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    GOES-S Prelaunch News Conference hosted by NASA Communications' Tori Mclendon, with Stephen Volz, Director for Satellite and Information Services, NOAA; Tim Walsh, GOES-R system program director (acting), NOAA; Sandra Smalley, Director, NASA Joint Agency Satellite Division; Tim Dunn, NASA Launch Director, Kennedy Space Center, Florida; Scott Messer, Program Manager, NASA Missions, United Launch Alliance; and Kathy Winters, Launch Weather Officer, 45th Weather Squadron, Cape Canaveral Air Force Station, Florida.

  20. ISS Service Module Pre-Launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Various shots show Discovery at the launch pad during the final 30-minute countdown. The prelaunch conditions are described and information is given on the upcoming launch and the orbiter's docking with the International Space Station (ISS). A brief collage of rollout and launch footage of STS-92 Endeavour commemorates the 100th Space Shuttle mission and the 100th anniversary of the Philadelphia Orchestra (also seen). The music of '2001: A Space Odyssey) is played by the orchestra.

  1. SpaceX CRS-10 Prelaunch News Conference

    NASA Image and Video Library

    2017-02-17

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media at a prelaunch news conference for the SpaceX CRS-10 commercial resupply services mission to the International Space Station. Jessica Jensen, director of Dragon mission management for SpaceX, answers questions.

  2. OSIRIS-REx Prelaunch News Conference

    NASA Image and Video Library

    2016-09-06

    In the Kennedy Space Center’s Press Site auditorium, Scott Messer, program manager for NASA missions at United Launch Alliance in Centennial, Colorado; Michael Donnelly, OSIRIS-REx project manager at NASA’s Goddard Space Flight Center in Greenbelt, Maryland; and Rich Kuhns, OSIRIS-REx program manager for Lockheed Martin Space Systems in Denver; speak to members of the media at a prelaunch news conference for the agency’s Origins, Spectral Interpretation, Resource Identification, Security-Regolith Explorer, or OSIRIS-REx spacecraft.

  3. APOLLO 17 PRELAUNCH ASTRONAUT TRAINING

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Apollo 17 Mission Commander Eugene A. Cernan, a Navy Captain, and Lunar Module Pilot Dr. Harrison H. [Jack] Schmitt, civilian scientist-astronaut, at right, familiarize themselves with equipment used in the Lunar Module in which the pair will descent to the lunar surface during December. Cernan and Dr. Schmitt are undergoing prelaunch training in the Lunar Module Simulator at the Flight Crew Training Building at the Kennedy Space Center. Navy Commander Ronald E. Evans, Command Module Pilot, will accompany Cernan and Dr. Schmitt on the mission.

  4. SpaceX CRS-10 Prelaunch News Conference

    NASA Image and Video Library

    2017-02-17

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media at a prelaunch news conference for the SpaceX CRS-10 commercial resupply services mission to the International Space Station. Tara Ruttley, associate scientist for the International Space Station Program at Johnson Space Center in Houston, answers questions.

  5. SpaceX CRS-10 Prelaunch News Conference

    NASA Image and Video Library

    2017-02-17

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media at a prelaunch news conference for the SpaceX CRS-10 commercial resupply services mission to the International Space Station. Tara Ruttley, associate scientist for the International Space Station Program at Johnson Space Center in Houston answers questions.

  6. Best Practice Guidelines for Pre-Launch Characterization and Calibration of Instruments for Passive Optical Remote Sensing1

    PubMed Central

    Datla, R. U.; Rice, J. P.; Lykke, K. R.; Johnson, B. C.; Butler, J. J.; Xiong, X.

    2011-01-01

    The pre-launch characterization and calibration of remote sensing instruments should be planned and carried out in conjunction with their design and development to meet the mission requirements. The onboard calibrators such as blackbodies and the sensors such as spectral radiometers should be characterized and calibrated using SI traceable standards. In the case of earth remote sensing, this allows inter-comparison and intercalibration of different sensors in space to create global time series of climate records of high accuracy where some inevitable data gaps can be easily bridged. The recommended best practice guidelines for this pre-launch effort is presented based on experience gained at National Institute of Standards and Technology (NIST), National Aeronautics and Space Administration (NASA) and National Oceanic and Atmospheric Administration (NOAA) programs over the past two decades. The currently available radiometric standards and calibration facilities at NIST serving the remote sensing community are described. Examples of best practice calibrations and intercomparisons to build SI (international System of Units) traceable uncertainty budget in the instrumentation used for preflight satellite sensor calibration and validation are presented. PMID:26989588

  7. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    NASA and industry leaders participate in a Geostationary Operational Environmental Satellite (GOES-R), prelaunch news conference in the Kennedy Space Center's Press Site auditorium in Florida. NASA and industry leaders include: Michael Curie, of NASA Communications; Stephen Volz, assistant administrator for satellite and information services, National Oceanic and Atmospheric Administration (NOAA's); Greg Mandt, GOES-R system program director, NOAA; Sandra Smalley, director, Joint Agency Satellite Division, NASA Headquarters; Omar Baez, launch director, NASA Kennedy; Scott Messer, program manager, NASA Missions, United Launch Alliance; and Clay Flinn, launch weather officer, 4th Weather Squadron, Cape Canaveral Air Force Station.

  8. GOES-R Prelaunch News Conference

    NASA Image and Video Library

    2016-11-17

    Members of the news media attend a Geostationary Operational Environmental Satellite (GOES-R) prelaunch news conference in the Kennedy Space Center's Press Site auditorium in Florida. NASA and industry leaders include: Michael Curie, of NASA Communications; Stephen Volz, assistant administrator for satellite and information services, National Oceanic and Atmospheric Administration (NOAA's); Greg Mandt, GOES-R system program director, NOAA; Sandra Smalley, director, Joint Agency Satellite Division, NASA Headquarters; Omar Baez, launch director, NASA Kennedy; Scott Messer, program manager, NASA Missions, United Launch Alliance; and Clay Flinn, launch weather officer, 4th Weather Squadron, Cape Canaveral Air Force Station.

  9. TDRS-L Pre-Launch Press Conference

    NASA Image and Video Library

    2014-01-21

    CAPE CANAVERAL, Fla. – During a news conference at NASA's Kennedy Space Center in Florida, agency and contractor officials discussed preparations for the launch of NASA's Tracking and Data Relay Satellite, or TDRS-L, spacecraft. Participants included Andy Kopito, Civil Space Programs director for Boeing Space & Intelligence Systems in El Segundo, Calif. The TDRS-L spacecraft is the second of three new satellites designed to ensure vital operational continuity for NASA by expanding the lifespan of the Tracking and Data Relay Satellite System TDRSS fleet, which consists of eight satellites in geosynchronous orbit. The spacecraft provide tracking, telemetry, command and high bandwidth data return services for numerous science and human exploration missions orbiting Earth. These include NASA's Hubble Space Telescope and the International Space Station. TDRS-L has a high-performance solar panel designed for more spacecraft power to meet the growing S-band communications requirements. TDRSS is one of NASA Space Communication and Navigation’s SCaN three networks providing space communications to NASA’s missions. For more information more about TDRS-L, visit: http://www.nasa.gov/tdrs To learn more about SCaN, visit: www.nasa.gov/scan Photo credit: NASA/Frankie Martin

  10. TDRS-L Pre-Launch Press Conference

    NASA Image and Video Library

    2014-01-21

    CAPE CANAVERAL, Fla. –During a news conference at NASA's Kennedy Space Center in Florida, agency and contractor officials discussed preparations for the launch of NASA's Tracking and Data Relay Satellite, or TDRS-L, spacecraft. Participating in the briefing, from the left, are Badri Younes, deputy associate administrator, Space Communications and Navigation SCaN NASA Human Exploration and Operations Mission Directorate at NASA Headquarters in Washington D.C., Tim Dunn, NASA launch director at Kennedy, Vernon Thorp, program manager for NASA Missions with United Launch Alliance in Denver, Colo., Jeffrey Gramling, NASA's TDRS-L project manager at the Goddard Space Flight Center in Greenbelt, Md., Andy Kopito, Civil Space Programs director for Boeing Space & Intelligence Systems in El Segundo, Calif., and Clay Flinn, launch weather officer for the 45th Weather Squadron at Cape Canaveral Air Force Station, Fla. The TDRS-L spacecraft is the second of three new satellites designed to ensure vital operational continuity for NASA by expanding the lifespan of the Tracking and Data Relay Satellite System TDRSS fleet, which consists of eight satellites in geosynchronous orbit. The spacecraft provide tracking, telemetry, command and high bandwidth data return services for numerous science and human exploration missions orbiting Earth. These include NASA's Hubble Space Telescope and the International Space Station. TDRS-L has a high-performance solar panel designed for more spacecraft power to meet the growing S-band communications requirements. TDRSS is one of NASA Space Communication and Navigation’s SCaN three networks providing space communications to NASA’s missions. For more information more about TDRS-L, visit: http://www.nasa.gov/tdrs To learn more about SCaN, visit: www.nasa.gov/scan Photo credit: NASA/Frankie Martin

  11. TDRS-L Pre-Launch Press Conference

    NASA Image and Video Library

    2014-01-21

    CAPE CANAVERAL, Fla. –During a news conference at NASA's Kennedy Space Center in Florida, agency and contractor officials discussed preparations for the launch of NASA's Tracking and Data Relay Satellite, or TDRS-L, spacecraft. Participating in the briefing, from the left, are George Diller of NASA Public Affairs, Badri Younes, deputy associate administrator, Space Communications and Navigation SCaN NASA Human Exploration and Operations Mission Directorate at NASA Headquarters in Washington D.C., Tim Dunn, NASA launch director at Kennedy, Vernon Thorp, program manager for NASA Missions with United Launch Alliance in Denver, Colo., Jeffrey Gramling, NASA's TDRS-L project manager at the Goddard Space Flight Center in Greenbelt, Md., Andy Kopito, Civil Space Programs director for Boeing Space & Intelligence Systems in El Segundo, Calif., and Clay Flinn, launch weather officer for the 45th Weather Squadron at Cape Canaveral Air Force Station, Fla. The TDRS-L spacecraft is the second of three new satellites designed to ensure vital operational continuity for NASA by expanding the lifespan of the Tracking and Data Relay Satellite System TDRSS fleet, which consists of eight satellites in geosynchronous orbit. The spacecraft provide tracking, telemetry, command and high bandwidth data return services for numerous science and human exploration missions orbiting Earth. These include NASA's Hubble Space Telescope and the International Space Station. TDRS-L has a high-performance solar panel designed for more spacecraft power to meet the growing S-band communications requirements. TDRSS is one of NASA Space Communication and Navigation’s SCaN three networks providing space communications to NASA’s missions. For more information more about TDRS-L, visit: http://www.nasa.gov/tdrs To learn more about SCaN, visit: www.nasa.gov/scan Photo credit: NASA/Frankie Martin

  12. TDRS-L Pre-Launch Press Conference

    NASA Image and Video Library

    2014-01-21

    CAPE CANAVERAL, Fla. – During a news conference at NASA's Kennedy Space Center in Florida, agency and contractor officials discussed preparations for the launch of NASA's Tracking and Data Relay Satellite, or TDRS-L, spacecraft. Participants included Clay Flinn, launch weather officer for the 45th Weather Squadron at Cape Canaveral Air Force Station, Fla. Seated behind Flinn is Andy Kopito, Civil Space Programs director for Boeing Space & Intelligence Systems in El Segundo, Calif. The TDRS-L spacecraft is the second of three new satellites designed to ensure vital operational continuity for NASA by expanding the lifespan of the Tracking and Data Relay Satellite System TDRSS fleet, which consists of eight satellites in geosynchronous orbit. The spacecraft provide tracking, telemetry, command and high bandwidth data return services for numerous science and human exploration missions orbiting Earth. These include NASA's Hubble Space Telescope and the International Space Station. TDRS-L has a high-performance solar panel designed for more spacecraft power to meet the growing S-band communications requirements. TDRSS is one of NASA Space Communication and Navigation’s SCaN three networks providing space communications to NASA’s missions. For more information more about TDRS-L, visit: http://www.nasa.gov/tdrs To learn more about SCaN, visit: www.nasa.gov/scan Photo credit: NASA/Frankie Martin

  13. STS-82 Flight Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The first day of the STS-82 mission begins with the crew, Commander Kenneth D. Bowersox, Pilot Scott J. Horowitz, Payload Commander Mark C. Lee, and Mission Specialists Gregory J. Harbaugh, Steven L. Smith, Joseph R. Tanner, and Steven A. Hawley performing pre-launch activities such as eating the traditional breakfast, being suited up, and riding out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch, and arm retraction, launch activities are shown including the countdown, engine ignition, launch, shuttle roll maneuver, and then the separation of the Solid Rocket Boosters (SRB) from the shuttle. Once in orbit the cargo bay doors are seen opening.

  14. GRACE-FO Prelaunch Briefing

    NASA Image and Video Library

    2018-05-21

    NASA Headquarters Public Affairs Officer Steve Cole, left, moderates the Gravity Recovery and Climate Experiment Follow-On (GRACE-FO) mission prelaunch media briefing with David Jarrett, GRACE-FO program executive in the Earth Science Division at NASA Headquarters; Frank Webb, GRACE-FO project scientist at JPL; Frank Flechtner, GRACE-FO project manager for the German Research Centre for Geosciences (GFZ) in Potsdam, Germany; Phil Morton, NASA GRACE-FO project manager at JPL; and Capt. Jennifer Haden, weather officer, 30th Space Wing, Vandenberg Air Force Base, right, Monday, May 21, 2018, at Vandenberg Air Force Base in California. The twin GRACE-FO spacecraft will measure changes in how mass is redistributed within and among Earth's atmosphere, oceans, land and ice sheets, as well as within Earth itself. Photo Credit: (NASA/Bill Ingalls)

  15. GOES-S Prelaunch News Conference

    NASA Image and Video Library

    2018-02-27

    In the Kennedy Space Center's Press Site auditorium, NASA and industry leaders speak to members of the media at a prelaunch news conference about National Oceanic and Atmospheric Administration's, or NOAA's, Geostationary Operational Environmental Satellite, or GOES-S. Participants from left are: Tori McLendon of NASA Communications; Stephen Volz, director for Satellite and Information Services for NOAA; Tim Walsh, acting GOES-R System Program director for NOAA; Sandra Smalley, director of the Joint Agency Satellite Division at NASA Headquarters in Washington D.C.; Tim Dunn, NASA launch director at Kennedy; Scott Messer, manager of NASA Programs for United launch Alliance; and Kathy Winters, launch weather officer for the U.S. Air Force 45th Weather Squadron at Cape Canaveral Air Force Station. The GOES series of satellites will significantly improve the detection and observation of environmental phenomena that directly affect public safety, protection of property and the nation's economic health and prosperity. GOES-S is slated to lift off at 5:02 p.m. EST on March 1, 2018 aboard a United Launch Alliance Atlas V rocket.

  16. STS-106 Crew Activity Report/Flight Day 1 Highlights

    NASA Technical Reports Server (NTRS)

    2000-01-01

    On this first day of the STS-106 Atlantis mission, the flight crew, Commander Terrence W. Wilcutt, Pilot Scott D. Altman, and Mission Specialists Daniel C. Burbank, Edward T. Lu, Richard A. Mastracchio, Yuri Ivanovich Malenchenko, and Boris V. Morukov are seen performing pre-launch activities. They are shown sitting around the breakfast table with the traditional cake, suiting-up, and riding out to the launch pad. The final inspection team is seen as they conduct their final check of the space shuttle on the launch complex. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  17. Prelaunch testing of the GEOS-3 laser reflector array

    NASA Technical Reports Server (NTRS)

    Minott, P. O.; Fitzmaurice, M. W.; Abshire, J. B.; Rowe, H. E.

    1978-01-01

    The prelaunch testing performed on the Geos-3 laser reflector array before launch was used to determine the lidar cross section of the array and the distance of the center of gravity of the satellite from the center of gravity of reflected laser pulses as a function of incidence angle. Experimental data are compared to computed results.

  18. PRELAUNCH - GEMINI-TITAN (GT)-12 - LEAVE TRAILER - CAPE

    NASA Image and Video Library

    1966-11-11

    S66-59916 (11 Nov. 1966) --- Prime crew for the Gemini-12 spaceflight, astronauts James A. Lovell Jr. (leading), command pilot, and Edwin E. Aldrin Jr., pilot, leave the suiting trailer at Launch Complex 16 during prelaunch countdown. Moments later they entered a transport van which carried them to Pad 19 and their waiting spacecraft. The liftoff was at 3:46 p.m. (EST), Nov. 11, 1966. Photo credit: NASA

  19. S-NPP ATMS Instrument Prelaunch and On-Orbit Performance Evaluation

    NASA Technical Reports Server (NTRS)

    Kim, Edward; Lyu, Cheng-Hsuan; Anderson, Kent; Leslie, Vincent R.; Blackwell, William J.

    2014-01-01

    The first of a new generation of microwave sounders was launched aboard the Suomi-National Polar-Orbiting Partnership satellite in October 2011. The Advanced Technology Microwave Sounder (ATMS) combines the capabilities and channel sets of three predecessor sounders into a single package to provide information on the atmospheric vertical temperature and moisture profiles that are the most critical observations needed for numerical weather forecast models. Enhancements include size/mass/power approximately one third of the previous total, three new sounding channels, the first space-based, Nyquist-sampled cross-track microwave temperature soundings for improved fusion with infrared soundings, plus improved temperature control and reliability. This paper describes the ATMS characteristics versus its predecessor, the advanced microwave sounding unit (AMSU), and presents the first comprehensive evaluation of key prelaunch and on-orbit performance parameters. Two-year on-orbit performance shows that the ATMS has maintained very stable radiometric sensitivity, in agreement with prelaunch data, meeting requirements for all channels (with margins of 40% for channels 1-15), and improvements over AMSU-A when processed for equivalent spatial resolution. The radiometric accuracy, determined by analysis from ground test measurements, and using on-orbit instrument temperatures, also shows large margins relative to requirements (specified as <1.0K for channels 1, 2, and 16-22 and <0.75 K for channels 3-15). A thorough evaluation of the performance of ATMS is especially important for this first proto-flight model unit of what will eventually be a series of ATMS sensors providing operational sounding capability for the U.S. and its international partners well into the next decade.

  20. SpaceX CRS-11 Prelaunch News Conference

    NASA Image and Video Library

    2017-05-31

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-11 commercial resupply services mission to the International Space Station. From left are: Mike Curie of NASA Communications, Kirk Shireman, NASA's International Space Station Program manager, Hans Koenigsmann, vice president of Flight Reliability for SpaceX, Camille Alleyne, associate program scientist for the International Space Station at NASA’s Johnson Space Center, and Mike McAleenan, launch weather officer for the U.S. Air Force 45th Weather Squadron. A Dragon spacecraft is scheduled to be launched from Kennedy’s Launch Complex 39A on June 1 atop a SpaceX Falcon 9 rocket on the company's 11th Commercial Resupply Services mission to the space station.

  1. STS-76 Flight Day 1

    NASA Technical Reports Server (NTRS)

    1996-01-01

    On this first day of the STS-76 mission, the flight crew, Cmdr. Kevin P. Chilton, Pilot Richard A Searfoss, and Mission Specialists Shannon W. Lucid, Linda M. Godwin, Michael R. Clifford, and Ronald M. Sega, are shown performing prelaunch and launch activities for the night launch of the Space Shuttle Atlantis. The primary objective of this mission is the third docking between the Mir Space Station and Atlantis and a crew transfer. Lucid will remain onboard the Mir for about four months. Other activities include an EVA by Godwin and Clifford, logistics operations, and scientific research with a SPACEHAB module, some middeck experiments, and a Get Away Special (GAS) canister. Also, almost a ton of equipment and supplies will be transferred to the Mir. Experiments include the Mir Electric Field Characterization (MEFC), European Space Agency (ESA) Biorack life sciences experiment, Queens University Experiment in Liquid Diffusion (QUELD), Optizone Liquid Phase Sintering Experiment (OLIPSE), and a Naval Research Laboratory (NRL) GAS payload Trapped Ions in Space (TRIS), which will measure low-energy particle radiation in the inner magnetosphere. This mission also will include a KidSat, a prototype of Earth viewing cameras and instruments, that allow students in grades K-12 to see and direct the capture of pictures from space. Footage from Mission control is also included.

  2. Aquarius Salinity Retrieval Algorithm: Final Pre-Launch Version

    NASA Technical Reports Server (NTRS)

    Wentz, Frank J.; Le Vine, David M.

    2011-01-01

    This document provides the theoretical basis for the Aquarius salinity retrieval algorithm. The inputs to the algorithm are the Aquarius antenna temperature (T(sub A)) measurements along with a number of NCEP operational products and pre-computed tables of space radiation coming from the galaxy and sun. The output is sea-surface salinity and many intermediate variables required for the salinity calculation. This revision of the Algorithm Theoretical Basis Document (ATBD) is intended to be the final pre-launch version.

  3. Pegasus XL CYGNSS Prelaunch News Conference

    NASA Image and Video Library

    2016-12-10

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. The model depicts the deployment module from which the eight micro-satellites will be deployed. In the background is Tim Dunn, NASA launch director at Kennedy. The CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.

  4. Pegasus XL CYGNSS Prelaunch News Conference

    NASA Image and Video Library

    2016-12-10

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: Tim Dunn, NASA launch director at Kennedy; and Bryan Baldwin, Pegasus launch vehicle program manager for Orbital ATK, Dulles, Virginia. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.

  5. SpaceX CRS-14 Prelaunch News Conference

    NASA Image and Video Library

    2018-04-01

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-14 commercial resupply services mission to the International Space Station. Stephanie Schierholz, of NASA Communications, moderates the news conference. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station at 4:30 p.m. EST, on April 2, 2018. The SpaceX Falcon 9 rocket will lift off on the company's 14th Commercial Resupply Services mission to the space station.

  6. SpaceX CRS-14 Prelaunch News Conference

    NASA Image and Video Library

    2018-04-01

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-14 commercial resupply services mission to the International Space Station. Jessica Jensen, director, Dragon Mission Management, SpaceX, participates in the news conference. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station at 4:30 p.m. EST, on April 2, 2018. The SpaceX Falcon 9 rocket will lift off on the company's 14th Commercial Resupply Services mission to the space station.

  7. Orbital ATK CRS-7 Prelaunch News Conference

    NASA Image and Video Library

    2017-04-17

    A prelaunch status briefing for Orbital ATK's seventh commercial resupply mission, CRS-7, to the International Space Station, is held at NASA Kennedy Space Center's Press Site in Florida. Participating in the briefing is Frank Culbertson, Space Systems Group president, Orbital ATK. Orbital ATK's Cygnus pressurized cargo module is set to launch atop the ULA Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station on April 18. Cygnus will deliver 7,600 pounds of supplies, equipment and scientific research materials to the space station. Liftoff is scheduled for 11:11 a.m. EDT.

  8. GEMINI-TITAN (GT)-7 - PRELAUNCH ACTIVITY - COMMAND PILOT (LEAVES SUITING TRAILER) - CAPE

    NASA Image and Video Library

    1965-12-04

    S65-59932 (4 Dec. 1965) --- Prime crew for the Gemini-7 spaceflight astronauts James A. Lovell Jr. (front), pilot, and Frank Borman, command pilot, leave the suiting trailer at Launch Complex 16 during prelaunch countdown at Cape Kennedy, Florida. Photo credit: NASA

  9. Pre-launch Performance Assessment of the VIIRS Ice Surface Temperature Algorithm

    NASA Astrophysics Data System (ADS)

    Ip, J.; Hauss, B.

    2008-12-01

    The VIIRS Ice Surface Temperature (IST) environmental data product provides the surface temperature of sea-ice at VIIRS moderate resolution (750m) during both day and night. To predict the IST, the retrieval algorithm utilizes a split-window approach with Long-wave Infrared (LWIR) channels at 10.76 μm (M15) and 12.01 μm (M16) to correct for atmospheric water vapor. The split-window approach using these LWIR channels is AVHRR and MODIS heritage, where the MODIS formulation has a slightly modified functional form. The algorithm relies on the VIIRS Cloud Mask IP for identifying cloudy and ocean pixels, the VIIRS Ice Concentration IP for identifying ice pixels, and the VIIRS Aerosol Optical Thickness (AOT) IP for excluding pixels with AOT greater than 1.0. In this paper, we will report the pre-launch performance assessment of the IST retrieval. We have taken two separate approaches to perform this assessment, one based on global synthetic data and the other based on proxy data from Terra MODIS. Results of the split- window algorithm have been assessed by comparison either to synthetic "truth" or results of the MODIS retrieval. We will also show that the results of the assessment with proxy data are consistent with those obtained using the global synthetic data.

  10. Pegasus XL CYGNSS Prelaunch News Conference

    NASA Image and Video Library

    2016-12-10

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: Christine Bonniksen, CYGNSS program executive in the Earth Science Division of the Science Mission Directorate at NASA Headquarters in Washington, D.C.; and Tim Dunn, NASA launch director at Kennedy. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.

  11. PRELAUNCH - (SUITING-UP) APOLLO 15 - KSC

    NASA Image and Video Library

    1971-07-26

    S71-41408 (26 July 1971) --- The three Apollo 15 astronauts go through suiting up operations in the Kennedy Space Center's (KSC) Manned Spacecraft Operations Building (MSOB) during the Apollo 15 prelaunch countdown. They are David R. Scott (foreground), commander; Alfred M. Worden (center), command module pilot; and James B. Irwin (background), lunar module pilot. Minutes later the crew rode a special transport van over to Pad A, Launch Complex 39, where their spacecraft awaited them. With the crew was Dr. Donald (Deke) K. Slayton (wearing dark blue sport shirt), director of Flight Crew Operations, Manned Spacecraft Center (MSC). The Apollo 15 space vehicle was launched at 9:34:00:79 a.m. (EDT), July 26, 1971, on a lunar landing mission.

  12. SpaceX CRS-14 Prelaunch News Conference

    NASA Image and Video Library

    2018-04-01

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-14 commercial resupply services mission to the International Space Station. Mike McAleenan, weather officer, 45th Weather Squadron, participates in the news conference. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station at 4:30 p.m. EST, on April 2, 2018. The SpaceX Falcon 9 rocket will lift off on the company's 14th Commercial Resupply Services mission to the space station.

  13. SpaceX CRS-14 Prelaunch News Conference

    NASA Image and Video Library

    2018-04-01

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-14 commercial resupply services mission to the International Space Station. Pete Hasbrook, associate program scientist, ISS Program Science Office at NASA's Johnson Space Center in Houston; participates in the news conference. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station at 4:30 p.m. EST, on April 2, 2018. The SpaceX Falcon 9 rocket will lift off on the company's 14th Commercial Resupply Services mission to the space station.

  14. Orbital ATK CRS-7 Prelaunch News Conference

    NASA Image and Video Library

    2017-04-17

    A prelaunch status briefing for Orbital ATK's seventh commercial resupply mission, CRS-7, to the International Space Station, is held at NASA Kennedy Space Center's Press Site in Florida. Participating in the briefing are, from left, Tara Ruttley, Johnson Space Center Program Science Office; and David Craft, weather officer, 45th Weather Squadron. Orbital ATK's Cygnus pressurized cargo module is set to launch atop the ULA Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station on April 18. Cygnus will deliver 7,600 pounds of supplies, equipment and scientific research materials to the space station. Liftoff is scheduled for 11:11 a.m. EDT.

  15. Pegasus XL CYGNSS Prelaunch News Conference

    NASA Image and Video Library

    2016-12-10

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: John Scherrer, CYGNSS project manager for the Southwest Research Institute in San Antonio, Texas; and Mike Rehbein, launch weather officer for the 45th Weather Squadron at Cape Canaveral Air Force Station, Florida. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.

  16. TDRS-L Media Day

    NASA Image and Video Library

    2014-01-03

    TITUSVILLE, Fla. – Members of the news media are given an up-close look at the Tracking and Data Relay Satellite, or TDRS-L, spacecraft undergoing preflight processing inside the Astrotech payload processing facility in Titusville. TDRS-L is being prepared for encapsulation inside its payload fairing prior to being transported to Launch Complex 41 at Cape Canaveral Air Force Station. Journalists visited Astrotech as part of TDRS-L Media Day to conduct interviews and photograph the satellite that will be a part of the second of three next-generation spacecraft designed to ensure vital operational continuity for the NASA Space Network. It is scheduled to launch from Cape Canaveral's Space Launch Complex 41 atop an Atlas V rocket in January 2014. The current Tracking and Data Relay Satellite system consists of eight in-orbit satellites distributed to provide near continuous information relay contact with orbiting spacecraft ranging from the International Space Station and Hubble Space Telescope to the array of scientific observatories. For more information, visit: http://www.nasa.gov/mission_pages/tdrs/home/index.html

  17. TDRS-L Media Day

    NASA Image and Video Library

    2014-01-03

    TITUSVILLE, Fla. – Members of the news media are given an opportunity for an up-close look at the Tracking and Data Relay Satellite, or TDRS-L, spacecraft undergoing preflight processing inside the Astrotech payload processing facility in Titusville. TDRS-L is being prepared for encapsulation inside its payload fairing prior to being transported to Launch Complex 41 at Cape Canaveral Air Force Station. Journalists visited Astrotech as part of TDRS-L Media Day to conduct interviews and photograph the satellite that will be a part of the second of three next-generation spacecraft designed to ensure vital operational continuity for the NASA Space Network. It is scheduled to launch from Cape Canaveral's Space Launch Complex 41 atop an Atlas V rocket in January 2014. The current Tracking and Data Relay Satellite system consists of eight in-orbit satellites distributed to provide near continuous information relay contact with orbiting spacecraft ranging from the International Space Station and Hubble Space Telescope to the array of scientific observatories. For more information, visit: http://www.nasa.gov/mission_pages/tdrs/home/index.html

  18. SpaceX CRS-12 Prelaunch News Conference

    NASA Image and Video Library

    2017-08-13

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-12 commercial resupply services mission to the International Space Station. Josh Finch of NASA Communications; Dan Hartman, NASA deputy manager of the International Space Station Program, Hans Koenigsmann, vice president of Build and Flight Reliability for SpaceX, and Pete Hasbrook, associate program scientist for the International Space Station Program. A Dragon spacecraft is scheduled to be launched from Kennedy’s Launch Complex 39A on Aug. 14 atop a SpaceX Falcon 9 rocket on the company's 12th Commercial Resupply Services mission to the space station.

  19. Skylab 2 prime crew suit up during prelaunch training activity

    NASA Image and Video Library

    1973-05-08

    S73-25399 (8 May 1973) --- Astronaut Paul J. Weitz, prime crew pilot of the first manned Skylab mission, is suited up in Bldg. 5 at Johnson Space Center (JSC) during prelaunch training activity. He is assisted by astronaut Charles Conrad, Jr., prime crew commander. The man in the left background is wearing a face mask to insure that Conrad, Joseph Kerwin and Weitz are not exposed to disease prior to launch. Photo credit: NASA

  20. A Pre-launch Analysis of NASA's SMAP Mission Data

    NASA Astrophysics Data System (ADS)

    Escobar, V. M.; Brown, M. E.

    2012-12-01

    an email-based review of expert end-users and earth science researchers to eliciting how pre-launch activities and research is being conducted in thematic group's organizations. Our focus through the SMAP Applications Program will be to (1) improve the missions understanding of the SMAP user community requirements, (2) document and communicate the perceived challenges and advantages to the mission scientists, and (3) facilitate the movement of science into policy and decision making arenas. We will analyze the data of this review to understand the perceived benefits to pre-launch efforts, user engagement and define areas were the connection between science development and user engagement can continue to improve and further benefit future mission pre launch efforts. The research will facilitate collaborative opportunities between agencies, broadening the fields of science where soil moisture observation data can be applied.

  1. Orbital ATK CRS-7 Prelaunch News Conference

    NASA Image and Video Library

    2017-04-17

    A prelaunch status briefing for Orbital ATK's seventh commercial resupply mission, CRS-7, to the International Space Station, is held at NASA Kennedy Space Center's Press Site in Florida. Participating in the briefing are, from left, George Diller, NASA Kennedy Public Affairs; Joel Montalbano, deputy manager, NASA International Space Station Program; Vern Thorp, program manager, commercial missions, United Launch Alliance; and Frank Culbertson, Space Systems Group president, Orbital ATK. Orbital ATK's Cygnus pressurized cargo module is set to launch atop the ULA Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station on April 18. Cygnus will deliver 7,600 pounds of supplies, equipment and scientific research materials to the space station. Liftoff is scheduled for 11:11 a.m. EDT.

  2. ASTRONAUT JAMES A. LOVELL, JR. - PRELAUNCH - GT-12 - LEAVE TRAILER - CAPE

    NASA Image and Video Library

    1966-11-11

    S66-59974 (11 Nov. 1966) --- Prime crew for the Gemini-12 spaceflight, astronauts James A. Lovell Jr., (leading), command pilot, and Edwin E. Aldrin Jr., pilot, leave the suiting trailer at Launch Complex 16 during prelaunch countdown. Moments later they entered a transport van which carried them to Pad 19 and their waiting spacecraft. The liftoff was at 3:46 p.m. (EST), Nov. 11, 1966. Photo credit: NASA

  3. TDRS-L Media Day

    NASA Image and Video Library

    2014-01-03

    TITUSVILLE, Fla. – Inside the Astrotech payload processing facility in Titusville, members of the news media are given an opportunity for an up-close look at the payload fairing that will encapsulate the Tracking and Data Relay Satellite, or TDRS-L, spacecraft. Journalists visited Astrotech as part of TDRS-L Media Day to conduct interviews and photograph the satellite that will be a part of the second of three next-generation spacecraft designed to ensure vital operational continuity for the NASA Space Network. It is scheduled to launch from Cape Canaveral's Space Launch Complex 41 atop an Atlas V rocket in January 2014. The current Tracking and Data Relay Satellite system consists of eight in-orbit satellites distributed to provide near continuous information relay contact with orbiting spacecraft ranging from the International Space Station and Hubble Space Telescope to the array of scientific observatories. For more information, visit: http://www.nasa.gov/mission_pages/tdrs/home/index.html

  4. SpaceX CRS-14 Prelaunch News Conference

    NASA Image and Video Library

    2018-04-01

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-14 commercial resupply services mission to the International Space Station. Stephanie Schierholz of NASA Communications; Joel Montalbano, NASA Deputy Manager of the International Space Station Program; Jessica Jensen, Director of Dragon Mission Management for SpaceX; Pete Hasbrook, Associate Program Scientist for the ISS Program Science Office; and Mike McAleenan the Launch Weather Officer from the U.S. Air Force 45th Weather Squadron. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida atop a SpaceX Falcon 9 rocket on the company's 14th Commercial Resupply Services mission to the space station.

  5. SpaceX CRS-13 Prelaunch News Conference

    NASA Image and Video Library

    2017-12-11

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-13 commercial resupply services mission to the International Space Station. Cheryl Warner of NASA Communications; Kirk Shireman, NASA Manager of the International Space Station Program; Jessica Jensen, Director of Dragon Mission Management for SpaceX; Kirt Costello, Deputy Chief Scientist for the ISS Program Science Office; and David Myers the Launch Weather Officer from the U.S. Air Force 45th Weather Squadron. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida atop a SpaceX Falcon 9 rocket on the company's 13th Commercial Resupply Services mission to the space station.

  6. Pegasus XL CYGNSS Prelaunch News Conference

    NASA Image and Video Library

    2016-12-10

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the agency’s Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. From left are: George Diller of NASA Communications; Christine Bonniksen, CYGNSS program executive in the Earth Science Division of the Science Mission Directorate at NASA Headquarters in Washington, D.C.; Tim Dunn, NASA launch director at Kennedy; Bryan Baldwin, Pegasus launch vehicle program manager for Orbital ATK, Dulles, Virginia; and John Scherrer, CYGNSS project manager for the Southwest Research Institute in San Antonio, Texas. The eight CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data will help scientists probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.

  7. Orbital ATK CRS-7 Prelaunch News Conference

    NASA Image and Video Library

    2017-04-17

    A prelaunch status briefing for Orbital ATK's seventh commercial resupply mission, CRS-7, to the International Space Station, is held at NASA Kennedy Space Center's Press Site in Florida. Participating in the briefing are, from left, George Diller, NASA Kennedy Public Affairs; Joel Montalbano, deputy manager, NASA International Space Station Program; Vern Thorp, program manager, commercial missions, United Launch Alliance; Frank Culbertson, Space Systems Group president, Orbital ATK; Tara Ruttley, Johnson Space Center Program Science Office; and David Craft, weather officer, 45th Weather Squadron. Orbital ATK's Cygnus pressurized cargo module is set to launch atop the ULA Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station on April 18. Cygnus will deliver 7,600 pounds of supplies, equipment and scientific research materials to the space station. Liftoff is scheduled for 11:11 a.m. EDT.

  8. Cygnus Orbtial ATK OA-6 Prelaunch Press Conference

    NASA Image and Video Library

    2016-03-21

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media at a prelaunch news conference for Orbital ATK CRS-6 commercial resupply services mission to the International Space Station. From left are: George Diller of NASA Communications; Kenneth Todd, NASA ISS Operations Integration manager; Frank Culbertson, president of Orbital ATK's Space System Group; Vern Thorp, United Space Alliance's program manager for NASA missions; Pete Hasbrook, NASA associate program scientist for the ISS Program at the Johnson Space Center in Houston; Dr. Michael Roberts deputy chief scientist for the Center for the Advancement for Science in Space, or CASIS; and Capt. Laura Godoy, launch weather officer of the U.S. Air Force 45th Weather Squadron.

  9. STS-87 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1997-01-01

    On this first day of the STS-87 mission, the flight crew, Cmdr. Kevin R. Kregel, Pilot Steven W. Lindsey, Mission Specialists Winston E. Scott, Kalpana Chawla, and Takao Doi, and Payload Specialist Leonid K. Kadenyuk can be seen preforming pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is seen being readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  10. Prelaunch Science briefing for Orbital Resupply Mission to the Space Station

    NASA Image and Video Library

    2018-05-19

    Orbital ATK is scheduled to launch its ninth contracted cargo resupply mission to the International Space Station from NASA's Wallops Flight Facility in Virginia, no earlier than Monday, May 21, at 4:39 a.m. EDT. During a prelaunch briefing on May 20, mission managers provided an overview and status of launch operations for the mission. Populations all along the U.S. east coast will have the chance to catch a glimpse of the Antares rocket as it powers the Cygnus cargo spacecraft to orbit.

  11. SpaceX CRS-14 Prelaunch News Conference

    NASA Image and Video Library

    2018-04-01

    In the Kennedy Space Center’s Press Site auditorium, NASA and industry leaders speak to members of the media during a prelaunch news conference for the SpaceX CRS-14 commercial resupply services mission to the International Space Station. From left, are Stephanie Schierholz, of NASA Communications; Jessica Jensen, director, Dragon Mission Management, SpaceX; Pete Hasbrook, associate program scientist, ISS Program Science Office at NASA's Johnson Space Center in Houston; and Mike McAleenan, weather officer, 45th Weather Squadron. Joining on the phone is Joel Montalbano, deputy manager, ISS Program at Johnson. A Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station at 4:30 p.m. EST, on April 2, 2018. The SpaceX Falcon 9 rocket will lift off on the company's 14th Commercial Resupply Services mission to the space station.

  12. Orbital ATK CRS-7 Prelaunch News Conference

    NASA Image and Video Library

    2017-04-17

    Members of the media listen to a prelaunch status briefing for Orbital ATK's seventh commercial resupply mission, CRS-7, to the International Space Station, at NASA Kennedy Space Center's Press Site in Florida. Moderating the briefing is George Diller, NASA Kennedy Public Affairs. Participants in the briefing are Joel Montalbano, deputy manager, NASA International Space Station Program; Vern Thorp, program manager, commercial missions, United Launch Alliance; Frank Culbertson, Space Systems Group president, Orbital ATK; Tara Ruttley, Johnson Space Center Program Science Office; and David Craft, weather officer, 45th Weather Squadron. Orbital ATK's Cygnus pressurized cargo module is set to launch atop the ULA Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station on April 18. Cygnus will deliver 7,600 pounds of supplies, equipment and scientific research materials to the space station. Liftoff is scheduled for 11:11 a.m. EDT.

  13. Pre-Launch Characterization of the Advanced Technology Microwave Sounder (ATMS) on the Joint Polar Satellite System-1 Satellite (JPSS-1)

    NASA Astrophysics Data System (ADS)

    Kim, Edward; Leslie, Vince; Lyu, Joseph; Smith, Craig; McCormick, Lisa; Anderson, Kent

    2016-04-01

    The Advanced Technology Microwave Sounder (ATMS) is the newest generation of microwave sounder in the international fleet of polar-orbiting weather satellites, replacing the Advanced Microwave Sounding Unit (AMSU) which first entered service in 1998. The first ATMS was launched aboard the Suomi NPP (S-NPP) satellite in late 2011. The second ATMS is manifested on the Joint Polar Satellite System-1 Satellite (JPSS-1). ATMS provides 22 channels of temperature and humidity sounding observations over a frequency range from 23 to 183 GHz. These microwave soundings provide the highest impact data ingested by operational Numerical Weather Prediction (NWP) models, and are the most critical of the polar-orbiting satellite observations, particularly because microwave sensing can penetrate clouds. This paper will present performance characterizations from pre-launch calibration measurements of the JPSS-1 ATMS just completed in December, 2015. The measurements were conducted in a thermal vacuum chamber with blackbody targets simulating cold space, ambient, and a variable Earth scene. They represent the best opportunity for calibration characterization of the instrument since the environment can be carefully controlled. We will present characterizations of the sensitivity (NEDT), accuracy, nonlinearity, noise spectral characteristics, gain stability, repeatability, and inter-channel correlation. An estimate of expected "striping" will be presented, and a discussion of reflector emissivity effects will also be provided. Comparisons will be made with the S-NPP flight unit. Finally, we will describe planned on-orbit characterizations - such as pitch and roll maneuvers - that will further improve both the measurement quality and the understanding of various error contributions.

  14. Pre-Launch Algorithms and Risk Reduction in Support of the Geostationary Lightning Mapper for GOES-R and Beyond

    NASA Technical Reports Server (NTRS)

    Goodman, Steven; Blakeslee, Richard; Koshak, William

    2008-01-01

    The Geostationary Lightning Mapper (GLM) is a single channel, near-IR optical transient event detector, used to detect, locate and measure total lightning activity over the full-disk as part of a 3-axis stabilized, geostationary weather satellite system. The next generation NOAA Geostationary Operational Environmental Satellite (GOES-R) series with a planned launch in 2014 will carry a GLM that will provide continuous day and night observations of lightning from the west coast of Africa (GOES-E) to New Zealand (GOES-W) when the constellation is fully operational. The mission objectives for the GLM are to 1) provide continuous,full-disk lightning measurements for storm warning and Nowcasting, 2) provide early warning of tornado activity, and 3) accumulate a long-term database to track decadal changes of lightning. The GLM owes its heritage to the NASA Lightning Imaging Sensor (1997-Present) and the Optical Transient Detector (1995-2000), which were developed for the Earth Observing System and have produced a combined 13 year data record of global lightning activity. Instrument formulation studies were completed in March 2007 and the implementation phase to develop a prototype model and up to four flight units is expected to begin in latter part of the year. In parallel with the instrument development, a GOES-R Risk Reduction Team and Algorithm Working Group Lightning Applications Team have begun to develop the Level 2B algorithms and applications. Proxy total lightning data from the NASA Lightning Imaging Sensor on the Tropical Rainfall Measuring Mission (TRMM) satellite and regional test beds (e.g., Lightning Mapping Arrays in North Alabama and the Washington DC Metropolitan area) are being used to develop the pre-launch algorithms and applications, and also improve our knowledge of thunderstorm initiation and evolution. Real time lightning mapping data provided to selected National Weather Service forecast offices in Southern and Eastern Region are also improving

  15. STS-89 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first day of the STS-89 mission, the flight crew, Cmdr. Terrence W. Wilcutt, Pilot Frank Edwards, and Mission Specialists Michael P. Anderson, James F. Reilly, Bonnie J. Dunbar, Salizhan Shakirovich Sharipov, David A. Wolf and Andrew S.W. Thomas, can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  16. STS-86 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1997-01-01

    On this first day of the STS-86 mission, the flight crew, Cmdr. James D. Wetherbee, Jr., Pilot Michael J. Bloomfield, Mission Specialists Scott E. Parazynski, Jean-Loup Chretien, Vladimir G. Titov, Wendy B. Lawrence and David A. Wolf can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also included are various panoramic views of the shuttle on the pad. The crew can be seen being readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  17. STS-90 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk, can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters. The shuttle's payload bay doors are then opened in anticipation of the 16-day scientific mission. The astronauts then are seen readying the Spacelab module for various experiments.

  18. Prelaunch Status Briefing for Orbital ATK Resupply Mission to the Space Station

    NASA Image and Video Library

    2018-05-20

    Orbital ATK is scheduled to launch its ninth contracted cargo resupply mission to the International Space Station from NASA's Wallops Flight Facility in Virginia, no earlier than Monday, May 21, at 4:39 a.m. EDT. During a prelaunch briefing on May 20, mission managers provided an overview and status of launch operations for the mission. Populations all along the U.S. east coast will have the chance to catch a glimpse of the Antares rocket as it powers the Cygnus cargo spacecraft to orbit.

  19. Coexistence of Bilirubin ≥10 mg/dL and Prothrombin Time-International Normalized Ratio ≥1.6 on Day 7: A Strong Predictor of Early Graft Loss After Living Donor Liver Transplantation.

    PubMed

    Okamura, Yusuke; Yagi, Shintaro; Sato, Toshiya; Hata, Koichiro; Ogawa, Eri; Yoshizawa, Atsushi; Kamo, Naoko; Yamashiki, Noriyo; Okajima, Hideaki; Kaido, Toshimi; Uemoto, Shinji

    2018-03-01

    Early allograft dysfunction (EAD) defined by serum total bilirubin (TB) of 10 mg/dL or greater or prothrombin time-international normalized ratio (PT-INR) of 1.6 or greater on postoperative day 7 (POD 7) or aminotransferase greater than 2000 IU/L within the first week, is associated with early graft loss after deceased-donor liver transplantation. We aimed to determine the prognostic impact of the EAD definition in living-donor liver transplantation (LDLT). We analyzed the validity of the EAD definition and its impact on early graft survival in 260 adult recipients who underwent primary LDLT. Eighty-four (32.3%) patients met the EAD criteria; 59 (22.7%) and 46 (17.7%) patients had TB of 10 mg/dL or greater and PT-INR of 1.6 or greater on POD 7, respectively, and 22 (8.5%) patients satisfied both criteria. Graft survival differed significantly when stratified according to TB of 10 mg/dL or greater and PT-INR of 1.6 or greater (P < 0.0001). PT-INR of 1.6 or greater resulted in higher graft mortality (risk ratio [RR], 3.87; P < 0.0001 at 90 days; RR, 2.97; P < 0.0001 at 180 days), as did TB of 10 mg/dL or greater (RR, 1.89; P = 0.027 at 90 days; RR, 1.91; P = 0.006 at 180 days). Coexistence of TB of 10 mg/dL or greater and PT-INR of 1.6 or greater was strongly associated with early graft loss (59.1%, RR, 6.97 at 90 days; 68.2%; RR, 5.75 at 180 days). In Cox regression analysis, PT-INR of 1.6 or greater and TB of 10 mg/dL or greater on POD 7 were significant risk factors for early graft loss (hazard ratio, 4.10; 95% confidence interval, 2.35-7.18; P < 0.0001, and hazard ratio, 2.43; 95% confidence interval, 1.39-4.24; P = 0.0018, respectively). TB of 10 mg/dL or greater and/or PT-INR of 1.6 or greater on POD 7 predicted early graft loss after LDLT, and their coexistence worsened patient outcomes.

  20. Best Practice Guidelines for Pre-Launch Characterization and Calibration of Instruments for Passive Optical Remote Sensing.

    PubMed

    Datla, R U; Rice, J P; Lykke, K R; Johnson, B C; Butler, J J; Xiong, X

    2011-01-01

    The pre-launch characterization and calibration of remote sensing instruments should be planned and carried out in conjunction with their design and development to meet the mission requirements. The onboard calibrators such as blackbodies and the sensors such as spectral radiometers should be characterized and calibrated using SI traceable standards. In the case of earth remote sensing, this allows inter-comparison and intercalibration of different sensors in space to create global time series of climate records of high accuracy where some inevitable data gaps can be easily bridged. The recommended best practice guidelines for this pre-launch effort is presented based on experience gained at National Institute of Standards and Technology (NIST), National Aeronautics and Space Administration (NASA) and National Oceanic and Atmospheric Administration (NOAA) programs over the past two decades. The currently available radiometric standards and calibration facilities at NIST serving the remote sensing community are described. Examples of best practice calibrations and intercomparisons to build SI (international System of Units) traceable uncertainty budget in the instrumentation used for preflight satellite sensor calibration and validation are presented.

  1. Pre-Launch Algorithms and Risk Reduction in Support of the Geostationary Lightning Mapper for GOES-R and Beyond

    NASA Technical Reports Server (NTRS)

    Goodman, Steven; Blakeslee, Richard; Koshak, William; Petersen, Walt; Buechler, Dennis; Krehbiel, Paul; Gatlin, Patrick; Zubrick, Steven

    2008-01-01

    The Geostationary Lightning Mapper (GLM) is a single channel, near-IR optical transient event detector, used to detect, locate and measure total lightning activity over the full-disk as part of a 3-axis stabilized, geostationary weather satellite system. The next generation NOAA Geostationary Operational Environmental Satellite (GOES-R) series with a planned launch in 2014 will carry a GLM that will provide continuous day and night observations of lightning from the west coast of Africa (GOES-E) to New Zealand (GOES-W) when the constellation is fully operational.The mission objectives for the GLM are to 1) provide continuous,full-disk lightning measurements for storm warning and Nowcasting, 2) provide early warning of tornadic activity, and 3) accumulate a long-term database to track decadal changes of lightning. The GLM owes its heritage to the NASA Lightning Imaging Sensor (1997-Present) and the Optical Transient Detector (1995-2000), which were developed for the Earth Observing System and have produced a combined 13 year data record of global lightning activity. Instrument formulation studies were completed in March 2007 and the implementation phase to develop a prototype model and up to four flight units is expected to begin in latter part of the year. In parallel with the instrument development, a GOES-R Risk Reduction Team and Algorithm Working Group Lightning Applications Team have begun to develop the Level 2B algorithms and applications. Proxy total lightning data from the NASA Lightning Imaging Sensor on the Tropical Rainfall Measuring Mission (TRMM) sate]lite and regional test beds (e.g., Lightning Mapping Arrays in North Alabama and the Washington DC Metropolitan area) are being used to develop the pre-launch algorithms and applications, and also improve our knowledge of thunderstorm initiation and evolution. Real time lightning mapping data provided to selected National Weather Service forecast offices in Southern and Eastern Region are also improving

  2. APOLLO XII - LAUNCH DAY ACTIVITIES - LAUNCH COMPLEX 39A - KSC

    NASA Image and Video Library

    1969-11-14

    S69-58880 (14 Nov. 1969) --- Astronaut Alan L. Bean, Apollo 12 lunar module pilot, suits up in the Kennedy Space Center's (KSC) Manned Spacecraft Operations Building during the Apollo 12 prelaunch countdown. Minutes later astronauts Bean; Charles Conrad Jr., commander; and Richard F. Gordon Jr., command module pilot, rode a special transport van over to Pad A, Launch Complex 39, where their spacecraft awaited. The Apollo 12 liftoff occurred at 11:22 a.m. (EST), Nov. 14, 1969. Apollo 12 is the United States' second lunar landing mission.

  3. Pre-Launch Risk Reduction Activities Conducted at KSC for the International Space Station

    NASA Technical Reports Server (NTRS)

    Kirkpatrick, Paul

    2011-01-01

    In the development of any large scale space-based multi-piece assembly effort, planning must include provisions for testing and verification; not only of the individual pieces but also of the pieces together. Without such testing on the ground, the risk to cost, schedule and technical performance increases substantially. This paper will review the efforts undertaken by the International Space Station (ISS), including the International Partners, during the pre-launch phase, primarily at KSC, to reduce the risks associated with the on-orbit assembly and operation of the ISS.

  4. 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

  5. KSC-20170217-VP_DNG03-0001_SpaceX_CRS-10_Prelaunch_News_Conference-3146081

    NASA Image and Video Library

    2017-02-17

    In the Kennedy Space Center’s Press Site auditorium, agency and industry leaders speak to members of the media at a prelaunch news conference for the SpaceX CRS-10 commercial resupply services mission to the International Space Station. From left are: George Diller of NASA Communications; Dan Hartman, deputy manager for the International Space Station Program at NASA's Johnson Space Center in Texas; Jessica Jensen, director of Dragon mission management for SpaceX; and Tara Ruttley, associate scientist for the International Space Station Program at Johnson.

  6. [Oral toxicity at 60-days of sacha inchi oil (Plukenetia volubilis L.) and linseed (Linum usitatissimum L.), and determination of lethal dose 50 in rodents].

    PubMed

    Gorriti, Arilmi; Arroyo, Jorge; Quispe, Fredy; Cisneros, Braulio; Condorhuamán, Martín; Almora, Yuan; Chumpitaz, Víctor

    2010-09-01

    To evaluate the oral toxicity at 60 days and to determine the lethal dose 50 (LD 50) of raw sacha inchi (Plukenetia volubilis L.) and linseed (Linum ussitatisimum) oils in Holtzman rats and mice of the strain Balb C57 respectively. For the evaluation of the oral toxicity of repeated doses for 60 days, 24 male Holtzman rats were used, divided in three groups of 8 each, the groups were: physiologic saline solution 4 mL/kg (FSS), sacha inchi oil 0.5 mL/kg (SI05) and linseed oil 0.5 mL/kg (L05), during the experiment the body weight was controlled weekly, and signs of toxicity in the research groups, as well as total cholesterol, HDL, glucose, triglycerides and alkaline phosphatase at days 30 and 60 after initiating the experiment. For the evaluation of the LD50 male mice of the Balb C57 strain were used in groups of 10 animals, and they were administered increasing oral doses of raw oils until reaching 1 mL/kg (37 g/kg). The serum parameters in the rats indicated there is no toxicity at 60 days and that the administration of the oils lowered the levels of cholesterol, triglycerides and increased the HDL in comparison with the control group. The LD50 shows that the raw sacha inchi and linseed oils have doses above 37 g/kg of body weight. Sacha inchi and linseed oils are harmless at 60 days and present a LD50 above the 37 g/kg of animal.

  7. A Nimbus G pre-launch field experiment in the Gulf of Mexico, October 1977

    NASA Technical Reports Server (NTRS)

    Vanderpiepen, H.

    1977-01-01

    A large scale field experiment, which was arranged in support of the Nimbus G - Coastal Zone Color Scanner (CZCS) project was studied. The experiment was to provide three air and two shipborne platforms simultaneously to members of the Nimbus G Experiment Team (NET) and to other scientists in order to collect data from common test sites. Besides establishing fundamental relations between the light in the sea and the biochemical properties of water, the data will be used mainly for the development of algorithms during the prelaunch phase of Nimbus G.

  8. Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

    PubMed

    de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

    2013-09-16

    To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. Same-day PEG-CS is feasible, effective

  9. 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.

  10. Pre-Launch Performance Assessment of the VIIRS Land Surface Temperature Environmental Data Record

    NASA Astrophysics Data System (ADS)

    Hauss, B.; Ip, J.; Agravante, H.

    2009-12-01

    The Visible/Infrared Imager Radiometer Suite (VIIRS) Land Surface Temperature (LST) Environmental Data Record (EDR) provides the surface temperature of land surface including coastal and inland-water pixels at VIIRS moderate resolution (750m) during both day and night. To predict the LST under optimal conditions, the retrieval algorithm utilizes a dual split-window approach with both Short-wave Infrared (SWIR) channels at 3.70 µm (M12) and 4.05 µm (M13), and Long-wave Infrared (LWIR) channels at 10.76 µm (M15) and 12.01 µm (M16) to correct for atmospheric water vapor. Under less optimal conditions, the algorithm uses a fallback split-window approach with M15 and M16 channels. By comparison, the MODIS generalized split-window algorithm only uses the LWIR bands in the retrieval of surface temperature because of the concern for both solar contamination and large emissivity variations in the SWIR bands. In this paper, we assess whether these concerns are real and whether there is an impact on the precision and accuracy of the LST retrieval. The algorithm relies on the VIIRS Cloud Mask IP for identifying cloudy and ocean pixels, the VIIRS Surface Type EDR for identifying the IGBP land cover type for the pixels, and the VIIRS Aerosol Optical Thickness (AOT) IP for excluding pixels with AOT greater than 1.0. In this paper, we will report the pre-launch performance assessment of the LST EDR based on global synthetic data and proxy data from Terra MODIS. Results of both the split-window and dual split-window algorithms will be assessed by comparison either to synthetic "truth" or results of the MODIS retrieval. We will also show that the results of the assessment with proxy data are consistent with those obtained using the global synthetic data.

  11. White Room - MA 9 Prelaunch suit test - Cooper

    NASA Image and Video Library

    1963-02-01

    S63-03966 (1963) --- Astronaut L. Gordon Cooper Jr., prime pilot for the Mercury-Atlas 9 (MA-9) mission, carrying the portable air conditioner to his spacesuit, leaves Hanger S after completing the day's simulated flight tests. Photo credit: NASA

  12. Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy

    PubMed Central

    de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

    2013-01-01

    AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same-day

  13. 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

  14. L-Arginine supplementation 0.5% of diet during the last 90 days of gestation and 14 days postpartum reduced uterine fluid accumulation in the broodmare.

    PubMed

    Mesa, A M; Warren, L K; Sheehan, J M; Kelley, D E; Mortensen, C J

    2015-08-01

    L-Arginine is an essential amino acid in many species that has been shown to influence reproduction. However, in horses a dose of 1% L-arginine of total dietary intake impaired absorption of other amino acids, whereas a dose of 0.5% did not. The objectives of this experiment were to evaluate postpartum parameters on mares supplemented with 0.5% L-arginine through the last 90d of gestation and 14d postpartum. Sixteen light-horse mares were randomly divided in two groups: 8 mares supplemented with 0.5% L-arginine and 8 mares fed an isonitrogenous equivalent. Gestation length, days to uterine clearance and days to first ovulation were compared. Uterine body depth, diameter of uterine horns, and length of largest pocket of uterine fluid were recorded daily via transrectal ultrasound. Measurements of foal weight, height, and cannon bone circumference were recorded for 9 weeks. Arginine treatment had no effect on gestation length (P=0.58). Supplemented mares cleared fluid quicker postpartum (6.8±0.53d; P=0.026) compared to control (9.0±0.38d). Mares supplemented with L-arginine had smaller diameter of fluid present in the postpartum uterus (P≤0.05). Days to first postpartum ovulation were not affected by treatment nor any influence on uterine involution. Finally, treatment had no effect on any foal's measured parameters. L-Arginine supplementation fed at 0.5% of daily intake during the last 90d of gestation and early postpartum in mares decreased uterine fluid accumulation, yet did not appear to have any effect on any other parameters measured. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. STS-3 FLIGHT DAY 1 ACTIVITIES - MISSION OPERATIONS CONTROL ROOM (MOCR) - JSC

    NASA Image and Video Library

    1982-03-22

    MOCR during Flight Day 1 of the STS-3 Mission. View: Thomas L. Moser, of the Structures and Mechanics Division, briefing Flight Director Eugene Kranz, Flight Operations, and Dr. Kraft, JSC Director. JSC, HOUSTON, TX

  16. Application of Space Environmental Observations to Spacecraft Pre-Launch Engineering and Spacecraft Operations

    NASA Technical Reports Server (NTRS)

    Barth, Janet L.; Xapsos, Michael

    2008-01-01

    This presentation focuses on the effects of the space environment on spacecraft systems and applying this knowledge to spacecraft pre-launch engineering and operations. Particle radiation, neutral gas particles, ultraviolet and x-rays, as well as micrometeoroids and orbital debris in the space environment have various effects on spacecraft systems, including degradation of microelectronic and optical components, physical damage, orbital decay, biasing of instrument readings, and system shutdowns. Space climate and weather must be considered during the mission life cycle (mission concept, mission planning, systems design, and launch and operations) to minimize and manage risk to both the spacecraft and its systems. A space environment model for use in the mission life cycle is presented.

  17. Pre-Launch End-to-End Testing Plans for the SPAce Readiness Coherent Lidar Experiment (SPARCLE)

    NASA Technical Reports Server (NTRS)

    Kavaya, Michael J.

    1999-01-01

    The SPAce Readiness Coherent Lidar Experiment (SPARCLE) mission was proposed as a low cost technology demonstration mission, using a 2-micron, 100-mJ, 6-Hz, 25-cm, coherent lidar system based on demonstrated technology. SPARCLE was selected in late October 1997 to be NASA's New Millennium Program (NMP) second earth-observing (EO-2) mission. To maximize the success probability of SPARCLE, NASA/MSFC desired expert guidance in the areas of coherent laser radar (CLR) theory, CLR wind measurement, fielding of CLR systems, CLR alignment validation, and space lidar experience. This led to the formation of the NASA/MSFC Coherent Lidar Technology Advisory Team (CLTAT) in December 1997. A threefold purpose for the advisory team was identified as: 1) guidance to the SPARCLE mission, 2) advice regarding the roadmap of post-SPARCLE coherent Doppler wind lidar (CDWL) space missions and the desired matching technology development plan 3, and 3) general coherent lidar theory, simulation, hardware, and experiment information exchange. The current membership of the CLTAT is shown. Membership does not result in any NASA or other funding at this time. We envision the business of the CLTAT to be conducted mostly by email, teleconference, and occasional meetings. The three meetings of the CLTAT to date, in Jan. 1998, July 1998, and Jan. 1999, have all been collocated with previously scheduled meetings of the Working Group on Space-Based Lidar Winds. The meetings have been very productive. Topics discussed include the SPARCLE technology validation plan including pre-launch end-to-end testing, the space-based wind mission roadmap beyond SPARCLE and its implications on the resultant technology development, the current values and proposed future advancement in lidar system efficiency, and the difference between using single-mode fiber optical mixing vs. the traditional free space optical mixing. attitude information from lidar and non-lidar sensors, and pointing knowledge algorithms will

  18. STS-96 FD Highlights and Crew Activities Report: Flight Day 01

    NASA Technical Reports Server (NTRS)

    1999-01-01

    On this first day of the STS-96 Discovery mission, the flight crew, Commander Kent V. Rominger, Pilot Rick D. Husband, and Mission Specialists Ellen Ochoa, Tamara E. Jernigan, Daniel T. Barry, Julie Payette, and Valery Ivanovich Tokarev are seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the 'white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters.

  19. STS-111/Endeavour/ISS UF2 Pre-Launch Activities: Launch with Playbacks

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This video of the preflight preparations for and launch of Space Shuttle Endeavour on STS-111 begins with a view of Endeavour on the launch pad. Additional launch pad views leading up to liftoff are interspersed with footage from the Firing Room at Kennedy Space Center, the crew's prelaunch activities, and inspection of the crew members in the White Room before boarding Endeavour. The crew is introduced by a narrator during the preflight banquet and suiting up, and a later clip shows them departing to the launch site. The crew consists of Commander Kenneth Cockrell, Pilot Paul Lockhart, Mission Specialists Philippe Perrin and Franklin Chang-Diaz, and the Expedition 5 crew of the International Space Station (ISS) (Commander Valery Korzun and Flight Engineers Peggy Whitsun and Sergei Treschev). The nozzles on Endeavour's Space Shuttle Main Engine (SSME) are swiveled before liftoff, and the launch is shown past the separation of the solid rocket boosters. After a brief clip from the Mission Control Center at Johnson Space Center, the following launch replays are shown: Beach Tracker, VAB, Pad A, Tower 1, UCS-15, Grandstand, Cocoa Beach DOAMS, Playalinda DOAMS, UCS-23, and OTV-070.

  20. Pre-Launch Noise Characterization of the Landsat-7 Enhanced Thematic Mapper Plus (ETM Plus)

    NASA Technical Reports Server (NTRS)

    Pedelty, J. A.; Markham, B. L.; Barker, J. L.; Seiferth, J. C.

    1999-01-01

    A noise characterization of the Landsat-7 Enhanced Thematic Mapper Plus (ETM+) instrument was performed as part of a near-real time performance assessment and health monitoring program. Perl'ormance data for the integrated Landsat-7 spacecraft and ETM+ were collected before, during, and after the spacecraft thermal vacuum testing program at the Lockheed Martin Missiles and Space (LMMS) facilities in Valley Forge, PA. The Landsat-7 spacecraft and ETM+ instrument were successfully launched on April 15, 1999. The spacecraft and ETM+ are now nearing the end of the on orbit engineering checkout phase, and Landsat-7 is expected to be declared operational on or about July 15, 1999. A preliminary post-launch noise characterization was performed and compared with the pre-launch characterization. In general the overall noise levels in the ETM+ are at or below the specification levels. Coherent noise is seen in most bands, but is only operationally significant when imaging in (he panchromatic band (band 8). This coherent noise has an amplitude as high as approximately 3 DN (peak-to-peak, high gain) at the Nyquist rate of 104 kHz, and causes the noise levels in panchromatic band images at times to exceed the total noise specification by up to approximately 10%. However, this 104 kHz noise is now much weaker than it was prior to the successful repair of the ETM+ power supplies that was completed in May 1998. Weak and stable coherent noise at approximately 5 kHz is seen in all bands in the prime focal plane (bands 1-4 and 8) with the prime (side A) electronics. Very strong coherent noise at approximately 20 kHz is seen in a few detectors of bands 1 and 8, but this noise is almost entirely in the turn-around region between scans when the ETM+ is not imaging the Earth. Strong coherent noise was seen in 2 detectors of band 5 during some of the pre-launch testing; however, this noise seems to be temperature dependent, and has not been seen in the current on orbit environment. Strong

  1. ERMs colocalize transiently with L1 during neocortical axon outgrowth.

    PubMed

    Mintz, C David; Dickson, Tracey C; Gripp, Mark L; Salton, Stephen R J; Benson, Deanna L

    2003-09-29

    L1 is a member of the Ig superfamily of cell adhesion molecules (CAMs) that functions in many aspects of neuronal development including axonal outgrowth and neuronal migration. These functions require coordination between L1 and the actin cytoskeleton. Because CAMs and the cytoskeleton do not bind directly, membrane-cytoskeletal linkers (MCLs) such as ankyrin are thought to be crucial to their interactions, but data from a knockout mouse suggest that ankyrin is not necessary for the earliest events attributed to L1 function. Recent findings in hippocampal cell culture show that members of the ERM family of proteins (ezrin, radixin, and moesin) can also serve as MCLs between L1 and actin in neurons. Here, we demonstrate that ERM proteins are expressed in extending neuronal processes in the intermediate zone of the developing cortex, a region that is densely packed with migrating neurons and growing axons. ERMs and L1 are codistributed extensively over a transient time course that coincides with rapid axon growth and cortical expansion. This codistribution is strong at embryonic day 17 and 19 but diminishes by postnatal day 0, at which time ankyrin-L1 codistribution increases dramatically. These findings suggest that in the developing neocortex, ERMs are the predominant MCL for L1 during migration and axon extension, neither of which requires ankyrin function. Furthermore, these data suggest that there is a developmentally regulated switch in MCL function in the developing brain. Copyright 2003 Wiley-Liss, Inc.

  2. Word Criticality Analysis. MOS: 26L. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-09-01

    ch-1l* 94.01 25,1 9, I CO’IL bpi, ICI.MPLFTh $%&I I CIIINU ITV los1 Sol I EGflHI1 ai-1 19,1 12,1 I CI(PiVtf;T~k 303 2.1 a** 7.2 0,2 4.1 90#1 2902 25a2...26.1 3.1 -- ------------- 1. DAYS 6.1 6;4 d I ."~A,4f 283 1li& 601 3. Imk l 11.3. I EXCHANGE los1 11.1 I1 EXPENDABLE 1#1 I F EDERAL --- -----. got

  3. ASTRONAUT COOPER, GORDON L. - MERCURY-ATLAS (MA)-9 - PRELAUNCH - PREFLIGHT CHECK - CAPE

    NASA Image and Video Library

    1963-05-01

    S63-06129 (1963) --- Astronaut L. Gordon Cooper Jr., prime pilot for the Mercury-Atlas 9 (MA-9) mission, inside his Mercury spacecraft, runs through one of the numerous preflight checks surrounded by dials, switches, indicators and buttons. Photo credit: NASA

  4. 26 CFR 36.3121(l)(2)-1 - Effective period of agreement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... such agreement first became effective. However, if the amendment is signed by the district director or... beginning with the first day of the calendar quarter following the calendar quarter in which the amendment... provided in § 36.3121(l) (1)-1 shall be in effect for the period beginning with the first day of the...

  5. 26 CFR 36.3121(l)(2)-1 - Effective period of agreement.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... such agreement first became effective. However, if the amendment is signed by the district director or... beginning with the first day of the calendar quarter following the calendar quarter in which the amendment... provided in § 36.3121(l) (1)-1 shall be in effect for the period beginning with the first day of the...

  6. 26 CFR 36.3121(l)(2)-1 - Effective period of agreement.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... such agreement first became effective. However, if the amendment is signed by the district director or... beginning with the first day of the calendar quarter following the calendar quarter in which the amendment... provided in § 36.3121(l) (1)-1 shall be in effect for the period beginning with the first day of the...

  7. Using L-M BP Algorithm Forecase the 305 Days Production of First-Breed Dairy

    NASA Astrophysics Data System (ADS)

    Wei, Xiaoli; Qi, Guoqiang; Shen, Weizheng; Jian, Sun

    Aiming at the shortage of conventional BP algorithm, a BP neural net works improved by L-M algorithm is put forward. On the basis of the network, a Prediction model for 305 day's milk productions was set up. Traditional methods finish these data must spend at least 305 days, But this model can forecast first-breed dairy's 305 days milk production ahead of 215 days. The validity of the improved BP neural network predictive model was validated through the experiments.

  8. 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…

  9. Skylab (SL)-3 Crew - KSC

    NASA Image and Video Library

    2006-03-21

    S73-31800 (28 July 1973) --- The three crewmen of the second manned Skylab mission (Skylab 3) participate in prelaunch suiting up activities in the Manned Spacecraft Operations Building at the Kennedy Space Center on the morning of the Skylab 3 launch. They are (from foreground) astronaut Alan L. Bean, commander; scientist-astronaut Owen K. Garriott, science pilot; and astronaut Jack R. Lousma, pilot. Dr. Donald K. Slayton (left foreground), Director of Flight Crew Operations, Johnson Space Center, monitors the prelaunch activities. Skylab 3 lifted off at 7:11 a.m. (EDT), Saturday, July 28, 1973. The three astronauts were scheduled to spend 59 days at the Skylab space station in Earth orbit. Photo credit: NASA

  10. Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 as Outcome Predictors in Traumatic Brain Injury.

    PubMed

    Takala, Riikka S K; Posti, Jussi P; Runtti, Hilkka; Newcombe, Virginia F; Outtrim, Joanne; Katila, Ari J; Frantzén, Janek; Ala-Seppälä, Henna; Kyllönen, Anna; Maanpää, Henna-Riikka; Tallus, Jussi; Hossain, Md Iftakher; Coles, Jonathan P; Hutchinson, Peter; van Gils, Mark; Menon, David K; Tenovuo, Olli

    2016-03-01

    Biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) may help detect brain injury, assess its severity, and improve outcome prediction. This study aimed to evaluate the prognostic value of these biomarkers during the first days after brain injury. Serum UCH-L1 and GFAP were measured in 324 patients with traumatic brain injury (TBI) enrolled in a prospective study. The outcome was assessed using the Glasgow Outcome Scale (GOS) or the extended version, Glasgow Outcome Scale-Extended (GOSE). Patients with full recovery had lower UCH-L1 concentrations on the second day and patients with favorable outcome had lower UCH-L1 concentrations during the first 2 days compared with patients with incomplete recovery and unfavorable outcome. Patients with full recovery and favorable outcome had significantly lower GFAP concentrations in the first 2 days than patients with incomplete recovery or unfavorable outcome. There was a strong negative correlation between outcome and UCH-L1 in the first 3 days and GFAP levels in the first 2 days. On arrival, both UCH-L1 and GFAP distinguished patients with GOS score 1-3 from patients with GOS score 4-5, but not patients with GOSE score 8 from patients with GOSE score 1-7. For UCH-L1 and GFAP to predict unfavorable outcome (GOS score ≤ 3), the area under the receiver operating characteristic curve was 0.727, and 0.723, respectively. Neither UCHL-1 nor GFAP was independently able to predict the outcome when age, worst Glasgow Coma Scale score, pupil reactivity, Injury Severity Score, and Marshall score were added into the multivariate logistic regression model. GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more prominent in Hodgkin lymphoma than DLBCL

    PubMed Central

    Vari, Frank; Arpon, David; Keane, Colm; Hertzberg, Mark S.; Talaulikar, Dipti; Jain, Sanjiv; Cui, Qingyan; Han, Erica; Tobin, Josh; Bird, Robert; Cross, Donna; Hernandez, Annette; Gould, Clare; Birch, Simone

    2018-01-01

    Much focus has been on the interaction of programmed cell death ligand 1 (PD-L1) on malignant B cells with programmed cell death 1 (PD-1) on effector T cells in inhibiting antilymphoma immunity. We sought to establish the contribution of natural killer (NK) cells and inhibitory CD163+ monocytes/macrophages in Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Levels of PD-1 on NK cells were elevated in cHL relative to DLBCL. Notably, CD3−CD56hiCD16-ve NK cells had substantially higher PD-1 expression relative to CD3−CD56dimCD16+ cells and were expanded in blood and tissue, more marked in patients with cHL than patients with DLBCL. There was also a raised population of PD-L1-expressing CD163+ monocytes that was more marked in patients with cHL compared with patients with DLBCL. The phenotype of NK cells and monocytes reverted back to normal once therapy (ABVD [doxorubicin 25 mg/m2, bleomycin 10 000 IU/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2, all given days 1 and 15, repeated every 28 days] or R-CHOP [rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 IV, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (2 mg maximum) IV, prednisone 100 mg/day by mouth days 1-5, pegfilgrastim 6 mg subcutaneously day 4, on a 14-day cycle]) had commenced. Tumor-associated macrophages (TAMs) expressed high levels of PD-L1/PD-L2 within diseased lymph nodes. Consistent with this, CD163/PD-L1/PD-L2 gene expression was also elevated in cHL relative to DLBCL tissues. An in vitro functional model of TAM-like monocytes suppressed activation of PD-1hi NK cells, which was reversed by PD-1 blockade. In line with these findings, depletion of circulating monocytes from the blood of pretherapy patients with cHL and patients with DLBCL enhanced CD3−CD56hiCD16-ve NK-cell activation. We describe a hitherto unrecognized immune evasion strategy mediated via skewing toward an exhausted PD-1-enriched CD3−CD56hiCD16-ve NK-cell phenotype. In addition to direct inhibition of NK

  12. Glycemic control during consecutive days with prolonged walking exercise in individuals with type 1 diabetes mellitus.

    PubMed

    van Dijk, Jan-Willem; Eijsvogels, Thijs M; Nyakayiru, Jean; Schreuder, Tim H A; Hopman, Maria T; Thijssen, Dick H; van Loon, Luc J C

    2016-07-01

    Despite its general benefits for health, exercise complicates the maintenance of stable blood glucose concentrations in individuals with type 1 diabetes. The aim of the current study was to examine changes in food intake, insulin administration, and 24-h glycemic control in response to consecutive days with prolonged walking exercise (∼8h daily) in individuals with type 1 diabetes. Ten individuals with type 1 diabetes participating in the worlds' largest walking event were recruited for this observational study. Simultaneous measurements of 24-h glycemic control (continuous glucose monitoring), insulin administration and food intake were performed during a non-walking day (control) and during three subsequent days with prolonged walking exercise (daily distance 40 or 50km). Despite an increase in daily energy (31±18%; p<0.01) and carbohydrate (82±71g; p<0.01) intake during walking days, subjects lowered their insulin administration by 26±16% relative to the control day (p<0.01). Average 24-h blood glucose concentrations, the prevalence of hyperglycemia (blood glucose >10 mmol/L) and hypoglycemia (blood glucose <3.9mmol/L) did not differ between the control day and walking days (p>0.05 for all variables). The prolonged walking exercise was associated with a modest increase in glycemic variability compared with the control day (p<0.05). Prolonged walking exercise allows for profound reductions in daily insulin administration in persons with type 1 diabetes, despite large increments in energy and carbohydrate intake. When taking such adjustments into account, prolonged moderate-intensity exercise does not necessarily impair 24-h glycemic control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Tracking and data system support for the Mariner Mars 1971 mission. Prelaunch phase through first trajectory correction maneuver, volume 1

    NASA Technical Reports Server (NTRS)

    Laeser, R. P.; Textor, G. P.; Kelly, L. B.; Kelly, M.

    1972-01-01

    The DSN command system provided the capability to enter commands in a computer at the deep space stations for transmission to the spacecraft. The high-rate telemetry system operated at 16,200 bits/sec. This system will permit return to DSS 14 of full-resolution television pictures from the spacecraft tape recorder, plus the other science experiment data, during the two playback periods of each Goldstone pass planned for each corresponding orbit. Other features included 4800 bits/sec modem high-speed data lines from all deep space stations to Space Flight Operations Facility (SFOF) and the Goddard Space Flight Center, as well as 50,000 bits/sec wideband data lines from DSS 14 to the SFOF, thus providing the capability for data flow of two 16,200 bits/sec high-rate telemetry data streams in real time. The TDS performed prelaunch training and testing and provided support for the Mariner Mars 1971/Mission Operations System training and testing. The facilities of the ETR, DSS 71, and stations of the MSFN provided flight support coverage at launch and during the near-earth phase. The DSSs 12, 14, 41, and 51 of the DSN provided the deep space phase support from 30 May 1971 through 4 June 1971.

  14. Day to day variability in fat oxidation and the effect after only 1 day of change in diet composition.

    PubMed

    Støa, Eva Maria; Nyhus, Lill-Katrin; Børresen, Sandra Claveau; Nygaard, Caroline; Hovet, Åse Marie; Bratland-Sanda, Solfrid; Helgerud, Jan; Støren, Øyvind

    2016-04-01

    Indirect calorimetry is a common and noninvasive method to estimate rate of fat oxidation (FatOx) during exercise, and test-retest reliability should be considered when interpreting results. Diet also has an impact on FatOx. The aim of the present study was to investigate day to day variations in FatOx during moderate exercise given the same diet and 2 different isoenergetic diets. Nine healthy, moderately-trained females participated in the study. They performed 1 maximal oxygen uptake test and 4 FatOx tests. Habitual diets were recorded and repeated to assess day to day variability in FatOx. FatOx was also measured after 1 day of fat-rich (26.8% carbohydrates (CHO), 23.2% protein, 47.1% fat) and 1 day of CHO-rich diet (62.6% CHO, 20.1% protein, 12.4% fat). The reliability test revealed no differences in FatOx, respiratory exchange ratio (RER), oxygen uptake, carbon dioxide production, heart rate, blood lactate concentration, or blood glucose between the 2 habitual diet days. FatOx decreased after the CHO-rich diet compared with the habitual day 2 (from 0.42 ± 0.15 to 0.29 ± 0.13 g·min(-1), p < 0.05). No difference was found in FatOx between fat-rich diet and the 2 habitual diet days. FatOx was 31% lower (from 0.42 ± 0.14 to 0.29 ± 0.13 g·min(-1), p < 0.01) after the CHO-rich diet compared with the fat-rich diet. Using RER data to measure FatOx is a reliable method as long as the diet is strictly controlled. However, even a 1-day change in macronutrient composition will likely affect the FatOx results.

  15. 6-gingerol inhibits rosiglitazone-induced adipogenesis in 3T3-L1 adipocytes.

    PubMed

    Tzeng, Thing-Fong; Chang, Chia Ju; Liu, I-Min

    2014-02-01

    We investigated the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) on the inhibition of rosiglitazone (RGZ)-induced adipogenesis in 3T3-L1 cells. The morphological changes were photographed based on staining lipid accumulation by Oil-Red O in RGZ (1 µmol/l)-treated 3T3-L1 cells without or with various concentrations of 6-gingerol on differentiation day 8. Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction. Differentiated cells were lysed to detect mRNA and protein levels of adipocyte-specific transcription factors by real-time reverse transcription-polymerase chain reaction and Western blot analysis, respectively. 6-gingerol (50 µmol/l) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ-induced adipocyte differentiation in 3T3-L1 cells. The triglyceride accumulation induced by RGZ in differentiated 3T3-L1 cells was also reduced by 6-gingerol (50 µmol/l). Treatment of differentiated 3T3-L1 cells with 6-gingerol (50 µmol/l) antagonized RGZ-induced gene expression of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein α. Additionally, the increased levels of mRNA and protein in adipocyte-specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3-L1 cells were decreased upon treatment with 6-gingerol. Our data suggests that 6-gingerol may be beneficial in obesity, by reducing adipogenesis partly through the down-regulating PPARγ activity. Copyright © 2013 John Wiley & Sons, Ltd.

  16. KSC-20170817-CDC01_0001-TDRS_M_Prelaunch_News_Conference-3166840

    NASA Image and Video Library

    2017-08-17

    In the Kennedy Space Center's Press Site auditorium, NASA and industry leaders speak to members of the media at a prelaunch news conference for NASA's Tracking and Data Relay Satellite, TDRS-M. Participants from left are: Kathryn Hambleton of NASA Communications, Tim Dunn, launch director at NASA Kennedy, Badri Younes, deputy associate administrator for Space Communications and Navigation at NASA Headquarters in Washington, Dave Littmann, project manager for TDRS-M at NASAâs Goddard Space Flight Center in Greenbelt, Maryland, James Wilson III, Boeing program manager for NASA/Civil Space Programs, Scott Messer, United Launch Alliance program manager for NASA missions, and Clay Flinn, launch weather officer with the 45th Space Wing at Cape Canaveral Air Force Station. TDRS-M is the latest spacecraft destined for the agency's constellation of communications satellites that allows nearly continuous contact with orbiting spacecraft ranging from the International Space Station and Hubble Space Telescope to the array of scientific observatories. Liftoff atop a United Launch Alliance Atlas V rocket is scheduled to take place from Space Launch Complex 41 at Cape Canaveral Air Force Station at 8:03 a.m. EDT Aug. 18.

  17. Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles

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

    Stępnik, Maciej, E-mail: mstep@imp.lodz.pl; Arkusz, Joanna; Smok-Pieniążek, Anna

    The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but notmore » to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells. -- Highlights: ► Ludox CL silica NPs are cytotoxic to WI-38 fibroblasts but not to 3T3-L1 fibroblasts. ► Ludox CL-X silica NPs are cytotoxic to both cell lines. ► In clonogenic assay both silica NPs induce cytotoxicity, higher for CL-X silica. ► Cell cycle analysis

  18. ASTRONAUT COOPER, GORDON L., JR. - MERCURY-ATLAS (MA)-9 PRELAUNCH -HANGAR "S" - CAPE

    NASA Image and Video Library

    1963-05-01

    S63-06252 (May 1963) --- Mercury workers and news media are greeted by astronaut L. Gordon Cooper Jr., prime pilot for the Mercury-Atlas 9 (MA-9) mission, as he leaves Hanger "S" for Pad 14 to start his 22-orbit MA-9 mission. Photo credit: NASA

  19. 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.

  20. Serine protease activity of Cur l 1 from Curvularia lunata augments Th2 response in mice.

    PubMed

    Tripathi, Prabhanshu; Kukreja, Neetu; Singh, B P; Arora, Naveen

    2009-05-01

    Studies with mite allergens demonstrated that proteolytic activity augments allergic airway inflammation. This knowledge is limited to few enzyme allergens. The objective of this study is to investigate the effect of serine protease Cur l 1 from Curvularia lunata in airway inflammation/hyper-responsiveness. Cur l 1 was purified and inactivated using a serine protease inhibitor. Balb/c mice were sensitized with enzymatically active Cur l 1 or C. lunata extract. Sensitized mice were given booster dose on day 14 with active or inactivated Cur l 1. Intranasal challenge was given on day 28, 29, and 30. Airway hyper-responsiveness was measured by plethysmography. Blood, bronchoalveolar lavage fluid (BALF), spleen, and lungs from mice were analyzed for cellular infiltration, immunoglobulins, and cytokine levels. Mice challenged with enzymatically active Cur l 1 demonstrated significantly higher airway inflammation than inactive Cur l 1 group mice (p < 0.01). There was a significant difference in serum IgE and IgG1 levels among mice immunized with active Cur l 1 and inactive Cur l 1 (p < 0.01). IL-4 and IL-5 were higher in BALF and splenocyte culture supernatant of active Cur l 1 than inactive Cur l 1 mice. Lung histology revealed increased eosinophil infiltration, goblet cell hyperplasia and mucus secretion in active group. Proteolytic activity of Cur l 1 plays an important role in airway inflammation and the inactivated Cur l 1 has potential to be explored for immunotherapy.

  1. 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.

  2. Use of day 1 early morning cortisol to predict the need for glucocorticoid replacement after pituitary surgery.

    PubMed

    Bondugulapati, L N Rao; Campbell, Christopher; Chowdhury, Sharmistha Roy; Goetz, Pablo; Davies, J Stephen; Rees, D Aled; Hayhurst, Caroline

    2016-01-01

    Assessment of adrenal reserve in patients who have undergone pituitary surgery is crucial. However, there is no clear consensus with regards to the type and timing of the test that should be used in the immediate post-operative period. Recently, there has been increased interest in measuring post-operative cortisol levels. We present our data utilising day 1 post-operative early morning cortisol as a tool to assess adrenal reserve in steroid-naive patients. A retrospective analysis of endoscopic pituitary surgery undertaken over a 2-year period. 82 patients underwent 84 surgeries in total. Patients who were already on glucocorticoids pre-operatively and patients with Cushing's disease, pituitary apoplexy and those without follow-up data were excluded, leaving a study group of 44 patients with 45 operations. A 9am day 1 post-operative cortisol value of > 400 nmol/L was taken as an indicator of adequate adrenal reserve. All the patients were reassessed at 6 weeks with a standard short synacthen test (SST) using 250 micrograms of intravenous synacthen. 22 out of 45 patients had a cortisol value of > 400 nmol/L on day 1 post-operatively and were discharged without glucocorticoid supplementation. Of these, only 2 patients subsequently failed the SST when reassessed at 6-8 weeks. The remaining 23 patients had a cortisol value of < 400 nmol/L on day 1 post-operatively and were discharged on hydrocortisone 10 mg twice daily. At 6-8 weeks, nine continued to show suboptimal stimulated cortisol levels whereas the remaining fourteen patients showed adequate adrenal reserve. The 9 am cortisol value had high specificity (81.8%) and positive predictive value (90.9%) for integrity of the HPA axis. Sensitivity was 58.8% and negative predictive value was 39.1%. A day 1 post-operative early morning cortisol is a useful tool to predict adrenal reserve post-pituitary surgery, enabling clinicians to avoid unnecessary blanket glucocorticoid replacement.

  3. Circulating mannan-binding lectin, M-, L-, H-ficolin and collectin-liver-1 levels in patients with acute liver failure.

    PubMed

    Laursen, Tea L; Sandahl, Thomas D; Støy, Sidsel; Schiødt, Frank V; Lee, William M; Vilstrup, Hendrik; Thiel, Steffen; Grønbaek, Henning

    2015-03-01

    The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M-, L-, and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome. Serum samples from 75 patients enrolled by the US ALF Study Group were collected on days 1 and 3. We included 75 healthy blood donors and 20 cirrhosis patients as controls. Analyses were performed using sandwich-type immunoassays (ELISA, TRIFMA). At day 1, the MBL level in ALF patients was 40% lower compared with healthy controls {[median (interquartile range) 0.72 μg/ml(0.91) vs. 1.15 (1.92)(P = 0.02]}, and increased significantly by day 3 [0.83 μg/ml(0.94)(P = 0.01)]. The M-ficolin level was 60% lower [0.54 μg/ml(0.50) vs. 1.48(1.01)(P < 0.0001)]. The CL-L1 level at day 1 was slightly higher compared with healthy controls [3.20 μg/ml(2.37) vs. 2.64(0.72)(P = 0.11)]; this was significant at day 3 [3.35(1.84)(P = 0.006)]. H- and L-ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 [0.96 μg/ml(1.15) vs. 0.60(0.60)(P = 0.02)] and lower levels of L-ficolin by day 3 compared with patients who died or were transplanted [1.61 μg/ml(1.19) vs. 2.17(2.19)(P = 0.02)]. We observed significant dynamics in lectin levels in ALF patients, which may suggest they play a role in ALF pathogenesis. High MBL and low L-ficolin levels are associated with survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Mutant Alleles of Photoperiod-1 in Wheat (Triticum aestivum L.) That Confer a Late Flowering Phenotype in Long Days

    PubMed Central

    Shaw, Lindsay M.; Turner, Adrian S.; Herry, Laurence; Griffiths, Simon; Laurie, David A.

    2013-01-01

    Flowering time in wheat and barley is known to be modified by mutations in the Photoperiod-1 (Ppd-1) gene. Semi-dominant Ppd-1a mutations conferring an early flowering phenotype are well documented in wheat but gene sequencing has also identified candidate loss of function mutations for Ppd-A1 and Ppd-D1. By analogy to the recessive ppd-H1 mutation in barley, loss of function mutations in wheat are predicted to delay flowering under long day conditions. To test this experimentally, introgression lines were developed in the spring wheat variety ‘Paragon’. Plants lacking a Ppd-B1 gene were identified from a gamma irradiated ‘Paragon’ population. These were crossed with the other introgression lines to generate plants with candidate loss of function mutations on one, two or three genomes. Lines lacking Ppd-B1 flowered 10 to 15 days later than controls under long days. Candidate loss of function Ppd-A1 alleles delayed flowering by 1 to 5 days while candidate loss of function Ppd-D1 alleles did not affect flowering time. Loss of Ppd-A1 gave an enhanced effect, and loss of Ppd-D1 became detectable in lines where Ppd-B1 was absent, indicating effects may be buffered by functional Ppd-1 alleles on other genomes. Expression analysis revealed that delayed flowering was associated with reduced expression of the TaFT1 gene and increased expression of TaCO1. A survey of the GEDIFLUX wheat collection grown in the UK and North Western Europe between the 1940s and 1980s and the A.E. Watkins global collection of landraces from the 1920s and 1930s showed that the identified candidate loss of function mutations for Ppd-D1 were common and widespread, while the identified candidate Ppd-A1 loss of function mutation was rare in countries around the Mediterranean and in the Far East but was common in North Western Europe. This may reflect a possible benefit of the latter in northern locations. PMID:24244507

  5. ASTRONAUT COOPER - MERCURY-ATLAS (MA)-9 PRELAUNCH - PREFLIGHT SIMULATED LAUNCH - CAPE

    NASA Image and Video Library

    1963-05-11

    S63-06124 (1963) --- Astronaut L. Gordon Cooper Jr., prime pilot for the Mercury Atlas 9 (MA-9) mission, arrives at the top of the gantry during a preflight simulated mission, three days before he is scheduled to take "Faith 7" on the 22-orbit flight. Photo credit: NASA

  6. 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.

  7. [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.

  8. 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

  9. VO2max and ventilatory threshold of trained cyclists are not affected by 28-day L-arginine supplementation.

    PubMed

    Sunderland, Kyle L; Greer, Felicia; Morales, Jacobo

    2011-03-01

    The ergogenic effect of L-arginine on an endurance-trained population is not well studied. The few studies that have investigated L-arginine on this population have not been conducted in a laboratory setting or measured aerobic variables. The purpose of the current study is to determine if 28 days of L-arginine supplementation in trained male cyclists affects VO2max and ventilatory threshold (VT). Eighteen (18) endurance-trained male cyclists (mean ± SD, age: 36.3 ± 7.9 years; height: 182.4 ± 4.6 cm; and body mass: 79.5 ± 4.7 kg) performed a graded exercise test (GXT; 50 W + 25 W·min) before and after 28 days of supplementation with L-arginine (ARG; 2 × 6 g·d) or placebo (PLA; cornstarch). The GXT was conducted on the subject's own bicycle using the RacerMate CompuTrainer (Seattle, WA, USA). VO2 was continuously recorded using the ParvoMedics TrueOne 2400 metabolic cart (Salt Lake City, UT, USA) and VT was established by plotting the ventilatory equivalent for O2 (VE/VO2) and the ventilatory equivalent for CO2 (VE/VCO2) and identifying the point at which VE/VO2 increases with no substantial changes in VE/VCO2. L-arginine supplementation had no effect from initial VO2max (PL, 58.7 ± 7.1 ml·kg·min; ARG, 63.5 ± 7.3 ml·kg·min) to postsupplement VO2max (PL, 58.9 ± 6.0 ml·kg·min; ARG, 63.2 ± 7.2 ml·kg·min). Also, no effect was seen from initial VT (PL, 75.7 ± 4.6% VO2max; ARG, 76.0 ± 5.3% VO2max) to postsupplement VT (PL, 74.3 ± 8.1% VO2max; ARG, 74.2 ± 6.4% VO2max). These results indicate that L-arginine does not impact VO2max or VT in trained male cyclists.

  10. 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

  11. 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.

  12. Sweat Sodium, Potassium, and Chloride Concentrations Analyzed Same Day as Collection Versus After 7 Days Storage in a Range of Temperatures.

    PubMed

    Baker, Lindsay B; Barnes, Kelly A; Sopeña, Bridget C; Nuccio, Ryan P; Reimel, Adam J; Ungaro, Corey T

    2018-05-22

    The purpose of this study was to determine the effect of storage temperature on sodium ([Na + ]), potassium ([K + ]), and chloride ([Cl - ]) concentrations of sweat samples analyzed 7 days after collection. Using the absorbent patch technique, 845 sweat samples were collected from 39 subjects (32 ± 7 years, 72.9 ± 10.5 kg) during exercise. On the same day as collection (PRESTORAGE), 609 samples were analyzed for [Na + ], [Cl - ], and [K + ] by ion chromatography (IC) and 236 samples were analyzed for [Na + ] using a compact ion-selective electrode (ISE). Samples were stored at one of the four conditions: -20 °C (IC, n = 138; ISE, n = 60), 8 °C (IC, n = 144; ISE, n = 59), 23 °C (IC, n = 159; ISE, n = 59), or alternating between 8 °C and 23 °C (IC, n = 168; ISE, n = 58). After 7 days in storage (POSTSTORAGE), samples were reanalyzed using the same technique as PRESTORAGE. PRESTORAGE sweat electrolyte concentrations were highly related to that of POSTSTORAGE (intraclass correlation coefficient: .945-.989, p < .001). Mean differences (95% confidence intervals) between PRESTORAGE and POSTSTORAGE were statistically, but not practically, significant for most comparisons: IC [Na + ]: -0.5(0.9) to -2.1(0.9) mmol/L; IC [K + ]: -0.1(0.1) to -0.2(0.1) mmol/L; IC [Cl - ]: -0.4(1.4) to -1.3(1.3) mmol/L; ISE [Na + ]: -2.0(1.1) to 1.3(1.1) mmol/L. Based on typical error of measurement results, 95% of the time PRESTORAGE and POSTSTORAGE sweat [Na + ], [K + ], and [Cl - ] by IC analysis fell within ±7-9, ±0.6-0.7, and ±9-13 mmol/L, respectively, while sweat [Na + ] by ISE was ±6 mmol/L. All conditions produced high reliability and acceptable levels of agreement in electrolyte concentrations of sweat samples analyzed on the day of collection versus after 7 days in storage.

  13. 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…

  14. 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…

  15. 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…

  16. C-Reactive Protein on Postoperative Day 1 Is a Reliable Predictor of Pancreas-Specific Complications After Pancreaticoduodenectomy.

    PubMed

    Guilbaud, Théophile; Birnbaum, David Jérémie; Lemoine, Coralie; Chirica, Mircea; Risse, Olivier; Berdah, Stéphane; Girard, Edouard; Moutardier, Vincent

    2018-05-01

    Postoperative pancreatic fistula and pancreas-specific complications have a significant influence on patient management and outcomes after pancreatoduodenectomy. The aim of the study was to assess the value of serum C-reactive protein on the postoperative day 1 as early predictor of pancreatic fistula and pancreas-specific complications. Between 2013 and 2016, 110 patients underwent pancreaticoduodenectomy. Clinical, biological, intraoperative, and pathological characteristics were prospectively recorded. Pancreatic fistula was graded according to the International Study Group on Pancreatic Fistula classification. A composite endpoint was defined as pancreas-specific complications including pancreatic fistula, intra-abdominal abscess, postoperative hemorrhage, and bile leak. The diagnostic accuracy of serum C-reactive protein on postoperative day 1 in predicting adverse postoperative outcomes was assessed by ROC curve analysis. Six patients (5%) died and 87 (79%) experienced postoperative complications (pancreatic-specific complications: n = 58 (53%); pancreatic fistula: n = 48 (44%)). A soft pancreatic gland texture, a main pancreatic duct diameter < 3 mm and serum C-reactive protein ≥ 100 mg/L on postoperative day 1 were independent predictors of pancreas-specific complications (p < 0.01) and pancreatic fistula (p < 0.01). ROC analysis showed that serum C-reactive protein ≥ 100 mg/L on postoperative day 1 was a significant predictor of pancreatic fistula (AUC: 0.70; 95%CI: 0.60-0.79, p < 0.01) and pancreas-specific complications (AUC: 0.72; 95%CI: 0.62-0.82, p < 0.01). ROC analysis showed that serum C-reactive protein ≥ 50 mg/L at discharge was a significant predictor of 90-day hospital readmission (AUC: 0.70; 95%CI: 0.60-0.79, p < 0.01). C-reactive protein levels reliably predict risks of pancreatic fistula, pancreas-specific complications, and hospital readmission, and should be inserted in risk

  17. 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.

  18. L-glutamine supplementations enhance liver glutamine-glutathione axis and heat shock factor-1 expression in endurance-exercise trained rats.

    PubMed

    Petry, Éder Ricardo; Cruzat, Vinicius Fernandes; Heck, Thiago Gomes; Homem de Bittencourt, Paulo Ivo; Tirapegui, Julio

    2015-04-01

    Liver L-glutamine is an important vehicle for the transport of ammonia and intermediary metabolism of amino acids between tissues, particularly under catabolic situations, such as high-intensity exercise. Hence, the aim of this study was to investigate the effects of oral supplementations with L-glutamine in its free or dipeptide forms (with L-alanine) on liver glutamine-glutathione (GSH) axis, and 70 kDa heat shock proteins (HSP70)/heat shock transcription factor 1 (HSF1) expressions. Adult male Wistar rats were 8-week trained (60 min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were daily supplemented with 1 g of L-glutamine/kg body weight per day in either l-alanyl-L-glutamine dipeptide (DIP) form or a solution containing L-glutamine and l-alanine in their free forms (GLN+ALA) or water (controls). Exercise training increased cytosolic and nuclear HSF1 and HSP70 expression, as compared with sedentary animals. However, both DIP and GLN+ALA supplements enhanced HSF1 expression (in both cytosolic and nuclear fractions) in relation to exercised controls. Interestingly, HSF1 rises were not followed by enhanced HSP70 expression. DIP and GLN+ALA supplements increased plasma glutamine concentrations (by 62% and 59%, respectively) and glutamine to glutamate plasma ratio in relation to trained controls. This was in parallel with a decrease in plasma ammonium levels. Supplementations increased liver GSH (by 90%), attenuating the glutathione disulfide (GSSG) to GSH ratio, suggesting a redox state protection. In conclusion, oral administration with DIP and GLN+ALA supplements in endurance-trained rats improve liver glutamine-GSH axis and modulate HSF1 pathway.

  19. Bioproduction of L-Aspartic Acid and Cinnamic Acid by L-Aspartate Ammonia Lyase from Pseudomonas aeruginosa PAO1.

    PubMed

    Patel, Arti T; Akhani, Rekha C; Patel, Manisha J; Dedania, Samir R; Patel, Darshan H

    2017-06-01

    Aspartase (L-aspartate ammonia lyase, EC 4.3.1.1) catalyses the reversible amination and deamination of L-aspartic acid to fumaric acid which can be used to produce important biochemical. In this study, we have explored the characteristics of aspartase from Pseudomonas aeruginosa PAO1 (PA-AspA). To overproduce PA-AspA, the 1425-bp gene was introduced in Escherichia coli BL21 and purified. A 51.0-kDa protein was observed as a homogenous purified protein on SDS-PAGE. The enzyme was optimally active at pH 8.0 and 35 °C. PA-AspA has retained 56% activity after 7 days of incubation at 35 °C, which displays the hyperthermostablility characteristics of the enzyme. PA-AspA is activated in the presence of metal ions and Mg2+ is found to be most effective. Among the substrates tested for specificity of PA-AspA, L-phenylalanine (38.35 ± 2.68) showed the highest specific activity followed by L-aspartic acid (31.21 ± 3.31) and fumarate (5.42 ± 2.94). K m values for L-phenylalanine, L-aspartic acid and fumarate were 1.71 mM, 0.346 μM and 2 M, respectively. The catalytic efficiency (k cat /K m ) for L-aspartic acid (14.18 s -1  mM -1 ) was higher than that for L-phenylalanine (4.65 s -1  mM -1 ). For bioconversion, from an initial concentration of 1000 mM of fumarate and 30 mM of L-phenylalanine, PA-AspA was found to convert 395.31 μM L-aspartic acid and 3.47 mM cinnamic acid, respectively.

  20. STS-99 Mission Highlights Resource Tape, Part 1 of 2

    NASA Technical Reports Server (NTRS)

    2000-01-01

    An overview of the STS-99 Endeavour mission is given through footage of each flight day. Scenes from flight days one through ten show activities such as astronaut prelaunch procedures (breakfast, suit-up, and boarding Endeavour), launch, and on-orbit activities such as the deployment of the Shuttle Radar Topography Mission (SRTM) instrument. Crewmembers are seeing during such everyday activities as brushing their teeth, exercising (bicycle), and emerging from their sleeping bunks. One of the crewmembers shows the contents of the onboard medical kit. See 'STS-99 Mission Highlights Resource Tape, Part 2 of 2' for the activities of flight days 11-12 and the landing of Endeavour.

  1. Pre-Launch GOES-R Risk Reduction Activities for the Geostationary Lightning Mapper

    NASA Technical Reports Server (NTRS)

    Goodman, S. J.; Blakeslee, R. J.; Boccippio, D. J.; Christian, H. J.; Koshak, W. J.; Petersen, W. A.

    2005-01-01

    The GOES-R Geostationary Lightning Mapper (GLM) is a new instrument planned for GOES-R that will greatly improve storm hazard nowcasting and increase warning lead time day and night. Daytime detection of lightning is a particularly significant technological advance given the fact that the solar illuminated cloud-top signal can exceed the intensity of the lightning signal by a factor of one hundred. Our approach is detailed across three broad themes which include: Data Processing Algorithm Readiness, Forecast Applications, and Radiance Data Mining. These themes address how the data will be processed and distributed, and the algorithms and models for developing, producing, and using the data products. These pre-launch risk reduction activities will accelerate the operational and research use of the GLM data once GOES-R begins on-orbit operations. The GLM will provide unprecedented capabilities for tracking thunderstorms and earlier warning of impending severe and hazardous weather threats. By providing direct information on lightning initiation, propagation, extent, and rate, the GLM will also capture the updraft dynamics and life cycle of convective storms, as well as internal ice precipitation processes. The GLM provides information directly from the heart of the thunderstorm as opposed to cloud-top only. Nowcasting applications enabled by the GLM data will expedite the warning and response time of emergency management systems, improve the dispatch of electric power utility repair crews, and improve airline routing around thunderstorms thereby improving safety and efficiency, saving fuel and reducing delays. The use of GLM data will assist the Bureau of Land Management (BLM) and the Forest Service in quickly detecting lightning ground strikes that have a high probability of causing fires. Finally, GLM data will help assess the role of thunderstorms and deep convection in global climate, and will improve regional air quality and global chemistry/climate modeling

  2. Floodlights illuminate view of Skylab 3 vehicle at Pad B, Launch Complex 39

    NASA Image and Video Library

    1973-07-20

    S73-32568 (20 July 1973) --- Floodlights illuminate this nighttime view of the Skylab 3/Saturn 1B space vehicle at Pad B, Launch Complex 39, Kennedy Space Center, Florida, during prelaunch preparations. The reflection is the water adds to the scene. In addition to the Command/Service Module and its launch escapte system, the Skylab 3 space vehicle consists of the Saturn 1B first (S-1B) stage and the Saturn 1B second (S-IVB) stage. The crew for the scheduled 59-day Skylab 3 mission in Earth orbit will be astronauts Alan L. Bean, Owen K. Garriott and Jack R. Lousma. Skylab 3 was launched on July 28, 1973. Photo credit: NASA

  3. 14 CFR 417.1 - General information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... package, (3) Preliminary and final flight data packages, (4) A tailored version of EWR 127-1, (5) Range...) Missile system pre-launch safety package, (3) Preliminary and final flight data packages, (4) A tailored...

  4. 14 CFR 417.1 - General information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... package, (3) Preliminary and final flight data packages, (4) A tailored version of EWR 127-1, (5) Range...) Missile system pre-launch safety package, (3) Preliminary and final flight data packages, (4) A tailored...

  5. 14 CFR 417.1 - General information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... package, (3) Preliminary and final flight data packages, (4) A tailored version of EWR 127-1, (5) Range...) Missile system pre-launch safety package, (3) Preliminary and final flight data packages, (4) A tailored...

  6. 14 CFR 417.1 - General information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... package, (3) Preliminary and final flight data packages, (4) A tailored version of EWR 127-1, (5) Range...) Missile system pre-launch safety package, (3) Preliminary and final flight data packages, (4) A tailored...

  7. Airborne active and passive L-band measurements using PALS instrument in SMAPVEX12 soil moisture field campaign

    NASA Astrophysics Data System (ADS)

    Colliander, Andreas; Yueh, Simon; Chazanoff, Seth; Dinardo, Steven; O'Dwyer, Ian; Jackson, Thomas; McNairn, Heather; Bullock, Paul; Wiseman, Grant; Berg, Aaron; Magagi, Ramata; Njoku, Eni

    2012-10-01

    NASA's (National Aeronautics and Space Administration) Soil Moisture Active Passive (SMAP) Mission is scheduled for launch in late 2014. The objective of the mission is global mapping of soil moisture and freeze/thaw state. Merging of active and passive L-band observations of the mission will enable unprecedented combination of accuracy, resolution, coverage and revisit-time for soil moisture and freeze/thaw state retrieval. For pre-launch algorithm development and validation the SMAP project and NASA coordinated a field campaign named as SMAPVEX12 (Soil Moisture Active Passive Validation Experiment 2012) together with Agriculture and Agri-Food Canada, and other Canadian and US institutions in the vicinity of Winnipeg, Canada in June-July, 2012. The main objective of SMAPVEX12 was acquisition of a data record that features long time-series with varying soil moisture and vegetation conditions over an aerial domain of multiple parallel flight lines. The coincident active and passive L-band data was acquired with the PALS (Passive Active L-band System) instrument. The measurements were conducted over the experiment domain every 2-3 days on average, over a period of 43 days. The preliminary calibration of the brightness temperatures obtained in the campaign has been performed. Daily lake calibrations were used to adjust the radiometer calibration parameters, and the obtained measurements were compared against the raw in situ soil moisture measurements. The evaluation shows that this preliminary calibration of the data produces already a consistent brightness temperature record over the campaign duration, and only secondary adjustments and cleaning of the data is need before the data can be applied to the development and validation of SMAP algorithms.

  8. 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.…

  9. 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.

  10. Expedition 6 Crew Interviews: Nikolai Budarin FEI (Flight Engineer 1)

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Expedition 6 Flight Engineer Nikolai Budarin is seen during a prelaunch interview. He provides details on the mission's goals and significance, his role in the mission, what his responsibilities will be, what the crew activities will be like (docking of a Progress unpiloted supply vehicle, maintaining the space station, conducting science experiments and performing one spacewalk), the day-to-day life on an extended stay mission, and the experiments he will be conducting on board. Budarin also discusses how his previous experiences on mir space missions will help him and ends his thoughts on how valuable the International Space Station has proven.

  11. Hydroponically cultivated radish fed L-galactono-1,4-lactone exhibit increased tolerance to ozone.

    PubMed

    Maddison, Joanna; Lyons, Tom; Plöchl, Matthias; Barnes, Jeremy

    2002-01-01

    Leaf L-ascorbate content of an ozone (O3)-sensitive radish genotype (Raphanus sativus L. cv. Cherry Belle) was increased 2-fold by feeding hydroponically cultivated plants L-galactono- 1,4-lactone (GalL). Plants were grown in controlled-environment chambers ventilated with charcoal/Purafil-filtered air, and administered one of two O3 fumigation regimes: chronic exposure (75 nmol O3 mol(-1) for 7 h day(-1) for 21 days) and acute exposure (180 nmol O3 mol(-1) for 9 h). Chronic O3 exposure decreased root growth by 11% in plants maintained in pure nutrient solution (-GalL), but resulted in no change in root growth in GalL-fed plants (+GalL). Similarly, GalL-feeding counteracted the negative effects of O3 on CO2 assimilation rate observed in control plants (-GalL). Under acute O3 exposure, GalL-fed plants showed none of the visible symptoms of injury, which were extensive in plants not fed GalL. Leaf CO2 assimilation rate was decreased by acute 03 exposure in both GalL treatments, but the extent of the decline was less marked in GalL-fed plants. No significant changes in stomatal conductance resulted from GalL treatment, so O3 Uptake into leaves was equivalent in + GalL and -GalL plants. Feeding GalL, on the other hand, enhanced the level of ascorbate, and resulted in the maintenance of the redox state of ascorbate under acute O3 fumigation, in both the leaf apoplast and symplast. The effect of GalL treatment on ascorbate pools was consistent with the reduction in O3 damage observed in GalL-fed plants. Attempts to model O3 interception by the ascorbate pool in the leaf apoplast suggested a greater capacity for O3 detoxification in GalL-fed plants, which corresponded with the increase in O3 tolerance observed. However, modelled data for GalL-fed plants suggested that additional constituents of the leaf apoplast may play an important role in the attenuation of environmentally-relevant O3 fluxes.

  12. 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…

  13. 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…

  14. 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

  15. 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.

  16. Measurement of the np total cross section difference Δ σ L(np) at 1.39, 1.69, 1.89 and 1.99 GeV

    NASA Astrophysics Data System (ADS)

    Sharov, V. I.; Anischenko, N. G.; Antonenko, V. G.; Averichev, S. A.; Azhgirey, L. S.; Bartenev, V. D.; Bazhanov, N. A.; Belyaev, A. A.; Blinov, N. A.; Borisov, N. S.; Borzakov, S. B.; Borzunov, Yu T.; Bushuev, Yu P.; Chernenko, L. P.; Chernykh, E. V.; Chumakov, V. F.; Dolgii, S. A.; Fedorov, A. N.; Fimushkin, V. V.; Finger, M.; Finger, M.; Golovanov, L. B.; Gurevich, G. M.; Janata, A.; Kirillov, A. D.; Kolomiets, V. G.; Komogorov, E. V.; Kovalenko, A. D.; Kovalev, A. I.; Krasnov, V. A.; Krstonoshich, P.; Kuzmin, E. S.; Ladygin, V. P.; Lazarev, A. B.; Lehar, F.; de Lesquen, A.; Liburg, M. Yu; Livanov, A. N.; Lukhanin, A. A.; Maniakov, P. K.; Matafonov, V. N.; Matyushevsky, E. A.; Moroz, V. D.; Morozov, A. A.; Neganov, A. B.; Nikolaevsky, G. P.; Nomofilov, A. A.; Panteleev, Tz; Pilipenko, Yu K.; Pisarev, I. L.; Plis, Yu A.; Polunin, Yu P.; Prokofiev, A. N.; Prytkov, V. Yu; Rukoyatkin, P. A.; Schedrov, V. A.; Schevelev, O. N.; Shilov, S. N.; Shindin, R. A.; Slunečka, M.; Slunečková, V.; Starikov, A. Yu; Stoletov, G. D.; Strunov, L. N.; Svetov, A. L.; Usov, Yu A.; Vasiliev, T.; Volkov, V. I.; Vorobiev, E. I.; Yudin, I. P.; Zaitsev, I. V.; Zhdanov, A. A.; Zhmyrov, V. N.

    2004-09-01

    New accurate results of the neutron-proton spin-dependent total cross section difference Δσ_L(np) at the neutron beam kinetic energies 1.39, 1.69, 1.89 and 1.99 GeV are presented. Measurements were carried out in 2001 at the Synchrophasotron of the Veksler and Baldin Laboratory of High Energies of the Joint Institute for Nuclear Research. A quasi-monochromatic neutron beam was produced by break-up of extracted polarized deuterons. The deuteron (and hence neutron) polarization direction was flipped every accelerator burst. The vertical neutron polarization direction was rotated onto the neutron beam direction and longitudinally (L) polarized neutrons were transmitted through a large proton L-polarized target. The target polarization vector was inverted after 1-2 days of measurements. The data were recorded for four different combinations of the beam and target parallel and antiparallel polarization directions at each energy. A fast decrease of Δσ_L(np) with increasing energy above 1.1 GeV was confirmed. The structure in the Δσ_L(np) energy dependence around 1.8 GeV, first observed from our previous data, seems to be well pronounced. The new results are also compared with model predictions and with phase shift analysis fits. The Δσ_L quantities for isosinglet state I = 0, deduced from the measured Δσ_L(np) values and the known Δσ_L(pp) data, are also given. The results were completed by the measurements of unpolarized total cross sections σ_{0tot}(np) at 1.3, 1.4 and 1.5 GeV and σ_{0tot}(nC) at 1.4 and 1.5 GeV. These data were obtained using the same apparatus and high intensity unpolarized deuteron beams were extracted either from the Synchrophasotron, or from the Nuclotron.

  17. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

    PubMed Central

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-01-01

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

  18. 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.

  19. Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

    PubMed

    Flynn, K M; Kellihan, H B; Trepanier, L A

    2017-08-01

    To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Mechanisms of EDDHA effects on the promotion of floral induction in the long-day plant Lemna minor (L.).

    PubMed

    Krajncic, Bozidar; Nemec, Joze

    2003-02-01

    EDDHA added in an optimal concentration (20.5 mumol.L-1) to a modified Pirson-Seidel nutrient solution induces flowering in some clones of the species Lemna minor, Lemna gibba and Spirodela polyrrhiza, which in the absence of EDDHA in the same nutrient solution do not flower. By adding EDDHA (20.5 mumol.L-1), floral induction under LD conditions is optimally promoted in the long-day (LD) species Lemna minor. After adding EDDHA to the nutrient solution, before floral induction and during flowering, Zn, Mn and Cu content is significantly increased in plants. Zn-EDDHA (0.86 mumol.L-1), Mn-EDDHA (1.51 mumol.L-1) and Cu-EDDHA (0.12 mumol.L-1), when used individually, greatly promote flowering under LD conditions as compared to flowering in the same nutrient solution with an equivalent quantity of Zn, Mn or Cu in the nonchelate form. If, on the other hand, Zn-EDDHA and Mn-EDDHA are added to the nutrient solution together (instead of Zn and Mn in nonchelate form), their effect on the promotion of flowering is less than in the case of their individual use. This shows that there is antagonism between Zn-EDDHA and Mn-EDDHA that is eliminated by adding EDDHA to the nutrient solution. We obtained the highest percentage of flowering plants (i.e. 74%) if we added EDDHA (20.5 mumol.L-1) to the nutrient solution containing Mn, Zn and Cu in chelate form. 74% of flowering plants actually means that flowering was achieved in all physiologically mature plants. Our results show that EDDHA promotes floral induction in Lemna minor under LD conditions, especially through chelating Zn, Mn and Cu, and, in addition, through eliminating the antagonism between Mn and Zn chelates EDDHA. Zn-EDDHA (0.86 mumol.L-1) also promote floral differentiation, especially cell division of microspore mother cells into dyads and those into microspore tetrads, which can be seen in microphotographs. When investigating possible pathways through which Mn-EDDHA, Zn-EDDHA and Cu-EDDHA promote flowering, we studied

  1. 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.

  2. Hyperspectral IASI L1C Data Compression.

    PubMed

    García-Sobrino, Joaquín; Serra-Sagristà, Joan; Bartrina-Rapesta, Joan

    2017-06-16

    The Infrared Atmospheric Sounding Interferometer (IASI), implemented on the MetOp satellite series, represents a significant step forward in atmospheric forecast and weather understanding. The instrument provides infrared soundings of unprecedented accuracy and spectral resolution to derive humidity and atmospheric temperature profiles, as well as some of the chemical components playing a key role in climate monitoring. IASI collects rich spectral information, which results in large amounts of data (about 16 Gigabytes per day). Efficient compression techniques are requested for both transmission and storage of such huge data. This study reviews the performance of several state of the art coding standards and techniques for IASI L1C data compression. Discussion embraces lossless, near-lossless and lossy compression. Several spectral transforms, essential to achieve improved coding performance due to the high spectral redundancy inherent to IASI products, are also discussed. Illustrative results are reported for a set of 96 IASI L1C orbits acquired over a full year (4 orbits per month for each IASI-A and IASI-B from July 2013 to June 2014) . Further, this survey provides organized data and facts to assist future research and the atmospheric scientific community.

  3. Individual differences and day-to-day fluctuations in goal planning and type 1 diabetes management.

    PubMed

    Wiebe, Deborah J; Baker, Ashley C; Suchy, Yana; Stump, Tammy K; Berg, Cynthia A

    2018-04-26

    To examine whether individual differences and day-to-day fluctuations in diabetes goal planning are associated with Type 1 diabetes (T1D) management during late adolescence, and whether lapses in daily diabetes goal planning are more disruptive to diabetes management among those with poorer executive functioning (EF). Late adolescents with T1D (N = 236, Mage = 17.77 years) completed survey measures assessing individual differences in levels of diabetes goal planning and adherence, as well as survey and performance-based measures of EF; glycemic control was assessed through glycated hemoglobin (HbA1c) assays. Participants then completed a 2-week daily diary, rating items measuring daily diabetes goal planning, goal effort, and adherence, and recording blood-glucose tests from their glucometer at the end of each day. Analyses of survey measures indicated that higher individual differences in diabetes goal planning were associated with better adherence and glycemic control. Analyses of daily data using hierarchical linear modeling indicated that adolescents displayed higher daily adherence and lower blood-glucose levels on days when they had higher-than-their-average levels of daily goal planning and daily goal effort. EF moderated the association between daily goal planning and daily adherence, indicating that lapses in daily goal planning were more disruptive for adolescents with poorer EF. Both individual differences and day-to-day fluctuations in diabetes goal planning are associated with diabetes management, highlighting the challenges of managing T1D in daily life. Youth in late adolescence with poorer EF may especially benefit from planning to attain diabetes goals on a daily basis. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. 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…

  5. KSC-05PD-0359

    NASA Technical Reports Server (NTRS)

    2005-01-01

    KENNEDY SPACE CENTER, FLA. During an End-to-End (ETE) Mission Management Team (MMT) launch simulation at KSC, Mike Rein, division chief of Media Services, and Lisa Malone, director of External Relations and Business Development at KSC, work the consoles. In Firing Room 1 at KSC, Shuttle launch team members put the Shuttle system through an integrated simulation. The control room is set up with software used to simulate flight and ground systems in the launch configuration. The ETE MMT simulation included L-2 and L-1 day Prelaunch MMT meetings, an external tanking/weather briefing, and a launch countdown. The ETE transitioned to the Johnson Space Center for the flight portion of the simulation, with the STS-114 crew in a simulator at JSC. Such simulations are common before a launch to keep the Shuttle launch team sharp and ready for liftoff.

  6. Stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride and polyolefin bags.

    PubMed

    Karlage, Kelly; Earhart, Zachary; Green-Boesen, Kelly; Myrdal, Paul B

    2011-08-15

    The stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride (PVC) and polyolefin bags under varying conditions was evaluated. Triplicate solutions of midazolam hydrochloride 1-mg/mL were prepared in polyolefin and PVC i.v. bags by diluting midazolam hydrochloride injection 5 mg/mL with 5% dextrose injection. Bags were then stored under refrigeration (3-4 °C), exposed to light at room temperature (20-25 °C), or protected from light in amber bags at room temperature. Samples were taken immediately after preparation (day 0) and on days 1, 2, 3, 6, 13, 20, and 27 for analysis with a stability-indicating high-performance liquid chromatography assay in order to determine solution concentration. Stability was defined as retention of at least 90% of the initial drug concentration. The pH of each solution was also measured weekly. Sterility of the i.v. bags was determined at the end of the study by microbiological testing with culture in growth media. Differences in concentrations under the various storage conditions and bags used were analyzed using analysis of variance. All solutions retained over 98% of the initial midazolam hydrochloride concentration, with no statistically significant (p ≥ 0.05) change in concentration over the four-week period. Stability was not affected by temperature, exposure to light, or bag type. The pH of all solutions remained between 3.2 and 3.4 throughout the study. Sterility after 28 days was retained. Midazolam hydrochloride 1-mg/mL solutions diluted in 5% dextrose injection remained stable over 27 days in both polyolefin and PVC i.v. bags, regardless of storage condition.

  7. Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

    PubMed

    Wang, I-Kuan; Liu, Chung-Hsiang; Yen, Tzung-Hai; Jeng, Jiann-Shing; Hsu, Shih-Pin; Chen, Chih-Hung; Lien, Li-Ming; Lin, Ruey-Tay; Chen, An-Chih; Lin, Huey-Juan; Chi, Hsin-Yi; Lai, Ta-Chang; Sun, Yu; Lee, Siu-Pak; Sung, Sheng-Feng; Chen, Po-Lin; Lee, Jiunn-Tay; Chiang, Tsuey-Ru; Lin, Shinn-Kuang; Muo, Chih-Hsin; Ma, Henry; Wen, Chi-Pang; Sung, Fung-Chang; Hsu, Chung Y

    2017-06-01

    We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. A 3-day-old neonate with severe hypertriglyceridemia from novel mutations of the GPIHBP1 gene.

    PubMed

    Buonuomo, Paola Sabrina; Bartuli, Andrea; Rabacchi, Claudio; Bertolini, Stefano; Calandra, Sebastiano

    2015-01-01

    Familial chylomicronemia is a genetic defect of the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. Intravascular lipolysis involves the TG-hydrolase lipoprotein lipase (LPL) as well as other factors such as apolipoprotein CII and apolipoprotein AV (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface), and LMF1 (a factor required for intracellular formation of active LPL). We sequenced the familial chylomicronemia candidate genes in a neonate with chylomicronemia. A 3-day-old newborn was found to have chylomicronemia (plasma TG 18.8 mmol/L, 1.667 mg/dL). The discontinuation of breastfeeding for 24 hours reduced plasma TG to 2.3 mmol/L (201 mg/dL), whereas its resumption induced a sharp TG increase (7.9 mmol/L, 690 mg/dL). The child was switched to a low-fat diet, which was effective in maintaining TG level below 3.5 mmol/L (294 mg/dL) during the first months of life. The child was found to be a compound heterozygous for 2 novel mutations in GPIHBP1 gene. The first mutation was a 9-bp deletion and 4-bp insertion in exon 2, causing a frameshift that abolished the canonical termination codon TGA. The predicted translation product of the mutant messenger RNA is a peptide that contains 51 amino acids of the N-terminal end of the wild-type protein followed by 252 novel amino acids. The second mutation was a nucleotide change (c.319T>C), causing an amino acid substitution p.(Ser107Pro) predicted in silico to be damaging. GPIHBP1 mutations should be considered in neonates with chylomicronemia negative for mutations in LPL gene. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  10. Observations of geographically correlated orbit errors for TOPEX/Poseidon using the global positioning system

    NASA Technical Reports Server (NTRS)

    Christensen, E. J.; Haines, B. J.; Mccoll, K. C.; Nerem, R. S.

    1994-01-01

    We have compared Global Positioning System (GPS)-based dynamic and reduced-dynamic TOPEX/Poseidon orbits over three 10-day repeat cycles of the ground-track. The results suggest that the prelaunch joint gravity model (JGM-1) introduces geographically correlated errors (GCEs) which have a strong meridional dependence. The global distribution and magnitude of these GCEs are consistent with a prelaunch covariance analysis, with estimated and predicted global rms error statistics of 2.3 and 2.4 cm rms, respectively. Repeating the analysis with the post-launch joint gravity model (JGM-2) suggests that a portion of the meridional dependence observed in JGM-1 still remains, with global rms error of 1.2 cm.

  11. 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…

  12. Antimüllerian hormone as a predictor of good-quality supernumerary blastocyst cryopreservation among women with levels <1 ng/mL versus 1-4 ng/mL.

    PubMed

    Kavoussi, Shahryar K; Odenwald, Kate C; Boehnlein, Lynn M; Summers-Colquitt, Roxanne B; Pool, Thomas B; Swain, Jason E; Jones, Jeffrey M; Lindstrom, Mary J; Lebovic, Dan I

    2015-09-01

    To determine whether antimüllerian hormone (AMH) levels predict the availability of good-quality supernumerary blastocysts for cryopreservation. Retrospective study. Two fertility centers. First fresh IVF cycles (n = 247) grouped as follows: 40 women <35 year old with AMH <1 ng/mL and 77 women with AMH 1-4 ng/mL; 62 women ≥35 year old with AMH <1 ng/mL, and 68 women with AMH 1-4 ng/mL. AMH level measured before IVF with ovarian stimulation protocols based on patient age and AMH level, including short gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, or GnRH agonist microdose flare; supernumerary good-quality blastocysts cryopreserved on days 5 or 6 after retrieval. Supernumerary good-quality blastocysts for cryopreservation in relation to AMH levels. Among women <35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocysts for cryopreservation between the groups with AMH <1 ng/mL and AMH 1-4 ng/mL (30.0% vs. 58.4%) when adjusted for age. Among women ≥35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocyst cryopreservation between groups with AMH <1 ng/mL and AMH 1-4 ng/mL (16.1% vs. 42.6%), when adjusted for age. Low AMH levels are associated with a statistically significantly lower likelihood of blastocysts for cryopreservation as compared with higher AMH levels. This effect was seen among women both <35 and ≥35 years of age. Patient counseling should include realistic expectations for the probability of good-quality supernumerary blastocysts available for cryopreservation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Safety of a 1-Day Polyethylene Glycol 3350 Bowel Preparation for Colonoscopy in Children.

    PubMed

    Sahn, Benjamin; Chen-Lim, Mei Lin; Ciavardone, Denise; Farace, Lisa; Jannelli, Frances; Nieberle, Megan; Ely, Elizabeth; Zhang, Xuemei; Kelsen, Judith; Puma, Anita; Mamula, Petar

    2016-07-01

    Electrolyte-free polyethylene glycol powder (PEG-3350) has been widely used for colonoscopy preparation (prep); however, limited safety data on electrolyte changes exists with 1-day prep regimens. The primary aim of this study was to determine the proportion of patients with significant serum chemistry abnormalities before and at the time of colonoscopy. Secondary aims included evaluation of prep tolerance and bowel cleansing efficacy. We performed a prospective descriptive observational study of pediatric patients scheduled for outpatient colonoscopy who received our standard 1-day, weight-based 4 g/kg PEG-3350 prep with a single stimulant laxative dose and had serum chemistry testing within 60 days before and at the time of colonoscopy. A standardized bowel cleanliness tool (Aronchick scale) was completed by the endoscopist. One hundred fifty-five patients had serum electrolytes data pre- and postprep. Comparison of each patient's chemistries demonstrated statistical equivalence with the 1 exception of blood urea nitrogen levels (P = 0.56). Hypokalemia was detected postprep in 37 subjects (24%), but none had a serum level <3.3 mmol/L, which was deemed to be of no clinical significance. Five patients were hypoglycemic post prep; 3 were 7 years or younger (P = 0.02). The colon cleanliness rating was excellent or good in 77% and suboptimal in 23% of patients. A 1-day, weight-based PEG-3350 bowel prep in children appears safe. Changes in electrolyte levels and renal function were not clinically significant. Children of 7 years or younger seem to be at a higher risk of hypoglycemia compared with older children.

  14. Correlation of the Hubble Space Telescope (HST) Space Telescope Imaging Spectrometer (STIS) On-Orbit Data with Pre-launch Predictions and Ground Contamination Controls

    NASA Technical Reports Server (NTRS)

    Hansen, Patricia A.

    2003-01-01

    The Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS) was deployed on-orbit in February 1997. The contamination program for STIS was stringently controlled as the five-year end-of-life deposition was set at 158, per optical element. Contamination was controlled through materials selection, extensive vacuum outgassing certifications, cleaning techniques, and environmental controls. In addition to ground contamination controls, on-orbit contamination controls were implemented for both the HST servicing mission activities and early post-servicing mission checkout. The extensive contamination control program will be discussed and the STIS on-orbit data will be correlated with the prelaunch analytical predictions.

  15. 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.

  16. 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

  17. 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…

  18. Day-night and depth differences in haemolymph melatonin of the Norway lobster, Nephrops norvegicus (L.)

    NASA Astrophysics Data System (ADS)

    Aguzzi, J.; Sanchez-Pardo, J.; García, J. A.; Sardà, F.

    2009-10-01

    Few studies have been conducted to quantify and understand the role of melatonin in invertebrates, and particularly in crustaceans and in deep-sea animals. In this study, we examined day-night differences in haemolymph melatonin of the burrowing decapod crustacean Nephrops norvegicus (L.) during exposure to cycles of monochromatic blue light (480 nm) and darkness cycles of 10 and 0.1 lx. These differential intensity conditions simulate illumination at the depth of the shelf (80-100 m) and of the slope (300-400 m), where these lobster populations are chiefly found in the Western Mediterranean Sea. Our objectives were: (a) to verify the presence of melatonin in the haemolymph of this species using liquid chromatography/tandem mass spectrometry (LC-MS/MS) and fluorescence HPLC (HPLC); and (b) to study the relationship between diel variations in melatonin concentration and locomotor rhythms, in order to examine whether the former influences behaviour. Melatonin was identified in LC-MS/MS by Q1 and Q3 mass peaks at an elution time of 3.7 min, and it was also detected by HPLC. Melatonin concentration was found to be two orders of magnitude higher at 10 lx (4.8±5.3 ng ml -1) than at 0.1 lx (0.06±0.03 ng ml -1). Also, the increase at daytime in 10 lx was absent in 0.1 lx. When the locomotor rhythm of animals exposed to both photoperiod regimes was compared, the diel periodicity was found to be preserved, but the timing of activity shifted from night to day. Extrapolating these data to the field, we interpret our results to mean that locomotor activity preserves its diel character, but not its phase and amplitude, in a bathymetric range where haemolymph melatonin reduces its concentration and rhythmic fluctuation.

  19. 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

  20. 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…

  1. L-Citrulline Supplementation-Increased Skeletal Muscle PGC-1α Expression is Associated With Exercise Performance and Increased Skeletal Muscle Weight.

    PubMed

    Villareal, Myra O; Matsukawa, Toshiya; Isoda, Hiroko

    2018-05-24

    L-citrulline has recently been reported as a more effective supplement for promoting intracellular NO production compared to L-arginine. Here, the effect of L-citrulline on skeletal muscle and its influence on exercise performance were investigated. The underlying mechanism of its effect, specifically on the expression of skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), was also elucidated. Six-week-old ICR mice were orally supplemented with L-citrulline (250 mg kg -1 ) daily, and their performance in weight-loaded swimming exercise every other day for 15 days, was evaluated. In addition, mice muscles were weighed and evaluated for the expression of PGC-1α and PGC-1α-regulated genes. Mice orally supplemented with L-citrulline had significantly higher gastrocnemius and biceps femoris muscle mass. Although not statistically significant, L-citrulline prolonged the swimming time to exhaustion. PGC-1α upregulation was associated with vascular endothelial growth factor α (VEGFα) and insulin-like growth factor 1 (IGF1) upregulation. VEGFα and IGF1 are important for angiogenesis and muscle growth, respectively, and are regulated by PGC-1α. Treatment with L-NAME, a nitric oxide synthesis inhibitor, suppressed the L-citrulline-induced PGC-1α upregulation in-vitro. Supplementation with L-citrulline upregulates skeletal muscle PGC-1α levels resulting to higher skeletal muscle weight that improves time to exhaustion during exercise. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. 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.

  3. 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…

  4. Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

    PubMed Central

    Lee, Ada; Rubinow, Katya; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Zhi, Hui; Roth, Mara Y; Page, Stephanie T.; Bremner, William J.; Amory, John K.

    2014-01-01

    Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 µg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone–binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P > .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency. PMID:21868746

  5. [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.

  6. 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.

  7. 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.

  8. 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.

  9. 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…

  10. ROCHFORD, AL - ASTRONAUT COOPER, GORDON L. - LIFE VEST CHECK - PRELAUNCH ACTIVITIES - MERCURY-ATLAS (MA)-9 - MSC

    NASA Image and Video Library

    1963-03-01

    S63-03964 (1963) --- Al Rochford, Crew Systems, Manned Space Center, assists astronaut L. Gordon Cooper Jr., in checking his life vest, normally stowed in a pocket in the lower left leg. Photo credit: NASA

  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. 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 ...

  13. 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 ...

  14. 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.

  15. Macroanatomical investigation of the aorticorenal ganglion in 1-day-old infant sheep.

    PubMed

    Klećkowska-Nawrot, J; Kaczyńska, K; Jakubowska, W

    2009-06-01

    The aorticorenal gland belongs to the paired splanchnic ganglion, which is the main component of the coeliac plexus. It lies near the renal artery and suprarenal gland. The research was conducted on 13 1-day-old infant sheep - eight males and five females. Based on the conducted studies, it was concluded that the aorticorenal ganglion is characterized by the variable location in relation to the abdominal aorta, renal artery, caudal vena cava and suprarenal gland (holotopy), the thoracic and lumbar segment of the vertebral column (skeletotopy) (between L(1) and L(3)) and also a different shape (elongated, round, triangular, oval) as well as variable length (the aorticorenal ganglion is longer on the left side of the body; 2.72 mm) and distance from the caudal end of the suprarenal gland (longer on the left side of the body; 8.34 mm). With regard to the sex of the animal, the ganglion is the longest on the left side in ewes (3.02 mm), while in rams it is the longest on the right side (2.68 mm). Regarding the division according to sex, the longest segment was observed on the right side in ewes (9.27 mm), and the shortest segment in rams was also on the right side (6.84 mm).

  16. 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

  17. Anti-helminthic activity of Momordica charantia L. against Fasciola hepatica eggs after twelve days of incubation in vitro.

    PubMed

    Pereira, Cíntia A J; Oliveira, Laura L S; Coaglio, Aytube L; Santos, Fernanda S O; Cezar, Rodolfo S M; Mendes, Tiago; Oliveira, Fernando L P; Conzensa, Gustavo; Lima, Walter S

    2016-09-15

    Fasciolosis, a parasitic disease caused by the trematode Fasciola hepatica underreported is expanding both in human and animal population, throughout the world. The constant use of synthetic drugs to treat this condition has led to the natural selection of resistant strains of the parasite. Hence, there is a growing focus on the potential anti-helminthic properties of medicinal plants and phytopharmaceuticals. The current study assessed the potential anti-fasciolicide action of Momordica charantia leaf extracts and fractions on the eggs of F. hepatica parasites. The lyophilized crude extract (CE) of M. charantia leaves and its sub-fractions, obtained from liquid-liquid partitioning with organic solvents, were analysed by High Performance Liquid Chromatography (HPLC), suspended in 1% DMSO and used in in vitro tests. Quadruplicates of 50F. hepatica eggs were incubated at 23°C with M. charantia leaf CE in different concentrations. After 12days no larvae were formed in eggs incubated with CE concentrations above 12.5mg/mL. Eggs incubated with CE sub-fractions at concentrations of 1000, 100, 10, 1, 0.1, 0.01μg/mL affected embryonic development, with n-butanol presenting the strongest inhibition of miracidia formation. In contrast, on the 12th day, 90% of the miracidia hatched in the control experiments using 0.03% DMSO whereas embryogenesis was completely abolished with any concentration of albendazole sulphoxide ABZ(SO). Chemical analysis of the CE and sub-fractions revealed a prominent presence of flavonoids. HPLC-MS confirmed Quercetin to be one of the main flavonoids present in the CE and the n-butanol subfraction. This is the first study to analyse the potential anti-fasciolicide action of M. charantia leaf CE and subfractions. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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…

  19. Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.

    PubMed

    Okiyama, Naoko; Katz, Stephen I

    2014-09-01

    Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases. Published by Elsevier Ltd.

  20. 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…

  1. L1-CAM-targeted antibody therapy and (177)Lu-radioimmunotherapy of disseminated ovarian cancer.

    PubMed

    Fischer, Eliane; Grünberg, Jürgen; Cohrs, Susan; Hohn, Alexander; Waldner-Knogler, Karin; Jeger, Simone; Zimmermann, Kurt; Novak-Hofer, Ilse; Schibli, Roger

    2012-06-01

    The L1-cell adhesion molecule (L1-CAM) is highly expressed in various cancer types including ovarian carcinoma but is absent from most normal tissue. A chimeric monoclonal antibody, chCE7, specifically binds to human L1-CAM and exhibits anti-proliferative effects on L1-CAM-expressing tumor cells. The goal of this study was to evaluate the efficacy of a novel (177)Lu-chCE7 radioimmunotherapeutic agent and to compare it to a treatment protocol with unlabeled, growth-inhibiting chCE7 in a mouse xenograft model of disseminated ovarian cancer. chCE7agl, an aglycosylated IgG1 variant with improved pharmacokinetics, was conjugated with 1,4,7,10-tetraazacyclododecane-N-N'-N'-N‴-tetraacetic acid (DOTA) and labeled with the low-energy β-emitter (177)Lu. Tumor growth and survival were assessed after a single i.v. dose of 8 MBq (60 μg) radioimmunoconjugate in nude mice bearing either subcutaneous or intraperitoneal SKOV3.ip1 human ovarian cancer tumors. Therapeutic efficacy was compared with three times weekly i.p. administration of 10 mg/kg unconjugated chCE7. In vivo analysis of (177)Lu-chCE7agl biodistribution demonstrated high and specific accumulation of radioactivity at the tumor site with maximal tumor uptake of up to 48.0 ± 8.1% ID/g at 168 h postinjection. A single treatment with (177)Lu-DOTA-chCE7agl caused significant retardation of tumor growth and prolonged median survival from 33 to 71 days, while administration of a nontargeted (177)Lu-immunoconjugate had no beneficial effect. Three times weekly i.p. application of unlabeled chCE7 10 mg/kg similarly increased survival from 44 to 72 days. We conclude that a single dose of (177)Lu-DOTA-chCE7agl is as effective as repeated administration of nonradioactive chCE7 for treatment of small intraperitoneal tumors expressing L1-CAM. Copyright © 2011 UICC.

  2. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

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

    Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun

    2011-06-17

    Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from themore » edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.« less

  3. 14 CFR 417.1 - General information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... safety for a launch if written evidence demonstrates that a Federal launch range has, by the effective... provision. Written evidence includes: (1) Range flight plan approval, (2) Missile system pre-launch safety... email to the FAA stating that the MIC was approved, or (6) Operation approval. (d) Waiver. For a...

  4. Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1.

    PubMed

    Kabel, Ahmed M; Omar, Mohamed S; Alhadhrami, A; Alharthi, Salman S; Alrobaian, Majed M

    2018-05-01

    Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-β1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondrial complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination. The combination of l-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant improvement of the behavioural changes, striatal dopamine, antioxidant parameters, Nrf2/HO-1 content, GLP-1, ATP and mitochondrial complex I activity with significant decrease in striatal RAGE, TGF-β1, TNF-α, IL-10, TLR4 and alleviated the immunohistochemical changes better than the groups that received either l-dopa/Carbidopa or linagliptin alone. The combination of l-dopa/Carbidopa and linagliptin might represent a promising therapeutic modality for management of parkinsonism. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. New insulin glargine 300 Units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units · mL-1.

    PubMed

    Becker, Reinhard H A; Dahmen, Raphael; Bergmann, Karin; Lehmann, Anne; Jax, Thomas; Heise, Tim

    2015-04-01

    To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units · mL(-1) (Gla-300), compared with insulin glargine 100 units · mL(-1) (Gla-100) at steady state in people with type 1 diabetes. A randomized, double-blind, crossover study (N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units · kg(-1) (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units · kg(-1) Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units · kg(-1) of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h. At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼ 3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤ 105 mg · dL(-1)) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100. Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

    PubMed Central

    Boudalia, Sofiane; Belloir, Christine; Miller, Marie-Louise; Canivenc-Lavier, Marie-Chantal

    2017-01-01

    Introduction: Data from last years suggested that early exposure to endocrine disruptors (EDs) can predispose newborns to endocrine dysfunction of adipocytes, obesity, and associated disorders. The implication of EDs at low doses on adipocyte development has been poorly investigated. For instance, vinclozolin (V) is a dicarboximide fungicide widely used in agriculture since the 90's, alone or in mixture with genistein (G), an isoflavonoid from Leguminosae. This study aims to identify the effect of vinclozolin alone or with genistein, on adipose tissue properties using cell culture. Methods: In steroid-free conditions, 3T3-L1 pre-adipocytes were induced to differentiate in the presence of EDs, singularly or in mixtures, for 2 days. DNA and triglyceride (TG) levels were measured on days 0, 2 and 8 of differentiation. Leptin secretion was measured only on the eighth day. Results: We show that low doses of G (25 µM) and V (0.1 µM) inhibit pre-adipocytes differentiation. This inhibition has been represented by a decreasing in DNA content (µg/well) and decreasing in TG accumulation (mg/mL) in 3T3-L1 cells. Nevertheless, V increased the anti-adipogenic properties of G. Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity. PMID:28752072

  7. 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…

  8. Safety of long-term dietary supplementation with L-arginine in pigs.

    PubMed

    Hu, Shengdi; Li, Xilong; Rezaei, Reza; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

    2015-05-01

    This study was conducted with a swine model to determine the safety of long-term dietary supplementation with L-arginine-HCl or L-arginine free base. Beginning at 30 days of age, pigs were fed a corn- and soybean meal-based diet (31.5 g/kg body weight/day) supplemented with 0, 1.21, 1.81 or 2.42 % L-arginine-HCl (Experiment 1) or with 0, 1, 1.5 or 2 % L-arginine (Experiment 2). The supplemental doses of 0, 1, 1.5, and 2 % L-arginine provided pigs with 0, 315, 473, and 630 mg L-arginine/kg body weight/day, respectively, which were equivalent to 0, 286, 430, and 573 mg L-arginine/kg body weight/day, respectively, in humans. At 121 days of age (91 days after initiation of supplementation), blood samples were obtained from the jugular vein of pigs at 1 and 4 h after feeding for hematological and clinical chemistry tests. Dietary supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, albumin and reticulocytes, while reducing plasma concentrations of ammonia, free fatty acids, triglyceride, cholesterol, and neutrophils. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Other variables in standard hematology and clinical chemistry tests, serum concentrations of insulin, growth hormone and insulin-like growth factor-I did not differ among all the groups of pigs. These results indicate that dietary supplementation with L-arginine (up to 630 mg/kg body weight/day) is safe in pigs for at least 91 days. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.

  9. Amelioration of L-thyroxine-induced hyperthyroidism by coumarin (1,2-benzopyrone) in female rats.

    PubMed

    Panda, Sunanda; Kar, Anand

    2007-11-01

    1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associated parameters, such as serum cholesterol, activity of hepatic 5'-monodeiodinase (5'DI) and glucose-6-phosphatase (G-6-Pase), glycogen content, bodyweight and daily food consumption, were analysed. Simultaneously, changes in hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also investigated. 3. Although L-T(4) administration increased serum levels of thyroid hormones, the activity of hepatic 5'DI, G-6-Pase and LPO and daily food consumption, it decreased the level of serum cholesterol, hepatic glycogen content and the activities of anti-oxidant enzymes, such as SOD, CAT and GSH. 4. However, simultaneous administration of coumarin for 15 days to a group of hyperthyroid animals reversed most of the aforementioned changes, indicating its potential to ameliorate hyperthyroidism. Moreover, the drug did not increase, but rather decreased, hepatic LPO, suggesting its safe nature. 5. The present findings reveal a positive role for coumarin in the regulation of hyperthyroidism without any hepatotoxicity. It also appears that the test compound inhibits thyroid function at both a glandular level and at the level of peripheral conversion of T(4) to tri-iodothyronine.

  10. 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

  11. 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…

  12. 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…

  13. Storm Prediction Center May 28, 2018 0100 UTC Day 1 Convective Outlook

    Science.gov Websites

    services. Day 2 Outlook > May 28, 2018 0100 UTC Day 1 Convective Outlook Updated: Mon May 28 01:01:01 UTC 2018 (Print Version | 20180528 0100Z Day 1 shapefile | 20180528 0100Z Day 1 KML ) Probabilistic to . Forecast Discussion SPC AC 280101 Day 1 Convective Outlook NWS Storm Prediction Center Norman OK 0801 PM

  14. [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

  15. 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.

  16. EVA 1 activity on Flight Day 4 to service the Hubble Space Telescope

    NASA Image and Video Library

    1997-02-14

    STS082-730-090 (11-21 Feb. 1997) --- Astronaut Steven L. Smith handles one of the Goddard High Resolution Spectrograph (GHRS) boxes, changed out on the Hubble Space Telescope (HST) on Flight Day 4. Astronauts Smith and Mark C. Lee were participating in the first of five eventual days of Extravehicular Activity (EVA) to service the giant orbital observatory. Smith is standing on the end of the Remote Manipulator System (RMS) arm, which was controlled by astronaut Steven A. Hawley inside the Space Shuttle Discovery's crew cabin.

  17. Effects of L-arginine pre-treatment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s diseases in Balb/c mice

    PubMed Central

    Hami, Javad; Hosseini, Mehran; Shahi, Sekineh; Lotfi, Nassim; Talebi, Abolfazl; Afshar, Mohammad

    2015-01-01

    Background: Parkinson’s disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage. This study aimed to evaluate the effects of L-arginine on the numerical density of dark neurons (DNs) in the SNc of Balb/c mice subjected to MPTP administration. Methods: In the present study, we demonstrated that repeated treatment with L-arginine (300 mg/kg, i.p.) during 7 consecutive days attenuated the production of DNs in SNc of adult male Balb/c mice infused with a single intranasal administration of MPTP (1 mg/nostril). Results: Pre-treatment with L-arginine significantly decreased the numerical density of DNs in SNc of mice 21 days after intranasal MPTP administration. Conclusion: This investigation provides new insights in experimental models of PD, indicating that L-arginine represents a potential neuroprotective agent for the prevention of DA neuron degeneration in SNc observed in PD patients. PMID:26885338

  18. 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…

  19. SeaWiFS Technical Report Series. Volume 43; SeaWiFS Prelaunch Technical Report Series Final Cumulative Index

    NASA Technical Reports Server (NTRS)

    Firestone, Elaine R. (Editor); Hooker, Stanford B.

    1998-01-01

    The Sea-viewing Wide Field-of-view Sensor (SeaWiFS) is the follow-on ocean color instrument to the Coastal Zone Color Scanner (CZCS), which ceased operations in 1986, after an eight-year mission. SeaWiFS was launched on 1 August 1997, on the SeaStar satellite, built by Orbital Sciences Corporation (OSC). The SeaWiFS Project at the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC), undertook the responsibility of documenting all aspects of this mission, which is critical to the ocean color and marine science communities. This documentation, entitled the SeaWiFS Technical Report Series, is in the form of NASA Technical Memorandum Number 104566 and 1998-104566. All reports published are volumes within the series. This particular volume, which is the last of the so-called Prelaunch Series serves as a reference, or guidebook, to the previous 42 volumes and consists of 6 sections including: an addenda, an errata, an index to key words and phrases, lists of acronyms and symbols used, and a list of all references cited. The editors have published a cumulative index of this type after every five volumes. Each index covers the reference topics published in all previous editions, that is, each new index includes all of the information contained in the preceding indexes with the exception of any addenda.

  20. ATV during Demonstration Day 1 Rendezvous Test

    NASA Image and Video Library

    2008-03-29

    ISS016-E-033720 (29 March 2008) --- Cosmonaut Yuri Malenchenko, Expedition 16 flight engineer, aboard the International Space Station used a digital still camera to record several images of the Jules Verne Automated Transfer Vehicle (ATV) during a rendezvous test March 29, 2008. Malenchenko fitted the camera with an 800mm lens typically employed for Shuttle RPM photography while the ATV sat 2.1 statute miles from the ISS during the first of two demonstration days in the lead up to a docking on April 3. On March 31, Demonstration Day 2 will see ATV approach to within 11 meters of the ISS.

  1. Unhealthy Days and Quality of Life in Irish Patients with Diabetes

    PubMed Central

    Clifford, Emma Louise; Collins, Margaret M.; Buckley, Claire M.; Fitzgerald, Anthony P.; Perry, Ivan J.

    2013-01-01

    Objectives To study the determinants of health-related quality of life (HRQoL) in Irish patients with diabetes using the Centres for Disease Controls' (CDC's) ‘Unhealthy Days’ summary measure and to assesses the agreement between this generic HRQoL measure and the disease-specific Audit of Diabetes Dependant Quality of Life (ADDQoL) measure. Research Design and Methods Data were analysed from the Diabetes Quality of Life Study, a cross-sectional study of 1,456 people with diabetes in Ireland (71% response rate). Unhealthy days were assessed using the CDC's ‘Unhealthy days’ summary measure. Quality of life (QoL) was also assessed using the ADDQoL measure. Analyses were conducted primarily using logistic regression. The agreement between the two QoL instruments was measured using the kappa co-efficient. Results Participants reported a median of 2 unhealthy days per month. In multivariate analyses, female gender (P = 0.001), insulin use (P = 0.030), diabetes complications (P = <0.001) were significantly associated with more unhealthy days. Older patients had fewer unhealthy days per month (P = 0.003). Agreement between the two measures of QoL (unhealthy days measure and ADDQoL) was poor, Kappa = 0.234 Conclusions The findings highlight the determinants of HRQoL in patients with diabetes using a generic HRQoL summary measure. The ‘Unhealthy Days’ and the ADDQoL have poor agreement, therefore the ‘Unhealthy Days’ summary measure may be assessing a different construct. Nonetheless, this study demonstrates that the generic ‘Unhealthy Days’ summary measure can be used to detect determinants of HRQoL in patients with diabetes. PMID:24349036

  2. PALS (Passive Active L-band System) Radiometer-Based Soil Moisture Retrieval for the SMAP Validation Experiment 2012 (SMAPVEX12)

    NASA Astrophysics Data System (ADS)

    Colliander, A.; Jackson, T. J.; Chan, S.; Bindlish, R.; O'Neill, P. E.; Chazanoff, S. L.; McNairn, H.; Bullock, P.; Powers, J.; Wiseman, G.; Berg, A. A.; Magagi, R.; Njoku, E. G.

    2014-12-01

    NASA's (National Aeronautics and Space Administration) Soil Moisture Active Passive (SMAP) mission is scheduled for launch in early January 2015. For pre-launch soil moisture algorithm development and validation, the SMAP project and NASA coordinated a SMAP Validation Experiment 2012 (SMAPVEX12) together with Agriculture and Agri-Food Canada in the vicinity of Winnipeg, Canada in June 7-July 19, 2012. Coincident active and passive airborne L-band data were acquired using the Passive Active L-band System (PALS) on 17 days during the experiment. Simultaneously with the PALS measurements, soil moisture ground truth data were collected manually. The vegetation and surface roughness were sampled on non-flight days. The SMAP mission will produce surface (top 5 cm) soil moisture products a) using a combination of its L-band radiometer and SAR (Synthetic Aperture Radar) measurements, b) using the radiometer measurement only, and c) using the SAR measurements only. The SMAPVEX12 data are being utilized for the development and testing of the algorithms applied for generating these soil moisture products. This talk will focus on presenting results of retrieving surface soil moisture using the PALS radiometer. The issues that this retrieval faces are very similar to those faced by the global algorithm using the SMAP radiometer. However, the different spatial resolution of the two observations has to be accounted for in the analysis. The PALS 3 dB footprint in the experiment was on the order of 1 km, whereas the SMAP radiometer has a footprint of about 40 km. In this talk forward modeled brightness temperature over the manually sampled fields and the retrieved soil moisture over the entire experiment domain are presented and discussed. In order to provide a retrieval product similar to that of the SMAP passive algorithm, various ancillary information had to be obtained for the SMAPVEX12 domain. In many cases there are multiple options on how to choose and reprocess these data

  3. 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…

  4. 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

  5. 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…

  6. Health-related quality of life of day-case surgery patients: a pre/posttest survey using the EuroQoL-5D.

    PubMed

    Suhonen, Riitta; Virtanen, Heli; Heikkinen, Katja; Johansson, Kirsi; Kaljonen, Anne; Leppänen, Tiina; Salanterä, Sanna; Leino-Kilpi, Helena

    2008-02-01

    This paper describes and compares the perceived health-related quality of life (HRQoL) of day-case surgery patients before and after their procedures and examines some associated patient-related factors. A pre/posttest survey design was employed to collect data from Finnish adult day-case surgery patients using participant-completed EuroQoL 5-Dimensional Classification Component Scores (EQ-5D) questionnaires given 2 weeks presurgery (n = 131) and 2 weeks postsurgery (n = 131) in 2004. No noticeable change after minor surgery was found using the EQ-5D. Using the EQ-5D index, patients perceived their HRQoL as high before and after surgery. Almost one fifth (17%) reported no pain or discomfort before the procedure compared with 40% after it. As measured by the EuroQol visual analogue scale (EQ(VAS)), those patients who reported chronic illness before the operation had a lower perception of their HRQoL compared with those who did not. It was also found that self-care and usual activities were more disturbed after surgery. Although there were increases and decreases within items of the EQ-5D, overall, there was no improvement on EQ-5D scores. More research is needed to explore the sensitivity and responsiveness of the EQ-5D measure in day-case surgery patients.

  7. Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

    PubMed

    Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein

    2017-02-01

    Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. How satisfied are mothers with 1-day hospital stays for routine delivery?

    PubMed

    Klingner, J M; Solberg, L I; Knudson-Schumacher, S; Carlson, R R; Huss, K L

    1999-01-01

    Payers and health plans are encouraging shorter hospital stays after routine vaginal delivery. To assess the satisfaction of mothers who had 1-day or 2-day stays after routine delivery. We mailed questionnaires to mothers 7 to 9 months after delivery. The self-administered survey contained questions about the mothers' satisfaction with the care they received, clinical complications, and the mothers' preparedness after discharge. A mixed-staff, network-model managed care plan in Minnesota that encourages but does not require 1-day hospital stays after routine delivery. All plan members who delivered a baby vaginally in the first quarter of 1995 (n = 1009). 56% of the mothers responded to the survey. Of these, 202 had 1-day stays and 292 had 2-day stays. Mothers with 1-day stays were more likely than mothers with 2-day stays to report that their length of stay was "too short" (75% vs. 37%; P < 0.001), and 81% of mothers with 1-day stays would want to stay longer if they had another child. The frequency of self-reported maternal or infant complications did not differ substantially between the two groups. More mothers with 1-day stays than mothers with 2-day stays received home health care visits (44% vs. 10%; P < 0.001). Although length of stay does not seem to be related to clinical outcomes after vaginal delivery, mothers with 1-day stays are less satisfied with their length of stay.

  9. 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.

  10. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.

    PubMed

    Devereaux, P J; Chan, Matthew T V; Alonso-Coello, Pablo; Walsh, Michael; Berwanger, Otavio; Villar, Juan Carlos; Wang, C Y; Garutti, R Ignacio; Jacka, Michael J; Sigamani, Alben; Srinathan, Sadeesh; Biccard, Bruce M; Chow, Clara K; Abraham, Valsa; Tiboni, Maria; Pettit, Shirley; Szczeklik, Wojciech; Lurati Buse, Giovanna; Botto, Fernando; Guyatt, Gordon; Heels-Ansdell, Diane; Sessler, Daniel I; Thorlund, Kristian; Garg, Amit X; Mrkobrada, Marko; Thomas, Sabu; Rodseth, Reitze N; Pearse, Rupert M; Thabane, Lehana; McQueen, Matthew J; VanHelder, Tomas; Bhandari, Mohit; Bosch, Jackie; Kurz, Andrea; Polanczyk, Carisi; Malaga, German; Nagele, Peter; Le Manach, Yannick; Leuwer, Martin; Yusuf, Salim

    2012-06-06

    Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days. To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality. A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery. Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death. A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C

  11. The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis.

    PubMed

    Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Singh, Amar; Lokensgard, James R

    2017-04-13

    Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bT RM ) following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8 + T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bT RMs . In wild-type (WT) animals, we observed a switch in the phenotype of brain-infiltrating CD8 + T cell populations from KLRG1 + CD127 - (SLEC) to KLRG1 - CD127 + (MPEC) during transition from acute through chronic phases of infection. At 14 and 30 dpi, the majority of CD8 + T cells expressed CD127, a marker of memory cells. In contrast, fewer CD8 + T cells expressed CD127 within brains of infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of CD8 + T cells was phenotyped as CD103 + CD69 + , markers of bT RM , and differences were observed in the numbers of these cells when compared to PD-L1 KOs. Immunohistochemical studies revealed that brain-resident CD103 + bT RM cells were localized to the parenchyma. Higher frequencies of CXCR3 were also observed among WT animals in contrast to PD-L1 KOs. Taken together, our results indicate that bT RMs are present within the CNS following viral infection and the PD-1: PD-L1 pathway plays a role in the generation of this brain-resident population.

  12. Infants 1-90 days old hospitalized with human rhinovirus infection.

    PubMed

    Bender, Jeffrey M; Taylor, Charla S; Cumpio, Joven; Novak, Susan M; She, Rosemary C; Steinberg, Evan A; Marlowe, Elizabeth M

    2014-09-01

    Human rhinovirus (HRV) is a common cause of respiratory illness in children. The impact of HRV infection on 1- to 90-day-old infants is unclear. We hypothesized that HRV infection would be clinically similar to respiratory syncytial virus (RSV) infection in the hospitalized infants. We conducted a retrospective study of hospitalized infants, who were 1-90 days old, with HRV or RSV within the Southern California Kaiser Permanente network over a 1-year period (August 2010 to October 2011). We identified 245 hospitalized infants who underwent respiratory virus testing. HRV was found in 52 infants (21%) compared to 79 infants (32%) with RSV (P = 0.008). Infants with HRV infection experienced longer hospital stays compared to those with RSV (median length of stay 4 days vs. 3 days, P = 0.009) and had fewer short hospital stays ≤3 days (P = 0.029). There was a trend in infants with HRV infection to be younger (P = 0.071) and have more fevers (P = 0.052). Recent advances in diagnostics allow for identification of a broad range of viral pathogens in infants. Compared to RSV, HRV was associated with longer hospital stays. Additional studies and improved, more specific testing, methods are needed to further define the effects of HRV infection in infants 1-90 days old. © 2014 Wiley Periodicals, Inc.

  13. 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.

  14. 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.

  15. E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox.

    PubMed

    Volz, Asisa; Jany, Sylvia; Freudenstein, Astrid; Lantermann, Markus; Ludwig, Holger; Sutter, Gerd

    2018-01-04

    The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L . Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV) challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

  16. 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.

  17. 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…

  18. 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

  19. Apollo 9 crew leaves Spacecraft Operations Building during countdown

    NASA Image and Video Library

    1969-03-03

    S69-25883 (3 March 1969) --- The Apollo 9 crew leaves the Kennedy Space Center's Manned Spacecraft Operations Building during the Apollo 9 prelaunch countdown. Leading is astronaut James A. McDivitt, commander; followed by astronaut David R. Scott, command module pilot; and Russell L. Schweickart, lunar module pilot. Moments later they entered the special transfer van which transported them to their waiting spacecraft at Pad A, Launch Complex 39. Apollo 9 was launched at 11 a.m. (EST), March 3, 1969, on a 10-day Earth-orbital mission.

  20. Dexamethasone Protects Neonatal Hypoxic-Ischemic Brain Injury via L-PGDS-Dependent PGD2-DP1-pERK Signaling Pathway

    PubMed Central

    Gonzalez-Rodriguez, Pablo J.; Li, Yong; Martinez, Fabian; Zhang, Lubo

    2014-01-01

    Background and Purpose Glucocorticoids pretreatment confers protection against neonatal hypoxic-ischemic (HI) brain injury. However, the molecular mechanism remains poorly elucidated. We tested the hypothesis that glucocorticoids protect against HI brain injury in neonatal rat by stimulation of lipocalin-type prostaglandin D synthase (L-PGDS)-induced prostaglandin D2 (PGD2)-DP1-pERK mediated signaling pathway. Methods Dexamethasone and inhibitors were administered via intracerebroventricular (i.c.v) injections into 10-day-old rat brains. Levels of L-PGD2, D prostanoid (DP1) receptor, pERK1/2 and PGD2 were determined by Western immunoblotting and ELISA, respectively. Brain injury was evaluated 48 hours after conduction of HI in 10-day-old rat pups. Results Dexamethasone pretreatment significantly upregulated L-PGDS expression and the biosynthesis of PGD2. Dexamethasone also selectively increased isoform pERK-44 level in the neonatal rat brains. Inhibitors of L-PGDS (SeCl4), DP1 (MK-0524) and MAPK (PD98059) abrogated dexamethasone-induced increases in pERK-44 level, respectively. Of importance, these inhibitors also blocked dexamethasone-mediated neuroprotective effects against HI brain injury in neonatal rat brains. Conclusion Interaction of glucocorticoids-GR signaling and L-PGDS-PGD2-DP1-pERK mediated pathway underlies the neuroprotective effects of dexamethasone pretreatment in neonatal HI brain injury. PMID:25474649

  1. 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. ...

  2. 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.

  3. Apollo-Soyuz test project. Operations handbook command/service/docking modules (CSM 119/DM 1): Operational procedures reference issue

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Operational and configuration checks for the Apollo-Soyuz Test Project are presented. The checks include: backup crew prelaunch, prime crew prelaunch, boost and insertion, G and C reference data, G and N reference modes, rendezvous, navigation, Apollo-Soyuz operations, abort procedures, and emergency procedures.

  4. 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.

  5. Effect of Flooding on Starch Accumulation in Chloroplasts of Sunflower (Helianthus annuus L.) 1

    PubMed Central

    Wample, Robert L.; Davis, Ronald W.

    1983-01-01

    Chloroplasts in leaves of sunflower (Helianthus annuus L. cv hybrid 894) whose roots were flooded for 4 days showed an increase in the level of starch in chloroplasts when examined with the electron microscope. Starch determination showed significantly higher levels in leaves of flooded plants. Chloroplast and mitochondrial structure seemed otherwise normal. Images Fig. 1 Fig. 2 PMID:16663176

  6. Wind Prelaunch Mission Operations Report (MOR)

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The National Aeronautics and Space Administration (NASA) Wind mission is the first mission of the Global Geospace Science (GGS) initiative. The Wind laboratory will study the properties of particles and waves in the region between the Earth and the Sun. Using the Moon s gravity to save fuel, dual lunar swing-by orbits enable the spacecraft to sample regions close to and far from the Earth. During the three year mission, Wind will pass through the bow shock of Earth's magnetosphere to begin a thorough investigation of the solar wind. Mission objectives require spacecraft measurements in two orbits: lunar swing- by ellipses out to distances of 250 Earth radii (RE) and a small orbit around the Lagrangian point L-l that remains between the Earth and the Sun. Wind will be placed into an initial orbit for approximately 2 years. It will then be maneuvered into a transition orbit and ultimately into a halo orbit at the Earth-Sun L-l point where it will operate for the remainder of its lifetime. The Wind satellite development was managed by NASA's Goddard Space Flight Center with the Martin Marietta Corporation, Astro-Space Division serving as the prime contractor. Overall programmatic direction was provided by NASA Headquarters, Office of Space Science. The spacecraft will be launched under a launch service contract with the McDonnell Douglas Corporation on a Delta II Expendable Launch Vehicle (ELV) within a November l-l4, 1994 launch window. The Wind spacecraft carries six U.S. instruments, one French instrument, and the first Russian instrument ever to fly on an American satellite. The Wind and Polar missions are the two components of the GGS Program. Wind is also the second mission of the International Solar Terrestrial Physics (ISTP) Program. The first ISTP mission, Geotail, is a joint project of the Institute of Space and Astronautical Science of Japan and NASA which launched in 1992. The Wind mission is planned to overlap Geotail by six months and Polar by one year

  7. Predictors of 30-day mortality in patients admitted to ED for acute heart failure.

    PubMed

    Marchetti, Matthieu; Benedetti, Antoine; Mimoz, Olivier; Lardeur, Jean-Yves; Guenezan, Jérémy; Marjanovic, Nicolas

    2017-03-01

    Acute heart failure (AHF) is a leading cause of admission in emergency departments (ED). It is associated with significant in-hospital mortality, suggesting that there is room for improvement of care. Our aims were to investigate clinical patterns, biological characteristics and determinants of 30-day mortality. We conducted a single site, retrospective review of adult patients (≥18years) admitted to ED for AHF over a 12-month period. Data collected included demographics, clinical, biological and outcomes data. Epidemiologic data were collected at baseline, and patients were followed up during a 30-day period. There were a total of 322 patients. Mean age was 83.9±9.1years, and 47% of the patients were men. Among them, 59 patients (18.3%) died within 30days of admission to the ED. The following three characteristics were associated with increased mortality: age>85years (OR=1.5[95%CI:0.8-2.7], p=0.01), creatinine clearance <30mL/min (OR=2.6[95%CI:1.4-5], p<0.001) and Nt-proBNP >5000pg/mL (OR=2.2[95%CI:1.2-4], p<0.001). The best Nt-proBNP cut-off value to predict first-day mortality was 9000pg/mL (area under the curve (AUC) [95%CI] of 0.790 [0.634-0.935], p<0.001). For 7-day mortality, it was 7900pg/mL (0.698 [0.578-0.819], p<0.001) and for 30-day mortality, 5000pg/mL (0.667 [0.576-0.758], p<0.001). Nt-proBNP level on admission, age and creatinine clearance, are predictive of 30-day mortality in adult patients admitted to ED for AHF. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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

  9. 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

  10. 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…

  11. [Stress among nurses: an examination of salivary cortisol levels on work and day off].

    PubMed

    Pires da Rocha, Maria Cecília; Figueiredo de Martino, Milva Maria; Grassi-Kassisse, Dora Maria; Luiz de Souza, Aglécio

    2013-10-01

    The present study evaluates the use of salivary cortisol concentration as a physiological index of the stress level among nurses on their work day and day off and correlates it with the questionnaire used to measure occupational stress in nurses (Inventário de Estresse em Enfermeiros - IEE). This is a comparative, cross-sectional descriptive study in which sociodemographic data, IEE results and salivary cortisol levels were used. Fifty-seven nurses participated in the study (80.7% females and a mean age of 37.1 years old). The IEE average score was 124.5. The average cortisol level was 564.1 ng/m on work day and 354.1 ng/mL on day off. Nurses who had double workdays presented high values of salivary cortisol during the work day (638.1 ng/mL). In conclusion, salivary cortisol identified the nurses' stress level, and differences were found between a work day and day off. On the nurses' day off, their salivary cortisol levels and stress scores were lower.

  12. 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…

  13. SKYLAB IV - PRELAUNCH (KSC)

    NASA Image and Video Library

    1973-11-16

    S73-36905 (8 Nov. 1973) --- Astronaut William R. Pogue, pilot of the Skylab 4 mission, relaxes during spacesuit pressure and fit checks at the Kennedy Space Center, Florida. This shoulder and head shot of Pogue was taken a few days before the scheduled Skylab 4 launch. This third and last visit to the Skylab space station in Earth orbit will return additional information on the Earth and sun, as well as provide favorable location from which to observe the recently discovered Comet Kohoutek. The other two members of the Skylab 4 crew will be astronaut Gerald P. Carr, commander; and scientist-astronaut Edward G. Gibson, science pilot. Photo credit: NASA

  14. SKYLAB IV - PRELAUNCH (KSC)

    NASA Image and Video Library

    1973-11-16

    S73-36908 (8 Nov. 1973) --- Astronaut Gerald P. Carr, commander of the Skylab 4 mission, undergoes spacesuit pressure and fit checks at the Kennedy Space Center, Florida. This shoulder and head shot of Carr was taken a few days before the scheduled Skylab 4 launch. This third and last visit to the Skylab space station in Earth orbit will return additional information on the Earth and sun, as well as provide a favorable location from which to observe the recently discovered Comet Kohoutek. The other two members of the Skylab 4 crew will be astronaut William R. Pogue, pilot; and scientist-astronaut Edward G. Gibson, science pilot. Photo credit: NASA

  15. 2011 Earth Day

    NASA Image and Video Library

    2011-04-21

    Pat Drackett of the Crosby Arboretum in Picayune (l) speaks with Helen Robinson and Arlene Brown, both employees of the Naval Oceanographic Office at Stennis Space Center, during Earth Day 2011 activities April 21. During the day, Stennis employees were able to visit various exhibits featuring environmentally friendly and energy-conscious items and information. The activities were coordinated by the Stennis Environmental Office.

  16. 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

  17. RNA interference of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO1 and ACO2) genes expression prolongs the shelf life of Eksotika (Carica papaya L.) papaya fruit.

    PubMed

    Sekeli, Rogayah; Abdullah, Janna Ong; Namasivayam, Parameswari; Muda, Pauziah; Abu Bakar, Umi Kalsom; Yeong, Wee Chien; Pillai, Vilasini

    2014-06-19

    The purpose of this study was to evaluate the effectiveness of using RNA interference in down regulating the expression of 1-aminocyclopropane-1-carboxylic acid oxidase gene in Eksotika papaya. One-month old embryogenic calli were separately transformed with Agrobacterium strain LBA 4404 harbouring the three different RNAi pOpOff2 constructs bearing the 1-aminocyclopropane-1-carboxylic acid oxidase gene. A total of 176 putative transformed lines were produced from 15,000 calli transformed, selected, then regenerated on medium supplemented with kanamycin. Integration and expression of the targeted gene in putatively transformed lines were verified by PCR and real-time RT-PCR. Confined field evaluation of a total of 31 putative transgenic lines planted showed a knockdown expression of the targeted ACO1 and ACO2 genes in 13 lines, which required more than 8 days to achieve the full yellow colour (Index 6). Fruits harvested from lines pRNAiACO2 L2-9 and pRNAiACO1 L2 exhibited about 20 and 14 days extended post-harvest shelf life to reach Index 6, respectively. The total soluble solids contents of the fruits ranged from 11 to 14° Brix, a range similar to fruits from non-transformed, wild type seed-derived plants.

  18. 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

  19. Safety of sucrose esters from Physalis peruviana L. in a 28-day repeated-dose study in mice.

    PubMed

    Ocampo, Yanet C; Caro, Daneiva C; Rivera, David E; Franco, Luis A

    2017-06-01

    Although extracts and consumed foods from Physalis species contain sucrose esters from their glandular trichomes, there is no experimental data available on their toxicological effects. As peruvioses A and B isolated from Physalis peruviana L. calyces have proved to be effective anti-inflammatory and immunomodulatory compounds, this work aimed to investigate their sub-acute toxicity study and genotoxicity. For this, CD-1(ICR) mice were treated intraperitoneally with peruvioses at doses of 2.5, 5, and 10mg/kg/day for 28 consecutive days, to simulate therapeutic and over-therapeutic dosage levels. At the end of the treatment, animals were sacrificed and their organs weighted, and blood and tissue samples were collected. Toxicological endpoints included clinical signs; food consumption; body and organ weights; hematological and biochemical parameters; as well as macroscopic and microscopic examination of tissues. The results showed no significant differences between treated animals and control group at macroscopic, histological, molecular, and biochemical levels. In addition, a combination of mammalian erythrocyte micronucleus test, comet assay in peripheral blood cells, and Ames test, did not reveal genotoxic effects induced by peruvioses. Taken together, our data suggests that peruvioses A and B can be safely employed to treat inflammatory diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Mcl-1 and Bcl-xL Cooperatively Maintain Integrity of Hepatocytes in Developing and Adult Murine Liver

    PubMed Central

    Hikita, Hayato; Takehara, Tetsuo; Shimizu, Satoshi; Kodama, Takahiro; Li, Wei; Miyagi, Takuya; Hosui, Atsushi; Ishida, Hisashi; Ohkawa, Kazuyoshi; Kanto, Tatsuya; Hiramatsu, Naoki; Yin, Xiao-Ming; Hennighausen, Lothar; Tatsumi, Tomohide; Hayashi, Norio

    2013-01-01

    Anti-apoptotic members of the Bcl-2 family, including Bcl-2, Bcl-xL, Mcl-1, Bcl-w and Bfl-1, inhibit the mitochondrial pathway of apoptosis. Bcl-xL and Mcl-1 are constitutively expressed in the liver. Although previous research established Bcl-xL as a critical apoptosis antagonist in differentiated hepatocytes, the significance of Mcl-1 in the liver, especially in conjunction with Bcl-xL, has not been clear. To examine this question, we generated hepatocyte-specific Mcl-1– deficient mice by crossing mcl-1flox/flox mice and AlbCre mice and further crossed them with bcl-xflox/flox mice, giving Mcl-1/Bcl-xL– deficient mice. The mcl-1flox/flox AlbCre mice showed spontaneous apoptosis of hepatocytes after birth, as evidenced by elevated levels of serum alanine aminotransferase (ALT) and caspase-3/7 activity and an increased number of terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL)-positive cells in the liver; these phenotypes were very close to those previously found in hepatocyte-specific Bcl-xL– deficient mice. Although mcl-1flox/+ AlbCre mice did not display apoptosis, their susceptibility to Fas-mediated liver injury significantly increased. Further crossing of Mcl-1 mice with Bcl-xL mice showed that bcl-xflox/+ mcl-1flox/+ AlbCre mice also showed spontaneous hepatocyte apoptosis similar to Bcl-xL– deficient or Mcl-1– deficient mice. In contrast, bcl-xflox/flox mcl-1flox/+ AlbCre, bcl-xflox/+ mcl-1flox/flox AlbCre, and bcl-xflox/flox mcl-1flox/flox AlbCre mice displayed a decreased number of hepatocytes and a reduced volume of the liver on day 18.5 of embryogenesis and rapidly died within 1 day after birth, developing hepatic failure evidenced by increased levels of blood ammonia and bilirubin. Conclusion: Mcl-1 is critical for blocking apoptosis in adult liver and, in the absence of Bcl-xL, is essential for normal liver development. Mcl-1 and Bcl-xL are two major anti-apoptotic Bcl-2 family

  1. CHOLINE PARTIALLY PREVENTS THE IMPACT OF ETHANOL ON THE LIPID RAFT DEPENDENT FUNCTIONS OF L1 CELL ADHESION MOLECULE

    PubMed Central

    Tang, Ningfeng; Bamford, Penny; Jones, Jace; He, Min; Kane, Maureen A.; Mooney, Sandra M.; Bearer, Cynthia F.

    2014-01-01

    Background Fetal Alcohol Spectrum Disorder, the leading known cause of mental retardation, is caused by alcohol exposure during pregnancy. One mechanism of ethanol teratogenicity is the disruption of the function of L1 cell adhesion molecule (L1). These functions include enhancement of neurite outgrowth, trafficking through lipid rafts, and signal transduction. Recent data have shown that choline supplementation of rat pups reduces the effects of ethanol on neurobehavior. We sought to determine if choline could prevent the effect of ethanol on L1 function using a simple experimental system. Methods Cerebellar granule neurons (CGN) from postnatal day 6 rat pups were cultured with and without supplemental choline, and the effects on L1 signaling, lipid raft distribution and neurite outgrowth were measured in the presence or absence of ethanol. Results Choline significantly reduced the effect of ethanol on L1 signaling, the distribution of L1 in lipid rafts and L1 mediated neurite outgrowth. However, choline supplemented ethanol exposed cultures remained significantly different than controls. Conclusions Choline pretreatment of CGN significantly reduces the disruption of L1 function by ethanol, but does not completely return L1 function to baseline. This experimental system will enable discovery of the mechanism of the neuroprotective effect of choline. PMID:25421509

  2. Fluorescence lifetime imaging of lipids during 3T3-L1 cell differentiation

    NASA Astrophysics Data System (ADS)

    Song, Young Sik; Won, Young Jae; Lee, Sang-Hak; Kim, Dug Young

    2014-03-01

    Obesity is becoming a big health problem in these days. Since increased body weight is due to increased number and size of the triglyceride-storing adipocytes, many researchers are working on differentiation conditions and processes of adipocytes. Adipocytes also work as regulators of whole-body energy homeostasis by secreting several proteins that regulate processes as diverse as haemostasis, blood pressure, immune function, angiogenesis and energy balance. 3T3-L1 cells are widely used cell line for studying adipogenesis because it can differentiate into an adipocyte-like phenotype under appropriate conditions. In this paper, we propose an effective fluorescence lifetime imaging technique which can easily distinguish lipids in membrane and those in lipid droplets. Nile red dyes are attached to lipids in 3T3-L1 cells. Fluorescence lifetime images were taken for 2 week during differentiation procedure of 3T3-L1 cells into adipocytes. We used 488 nm pulsed laser with 5MHz repetition rate and emission wavelength is 520 nm of Nile Red fluorescent dye. Results clearly show that the lifetime of Nile red in lipid droplets are smaller than those in cell membrane. Our results suggest that fluorescence lifetime imaging can be a very powerful tool to monitor lipid droplet formation in adipocytes from 3T3-L1 cells.

  3. 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

  4. 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

  5. jsc2017e136939 - At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, the Expedition 54-55 backup crewmembers take a stroll down the Walk of Cosmonauts Dec. 6 to lay flowers in traditional pre-launch ceremonies. From left to right are Jeanette Epp

    NASA Image and Video Library

    2017-12-06

    jsc2017e136939 - At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, the Expedition 54-55 backup crewmembers take a stroll down the Walk of Cosmonauts Dec. 6 to lay flowers in traditional pre-launch ceremonies. From left to right are Jeanette Epp

  6. Expedition 34 Prelaunch photo

    NASA Image and Video Library

    2012-11-27

    At the Gagarin Cosmonaut Training Center in Star City, Russia, Expedition 34/35 backup crewmember Karen Nyberg of NASA looks on during a round of questions from reporters Nov. 27, 2012 and she and her crewmates, Luca Parmitano of the European Space Agency and Soyuz Commander Fyodor Yurchikhin participated in the first of two days of certification exams. The trio was joined by prime crew members Tom Marshburn of NASA, cosmonaut Roman Romanenko and Chris Hadfield of the Canadian Space Agency, who are preparing for launch Dec. 19 from the Baikonur Cosmodrome in Kazakhstan in their Soyuz TMA-07M spacecraft for 5 ½ months on the International Space Station. NASA/Stephanie Stoll

  7. Expedition 34 Prelaunch photo

    NASA Image and Video Library

    2012-11-27

    At the Gagarin Cosmonaut Training Center in Star City, Russia, the Expedition 34/35 backup crewmembers pose for pictures in front of a Soyuz spacecraft mockup Nov. 27, 2012 at the start of two days of certification exams. NASA Flight Engineer Karen Nyberg (left), Soyuz Commander Fyodor Yurchikhin (center) and Flight Engineer Luca Parmitano of the European Space Agency (right) were joined by prime crew members Tom Marshburn of NASA, cosmonaut Roman Romanenko and Chris Hadfield of the Canadian Space Agency, who are preparing for launch Dec. 19 from the Baikonur Cosmodrome in Kazakhstan in their Soyuz TMA-07M spacecraft for 5 ½ months on the International Space Station. NASA/Stephanie Stoll

  8. 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.

  9. 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…

  10. 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).

  11. Nonintrusive techniques of inspections during the pre-launch phase of space vehicle

    NASA Astrophysics Data System (ADS)

    Thirumalainambi, Rajkumar; Bardina, Jorge E.; Miyazawa, Osamu

    2005-05-01

    As missions expand to a sustainable presence in the Moon, and extend for durations longer than one year in lunar outpost, the effectiveness of the instrumentation and hardware has to be revolutionized if NASA is to meet high levels of mission safety, reliability, and overall success. This paper addresses a method of non-intrusive local inspection of surface and sub-surface conditions, interfaces, laminations and seals in both space vehicle and ground operations with an integrated suite of imaging sensors during pre-launch operations. It employs an advanced Raman spectrometer with additional spectrometers and lidar mounted on a flying robot to constantly monitor the space hardware as well as inner surface of the vehicle and ground operations hardware. A team of micro flying robots with necessary sensors and photometers is required to internally and externally monitor the entire space vehicle. The micro flying robots should reach an altitude with least amount of energy, where astronauts have difficulty in reaching and monitoring the materials and subsurface faults. The micro flying robots have an embedded fault detection system which acts as an advisory system and in many cases micro flying robots act as a `Supervisor' to fix the problems. The micro flying robot uses contra-rotating propellers powered by an ultra-thin, ultrasonic motor with currently the world's highest power weight ratio, and is balanced in mid-air by means of the world's first stabilizing mechanism using a linear actuator. The essence of micromechatronics has been brought together in high-density mounting technology to minimize the size and weight. Each robot can take suitable payloads of photometers, embedded chips for image analysis and micro pumps for sealing cracks or fixing other material problems. This paper also highlights advantages that this type of non-intrusive techniques offer over costly and monolithic traditional techniques.

  12. 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.

  13. Caenorhabditis elegans Battling Starvation Stress: Low Levels of Ethanol Prolong Lifespan in L1 Larvae

    PubMed Central

    Castro, Paola V.; Khare, Shilpi; Young, Brian D.; Clarke, Steven G.

    2012-01-01

    The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%); higher concentrations to 68 mM (0.4%) did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response. PMID:22279556

  14. 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.

  15. Efficacy of Myrtus communis L. and Descurainia sophia L. Versus Salicylic Acid for Wart Treatment.

    PubMed

    Ghadami Yazdi, Elham; Minaei, Mohamad Bagher; Hashem Dabaghian, Fataneh; Ebrahim Zadeh Ardakani, Mohamad; Ranjbar, Ali Mohammad; Rastegari, Mohamad; Ghadami Yazdi, Ali

    2014-10-01

    Wart is a skin disease with circular appendages, which is called "suloul" in Iranian traditional medicine (ITM). According to ITM literature, warts have different types and causes. The most important mechanism is excretion of materials (Khelt) from body to skin and mucus; its causative material is often phlegm, black bile or a combination of them. To treat warts, it is necessary to consider the patient's life style, modify his dietary intake and moisturize his temperament. This study aimed to compare Myrtus communis L. and Descurainia sophia L. as a method of ITM, versus salicylic acid in treatment of wart. In this study, conducted in Yazd, Iran, 100 patients were selected and randomly divided into four groups. Group 1) salicylic acid, group 2) salicylic acid and D. sophia L. group 3) M. communis L. group 4) M. communis L. and D. sophia L. Numbers, sizes of lesions and symptoms, on days 0, 20, 40 and 90 were examined and analyzed. The relapse rate was investigated three months after. Changes of sizes and numbers of warts in each period of time in each group, compared to baseline, were assessed by Wilcoxon Signed Rank test. To compare these changes between the groups, Kruskal Wallis test was used. In this study 100 patients participated, 69% of which were female. Compared to baseline, mean ± SD of changes for the number of warts in day 40 were 1.12 ± 4.2, 0.96 ± 2.5, 1.32 ± 5.1 and 0.04 ± 0.2 respectively in the four groups (P = 0.02). Mean ± SD of changes for the number of warts in day 90 were 1.84 ± 4.5, 1.56 ± 2.8, 1.24 ± 5.1 and 0.04 ± 0.6 respectively in the four groups (P = 0.03). In addition mean ± SD of changes for the size of warts in day 40 were 0.96 ± 1.8, 1.03 ± 2.4, 2.47 ± 3.0 and 0.45 ± 1.7 respectively in the four groups (P < 0.001). Mean ± SD of changes for the size of warts in day 90 were 1.24 ± 2.1, 1.3 ± 2.3, 2.45 ± 3.1 and 0.45 ± 1.7 respectively in the four groups (P < 0.001). Relapse was not seen in any groups after three

  16. 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…

  17. 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.…

  18. 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

  19. 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

  20. 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…

  1. 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.

  2. Node 1 and PMA-1 are moved for weight and center of gravity determination

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Node 1, the first U.S. element for the International Space Station, and Pressurized Mating Adapter-1 (PMA-1) continue with prelaunch preparation activities at KSC's Space Station Processing Facility. Node 1 is a connecting passageway to the living and working areas of the space station. The node and PMA-1 are being moved to an element rotation stand, or test stand, where they will undergo an interim weight and center of gravity determination. The final determination is planned to be performed prior to transporting Node 1 to the launch pad. Node 1 is scheduled to fly on STS-88.

  3. A Novel Regulatory Function of Sweet Taste-Sensing Receptor in Adipogenic Differentiation of 3T3-L1 Cells

    PubMed Central

    Masubuchi, Yosuke; Nakagawa, Yuko; Ma, Jinhui; Sasaki, Tsutomu; Kitamura, Tadahiro; Yamamoto, Yoritsuna; Kurose, Hitoshi; Kojima, Itaru; Shibata, Hiroshi

    2013-01-01

    Background Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells. Methodology/Principal Findings In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6). The α subunits of Gs (Gαs) and G14 (Gα14) but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects. Conclusions 3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism. PMID:23336004

  4. Persistence behavior of imidacloprid and carbosulfan in mango (Mangifera indica L.).

    PubMed

    Bhattacherjee, A K

    2013-02-01

    Imidacloprid was sprayed on mango cv. Dashehari at 0.3 mL L(-1) of water during pre-bloom stage with 6-8 cm panicle size (first week of March) to control hopper and carbosulfan was sprayed at 2.0 mL L(-1) of water in the trees of mango hybrid (H-1000) during fruit development stage (first week of May) to control leaf webber. Residues of both the insecticides were analysed in peel, pulp and fruit at different stages of fruit development and maturity. The initial residues of imidacloprid, after 30 days of spraying, were 1.21, 0.56 and 1.77 mg kg(-1) in peel, pulp and whole fruit, respectively. The residues persisted in peel for 60 days and in pulp for 50 days and dissipated with a half-life of 38 days. Mature Dashehari fruits at harvest (after 85 days of spraying) were free from imidacloprid residues. Carbosulfan in mango peel dissipated from 5.30 mg kg(-1) (after 1 h of spraying) to 0.05 mg kg(-1) at the time of harvest (after 45 days of spraying). Carbosulfan residue in pulp was very low (0.08 mg kg(-1)) after 1 h of spraying, which increased gradually to 0.90 mg kg(-1) after 10 days and finally came down to 0.04 mg kg(-1) after 26 days of spraying. The insecticide residue was not detected in the pulp at the time of harvest. The residues persisted in pulp for 26 days and in peel for 45 days and degraded with a half-life of 7 days. The dissipation of both imidacloprid and carbosulfan followed first order rate kinetics in whole fruit (peel + pulp). Therefore, the safe pre-harvest intervals were suggested to be 55 days for imidacloprid and 46 days for carbosulfan before consumption of mango fruits after spraying of these insecticides.

  5. Choline partially prevents the impact of ethanol on the lipid raft dependent functions of l1 cell adhesion molecule.

    PubMed

    Tang, Ningfeng; Bamford, Penny; Jones, Jace; He, Min; Kane, Maureen A; Mooney, Sandra M; Bearer, Cynthia F

    2014-11-01

    Fetal alcohol spectrum disorder, the leading known cause of mental retardation, is caused by alcohol exposure during pregnancy. One mechanism of ethanol (EtOH) teratogenicity is the disruption of the functions of L1 cell adhesion molecule (L1). These functions include enhancement of neurite outgrowth, trafficking through lipid rafts, and signal transduction. Recent data have shown that choline supplementation of rat pups reduces the effects of EtOH on neurobehavior. We sought to determine whether choline could prevent the effect of EtOH on L1 function using a simple experimental system. Cerebellar granule neurons (CGN) from postnatal day 6 rat pups were cultured with and without supplemental choline, and the effects on L1 signaling, lipid raft distribution, and neurite outgrowth were measured in the presence or absence of EtOH. Choline significantly reduced the effect of EtOH on L1 signaling, the distribution of L1 in lipid rafts and L1-mediated neurite outgrowth. However, choline supplemented EtOH-exposed cultures remained significantly different than controls. Choline pretreatment of CGN significantly reduces the disruption of L1 function by EtOH, but does not completely return L1 function to baseline. This experimental system will enable discovery of the mechanism of the neuroprotective effect of choline. Copyright © 2014 by the Research Society on Alcoholism.

  6. Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial.

    PubMed

    Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Thabit, Hood; Stewart, Zoë; Cheng, Peiyao; Kollman, Craig; Acerini, Carlo L; Dunger, David B; Hovorka, Roman

    2016-07-01

    To evaluate feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions without remote monitoring or supervision. In an open-label, randomized, free-living, crossover study design, 12 adolescents receiving insulin pump therapy (mean [±SD] age 15.4 ± 2.6 years; HbA1c 8.3 ± 0.9%; duration of diabetes 8.2 ± 3.4 years) underwent two 7-day periods of sensor-augmented insulin pump therapy or hybrid closed-loop insulin delivery without supervision or remote monitoring. During the closed-loop insulin delivery, a model predictive algorithm automatically directed insulin delivery between meals and overnight; prandial boluses were administered by participants using a bolus calculator. The proportion of time when the sensor glucose level was in the target range (3.9-10 mmol/L) was increased during closed-loop insulin delivery compared with sensor-augmented pump therapy (72 vs. 53%, P < 0.001; primary end point), the mean glucose concentration was lowered (8.7 vs. 10.1 mmol/L, P = 0.028), and the time spent above the target level was reduced (P = 0.005) without changing the total daily insulin amount (P = 0.55). The time spent in the hypoglycemic range was low and comparable between interventions. Unsupervised day-and-night hybrid closed-loop insulin delivery at home is feasible and safe in young people with type 1 diabetes. Compared with sensor-augmented insulin pump therapy, closed-loop insulin delivery may improve glucose control without increasing the risk of hypoglycemia in adolescents with suboptimally controlled type 1 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. 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.

  8. 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.

  9. Which is the better timing between embolization and surgery for hypervascular spinal tumors, the same day or the next day?: A retrospective comparative study.

    PubMed

    Tang, Benqiang; Ji, Tao; Guo, Wei; Tang, Xiaodong; Jin, Long; Dong, Sen; Xie, Lu

    2018-06-01

    Previous series presented the timing between embolization and surgery in a wide range on the basis of their experience rather than supportive data. And comparative studies were limited to small samples. In addition, there is no study publishing the timing by considering both safety and efficacy of embolization. The aim of this study was to determine the better timing (the same day or the next day) between embolization and surgery for hypervascular spinal tumors by assessing the safety and efficacy of embolization.One hundred twenty-five embolizations with subsequent 120 operations for hypervascular spinal tumors between January 2010 and April 2013 were retrospectively reviewed. The time between embolization and surgery was mainly determined by interventional radiologist schedules and operating room available. Major complications of embolization were documented. The efficacy of embolization was compared between the same day and the next day group.Of the 125 embolizations, there were 4 major complications, all of which occurred on the same day of procedure. Of the 120 operations, 36 cases were operated on the same day of embolization, 74 on the next day, and 10 on the second day. When comparing the efficacy of embolization between the same day and the next day group, intraoperative blood loss (1483 ± 1475 vs 1548 ± 1099 mL, P = .80), intraoperative transfusion requirement (1011 ± 1200 vs 1112 ± 890 mL, P = .62), and postoperative blood loss (1146 ± 933 vs 1031 ± 777 mL, P = .50) were not significantly different.Embolization carries certain risks (4/125, 3.2%) for major complications, which may occur within the time window of 1 day. Two patient groups showed no difference on the efficacy of embolization. Operation should be scheduled on the next day of embolization if possible.

  10. 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…

  11. 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.

  12. 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…

  13. [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.

  14. 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…

  15. 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…

  16. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

    PubMed

    Brahmer, Julie R; Tykodi, Scott S; Chow, Laura Q M; Hwu, Wen-Jen; Topalian, Suzanne L; Hwu, Patrick; Drake, Charles G; Camacho, Luis H; Kauh, John; Odunsi, Kunle; Pitot, Henry C; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M; Alaparthy, Suresh; Grosso, Joseph F; Korman, Alan J; Parker, Susan M; Agrawal, Shruti; Goldberg, Stacie M; Pardoll, Drew M; Gupta, Ashok; Wigginton, Jon M

    2012-06-28

    Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).

  17. Continuous Glucose Monitoring During Basal-Bolus Therapy Using Insulin Glargine 300 U mL(-1) and Glargine 100 U mL (-1) in Japanese People with Type 1 Diabetes Mellitus: A Crossover Pilot Study.

    PubMed

    Jinnouchi, Hideaki; Koyama, Masayoshi; Amano, Atsushi; Takahashi, Yoshinori; Yoshida, Akira; Hieshima, Kunio; Sugiyama, Seigo; Kurinami, Noboru; Jinnouchi, Tomio; Becker, Reinhard

    2015-06-01

    New insulin glargine 300 U mL(-1) (Gla-300) is a basal insulin that shows more stable and prolonged pharmacokinetic and pharmacodynamic profiles than insulin glargine 100 U mL(-1) (Gla-100). This study used continuous glucose monitoring (CGM) to compare 24-h glucose profiles in a Japanese population using Gla-300 versus Gla-100. This was an exploratory 8.4-week, single-center, 2-sequence, 2-period, open-label crossover study. Japanese adults with type 1 diabetes mellitus (T1DM) treated with basal-bolus insulin, with glycated hemoglobin (HbA1c) 6.5-10.0% and median fasting self-monitored plasma glucose concentration ≤13 mmol L(-1), were randomized to Gla-300 followed by Gla-100 (subgroup 1) or vice versa (subgroup 2), with no washout period. CGM was performed on the last 3 days of the screening period and each treatment period. Primary endpoint was comparison of 24-h glucose variability (area under the curve [AUC]mean_24 h) on the second day of each CGM measurement with Gla-300 versus Gla-100. Baseline and end of treatment period values for HbA1c, fasting plasma glucose (FPG) and daily basal/mealtime insulin doses were recorded. Hypoglycemia and adverse events (AEs) were recorded. Twenty participants were randomized (10 to subgroup 1 and 10 to subgroup 2). Participants showed comparable glucose variability over 24 h (AUCmean_24 h during treatment with Gla-300 or Gla-100 (treatment ratio 0.96; 90% confidence interval 0.79, 1.16). HbA1c and FPG were generally stable across both treatment periods. There was a trend towards fewer participants experiencing ≥1 hypoglycemia event at any time (24 h) and at night (00:00-05:59 h) with Gla-300 versus Gla-100. Treatment-emergent AEs, reported by 9/20 (45%) and 4/20 (20%) participants during Gla-300 and Gla-100 treatment, respectively, were unrelated to study medication. In this cohort of Japanese people with T1DM, no between-treatment difference was observed in glucose variability with Gla-300 versus Gla-100, as

  18. Effects of prescribing 1,000 versus 1,500 kilocalories per day in the behavioral treatment of obesity: a randomized trial.

    PubMed

    Nackers, Lisa M; Middleton, Kathryn R; Dubyak, Pamela J; Daniels, Michael J; Anton, Stephen D; Perri, Michael G

    2013-12-01

    Controversy exists regarding the optimal energy prescription to promote successful long-term behavioral management of obesity. Prescribing intake of 1,000 (vs. 1,500) kcal/day may produce larger initial weight reduction, but long-term advantage remains unclear. The effects of prescribing 1,000 versus 1,500 kcal/day on 6- and 12-month weight changes within behavioral treatment of obesity were examined. Participants were 125 obese women (mean ± SD; BMI = 37.84 ± 3.94 kg/m(2) ) randomly assigned goals of 1,000 or 1,500 kcal/day. From months 0 to 6, participants prescribed 1,000 kcal/day lost more weight than those prescribed 1,500 kcal/day (mean ± SE = -10.03 ± 0.92g vs. -6.23 ± 0.94 kg, P = 0.045); however, from months 7 through 12, only the 1,000 kcal/day condition experienced a significant weight regain (1.51 ± 0.77 kg, P = 0.025). Baseline caloric consumption moderated the effect of treatment on regain; participants with baseline intakes ≧2,000 kcal/day who were assigned 1,000 kcal/day were significantly more susceptible to weight regain than those assigned 1,500 kcal/day (P = 0.049). At month 12, a significantly greater percentage of 1,000 kcal/day participants achieved weight reductions of 5% or more than those prescribed 1,500 kcal/day. Encouraging obese individuals in behavioral treatment to adhere to a 1,000 kcal/day intake may increase their likelihood of achieving clinically meaningful weight losses. Copyright © 2013 The Obesity Society.

  19. Hydroxyframoside B, a secoiridoid of Fraxinus rhynchophylla, inhibits adipocyte differentiation in 3T3-L1 cells.

    PubMed

    Choi, Kyeong-Mi; Shin, Eunjin; Liu, Qing; Yoo, Hwan-Soo; Kim, Young Choong; Sung, Sang Hyun; Hwang, Bang Yeon; Lee, Mi Kyeong

    2011-07-01

    Fraxinus rhynchophylla showed significant inhibitory activity on adipocyte differentiation in the 3T3-L1 preadipocyte cell line as assessed by measuring fat accumulation using Oil Red O staining. Further fractionation led to the isolation of two secoiridoids, oleuropein and hydroxyframoside B. Hydroxyframoside B significantly reduced fat accumulation and triglyceride content in differentiated 3T3-L1 cells without affecting cell viability, whereas oleuropein showed little effect. Further studies with interval treatment demonstrated that hydroxyframoside B exerted inhibitory activity on adipocyte differentiation when treated within 2 days (days 0-2) after differentiation induction. In addition, hydroxyframoside B significantly blocked the induction of adipogenic transcription factors such as C/EBP α, C/EBP β, and PPAR γ. Taken together, these results suggest that hydroxyframoside B inhibited early/middle stage of adipogenic differentiation, in part, via inhibition of C/EBP α, C/EBP β, and PPAR γ-dependent pathways. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Magnetospheric electron density long-term (>1 day) refilling rates inferred from passive radio emissions measured by IMAGE RPI during geomagnetically quiet times

    NASA Astrophysics Data System (ADS)

    Denton, R. E.; Wang, Y.; Webb, P. A.; Tengdin, P. M.; Goldstein, J.; Redfern, J. A.; Reinisch, B. W.

    2012-03-01

    Using measurements of the electron density ne found from passive radio wave observations by the IMAGE spacecraft RPI instrument on consecutive passes through the magnetosphere, we calculate the long-term (>1 day) refilling rate of equatorial electron density dne,eq/dt from L = 2 to 9. Our events did not exhibit saturation, probably because our data set did not include a deep solar minimum and because saturation is an unusual occurrence, especially outside of solar minimum. The median rate in cm-3/day can be modeled with log10(dne,eq/dt) = 2.22 - 0.006L - 0.0347L2, while the third quartile rate can be modeled with log10(dne,eq/dt) = 3.39 - 0.353L, and the mean rate can be modeled as log10(dne,eq/dt) = 2.74 - 0.269L. These statistical values are found from the ensemble of all observed rates at each L value, including negative rates (decreases in density due to azimuthal structure or radial motion or for other reasons), in order to characterize the typical behavior. The first quartile rates are usually negative for L < 4.7 and close to zero for larger L values. Our rates are roughly consistent with previous observations of ion refilling at geostationary orbit. Most previous studies of refilling found larger refilling rates, but many of these examined a single event which may have exhibited unusually rapid refilling. Comparing refilling rates at solar maximum to those at solar minimum, we found that the refilling rate is larger at solar maximum for small L < 4, about the same at solar maximum and solar minimum for L = 4.2 to 5.8, and is larger at solar minimum for large L > 5.8 such as at geostationary orbit (L ˜ 6.8) (at least to L of about 8). These results agree with previous results for ion refilling at geostationary orbit, may agree with previous results at lower L, and are consistent with some trends for ionospheric density.

  1. 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).

  2. STS-111 Mission Highlights Resource Tape. Part 1 of 4; Flight Days 1 - 4

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This video, Part 1 of 4, shows the activities of the STS-111 crew (Kenneth Cockrell, Commander; Paul Lockhart, Pilot; Franklin Chang-Diaz, Phillipe Perrin, Mission Specialists) during flight days 1 through 4. Also shown are the incoming Expedition 5 (Valeri Korzun, Commander; Peggy Whitson, NASA ISS Science Officer; Sergei Treschev, Flight Engineer) and outgoing Expedition 4 (Yuri Onufriyenko, Commander; Carl Walz, Daniel Bursch, Flight Engineers) crews of the ISS (International Space Station). The activities from other flight days can be seen on 'STS-111 Mission Highlights Resource Tape' Part 2 of 4 (internal ID 2002139469), 'STS-111 Mission Highlights Resource Tape' Part 3 of 4 (internal ID 2002139468), and 'STS-111 Mission Highlights Resource Tape' Part 4 of 4 (internal ID 2002139474). The primary activity of flight day 1 is the launch of Space Shuttle Endeavour. The crew is seen before the launch at a meal and suit-up, and some pre-flight procedures are shown. Perrin holds a sign with a personalized message. The astronauts communicate with Mission Control extensively after launch, and an inside view of the shuttle cabin is shown. The replays of the launch include close-ups of the nozzles at liftoff, and the fall of the solid rocket boosters and the external fuel tank. Flight day 2 shows footage of mainland Asia at night, and daytime views of the eastern United States and Lake Michigan. Flight day three shows the Endeavour orbiter approaching and docking with the ISS. After the night docking, the crews exchange greetings, and a view of the Nile river and Egypt at night is shown. On flight day 4, the MPLM (Multi-Purpose Logistics Module) Leonardo was temporarily transferred from Endeavour's payload bay to the ISS.

  3. Growth Recovery of Lemna gibba and Lemna minor Following a 7-Day Exposure to the Herbicide Diuron.

    PubMed

    Burns, Mitchell; Hanson, Mark L; Prosser, Ryan S; Crossan, Angus N; Kennedy, Ivan R

    2015-08-01

    In agricultural catchments, aquatic ecosystems can experience a pulse exposure to pesticides. Following such exposure, non-target organisms that are not extirpated may recover. This paper investigates the potential of two duckweed species (Lemna minor and Lemna gibba) to recover from a 7-day exposure to different concentrations (0.4-208 µg L(-1)) of the herbicide diuron. There was significant inhibition in the growth and biomass after the initial 7-day exposure (e.g. frond number EC50=59.2 and 52.2 µg L(-1) for L. minor and L. gibba, respectively). Following transfer to clean media, recovery (the highest concentration yielding no significant difference in the effect endpoint from the control) was observed for all effects endpoints at concentrations ranging 60-111 µg L(-1) for L. minor and 60-208 µg L(-1) for L. gibba. These results suggest that recovery is possible for primary producers at environmentally relevant concentrations considered significant in ecological risk assessment.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. Flight Set 360L002 (STS-27) field joint protection system, volume 7

    NASA Technical Reports Server (NTRS)

    Hale, Elgie

    1989-01-01

    This report contains the pre-launch functioning data of the Field Joint Protection System (JPS) used on STS-27. Also included is the post flight condition of the JPS components following the launch and recovery of the two redesigned solid rocket motors (RSRM) boosters. The JPS components are: (1) field joint heaters; (2) field joint sensors; (3) field joint moisture seal; (4) moisture seal Kevlar retaining straps; (5) field joint external insulation; (6) vent valve; (7) power cables; and (8) igniter heater.

  9. 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

  10. Expedition 21 Prelaunch Press Conference

    NASA Image and Video Library

    2009-09-28

    Spaceflight Participant Guy Laliberté, left, Expedition 21 Flight Engineer Maxim Suraev, center, and Expedition 21 Flight Engineer Jeffrey N. Williams reveal t-shirts showing their faces superimposed on characters from the Russian movie "White Sun of the Desert" at the end of the press conference, Tuesday, Sept. 29, 2009 at the Cosmonaut Hotel in Baikonur, Kazakhstan. It is tradition for all crews flying on the Soyuz to watch this movie several days before they launch. Photo Credit: (NASA/Bill Ingalls)

  11. Ursolic Acid Inhibits Adipogenesis in 3T3-L1 Adipocytes through LKB1/AMPK Pathway

    PubMed Central

    He, Yonghan; Li, Ying; Zhao, Tiantian; Wang, Yanwen; Sun, Changhao

    2013-01-01

    Background Ursolic acid (UA) is a triterpenoid compound with multiple biological functions. This compound has recently been reported to possess an anti-obesity effect; however, the mechanisms are less understood. Objective As adipogenesis plays a critical role in obesity, the present study was conducted to investigate the effect of UA on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes. Methods and Results The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of UA for 6 days. The cells were determined for proliferation, differentiation, fat accumulation as well as the protein expressions of molecular targets that regulate or are involved in fatty acid synthesis and oxidation. The results demonstrated that ursolic acid at concentrations ranging from 2.5 µM to 10 µM dose-dependently attenuated adipogenesis, accompanied by reduced protein expression of CCAAT element binding protein β (C/EBPβ), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT element binding protein α (C/EBPα) and sterol regulatory element binding protein 1c (SREBP-1c), respectively. Ursolic acid increased the phosphorylation of acetyl-CoA carboxylase (ACC) and protein expression of carnitine palmitoyltransferase 1 (CPT1), but decreased protein expression of fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Ursolic acid increased the phosphorylation of AMP-activated protein kinase (AMPK) and protein expression of (silent mating type information regulation 2, homolog) 1 (Sirt1). Further studies demonstrated that the anti-adipogenic effect of UA was reversed by the AMPK siRNA, but not by the Sirt1 inhibitor nicotinamide. Liver kinase B1 (LKB1), the upstream kinase of AMPK, was upregulated by UA. When LKB1 was silenced with siRNA or the inhibitor radicicol, the effect of UA on AMPK activation was diminished. Conclusions Ursolic acid inhibited 3T3-L1 preadipocyte differentiation and adipogenesis through the LKB1/AMPK pathway

  12. 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.

  13. 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

  14. 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…

  15. 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…

  16. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

    PubMed Central

    Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-01-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells. PMID:24860943

  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. 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...

  19. [Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

    PubMed

    Péter, Ferenc; Muzsnai, Agota

    2013-05-12

    L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

  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. 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.

  2. [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.

  3. 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.

  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. Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells

    PubMed Central

    2013-01-01

    Background The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. Methods To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0–2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Results Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. Conclusions These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway

  9. Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells.

    PubMed

    Gwon, So Young; Ahn, Ji Yun; Jung, Chang Hwa; Moon, Bo Kyung; Ha, Tae Youl

    2013-08-06

    The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0-2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway during the early stages of adipogenesis.

  10. Adenosine A1 receptor antagonist, L-97-1, improves survival and protects the kidney in a rat model of cecal ligation and puncture induced sepsis☆

    PubMed Central

    Wilson, Constance N.; Vance, Constance O.; Lechner, Melissa G.; Matuschak, George M.; Lechner, Andrew J.

    2014-01-01

    Previously it was reported that combining antibiotics with L-97-1, an adenosine A1 receptor antagonist, significantly improves survival and blocks acute lung injury induced by Yersinia pestis CO 99 in a rat model of pneumonic plague. In the current studies using a conscious rat model of cecal ligation and puncture (CLP) sepsis, L-97-1 was administered in daily intravenous infusions in combination with antibiotics to simulate the use of L-97-1 as an anti-sepsis therapeutic in the clinical setting. In these studies, when administered at 12 hours (h) following CLP, in combination with broad spectrum antibiotics, ceftriaxone and clindamycin, L-97-1 improves 7 day (d) survival [25%, 35%, and 75%, respectively for L-97-1 (10 mg/kg/h, 12.5 mg/kg/h, and 15 mg/kg/h) versus (vs.) 25% for antibiotics alone] in a dose-dependent manner. The addition of L-97-1, 15 mg/kg/h to antibiotics significantly increased 7 d survival following CLP compared to therapy with either antibiotics alone (P = 0.002) or L-97-1 at 15 mg/kg/h alone (P < 0.001) and was not significantly different than survival in sham CLP animals (Log-rank (Mantel-Cox) test with Bonferroni’s correction for multiple comparisons). Moreover, in these studies, in combination with antibiotics L-97-1 dose-dependently protects the kidney, significantly improving renal function at 24 h post CLP at 10 mg/kg/h (P < 0.001), 12.5 mg/kg/h (P < 0.0001), and 15 mg/kg/h (P < 0.0001) vs. antibiotics alone (ANOVA followed by Tukey’s post-hoc test for pair-wise comparisons). The results of these studies support efficacy for L-97-1 as an anti-sepsis therapeutic. PMID:25041842

  11. Differential phosphorylation of ribosomal proteins in Arabidopsis thaliana plants during day and night.

    PubMed

    Turkina, Maria V; Klang Årstrand, Hanna; Vener, Alexander V

    2011-01-01

    Protein synthesis in plants is characterized by increase in the translation rates for numerous proteins and central metabolic enzymes during the day phase of the photoperiod. The detailed molecular mechanisms of this diurnal regulation are unknown, while eukaryotic protein translation is mainly controlled at the level of ribosomal initiation complexes, which also involves multiple events of protein phosphorylation. We characterized the extent of protein phosphorylation in cytosolic ribosomes isolated from leaves of the model plant Arabidopsis thaliana harvested during day or night. Proteomic analyses of preparations corresponding to both phases of the photoperiod detected phosphorylation at eight serine residues in the C-termini of six ribosomal proteins: S2-3, S6-1, S6-2, P0-2, P1 and L29-1. This included previously unknown phosphorylation of the 40S ribosomal protein S6 at Ser-231. Relative quantification of the phosphorylated peptides using stable isotope labeling and mass spectrometry revealed a 2.2 times increase in the day/night phosphorylation ratio at this site. Phosphorylation of the S6-1 and S6-2 variants of the same protein at Ser-240 increased by the factors of 4.2 and 1.8, respectively. The 1.6 increase in phosphorylation during the day was also found at Ser-58 of the 60S ribosomal protein L29-1. It is suggested that differential phosphorylation of the ribosomal proteins S6-1, S6-2 and L29-1 may contribute to modulation of the diurnal protein synthesis in plants.

  12. 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.

  13. Effect of Day and Night Desflurane Anaesthesia on Melatonin Levels in Rats.

    PubMed

    Özer, Figen Datlı; Öçmen, Elvan; Akan, Pınar; Erdost, Hale Aksu; Korkut, Sezen; Gökmen, Ali Necati

    2016-08-01

    The aim of this study is to investigate the effect of day and night administration of desflurane anaesthesia on melatonin levels in rats. Twenty-four 15-day-old rats were included in the study and were divided into four groups. The rats were anaesthetised between 19:00-01:00 (night group) and 07:00-13:00 (day group) with 5.7% desflurane concentration in 6 L min -1 100% oxygen. 6 L min -1 oxygen was administered to the control groups. At the end of 6 h of anaesthesia, blood samples were taken, and rats were sacrificed. Blood samples were centrifuged and melatonin levels from plasma samples were measured with radioimmunoassay. There was a statistically significant difference between the groups (p=0.007). Between group day control and group night control there was a statistically significant difference (p=0.042). Further, there was a significant difference between group day control and night desfluran as well (p=0.024). We could not find any difference between other groups. This study showed that 6 hours of 5.7% desflurane anaesthesia during day and night hours did not significantly change melatonin levels.

  14. Non-Intrusive Techniques of Inspections During the Pre-Launch Phase of Space Vehicle

    NASA Technical Reports Server (NTRS)

    Thirumalainambi, Rejkumar; Bardina, Jorge E.

    2005-01-01

    This paper addresses a method of non-intrusive local inspection of surface and sub-surface conditions, interfaces, laminations and seals in both space vehicle and ground operations with an integrated suite of imaging sensors during pre-launch operations. It employs an advanced Raman spectrophotometer with additional spectrophotometers and lidar mounted on a flying robot to constantly monitor the space hardware as well as inner surface of the vehicle and ground operations hardware. This paper addresses a team of micro flying robots with necessary sensors and photometers to monitor the entire space vehicle internally and externally. The micro flying robots can reach altitude with least amount of energy, where astronauts have difficulty in reaching and monitoring the materials and subsurface faults. The micro flying robot has an embedded fault detection system which acts as an advisory system and in many cases micro flying robots act as a Supervisor to fix the problems. As missions expand to a sustainable presence in the Moon, and extend for durations longer than one year in lunar outpost, the effectiveness of the instrumentation and hardware has to be revolutionized if NASA is to meet high levels of mission safety, reliability, and overall success. The micro flying robot uses contra-rotating propellers powered by an ultra-thin, ultrasonic motor with currently the world's highest power weight ratio, and is balanced in mid-air by means of the world's first stabilizing mechanism using a linear actuator. The essence of micromechatronics has been brought together in high-density mounting technology to minimize the size and weight. The robot can take suitable payloads of photometers, embedded chips for image analysis and micro pumps for sealing cracks or fixing other material problems. This paper also highlights advantages that this type of non-intrusive techniques offer over costly and monolithic traditional techniques.

  15. 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

  16. 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

  17. Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles

    NASA Astrophysics Data System (ADS)

    Lu, Xuefeng; Chen, Qiuju; Fu, Yonglun; Ai, Ai; Lyu, Qifeng; Kuang, Yan Ping

    2016-08-01

    To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

  18. 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.

  19. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial.

    PubMed

    Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Thabit, Hood; Acerini, Carlo L; Dunger, David B; Hovorka, Roman

    2016-11-01

    This study evaluated the feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions. In an open-label randomized crossover study, 12 suboptimally controlled adolescents on insulin pump therapy (mean ± SD age 14.6 ± 3.1 years; HbA 1c 69 ± 8 mmol/mol [8.5 ± 0.7%]; duration of diabetes 7.8 ± 3.5 years) underwent two 21-day periods in which hybrid closed-loop insulin delivery was compared with sensor-augmented insulin pump therapy in random order. During the closed-loop intervention, a model predictive algorithm automatically directed insulin delivery between meals and overnight. Participants used a bolus calculator to administer prandial boluses. The proportion of time that sensor glucose was in the target range (3.9-10 mmol/L; primary end point) was increased during the closed-loop intervention compared with sensor-augmented insulin pump therapy by 18.8 ± 9.8 percentage points (mean ± SD; P < 0.001), the mean sensor glucose level was reduced by 1.8 ± 1.3 mmol/L (P = 0.001), and the time spent above target was reduced by 19.3 ± 11.3 percentage points (P < 0.001). The time spent with sensor glucose levels below 3.9 mmol/L was low and comparable between interventions (median difference 0.4 [interquartile range -2.2 to 1.3] percentage points; P = 0.33). Improved glucose control during closed-loop was associated with increased variability of basal insulin delivery (P < 0.001) and an increase in the total daily insulin dose (53.5 [39.5-72.1] vs. 51.5 [37.6-64.3] units/day; P = 0.006). Participants expressed positive attitudes and experience with the closed-loop system. Free-living home use of day-and-night closed-loop in suboptimally controlled adolescents with type 1 diabetes is safe, feasible, and improves glucose control without increasing the risk of hypoglycemia. Larger and longer studies are warranted. © 2016 by the American Diabetes Association.

  20. 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…

  1. 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…

  2. STS-6 sixth Space Shuttle mission. First flight of the Challenger

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A prelaunch summary of the sixth Space Shuttle mission is provided. The Challenger orbiter; launching; uprated engines; lighter weight boosters; lightweight tank; external tank reduction; landing; the tracking and data relay satellite system (TDRSS), TDRS-1 deployment; the inertial upper stage (IUS), the spacewalk;electrophoresis, monodisperse latex reactor, night time/day time optical survey of lightning, and getaway special experiments are described.

  3. 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

  4. 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…

  5. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats

    PubMed Central

    da Rosa, Carlos Vinicius D.; Azevedo, Silvia C. S. F.; Bazotte, Roberto B.; Peralta, Rosane M.; Buttow, Nilza C.; Pedrosa, Maria Montserrat D.; de Godoi, Vilma A. F.; Natali, Maria Raquel M.

    2015-01-01

    We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a

  6. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats.

    PubMed

    da Rosa, Carlos Vinicius D; Azevedo, Silvia C S F; Bazotte, Roberto B; Peralta, Rosane M; Buttow, Nilza C; Pedrosa, Maria Montserrat D; de Godoi, Vilma A F; Natali, Maria Raquel M

    2015-01-01

    We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a

  7. Landsat 8 operational land imager on-orbit geometric calibration and performance

    USGS Publications Warehouse

    Storey, James C.; Choate, Michael J.; Lee, Kenton

    2014-01-01

    The Landsat 8 spacecraft was launched on 11 February 2013 carrying the Operational Land Imager (OLI) payload for moderate resolution imaging in the visible, near infrared (NIR), and short-wave infrared (SWIR) spectral bands. During the 90-day commissioning period following launch, several on-orbit geometric calibration activities were performed to refine the prelaunch calibration parameters. The results of these calibration activities were subsequently used to measure geometric performance characteristics in order to verify the OLI geometric requirements. Three types of geometric calibrations were performed including: (1) updating the OLI-to-spacecraft alignment knowledge; (2) refining the alignment of the sub-images from the multiple OLI sensor chips; and (3) refining the alignment of the OLI spectral bands. The aspects of geometric performance that were measured and verified included: (1) geolocation accuracy with terrain correction, but without ground control (L1Gt); (2) Level 1 product accuracy with terrain correction and ground control (L1T); (3) band-to-band registration accuracy; and (4) multi-temporal image-to-image registration accuracy. Using the results of the on-orbit calibration update, all aspects of geometric performance were shown to meet or exceed system requirements.

  8. The study of immunogenicity of the antigenic protein of high risk oncogenic type of the human papillomavirus HPV16 L1 produced in the plant expression system on the base of transgenic tomato.

    PubMed

    Salyaev, R K; Rekoslavskaya, N I; Stolbikov, A S; Tretyakova, A V

    2017-05-01

    The immunogenicity of plant-made peroral vaccine against cervical cancer was studied in mice during 342 days after vaccination with the material of tomato fruits genetically transformed with HPV16 L1 Ώ 5'UTR TMV. The immune response was found on day 4 after vaccination in blood serum of vaccinated mice. On days 90-100, the rise to maximum value of the level of antibodies to HPV16 L1 was in the range of 500 ng of the standard antibodies to HPV16 L1 (Santa Cruz Biotechnology, United States). This level of antibodies was retained until the end of the study.

  9. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    PubMed Central

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  10. 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

  11. 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 ...

  12. 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

  13. 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.

  14. Simultaneous removal of carbon and nitrogen by mycelial pellets of a heterotrophic nitrifying fungus-Penicillium sp. L1.

    PubMed

    Liu, Yuxiang; Hu, Tingting; Zhao, Jing; Lv, Yongkang; Ren, Ruipeng

    2017-02-01

    A novel heterotrophic nitrifying fungus, defined as Penicillium sp. L1, can form mycelial pellets in liquid medium in this study. The effects of inoculation method, C/N ratio, initial pH, and temperature were gradually evaluated to improve the simultaneous removal of total nitrogen (TN) and chemical oxygen demand (COD) in wastewater by Penicillium sp. L1. Results showed that compared with spore inoculation, 48 h pellet inoculum could significantly increase the pellet size (from about 1.5 mm to 3.2 mm) and improve the removal capability, particularly for COD removal (from less than 50-86.20%). The removal efficiencies of TN and COD reached 98.38% (from 136.01 mg/L to 2.20 mg/L) and 92.40% (from 10,720 mg/L to 815 mg/L) under the following conditions: C/N 36, pH 3, 30°C, and inoculation with 48 h pellets. The pellet diameter reached 4.8 mm after 4-day cultivation. In this case, Penicillium sp. L1 removed TN from 415.93 mg/L to 43.39 mg/L, as well as COD from 29,533 mg/L to 8850 mg/L. Overall, the results indicated that the pellet size was closely related to the pollutant-removal ability of Penicillium sp. L1. Furthermore, mycelial pellets (4.8 mm, dead) only adsorbed 38.08% TN (from 125.45 mg/L to 77.78 mg/L), which indicated that adsorption did not play a major role in the nitrogen-removal process. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  15. 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…

  16. 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...

  17. The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study

    PubMed Central

    Kuffner, EK; Green, JL; Bogdan, GM; Knox, PC; Palmer, RB; Heard, K; Slattery, JT; Dart, RC

    2007-01-01

    Background Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. Methods Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. Results A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 ± 45 IU/L and 55 ± 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. Conclusion Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care. PMID:17537264

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Daily Profiles of Fibrinogen Metabolism for 5 Days Following Hemorrhage and Lactated Ringer’s Resuscitation in Pigs

    DTIC Science & Technology

    2012-01-01

    Sterile stable isotope solutions of 1 13C phenylalanine (1 13C phe, 100 2mol/mL) and d5 phe (100 2mol/mL) were made in 0.45% saline and infused via the left...described by Stein et al. (15). The enrichments of phenylalanine from isolated fibrinogen were determined by gas chromatography mass spectrometry (GC MS...baseline of 5.5 T 0.3 to 4.3 T 0.3 g/ dL (P G 0.05) on day 1 but returned to baseline on day 2 and thereafter. Changes in plasma fibrinogen

  4. 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…

  5. 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.

  6. Syncom 4 deploy, LDEF retrieval highlight 10-day Columbia flight

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The objectives of Space Shuttle Mission STS-32 are described along with major flight activities, prelaunch and launch operations, trajectory sequence of events, and landing and post-landing operations. The primary objectives of STS-32 are the deployment of a Navy synchronous communications satellite (Syncom 4) and the retrieval of the Long Duration Exposure Facility (LDEF) launched from the Challenger in April 1984. Secondary STS-32 payloads include a protein crystal growth experiment, the Fluids Experiment Apparatus (FEA) for the investigation of microgravity materials processing, the Mesoscale Lighting Experiment, the Latitude-Longitude Locator Experiment, the Americal Flight Echocardiograph, and an experiment to investigate neurospora circadian rhythms in a microgravity environment.

  7. 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

  8. 2012 Earth Day

    NASA Image and Video Library

    2012-04-24

    Bonnie Humphrey of NASA (l to r), Van Ward of NASA, Kim Maddox of the Naval Oceanographic Office, and Al Bryden of the NASA Shared Services Center learn about the Crosby Arboretum in Picayune, Miss., during the Earth Day celebration at Stennis Space Center on April 24, 2012.

  9. 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

  10. 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.

  11. 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…

  12. The potential of Lemna gibba L. and Lemna minor L. to remove Cu, Pb, Zn, and As in gallery water in a mining area in Keban, Turkey.

    PubMed

    Sasmaz, Merve; Arslan Topal, Emine Işıl; Obek, Erdal; Sasmaz, Ahmet

    2015-11-01

    This study was designed to investigate removal efficiencies of Cu, Pb, Zn, and As in gallery water in a mining area in Keban, Turkey by Lemna gibba L. and Lemna minor L. These plants were placed in the gallery water of Keban Pb-Zn ore deposits and adapted individually fed to the reactors. During the study period (8 days), the plant and water samples were collected daily and the temperature, pH, and electric conductivity of the gallery water were measured daily. The plants were washed, dried, and burned at 300 °C for 24 h in a drying oven. These ash and water samples were analyzed by ICP-MS to determine the amounts of Cu, Pb, Zn, and As. The Cu, Pb, Zn and As concentrations in the gallery water of the study area detected 67, 7.5, 7230, and 96 μg L(-1), respectively. According to the results, the obtained efficiencies in L. minor L. and L. gibba L. are: 87% at day 2 and 36% at day 3 for Cu; 1259% at day 2 and 1015% at day 2 for Pb; 628% at day 3 and 382% at day 3 for Zn; and 7070% at day 3 and 19,709% at day 2 for As, respectively. The present study revealed that both L. minor L. and L. gibba L. had very high potential to remove Cu, Pb, Zn, and As in gallery water contaminated by different ores. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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.

  15. Clinical efficacy of a 1% Matricaria chamomile L. mouthwash and 0.12% chlorhexidine for gingivitis control in patients undergoing orthodontic treatment with fixed appliances.

    PubMed

    Goes, Paula; Dutra, Caio S; Lisboa, Mário R P; Gondim, Delane V; Leitão, Renata; Brito, Gerly A C; Rego, Rodrigo O

    2016-01-01

    This pilot study evaluated the clinical efficacy of a mouthwash containing 1% Matricaria chamomilla L. (MTC) extract in reducing gingival inflammation and plaque formation in patients undergoing orthodontic treatment with fixed appliances. This randomized, double-blind, placebo-controlled study enrolled a total of 30 males and females (age, 10-40 years) with fixed orthodontic appliances and a minimum of 20 natural teeth. The participants were allocated to three groups (n = 10 each) and asked to rinse with 15 mL of a placebo, 0.12% chlorhexidine (CHX), or 1% MTC mouthwash, immediately after brushing for 1 min, in the morning and evening, for 15 days. Data (mean ± SD) on visible plaque index (VPI) and gingival bleeding index (GBI) were recorded on days 1 and 15. The placebo group exhibited increases in VPI and GBI (10.2% and 23.1%, respectively) from day 1 to day 15. As compared with placebo, VPI and GBI significantly decreased in the MTC group (-25.6% and -29.9%, respectively) and the CHX group (-39.9% and -32.0%, respectively). In summary, MTC reduced biofilm accumulation and gingival bleeding in patients with gingivitis, probably because of its antimicrobial and anti-inflammatory activities.(J Oral Sci 58, 569-574, 2016).

  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. 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.

  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. 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…

  1. 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

  2. MERCURY-ATLAS (MA)-9 - "FRIENDSHIP 7" SPACECRAFT - PRELAUNCH ACTIVITIES - CAPE

    NASA Image and Video Library

    1963-02-01

    S63-03960 (1 Feb. 1963) --- Astronaut L. Gordon Cooper Jr., prime pilot for the Mercury-Atlas 9 (MA-9) mission, checks over the instrument panel from Mercury spacecraft #20 with Robert Graham, McDonnell Aircraft Corp. spacecraft engineer. It contains the instruments necessary to monitor spacecraft systems and sequencing, the controls required to initiate primary sequences manually, and flight control displays. Photo credit: NASA

  3. A 28-Day Repeated Dose Toxicological Study of an Aqueous Extract of Morus Alba L.

    PubMed

    Marx, Tennille K; Glávits, Róbert; Endres, John R; Palmer, Philip A; Clewell, Amy E; Murbach, Timothy S; Hirka, Gábor; Pasics, Ilona

    2016-11-01

    Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Although there is an extensive history of consumption of M alba leaves by humans and animals worldwide, suggesting that the leaves and their extracts have a relatively good safety profile, we are unaware of safety assessments on an extract containing a higher amount of DNJ than that occurs naturally. The current 28-day repeated dose oral toxicity study in rats, conducted according to Organisation for Economic Co-operation and Development guidelines, was carried out to assess the safety of Reducose. Male and female Hsd.Han Wistar rats (4 groups of 10 animals/sex) were administered Reducose via gavage at doses of 0, 1,000, 2,000 and 4,000 mg/kg body weight (bw)/d. No treatment-related mortality or adverse effects (per clinical observations, body weight/weight gain, food consumption, ophthalmoscopy, clinical pathology, gross pathology, organ weights, or histopathology) were observed, and no target organs were identified. The no observed adverse effect level was determined to be 4,000 mg/kg bw/d for both male and female rats, the highest dose tested. © The Author(s) 2016.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Active-passive synergy for interpreting ocean L-band emissivity: Results from the CAROLS airborne campaigns

    NASA Astrophysics Data System (ADS)

    Martin, A. C. H.; Boutin, J.; Hauser, D.; Dinnat, E. P.

    2014-08-01

    The impact of the ocean surface roughness on the ocean L-band emissivity is investigated using simultaneous airborne measurements from an L-band radiometer (CAROLS) and from a C-band scatterometer (STORM) acquired in the Gulf of Biscay (off-the French Atlantic coasts) in November 2010. Two synergetic approaches are used to investigate the impact of surface roughness on the L-band brightness temperature (Tb). First, wind derived from the scatterometer measurements is used to analyze the roughness contribution to Tb as a function of wind and compare it with the one simulated by SMOS and Aquarius roughness models. Then residuals from this mean relationship are analyzed in terms of mean square slope derived from the STORM instrument. We show improvement of new radiometric roughness models derived from SMOS and Aquarius satellite measurements in comparison with prelaunch models. Influence of wind azimuth on Tb could not be evidenced from our data set. However, we point out the importance of taking into account large roughness scales (>20 cm) in addition to small roughness scale (5 cm) rapidly affected by wind to interpret radiometric measurements far from nadir. This was made possible thanks to simultaneous estimates of large and small roughness scales using STORM at small (7-16°) and large (30°) incidence angles.

  10. 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.

  11. Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.

    PubMed

    Moise, Pamela A; Culshaw, Darren L; Wong-Beringer, Annie; Bensman, Joyce; Lamp, Kenneth C; Smith, Winter J; Bauer, Karri; Goff, Debra A; Adamson, Robert; Leuthner, Kimberly; Virata, Michael D; McKinnell, James A; Chaudhry, Saira B; Eskandarian, Romic; Lodise, Thomas; Reyes, Katherine; Zervos, Marcus J

    2016-01-01

    Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation. This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance. A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P < 0.01) and ICU stay (odds ratio, 2.64; P = 0.03). Notable differences between treatment groups were seen with: (1) end of therapy failure rates (11% vs 24% for daptomycin vs vancomycin; P = 0.025); (2) acute kidney

  12. 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

  13. Low-tidal volume mechanical ventilation in patients with acute respiratory distress syndrome caused by pandemic influenza A/H1N1 infection.

    PubMed

    Oh, Dong Kyu; Lee, Myung Goo; Choi, Eun Young; Lim, Jaemin; Lee, Hyun-Kyung; Kim, Seok Chan; Lim, Chae-Man; Koh, Younsuck; Hong, Sang-Bum

    2013-08-01

    Low-tidal volume (TV) mechanical ventilation is an important manipulation in managing patients with acute respiratory distress syndrome (ARDS). However, there is no definite evidence to support the use of this intervention in patients with viral etiologies. A retrospective observational study of 104 patients with ARDS caused by pandemic influenza A/H1N1 infection admitted to 28 intensive care units (ICUs) in Korea was performed. Patients were categorized into 3 groups according to the TV they received: TV less than or equal to 7 mL/kg, TV greater than 7 mL/kg but less than or equal to 9 mL/kg, or TV greater than 9 mL/kg. The mean age was 55.1 years, and 55.8% were male (n = 58). Patients with TV greater than 9 mL/kg showed higher 28-day ICU mortality than the 2 other groups (vs TV < 7 mL/kg, P = .007 and vs 7 mL/kg < TV ≤ 9 mL/kg, P = .004, respectively). Patients with TV less than or equal to 7 mL/kg required ventilators, ICU admissions, and hospitalizations for fewer days than those with TV greater than 7 mL/kg (11.4 vs 6.1 days for 28-day ventilator-free days, 9.7 vs 4.9 days for 28-day ICU-free days, and 5.2 vs 2.4 days for 28-day hospital-free days, respectively). Tidal volume greater than 9 mL/kg (hazard rate, 2.459; P = .003) and Sequential Organ Failure Assessment score (hazard rate, 1.158; P = .014) were significant predictors of 28-day ICU mortality. Low-TV mechanical ventilation still benefits patients with ARDS caused by viral pneumonia. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. STS-103 Mission Highlights Resource Tape (1 of 2)

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The STS-103 flight crew, Commander Curtis L. Brown, Pilot Scott J. Kelly, Mission Specialists Steven L. Smith, C. Michael Foale, John M. Grunsfeld, Claude Nicollier, and Jean-Francois Clervoy, are seen performing pre-launch activities such as crew suit-up, and ride out to the launch pad for a night launch. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the White Room for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters. Once on-orbit the primary objective is to capture and service the Hubble Space Telescope. Included are various live shots of the payload bay showing the flight support system, the orbiter replacement unit carrier and the forward fixture that house the new Fine Guidance System (FGS). Smith and Grunsfeld replaces and changes the sensor units during the first space walk of this mission. The second space walk by Nicollier and Foale includes the changing of the computer and installation of the FGS. This is tape 1 of 2, tape 2 has a report number of NONP-NASA-VT-2000036031.

  15. L-dopa-induced desensitization depends on 5-hydroxytryptamine imbalance in hemiparkinsonian rats.

    PubMed

    Kääriäinen, Tiina M; García-Horsman, Juan Arturo; Piltonen, Marjo; Männistö, Pekka T

    2009-02-18

    We have shown before that 2-week intrastriatal L-3,4-dihydroxyphenylalanine (L-dopa) infusion significantly decreased contralateral rotations induced by acute intraperitoneal L-dopa/carbidopa and increased striatal tryptophan hydroxylase in 6-hydroxydopamine-lesioned rats. Here, we examined the effect of acutely administered L-dopa (10 microg) into 6-hydroxydopamine-lesioned rat striata under the inhibition of tryptophan hydroxylase by 4-chloro-DL-phenylalanine. Acute intrastriatal L-dopa infusion significantly decreased contralateral rotations induced by intraperitoneal L-dopa/carbidopa (10/30 mg/kg) 1 and 7 days after intrastriatal L-dopa. This desensitization to L-dopa occurred only when there was a striatal 5-hydroxytryptamine (5-HT) imbalance, not when 5-HT levels in the intact and lesioned sides were similar, either very low (day 1 postinfusion) or similarly recovered (day 7 postinfusion). We conclude that 5-HT plays a significant role in the striatal dopaminergic imbalance that evokes the rotational behavior.

  16. 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.

  17. 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.

  18. A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations.

    PubMed

    Vita, Roberto; Saraceno, Giovanna; Trimarchi, Francesco; Benvenga, Salvatore

    2013-02-01

    The purpose of this work is to evaluate if the coffee-associated malabsorption of tablet levothyroxine (L-T4) is reduced by soft gel capsule. We recruited 8 patients with coffee-associated L-T4 malabsorption including one hypothyroid patient. For 6 months, the patients were switched to the capsule maintaining the L-T4 daily dose. Patients took the capsule with water, having coffee 1 h later (proper habit, PH) on days 1-90, or with coffee ≤ 5 min later (improper habit, IH) on days 91-180. After 6 months, 2 patients volunteered for an acute loading test of 600 μg L-T4 (capsule) ingested with water (PH) or with coffee (IH). In the single hypothyroid patient, the post-switch TSH ranged 0.06-0.16 mU/L (PH) versus 5.8-22.4 mU/L pre-switch (PH) and 0.025-0.29 mU/L (IH) versus 26-34 mU/L pre-switch (IH). In the other 7 patients, post-switch TSH was 0.41 ± 0.46 (PH) versus 0.28 ± 0.20 pre-switch (PH) (P = 0.61) and 0.34 ± 0.30 (IH) versus 1.23 ± 1.47 pre-switch (IH) (P < 0.001). Importantly, TSH levels in PH versus IH habit did not differ post-switch (P = 0.90), but they did pre-switch (P < 0.0001). The proportions of post-switch TSH levels <0.10 mU/L with PH (33.3 %) or with IH (33.3 %) were borderline significantly greater than the corresponding pre-switch levels with PH (10.3 %) (P = 0.088) or with IH (0 %) (P = 0.0096). In the two volunteers, the L-T4 loading test showed that coffee influenced L-T4 pharmacokinetics minimally. Soft gel capsules can be used in patients who are unable/unwilling to change their IH of taking L-T4.

  19. 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.

  20. 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

  1. Morinda citrifolia L. leaf extract as antibacterial Salmonella typhimurium to increase productivity of quail (Coturnix coturnix japonica).

    PubMed

    Retnani, Y; Dan, T M Wardiny; Taryati

    2014-04-01

    The objective of this study was to apply effect of Morinda citrifolia L. citrifolia L. leaf extract as antibacterial of Salmonella typhimurium on mortality of Day Old Quail (DOQ), egg production and Hen day, hatchability of layer quail. This research was conducted at Laboratory of microbiology and laboratory of poultry nutrition, faculty of animal science, bogor agricultural university and slamet quail farms cilangkap, sukabumi, west java, Indonesia on March-July 2012. Two hundred and forty heads of quail were randomly assigned to four dietary treatments (sixty heads of quail/treatment). Experimental design used was Completely Randomized Design (CRD). The treatments consist of level of biscuit Morinda citrifolia L. Citrifolia L. leaf extract i.e R1 = 0%, R2 = 5%, R3 = 10%, R4 = 15%. The results indicated the treatments had significant effect (p < 0.05) on mortality of Day Old Quail (DOQ). The average mortality of Day Old Quail (DOQ) was given extract Morinda citrifolia L. leaf were R1 (4.00%), R2 (1.00%), R3 (1.33%), R4 (0.67%). The average mortality of Day Old Quail (DOQ) was given 15% extract Morinda citrifolia L. leaf (R4) was lowest than control treatment (R1). The results of the analysis indicated that Morinda citrifolia L. leaf of quail drink had not significant effect (p > 0.05) on egg production, hen day and hatchability. It was concluded that the Morinda citrifolia L. leaf extract 15% can reduce mortality of Day Old Quail (DOQ) and can increase its egg production, hen day and hatchability.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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…

  7. 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.

  8. Can recording only the day-time voided volumes predict bladder capacity?

    PubMed

    Cho, Won Yeol; Kim, Seong Cheol; Kim, Sun-Ouck; Park, Sungchan; Lee, Sang Don; Chung, Jae Min; Kim, Kyung Do; Moon, Du Geon; Kim, Young Sig; Kim, Jun Mo

    2018-05-01

    This study aimed to demonstrate a method to easily assess bladder capacity using knowledge of day-time voided volumes, which can be obtained even from patients with nocturnal enuresis where the first morning void cannot accurately predict the bladder capacity due to bladder emptying overnight. We evaluated 177 healthy children from 7 Korean medical centres entered the study between January 2008 and January 2009. Voided volumes measured for more than 48 hours were recorded in the frequency volume chart (FVC). Most voided volumes during day-time were showed between 30% and 80% of the maximal voided volume (MVV). The maximal voided volume during day-time (MVVDT) was significantly less than the MVV (179.5±71.1 mL vs. 227.0±79.2 mL, p<0.001). The correlation coefficients with the MVV were 0.801 for the estimated MVV using the MVVDT (MVVDT×1.25), which suggested a fairly strong relationship between the MVVDT×1.25 and the MVV. The MVV derived from the FVC excluding the FMV was less than if the FMV had been included. When an accurate first morning voided volume cannot be obtained, as in patients with nocturnal enuresis, calculating MVVDT×1.25 allows estimation of the bladder capacity in place of the MVV.

  9. 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.

  10. Atmospheric Soundings from AIRS/AMSU/HSB

    NASA Technical Reports Server (NTRS)

    Susskind, Joel; Atlas, Robert

    2004-01-01

    AIRS was launched on EOS Aqua on May 4, 2002, together with AMSU A and HSB, to form a next generation polar orbiting infrared and microwave atmospheric sounding system. The primary products of AIRS/AMSU/HSB are twice daily global fields of atmospheric temperature-humidity profiles, ozone profiles, sea/land surface skin temperature, and cloud related parameters including OLR. The sounding goals of AIRS are to produce 1 km tropospheric layer mean temperatures with an rms error of lK, and 1 km tropospheric layer precipitable water with an rms error of 20%, in cases with up to 80% effective cloud cover. Pre-launch simulation studies indicated that these results should be achievable. Minor modifications have been made to the pre-launch retrieval algorithm as alluded to in this paper. Sample fields of parameters retrieved from AIRS/AMSU/HSB data are presented and temperature profiles are validated as a function of retrieved effective fractional cloud cover. As in simulation, the degradation of retrieval accuracy with increasing cloud cover is small. Select fields are also compared to those contained in the ECMWF analysis, done without the benefit of AIRS data, to demonstrate information that AIRS can add to that already contained in the ECMWF analysis. Assimilation of AIRS temperature soundings in up to 80% cloud cover for the month of January 2003 into the GSFC FVSSI data assimilation system resulted in improved 5 day forecasts globally, both with regard to anomaly correlation coefficients and the prediction of location and intensity of cyclones.

  11. An evaluation of 1-day disposable contact lens wear in a population of allergy sufferers.

    PubMed

    Hayes, Valérie Y; Schnider, Cristina M; Veys, Jane

    2003-06-01

    This was a multi-site, 128-subject, bilateral crossover study to evaluate subjective comfort and slit-lamp findings with 1-day disposable contact lenses in a population of allergy sufferers during periods when allergen levels were elevated. The study involved 1-month of single-use daily wear with a 1-day disposable test lens (1. DAY ACUVUE Brand Contact Lenses, Johnson & Johnson Vision Care) and 1-month of daily wear with subjects' habitual lenses replaced to their usual replacement schedule. Pollen and mould counts were obtained for each site 1 week prior to the study and twice weekly throughout the study period. Subjective comfort and slit-lamp findings were recorded at baseline and after 1-month's wear of each modality. Sixty-seven percent of subjects agreed that the 1-day disposable lenses provided improved comfort when compared to the lenses they wore prior to the study, compared with 18% agreeing that the new pair of habitual lenses provided improved comfort. The 1-day disposable lenses showed greater improvement in slit-lamp findings from baseline than new habitual lenses. The use of 1-day disposable lenses is an effective strategy for managing allergy-suffering contact lens wearers.

  12. Customer Avionics Interface Development and Analysis (CAIDA) Lab DEWESoft Display Creation

    NASA Technical Reports Server (NTRS)

    Coffey, Connor

    2015-01-01

    The Customer Avionics Interface Development and Analysis (CAIDA) Lab supports the testing of the Launch Control System (LCS), NASA's command and control system for the Space Launch System (SLS), Orion Multi-Purpose Crew Vehicle (MPCV), and ground support equipment. The objectives of the year-long internship were to support day-to-day operations of the CAIDA Lab, create prelaunch and tracking displays for Orion's Exploration Flight Test 1 (EFT-1), and create a program to automate the creation of displays for SLS and MPCV to be used by CAIDA and the Record and Playback Subsystem (RPS).

  13. 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

  14. 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

  15. Influence of L-arginine during bovine in vitro fertilization.

    PubMed

    Silva, Thiago Velasco Guimarães; da Silva, Bruno Baraúna; de Sá, André Luiz Alves; da Costa, Nathalia Nogueira; Sampaio, Rafael Vilar; Cordeiro, Marcela da Silva; Santana, Priscila Di Paula Bessa; Adona, Paulo Roberto; Santos, Simone do Socorro Damasceno; Miranda, Moysés dos Santos; Ohashi, Otávio Mitio

    2014-12-01

    The objective of this work was to evaluate the effect of using L-arginine during in vitro fertilization (IVF) on in vitro embryonic development using Bos taurus and Bos indicus semen. Effect of different concentrations (0, 1, 10 and 50 mM) of L-arginine, added to the IVF medium, was evaluated on the fertilization rate at 18 h post-fertilization (hpf), NO3(-)/NO2(-) production during IVF by the Griess colorimetric method (30 hpf), cleavage and blastocyst rates (on Day 2 and Day 7 of culture, respectively) and total blastocyst cell number (Day 7 of culture). The results reveal that the addition of 50 mM L-arginine to IVF medium, with either Bos taurus or Bos indicus spermatozoa, decreased the cleavage rate and blastocyst rate compared to the control group. Other concentrations did not affect embryo production. However, 1 mM L-arginine with Bos indicus semen increased the proportion of hatched blastocysts. These results indicate that high L-arginine concentrations may exhibit toxic effects on bovine gametes during in vitro fertilization.

  16. 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.

  17. 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

  18. 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

  19. Enhancement of ginsenoside Rg(1) in Panax ginseng hairy root by overexpressing the α-L-rhamnosidase gene from Bifidobacterium breve.

    PubMed

    Zhang, Ru; Zhang, Bian-Ling; Li, Gu-Cai; Xie, Tao; Hu, Teng; Luo, Zhi-Yong

    2015-10-01

    To improve the production of ginsenoside Rg1 in Panax ginseng. The α-L-rhamnosidase gene from Bifidobacterium breve (BbRha) was overexpressed into hairy root culture system using Agrobacterium rhizogenes A4. Ginsenoside Rg1 in hairy roots was obtained following transformation via overexpressed gene representing 2.2-fold higher than those of control lines. Several overexpression transgenic hairy root lines were obtained exhibiting markedly increased levels of the corresponding α-L-rhamnosidase enzymatic activity relative to control. Ginsenoside Rg1 levels in the transgenic lines were higher (2.2-fold) than those of control after following 30 days culturing, while ginsenoside Re contents in tested transgenic lines were found to be lower. The transgenic hairy roots harboring α-L-rhamnosidase gene improved the accumulation of ginsenoside Rg1 up to 3.6 mg g(-1) dry weight. BbRha gene selectively enhances the production of ginsenoside Rg1 in P. ginseng hairy roots.

  20. 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

  1. Parallel Workflow for High-Throughput (>1,000 Samples/Day) Quantitative Analysis of Human Insulin-Like Growth Factor 1 Using Mass Spectrometric Immunoassay

    PubMed Central

    Oran, Paul E.; Trenchevska, Olgica; Nedelkov, Dobrin; Borges, Chad R.; Schaab, Matthew R.; Rehder, Douglas S.; Jarvis, Jason W.; Sherma, Nisha D.; Shen, Luhui; Krastins, Bryan; Lopez, Mary F.; Schwenke, Dawn C.; Reaven, Peter D.; Nelson, Randall W.

    2014-01-01

    Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications. PMID:24664114

  2. 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.

  3. 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

  4. Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes.

    PubMed

    Ritzel, Robert; Roussel, Ronan; Giaccari, Andrea; Vora, Jiten; Brulle-Wohlhueter, Claire; Yki-Järvinen, Hannele

    2018-03-01

    To investigate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) over 12 months in a patient-level meta-analysis, using data from the EDITION studies in people with type 2 diabetes (T2DM). EDITION 1, 2 and 3 were multicentre, randomized, open-label, 2-arm, parallel-group, treat-to-target phase IIIa studies. Similar study designs and endpoints enabled a meta-analysis to be conducted. Reductions in glycated haemoglobin (HbA1c) were better sustained over 12 months with Gla-300 than with Gla-100 (least squares [LS] mean difference in change from baseline: -0.10 % [95% confidence interval {CI} -0.18 to -0.02] or -1.09 mmol/mol [95% CI -2.01 to -0.20]; P = .0174). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycaemia was 15% lower with Gla-300 vs Gla-100 at night (relative risk 0.85 [95% CI 0.77-0.92]) and 6% lower at any time of day (relative risk 0.94 [95% CI 0.90-0.98]). Rates of hypoglycaemia were 18% lower with Gla-300 vs Gla-100 at night (rate ratio 0.82 [95% CI 0.67-0.99]), but comparable at any time of day. HbA1c <7.0 % without nocturnal hypoglycaemia was achieved by 24% more participants with Gla-300 than with Gla-100 (relative risk 1.24 [95% CI 1.03-1.50]). Severe hypoglycaemia was rare; in both treatment groups the incidence of events at any time of day was ≤3.6%, while rates were ≤0.08 events per participant-year. In a broad population of people with T2DM over 12 months, use of Gla-300 provided more sustained glycaemic control and significantly lower hypoglycaemia risk at night and at any time of day compared with Gla-100. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  5. 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

  6. Postoperative Calcium Management in Same-Day Discharge Thyroid and Parathyroid Surgery.

    PubMed

    Nelson, Kurt L; Hinson, Andrew M; Lawson, Bradley R; Middleton, Derek; Bodenner, Donald L; Stack, Brendan C

    2016-05-01

    To describe a safe and effective postoperative prophylactic calcium regimen for same-day discharge thyroid and parathyroid surgery. Case series with chart review. Tertiary referral academic institution. In total, 162 adult patients who underwent total thyroidectomy, completion thyroidectomy, unilateral parathyroidectomy, parathyroidectomy with bilateral neck exploration, or revision parathyroidectomy were identified preoperatively to be candidates for same-day discharge. All patients in this study were successfully discharged the same day on our standard prophylactic calcium regimen. Less than 1% (1/162) of patients re-presented to the hospital within 30 days of surgery, and that patient was successfully discharged from the emergency department after negative workup for hypocalcemia. There was no significant difference between preoperative and postoperative calcium levels in the total/completion thyroidectomy groups (9.3 vs 9.2 mg/dL, respectively; P = .14). The average postoperative calcium level in the parathyroid group was well within normal limits (9.5 mg/dL), and the difference in postoperative calcium levels between revision and primary parathyroidectomy cases was not significantly different (P = .34). The reported calcium regimen demonstrates a safe, effective, and objective means of postoperative calcium management in outpatient thyroid and parathyroid surgery in appropriately selected patients. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  7. Optimization of adventitious root culture for production of biomass and secondary metabolites in Prunella vulgaris L.

    PubMed

    Fazal, Hina; Abbasi, Bilal Haider; Ahmad, Nisar

    2014-11-01

    Adventitious root cultures of Prunella vulgaris L. were established in shaking flask system for the production of biomass and secondary metabolites. Adventitious root cultures were induced from callus cultures obtained from leaf explants on solid Murashige and Skoog (MS) medium containing combination of 6-benzyladenine (BA; 1.0 mg l(-1)) and naphthalene acetic acid (NAA; 1.5 mg l(-1)). Thereafter, 0.49 g inoculum was transferred to liquid MS medium supplemented with different concentrations of NAA (0.5-2.0 mg l(-1)). Growth kinetics of adventitious roots was recorded with an interval of 7 days for 49 days period. Highest biomass accumulation (2.13 g/l) was observed in liquid medium containing 1.0 mg l(-1) NAA after 21 days of inoculation. However, other concentrations of NAA also showed similar accumulation pattern but the biomass gradually decreases after 49 days of inoculation. Adventitious roots were collected and dried for investigation of total phenolics (TP), total flavonoids (TF), and antioxidant activities. Higher TPC (0.995 GAE mg/g-DRB) and TFC (6.615 RE mg/g-DRB) were observed in 0.5 mg l(-1) NAA treated cultures. In contrast, higher antioxidant activity (83.53 %) was observed 1.5 mg l(-1) NAA treated cultures. These results are helpful in up scaling of root cultures into bioreactor for secondary metabolites production.

  8. Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

    PubMed

    Zhang, YanPing; Kawedia, Jitesh D; Myers, Alan L; McIntyre, Chelsey M; Anderson, Peter M; Kramer, Mark A; Culotta, Kirk S

    2014-02-01

    Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.

  9. 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.

  10. Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols.

    PubMed

    Dimopoulos, Panagiotis; Christopoulos, Panagiotis; Shilito, Sam; Gall, Zara; Murby, Brian; Ashworth, David; Taylor, Ben; Carrington, Bernadette; Shanks, Jonathan; Clarke, Noel; Ramani, Vijay; Parr, Nigel; Lau, Maurice; Sangar, Vijay

    2016-06-01

    To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien-Dindo grading system). In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien-Dindo Grade 1-2. DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  11. Progesterone levels and days to luteolysis in mares treated with intrauterine fractionated coconut oil.

    PubMed

    Diel de Amorim, Mariana; Nielsen, Kayla; Cruz, Raissa Karolliny Salgueiro; Card, Claire

    2016-07-15

    Intrauterine plant oil infusion, including fractionated coconut oil, has been previously found to be a safe, inexpensive, and reversible method of prolonging the luteal phase in mares when administered on Day 10 of the estrous cycle. Our objective was to understand the uteroovarian response to the administration of fractionated coconut oil infusion in the uterus of diestrous mares. We hypothesized that intrauterine coconut oil administration on Day 10 would prolong luteal life span in a dose-dependent fashion and would result in higher serum progesterone levels than untreated mares at the expected time of luteolysis. Light-horse mares (n = 18) were examined using transrectal palpation and ultrasonography to determine if they had a normal interovulatory interval and were then examined daily in estrus until the day of ovulation (Day 0) and then every other day during an estrous cycle. Jugular blood was drawn on Day 11, Day 13, Day 15, and Day 17, centrifuged, and serum stored until assayed for progesterone (P4; Siemens Coat-a-Count Progesterone RIA, Los Angeles, CA, USA). Mares were randomly assigned to treatment and studied over one to two estrous cycles with a rest cycle after each treatment cycle. Groups were: control (n = 5), fractionated coconut oil 1.0 mL (Miglyol 810; Sasol Oil, Witten, Germany) infused in the uterus with an artificial insemination pipette on Day 10 (Group 1; n = 5) and fractionated coconut oil 0.5 mL infused in the uterus with an embryo transfer gun, on Day 10 (Group 2; n = 5). All statistical analyses were performed using analytical software (Stata SE, version 13.1, College Station, TX, USA) at P < 0.05. Data were first evaluated using the Shapiro-Wilk test for normality. Differences between groups in days to luteolysis (DTL) were examined using analysis of variance and Bonferroni, and the effect of day and treatment on P4 levels were examined using the Kruskal-Wallis and Dunn's all pairwise test. There was a significant

  12. 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.

  13. 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...

  14. Evaluation of pre-rigor injection of beef with proteases on cooked meat volatile profile after 1 day and 21 days post-mortem storage.

    PubMed

    Ma, Q L; Hamid, N; Bekhit, A E D; Robertson, J; Law, T F

    2012-12-01

    This research was carried out to determine the effects of pre-rigor injection of beef semimembranosus muscle with nine proteases from plant and microbial sources, on the volatile profile of cooked beef after 1 day and 21 days post-mortem (PM) storage using Solid-phase microextraction gas chromatography mass spectrometry analysis. A total of 23 aldehydes, 5 ketones, 3 furans, 8 nitrogen and sulphur compounds, 4 alkanes, 7 alcohols and 6 terpenes were detected. Eleven volatile compounds characteristic of ginger flavour were detected in zingibain-treated meat. Benzaldehyde significantly increased (p<0.05) only in kiwifruit juice (KJ), fungal 31 protease and Asparagus protease (ASP) treated samples from 1 day to 21 days PM storage. A significant increase (p<0.05) in 3-methylbutanal was observed in KJ, bacterial and fungal protease treated samples at 21 days PM storage. Treatments with bromelain, papain, ASP, actinidin, and KJ (except KJ 21 days) proteases resulted in flavour profiles closer to that of the control beef sample. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. 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

  16. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

    PubMed

    Luetic, Krešimir; Sucic, Mario; Vlainic, Josipa; Halle, Zeljka Belosic; Strinic, Dean; Vidovic, Tinka; Luetic, Franka; Marusic, Marinko; Gulic, Sasa; Pavelic, Tatjana Turudic; Kokot, Antonio; Seiwerth, Ranka Serventi; Drmic, Domagoj; Batelja, Lovorka; Seiwerth, Sven; Sikiric, Predrag

    2017-04-01

    We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

  17. Underway Recovery Test 6 (URT-6) - Day 1 Activities

    NASA Image and Video Library

    2018-01-17

    The USS Anchorage leaves Naval Base San Diego for a multi-day Underway Recovery Test with NASA. The NASA Recovery Team from Kennedy Space Center and the U.S. Navy are working together to hone recovery procedures and hardware ahead of Orion’s next flight, Exploration Mission-1, when it splashes down in the Pacific Ocean.

  18. 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...

  19. 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...

  20. Pediatric community-acquired pneumonia treated with a three-day course of tebipenem pivoxil.

    PubMed

    Sakata, Hiroshi; Kuroki, Haruo; Ouchi, Kazunobu; Tajima, Takeshi; Iwata, Satoshi

    2017-05-01

    We evaluated the efficacy and safety of a 3-day treatment regimen of tebipenem pivoxil for pediatric community-acquired pneumonia. Tebipenem pivoxil was administered to 49 patients, and its effectiveness was evaluated in 36 patients 2-4 days after initiation of treatment. Thirty-two patients were cured 7-15 days after initiation of treatment. Body temperature was significantly lower on the day following initial administration (median 38.8 to 37.0 °C, n = 33). Leukocyte counts and C-reactive protein levels were significantly reduced by Day 2-4 of treatment (median 16,100 to 7800 white blood cells/μL, and 5.6 to 1.5 mg/dL, respectively; n = 28). Six of the 49 patients had mild diarrhea. Thus, we concluded that 3-day treatment with tebipenem pivoxil was safe and efficacious for treating pediatric community-acquired pneumonia. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. 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.

  2. 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.

  3. Day and Night Closed-Loop Control Using the Integrated Medtronic Hybrid Closed-Loop System in Type 1 Diabetes at Diabetes Camp.

    PubMed

    Ly, Trang T; Roy, Anirban; Grosman, Benyamin; Shin, John; Campbell, Alex; Monirabbasi, Salman; Liang, Bradley; von Eyben, Rie; Shanmugham, Satya; Clinton, Paula; Buckingham, Bruce A

    2015-07-01

    To evaluate the feasibility and efficacy of a fully integrated hybrid closed-loop (HCL) system (Medtronic MiniMed Inc., Northridge, CA), in day and night closed-loop control in subjects with type 1 diabetes, both in an inpatient setting and during 6 days at diabetes camp. The Medtronic MiniMed HCL system consists of a fourth generation (4S) glucose sensor, a sensor transmitter, and an insulin pump using a modified proportional-integral-derivative (PID) insulin feedback algorithm with safety constraints. Eight subjects were studied over 48 h in an inpatient setting. This was followed by a study of 21 subjects for 6 days at diabetes camp, randomized to either the closed-loop control group using the HCL system or to the group using the Medtronic MiniMed 530G with threshold suspend (control group). The overall mean sensor glucose percent time in range 70-180 mg/dL was similar between the groups (73.1% vs. 69.9%, control vs. HCL, respectively) (P = 0.580). Meter glucose values between 70 and 180 mg/dL were also similar between the groups (73.6% vs. 63.2%, control vs. HCL, respectively) (P = 0.086). The mean absolute relative difference of the 4S sensor was 10.8 ± 10.2%, when compared with plasma glucose values in the inpatient setting, and 12.6 ± 11.0% compared with capillary Bayer CONTOUR NEXT LINK glucose meter values during 6 days at camp. In the first clinical study of this fully integrated system using an investigational PID algorithm, the system did not demonstrate improved glucose control compared with sensor-augmented pump therapy alone. The system demonstrated good connectivity and improved sensor performance. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  4. 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%.

  5. Evaluation of drug content (potency) for compounded and FDA-approved formulations of doxycycline on receipt and after 21 days of storage.

    PubMed

    KuKanich, Kate; KuKanich, Butch; Slead, Tanner; Warner, Matt

    2017-10-01

    OBJECTIVE To determine drug content (potency) of compounded doxycycline formulations for veterinary use and of US FDA-approved doxycycline formulations for human use < 24 hours after receipt (day 1) and after 21 days of storage under recommended conditions (day 21). DESIGN Evaluation study. SAMPLE FDA-approved doxycycline tablets (100 mg), capsules (100 mg), and liquid suspension (10 mg/mL) and compounded doxycycline formulations from 3 pharmacies (tablets [25, 100, and 150 mg; 1 product/source], chews [100 mg; 1 product/source], and liquid suspensions or solution [6 mg/mL {2 sources} and 50 mg/mL {1 source}]). PROCEDURES Doxycycline content was measured in 5 samples of each tablet, chew, or capsule formulation and 5 replicates/bottle of liquid formulation on days 1 and 21 by liquid chromatography and compared with US Pharmacopeia acceptable ranges. RESULTS All FDA-approved formulations had acceptable content on days 1 and 21. On day 1, mean doxycycline content for the 3 compounded tablet formulations was 89%, 98%, and 116% (3/5, 5/5, and 1/5 samples within acceptable ranges); day 21 content range was 86% to 112% (1/5, 5/5, and 4/5 samples within acceptable ranges). Day 1 content of chews was 81%, 78%, and 98% (0/5, 0/5, and 5/5 samples within acceptable ranges), and that of compounded liquids was 50%, 52%, and 85% (no results within acceptable ranges). No chews or compounded liquid formulations met USP standards on day 21. CONCLUSIONS AND CLINICAL RELEVANCE FDA-approved doxycycline should be prescribed when possible. Whole tablets yielded the most consistent doxycycline content for compounded formulations.

  6. Outpatient 60-hour day-and-night glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or sensor-augmented pump therapy in adults with type 1 diabetes: An open-label, randomised, crossover, controlled trial.

    PubMed

    Haidar, Ahmad; Messier, Virginie; Legault, Laurent; Ladouceur, Martin; Rabasa-Lhoret, Rémi

    2017-05-01

    To assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared to the single-hormone (insulin alone) artificial pancreas in outpatient settings during the day and night. In a randomized, three-way, crossover trial we compared the dual-hormone artificial pancreas, the single-hormone artificial pancreas and sensor-augmented pump therapy (control) in 23 adults with type 1 diabetes. Each intervention was applied from 8 AM Day 1 to 8 PM Day 3 (60 hours) in outpatient free-living conditions. The primary outcome was time spent with sensor glucose levels below 4.0 mmol/L. A P value of less than .017 was regarded as significant. The median difference between the dual-hormone system and the single-hormone system was -2.3% (P = .072) for time spent below 4.0 mmol/L, -1.3% (P = .017) for time below 3.5 mmol/L, and -0.7% (P = .031) for time below 3.3 mmol/L. Both systems reduced (P < .017) hypoglycaemia below 4.0, 3.5 and 3.3 mmol/L compared to control therapy, but reductions were larger with the dual-hormone system than with the single-hormone system (medians -4.0% vs -3.4% for 4.0 mmol/L; -2.7% vs -2.2% for 3.5 mmol/L; and -2.2% vs -1.2% for 3.3 mmol/L). There were 34 hypoglycaemic events (<3.0 mmol/L for 20 minutes) with control therapy, 14 with the single-hormone system and 6 with the dual-hormone system. These differences in hypoglycaemia were observed while mean glucose level was low and comparable in all interventions (P = NS). The dual-hormone artificial pancreas had the lowest risk of hypoglycaemia, but the differences were not statistically significant. Larger studies are needed. © 2017 John Wiley & Sons Ltd.

  7. 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.

  8. 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.

  9. Mutations in the Arabidopsis Homolog of LST8/GβL, a Partner of the Target of Rapamycin Kinase, Impair Plant Growth, Flowering, and Metabolic Adaptation to Long Days[C][W

    PubMed Central

    Moreau, Manon; Azzopardi, Marianne; Clément, Gilles; Dobrenel, Thomas; Marchive, Chloé; Renne, Charlotte; Martin-Magniette, Marie-Laure; Taconnat, Ludivine; Renou, Jean-Pierre; Robaglia, Christophe; Meyer, Christian

    2012-01-01

    The conserved Target of Rapamycin (TOR) kinase forms high molecular mass complexes and is a major regulator of cellular adaptations to environmental cues. The Lethal with Sec Thirteen 8/G protein β subunit-like (LST8/GβL) protein is a member of the TOR complexes, and two putative LST8 genes are present in Arabidopsis thaliana, of which only one (LST8-1) is significantly expressed. The Arabidopsis LST8-1 protein is able to complement yeast lst8 mutations and interacts with the TOR kinase. Mutations in the LST8-1 gene resulted in reduced vegetative growth and apical dominance with abnormal development of flowers. Mutant plants were also highly sensitive to long days and accumulated, like TOR RNA interference lines, higher amounts of starch and amino acids, including proline and glutamine, while showing reduced concentrations of inositol and raffinose. Accordingly, transcriptomic and enzymatic analyses revealed a higher expression of genes involved in nitrate assimilation when lst8-1 mutants were shifted to long days. The transcriptome of lst8-1 mutants in long days was found to share similarities with that of a myo-inositol 1 phosphate synthase mutant that is also sensitive to the extension of the light period. It thus appears that the LST8-1 protein has an important role in regulating amino acid accumulation and the synthesis of myo-inositol and raffinose during plant adaptation to long days. PMID:22307851

  10. 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.

  11. 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…

  12. STS-102 Launch Activities inside the MCC.

    NASA Image and Video Library

    2001-03-08

    JSC2001-E-06208 (8 March 2001) --- At his console in Houston's Mission Control Center, ascent flight director Wayne Hale monitors Discovery's pre-launch activities several hundred miles away in Florida on STS-102 launch day.

  13. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

    PubMed

    Trepanowski, John F; Kroeger, Cynthia M; Barnosky, Adrienne; Klempel, Monica C; Bhutani, Surabhi; Hoddy, Kristin K; Gabel, Kelsey; Freels, Sally; Rigdon, Joseph; Rood, Jennifer; Ravussin, Eric; Varady, Krista A

    2017-07-01

    -reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group. Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction. clinicaltrials.gov Identifier: NCT00960505.

  14. 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

  15. 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

  16. A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism.

    PubMed

    Page, S R; Sheard, C E; Herbert, M; Hopton, M; Jeffcoate, W J

    1996-11-01

    The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism. Prospective open multicentre trial. Sixty-three patients presenting with hyperthyroidism. Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks. Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 +/- 10 vs 158 +/- 11 nmol/l, P < 0.001) and free T4 (19.4 +/- 2.6 vs 35.2 +/- 3.7 pmol/l, P < 0.001) and total (2.6 +/- 0.3 vs 4.3 +/- 0.4 nmol/l, P < 0.001) and free T3 (8.3 +/- 1.0 vs 13.7 +/- 1.2 pmol/l, P < 0.01) at 4 weeks than those receiving 20 mg/day. Clinical responses at 6 and 12 weeks (weight, pulse, symptom score) and SHBG concentrations were similar. Drug-related hypothyroidism was less likely to occur at 4 and 10 weeks in those patient who initially received 20 mg CBZ/day, but this dose was less effective at controlling hyperthyroidism in those with more severe hyperthyroidism with baseline TT4 > 260 nmol/l. In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with mild or moderate hyperthyroidism. Higher doses are required for those with severe hyperthyroidism.

  17. STS-85 Day 08 Highlights

    NASA Technical Reports Server (NTRS)

    1997-01-01

    On this eighth day of the STS-85 mission, the flight crew, Cmdr. Curtis L. Brown, Jr., Pilot Kent V. Rominger, Payload Cmdr. N. Jan Davis (Ph.D.), Mission Specialists Robert L. Curbeam, Jr. and Stephen K. Robinson (Ph.D.), and Payload Specialist Bjarni V. Tryggvason entered the final portion of its flight. The new Mir 24 crew of Commander Anatoly Solovyev and Flight Engineer Pavel Vinogradov, who arrived on the station the same day Discovery was launched, bid farewell to Mir 23 Commander Vasily Tsibliev and Flight Engineer Alexander Lazutkin who are returning home after 185 days in space. The Soyuz vehicle carrying the Mir 23 crew home undocked from the station. Robinson again used the Southwest Ultraviolet Imaging System (SWUIS), a 7-inch imaging telescope that is pointed out of the orbiter's middeck hatch window, to observe the Hale-Bopp comet. Curbeam continued his work with the Bioreactor Demonstration System designed to perform cell biology experiments under controlled conditions. Tryggvason spent part of his time troubleshooting a computer hard drive system that supports the Microgravity Vibration Isolation Mount experiment.

  18. 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.

  19. [Fertility after treatment with Eazi-breedTM CIDR G for 6 or 12 days outside the breeding season in Lacaune dairy sheep].

    PubMed

    Fleisch, A; Piechotta, M; Bollwein, H; Janett, F

    2013-07-01

    This study compares the fertility after short- and long-term synchronization using a progesterone intravaginal device in Lacaune dairy sheep outside the breeding season. For the experiment 108 Lacaune sheep were treated with Eazi-breed™ CIDR® G intravaginal devices (Pfizer Animal Health, Zürich) for 12 days (Group L, n = 60) or 6 days (Group K, n = 48) in combination with eCG (Group L) or with eCG and 125 μg Cloprostenol (Group K) at device removal. Thereafter the ewes were kept together with rams for 60 days, ewes in estrus were recorded and the fertility was assessed after lambing. Blood progesterone concentration was measured at device application, withdrawal and 14 days later. Results show that neither treatment nor parity had an influence on estrus rate (Group L 91.7 %, Group K 93.8 %, nulli- and pluriparous animals 96.9 % and 90.8 %, respectively). Group L showed a tendency towards a better first cycle lambing rate and a significantly (P < 0.05) higher overall lambing rate compared to sheep of Group K (71.7 % vs. 60.4 % and 83.3 % vs. 72.9 %). Pluriparous ewes had higher (P < 0.05) lambing rates and greater (P < 0.05) numbers of lambs born per synchronized ewe than nulliparous sheep for the first cycle (75.0 % vs. 46.9 % and 1.4 ± 1.0 vs. 0.9 ± 1.1) as well as for the overall service period (92.1 % vs. 46.9 % and 1.7 ± 0.8 vs. 0.9 ± 1.1). Fourteen days after insert withdrawal progesterone concentrations were higher (P < 0.05) in Group L than in Group K (7.7 ± 4.3 vs. 5.6 ± 2.7 ng/mL) and in nulli- compared to pluriparous (9.1 ± 5.6 vs. 5.7 ± 2.1 ng/mL) ewes. In conclusion, the overall lambing rate was higher after long-term compared to short progesterone treatment and nulliparous ewes were less suitable for estrus induction outside the breeding season.

  20. 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…