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Sample records for bk030007 olympus pk

  1. The OLYMPUS Experiment

    OpenAIRE

    Milner, R; Hasell, D. K.; Beck, R; S. Belostotski(St. Petersburg, INP); Bernauer, J. C.; Bessuille, J.; Brinker, F.; Buck, B.; Calarco, J.R.; V. Carassiti; Cisbani, E.; Ciullo, G.; Kohl, M.; Contalbrigo, M; D'Ascenzo, N.

    2014-01-01

    The OLYMPUS experiment was designed to measure the ratio between the positron-proton and electron-proton elastic scattering cross sections, with the goal of determining the contribution of two-photon exchange to the elastic cross section. Two-photon exchange might resolve the discrepancy between measurements of the proton form factor ratio, $\\mu_p G^p_E/G^p_M$, made using polarization techniques and those made in unpolarized experiments. OLYMPUS operated on the DORIS storage ring at DESY, alt...

  2. The OLYMPUS Experiment

    CERN Document Server

    Milner, R; Kohl, M; Schneekloth, U; Akopov, N; Alarcon, R; Andreev, V A; Ates, O; Avetisyan, A; Bayadilov, D; Beck, R; Belostotski, S; Bernauer, J C; Bessuille, J; Brinker, F; Buck, B; Calarco, J R; Carassiti, V; Cisbani, E; Ciullo, G; Contalbrigo, M; D'Ascenzo, N; De Leo, R; Diefenbach, J; Donnelly, T W; Dow, K; Elbakian, G; Eversheim, D; Frullani, S; Funke, Ch; Gavrilov, G; Gläser, B; Görrissen, N; Hauschildt, J; Henderson, B S; Hoffmeister, Ph; Holler, Y; Ice, L D; Izotov, A; Kaiser, R; Karyan, G; Kelsey, J; Khaneft, D; Klassen, P; Kiselev, A; Krivshich, A; Lehmann, I; Lenisa, P; Lenz, D; Lumsden, S; Ma, Y; Maas, F; Marukyan, H; Miklukho, O; Movsisyan, A; Murray, M; Naryshkin, Y; O'Connor, C; Benito, R Perez; Perrino, R; Redwine, R P; Piñeiro, D Rodríguez; Rosner, G; Russell, R L; Schmidt, A; Seitz, B; Statera, M; Thiel, A; Vardanyan, H; Veretennikov, D; Vidal, C; Winnebeck, A; Yeganov, V

    2014-01-01

    The OLYMPUS experiment was designed to measure the ratio between the positron-proton and electron-proton elastic scattering cross sections, with the goal of determining the contribution of two-photon exchange to the elastic cross section. Two-photon exchange might resolve the discrepancy between measurements of the proton form factor ratio, $\\mu_p G^p_E/G^p_M$, made using polarization techniques and those made in unpolarized experiments. OLYMPUS operated on the DORIS storage ring at DESY, alternating between 2.01~GeV electron and positron beams incident on an internal hydrogen gas target. The experiment used a toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight detectors to measure rates for elastic scattering over the polar angular range of approximately $25^\\circ$--$75^\\circ$. Symmetric M{\\o}ller/Bhabha calorimeters at $1.29^\\circ$ and telescopes of GEM and MWPC detectors at $12^\\circ$ served as luminosity monitors. A total luminosity of approximately 4.5~fb$^{-1}$ was collect...

  3. The OLYMPUS experiment

    Energy Technology Data Exchange (ETDEWEB)

    Milner, R. [Massachusetts Institute of Technology, Cambridge, MA (United States); Hasell, D.K., E-mail: hasell@mit.edu [Massachusetts Institute of Technology, Cambridge, MA (United States); Kohl, M. [Hampton University, Hampton, VA (United States); Schneekloth, U. [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany); Akopov, N. [Alikhanyan National Science Laboratory (Yerevan Physics Institute), Yerevan (Armenia); Alarcon, R. [Arizona State University, Tempe, AZ (United States); Andreev, V.A. [Petersburg Nuclear Physics Institute, Gatchina (Russian Federation); Ates, O. [Hampton University, Hampton, VA (United States); Avetisyan, A. [Alikhanyan National Science Laboratory (Yerevan Physics Institute), Yerevan (Armenia); Bayadilov, D.; Beck, R. [Friedrich Wilhelms Universität, Bonn (Germany); Belostotski, S. [Petersburg Nuclear Physics Institute, Gatchina (Russian Federation); Bernauer, J.C.; Bessuille, J. [Massachusetts Institute of Technology, Cambridge, MA (United States); Brinker, F. [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany); Buck, B. [Massachusetts Institute of Technology, Cambridge, MA (United States); Calarco, J.R. [University of New Hampshire, Durham, NH (United States); Carassiti, V. [Università di Ferrara and Istituto Nazionale di Fisica Nucleare, Ferrara (Italy); Cisbani, E. [Istituto Superiore di Sanità and Istituto Nazionale di Fisica Nucleare, Rome (Italy); Ciullo, G. [Università di Ferrara and Istituto Nazionale di Fisica Nucleare, Ferrara (Italy); and others

    2014-03-21

    The OLYMPUS experiment was designed to measure the ratio between the positron–proton and electron–proton elastic scattering cross-sections, with the goal of determining the contribution of two-photon exchange to the elastic cross-section. Two-photon exchange might resolve the discrepancy between measurements of the proton form factor ratio, μ{sub p}G{sub E}{sup p}/G{sub M}{sup p}, made using polarization techniques and those made in unpolarized experiments. OLYMPUS operated on the DORIS storage ring at DESY, alternating between 2.01 GeV electron and positron beams incident on an internal hydrogen gas target. The experiment used a toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight detectors to measure rates for elastic scattering over the polar angular range of approximately 25°–75°. Symmetric Møller/Bhabha calorimeters at 1.29° and telescopes of GEM and MWPC detectors at 12° served as luminosity monitors. A total luminosity of approximately 4.5 fb{sup −1} was collected over two running periods in 2012. This paper provides details on the accelerator, target, detectors, and operation of the experiment.

  4. The OLYMPUS experiment

    International Nuclear Information System (INIS)

    The OLYMPUS experiment was designed to measure the ratio between the positron-proton and electron-proton elastic scattering cross sections, with the goal of determining the contribution of two-photon exchange to the elastic cross section. Two-photon exchange might resolve the discrepancy between measurements of the proton form factor ratio, μpGpE/GpM, made using polarization techniques and those made in unpolarized experiments. OLYMPUS operated on the DORIS storage ring at DESY, alternating between 2.01 GeV electron and positron beams incident on an internal hydrogen gas target. The experiment used a toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight detectors to measure rates for elastic scattering over the polar angular range of approximately 25 -75 . Symmetric Moeller/Bhabha calorimeters at 1.29 and telescopes of GEM and MWPC detectors at 12 served as luminosity monitors. A total luminosity of approximately 4.5 fb-1 was collected over two running periods in 2012. This paper provides details on the accelerator, target, detectors, and operation of the experiment.

  5. The OLYMPUS experiment

    Energy Technology Data Exchange (ETDEWEB)

    Milner, R.; Hasell, D.K. [Massachusetts Institute of Technology, Cambridge, MA (United States); Kohl, M. [Hampton Univ., Hampton, VA (United States); Collaboration: The OLYMPUS Collaboration; and others

    2013-12-15

    The OLYMPUS experiment was designed to measure the ratio between the positron-proton and electron-proton elastic scattering cross sections, with the goal of determining the contribution of two-photon exchange to the elastic cross section. Two-photon exchange might resolve the discrepancy between measurements of the proton form factor ratio, {mu}{sub p}G{sup p}{sub E}/G{sup p}{sub M}, made using polarization techniques and those made in unpolarized experiments. OLYMPUS operated on the DORIS storage ring at DESY, alternating between 2.01 GeV electron and positron beams incident on an internal hydrogen gas target. The experiment used a toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight detectors to measure rates for elastic scattering over the polar angular range of approximately 25 -75 . Symmetric Moeller/Bhabha calorimeters at 1.29 and telescopes of GEM and MWPC detectors at 12 served as luminosity monitors. A total luminosity of approximately 4.5 fb{sup -1} was collected over two running periods in 2012. This paper provides details on the accelerator, target, detectors, and operation of the experiment.

  6. Olympus beacon receiver

    Science.gov (United States)

    Ostergaard, Jens

    1988-01-01

    A medium-size Beacon Receiving System for reception and processing of the B1 (20 GHz) and B2 (30 GHz) beacons from Olympus has been developed. Integration of B1 and B2 receiving equipment into one system using one antenna and a common computer for control and data processing provides the advantages of a compact configuration and synchronization of the two receiver chains. Range for co-polar signal attenuation meaurement is about 30 dB for both beacons, increasing to 40 dB for B2 if the receivers are synchronized to B1. The accuracy is better than 0.5 dB. Cross-polarization discriminations of the order of 10 to 30 dB may be determined with an accuracy of 1 to 2 dB. A number of radiometers for complementary measurements of atmospheric attenuation of 13 to 30 GHz has also been constructed. A small multi-frequency system for operation around 22 GHz and 31 GHz is presently under development.

  7. Olympus Mons in Color

    Science.gov (United States)

    1997-01-01

    Sections of MOC images P024_01 and P024_02, shown here in color composite form, were acquired with the low resolution red and blue wide angle cameras over a 5 minute period starting when Mars Global Surveyor was at its closest point to the planet at the beginning of its 24th orbit (around 4:00 AM PDT on October 20, 1997). To make this image, a third component (green) was synthesized from the red and blue images. During the imaging period, the camera was pointed straight down towards the martian surface, 176 km (109 miles) below the spacecraft. During the time it took to acquire the image, the spacecraft rose to an altitude of 310 km (193 miles). Owing to data camera scanning rate and data volume constraints, the image was acquired at a resolution of roughly 1 km (0.609 mile) per pixel. The image shown here covers an area from 12o to 26o N latitude and 126o N to 138o W longitude. The image is oriented with north to the top.As has been noted in other MOC releases, Olympus Mons is the largest of the major Tharsis volcanoes, rising 25 km (15.5 miles) and stretching over nearly 550 km (340 miles) east-west. The summit caldera, a composite of as many as seven roughly circular collapse depressions, is 66 by 83 km (41 by 52 miles) across. Also seen in this image are water-ice clouds that accumulate around and above the volcano during the late afternoon (at the time the image was acquired, the summit was at 5:30 PM local solar time). To understand the value of orbital observations, compare this image with the two taken during approach (PIA00929 and PIA00936), that are representative of the best resolution from Earth.Through Monday, October 28, the MOC had acquired a total of 132 images, most of which were at low sun elevation angles. Of these images, 74 were taken with the high resolution narrow angle camera and 58 with the low resolution wide angle cameras. Twenty-eight narrow angle and 24 wide angle images were taken after the suspension of aerobraking. These images

  8. The OLYMPUS internal hydrogen target

    Energy Technology Data Exchange (ETDEWEB)

    Bernauer, J.C., E-mail: bernauer@mit.edu [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); Carassiti, V.; Ciullo, G. [Istituto Nazionale di Fisica Nucleare and Università, 44100 Ferrara (Italy); Henderson, B.S. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); Ihloff, E.; Kelsey, J. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); MIT-Bates Linear Accelerator Center, Middleton, MA 01949 (United States); Lenisa, P. [Istituto Nazionale di Fisica Nucleare and Università, 44100 Ferrara (Italy); Milner, R. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); MIT-Bates Linear Accelerator Center, Middleton, MA 01949 (United States); Schmidt, A. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); Statera, M. [Istituto Nazionale di Fisica Nucleare and Università, 44100 Ferrara (Italy)

    2014-08-01

    An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

  9. The OLYMPUS Internal Hydrogen Target

    CERN Document Server

    Bernauer, J C; Ciullo, G; Henderson, B S; Ihloff, E; Kelsey, J; Lenisa, P; Milner, R; Schmidt, A; Statera, M

    2014-01-01

    An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

  10. Olympus Realizes Its Three "Social INs"

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Founded in 1919, Olympus has been manufacturing optical products ranging from medical imaging to life sciences equipment, among others, for 90 years. Olympus’ core market is optical and digital technologies and it produces medical endoscopes,

  11. Lava Flows around Olympus Mons

    Science.gov (United States)

    2002-01-01

    [figure removed for brevity, see original site] At first glance, this image of lava flows around the large scarp of Olympus Mons shows little contrast in surface materials due to dust cover, but a closer look reveals textures characteristic of the variable surface roughness associated with different lava flows in this region. The lobate edges of the flows are distinctive, and permit the discrimination of many overlapping individual flows. On small scales, the surfaces of some flows look wrinkly and ropy, indicating a relatively fluid type of lava flow referred to as pahoehoe. Other surfaces appear more rough and broken, and might be referred to as a'a flows, which have higher viscosities and effusion rates compared to pahoehoe flows. The surface textures of lava flows can thus sometimes be used for comparative purposes to infer lava viscosity and effusion rates. There is also a bright streak in the wind shadow of the impact crater in the lower left of the image where dust that settles onto the surface is not easily scoured away.Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the

  12. Olympus Imaging Fraud Scandal: A Case Study

    Science.gov (United States)

    Elam, Dennis; Madrigal, Marion; Jackson, Maura

    2014-01-01

    This case examines the two decade long tobashi scheme by Olympus Imaging Executives to hide $1.7 billion in losses. In the 1980s, a soaring yen and falling dollar caused bottom line income problems for many Japanese companies. Some companies sought to offset the declining revenue with zaiteku, a form of speculative investment. While early…

  13. Major Martian Volcanoes from MOLA - Olympus Mons

    Science.gov (United States)

    2000-01-01

    Two views of Olympus Mons, shown as topography draped over a Viking image mosaic. MOLA's regional topography has shown that this volcano sits off to the west of the main Tharsis rise rather than on its western flank. The topography also clearly shows the relationship between the volcano's scarp and massive aureole deposit that was produced by flank collapse. The vertical exaggeration is 10:1.

  14. Evaluation of the Olympus AU 400 clinical chemistry analyzer.

    Science.gov (United States)

    Bilić, A; Alpeza, I; Rukavina, A S

    2000-01-01

    The performance of the Olympus AU 400 clinical chemistry analyzer was evaluated according to the guidelines of the European Committee for Clinical Laboratory Standards. The following analytes were tested: glucose, urea, creatinine, calcium, AST, ALT, CK, LDH, ALP and amylase. The Olympus AU 400 was compared with the Olympus AU 800. Coefficients of correlation showed high correlation between the compared analyzers. Other performances (intra- and inter-assay variation, carry-over and interferences) of the analyzer were satisfactory.

  15. DNA-PK assay

    Science.gov (United States)

    Anderson, Carl W.; Connelly, Margery A.

    2004-10-12

    The present invention provides a method for detecting DNA-activated protein kinase (DNA-PK) activity in a biological sample. The method includes contacting a biological sample with a detectably-labeled phosphate donor and a synthetic peptide substrate defined by the following features to provide specific recognition and phosphorylation by DNA-PK: (1) a phosphate-accepting amino acid pair which may include serine-glutamine (Ser-Gln) (SQ), threonine-glutamine (Thr-Gln) (TQ), glutamine-serine (Gln-Ser) (QS), or glutamine-threonine (Gln-Thr) (QT); (2) enhancer amino acids which may include glutamic acid or glutamine immediately adjacent at the amino- or carboxyl- side of the amino acid pair and forming an amino acid pair-enhancer unit; (3) a first spacer sequence at the amino terminus of the amino acid pair-enhancer unit; (4) a second spacer sequence at the carboxyl terminus of the amino acid pair-enhancer unit, which spacer sequences may include any combination of amino acids that does not provide a phosphorylation site consensus sequence motif; and, (5) a tag moiety, which may be an amino acid sequence or another chemical entity that permits separating the synthetic peptide from the phosphate donor. A compostion and a kit for the detection of DNA-PK activity are also provided. Methods for detecting DNA, protein phosphatases and substances that alter the activity of DNA-PK are also provided. The present invention also provides a method of monitoring protein kinase and DNA-PK activity in living cells. -A composition and a kit for monitoring protein kinase activity in vitro and a composition and a kit for monitoring DNA-PK activities in living cells are also provided. A method for identifying agents that alter protein kinase activity in vitro and a method for identifying agents that alter DNA-PK activity in living cells are also provided.

  16. The First Olympus Confocal Micro Imaging Competition China Award Ceremony

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    On January 20, 2010, the award ceremony for the First Olympus Confocal Micro Imaging Competition China was held in Beijing. After rounds of judging and competition, 16 photos finally won the prize.The First Olympus Confocal MicroImaging Competition China Award Ceremony was organized by Sciencenet.cn

  17. Evaluation of the Olympus AU-510 analyser.

    Science.gov (United States)

    Farré, C; Velasco, J; Ramón, F

    1991-01-01

    The selective multitest Olympus AU-510 analyser was evaluated according to the recommendations of the Comision de Instrumentacion de la Sociedad Española de Quimica Clinica and the European Committee for Clinical Laboratory Standards. The evaluation was carried out in two stages: an examination of the analytical units and then an evaluation in routine work conditions. The operational characteristics of the system were also studied.THE FIRST STAGE INCLUDED A PHOTOMETRIC STUDY: dependent on the absorbance, the inaccuracy varies between +0.5% to -0.6% at 405 nm and from -5.6% to 10.6% at 340 nm; the imprecision ranges between -0.22% and 0.56% at 405 nm and between 0.09% and 2.74% at 340 nm. Linearity was acceptable, apart from a very low absorbance for NADH at 340 nm; and the imprecision of the serum sample pipetter was satisfactory.TWELVE SERUM ANALYTES WERE STUDIED UNDER ROUTINE CONDITIONS: glucose, urea urate, cholesterol, triglycerides, total bilirubin, creatinine, phosphate, iron, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase.The within-run imprecision (CV%) ranged from 0.67% for phosphate to 2.89% for iron and the between-run imprecision from 0.97% for total bilirubin to 7.06% for iron. There was no carryover in a study of the serum sample pipetter. Carry-over studies with the reagent and sample pipetters shows some cross contamination in the iron assay.

  18. The RAI DBS experiment with Olympus

    Science.gov (United States)

    Castelli, Enzo

    The Italian broadcasting network (RAI) has studied the development of a national DBS service in an effort to outline a proposal for a space segment configuration compatible with development of new services, including HDTV. Proposals so far considered feature the integration of RAI's channel on Olympus in a future operational system and after extensive experimental use. Contents of the experimental program are discussed, and need for a broadcasting standard which considers projected introduction of HDTV is noted. The debate between RAI and consumer electronic industries on the use of broadcasting standards is outlined. The position of RAI in the context of HDTV and DBS is defined and the issue of determining the most effective transmission standard during the experimental stage is raised. It is pointed out that, in the absence of new production facilities for HDTV, the maximum quality which MAC will yield will be that of PAL since programs must be produced in PAL and then converted into MAC. Two alternatives for strategy on the use of broadcasting standards for DBS are offered. Finally, technical experiments and a market survey are discussed.

  19. The Olympus PAX, measurement of mechanism induced vibration

    Science.gov (United States)

    Tunbridge, D.

    1993-04-01

    The ultrasensitive accelerometer package known as the PSDE (Payload and Spacecraft Demonstration and Experimentation program) Accelerometer Experiment, or 'PAX', is described. This package, which is onboard the Olympus telecommunication satellite, was designed to measure the minute disturbances caused by the operation of onboard equipment. This data was used to study the operating environment to be experienced by a highly sensitive laser based communications package called SILEX to be flown on the next generation of ESA telecommunications spacecraft, Artemis and DRS (Data Relay Satellite). A secondary purpose of PAX is to monitor the different mechanisms on board Olympus at intervals throughout their lifetime, in order to detect trends in performance.

  20. Symmetric Moeller/Bhabha luminosity monitor for the OLYMPUS experiment

    Energy Technology Data Exchange (ETDEWEB)

    Perez Benito, Roberto [Helmholtz-Institut Mainz (Germany); Collaboration: OLYMPUS-Collaboration

    2014-07-01

    The OLYMPUS experiment ran on the DORIS storage ring at DESY, Hamburg to measure the elastic cross sections for both positron and electron scattering from hydrogen to quantify the two-photon contribution to elastic ep scattering. Two-photon exchange is widely considered to be responsible for the the discrepancy in the proton form factor ratio determined using the Rosenbluth technique and polarization transfer. The experiment alternated daily between positron and electron beams at 2.01 GeV incident on an unpolarized, internal, hydrogen gas target. The luminosity delivered to the experiment was monitored by a redundant set of detectors: a high precision, symmetric Moeller/Bhabha calorimeter and a tracking telescope at 12 degrees. The symmetric Moeller/Bhabha calorimeter was built at Mainz and consisted of two symmetric arrays of lead fluoride crystals. Results on the performance of the SYMB luminosity monitor will be presented together with an overview of the OLYMPUS experiment.

  1. Symmetric Moller/Bhabha luminosity monitor for the Olympus experiment

    Energy Technology Data Exchange (ETDEWEB)

    Perez Benito, Roberto Francisco [Helmholtz-Institut Mainz (Germany)

    2012-07-01

    Recent determinations of the proton electric to magnetic form factor ratio indicate an unexpected discrepancy between the obtained ratio using polarization transfer measurements and the ratio from Rosenbluth separation technique in unpolarized cross section measurements. This discrepancy has been explained as the effect of two-photon exchange. OLYMPUS experiment at DESY has been proposed to measure the ratio of positron-proton and electron-proton elastic scattering cross sections. The experiment will utilize intense beams of electrons and positrons in the DORIS ring incident on an internal hydrogen gas target. Results of the performance of the Symmetric Moller and Bhabha Luminosity Monitor are presented in this contribution together with the physics case for the OLYMPUS and the current status of the project.

  2. Mars - Stratigraphy and gravimetry of Olympus Mons and its aureole

    Science.gov (United States)

    Hiller, K. H.; Neukum, G. P. O.; Janle, P.; Guest, J. E.; Lopes, R. M. C.

    1982-01-01

    The relative ages of the major geologic units on and around Olympus Mons are considered, together with an interpretation of the gravity anomaly found for this area. The crater data for this investigation have been acquired and interpreted according to the method outlined by Neukum and Hiller (1981). After careful geological mapping, craters clearly identified as impacts are measured and counted. Crater frequency values per sq km for craters greater than or equal to 1 km ('crater retention ages') are read from the individual counts by fitting the Martian cumulative crater production size-frequency distribution to the individual counts. In addition to age dating, the problem of the origin and nature of the aureole materials using gravity data is addressed. This is done by determining whether the line-of-sight gravity extending from Olympus Mons to the northwestern part of the aureole can be explained by the aureole masses alone or whether additional high-density intrusive masses must be assumed in the aureola area.

  3. Joukkovelkakirjat pk-yrityksen rahoitusmuotona

    OpenAIRE

    Leino, Eveliina

    2014-01-01

    Tämän tutkimuksen tavoitteena on tarkastella joukkovelkakirjoja pk-yrityksen rahoitusmuotona. Tutkimuksessa keskitytään tarkastelemaan joukkovelkakirjoja, jotka listataan First North Bond Market Finland -markkinapaikalla. Tutkimus tehdään toimeksiantona Juras Oy:n asiakasyrityksille. Tutkimuksen teoreettinen viitekehys pohjautuu joukkovelkakirjan käsitteen määrittelyyn, sen eri ominaisuuksiin ja tyyppeihin sekä riskeihin. Lisäksi käsitellään lyhyesti euroalueen pankkisääntely. Tutkimuksen...

  4. Using THEMIS and TES to conduct a mineral analysis on Olympus Mons

    Science.gov (United States)

    Chase, Nicole Danielle

    2016-10-01

    Olympus Mons is the largest shield volcano in our known solar system. In previous studies, the composition of the basaltic lava flows on Olympus Mons was shown to be similar to the composition of those lava flows of Earth's shield volcanoes. It has been suggested that basalt located near volcanoes contained bacteria living below the surface of the Earth. In this pilot study, the effect of Olympus Mons' aspect (i.e. north- vs. south-facing slope) on its mineral composition was examined. Imagery from Thermal Emission Imaging System (THEMIS), onboard the Mars Odyssey spacecraft, were used because Olympus Mons' size and surface roughness hinder rover exploration. After removing transmission errors and performing an atmospheric correction, the THEMIS images were ready to be analyzed via a mineral spectral library. Using Arizona State University's Thermal Emission Spectrometer (TES) derived mineral spectral library, the images were classified in ENVI. These classifications were verified using ASU's GIS tool, Java Mission-planning and Analysis for Remote Sensing (JMARS) and TES. Results show differences in the mineral composition and in the geological features on Olympus Mons' surface. The mineral vanadinite was shown to be prevalent on the sampled southern portions of Olympus Mons, but was sparse on the sampled northern portions. Previous studies suggested that the mineral ilmenite, which this study found in high concentrations on the sampled northern portions of Olympus Mons, might serve as a food source for iron-oxidizing and iron-scavenging bacteria. Future research should focus on better understanding the concentrations of vanadinite and ilmenite on Olympus Mons to see if these minerals have a role in the potential presence of bacteria on Olympus Mons.

  5. Red blood cell PK deficiency: An update of PK-LR gene mutation database.

    Science.gov (United States)

    Canu, Giulia; De Bonis, Maria; Minucci, Angelo; Capoluongo, Ettore

    2016-03-01

    Pyruvate kinase (PK) deficiency is known as being the most common cause of chronic nonspherocytic hemolytic anemia (CNSHA). Clinical PK deficiency is transmitted as an autosomal recessive trait, that can segregate neither in homozygous or in a compound heterozygous modality, respectively. Two PK genes are present in mammals: the pyruvate kinase liver and red blood cells (PK-LR) and the pyruvate kinase muscle (PK-M), of which only the first encodes for the isoenzymes normally expressed in the red blood cells (R-type) and in the liver (L-type). Several reports have been published describing a large variety of genetic defects in PK-LR gene associated to CNSHA. Herein, we present a review of about 250 published mutations and six polymorphisms in PK-LR gene with the corresponding clinical and molecular data. We consulted the PubMed website for searching mutations and papers, along with two main databases: the Leiden Open Variation Database (LOVD, https://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=PKLR) and Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PKLR) for selecting, reviewing and listing the annotated PK-LR gene mutations present in literature. This paper is aimed to provide useful information to clinicians and laboratory professionals regarding overall reported PK-LR gene mutations, also giving the opportunity to harmonize data regarding PK-deficient individuals. PMID:26832193

  6. Symmetric Moeller/Bhabha luminosity monitor for the OLYMPUS experiment

    Energy Technology Data Exchange (ETDEWEB)

    Perez Benito, Roberto [Johannes Gutenberg Universitaet Mainz (Germany); Collaboration: OLYMPUS-Collaboration

    2013-07-01

    Recent determinations of the proton electric to magnetic form factor ratio indicate an unexpected discrepancy between the ratio obtained using polarisation transfer measurements and the ratio from the Rosenbluth separation technique in unpolarised cross section measurements. This discrepancy has been explained theoretically as the effect of two-photon exchange. The OLYMPUS experiment at DESY proposed to measure the ratio of positron-proton and electron-proton elastic scattering cross sections. The experiment utilised beams of electrons and positrons in the DORIS ring at 2.0 GeV incident on an unpolarized internal hydrogen gas target and the BLAST detector from the MIT-Bates Linear Accelerator Center with modest upgrades. In order to reduce the systematic error from the determination of luminosity, redundant measurements of the relative luminosity were necessary. The symmetric Moeller/Bhabha luminosity monitor built at the University of Mainz consisted of two symmetric arrays of lead fluoride (PbF{sub 2}) crystals. Results on the performance of the symmetric Moeller/Bhabha luminosity monitor are presented in this contribution.

  7. Geologic Mapping of the Olympus Mons Volcano, Mars

    Science.gov (United States)

    Bleacher, J. E.; Williams, D. A.; Shean, D.; Greeley, R.

    2012-01-01

    We are in the third year of a three-year Mars Data Analysis Program project to map the morphology of the Olympus Mons volcano, Mars, using ArcGIS by ESRI. The final product of this project is to be a 1:1,000,000-scale geologic map. The scientific questions upon which this mapping project is based include understanding the volcanic development and modification by structural, aeolian, and possibly glacial processes. The project s scientific objectives are based upon preliminary mapping by Bleacher et al. [1] along a approx.80-km-wide north-south swath of the volcano corresponding to High Resolution Stereo Camera (HRSC) image h0037. The preliminary project, which covered approx.20% of the volcano s surface, resulted in several significant findings, including: 1) channel-fed lava flow surfaces are areally more abundant than tube-fed surfaces by a ratio of 5:1, 2) channel-fed flows consistently embay tube-fed flows, 3) lava fans appear to be linked to tube-fed flows, 4) no volcanic vents were identified within the map region, and 5) a Hummocky unit surrounds the summit and is likely a combination of non-channelized flows, dust, ash, and/or frozen volatiles. These results led to the suggestion that the volcano had experienced a transition from long-lived tube-forming eruptions to more sporadic and shorter-lived, channel-forming eruptions, as seen at Hawaiian volcanoes between the tholeiitic shield building phase (Kilauea to Mauna Loa) and alkalic capping phase (Hualalai and Mauna Kea).

  8. Deutsche Bundespost/FTZ activities in the Olympus experimentation program: Ojectives and experiment set-ups

    Science.gov (United States)

    Lugert, M.

    1989-05-01

    The activities of the Telecommunications Engineering Center (FTZ) of the Deutsche Bundespost in the Olympus Experimentation Program are presented. The various communication experiments which are to be carried out in the framework of the GECO (Group of Experimenters of CEPT Administrations for Olympus) are described. These include: TV news gathering/TV distribution, teleseminar experiments, data distribution to microterminal experiments, SMS-TDMA (time division multiple access) experiments, and TDMA frequency diversity experiments. The applied experiment configurations and the layout and design of the transportable 20/30 GHz earth stations to be used in the experiments are described.

  9. Digitaalisen markkinoinnin tehostaminen PK-sektorilla

    OpenAIRE

    Viisteensaari, Keijo

    2015-01-01

    Opinnäytetyössä käsiteltiin digitaalista markkinointia. Työssä annetaan tietoa, miten PK-sektorin yrityksessä voidaan toteuttaa tuloksellista digitaalista markkinointia. Opinnäytetyö sisältää oppaan, jonka avulla PK-sektorin yrityksessä voidaan toteuttaa digitaalinen markkinointi. Työ ei paneudu teknisiin yksityiskohtiin vaan markkinoinnin näkökulmaan digitaalisen markkinoinnin toteuttamisessa. Aiheena digitaalinen markkinointi on ajankohtainen ja tärkeä, koska markkinointi on yhä enemmän sii...

  10. Setup of a LED light-pulser system for the OLYMPUS experiment; Aufbau eines LED-Lichtpulsersystems fuer das OLYMPUS-Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Rehman, Waqaas

    2011-12-15

    The aim of this thesis consists in the construction and test of an external light-calibration system based on light-emitting diodes (LED) for the application at the symmetric Moller/Bhabha (SYMB) luminosity monitor. In chapter 2 the theoretical foundations of the OLYMPUS experiment, especially of the SYMB luminosity monitor are explained. Thereafter in chapter 3 the details of the setup of the OLYMPUS experiment and the fundamental properties of the SYMB detectors are discussed. In chapter 4 the whole concept of the LED light-pulser system is treated. In chapter 5 then test measurements with the ready LED light-pulser system are described. Thereby the light source shall be optimized in the shape that thereafter light pulses with short signal width are producable. Also different measurements for the unique characterization of the systems are performed. In chapter 6 light-intensity measurements during the operation of the LED light-pulser system are described.

  11. Number & operations drill sheets : grades PK-2

    CERN Document Server

    Reed, Nat

    2010-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the number & operations concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. Each drill sheet contains warm-up and timed drill activities for the student to practice number & operations concepts.

  12. Geometry task sheets : grades pk-2

    CERN Document Server

    Rosenberg, Mary

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the geometry concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  13. Algebra task sheets : grades pk-2

    CERN Document Server

    Reed, Nat

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the algebraic concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  14. Cloning of the Streptococcus gordonii PK488 gene, encoding an adhesin which mediates coaggregation with Actinomyces naeslundii PK606.

    OpenAIRE

    Andersen, R N; Ganeshkumar, N.; Kolenbrander, P. E.

    1993-01-01

    Coaggregation between Streptococcus gordonii PK488 and Actinomyces naeslundii PK606 is mediated by a 38-kDa streptococcal protein, designated ScaA. The gene, scaA, which encodes this protein has been cloned into Escherichia coli. A genomic S. gordonii PK488 library (in Lambda ZAP II) was screened with anti-S. gordonii immunoglobulin G absorbed with S. gordonii PK1804, an isogenic coaggregation-defective mutant of strain PK488. A positive recombinant phage was isolated, and a phagemid designat...

  15. The European Satellite Users' Association as an education broadcaster on Olympus

    Science.gov (United States)

    Groombridge, Brian

    1989-05-01

    The possibilities opened to educators by the offer of transmission time on the Olympus DBS (Direct Broadcast Satellite) are outlined. The need for proper organization and funding of potential education and training programs is stressed. Eurostep, a cooperative association for educators using satellites is introduced. New markets for tele-education in the fields of medical consultation, vocational and corporate training, and language teaching are described. The need for cooperation between various tele-education programs is stressed.

  16. Riskianalyysi pk-sektorin case yritykselle

    OpenAIRE

    Lehtimäki, Tuukka

    2015-01-01

    Tutkimus toteutettiin toimeksiantona rakennusalan pk-kohdeyritykselle. Yritys on toiminut alalla vuodesta 2011, jossa on yhteensä 3 työntekijää. Työn tavoitteena oli kartoittaa yrityksen riskitekijöitä, arvioida niiden vakavuutta sekä selvittää miten niihin on kohdeyrityksessä varauduttu. Tutkimus toteutettiin kvalitatiivisena tutkimuksena. Tutkimuksen teoriaosuudessa määriteltiin riski sekä käytiin läpi erilaisia riskiryhmiä, jotka olivat liiketoimintariskit, vahinkoriskit, henkilöriskit ...

  17. Finanssikriisin vaikutukset vakkasuomalaisten pk-yritysten investointeihin

    OpenAIRE

    Nieminen, Saija

    2011-01-01

    Opinnäytetyön tarkoituksena oli tutkia vuonna 2007 USA:sta levinneen finanssikriisin vaikutuksia vakkasuomalaisiin pk-yrityksiin. Pääasiallisesti tarkastelun kohteena olivat yritysten investoinnit, jotka usein vähenevät talouden laskusuhdanteissa. Toissijaisesti tarkasteltiin yrityksissä tapahtuneita henkilöstömuutoksia, kuten irtisanomisia ja lomautuksia, sekä investointirahoituksen saannissa ja käytössä tapahtuneita muutoksia. Opinnäytetyössä kartoitettiin myös yritysten tulevaisuuden suunn...

  18. Selvitys Pietarin liiketoimintamahdollisuuksista suomalaisille pk-yrityksille

    OpenAIRE

    Murtomäki, Jesse

    2014-01-01

    Opinnäytetyön tavoitteena oli selvittää, minkälaisia liiketoimintamahdollisuuksia Pietari voisi tarjota suomalaisille pk-yrityksille. Alatavoitteena oli löytää Pietarin markkina-alueella vallitsevia trendejä ja kasvavia potentiaalisia toimialoja sekä tarkastella, mitkä tekijät tekevät liiketoimintaympäristöstä kannattavan. Opinnäytetyön suorittaminen alkoi keväästä 2013 ja se saatiin päätökseen vuoden 2014 alkupuoliskolla. Työllä ei ole toimeksiantajaa, vaan työ on tehty yleisluontoiseksi...

  19. Photoregulated expression of the PsPK3 and PsPK5 genes in pea seedlings.

    Science.gov (United States)

    Khanna, R; Lin, X; Watson, J C

    1999-01-01

    The PsPK3 and PsPK5 genes of the garden pea encode protein-serine/threonine kinases whose catalytic domains are closely related to known signal transducing kinases from animals and fungi. The PsPK3 polypeptide is predicted to be located in the nucleus, whereas PsPK5 is a homologue of NPH1, the probable blue light receptor for phototropism from Arabidopsis. We found previously that when etiolated pea seedlings are illuminated with continuous white light, PsPK3 and PsPK5 transcript levels within apical buds decline substantially, reaching their minimum levels within one day of exposure to light. The role of light in regulating the expression of the PsPK3 and PsPK5 genes was investigated further. To gain insight into the rapidity with which expression changes, 6-day old, dark-grown pea seedlings were transferred to continuous white light, and PsPK3 and PsPK5 RNA levels monitored over the ensuing 24 h. While transcripts from the RbcS gene family increase, the PsPK3 and PsPK5 mRNAs decline rapidly to their minimum levels. PsPK5 mRNA declines 10-fold in ca. 2 h, whereas PsPK3 mRNA declines 4-fold in ca. 8 h. We used single pulses of light to elucidate which photoreceptor triggers the negative regulation of PsPK3 and PsPK5 gene expression. To assess phytochrome involvement, etiolated seedlings were treated with single pulses of red light, red followed by far-red light, or far-red light alone. RbcS induction by a red light pulse is reversible with a subsequent far-red light pulse, clearly showing that phytochrome mediates its induction. Likewise, RbcS expression is induced with a single pulse of blue light or a dichromatic pulse of red+blue light. However, none of these pulses trigger the PsPK3 and PsPK5 mRNA levels to decline. Given the lack of effectiveness of light pulses, etiolated seedlings were transferred to continuous light of three different qualities to determine the spectral sensitivity of PsPK3 and PsPK5 gene expression. Exposure to continuous red, continuous

  20. Complex plasma research on ISS PKE-Nefedov, PK-3 Plus, PK-4, and impact laboratory

    Science.gov (United States)

    Seurig, R.; Morfill, G.; Fortov, V.; Hofmann, P.

    2009-09-01

    The international research on ISS in dusty plasma (also known as complex plasma) under prolonged microgravity condition entered a new area in March 2001: The PKE-Nefedov facility (formerly called PKE 3) performed its first experiment in radio-frequency induced complex plasmas. This bilateral German-Russian research facility operated successfully in over 13 missions over 5 years until its internal resources were consumed—resulting so far in over 30 peer-reviewed scientific publications. In place of PKE-Nefedov is the next generation experiment apparatus PK 3 Plus with refined and more powerful instruments and diagnostics, which had its on-orbit commissioning in January 2006. While PK 3 Plus will further investigate the radio-frequency induced plasmas for the next few years the new PK-4 research facility is under development for investigation of direct-current induced complex plasma. Because the highly successful series of stand-alone PK experiment facilities cover only a fraction of the overall complex plasma research field the IMPACT (International Multi-User Plasma, Atmospheric and Cosmic Dust Twin) Laboratory project was initiated. The IMPF/ICAPS (IMPACT) Laboratory is the logical next step to provide a home and rallying point for the worldwide growing research efforts under microgravity conditions in the fields of dusty plasma and interactions of cosmic and atmospheric particle systems.

  1. [PK/PD modeling of aminoglycoside nephrotoxicity].

    Science.gov (United States)

    Rougier, F; Corvaisier, S; Ducher, M; Claude, D; Jelliffe, R W; Maire, P

    2003-06-01

    Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.

  2. Investigating Late Amazonian Volcanotectonic Activity on Olympus Mons, Mars using Flank Vents and Arcuate Graben

    Science.gov (United States)

    Peters, S.; Christensen, P. R.

    2015-12-01

    Volcanism, a fundamental process in shaping the Martian surface, is crucial to understanding its evolution. Olympus Mons, the largest volcano on Mars, is one of several large shield volcanoes. Previous studies were technologically limited to large features associated with these constructs. With the advent of high resolution datasets, we are now able to investigate smaller features, such as flank vents and arcuate graben. Flank vents, common on polygenetic volcanoes, indicate that magma has propagated away from the main conduit and/or magma chamber. Vent morphology allows for the characterization of magma properties and eruption rates. Graben indicate extensional deformation. The distribution of graben provides information on stresses that acted on the volcano. In lieu of geophysical, spectral and in-situ data, morphology, morphometry and spatial relationships are powerful tools. We utilized high resolution image data (CTX, HiRISE and THEMIS IR) and topographic data (HRSC DTM, MOLA) to identify and characterize flank vents and graben. We observed 60 flank vents and 84 arcuate graben on Olympus Mons. Flank vents display varying morphologies and morphometries, suggesting different eruption styles and variable magma volatility. Vents occur primarily on the lower flank. This suggests magma has propagated substantial distances from the magma chamber. Observed clustering of vents may also indicate shallow magma sources. Similarly, graben are observed on the lower flank crosscutting young lava flows that have mantled portions of the escarpment. This indicates either gravitational spreading of Olympus Mons or flexure of the lithosphere in response to the load of the edifice. Collectively, the distribution of flank vents and arcuate graben suggests a similar development to that proposed for Ascraeus Mons. Based on superposition relationships and dates from previous studies, the flank vents and graben formed in the Late Amazonian (≤500 Ma).

  3. Data acquisition, preprocessing and analysis for the Virginia Tech OLYMPUS experiment

    Science.gov (United States)

    Remaklus, P. Will

    1991-01-01

    Virginia Tech is conducting a slant path propagation experiment using the 12, 20, and 30 GHz OLYMPUS beacons. Beacon signal measurements are made using separate terminals for each frequency. In addition, short baseline diversity measurements are collected through a mobile 20 GHz terminal. Data collection is performed with a custom data acquisition and control system. Raw data are preprocessed to remove equipment biases and discontinuities prior to analysis. Preprocessed data are then statistically analyzed to investigate parameters such as frequency scaling, fade slope and duration, and scintillation intensity.

  4. PK-sensitive PrPSc is infectious and shares basic structural features with PK-resistant PrPSc

    Science.gov (United States)

    One of the main characteristics of the transmissible isoform of the prion protein (PrPSc) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrPSc following Western blot or ELISA. More recently, researchers determ...

  5. The aureole of Olympus Mons (Mars) as the compound deposit of submarine landslides

    Science.gov (United States)

    De Blasio, Fabio Vittorio

    2011-12-01

    The enigmatic deposits building up the Olympus Mons aureole on Mars are likely among the largest landslide remnants in the Solar System. These deposits exhibit an extraordinary run-out distance (up to nearly 700 km), in spite of a fall height some 100 times smaller. After quantifying the mobility of the Olympus Mons aureole lobes it is suggested, based on dynamical considerations and morphological analysis, that the aureole could be the consequence of a series of gigantic subaqueous landslides. In order to bring evidence in favor of this interpretation, comparisons are drawn between the different landslide deposits on Earth and Mars, emphasizing the similarity with the rock avalanches of the Canary Islands and the Hawaii. The results of experimental subaqueous debris flows are also analyzed, and numerical calculations are introduced to simulate the dynamics of flow. In analogy with certain subaqueous landslides on Earth, it is possible that the outstanding run-out of the aureole lobes was a consequence of hydroplaning, a natural lubrication by water during flow.

  6. Emerging roles of DNA-PK besides DNA repair.

    Science.gov (United States)

    Kong, Xianming; Shen, Ying; Jiang, Na; Fei, Xin; Mi, Jun

    2011-08-01

    The DNA-dependent protein kinase (DNA-PK) is a DNA-activated serine/threonine protein kinase, and abundantly expressed in almost all mammalian cells. The roles of DNA-PK in DNA-damage repair pathways, including non-homologous end-joining (NHEJ) repair and homologous recombinant (HR) repair, have been studied intensively. However, the high levels of DNA-PK in human cells are somewhat paradoxical in that it does not impart any increased ability to repair DNA damage. If DNA-PK essentially exceeds the demand for DNA damage repair, why do human cells universally express such high levels of this huge complex? DNA-PK has been recently reported to be involved in metabolic gene regulation in response to feeding/insulin stimulation; our studies have also suggested a role of DNA-PK in the regulation of the homeostasis of cell proliferation. These novel findings expand our horizons about the importance of DNA-PK. PMID:21514376

  7. OlyMPUS - The Ontology-based Metadata Portal for Unified Semantics

    Science.gov (United States)

    Huffer, E.; Gleason, J. L.

    2015-12-01

    The Ontology-based Metadata Portal for Unified Semantics (OlyMPUS), funded by the NASA Earth Science Technology Office Advanced Information Systems Technology program, is an end-to-end system designed to support data consumers and data providers, enabling the latter to register their data sets and provision them with the semantically rich metadata that drives the Ontology-Driven Interactive Search Environment for Earth Sciences (ODISEES). OlyMPUS leverages the semantics and reasoning capabilities of ODISEES to provide data producers with a semi-automated interface for producing the semantically rich metadata needed to support ODISEES' data discovery and access services. It integrates the ODISEES metadata search system with multiple NASA data delivery tools to enable data consumers to create customized data sets for download to their computers, or for NASA Advanced Supercomputing (NAS) facility registered users, directly to NAS storage resources for access by applications running on NAS supercomputers. A core function of NASA's Earth Science Division is research and analysis that uses the full spectrum of data products available in NASA archives. Scientists need to perform complex analyses that identify correlations and non-obvious relationships across all types of Earth System phenomena. Comprehensive analytics are hindered, however, by the fact that many Earth science data products are disparate and hard to synthesize. Variations in how data are collected, processed, gridded, and stored, create challenges for data interoperability and synthesis, which are exacerbated by the sheer volume of available data. Robust, semantically rich metadata can support tools for data discovery and facilitate machine-to-machine transactions with services such as data subsetting, regridding, and reformatting. Such capabilities are critical to enabling the research activities integral to NASA's strategic plans. However, as metadata requirements increase and competing standards emerge

  8. Global Citizenship Education within a Context of Accountability and 21st Century Skills: The Case of Olympus High School

    Science.gov (United States)

    DiCicco, Marzia Cozzolino

    2016-01-01

    This article addresses the present gap in empirical research on the possibilities and challenges of global citizenship education in U.S. public schools by presenting findings from a five-year, ethnographic case study. The setting for this study is Olympus High School, a small, suburban public high school in Pennsylvania. Beginning in the 2009-2010…

  9. Ground based measurements of particulate emissions from supersonic transports. Concorde olympus engine

    Energy Technology Data Exchange (ETDEWEB)

    Whitefield, Ph.D.; Hagen, D.E. [Missouri Univ., Rolla, MO (United States). Cloud and Aerosol Sciences Lab.; Lilenfeld, H.V. [McDonnell Douglas Corp., St. Louis, MO (United States)

    1997-12-31

    The application of a mobile aerosol monitoring facility, the Mobile Aerosol Sampling System (MASS) is described to characterize engine aerosol emissions from the Rolls Royce Olympus Engine. The multi-configurational MASS has been employed in both ground and airborne field operations. It has been successfully flown on research aircrafts. In ground tests the MASS has participated in numerous jet engine related ground tests, and has been deployed to resolve aerosol generation problems in a high power chemical laser system. In all cases the measurements were made on samples taken from a harsh physical and chemical environment, with both high and low temperature and pressure, and in the presence of highly reactive gases. (R.P.) 9 refs.

  10. Measurement and tricubic interpolation of the magnetic field for the OLYMPUS experiment

    CERN Document Server

    Bernauer, J C; Elbakian, G; Gavrilov, G; Goerrissen, N; Hasel, D K; Henderson, B S; Holler, Y; Karyan, G; Ludwig, J; Marukyan, H; Naryshkin, Y; O'Connor, C; Russell, R L; Schmidt, A; Schneekloth, U; Suvorov, K; Veretennikov, D

    2016-01-01

    The OLYMPUS experiment used a 0.3 T toroidal magnetic spectrometer to measure the momenta of outgoing charged particles. In order to accurately determine particle trajectories, knowledge of the magnetic field was needed throughout the spectrometer volume. For that purpose, the magnetic field was measured at over 36,000 positions using a three-dimensional Hall probe actuated by a system of translation tables. We used these field data to fit a numerical magnetic field model, which could be employed to calculate the magnetic field at any point in the spectrometer volume. Calculations with this model were computationally intensive; for analysis applications where speed was crucial, we pre-computed the magnetic field and its derivatives on an evenly spaced grid so that the field could be interpolated between grid points. We developed a spline-based interpolation scheme suitable for SIMD implementations, with a memory layout chosen to minimize space and optimize the cache behavior to quickly calculate field values....

  11. OLYMPUS DISS - A Readily Implemented Geographic Data and Information Sharing System

    Science.gov (United States)

    Necsoiu, D. M.; Winfrey, B.; Murphy, K.; McKague, H. L.

    2002-12-01

    Electronic information technology has become a crucial component of business, government, and scientific organizations. In this technology era, many enterprises are moving away from the perception that information repositories are only a tool for decision-making. Instead, many organizations are learning that information systems, which are capable of organizing and following the interrelations between information and both the short-term and strategic organizational goals, are assets themselves, with inherent value. Olympus Data and Information Sharing System (DISS) is a system developed at the Center for Nuclear Waste Regulatory Analyses (CNWRA) to solve several difficult tasks associated with the management of geographical, geological and geophysical data. Three of the tasks were to (1) gather the large amount of heterogeneous information that has accumulated over the operational lifespan of CNWRA, (2) store the data in a central, knowledge-based, searchable database and (3) create quick, easy, convenient, and reliable access to that information. Faced with these difficult tasks CNWRA identified the requirements for designing such a system. Key design criteria were: (a) ability to ingest different data formats (i.e., raster, vector, and tabular data); (b) minimal expense using open-source and commercial off-the-shelf software; (c) seamless management of geospatial data, freeing up time for researchers to focus on analyses or algorithm development, rather than on time consuming format conversions; (d) controlled access; and (e) scalable architecture to meet new and continuing demands. Olympus DISS is a solution that can be easily adapted to small and mid-size enterprises dealing with heterogeneous geographic data. It uses established data standards, provides a flexible mechanism to build applications upon and output geographic data in multiple and clear ways. This abstract is an independent product of the CNWRA and does not necessarily reflect the views or

  12. In vitro dynamic pharmacokinetic/pharmacodynamic(PK/PD) modeling and PK/PD cutoff of cefquinome against Haemophilus parasuis

    OpenAIRE

    Xiao, Xia; Sun, Jian; Chen, Yi; Huang, Rui-Juan; Huang, Ting; Qiao, Guilin Gary; Zhou, Yu-Feng; Liu, Ya-Hong

    2015-01-01

    Background Haemophilus parasuis (H. parasuis) causes Glässer’s disease and multisystem infectious disease. It is one of the major causes of nursery mortality in swine herds. Cefquinome (CEQ) is proposed for the treatment of pigs against respiratory tract infection. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff of this drug against H. parasuis. Results A total of 213 H. parasuis strains were isolated from diseased pigs in China. The minimal inhibitory concen...

  13. Characterization of Streptococcus gordonii (S. sanguis) PK488 adhesin-mediated coaggregation with Actinomyces naeslundii PK606.

    OpenAIRE

    Kolenbrander, P. E.; Andersen, R N

    1990-01-01

    Intergeneric coaggregation of Streptococcus gordonii (S. sanguis) PK488 and Actinomyces naeslundii PK606 was studied by using coaggregation-defective (Cog-) mutants of both strains. A streptococcal protein of 38 kilodaltons was identified with anti-S. gordonii serum absorbed with Cog- cells of the streptococcus. Absorbed immunoglobulin G specifically blocked coaggregation of the streptococcus-actinomyces pair but did not affect the coaggregation of the streptococcus with other coaggregation p...

  14. Autographa californica multiple nucleopolyhedrovirus PK-1 is essential for nucleocapsid assembly

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Changyong, E-mail: cyliang@yzu.edu.cn [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Li, Min; Dai, Xuejuan; Zhao, Shuling; Hou, Yanling; Zhang, Yongli; Lan, Dandan [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Wang, Yun; Chen, Xinwen [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

    2013-09-01

    PK-1 (Ac10) is a baculovirus-encoded serine/threonine kinase and its function is unclear. Our results showed that a pk-1 knockout AcMNPV failed to produce infectious progeny, while the pk-1 repair virus could rescue this defect. qPCR analysis demonstrated that pk-1 deletion did not affect viral DNA replication. Analysis of the repaired recombinants with truncated pk-1 mutants demonstrated that the catalytic domain of protein kinases of PK-1 was essential to viral infectivity. Moreover, those PK-1 mutants that could rescue the infectious BV production defect exhibited kinase activity in vitro. Therefore, it is suggested that the kinase activity of PK-1 is essential in regulating viral propagation. Electron microscopy revealed that pk-1 deletion affected the formation of normal nucleocapsids. Masses of electron-lucent tubular structures were present in cell transfected with pk-1 knockout bacmid. Therefore, PK-1 appears to phosphorylate some viral or cellular proteins that are essential for DNA packaging to regulate nucleocapsid assembly. - Highlights: • A pk-1 knockout AcMNPV failed to produce infectious progeny. • The pk-1 deletion did not affect viral DNA replication. • The catalytic domain of protein kinases (PKc) of PK-1 was essential to viral infectivity. • The kinase activity of PK-1 is essential in regulating viral propagation. • PK-1 appears to phosphorylate some viral proteins that are essential for DNA packaging to regulate nucleocapsid assembly.

  15. The atmospheric temperatures over Olympus Mons on Mars: An atmospheric hot ring

    Science.gov (United States)

    Wolkenberg, P.; Formisano, V.; Rinaldi, G.; Geminale, A.

    2010-05-01

    We study the thermal fields over Olympus Mons separating seasons (northern spring and summer against southern spring and summer) and local time observations (day side versus night side). Temperature vertical profiles retrieved from Planetary Fourier Spectrometer on board Mars Express (PFS-MEX) data have been used. In many orbits (running north to south along a meridian) passing over the top of the volcano there is evidence of a hot air on top of the volcano, of two enhancement of the air temperature both north and south of it and in between a collar of air that is colder than nearby at low altitudes, and warmer than nearby at high altitudes. Mapping together many orbits passing over or near the volcano we find that the hot air has the tendency to form an hot ring around it. This hot structure occurs mostly between LT = 10.00 and 15.00 and during the northern summer. Distance of the hot structure from the top of the volcano is about 600 km (10° of latitude). The hot atmospheric region is 300-420 km (5-7°) wide. Hot ring temperature contrasts of about 40 K occur at 2 km above the surface and decrease to 20 K at 5 km and to 10 K at 10 km. The atmospheric circulation over an area of 40° × 40° (latitudes and longitudes) is affected by the topography and the presence of Olympus Mons (-133°W, 18°N). We discuss also the thermal stability of the atmosphere over the selected area using the potential temperatures. The temperature field over the top of the volcano shows unstable atmosphere within 10 km from the surface. Finally, we interpret the hot temperatures around volcano as an adiabatic compression of down-welling branch coming from over the top of volcano. Different air temperature profiles are observed in the same seasons during the night, or in different seasons. In northern spring-summer during the night the isothermal contours do not show the presence of the volcano until we reach close to the surface very much, where a thermal inversion is observed. The

  16. Measurement and tricubic interpolation of the magnetic field for the OLYMPUS experiment

    Science.gov (United States)

    Bernauer, J. C.; Diefenbach, J.; Elbakian, G.; Gavrilov, G.; Goerrissen, N.; Hasell, D. K.; Henderson, B. S.; Holler, Y.; Karyan, G.; Ludwig, J.; Marukyan, H.; Naryshkin, Y.; O'Connor, C.; Russell, R. L.; Schmidt, A.; Schneekloth, U.; Suvorov, K.; Veretennikov, D.

    2016-07-01

    The OLYMPUS experiment used a 0.3 T toroidal magnetic spectrometer to measure the momenta of outgoing charged particles. In order to accurately determine particle trajectories, knowledge of the magnetic field was needed throughout the spectrometer volume. For that purpose, the magnetic field was measured at over 36,000 positions using a three-dimensional Hall probe actuated by a system of translation tables. We used these field data to fit a numerical magnetic field model, which could be employed to calculate the magnetic field at any point in the spectrometer volume. Calculations with this model were computationally intensive; for analysis applications where speed was crucial, we pre-computed the magnetic field and its derivatives on an evenly spaced grid so that the field could be interpolated between grid points. We developed a spline-based interpolation scheme suitable for SIMD implementations, with a memory layout chosen to minimize space and optimize the cache behavior to quickly calculate field values. This scheme requires only one-eighth of the memory needed to store necessary coefficients compared with a previous scheme (Lekien and Marsden, 2005 [1]). This method was accurate for the vast majority of the spectrometer volume, though special fits and representations were needed to improve the accuracy close to the magnet coils and along the toroidal axis.

  17. [Bacteriological evaluation of a procedure for disinfecting the Olympus GIF-D2 panendoscope].

    Science.gov (United States)

    Ramírez Ramos, A; Domínguez, N; Makino, R; Barrera, C

    1980-01-01

    We have performed a total of 107 cultures from three critical areas of an Olympus Panendoscope Model GIF-D2 in order to evaluate bacteriologically cur system of desinfection of this endoscope. Samples were taken from the distal end, external surface and biopsy canal before and after an endoscopic examination was performed. The procedure of desinfection employed was as follows: washing of the distal end, external surface and biopsy canal with Hexaclorophel (Phisohex) diluted 50% with water and a second washing with tap water. In the middle of the study, we added a second washing of the biopsy canal with ten ml. of ether alcohol to allow for better drying. As a result of the present study we observed that in the distal end in 50% of the samples we encountered bacteria. Cultures of the external surface were positive in 20% of samples. The biopsy canal should be washed with ether alcohol to allow for complete drying, because when we did not use this method, Pseudomonas Aeruginosa was isolated. After this modification we did not isolate bacteria. The most frequent types of isolated bacteria were from the normal oropharyngeal flora. From the present study we can conclude that desinfection of the Panendespe with Hexaclorophen gives satisfactory results on the external surface of the endoscope. Biopsy canal requires additional washing with ether alcohol. However, both procedures do not assure a satisfactory desinfection of the distal end.

  18. Role of DNA-PK subunits in radiosensitization by hyperthermia

    NARCIS (Netherlands)

    Woudstra, EC; Konings, AWT; Jeggo, PA; Kampinga, HH

    1999-01-01

    Thermal radiosensitization is thought to result from inhibition of repair of radiation-induced DNA damage, DNA double-strand breaks in particular. Since the DNA-dependent protein kinase (DNA-PK) complex plays a major role in the nonhomologous end-joining of DSBs, it has been suggested that inactivat

  19. Data analysis & probability task sheets : grades pk-2

    CERN Document Server

    Cook, Tanya

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the data analysis & probability concepts addressed by the NCTM standards and encourages your students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  20. A comparison of the structure of the PK-sensitive and PK-resistant forms of PrPSc(Abstract)

    Science.gov (United States)

    Background/Introduction. One of the distinctive phenotypes of the infectious isoform of PrP(PrPSc)is its resistance to proteinase K (PK) digestion. The diagnosis of prion diseases is based on this phenotypic observation. More recently, researchers determined that there is a sizeable fraction of PrPS...

  1. n×k×m格图Pn×Pk×Pm的控制数%DOMINATION NUMBERS OF GRID GRAPHS Pn × Pk × Pm

    Institute of Scientific and Technical Information of China (English)

    姜伟; 杨德林; 刘焕平

    2002-01-01

    n×k× m格图Pn×Pk×Pm是长为n的路与长为k的路与长为m的路的积,本文给出了Pn×Pk×Pm的控制数的一些结论.①当| n|≤3,|k|≤3,| m|≤3时的Pn×Pk×Pm格图的控制数.②当n∈N,k∈N,m∈N时,Pn×Pk×Pm的控制数的一个上界.③利用"隔空配凑"方法,生成Pn×Pk×Pm格图,并用其将Pn×Pk×Pm的控制数的上界加以优化.

  2. Five strands of math drills big book : grades PK-2

    CERN Document Server

    Reed, Nat; Forest, Chris

    2011-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. Included are warm-up and timed drill activities which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  3. Five strands of math tasks big book : grades pk-2

    CERN Document Server

    Reed, Nat; Forest, Chris

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Included are challenging problem-solving tasks which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  4. DNA-PK Deficiency in Alzheimer’s Disease

    Science.gov (United States)

    Kanungo, Jyotshna

    2016-01-01

    Alzheimer’s disease (AD) is characterized by neuronal death with an accumulaton of intra-cellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. Reduced DNA repair ability has been reported in AD brains. In neurons, the predominant mechanism to repair double-strand DNA breaks (DSB) is non-homologous end joining (NHEJ) that requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD DNA-PK catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 (Ku80) and p70 (Ku70) subunits. Upon binding to double-stranded DNA ends, Ku recruits DNA-PKcs to process NHEJ. In AD brains, reduced NHEJ activity as well as DNA-PKcs and Ku protein levels have been shown. Normal aging brains also show a reduction in both DNA-PKcs and Ku levels questioning a direct link between NHEJ ability and AD, and suggesting additional players/events in AD pathogenesis. Deficiency of Ku80, a somatostatin receptor, can disrupt somatostatin signaling thus inducing amyloid beta (Aβ) generation, which in turn can potentiate DNA-PKcs degradation and consequently loss of NHEJ activity, an additional step negatively affecting DSB repair. Trigger of these two different pathways culminating in genome instability may differentiate the outcomes between AD and normal aging. PMID:27376156

  5. On the categorical nature of Korean /pk/ place assimilation

    Science.gov (United States)

    Son, Minjung; Kochetov, Alexei

    2001-05-01

    Korean exhibits regressive place assimilation in /pk/ clusters, which has been described as gradient and rate dependent. However, this assumption has empirically only been tested on the basis of air pressure data [Jun, 1996] which does not provide a direct record of articulator movement. The present study examines articulator movement using EMMA. For three Seoul-dialect speakers, stimuli containing /pk/ clusters were elicited word-medially (for words and nonwords) and in a phrase-boundary condition; two rates were employed. Results show that the labial can indeed reduce word medially, rendering [kk]. However, contrary to previous claims, the data demonstrate that reduction in /pk/ is always categorical, although it is optional or stochastic in its occurrence. Substantial interspeaker variation is observed, with the frequency of reduction being higher at fast rate and ranging overall from 6 at both rates and is never gradient. The lack of reduction in nonsense words and in the phrase boundary condition shows that the process is sensitive to lexical properties. The observed tendency for more gestural overlap word medially compared to the phrase-boundary condition supports the hypothesis that gestural overlap plays a role in the origins of place assimilation. [Work supported by NIH.

  6. Study of fade and inter-fade durations in Ku- and Ka- band frequencies using OLYMPUS satellite beacons

    OpenAIRE

    Ajaz, Haroon

    1993-01-01

    Fade and inter-fade duration data obtained from the three beacons at 12, 20, and 30 GHz aboard the OLYMPUS satellite were analyzed. The different types of signal impairments and their causes were highlighted and a literature survey conducted. Twelve months of fade and inter-fade data were analyzed and the results of these statistics are presented in the form of tables and figures. The analysis was done on both the monthly and annual data. These tables and figures show that at t...

  7. Improving the Accuracy of Predicting Maximal Oxygen Consumption (VO2pk)

    Science.gov (United States)

    Downs, Meghan E.; Lee, Stuart M. C.; Ploutz-Snyder, Lori; Feiveson, Alan

    2016-01-01

    Maximal oxygen (VO2pk) is the maximum amount of oxygen that the body can use during intense exercise and is used for benchmarking endurance exercise capacity. The most accurate method to determineVO2pk requires continuous measurements of ventilation and gas exchange during an exercise test to maximal effort, which necessitates expensive equipment, a trained staff, and time to set-up the equipment. For astronauts, accurate VO2pk measures are important to assess mission critical task performance capabilities and to prescribe exercise intensities to optimize performance. Currently, astronauts perform submaximal exercise tests during flight to predict VO2pk; however, while submaximal VO2pk prediction equations provide reliable estimates of mean VO2pk for populations, they can be unacceptably inaccurate for a given individual. The error in current predictions and logistical limitations of measuring VO2pk, particularly during spaceflight, highlights the need for improved estimation methods.

  8. Vanillins—a novel family of DNA-PK inhibitors

    OpenAIRE

    Durant, Stephen; Karran, Peter

    2003-01-01

    Non-homologous DNA end-joining (NHEJ) is a major pathway of double strand break (DSB) repair in human cells. Here we show that vanillin (3-methoxy-4-hydroxybenzaldehyde)—a naturally occurring food component and an acknowledged antimutagen, anticlastogen and anticarcinogen—is an inhibitor of NHEJ. Vanillin blocked DNA end-joining by human cell extracts by directly inhibiting the activity of DNA-PK, a crucial NHEJ component. Inhibition was selective and vanillin had no detectable effect on othe...

  9. Pk-yrityksen osakekannan ja osakasluettelon ylläpito

    OpenAIRE

    Pihlava, Matti

    2009-01-01

    Tämän opinnäytetyön aiheena oli pienten ja keskisuurten yritysten osakekannan ja osakasluettelon ylläpito. Opinnäytetyössä tutkittiin yritysten mahdollisuuksia toteuttaa ja ylläpitää osakerekisterijärjestelmää sekä osinkojärjestelmää. Tutkimuksen tarkoituksena oli tuottaa tuloksia, joita erikokoiset pk-sektorin yritykset voivat soveltaa omiin järjestelmiinsä. Tutkimusmenetelmänä käytettiin kvalitatiivista tutkimusmenetelmää. Tutkimuksessa selvitettiin muun muassa käytännön mahdollisuuksia tot...

  10. Mars Express HRSC View of Western Olympus Mons: Evidence for Ice-bearing Deposit and High-Altitude Glaciation

    Science.gov (United States)

    Basilevsky, A. T.; Neukam, G.; Ivanov, B. A.; Werner, S. C.; vanGesselt, S.; Head, J. W.; Hauber, E.

    2005-01-01

    This study is based on the geological analysis of the HRSC images taken on the orbit 0143 (12 m/px in nadir channel). The study area includes the western segment of Olympus Mons and the adjacent lowland plains (Fig. 1). Part of the volcano above the scarp is rather flat and is called "summit plateau" below. What is often called the volcano scarp is a slope classified into three morphologic types: Type 1 (S1 in Fig.1) is the steepest and dominated by ravines in its upper part and by talus beneath; Type 2 (S2) is intermediate in steepness and dominated by downslope trending linear depressions, part of which have channel-like morphology; and Type 3 (S3), is the most gentle and covered by lava flows, continuing from the summit plateau down to the lowland plains.

  11. Yhtiömuodon vaikutus pk-yrityksen verotukseen

    OpenAIRE

    Metsälä, Kimmo

    2015-01-01

    Opinnäytetyön aiheena oli tutkia, mikä yhtiömuoto on paras pk-yrittäjän kannalta verotuksellisesti. Huomioon lopullisessa tarkastelussa otettiin toki muitakin seikkoja, mutta pääpaino oli selvittää verotuksellisesti paras yhtiömuoto. Opinnäytetyössä tarkasteltiin myös tilannetta, jossa yrittäjän valitsema yhtiömuoto olisi väärä ja mitä sen vaihtamiseksi kevyemmin verotettavaan vaadittaisiin. Opinnäytetyössä lähteinä on käytetty sekä kirjallisuutta että www-lähteitä. Verotus oli muuttunut vuod...

  12. Native American Women Perceptions in Pk-12 Administrative Positions in North Dakota Public Schools

    Science.gov (United States)

    DeCoteau, Lanelia Irene

    2012-01-01

    Historically Native American women have experienced barriers in their rise to Pk-12 educational leadership positions. There is limited research available on Native American women in educational leadership. Therefore, the purpose for this survey study was to discover what inspired current Pk-12 Native American women educational leaders to choose…

  13. Expression pattern of the CsPK3 auxin-responsive protein kinase gene.

    Science.gov (United States)

    Chono, M; Suzuki, Y; Nemoto, K; Yamane, H; Murofushi, N; Yamaguchi, I

    2001-03-01

    We have previously cloned a cDNA of a putative serine/threonine protein kinase gene named CsPK3 from cucumber, the mRNA level of which was up-regulated by auxin and down-regulated by light irradiation. To examine the CsPK3 gene expression in detail, we cloned a genomic DNA of CsPK3 gene and made transgenic tobacco (Nicotiana tabacum L. cv. Petit Havana SR1) plants containing the fused CsPK3 promoter-beta-glucuronidase gene. The beta-glucuronidase expression was detected in the shoot apex, vascular tissues, and the outermost layer of cortex. The histological distribution of CsPK3 mRNA in cucumber seedlings was supported by in situ hybridization, where the positive signals were observed in similar tissues as those observed by beta-glucuronidase staining. The responsiveness of the CsPK3 gene to auxin and light was also confirmed for beta-glucuronidase activity. The pattern of beta-glucuronidase staining changed during the development of the tobacco seedlings. The results of our experiment showed that CsPK3 was expressed in a wide variety of tissues and cells in which the developmental and growth controls by auxin are suggested.

  14. Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining

    Directory of Open Access Journals (Sweden)

    Cynthia L. Hendrickson

    2010-01-01

    Full Text Available In mammalian cells, DNA double-strand breaks (DSBs are primarily repaired by nonhomologous end joining (NHEJ. The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA-dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that mediate DSB end joining. However, recent studies show that additional DNA-PK-independent NHEJ pathways also exist. Unfortunately, the presence of DNA-PKcs appears to inhibit DNA-PK-independent NHEJ, and in vitro analysis of DNA-PK-independent NHEJ in the presence of the DNA-PKcs protein remains problematic. We have developed an in vitro assay that is preferentially active for DNA-PK-independent DSB repair based solely on its reaction conditions, facilitating coincident differential biochemical analysis of the two pathways. The results indicate the biochemically distinct nature of the end-joining mechanisms represented by the DNA-PK-dependent and -independent NHEJ assays as well as functional differences between the two pathways.

  15. Cisplatin–DNA adducts inhibit translocation of the Ku subunits of DNA-PK

    OpenAIRE

    Turchi, John J.; Henkels, Karen M.; Zhou, Yun

    2000-01-01

    We have determined the effect of cisplatin–DNA damage on the ability of the DNA-dependent protein kinase (DNA-PK) to interact with duplex DNA molecules in vitro. The Ku DNA binding subunits of DNA-PK display a reduced ability to translocate on duplex DNA containing cisplatin–DNA adducts compared to control, undamaged duplex DNA. The decreased rates of translocation resulted in a decrease in the association of the p460 catalytic subunit of DNA-PK (DNA-PKcs) with the Ku–DNA complex. In addition...

  16. PK2025型细纱摇架的应用探讨%Application and Discussion of PK2025 Spinning Cradle

    Institute of Scientific and Technical Information of China (English)

    李忠民; 严绒飞

    2012-01-01

    探讨PK2025型摇架的使用性能.介绍了PK2025型摇架的技术规格及性能特点,与国产YJ142型摇架进行了对比试验,并对有关纺纱工艺参数进行了优选试验.结果表明:PK2025型摇架在纺纱质量及降低细纱断头率方面优于YJ142型摇架,但也存在摇架臂抬起角度较小、不利操作、配套胶辊硬度低、耐磨性较差等问题.认为:加压锭差小、配套胶辊质量好是该摇架成纱质量较优的主要原因,使用中应注意优化有关工艺参数,合理配置胶辊硬度,以获得更好的纺纱效果.%Application property of PK2025 spinning cradle was discussed. Technology characteristics and performance of PK2025 spinning cradle were introduced. Comparing to domestic YJ142 spinning cradle, tests were contrasted, related spinning parameter were optimized. The result shows that PK2025 spinning cradle is better than that of YJ142 spinning cradle in aspect of spinning quality and reducing spinning breakages. There are some problems existed in PK2025 spinning cradle,such as less cradle arm angle,inconvenient in operation,lower hardness and worse wear-resistance of supporting rubber-covered roll ect. It is considered that advantages of PK2025 spinning cradle including smaller differences among spindles, better quality of supporting rubber-covered roll. Related parameter should be optimized in application, rubber-covered roll hardness should be selected rationally to ensure better spinning effect.

  17. Defining interactions between DNA-PK and ligase IV/XRCC4

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Hsin-Ling; Yannone, Steven M.; Chen, David J.

    2001-04-10

    Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double-strand breaks in mammalian cells. DNA-dependent protein kinase (DNA-PK), ligase IV, and XRCC4 are all critical components of the NHEJ repair pathway. DNA-PK is composed of a heterodimeric DNA-binding component, Ku, and a large catalytic subunit, DNA-PKcs. Ligase IV and XRCC4 associate to form a multimeric complex that is also essential for NHEJ. DNA-PK and ligase IV/XRCC4 interact at DNA termini which results in stimulated ligase activity. Here we define interactions between the components of these two essential complexes, DNA-PK and ligase IV/XRCC4. We find that ligase IV/XRCC4 associates with DNA-PK in a DNA-independent manner. The specific protein-protein interactions that mediate the interaction between these two complexes are further identified. Direct physical interactions between ligase IV and Ku as well as between XRCC4 and DNA-PKcs are shown. No direct interactions are observed between ligase IV and DNA-PKcs or between XRCC4 and Ku. Our data defines the specific protein pairs involved in the association of DNA-PK and ligase IV/XRCC4, and suggests a molecular mechanism for coordinating the assembly of the DNA repair complex at DNA breaks.

  18. Cytotoxic effects of 125I-labeled PBZr ligand PK 11195 in prostatic tumor cells: therapeutic implications

    International Nuclear Information System (INIS)

    The effect of [125I]PK 11195 was examined in human prostatic tumor cells (DU 145) in culture and compared with Na[125I] and non-radioactive PK 11195. [125I]PK 11195 was clearly cytocidal. The data for dose-related cell survival with [125I]PK 11195 showed a linear relationship. Na[125I] or non-labeled PK 11195 at similar concentrations did not lead to any cell killing. The uptake of [125I]PK 11195 and [3H]PK 11195 in cells was very similar. Fragmentation of DNA measured by agarose gel electrophoresis showed that exposure of DU 145 cells to [125I]PK 11195 for 1, 4 or 24 h caused no fragmentation. These results indicate that nuclear DNA is not the prime binding site for [125I]PK 11195, which is consistent with the presence of specific peripheral benzodiazepine receptors (PBZr) in the mitochondria. The cell killing effect of [125I]PK 11195 suggests the use of PBZr ligand for radiotherapy

  19. Small molecules, inhibitors of DNA-PK, targeting DNA repair and beyond

    Directory of Open Access Journals (Sweden)

    David eDavidson

    2013-01-01

    Full Text Available Many current chemotherapies function by damaging genomic DNA in rapidly dividing cells ultimately leading to cell death. This therapeutic approach differentially targets cancer cells that generally display rapid cell division compared to normal tissue cells. However, although these treatments are initially effective in arresting tumor growth and reducing tumor burden, resistance and disease progression eventually occur. A major mechanism underlying this resistance is increased levels of cellular DNA repair. Most cells have complex mechanisms in place to repair DNA damage that occurs due to environmental exposures or normal metabolic processes. These systems, initially overwhelmed when faced with chemotherapy induced DNA damage, become more efficient under constant selective pressure and as a result chemotherapies become less effective. Thus, inhibiting DNA repair pathways using target specific small molecule inhibitors may overcome cellular resistance to DNA damaging chemotherapies. Non-homologous end joining (NHEJ a major mechanism for the repair of double strand breaks (DSB in DNA is regulated in part by the serine/threonine kinase, DNA dependent protein kinase (DNA-PK. The DNA-PK holoenzyme acts as a scaffold protein tethering broken DNA ends and recruiting other repair molecules. It also has enzymatic activity that may be involved in DNA damage signaling. Because of its’ central role in repair of DSBs, DNA-PK has been the focus of a number of small molecule studies. In these studies specific DNA-PK inhibitors have shown efficacy in synergizing chemotherapies in vitro. However, compounds currently known to specifically inhibit DNA-PK are limited by poor pharmacokinetics: these compounds have poor solubility and have high metabolic lability in vivo leading to short serum half-lives. Future improvement in DNA-PK inhibition will likely be achieved by designing new molecules based on the recently reported crystallographic structure of DNA-PK

  20. [Proliferation characteristics of a PK-15 cell-adapted strain of porcine parvovirus].

    Science.gov (United States)

    Wu, Yun-Fei; Zhu, Ling; Xu, Zhi-Wen; Fu, Meng-Jin; Chen, Lei; Yang, Ai-Guo; Guo, Wan-Zhu

    2013-06-01

    To study the proliferation characteristics of PPV in differently infected way and the variance of concentrations in different cells. A strain of porcine parvovirus(PPV) was adapted to PK-15 cells, and a Real-time fluorescent quantitative PCR (FQ-PCR) assay was developed based on the specific region of the NS1 gene of PPV to quantify the PPV. The FQ-PCR was used to measure the viral concentration of virus-infected cells by simultaneous or step by step inoculation and plot one-step growth curves. The proliferation characteristics of PPV strain in different cells lines (HeLa, MDBK, PK-15 ,ST, F81, BHK-21 and Marc-145) was also compared. The results showed the PK-15 cell -adapted strain of PPV produced CPE after 12 passages, and maintained stable CPE at the following 10 messages. The one-step growth curve showed that the virus concentration of simultaneous inoculation was higher than that of the step-by-step inoculation, and the proliferation cycle of step-by-step inoculation was shorter. The proliferation ability of PPV strain in different cells showed that CPE appeared first inPK-15, followed by ST, HeLa and MDBK, and the virus concentration was highest in ST, followed byPK-15, MDBK and HeLa. NO proliferation was observed in F81, BHK-21 and Marc-145 cells. These findings lay a material foundation for the basic researches on PPV and the development of vaccine.

  1. Porcine circovirus-2 capsid protein induces cell death in PK15 cells

    Energy Technology Data Exchange (ETDEWEB)

    Walia, Rupali; Dardari, Rkia, E-mail: rdardari@ucalgary.ca; Chaiyakul, Mark; Czub, Markus

    2014-11-15

    Studies have shown that Porcine circovirus (PCV)-2 induces apoptosis in PK15 cells. Here we report that cell death is induced in PCV2b-infected PK15 cells that express Capsid (Cap) protein and this effect is enhanced in interferon gamma (IFN-γ)-treated cells. We further show that transient PCV2a and 2b-Cap protein expression induces cell death in PK15 cells at rate similar to PCV2 infection, regardless of Cap protein localization. These data suggest that Cap protein may have the capacity to trigger different signaling pathways involved in cell death. Although further investigation is needed to gain deeper insights into the nature of the pathways involved in Cap-induced cell death, this study provides evidence that PCV2-induced cell death in kidney epithelial PK15 cells can be mapped to the Cap protein and establishes the need for future research regarding the role of Cap-induced cell death in PCV2 pathogenesis. - Highlights: • IFN-γ enhances PCV2 replication that leads to cell death in PK15 cells. • IFN-γ enhances nuclear localization of the PCV2 Capsid protein. • Transient PCV2a and 2b-Capsid protein expression induces cell death. • Cell death is not dictated by specific Capsid protein sub-localization.

  2. Simulation of the impact of rifampicin on darunavir/ritonavir PK and dose adjustment strategies in HIV-infected patients: a population PK approach

    Directory of Open Access Journals (Sweden)

    Laura Dickinson

    2014-11-01

    Full Text Available Introduction: Treatment of HIV/TB co-infection is challenging due to high drug–drug interaction potential between antiretrovirals and rifamycins, such as rifampicin (RIF. The PK interaction between darunavir/ritonavir (DRV/RTV and RIF has not been studied. Utilizing other protease inhibitor data, population PK modelling and simulation was applied to assess the impact of RIF on DRV/RTV PK and generate alternative dosing strategies to aid future clinical trial design. Materials and Methods: A previously developed model describing DRV/RTV PK including data from three studies in HIV patients was used [n=51, 7 female, DRV/RTV 800/100 mg (n=32 or 900/100 mg once daily (qd; n=19 (1. The PK interaction between DRV/RTV and RIF was assumed to mimic that observed in HIV-infected, TB negative patients receiving lopinavir (LPV/RTV (n=21 (2. Simulations of DRV/RTV 800/100 mg qd (n=1000 were performed (-RIF. The model was adapted to increase the typical value of apparent oral clearance (CL/F by 71% and 36% and decrease relative bioavailability (F by 20% and 45% for DRV and RTV, respectively (2; 1000 simulations were generated (+RIF. Dose adjustments of DRV/RTV 1200/200 mg qd, 800/100 mg and 1200/150 mg twice daily (bid were simulated to overcome the interaction. DRV trough (Ctrough for each dosing scenario was compared to the reference (-RIF by GMR (90% CI. Results: DRV and RTV were described by a 1 and 2-compartment model, respectively. A maximum effect model, with RTV inhibiting DRV CL/F, best described the relationship between the drugs. Compared to the reference (-RIF, simulated DRV Ctrough was 70%, 46% and 20% lower for 800/100 mg qd, 1200/200 mg qd and 800/100 mg bid all +RIF, respectively. Ctrough was 38% higher with 1200/150 mg bid +RIF (Table 1. Conclusions: Modelling and simulation was used to investigate the theoretical impact of RIF on DRV/RTV PK. Based on simulations, 800/100 mg and 1200/150 mg both bid could largely overcome the impact of the

  3. The decay of $\\Lambda_b\\rightarrow p~K^-$ in QCD factorization approach

    CERN Document Server

    Zhu, Jie; Wei, Zheng-Tao

    2016-01-01

    With only the tree level operator, the decay of $\\Lambda_b\\rightarrow pK$ is predicted to be one order smaller than the experimental data. The QCD penguin effects should be taken into account. In this paper, we explore the one-loop QCD corrections to the decay of $\\Lambda_b\\to pK$ within the framework of QCD factorization approach. For the baryon system, the diquark approximation is adopted. The transition hadronic matrix elements between $\\Lambda_b$ and $p$ are calculated in the light front quark model. The branching ratio of $\\Lambda_b\\rightarrow pK$ is predicted to be about $4.85\\times 10^{-6}$ which is consistent with experimental data $(4.9\\pm 0.9)\\times 10^{-6}$. The CP violation is about 5\\% in theory.

  4. The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    A line of investigation in the search for sensitizing tumor cells to chemotherapy or radiotherapy relies on the selection of DNA repair inhibitors. In the area of DNA repair mechanisms, DNA-dependent protein kinase (DNA-PK) represents a key complex. Indeed DNA-PK is involved in the non-homologous end joining (NHEJ) process that corresponds to the major activity responsible for cell survival after ionizing radiation or chemotherapeutic treatment producing DNA double strand breaks. DNA-PK belongs to the PI3-K related kinase family and specific inhibitors have been recently selected and evaluated as radio- and chemo-sensitizers. These drugs, along with other ways to inhibit the DSBs repair process, are presented and discussed. (authors)

  5. Hyperbolic measure of maximal entropy for generic rational maps of P^k

    CERN Document Server

    Vigny, Gabriel

    2011-01-01

    Let f be a dominant rational map of P^k such that there exists s lambda_l(f) for all l. Under mild hypotheses, we show that, for A outside a pluripolar set of the group of automorphisms of P^k, the map f o A admits a hyperbolic measure of maximal entropy log(lambda_s(f)) with explicit bounds on the Lyapunov exponents. In particular, the result is true for polynomial maps hence for the homogeneous extension of f to P^{k+1}. This provides many examples where non uniform hyperbolic dynamics is established. One of the key tools is to approximate the graph of a meromorphic function by a smooth positive closed current. This allows us to do all the computations in a smooth setting, using super-potentials theory to pass to the limit.

  6. pKD: re-designing protein pK a values

    OpenAIRE

    Tynan-Connolly, Barbara M.; Nielsen, Jens Erik

    2006-01-01

    The pK a values in proteins govern the pH-dependence of protein stability and enzymatic activity. A large number of mutagenesis experiments have been carried out in the last three decades to re-engineer the pH-activity and pH-stability profile of enzymes and proteins. We have developed the pKD webserver (), which predicts sets of point mutations that will change the pK a values of a set of target residues in a given direction, thus allowing for targeted re-design of the pH-dependent character...

  7. Construction of an integrated map of rose with AFLP, SSR, PK, RGA, SCAR and morphological markers

    NARCIS (Netherlands)

    Yan Zifu, Z.; Denneboom, C.; Hattendorf, A.; Dolstra, O.; Debener, T.; Stam, P.; Visser, P.B.

    2005-01-01

    A high-density genetic map with a number of anchor markers has been created to be used as a tool to dissect genetic variation in rose. Linkage maps for the diploid 94/1 population consisting of 88 individuals were constructed using a total of 520 molecular markers including AFLP, SSR, PK, RGA, RFLP,

  8. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B

    2009-01-01

    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS...

  9. The human DNA-activated protein kinase, DNA-PK: Substrate specificity

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, C.W.; Connelly, M.A.; Zhang, H.; Sipley, J.A. [Brookhaven National Lab., Upton, NY (United States). Biology Dept.; Lees-Miller, S.P.; Lintott, L.G. [Univ. of Calgary, Alberta (Canada). Dept. of Biological Sciences; Sakaguchi, Kazuyasu; Appella, E. [National Institutes of Health, Bethesda, MD (United States). Lab. of Cell Biology

    1994-11-05

    Although much has been learned about the structure and function of p53 and the probable sequence of subsequent events that lead to cell cycle arrest, little is known about how DNA damage is detected and the nature of the signal that is generated by DNA damage. Circumstantial evidence suggests that protein kinases may be involved. In vitro, human DNA-PK phosphorylates a variety of nuclear DNA-binding, regulatory proteins including the tumor suppressor protein p53, the single-stranded DNA binding protein RPA, the heat shock protein hsp90, the large tumor antigen (TAg) of simian virus 40, a variety of transcription factors including Fos, Jun, serum response factor (SRF), Myc, Sp1, Oct-1, TFIID, E2F, the estrogen receptor, and the large subunit of RNA polymerase II (reviewed in Anderson, 1993; Jackson et al., 1993). However, for most of these proteins, the sites that are phosphorylated by DNA-PK are not known. To determine if the sites that were phosphorylated in vitro also were phosphorylated in vivo and if DNA-PK recognized a preferred protein sequence, the authors identified the sites phosphorylated by DNA-PK in several substrates by direct protein sequence analysis. Each phosphorylated serine or threonine is followed immediately by glutamine in the polypeptide chain; at no other positions are the amino acid residues obviously constrained.

  10. Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

    Science.gov (United States)

    Savu, Simona Nicoleta; Silvestro, Luigi; Surmeian, Mariana; Remis, Lina; Rasit, Yuksel; Savu, Simona Rizea; Mircioiu, Constantin

    2016-09-01

    The existence of a glucuronide conjugate of the major circulating clopidogrel metabolites, called clopidogrel acyl glucuronide (CAG), is already known. However, information regarding its pharmacokinetics (PK), metabolism, and clearance are modest. We investigated in vivo the potential CAG trans-esterification to clopidogrel (reaction occurring in vitro in particular conditions) by administering the metabolite to mice. Experiments were then carried out on men, clopidogrel administered alone or followed by activated charcoal intake (intestinal reabsorption blockade). Study objectives included: PK comparison of CAG, clopidogrel carboxylic acid (CCA), and clopidogrel in plasma, determination of their elimination patterns in urine and feces, and tracking of charcoal-induced changes in PK and/or urinary excretion that would indicate relevant enterohepatic recycling of CAG. In mice, CAG was rapidly hydrolyzed to CCA after oral administration, whereas by intravenous route metabolic conversion to CCA was delayed. No levels of clopidogrel were detected in mice plasma, excluding any potential trans-esterification or other form of back-conversion in vivo. PK experiments in man showed that CAG is hydrolyzed in the gastrointestinal tract (very low concentrations in feces), but there is no evidence of enterohepatic recirculation. Quantitation of the three moieties in stool samples accounted for only 1.2% of an administered dose, suggesting that other yet unknown metabolites/degradation products formed through metabolic processes and/or the activity of local microflora are mainly excreted by this route. In man CAG was confirmed as one of the major terminal metabolites of clopidogrel, with a PK behavior similar to CCA. PMID:27402727

  11. Quantification of (R)-[{sup 11}C]PK11195 binding in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Kropholler, M.A.; Boellaard, R.; Kloet, R.W.; Lammertsma, A.A. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, PO Box 7057, Amsterdam (Netherlands); Elzinga, E.H.; Voskuyl, A.E. [VU University Medical Centre, Department of Rheumatology, Amsterdam (Netherlands); Laken, C.J. van der; Dijkmans, B.A.C. [VU University Medical Centre, Department of Rheumatology, Amsterdam (Netherlands); Jan van Breemen Instituut, Amsterdam (Netherlands); Maruyama, K. [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan)

    2009-04-15

    Rheumatoid arthritis (RA) involves migration of macrophages into inflamed areas. (R)-[{sup 11}C]PK11195 binds to peripheral benzodiazepine receptors, expressed on macrophages, and may be used to quantify inflammation using positron emission tomography (PET). This study evaluated methods for the quantification of (R)-[{sup 11}C]PK11195 binding in the knee joints of RA patients. Data from six patients with RA were analysed. Dynamic PET scans were acquired in 3-D mode following (R)-[{sup 11}C]PK11195 injection. During scanning arterial radioactivity concentrations were measured to determine the plasma (R)-[{sup 11}C]PK11195 concentrations. Data were analysed using irreversible and reversible one-tissue and two-tissue compartment models and input functions with various types of metabolite correction. Model preferences according to the Akaike information criterion (AIC) and correlations between measures were evaluated. Correlations between distribution volume (V{sub d}) and standardized uptake values (SUV) were evaluated. AIC indicated optimal performance for a one-tissue reversible compartment model including blood volume. High correlations were observed between V{sub d} obtained using different input functions (R {sup 2}=0.80-1.00) and between V{sub d} obtained with one- and two-tissue reversible compartment models (R {sup 2}=0.75-0.94). A high correlation was observed between optimal V{sub d} and SUV after injection (R {sup 2}=0.73). (R)-[{sup 11}C]PK11195 kinetics in the knee were best described by a reversible single-tissue compartment model including blood volume. Applying metabolite corrections did not increase sensitivity. Due to the high correlation with V{sub d}, SUV is a practical alternative for clinical use. (orig.)

  12. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance.

    Science.gov (United States)

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-11-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  13. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance12

    Science.gov (United States)

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-01-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  14. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance

    Directory of Open Access Journals (Sweden)

    Euan A. Stronach

    2011-11-01

    Full Text Available Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinumresistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK, and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Re-sensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage–mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors.

  15. The solution number about a class matrix equation over Z/pkZ%环Z/pkZ上一类矩阵方程的解数

    Institute of Scientific and Technical Information of China (English)

    吴炎

    2003-01-01

    设R=Z/pkZ是模整数pk的有限局部环,i=ODi-DiO,B=(p-)μ(B-)是R上任意取定的2si阶交错阵,Δ={Pi∈GL2si(R)|Pi(D-)iPi′-(D-)i=B},其中Di=diag{p-ri,…,p-ri},0<ri<k,ri<μ≤k,si≥1.本文计算了n(Δ),其中n(Δ)表示集合Δ中元素的个数.

  16. Total and unbound darunavir (DRV pharmacokinetics (PK in HIV-1-infected pregnant women

    Directory of Open Access Journals (Sweden)

    C Zorrilla

    2012-11-01

    Full Text Available Antiretroviral (ARV therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission (MTCT. Physiologic changes during pregnancy can affect PK. We present the PK of total and unbound (pharmacologically active DRV in HIV-1-infected pregnant women receiving twice-daily (bid DRV/ritonavir (rtv. This Phase IIIb study enrolled HIV-1-infected pregnant women≥18 years old in the 2nd trimester of pregnancy receiving DRV/rtv 600/100 mg bid and other ARVs. DRV (total and unbound and rtv (total plasma concentrations were obtained predose and 1, 2, 3, 4, 6, 9 and 12 hours postdose during the 2nd and 3rd trimesters and postpartum. Total DRV and rtv plasma concentrations were determined using a previously validated HPLC-MS/MS assay (lower limit of quantification 5.00 ng/mL. Unbound DRV was determined by fortifying plasma samples with 14-C DRV and separating total and unbound DRV using ultrafiltration. Total and unbound 14-C DRV were measured using liquid scintillation counting. Total and unbound PK parameters were derived using a noncompartmental analysis. Safety and efficacy were investigated at each visit and summarized using descriptive statistics. Sixteen women (10 black, 4 Hispanic, 2 white were enrolled; 11 had evaluable PK data. Total DRV AUC12h was 24% and 17% lower during 2nd and 3rd trimesters, respectively, vs postpartum (Table. Unbound DRV AUC12h was unchanged during 2nd and 3rd trimesters vs postpartum. Total and unbound DRV Cmin increased by 43% and 10%, respectively, during 2nd trimester and by 86% and 14%, respectively, during 3rd trimester vs postpartum. Unbound DRV was above the EC50 (27.5 ng/mL for PI-resistant HIV in all patients. Albumin and α1-acid glycoprotein (AAG concentrations were 22%–29% lower during pregnancy vs postpartum. Viral load decreased and CD4+ count increased over time. One serious adverse event was reported (increased transaminase. Three of 12 infants were born prior to 37 weeks (30, 36 and

  17. XRCC4: a candidate for in vivo substrate of DNA-PK

    International Nuclear Information System (INIS)

    Ionizing radiation can induce various types of DNA damages and, among them, double-strand break (DSB) is considered the most critical lesion. DNA-PK is activated in vitro upon binding to the ends of double-stranded DNA. While DNA-PK is composed of the catalytic subunit (DNA-PKcs or p470) and Ku antigen heterodimer (Ku86/Ku70), animals or cells lacking one of these subunits exhibit hypersensitivity to ionizing radiation with reduced DNA double-strand break repair (DSBR) ability as well as defective V(D)J recombination. These lines of evidence indicated that DNA-PK might be one of the critical enzymes in the non-homologous end-joining (NHEJ) repair and/or the signal transduction of radiation-induced DNA DSBs. Although DNA-PK has been reported to phosphorylate in vitro a number of proteins, such as p53, substrate(s) in vivo remain to be clarified. We recently demonstrated XRCC4, which is a DNA ligase IV-binding protein with supposed function in DSBR, as a candidate for in vivo substrate of DNA-PK in response to radiation: in Western blotting analysis, XRCC4 was mainly found as p55 form in unirradiated cells, but p60 form appeared 0.5hr after 40Gy X-irradiation. Since p60 was diminished by phosphatase treatment, p60 was considered the phosphorylated form. p60 was undetectable in DNA-PKcs-deficient cells, but was detectable in cells from ataxia-telangiectasia patients after X-irradiation. These lines of evidence indicated p60 as a radiation-induced, phosphorylated form of XRCC4, requiring DNA-PKcs but not ATM. We also analyzed the phosphorylation in vitro of recombinant XRCC4 by purified DNA-PK. The results indicated the presence of at least three phosphorylation sites. In order to clarify the biological significance of the phosphorylation, studies are now in progress using mutant XRCC4-expressing clones and phosphorylation-specific antibodies

  18. In Vitro Coinfection and Replication of Classical Swine Fever Virus and Porcine Circovirus Type 2 in PK15 Cells.

    Directory of Open Access Journals (Sweden)

    Niu Zhou

    Full Text Available Increasing clinical lines of evidence have shown the coinfection/superinfection of porcine circovirus type 2 (PCV2 and classical swine fever virus (CSFV. Here, we investigated whether PCV2 and CSFV could infect the same cell productively by constructing an in vitro coinfection model. Our results indicated that PCV2-free PK15 cells but not ST cells were more sensitive to PCV2, and the PK15 cell line could stably harbor replicating CSFV (PK15-CSFV cells with a high infection rate. Confocal and super-resolution microscopic analysis showed that PCV2 and CSFV colocalized in the same PK15-CSFV cell, and the CSFV E2 protein translocated from the cytoplasm to the nucleus in PK15-CSFV cells infected with PCV2. Moreover, PCV2-CSFV dual-positive cells increased gradually in PK15-CSFV cells in a PCV2 dose-dependent manner. In PK15-CSFV cells, PCV2 replicated well, and the production of PCV2 progeny was not influenced by CSFV infection. However, CSFV reproduction decreased in a PCV2 dose-dependent manner. In addition, cellular apoptosis was not strengthened in PK15-CSFV cells infected with PCV2 in comparison with PCV2-infected PK15 cells. Moreover, using this coinfection model we further demonstrated PCV2-induced apoptosis might contribute to the impairment of CSFV HCLV strain replication in coinfected cells. Taken together, our results demonstrate for the first time the coinfection/superinfection of PCV2 and CSFV within the same cell, providing an in vitro model to facilitate further investigation of the underlying mechanism of CSFV and PCV2 coinfection.

  19. In Vitro Coinfection and Replication of Classical Swine Fever Virus and Porcine Circovirus Type 2 in PK15 Cells.

    Science.gov (United States)

    Zhou, Niu; Xing, Gang; Zhou, Jianwei; Jin, Yulan; Liang, Cuiqin; Gu, Jinyan; Hu, Boli; Liao, Min; Wang, Qin; Zhou, Jiyong

    2015-01-01

    Increasing clinical lines of evidence have shown the coinfection/superinfection of porcine circovirus type 2 (PCV2) and classical swine fever virus (CSFV). Here, we investigated whether PCV2 and CSFV could infect the same cell productively by constructing an in vitro coinfection model. Our results indicated that PCV2-free PK15 cells but not ST cells were more sensitive to PCV2, and the PK15 cell line could stably harbor replicating CSFV (PK15-CSFV cells) with a high infection rate. Confocal and super-resolution microscopic analysis showed that PCV2 and CSFV colocalized in the same PK15-CSFV cell, and the CSFV E2 protein translocated from the cytoplasm to the nucleus in PK15-CSFV cells infected with PCV2. Moreover, PCV2-CSFV dual-positive cells increased gradually in PK15-CSFV cells in a PCV2 dose-dependent manner. In PK15-CSFV cells, PCV2 replicated well, and the production of PCV2 progeny was not influenced by CSFV infection. However, CSFV reproduction decreased in a PCV2 dose-dependent manner. In addition, cellular apoptosis was not strengthened in PK15-CSFV cells infected with PCV2 in comparison with PCV2-infected PK15 cells. Moreover, using this coinfection model we further demonstrated PCV2-induced apoptosis might contribute to the impairment of CSFV HCLV strain replication in coinfected cells. Taken together, our results demonstrate for the first time the coinfection/superinfection of PCV2 and CSFV within the same cell, providing an in vitro model to facilitate further investigation of the underlying mechanism of CSFV and PCV2 coinfection. PMID:26431319

  20. Construction of cytopathic PK-15 cell model of classical swine fever virus

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    No cytopathic effect (CPE) can be observed on classical swine fever virus (CSFV) infected cell culture in vitro. This brings an obstacle to the researches on reciprocity between CSFV and host cells. Based on the construction of full-length genomic infectious Cdna clone of Chinese CSFV standard virulent Shimen strain, partial deletion is intro- duced into genomic Cdna to obtain a 7.5 kb subgenomic Cdna. A new subgenomic CSFV is derived from transfection with the subgenomic Cdna on PK-15 cells pre-infected by CSFV Shimen virus. Typical CPE induced by this subgenomic virus is observed on PK-15 cells. Coexistence of wild- type and subgenomic virus in cytopathic cell culture is dem- onstrated by RT-PCR detection in cytopathic cells. For conclusion, the construction of cytopathic cell model exploited a new way for researches on the molecular mechanism of CSFV pathogenesis.

  1. PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

    Directory of Open Access Journals (Sweden)

    Tsuda Yuko

    2010-12-01

    Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

  2. PK-PD modeling of β-lactam antibiotics: in vitro or in vivo models?

    Science.gov (United States)

    de Araujo, Bibiana Verlindo; Diniz, Andrea; Palma, Eduardo Célia; Buffé, Cândida; Dalla Costa, Teresa

    2011-06-01

    A modified E(max)-pharmacokinetic-pharmacodynamic (PK-PD) model was previously proposed in literature for describing the antimicrobial activity of β-lactam antibiotics based on in vitro experiments. However, bacteria behave differently in vitro and in vivo. Thus, the aims of this study were to model the killing effect of piperacillin (PIP) against Escherichia coli on immunocompromised infected rats using this model and to compare the parameters obtained in vitro and in vivo for the same bacteria/drug combination. The PK-PD parameters determined in vitro and in vivo were as follows: generation rate constant of 1.30 ± 0.10 and 0.76 ± 0.20 h(-1), maximum killing effect of 3.11 ± 0.27 and 1.38 ± 0.20 h(-1) and concentration to produce 50% of the maximum effect of 5.44 ± 0.03 and 1.31 ± 0.27 μg ml(-1), respectively. The comparison between the in vitro and in vivo parameters was not straightforward and had to take into consideration the intrinsic differences of the models involved. So far, the main application of the PK-PD model evaluated is for the comparison of different antimicrobial agent's potency and efficacy, under equivalent conditions.

  3. A DNA-dependent stress response involving DNA-PK occurs in hypoxic cells and contributes to cellular adaptation to hypoxia.

    Science.gov (United States)

    Bouquet, Fanny; Ousset, Marielle; Biard, Denis; Fallone, Frédérique; Dauvillier, Stéphanie; Frit, Philippe; Salles, Bernard; Muller, Catherine

    2011-06-01

    DNA-dependent protein kinase (DNA-PK) is involved in DNA double-strand break (DSB) signalling and repair. We report that DNA-PK is activated by mild hypoxia conditions (0.1-1% O₂) as shown by (1) its autophosphorylation on Ser2056, and (2) its mobilisation from a soluble nucleoplasmic compartment to a less extractable nuclear fraction. The recruitment of DNA-PK was not followed by activation and recruitment of the XRCC4-DNA-ligase-IV complex, suggesting that DSBs are not responsible for activation of DNA-PK. To unravel the mechanism of DNA-PK activation, we show that exposure of cells to trichostatin A, a histone deacetylase inhibitor, leads to DNA-PK autophosphorylation and relocalisation to DNA. Histone acetylation (mainly H3K14) is increased in hypoxic cells and treatment with anacardic acid, an inhibitor of histone acetyl transferase, prevented both histone modifications and DNA-PK activation in hypoxic conditions. Importantly, in using either silenced DNA-PK cells or cells exposed to a specific DNA-PK inhibitor (NU7026), we demonstrated that hypoxic DNA-PK activation positively regulates the key transcription factor HIF-1 and one subsequent target gene, GLUT1. Our results show that hypoxia initiates chromatin modification and consequently DNA-PK activation, which positively regulate cellular oxygen-sensing and oxygen-signalling pathways. PMID:21576354

  4. Basel II ja III -säännöstöjen vaikutukset pk-yritysten pankkirahoitukseen.

    OpenAIRE

    Keinonen, Hanne-Mari

    2014-01-01

    Suomessa pankit ovat pk-yritysten tärkeimpiä ulkoisen rahoituksen lähteitä. Vakailla rahoi-tusmarkkinoilla on suuri merkitys pk-yrityksille. Pankkien sääntelyn keskeisen osan muodostavat oman pääoman vaatimukset, eli Basel II ja III –säännöstöt. Opinnäytetyön aiheena on Basel II ja III –säännöstöjen vaikutus pk-yritysten pankkirahoitukseen. Tarkoituksena opinnäytetyössä on selvittää, miten ja miksi Basel II –säännöstö vaikutti suomalaisten pk-yritysten pankkirahoitukseen. Basel III ...

  5. Absence of mutations in the coding sequence of the potential tumor suppressor 3pK in metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Houben Roland

    2005-12-01

    Full Text Available Abstract Background Activation of Ras or Raf contributes to tumorigenesis of melanoma. However, constitutive Raf activation is also a characteristic of the majority of benign melanocytic nevi and high intensity signaling of either Ras or Raf was found to induce growth inhibition and senescence rather than transformation. Since the chromosome 3p kinase (3pK is a target of the Ras/Raf/Mek/Erk signaling pathway which antagonizes the function of the oncogene and anti-differentiation factor Bmi-1, 3pK may function as a tumor suppressor in tumors with constitutive Ras/Raf activation. Consequently, we tested whether inactivating 3pK mutations are present in melanoma. Methods 30 metastatic melanoma samples, which were positive for activating mutations of either BRaf or NRas, were analyzed for possible mutations in the 3pk gene. The 10 coding exons and their flanking intron sequences were amplified by PCR and direct sequencing of the PCR products was performed. Results This analysis revealed that besides the presence of some single nucleotide polymorphisms in the 3pk gene, we could not detect any possible loss of function mutation in any of these 30 metastatic melanoma samples selected for the presence of activating mutations within the Ras/Raf/Mek/Erk signaling pathway. Conclusion Hence, in melanoma with constitutively active Ras/Raf inactivating mutations within the 3pk gene do not contribute to the oncogenic phenotype of this highly malignant tumor.

  6. 11C-PK11195的自动化合成及其生物学分布%Automated synthesis and biodistribution of 11C-PK11195

    Institute of Scientific and Technical Information of China (English)

    王明芳; 唐刚华; 李葆元; 梁明泉; 王全师; 吴湖炳; 罗志福

    2008-01-01

    目的 研究N-[11C]甲基-N-(1-甲基丙基)-1-(2.氯苯基)异喹啉-3-氨甲酰(11C-PK11195)在国内现有合成模块上的自动化合成程序及其在小鼠体内的生物学分布.方法 以1-(2-氯苯基)-N-(1-甲基丙基)-异喹啉-3-氨甲酰去甲基前体与国产模块生产的11C-CH3I在TracerLabFXF-N自动化合成模块中进行甲基化反应,制备11C-PK11195,测定11C-PK11195的纯度和稳定性,观察11C-PK11195在小鼠体内的生物学分布[以每克组织百分注射剂量率(%ID/g)表示]和异常毒性,并进行健康家猫PET显像.结果 从11C-CO2生产到11C-PK11195合成结束总的合成时间约35 min,甲基化合成11C-PK11195的放化产率为(47±3.6)%,其放化纯和化学纯度均>98%,比活度为30~65 GBq/μmol,"C-PK11195注射液室温放置1 h内放化纯>95%.生物学分布实验表明,11C-PK11195在小鼠体内的清除较快,1 min时为(21.44±3.08)%ID/g,60 ndn下降到(1.35±0.54)%ID/g,肾为其主要的排泄器官.注射后1~5 min内,鼠脑放射性水平较高,随后脑内放射性快速下降;心、肺和肾组织中的放射性较高.猫PET显像示肝和肠道摄取最高,其次为肾、肺、大脑、心肌、胃、脾和膀胱,脑组织中放射性分布均匀.结论 该方法可制备出满足临床应用的11C-PK11195,其合成程序也适合于在国内其他模块中应用.11C-PK11195可望用于国内临床PET显像研究.在注射显像剂后30~40 min进行PET显像,可获得较佳PET图像.%Objective The aims of this study was to synthesize 1-(2-chlorophenyl)-N-[11C] meth-yl-N-(1-methylpropyl)-3-isoquinoline carboxamide (11C-PK11195) on the commercial synthesizer, and to investigate its biodistribution in mice. Methods 11C-CH3I was synthesized via liquid phase distillation ap-proach on the 11C-iodomethane synthesizer.11C-PK11195 was prepared by 11C-methylation of a correspond-ing demethyl precursor (N-demethyl-PK11195) with 111C-CH3I on TracerLab FXF-N synthesizer. The radio-chemical purity

  7. Comparative analysis on blood glucose results detected by portable glucose meter and Olympus AU2700 automatic biochemical analyzer%便携式血糖仪与 Olympus AU2700血糖测定结果的比对分析

    Institute of Scientific and Technical Information of China (English)

    吴立春; 张莉; 刘明炎; 王左

    2014-01-01

    Objective To perform the comparative analysis on the blood glucose results detected by the portable glucose meter and the Olympus AU2700 biochemical analyzer.Methods 20 fresh whole blood samples with sodium fluoride and potassium oxalate anticoagulation were the Olympus AU2700 biochemical analyzer biochemical analyzer.Results In these 27 portable glucose meters, the comparison results in only 1 portable glucose meter was unqualified,which in the other 26 portable glucose meters were passed, the passing rate was 96.3%,which in 2 glucose meters were clinically acceptable and which in the other 24 glucose meters were completely acceptable and the clinical completely acceptable rate was 88.9%.Conclusion There are some biases of blood glucose results detected by the portable glucose meter and the fully automatic biochemical analyzer,but the overall correlation is well.The comparison and calibration of the blood glucose meters should be performed at the regular intervals for improving the consistency and accuracy of blood glucose detection results.%目的:对血糖仪和全自动生化分析仪测定血糖结果进行比对,评估其测定结果的偏倚及相关性。方法选择20份氟化钠-草酸钾抗凝全血对全院27台血糖仪和 Olympus AU2700全自动生化分析仪进行同时检测,对检测结果进行分析。结果27台血糖仪中1台血糖仪比对结果未通过,其余26台血糖仪均通过,通过率96.3%;2台血糖仪比对结果属于临床尚可接受水平,24台血糖仪属于临床完全可接受水平,临床完全可接受率为88.9%。结论血糖仪与全自动生化分析仪血糖测定结果虽然存在一定的偏差,但总体相关性较好,应定期对血糖仪进行比对和校准以提高检测结果的一致性和准确性。

  8. Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

    Science.gov (United States)

    O'Neill, Peter; Harper, Jane; Anderson, Jennifer a.; Cucinnota, Francis A.

    2007-01-01

    When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with DNA-PK(sub cs) deficient cells. Following 1 Gy gamma-radiation the induction of gamma-H2AX foci is similar in M059J and M059K cells. However, the repair rate

  9. Human biodistribution and radiation dosimetry of {sup 11}C-(R)-PK11195, the prototypic PET ligand to image inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Hirvonen, Jussi; Roivainen, Anne; Virta, Jere; Helin, Semi; Naagren, Kjell; Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, P.O. Box 52, Turku (Finland)

    2010-03-15

    The positron emission tomography (PET) radiotracer {sup 11}C-(R)-PK11195 allows the in vivo imaging in humans of the translocator protein 18 kDa (TSPO), previously called peripheral benzodiazepine receptor (PBR), a marker of inflammation. Despite its widespread use, the radiation burden associated with {sup 11}C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic whole-body imaging with PET and {sup 11}C-(R)-PK11195 in healthy humans. Five healthy male volunteers were scanned with PET and {sup 11}C-(R)-PK11195, using a dynamic whole-body imaging protocol. An organ-specific method was used to measure accumulated radioactivity in source organs, and residence times were calculated as areas under the curve of time-activity curves expressed as percentage of injected radioactivity. Residence times were used as input for OLINDA/EXM 1.0 software to model the equivalent organ doses and the effective dose for the 70-kg man. After intravenous injection of {sup 11}C-(R)-PK11195, radioactivity accumulated in organs rich in TSPO as well as routes of excretion: the hepatobiliary system and the urine. The mean effective dose was 4.8 {mu}Sv/MBq according to International Commission on Radiological Protection (ICRP) Publication 60 and 5.1 {mu}Sv/MBq according to ICRP Publication 103, and the highest equivalent organ doses were observed in the kidneys (14.0 {mu}Sv/MBq), spleen (12.5 {mu}Sv/MBq) and small intestine (12.2 {mu}Sv/MBq). Imaging of TSPO with PET using {sup 11}C-(R)-PK11195 is associated with modest radiation exposure, similar in magnitude to most other {sup 11}C-labelled PET tracers, suggesting feasibility of {sup 11}C-(R)-PK11195 imaging in clinical human studies involving multiple scans in the same subjects per year. (orig.)

  10. ICT-brändien ja ohjelmien vaikutus pk-yrityksiin : Markkinatutkimus

    OpenAIRE

    Härkälä, Michael

    2015-01-01

    Tämän opinnäytetyön tarkoituksena on selvittää, kuinka ohjelmistot ja brändituotteet vaikuttavat pk-yrityksien toimintaan. Opinnäytetyöhön on kerätty aineistoa kirjallisuudesta, jossa käsitellään aiheita markkinoinnin, brändin, kilpailun ja mainonnan alueilta. Tutkimusta on innoittanut myös lehtiartikkelit Linuxin suosiosta Saksassa ja Italiassa. Tutkimuksessa käsitellään markkinoita hallitsevien yhtiöiden, kuten Googlen, Applen ja Microsoftin historiaa lyhyesti. Vastaavan...

  11. Analisa Performansi Mesin Pendingin 1-Pk dengan Penambahan Subcool Menggunakan Refrigerant R-22

    OpenAIRE

    Manurung, Rikardo Goodlas

    2016-01-01

    An air conditioning system to condition the air of a room so as to achieve the expected temperature and humidity. Extra media subcool with water cooling block, add ice cubes is an effective way to improve system performance pendingin.Penggunaan subcool is to keep the bubble of steam passing through the expansion valve. So that all the refrigerant into the evaporator 100% liquid. The study was conducted on the air conditioning (AC) Split 1-PK. Testing is done by taking data on a pressure gauge...

  12. Pk-yritysten kasvun ja kansainvälistymisen road-map

    OpenAIRE

    Arpiainen, Niina

    2009-01-01

    Tämän toiminnallisen opinnäytetyön tarkoituksena oli luoda toimeksiantajille työväline parantamaan asiakaspalvelua. Finnveran, Finnpron, Tekesin ja TE-keskuksen asiakastyössä toimivat työntekijät voivat luodun työvälineen avulla löytää nopeasti ja vaivattomasti tietoa mainittujen organisaatioiden tuotteista ja palveluista, jotka ovat suunnattu pienille ja keskisuurille yritysasiakkaille (pk-yrityksille). Tutkimus kokosi yhteen tietoa siitä, millä eri tavoin toimeksiantajaorganisaatiot voi...

  13. A PK-PD model of ketamine-induced high-frequency oscillations

    Science.gov (United States)

    Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

    2015-10-01

    Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent

  14. Condicionament de Torregrosa a Juneda, Pk 7+028 al 11+583

    OpenAIRE

    Bordalba RIbalta, Isidro

    2010-01-01

    L'objecte del present projecte és definir a nivell constructiu les obres corresponents al projecte de reforçament de ferm i eixamplament puntual de la carretera LV-2001 del PK 7+028 al 11+583. Al seu pas per les localitats de Torregrossa i Juneda, localitats que delimiten les comarques del Pla d'Urgell amb les Garrigues, a la província de Lleida. A continuació es descriuen els factors principals a tenir en compte per a exposar una raó del projecte justificada i conseqüent am...

  15. Polarized $pK^-$ scattering in Unitary Baryon Chiral Perturbation Theory

    CERN Document Server

    Bouzas, Antonio O

    2010-01-01

    We study $pK^-$ scattering in the energy range from threshold through the $\\Lambda(1520)$ peak in UBChPT, taking into account $\\mathcal{O}(q)$ vertices from meson-baryon contact interactions and $s$- and $u$-channel ground-state baryon exchange, $s$- and $u$-channel decuplet- and nonet-baryon exchange and $t$-channel vector-meson exchange, as well as $\\mathcal{O}(q^2)$ flavor-breaking vertices. Detailed fits to data are presented, including a substantial body of differential cross-section data with meson momentum $q_\\mathrm{lab} > 300$ MeV not considered in previous treatments.

  16. DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange.

    Directory of Open Access Journals (Sweden)

    Hungjiun Liaw

    Full Text Available Hyperphosphorylation of RPA2 at serine 4 and serine 8 (S4, S8 has been used as a marker for activation of the DNA damage response. What types of DNA lesions cause RPA2 hyperphosphorylation, which kinase(s are responsible for them, and what is the biological outcome of these phosphorylations, however, have not been fully investigated. In this study we demonstrate that RPA2 hyperphosphorylation occurs primarily in response to genotoxic stresses that cause high levels of DNA double-strand breaks (DSBs and that the DNA-dependent protein kinase complex (DNA-PK is responsible for the modifications in vivo. Alteration of S4, S8 of RPA2 to alanines, which prevent phosphorylations at these sites, caused increased mitotic entry with concomitant increases in RAD51 foci and homologous recombination. Taken together, our results demonstrate that RPA2 hyperphosphorylation by DNA-PK in response to DSBs blocks unscheduled homologous recombination and delays mitotic entry. This pathway thus permits cells to repair DNA damage properly and increase cell viability.

  17. Monitorování provozu VoIP pomocí technologie OnePK

    OpenAIRE

    Spišiak, Matej

    2014-01-01

    Tato bakalářská práce se zabývá novou proprietární technologií od Cisco Systems zvanou OnePK (One Platform Kit). Soustřeďuje se na možnosti použití v oblasti zberu statistických dat o VoIP provozu. Používá DataPath service set, ktorý zabezpečuje sběr paketů ze síťových zařízení firmy Cisco. DataPath service set posílá pakety na vstup aplikace, která tvoří VoIP statistiku z příchozích SIP paketů. Tato aplikace a provedené testy na technologii OnePK jsou výsledky této práce....

  18. PKR activation enhances replication of classical swine fever virus in PK-15 cells.

    Science.gov (United States)

    Liu, Wen-Jun; Yang, You-Tian; Zhao, Ming-Qiu; Dong, Xiao-Ying; Gou, Hong-Chao; Pei, Jing-Jing; Chen, Jin-Ding

    2015-06-01

    Classical swine fever (CSF) is a highly contagious swine disease that is responsible for economic losses worldwide. Protein kinase R (PK)R is an important protein in the host viral response; however, the role of PKR in CSFV infection remains unknown. This issue was addressed in the present study using the PK-15 swine kidney cell line. We found that CSFV infection increased the phosphorylation of eukaryotic translation initiation factor (eIF)2α and its kinase PKR. However, the expression of viral proteins continued to increase. Furthermore, PKR overexpression enhanced CSFV replication, while PKR inhibition resulted in reduced CSFV replication and an increase in interferon (IFN) induction. In addition, PKR was responsible for eIF2α phosphorylation in CSFV-infected cells. These results suggest that the activation of PKR during CSFV infection is beneficial to the virus. The virus is able to commandeer the host cell's translation machinery for viral protein synthesis while evading innate immune defenses. PMID:25899421

  19. The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy; Le complexe de reparation de l'ADN DNA-PK, une cible pharmacologique en chimiotherapie et radiotherapie anticancereuse

    Energy Technology Data Exchange (ETDEWEB)

    Salles, B.; Calsou, P.; Frit, P.; Muller, C. [Institut de Pharmacologie et Biologie Structurale (IPBS), UMR CNRS 5089, 31 - Toulouse (France)

    2006-05-15

    A line of investigation in the search for sensitizing tumor cells to chemotherapy or radiotherapy relies on the selection of DNA repair inhibitors. In the area of DNA repair mechanisms, DNA-dependent protein kinase (DNA-PK) represents a key complex. Indeed DNA-PK is involved in the non-homologous end joining (NHEJ) process that corresponds to the major activity responsible for cell survival after ionizing radiation or chemotherapeutic treatment producing DNA double strand breaks. DNA-PK belongs to the PI3-K related kinase family and specific inhibitors have been recently selected and evaluated as radio- and chemo-sensitizers. These drugs, along with other ways to inhibit the DSBs repair process, are presented and discussed. (authors)

  20. NMR structure of the A. aeolicus tmRNA pseudoknot PK1: new insights into the recoding event of the ribosomal trans-translation.

    OpenAIRE

    Nonin-Lecomte, Sylvie; Felden, Brice; Dardel, Frédéric

    2006-01-01

    The transfer-messenger RNA (tmRNA) pseudoknot PK1 is essential for bacterial trans-translation, a ribosomal rescue mechanism. We report the solution structure of PK1 from Aquifex aeolicus, which despite an unprecedented small number of nucleotides and thus an unprecented compact size, displays a very high thermal stability. Several unusual structural features account for these properties and indicate that PK1 belongs to the class of ribosomal frameshift pseudoknots. This suggests a similarity...

  1. Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

    Science.gov (United States)

    O'Neill, Peter; Harper, Jane; Anderson, Jennifer a.; Cucinnota, Francis A.

    2007-01-01

    When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma

  2. DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells

    International Nuclear Information System (INIS)

    Highlights: ► We investigated the effect of DNA-PK inhibition on DSB repair using fish cells. ► A radiation sensitive mutant RIC1 strain showed a low level of DNA-PK activity. ► DNA-PK dysfunction leads defects in HR repair and DNA-PKcs autophosphorylation. ► DNA-PK dysfunction leads a slight increase in the number of 53BP1 foci after DSBs. ► DNA-PK dysfunction leads an alternative NHEJ that depends on 53BP1. -- Abstract: Nonhomologous end joining (NHEJ) and homologous recombination (HR) are known as DNA double-strand break (DSB) repair pathways. It has been reported that DNA-PK, a member of PI3 kinase family, promotes NHEJ and aberrant DNA-PK causes NHEJ deficiency. However, in this study, we demonstrate that a wild-type cell line treated with DNA-PK inhibitor and a mutant cell line with dysfunctional DNA-PK showed decreased HR efficiency in fish cells (Medaka, Oryzias latipes). Previously, we reported that the radiation-sensitive mutant RIC1 strain has a defect in the Histone H2AX phosphorylation after γ-irradiation. Here, we showed that a DNA-PK inhibitor, NU7026, treatment resulted in significant reduction in the number of γH2AX foci after γ-irradiation in wild-type cells, but had no significant effect in RIC1 cells. In addition, RIC1 cells showed significantly lower levels of DNA-PK kinase activity compared with wild-type cells. We investigated NHEJ and HR efficiency after induction of DSBs. Wild-type cells treated with NU7026 and RIC1 cells showed decreased HR efficiency. These results indicated that aberrant DNA-PK causes the reduction in the number of γH2AX foci and HR efficiency in RIC1 cells. We performed phosphorylated DNA-PKcs (Thr2609) and 53BP1 focus assay after γ-irradiation. RIC1 cells showed significant reduction in the number of phosphorylated DNA-PKcs foci and no deference in the number of 53BP1 foci compared with wild-type cells. These results suggest that low level of DNA-PK activity causes aberrant DNA-PKcs autophosphorylation

  3. DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells

    Energy Technology Data Exchange (ETDEWEB)

    Urushihara, Yusuke [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan); Kobayashi, Junya [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan); Matsumoto, Yoshihisa [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Tokyo 152-8550 (Japan); Komatsu, Kenshi [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan); Oda, Shoji [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan); Mitani, Hiroshi, E-mail: mitani@k.u-tokyo.ac.jp [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan)

    2012-12-14

    Highlights: Black-Right-Pointing-Pointer We investigated the effect of DNA-PK inhibition on DSB repair using fish cells. Black-Right-Pointing-Pointer A radiation sensitive mutant RIC1 strain showed a low level of DNA-PK activity. Black-Right-Pointing-Pointer DNA-PK dysfunction leads defects in HR repair and DNA-PKcs autophosphorylation. Black-Right-Pointing-Pointer DNA-PK dysfunction leads a slight increase in the number of 53BP1 foci after DSBs. Black-Right-Pointing-Pointer DNA-PK dysfunction leads an alternative NHEJ that depends on 53BP1. -- Abstract: Nonhomologous end joining (NHEJ) and homologous recombination (HR) are known as DNA double-strand break (DSB) repair pathways. It has been reported that DNA-PK, a member of PI3 kinase family, promotes NHEJ and aberrant DNA-PK causes NHEJ deficiency. However, in this study, we demonstrate that a wild-type cell line treated with DNA-PK inhibitor and a mutant cell line with dysfunctional DNA-PK showed decreased HR efficiency in fish cells (Medaka, Oryzias latipes). Previously, we reported that the radiation-sensitive mutant RIC1 strain has a defect in the Histone H2AX phosphorylation after {gamma}-irradiation. Here, we showed that a DNA-PK inhibitor, NU7026, treatment resulted in significant reduction in the number of {gamma}H2AX foci after {gamma}-irradiation in wild-type cells, but had no significant effect in RIC1 cells. In addition, RIC1 cells showed significantly lower levels of DNA-PK kinase activity compared with wild-type cells. We investigated NHEJ and HR efficiency after induction of DSBs. Wild-type cells treated with NU7026 and RIC1 cells showed decreased HR efficiency. These results indicated that aberrant DNA-PK causes the reduction in the number of {gamma}H2AX foci and HR efficiency in RIC1 cells. We performed phosphorylated DNA-PKcs (Thr2609) and 53BP1 focus assay after {gamma}-irradiation. RIC1 cells showed significant reduction in the number of phosphorylated DNA-PKcs foci and no deference in the

  4. Studies of beauty baryons decaying to $D^{0}p\\pi^{-}$ and $D^{0}pK^{-}$

    CERN Document Server

    The LHCb Collaboration

    2011-01-01

    We study decays of beauty baryons to the $D^{0}p\\pi^{-}$ and $D^{0}pK^{-}$ final states with the data collected by LHCb in March-June 2011. We present the first observation of the Cabibbo-suppressed decay $\\Lambda^0_b \\to D^{0}pK^{-}$ that can be used to measure the angle of $\\gamma$ of the CKM unitarity triangle. The ratio of branching fractions is measured: $\\cal{B}(\\Lambda^0_b \\to D^{0}pK^{-})/\\cal{B}(\\Lambda^0_b \\to D^{0}p\\pi^{-})$ = 0.112 $\\pm$ 0.019$^{+0.011}_{-0.014}$. We also find a hint, with 2.6$\\sigma$ significance, of the neutral beauty-strange baryon $\\Xi_b^0$ reconstructed in the exclusive final state $D^{0}pK^{-}$

  5. A Convenient Radiolabeling of [{sup 11}C](R)-PK11195 Using Loop Method in Automatic Synthesis Module

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jeong; Jeong, Jae Min; Lee, Yun Sang; Kim, Hyung Woo; Choi, Jae Yeon; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-08-15

    ((R)-1-(2-chlorophenyl)-N-1-[[{sup 11}C]methyl-N-(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [[{sup 11}C](R)-PK11195 in mild condition using NaH suspension in DMF and one-step loop method. (R)-NDesmethyl- PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [{sup 11}C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. The labeling efficiency of [[{sup 11}C](R)-PK11195 was 71.8{+-}8.5%. The specific activity was 11.8{+-}6.4 GBq/{mu}mol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. By the one-step loop method with the [[{sup 11}C]CH3I automated synthesis module, [[{sup 11}C](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.

  6. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    Science.gov (United States)

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

    2007-05-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  7. Ympäristöteknologian vienti Kiinaan : Kehittämisyhtiö pk-yrityksen tukena

    OpenAIRE

    Peltola, Heta

    2007-01-01

    Tutkimuksen toimeksiantaja oli Jyväskylän seudun kehittämisyhtiö Jykes Oy:n kansainvälistymispalveluiden yksikkö. Tarkoituksena oli selvittää, miten Jykes Oy on luonut suhteet virkamiestasolla Jyväskylän yhteistyökaupungissa Kunmingissa Kiinassa ja miten suhteiden kautta on syntynyt keskisuomalaiselle pk-yritykselle ympäristöteknologian vientimahdollisuus. Lisäksi tutkimuksen tavoitteena oli selvittää, millaista tukea pk-yritys on saanut Jykesiltä kahden vuoden neuvottelujen ja projektin valm...

  8. IPv6:n käyttöönotto PK-yrityksessä

    OpenAIRE

    Salonen, Arttu Petteri

    2011-01-01

    Tämän opinnäytetyön tarkoituksena on selvittää, kuinka IPv6-yhteydet otetaan käyt-töön PK-yrityksessä. Työssä selvitetään minkälaiset vaatimukset IPv6 asettaa lait-teistolle ja minkälaisia käytännön asioita yrityksen täytyy huomioida IPv6:n käyt-töönotossa. Lisäksi työssä on laboratoriosimulaation avulla havainnollistettu eri käyt-töjärjestelmien tukea IPv6:lle ja käyttöönottoon liittyviä reititin- ja osoitekonfiguraati-oita. Käyttöönoton lisäksi opinnäytetyössä esitellään IPv6-protokoll...

  9. Valores, Creencias Y Objectivos: Base del programa de la Escuela Experimental P.K. Yonge. (Values, Beliefs and Objectives: The Basis of Experimental Schools P.K. Yonge's Program.)

    Science.gov (United States)

    Florida Univ., Gainesville. Coll. of Education.

    The values, beliefs, and objectives that form the core of the program at the Experimental School P.K. Yonge in the University of Florida are presented in this paper which is written in Spanish. This experimental school serves approximately 900 students from grades one through twelve. The function of the school is to conduct research to solve…

  10. Prediction of PK-specific phosphorylation site based on information entropy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Phosphorylation is a crucial way to control the activity of proteins in many eukaryotic organisms in vivo. Experimental methods to determine phosphorylation sites in substrates are usually restricted by the in vitro condition of enzymes and very intensive in time and labor. Although some in silico methods and web servers have been introduced for automatic detection of phosphorylation sites, sophisticated methods are still in urgent demand to further improve prediction performances. Protein primary se-quences can help predict phosphorylation sites catalyzed by different protein kinase and most com-putational approaches use a short local peptide to make prediction. However, the useful information may be lost if only the conservative residues that are not close to the phosphorylation site are consid-ered in prediction, which would hamper the prediction results. A novel prediction method named IEPP (Information-Entropy based Phosphorylation Prediction) is presented in this paper for automatic de-tection of potential phosphorylation sites. In prediction, the sites around the phosphorylation sites are selected or excluded by their entropy values. The algorithm was compared with other methods such as GSP and PPSP on the ABL, MAPK and PKA PK families. The superior prediction accuracies were ob-tained in various measurements such as sensitivity (Sn) and specificity (Sp). Furthermore, compared with some online prediction web servers on the new discovered phosphorylation sites, IEPP also yielded the best performance. IEPP is another useful computational resource for identification of PK-specific phosphorylation sites and it also has the advantages of simpleness, efficiency and con-venience.

  11. Proliferation Characteristics of a PK-15 Cell-adapted Strain of Porcine Parvovirus%猪细小病毒PK-15细胞适应株的培育及增殖特性

    Institute of Scientific and Technical Information of China (English)

    吴云飞; 朱玲; 徐志文; 付梦瑾; 陈蕾; 阳爱国; 郭万柱

    2013-01-01

    To study the proliferation characteristics of PPV in differently infected way and the variance of concentrations in different cells.A strain of porcine parvovirus(PPV) was adapted to PK-15 cells,and a Real-time fluorescent quantitative PCR (FQ-PCR) assay was developed based on the specific region of the NS1 gene of PPV to quantify the PPV.The FQ-PCR was used to measure the viral concentration of virusinfected cells by simultaneous or step by step inoculation and plot one-step growth curves.The proliferation characteristics of PPV strain in different cells lines (HeLa,MDBK,PK-15,ST,F81,BHK-21 and Marc-145) was also compared.The results showed the PK-15 cell-adapted strain of PPV produced CPE after 12 passages,and maintained stable CPE at the following 10 messages.The one-step growth curve showed that the virus concentration of simultaneous inoculation was higher than that of the step-by-step inoculation,and the proliferation cycle of step-by-step inoculation was shorter.The proliferation ability of PPV strain in different ceils showed that CPE appeared first inPK-15,followed by ST,HeLa and MDBK,and the virus concentration was highest in ST,followed byPK-15,MDBK and HeLa.NO proliferation was observed in F81,BHK-21 and Marc-145 cells.These findings lay a material foundation for the basic researches on PPV and the development of vaccine.%为了研究猪细小病毒不同接毒方式的增殖规律及在不同细胞的病毒含量差异.本实验利用PK-15细胞对猪细小病毒(Porcine parvovirus,PPV)分离株进行适应性培养.针对PPV的NS1基因设计特异性引物,建立实时荧光定量PCR方法.利用该方法检测PPV分离株同步和分步接毒的病毒含量,绘制一步生长曲线;同时检测PPV在HeLa、MDBK、PK-15、ST、F81、BHK-21和Marc-145细胞上的增殖特性.结果显示,PPV分离株盲传至12代产生CPE,继续传代培养10代仍能产生稳定的细胞病变,成功培育出PK-15细胞适应株.一步生长曲线显示,

  12. Rapid and efficient radiosynthesis of [{sup 123}I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pimlott, Sally L. [Department of Clinical Physics, West of Scotland Radionuclide Dispensary, Western Infirmary, G11 6NT Glasgow (United Kingdom)], E-mail: s.pimlott@clinmed.gla.ac.uk; Stevenson, Louise [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom); Wyper, David J. [Institute of Neurological Sciences, Southern General Hospital, G51 4TF Glasgow (United Kingdom); Sutherland, Andrew [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom)

    2008-07-15

    Introduction: [{sup 123}I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [{sup 123}I]I-PK11195 in order to develop a rapid and efficient method that obtains [{sup 123}I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [{sup 123}I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [{sup 123}I]I-PK11195. Conclusions: [{sup 123}I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved.

  13. A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes for soman in multiple species

    NARCIS (Netherlands)

    Sweeney, R.E.; Langenberg, J.P.; Maxwell, D.M.

    2006-01-01

    A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50), m

  14. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends.

    Science.gov (United States)

    Bombarde, Oriane; Boby, Céline; Gomez, Dennis; Frit, Philippe; Giraud-Panis, Marie-Josèphe; Gilson, Eric; Salles, Bernard; Calsou, Patrick

    2010-05-01

    DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA-PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA-PK end binding and activation step and (2) DNA-PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells. PMID:20407424

  15. The radiosynthesis of [18F]PK 14105 as an alternative radioligand for peripheral type benzodiazepine binding sites.

    Science.gov (United States)

    Pascali, C; Luthra, S K; Pike, V W; Price, G W; Ahier, R G; Hume, S P; Myers, R; Manjil, L; Cremer, J E

    1990-01-01

    A method has been developed for labelling PK 14105 [N-methyl-N-(1-methyl-propyl)-1(2-fluoro-5-nitrophenyl)isoquinoline-3- carboxamide], a ligand that has high affinity and selectivity for peripheral type benzodiazepine binding sites (PBBS), with NCA fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%). The method involves treating the 2-chloro-analogue with cyclotron-produced NCA [18F]fluoride in dimethyl sulphoxide, with rubidium carbonate as base, at 140 degrees C for 20 min. Purification is achieved by separation on a reverse phase Sep-Pak followed by PHLC on a silica gel column, to give chemically and radiochemically pure product with a specific activity of ca 7.4 GBq/mumol (200 mCi/mumol), decay-corrected to the end of radionuclide production (EOB). The radiosynthesis requires 210 min. giving a radiochemical yield of 10-20%, decay-corrected to EOB. [18F]PK 14105 was found to bind avidly to sites associated with kainic acid-induced unilateral lesions of rat striata. Such binding was blocked by pre-dosing the rat with PK 11195, so providing evidence for specific binding to PBBS. These results suggest that [18F]PK 14105 has potential for studying phenomena associated with PBBS in man by PET. PMID:2166014

  16. DNA-PK. The major target for wortmannin-mediated radiosensitization by the inhibition of DSB repair via NHEJ pathway

    International Nuclear Information System (INIS)

    The effect of wortmannin posttreatment was studied in cells derived from different species (hamster, mouse, chicken, and human) with normal and defective DNA-dependent protein kinase (DNA-PK) activity, cells with and without the ataxia telangiectasia mutated (ATM) gene, and cells lacking other regulatory proteins involved in the DNA double-strand break (DSB) repair pathways. Clonogenic assays were used to obtain all results. Wortmannin radiosensitization was observed in Chinese hamster cells (V79-B310H, CHO-K1), mouse mammary carcinoma cells (SR-1), transformed human fibroblast (N2KYSV), chicken B lymphocyte wild-type cells (DT40), and chicken Rad54 knockout cells (Rad54-/-). However, mouse mammary carcinoma cells (SX9) with defects in the DNA-PK and chicken DNA-PK catalytic subunit (DNA-PKcs) knockout cells (DNA-PKcs-/-/-) failed to exhibit wortmannin radiosensitization. On the other hand, severe combined immunodeficiency (SCID) mouse cells (SC3VA2) exposed to wortmannin exhibited significant increases in radiosensitivity, possibly because of some residual function of DNA-PKcs. Moreover, the transformed human cells derived from AT patients (AT2KYSV) and chicken ATM knockout cells (ATM-/-) showed pronounced wortmannin radiosensitization. These studies demonstrate confirm that the mechanism underlying wortmannin radiosensitization is the inhibition of DNA-PK, but not of ATM, thereby resulting in the inhibition of DSB repair via nonhomologous endjoining (NHEJ). (author)

  17. Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling.

    Science.gov (United States)

    Samala, Sujatha; Veeresham, Ciddi

    2016-03-01

    The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored. PMID:26762235

  18. IMPLEMENTASI PEMERINTAHAN YANG BERSIH DALAM KERANGKA RENCANA AKSI DAERAH PEMBERANTASAN KORUPSI (RAD-PK (Studi Di Kabupaten Pemalang

    Directory of Open Access Journals (Sweden)

    Muhammad Fauzan

    2012-03-01

    Full Text Available This research related to the implementation of good governance, free from corruption, collusion and nepotism. The approach used in this research is a descriptive qualitative approach. The Location of research conducted in the District of Pemalang. Based on the research results can presented that the District of Pemalang is committed and fully supports the government policy in eradicating corruption. District of Pemalang support to efforts to more information accelerate the eradication of corruption stated in the the Regional Action Plan to Accelerate the Eradication of Corruption (RAD-PK in 2011 -2016 which refers to the Medium Term Development Plan (RPJM District of Pemalang from 2011 to 2016 and the National Action Plan for Eradication of Corruption (RAN-PK and the President of Republic of Indonesia Instruction No. 5 Year 2004 on Accelerating the eradication of corruption. RAD-PK 2011-2016 District of Pemalang is a document that contains an action program that aims to accelerate the eradication of corruption. RAD-PK as a program of action containing concrete measures that have been agreed by the stakeholders in the area, so it has been a commitment of local governments prevention efforts corruption through the development of programs and activities aimed at improving public services and the application of the principles of good governance.

  19. Apolonijo Rodiečio Argonautika. Olimpo epizodas (3. 1-166 ir jo poetinė tradicija. The episode in Olympus (Argonautica, 3. 1-166 and its poetic tradition

    Directory of Open Access Journals (Sweden)

    Audronė Kudulytė-Kairienė

    2011-01-01

    Full Text Available The article deals with the peculiar characteristics of the Argonautica, a Greek epic poem written by Apollonius Rhodius. Composed in the third century B.C., this poem is the only extant Greek epic of the Hellenistic age. Apollonius developed the classical traditions of the Homeric epic. The style and diction of the Argonautica are obviously on the model of Homer. The main focus of this article is on the episode in Olympus at the beginning of the third book of the Argonautica. This episode displays the most appealing characteristics of the Hellenistic poetry and is regarded as one of the best written and most memorable scenes of the Argonautica. The language of this episode is replete with allusions to Iliad an Odyssey, but the poet gives a new Alexandrian view of Olympus. Literary sources from which Apollonius Rhodius has taken some details are analysed as well. The conclusions are made that Eros of Apollonius Rhodius is a result of long development. The main features of Eros were sourced from archaic lyric. The influence of this episode on later Hellenistic poets like Bion, Moschus, Meleager, is mentioned.

  20. Olympus Turbo MO 640SII

    Institute of Scientific and Technical Information of China (English)

    蔡翰林

    2001-01-01

    @@ 此款由Olympus推出的TurboMO 640 SII,外观上,以全机身乳白色的优美色调,配合简洁的控制面板;规格上,可读取最大达640MB容量的磁盘片并可向下兼容.在众多的硬件中又多了一台美观实用的MO光盘机可供使用者选择.

  1. The expression of one ankyrin pk2 allele of the WO prophage is correlated with the Wolbachia feminizing effect in isopods

    Directory of Open Access Journals (Sweden)

    Pichon Samuel

    2012-04-01

    Full Text Available Abstract Background The maternally inherited α-Proteobacteria Wolbachia pipientis is an obligate endosymbiont of nematodes and arthropods, in which they induce a variety of reproductive alterations, including Cytoplasmic Incompatibility (CI and feminization. The genome of the feminizing wVulC Wolbachia strain harboured by the isopod Armadillidium vulgare has been sequenced and is now at the final assembly step. It contains an unusually high number of ankyrin motif-containing genes, two of which are homologous to the phage-related pk1 and pk2 genes thought to contribute to the CI phenotype in Culex pipiens. These genes encode putative bacterial effectors mediating Wolbachia-host protein-protein interactions via their ankyrin motifs. Results To test whether these Wolbachia homologs are potentially involved in altering terrestrial isopod reproduction, we determined the distribution and expression of both pk1 and pk2 genes in the 3 Wolbachia strains that induce CI and in 5 inducing feminization of their isopod hosts. Aside from the genes being highly conserved, we found a substantial copy number variation among strains, and that is linked to prophage diversity. Transcriptional analyses revealed expression of one pk2 allele (pk2b2 only in the feminizing Wolbachia strains of isopods. Conclusions These results reveal the need to investigate the functions of Wolbachia ankyrin gene products, in particular those of Pk2, and their host targets with respect to host sex manipulation.

  2. Experimental Study on the Cryopreservation of LLC-PK1 Epithelial Cells with Hypoxic UW Solution

    Institute of Scientific and Technical Information of China (English)

    WAN Chidan; WANG Chunyou; LIU Tao; WANG Hongbo; YANG Zhiyong

    2007-01-01

    The effects of oxygen partial pressure on cryopreservation of the cells with organ preservation solution were explored. Hypoxic UW solution was made by purging the UW solution with argon. The pig proximal tubule epithelial cells (LLC-PK1 cells) were cryopreserved in hypoxic UW solution (Ar-UW group) or standard UW solution (UW group) at 4℃ for 48 h. Trypan blue staining and LDH detection were performed to evaluate the injury of the cells. The results showed that the oxygen partial pressure in Ar-UW group was significantly declined from 242±6 mmHg to 83±10 mmHg. After cryopreservation at 4℃ for 48 h, LDH leakage rate and Trypan blue-stained rate in Ar-UW group were (11.3±3.4)% and (10.5±4.7)%, respectively, which were significantly lower than in UW group [(49.5±6.9)% and (47.6±9.3)% respectively, both P<0.01]. It was concluded that lower oxygen partial pressure of UW solution was more beneficial to the cryopreservation of LLC.

  3. A mechanism for DNA-PK activation requiring unique contributions from each strand of a DNA terminus and implications for microhomology-mediated nonhomologous DNA end joining

    OpenAIRE

    Pawelczak, Katherine S; Turchi, John J.

    2008-01-01

    DNA-dependent protein kinase (DNA-PK) is an essential component of the nonhomologous end joining pathway (NHEJ), responsible for the repair of DNA double-strand breaks. Ku binds a DSB and recruits the catalytic subunit, DNA-PKcs, where it is activated once the kinase is bound to the DSB. The precise mechanism by which DNA activates DNA-PK remains unknown. We have investigated the effect of DNA structure on DNA-PK activation and results demonstrate that in Ku-dependent DNA-PKcs reactions, DNA-...

  4. Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4 to enhance solubility for injection delivery

    Directory of Open Access Journals (Sweden)

    Fang YP

    2012-09-01

    Full Text Available Yi-Ping Fang,1 Pao-Chu Wu,2 Yaw-Bin Huang,3 Cherng-Chyi Tzeng,4 Yeh-Long Chen,4 Yu-Han Hung,2 Ming-Jun Tsai,5,6 Yi-Hung Tsai31Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan; 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 6School of Medicine, Medical College, China Medical University, Taichung, TaiwanBackground: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenylamino]furo[2,3-b]quinoline (PK-L4 is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection.Aims: To utilize solid lipid nanoparticles (SLNs modified with polyethylene glycol (PEG to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration.Results: The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE% of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%–64% in the human lung carcinoma cell line (A549, 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7, and 95% in

  5. Water cleaning of the fire box screens of the PK-14-2 boiler with combustion of shredded peat

    Energy Technology Data Exchange (ETDEWEB)

    Guzenko, S.I.; Vasil' ev, V.V.; Tyurin, E.A.; Novikov, B.P.; Timofeyev, A.P.; Perevezentsev, V.P.

    1981-04-01

    Combustion of shredded peat in the PK-14-2 boiler of the Yaroslav HPP-1 is accompanied by intensive slagging of the furnace screens, with the formation of connected tough deposits, which leads to slagging of the panel steam superheater and the convective steam superheater, limitations on the boiler load and to a decrease in its technico-economic indicators. The AVOD-1BL system for cleaning the fire box using long-range water spraying equipment is an effective means of removing connected and friable deposits forming with combustion of shredded peat. Considering the high concentration of calcium oxide in the ash of shredded peat, the results of studies of slagging and cleaning of fire box screens of the PK-14-2 boiler of the Yaroslav HPP-1 might be of interest in planning boiler units for Berezov coal, and also in operation of boilers operating on Kansko-Achin basin coals.

  6. Integration of biostatistics and pharmacometrics computing platforms for efficient and reproducible PK/PD analysis: a case study.

    Science.gov (United States)

    Ou, Ying C; Lo, Arthur; Lee, Brian; Liu, Phillip; Kimura, Karen; Eary, Charisse; Hopkins, Alan

    2013-11-01

    Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.

  7. Pk- yrityksen kansainvälistyminen Venäjälle Finnveran kansainvälistymislainan avulla

    OpenAIRE

    Olin, Henrik

    2009-01-01

    Opinnäytetyön aiheena oli tutkia suomalaisten pk- yritysten kansainvälistymistä Venäjälle Finnvera Oy:n kansainvälistymislainan avulla. Tämä työn tarkoituksena oli selvittää, miten suomalaiset pk- yritykset hyödyntävät kansainvälistymisessään erityisrahoituslaitoksen Finnvera Oy:n kansainvälistymislainaa yhtenä rahoitusinstrumenttina kansainvälistymisessään Venäjälle. Tutkimuksen tarkoituksena oli selvittää ne kriteerit, jotka tällä hetkellä vaikuttavat kansainvälistymislainan käyttöön. ...

  8. Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hongling; Huang, Yong; Du, Qian; Luo, Xiaomao; Zhang, Liang; Zhao, Xiaomin; Tong, Dewen, E-mail: dwtong@nwsuaf.edu.cn

    2015-01-09

    Highlights: • PPV reduces PK-15 cells viability by inducing apoptosis. • PPV infection induces apoptosis through mitochondria-mediated pathway. • PPV infection activates p53 to regulate the mitochondria apoptotic signaling. - Abstract: Porcine parvovirus (PPV) infection has been reported to induce the cytopathic effects (CPE) in some special host cells and contribute the occurrence of porcine parvovirus disease, but the molecular mechanisms underlying PPV-induced CPE are not clear. In this study, we investigated the morphological and molecular changes of porcine kidney cell line (PK-15 cells) infected with PPV. The results showed that PPV infection inhibited the viability of PK-15 cells in a time and concentration dependent manner. PPV infection induced typical apoptotic features including chromatin condensation, apoptotic body formation, nuclear fragmentation, and Annexin V-binding activity. Further studies showed that Bax was increased and translocated to mitochondria, whereas Bcl-2 was decreased in PPV-infected cells, which caused mitochondrial outer-membrane permeabilization, resulting in the release of mitochondrial cytochrome c, followed by caspase-9 and caspase-3 activation. However, the expression of Fas and Fas ligand (FasL) did not appear significant changes in the process of PPV-induced apoptosis. Moreover, PPV infection activated p53 signaling, which was involved in the activation of apoptotic signaling induced by PPV infection via regulation of Bax and Bcl-2. Taken together, our results demonstrated that PPV infection induced apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated apoptosis pathway. This study may contribute to shed light on the molecular pathogenesis of PPV infection.

  9. Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway

    International Nuclear Information System (INIS)

    Highlights: • PPV reduces PK-15 cells viability by inducing apoptosis. • PPV infection induces apoptosis through mitochondria-mediated pathway. • PPV infection activates p53 to regulate the mitochondria apoptotic signaling. - Abstract: Porcine parvovirus (PPV) infection has been reported to induce the cytopathic effects (CPE) in some special host cells and contribute the occurrence of porcine parvovirus disease, but the molecular mechanisms underlying PPV-induced CPE are not clear. In this study, we investigated the morphological and molecular changes of porcine kidney cell line (PK-15 cells) infected with PPV. The results showed that PPV infection inhibited the viability of PK-15 cells in a time and concentration dependent manner. PPV infection induced typical apoptotic features including chromatin condensation, apoptotic body formation, nuclear fragmentation, and Annexin V-binding activity. Further studies showed that Bax was increased and translocated to mitochondria, whereas Bcl-2 was decreased in PPV-infected cells, which caused mitochondrial outer-membrane permeabilization, resulting in the release of mitochondrial cytochrome c, followed by caspase-9 and caspase-3 activation. However, the expression of Fas and Fas ligand (FasL) did not appear significant changes in the process of PPV-induced apoptosis. Moreover, PPV infection activated p53 signaling, which was involved in the activation of apoptotic signaling induced by PPV infection via regulation of Bax and Bcl-2. Taken together, our results demonstrated that PPV infection induced apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated apoptosis pathway. This study may contribute to shed light on the molecular pathogenesis of PPV infection

  10. Proposal to study the reactions $\\gamma$p -> p $\\pi$ $^{+}$ $\\pi$ $^{-}$ $\\pi$ $^{0}$, p $\\pi$ $^{+}$ $\\pi$ $^{-}$ $\\pi$ $^{0}$ $\\pi$ $^{0}$ pK $^{+}$ K$^{-}$ $\\pi$ $^{0}$, pK$^{+}$ K$^{-}$ $\\pi$ $^{0}$ $\\pi$ $^{0}$ in the energy range E$\\gamma$ = 19

    CERN Document Server

    Aston, D; Bailey, R; Ball, A H

    1978-01-01

    Proposal to study the reactions $\\gamma$p -> p $\\pi$ $^{+}$ $\\pi$ $^{-}$ $\\pi$ $^{0}$, p $\\pi$ $^{+}$ $\\pi$ $^{-}$ $\\pi$ $^{0}$ $\\pi$ $^{0}$ pK $^{+}$ K$^{-}$ $\\pi$ $^{0}$, pK$^{+}$ K$^{-}$ $\\pi$ $^{0}$ $\\pi$ $^{0}$ in the energy range E$\\gamma$ = 19

  11. Identification of anti-PP1P(k) in a blood donor and her family: a case report following her pregnancy and review.

    Science.gov (United States)

    Benidt, Georgette R; Jaben, Elizabeth A; Winters, Jeffrey L; Stubbs, James R

    2010-12-01

    Anti-PP1P(k) is a rare, biphasic antibody with the ability to cause immediate hemolytic transfusion reactions and early spontaneous abortions. The antibody is formed by individuals with the p phenotype. A blood donor with anti-PP1P(k) and the p phenotype was identified through routine donor screening. A sister was found to also be p phenotype. At that time, the sister was 24weeks pregnant. Subsequently, the original blood donor became pregnant. Both individuals were followed throughout their pregnancies and delivered infants without complications from anti-PP1P(k) antibodies. The literature regarding anti-PP1P(k), the p phenotype, and recurrent pregnancy loss in this setting is reviewed. PMID:21030308

  12. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas;

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG...... axis, the half-life of LH was estimated to be 1.3 h and that of testosterone 7.69 h, which corresponds well with literature values. The estimated potency of LH with respect to testosterone secretion was 5.18 IU l-1, with a maximal stimulation of 77.5 times basal testosterone production. The estimated...

  13. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    Science.gov (United States)

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  14. Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK.

    Science.gov (United States)

    Schneider, Joachim; Bitterlich, Norman; Schulze, Guntram

    2005-01-01

    The aim of this study was to improve diagnostic efficiency in the detection of gastro-intestinal cancers by using fuzzy logic modeling in combination with a tumor marker panel (CEA, CA72-4, CA19-9) including Tumor M2-PK. In this prospective study histologically confirmed colorectal (n=247), esophageal (n=86) and gastric cancer (n=122) patients were investigated and compared to control (n=53) persons without any malignant diseases. Tumor M2-PK was measured in plasma with an ELISA (ScheBoBiotech, Germany); all other markers were measured in sera (Roche, Germany). At 95% specificity, tumor detection was possible by the best single marker in colorectal cancer patients in 48% (Tumor M2-PK), in gastric cancers in 61% (CA72-4) and in esophageal cancers in 56% (Tumor M2-PK). A fuzzy logic rule-based system employing a tumor marker panel increased sensitivity significantly in colorectal cancers (pTumor M2-PK and CEA), in gastric cancers (pTumor M2-PK and CA 72-4) and in esophageal cancers (pTumor M2-PK and CA72-4). Adding a third marker further improved the sensitivity only marginally. Fuzzy logic analysis has proven to be more powerful than measurement of single markers alone or combinations using multiple logistic regression analysis of the markers. Therefore, with the fuzzy logic method and a tumor marker panel (including Tumor M2-PK), a new diagnostic tool for the detection of gastro-intestinal cancers is available.

  15. Pharmacokinetic/Pharmacodynamic (PK/PD) Indices of Antibiotics Predicted by a Semimechanistic PKPD Model: a Step toward Model-Based Dose Optimization▿

    OpenAIRE

    Nielsen, Elisabet I.; Cars, Otto; Friberg, Lena E.

    2011-01-01

    A pharmacokinetic-pharmacodynamic (PKPD) model that characterizes the full time course of in vitro time-kill curve experiments of antibacterial drugs was here evaluated in its capacity to predict the previously determined PK/PD indices. Six drugs (benzylpenicillin, cefuroxime, erythromycin, gentamicin, moxifloxacin, and vancomycin), representing a broad selection of mechanisms of action and PK and PD characteristics, were investigated. For each drug, a dose fractionation study was simulated, ...

  16. Optimizing intravenous fosfomycin dosing in combination with carbapenems for treatment of Pseudomonas aeruginosa infections in critically ill patients based on pharmacokinetic/pharmacodynamic (PK/PD) simulation

    OpenAIRE

    O. Asuphon; P. Montakantikul; J. Houngsaitong; Kiratisin, P.; P. Sonthisombat

    2016-01-01

    Objective: The purpose of the study was to determine the optimal dosing regimen of intravenous fosfomycin for the treatment of Pseudomonas aeruginosa (PA) based on PK/PD targets. Method: A total of 120 PA isolates were recovered from various clinical specimens at university hospital in Thailand. Minimum Inhibitory Concentrations (MICs) of all the isolates were determined by the E-test method. PK parameters were obtained from a published study. Monte Carlo simulation was performed to calcul...

  17. Comparison of the Radiosensitizing Effect of ATR, ATM and DNA-PK Kinase Inhibitors on Cervical Carcinoma Cells.

    Science.gov (United States)

    Vávrová, J; Zárybnická, L; Jošt, P; Tichý, A; Řezáčová, M; Šinkorová, Z; Pejchal, J

    2016-01-01

    Here, we compared the effects of inhibitors of three phosphatidylinositol-3-kinase-related kinases, ATM, ATR a DNA-PK, on radiosensitization of cervical carcinoma cells. We demonstrated that DNA-PK inhibitor NU7441 enhanced phosphorylation of Chk1 and Chk2 kinases 2 h after irradiation of HeLa cells at a dose of 8 Gy in contrast to ATM kinase inhibitor KU55933, which completely blocked the Chk2 kinase phosphorylation on threonine 68, and ATR kinase inhibitor VE-821, which blocked the Chk1 kinase phosphorylation on serine 345. Most HeLa cells were accumulated in G2 phase of the cell cycle 24 h after irradiation at a high dose of 15 Gy, which was even potentiated after adding the inhibitors NU7441 and KU55933. Compared to all other irradiated groups, inhibitor VE-821 increased the number of cells in S phase and reduced the number of cells in G2 phase 24 h after irradiation at the high dose of 15 Gy. HeLa cells entered the mitotic cycle with unrepaired DNA, which resulted in cell death and the radiosensitizing effect of VE-821. Short-term application of the inhibitors (2 h before and 30 min after the irradiation by the dose of 8 Gy) significantly decreased the colony-forming ability of HeLa cells. Using real-time monitoring of cell proliferation by the xCELLigence system we demonstrated that while the radiosensitizing effect of VE-821 (ATR inhibitor) is manifested early after the irradiation, the radiosensitizing effect of KU55933 (ATM inhibitor) and NU7441 (DNA-PK inhibitor) is only observed as late as 72 h after the irradiation. PMID:27643582

  18. Hormone interactions and regulation of PsPK2::GUS compared with DR5::GUS and PID::GUS in Arabidopsis thaliana.

    Science.gov (United States)

    Bai, Fang; Demason, Darleen A

    2008-02-01

    The putative pea PINOID homolog, PsPK2, is expressed in all growing plant parts and is positively regulated by auxin, gibberellin, and cytokinin. Here, we studied hormonal regulation of PsPK2::GUS expression compared with DR5::GUS and PID::GUS in Arabidopsis. PsPK2::GUS, DR5::GUS, and PID::GUS expression in Arabidopsis shoots is mainly localized in the stipules, hydathodes, veins, developing leaves, and cotyledons. Unlike DR5::GUS, PsPK2::GUS, and PID::GUS are weakly expressed in root tips. Both DR5::GUS and PsPK2::GUS are induced by different auxins and are more sensitive to methyl indole acetic acid, 4-chloro-indole acetic acid, and α-naphthalene acetic acid than others. GA(3) has no significant effect on GUS activity in DR5::GUS-transformed seedlings compared to the control, but induction by auxin and gibberellin in combination is synergistic. Cytokinin increases auxin transport in Arabidopsis seedlings. Auxin, gibberellin, and cytokinin all increase GUS activity in shoots of PsPK2::GUS transformed plants compared to the control. However, only auxin and gibberellin increase GUS activity in PID::GUS shoots. In conclusion, auxin, gibberellin, and cytokinin positively regulate PsPK2 expression in shoots, but not in roots. Auxin and gibberellin also upregulate AtPIN1 and LEAFY expression, which is similar to PsPIN1 and Uni in pea. With minor exceptions, the orthologous genes from both species are regulated similarly. PMID:21632339

  19. Studi Eksperimental Performansi Mesin Pendingin (AC Split) 1 PK dengan Penambahan Alat Akumulator Menggunakan Refrigeran MC-22

    OpenAIRE

    Nasution, Muhammad Jasa

    2016-01-01

    Air conditioning systems is process air customize a room so as to achieve the expected temperature and humidity. The use of a accumulator is an effective way to increase the performance of the cooling system. The use of a accumulator on cooling system so that the refrigerant in a liquid-vapor phase did not enter into the compressor. Research done on the air conditioning (AC) Split 1-PK with a capacity of 9000 Btu/h. The test is done by taking the data size of the pressure on the incoming side...

  20. Kansainväliseen toimintaan tähtäävän pk-yrityksen logistiikkasuunnittelu

    OpenAIRE

    Hartikainen, Mika

    2013-01-01

    Tässä opinnäytetyössä käsitellään logistiikkasuunnitelmaa Kajaanilaisen pk-yrityksen PHD Nordic oy:lle joka on erikoistunut nestetestaussovelluksiin. Opinnäytetyön tavoitteena oli luoda yritykselle logistiikkatoimintojen pohjamalli. Työ käsittelee sitä miten yritys pystyy toimittamaan tuotteensa ulkomaalaisille asiakkaille, minkälaisia keinoja tavaran toimituksessa ulkomaille on ja miten tavarat jaetaan asiakkaille sekä kuka jakaa ne. Työ on jaoteltu kolmeen pääryhmään jotka ovat Logi...

  1. Neuer Test zum Nachweis von Darmkrebs : Von der Grundlagenforschung zur klinischen Anwendung - Krebszellennachweis anhand von Tumor M2-PK

    OpenAIRE

    Hardt, Philip D.; Mazurek, Sybille; Klör, Hans-Ulrich; Eigenbrodt, Erich

    2004-01-01

    Wissenschaftler der Universität Gießen haben im renommierten Fachmagazin 'British Journal of Cancer' einen zukunftsweisenden neuen Test vorgestellt, der in Stuhlproben Krebszellen anhand des Enzyms Tumor M2-PK (Tumor M2-Pyruvatkinase) aufspürt. Das 'British Journal of Cancer' gehört zu der berühmten 'Nature Publishing Group' und gilt auf dem Gebiet der Onkologie als eine der weltweit führenden Fachzeitschriften für die Krebsdiagnostik und -therapie. Der neue Test zum Nachweis v...

  2. Increasing the reach of the PK-3R continuous Miner; Desarrollo y Ensayo de un Sistema para aumentar el alcance de la Pina de Rozado en un Minador PK-3R

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    The objective of this project is the development and implementation of a system designed to increase the reach of the cutting head of a PK-3R continuous miner working in our coal operations. Justification for the project stems from our method of coal extraction, whereby once the sub-level gallery has been advanced to it`s limit, extraction of the coal is undertaken by retreat mining, using a room and pillar method. In this method the roof is blasted to allow greater coal recovery. Due to it`s short length, the original position of the cutting arm of the PK-3R miner did not permit the total recovery of the blasted coal piled up on the gallery floor. Therefore an increase in the reach of the arm is very beneficial, facilitating the recovery of coal that previously could not be recovered. The system also permits excavation for support methods to be undertaken more rapidly, and a better adaptation of the miner to the irregularities of the wall, thus permitting it to move up or down more quickly, reducing the movements required. The system has not caused significant breakdowns, and the availability of the miner is good. In addition, the substitution of the turret in the case of a breakdown is an easy task, as during the design stage, the ease of mounting and dismounting the turret was considered as a fundamental parameter. (Author)

  3. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

    Science.gov (United States)

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2014-05-01

    The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; pholes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression.

  4. Quantitative autoradiographic determination of binding sites for a peripheral benzodiazepine ligand ((/sup 3/H)PK 11195) in human iris

    Energy Technology Data Exchange (ETDEWEB)

    Valtier, D.; Malgouris, C.; Uzan, A.

    1987-01-01

    Specific binding sites of peripheral-type benzodiazepines were investigated in human iris/ciliary body (8 eyes). Examination of color-coded prints and densitometric quantification of autoradiograms were performed on slides (20 ..mu..m) labelled with (/sup 3/H)PK 11195 (1 nM) at 25 deg C. Nonspecific binding was determined with PK 11211 (5 ..mu..M) or Ro 5-4864 (5 ..mu..M). Binding sites were present on all the slides, with equivalent density in the 3 regions of the preparation (ciliary body, iris and pupil margin). The numbers of binding sites in ciliary body, iris, and pupil margin, respectively were: 42.7 +- 0.2, 30.1 +- 0.5 and 37.4 +- 0.4 femtomol/mg protein. Labelling on the pupil margin seemed to coincide with the iris sphincter muscle. The presence of peripheral benzodiazepine binding sites in iris muscular tissue, and particularly in the pupil margin, suggests that the iris preparation may be a valuable tool to detect putative physiological effects of peripheral benzodiazepines on muscular motility.

  5. Porcine Circovirus Type 2 Activates CaMMKβ to Initiate Autophagy in PK-15 Cells by Increasing Cytosolic Calcium

    Science.gov (United States)

    Gu, Yuanxing; Qi, Baozhu; Zhou, Yingshan; Jiang, Xiaowu; Zhang, Xian; Li, Xiaoliang; Fang, Weihuan

    2016-01-01

    Porcine circovirus type 2 (PCV2) induces autophagy via the 5′ adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) pathway in pig kidney PK-15 cells. However, the underlying mechanisms of AMPK activation in autophagy induction remain unknown. With specific inhibitors and RNA interference (RNAi), we show that PCV2 infection upregulated calcium/calmodulin-dependent protein kinase kinase-beta (CaMKKβ) by increasing cytosolic Ca2+ via inositol 1,4,5-trisphosphate receptor (IP3R). Elevation of cytosolic calcium ion (Ca2+) did not seem to involve inositol 1,4,5-trisphosphate (IP3) release from phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide phospholipase C-gamma (PLC-γ). CaMKKβ then activated both AMPK and calcium/calmodulin-dependent protein kinase I (CaMKI). PCV2 employed CaMKI and Trp-Asp (WD) repeat domain phosphoinositide-interacting protein 1 (WIPI1) as another pathway additional to AMPK signaling in autophagy initiation. Our findings could help better understanding of the signaling pathways of autophagy induction as part of PCV2 pathogenesis. Further research is warranted to study if PCV2 interacts directly with IP3R or indirectly with the molecules that antagonize IP3R activity responsible for increased cytosolic Ca2+ both in PK-15 cells and PCV2-targeted primary cells from pigs. PMID:27213427

  6. Porcine Circovirus Type 2 Activates CaMMKβ to Initiate Autophagy in PK-15 Cells by Increasing Cytosolic Calcium

    Directory of Open Access Journals (Sweden)

    Yuanxing Gu

    2016-05-01

    Full Text Available Porcine circovirus type 2 (PCV2 induces autophagy via the 5′ adenosine monophosphate-activated protein kinase (AMPK/extracellular signal-regulated kinase (ERK/tuberous sclerosis complex 2 (TSC2/mammalian target of rapamycin (mTOR pathway in pig kidney PK-15 cells. However, the underlying mechanisms of AMPK activation in autophagy induction remain unknown. With specific inhibitors and RNA interference (RNAi, we show that PCV2 infection upregulated calcium/calmodulin-dependent protein kinase kinase-beta (CaMKKβ by increasing cytosolic Ca2+ via inositol 1,4,5-trisphosphate receptor (IP3R. Elevation of cytosolic calcium ion (Ca2+ did not seem to involve inositol 1,4,5-trisphosphate (IP3 release from phosphatidylinositol 4,5-bisphosphate (PIP2 by phosphoinositide phospholipase C-gamma (PLC-γ. CaMKKβ then activated both AMPK and calcium/calmodulin-dependent protein kinase I (CaMKI. PCV2 employed CaMKI and Trp-Asp (WD repeat domain phosphoinositide-interacting protein 1 (WIPI1 as another pathway additional to AMPK signaling in autophagy initiation. Our findings could help better understanding of the signaling pathways of autophagy induction as part of PCV2 pathogenesis. Further research is warranted to study if PCV2 interacts directly with IP3R or indirectly with the molecules that antagonize IP3R activity responsible for increased cytosolic Ca2+ both in PK-15 cells and PCV2-targeted primary cells from pigs.

  7. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  8. De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology

    Directory of Open Access Journals (Sweden)

    Nijkamp Jurgen F

    2012-03-01

    Full Text Available Abstract Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV, insertions/deletions (indels and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN.PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN.PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN.PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN.PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.

  9. A phenylalanine ammonia-lyase ortholog (PkPAL1) from Picrorhiza kurrooa Royle ex. Benth: molecular cloning, promoter analysis and response to biotic and abiotic elicitors.

    Science.gov (United States)

    Bhat, Wajid Waheed; Razdan, Sumeer; Rana, Satiander; Dhar, Niha; Wani, Tariq Ahmad; Qazi, Parvaiz; Vishwakarma, Ram; Lattoo, Surrinder K

    2014-09-01

    Picrorhiza kurrooa Royle ex Benth. is a highly reputed medicinal herb utilised in the preparation of a number of herbal drug formulations, principally due to the presence of novel monoterpene iridoid glycosides kenned as picrosides. Phenylalanine ammonia-lyase catalyses an important rate-limiting step in phenylpropanoid pathway and supplies precursors like cinnamic acid, vanillic acid, ferulic acid, etc., to a variety of secondary metabolites including picrosides. The imperilled status of P. kurrooa coupled with lack of information regarding biogenesis of picrosides necessitates deciphering the biosynthetic pathway for picrosides. In the present study, a PAL gene, designated PkPAL1 was isolated from P. kurrooa. The cDNA is 2312 bp in length, consisting of an ORF of 2142 bp encoding for a 713 amino acid protein having a predicted molecular weight of 77.66 kDa and an isoelectric point of pH 6.82. qRT-PCR analysis of various tissues of P. kurrooa showed that PkPAL1 transcript levels were highest in the leaves, consistent with picroside accumulation pattern. Using Genome walking, a 718 bp promoter region was also isolated resulting in identification of distinct cis-regulatory elements including TGA-element, TGACG-motif, CGTCA-motif, etc. qRT-PCR indicated up-regulation of PkPAL1 by methyl jasmonate, salicylic acid, 2,4-dicholorophenoxy acetic acid and UV-B elicitations that corroborated positively with the identified cis-elements within the promoter region. Moreover, altitude was found to have a positive effect on the PkPAL1 transcript levels, driving the expression of PkPAL1 abundantly. Based on docking analysis, we identified eight residues as potentially essential for substrate binding in PkPAL1.

  10. Theoretical Determination of the pK a Values of Betalamic Acid Related to the Free Radical Scavenger Capacity: Comparison Between Empirical and Quantum Chemical Methods.

    Science.gov (United States)

    Tutone, Marco; Lauria, Antonino; Almerico, Anna Maria

    2016-06-01

    Health benefits of dietary phytochemicals have been suggested in recent years. Among 1000s of different compounds, Betalains, which occur in vegetables of the Cariophyllalae order (cactus pear fruits and red beet), have been considered because of reducing power and potential to affect redox-modulated cellular processes. The antioxidant power of Betalains is strictly due to the dissociation rate of the acid moieties present in all the molecules of this family of phytochemicals. Experimentally, only the pK a values of betanin were determined. Recently, it was evidenced it was evidenced as the acid dissociation, at different environmental pHs, affects on its electron-donating capacity, and further on its free radical scavenging power. The identical correlation was studied on another Betalains family compound, Betalamic Acid. Experimental evidences showed that the free radical scavenging capacity of this compound drastically decreases at pH > 5, but pK a values were experimentally not measured. With the aim to justify the Betalamic Acid behavior as free radical scavenger, in this paper we tried to predict in silico the pK a values by means different approaches. Starting from the known experimental pK as of acid compounds, both phytochemicals and small organic, two empirical approaches and quantum-mechanical calculation were compared to give reliable prediction of the pK as of Betalamic Acid. Results by means these computational approaches are consistent with the experimental evidences. As shown herein, in silico, the totally dissociated species, at the experimental pH > 5 in solution, is predominant, exploiting the higher electron-donating capability (HOMO energy). Therefore, the computational estimated pK a values of Betalamic Acid resulted very reliable. PMID:26253717

  11. Biodistribution and dosimetry of [{sup 123}I]iodo-Pk 11195: a potential agent for SPET imaging of the peripheral benzodiazepine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Versijpt, J. [Groningen Univ. Hospital (Netherlands). Dept. of Biological Psychiatry; Div. of Nuclear Medicine, Ghent Univ. Hospital (Belgium); Dumont, F.; Vos, F. de; Slegers, G. [Dept. of Radiopharmacy, Ghent Univ. (Belgium); Thierens, H. [Dept. of Biomedical Physics and Radiation Protection, Ghent Univ. (Belgium); Jansen, H.; Dierckx, R.A. [Div. of Nuclear Medicine, Ghent Univ. Hospital (Belgium); Santens, P. [Dept. of Neurology, Ghent Univ. Hospital (Belgium); Korf, J. [Groningen Univ. Hospital (Netherlands). Dept. of Biological Psychiatry

    2000-09-01

    The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PBR has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PBR. The aim of this study was to investigate in humans the biodistribution and dosimetry of [{sup 123}I]iodo-PK 11195, a potential single-photon emission tomography tracer for the PBR. Five healthy volunteers were injected with 112 MBq of [{sup 123}I]iodo-PK 11195. Sequential whole-body scans were performed up to 72 h post injection. Multiple blood samples were taken, and urine was collected to measure the fraction voided by the renal system. Decay-corrected regions of interest of the whole-body images were analysed, and geometric mean count rates were used to determine organ activity. Organ absorbed doses and effective dose were calculated using the MIRD method. [{sup 123}I]iodo-PK 11195 was rapidly cleared from the blood, mainly by the hepatobiliary system. Approximately 22% was voided in urine after 48 h. Average organ residence times were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large intestine, respectively. The testes received the highest dose, 109.4 {mu}Gy/MBq. All other organs investigated received doses of less than 50 {mu}Gy/MBq. The effective dose was 40.3 {mu}Sv/MBq. In conclusion, [{sup 123}I]iodo-PK 11195 is a suitable agent for the visualisation of the PBR and indirectly for the imaging of neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv following an administration of 185 MBq, a [{sup 123}I]iodo-PK 11195 investigation has to be considered an ICRP risk category IIb investigation. (orig.)

  12. Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells

    Directory of Open Access Journals (Sweden)

    Lin Tong

    2011-09-01

    Full Text Available Abstract Background shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF and cell enzyme linked immunosorbent assays (cell ELISA, and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells. Results Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 106 TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 102 TCID50 of FMDV. Conclusions Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.

  13. Biodistribution and dosimetry of [123I]iodo-Pk 11195: a potential agent for SPET imaging of the peripheral benzodiazepine receptor

    International Nuclear Information System (INIS)

    The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PBR has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PBR. The aim of this study was to investigate in humans the biodistribution and dosimetry of [123I]iodo-PK 11195, a potential single-photon emission tomography tracer for the PBR. Five healthy volunteers were injected with 112 MBq of [123I]iodo-PK 11195. Sequential whole-body scans were performed up to 72 h post injection. Multiple blood samples were taken, and urine was collected to measure the fraction voided by the renal system. Decay-corrected regions of interest of the whole-body images were analysed, and geometric mean count rates were used to determine organ activity. Organ absorbed doses and effective dose were calculated using the MIRD method. [123I]iodo-PK 11195 was rapidly cleared from the blood, mainly by the hepatobiliary system. Approximately 22% was voided in urine after 48 h. Average organ residence times were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large intestine, respectively. The testes received the highest dose, 109.4 μGy/MBq. All other organs investigated received doses of less than 50 μGy/MBq. The effective dose was 40.3 μSv/MBq. In conclusion, [123I]iodo-PK 11195 is a suitable agent for the visualisation of the PBR and indirectly for the imaging of neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv following an administration of 185 MBq, a [123I]iodo-PK 11195 investigation has to be considered an ICRP risk category IIb investigation. (orig.)

  14. Role of XRCC4 phosphorylation by DNA-PK in the regulation of NHEJ repair pathway of DNA double strand break

    International Nuclear Information System (INIS)

    Non-homologous end-joining (NHEJ) is the predominant pathway of DNA double strand breaks in higher eukaryotes and is active throughout the cell cycle. NHEJ repair includes many factors as Ku70/86, DNA-PKcs, XRCC4-Ligase IV complex and XLF (also known as Cernunnos). In these factors, DNA-PKcs acts as central regulator in NHEJ repair. It recruited at the DNA damages site after DNA damage and after association with Ku its kinase activity is activated. It phosphorylates many of important NHEJ proteins in vitro including XRCC4, Ku 70/86, Artemis, and even DNA-PKcs but till now, very less studies have been done to know the role and significance of phosphorylation in the NHEJ repair. Studies by other researchers identified various phosphorylation sites in XRCC4 by DNA-PK using mass spectrometry but these phosphorylation sites were shown to be dispensable for DSB repair. In the present investigation, we identified 3 serine and one new threonine phosphorylation sites in XRCC4 protein by DNA-PK. In vivo phosphorylation at these sites was verified by generating phosphorylation specific antibodies and the requirement for DNA-PK therein was verified by using DNA-PK inhibitor and DNA-PK proficient and deficient cell lines in response to radiation and zeocin treatment. We have also found that phosphorylation at these sites showed dose dependency in response to radiation treatment. The two serine and one threonine phosphorylation site is also biological important as their mutation into alanine significantly elevated radiosensitivity as measured by colony formation assay. Neutral comet assay showed delayed kinetics in DSB repair of these mutants. Furthermore, we have found a protein, with putative DSB repair function, which interacts with domain including the phosphorylation sites.These results indicate that these phosphorylation sites would mediate functional link between XRCC4 and DNA-PK. (author)

  15. Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells

    OpenAIRE

    Lin Tong; Shao Junjun; Cong Guozheng; Sun Jingjing; Zhang Guofeng; Gao Shandian; Du Junzheng; Luo Jihuai; Chang Huiyun

    2011-01-01

    Abstract Background shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV) receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integra...

  16. Prediction of sorption parameters for heavy-metal ions using sorption pH50 versus hydrolysis pK correlation relations

    International Nuclear Information System (INIS)

    A new type of correlation has been found between the hydrolytic properties of lead, zinc, cadmium, copper, cobalt and nickel cations (hydrolysis pK) and sorption pH50. The complexing properties of synthesized chelating polymeric sorbents, namely, derivatives of polystyrene-azosalicylic acid, have been studied. Correlations have been found between hydrolysis pK (pKH) of sal9cylic acid and chelation pH50 of toxicant elements with the goal of finding interaction tendencies in M2+-sorbent systems. The correlations found allow the prediction of the sorption pH50 of metal ions and they are useful for coordination and analytical chemistry

  17. {sup 18}F-GE-180: a novel TSPO radiotracer compared to {sup 11}C-R-PK11195 in a preclinical model of stroke

    Energy Technology Data Exchange (ETDEWEB)

    Boutin, Herve; Gerhard, Alexander [University of Manchester, Faculty of Medical and Human Sciences, Manchester (United Kingdom); University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Murray, Katie [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Pradillo, Jesus [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Universidad Complutense/Politecnica de Madrid, Madrid (Spain); Maroy, Renaud [SHFJ - CEA Orsay, Orsay (France); Smigova, Alison [University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Jones, Paul A.; Trigg, William [GE Healthcare Ltd., Amersham (United Kingdom)

    2014-10-29

    Neuroinflammation plays a critical role in various neuropathological conditions, and hence there is renewed interest in the translocator protein (TSPO) as a biomarker of microglial activation and macrophage infiltration in the brain. This is reflected in the large amount of research conducted seeking to replace the prototypical PET radiotracer {sup 11}C-R-PK11195 with a TSPO ligand with higher performance. Here we report the in vivo preclinical investigation of the novel TSPO tracer {sup 18}F-GE-180 in a rat model of stroke. Focal cerebral ischaemia was induced in Wistar rats by 60-min occlusion of the middle cerebral artery (MCAO). Brain damage was assessed 24 h after MCAO by T2 MRI. Rats were scanned with {sup 11}C-R-PK11195 and {sup 18}F-GE-180 5 or 6 days after MCAO. Specificity of binding was confirmed by injection of unlabelled R-PK11195 or GE-180 20 min after injection of {sup 18}F-GE-180. In vivo data were confirmed by ex vivo immunohistochemistry for microglial (CD11b) and astrocytic biomarkers (GFAP). {sup 18}F-GE-180 uptake was 24 % higher in the core of the ischaemic lesion and 18 % lower in the contralateral healthy tissue than that of {sup 11}C-R-PK11195 uptake (1.5 ± 0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BP{sub ND} = 3.5 ± 0.4 and 2.4 ± 0.5 for {sup 18}F-GE-180 and {sup 11}C-R-PK11195, respectively, with R{sub 1} = 1). Injection of unlabelled R-PK11195 or GE-180 20 min after injection of {sup 18}F-GE-180 significantly displaced {sup 18}F-GE-180 (69 ± 5 % and 63 ± 4 %, respectively). Specificity of the binding was also confirmed by in vitro autoradiography, and the location and presence of activated microglia and infiltrated macrophages were confirmed by immunohistochemistry. The in vivo binding characteristics of {sup 18}F-GE-180 demonstrate a better signal to noise ratio than {sup 11}C-R-PK11195 due to both a better signal in the lesion and lower nonspecific binding in

  18. PK/PD analysis of a novel pH-dependent antigen-binding antibody using a dynamic antibody-antigen binding model.

    Science.gov (United States)

    Haraya, Kenta; Tachibana, Tatsuhiko; Iwayanagi, Yuki; Maeda, Atsuhiko; Ozeki, Kazuhisa; Nezu, Junichi; Ishigai, Masaki; Igawa, Tomoyuki

    2016-04-01

    Previously, we have reported novel engineered antibody with pH-dependent antigen-binding (recycling antibody), and with both pH-dependent antigen-binding and increased FcRn-binding at neutral pH (sweeping antibody). The purpose of this study is to perform PK/PD predictions to better understand the potential applications of the antibodies as therapeutics. To demonstrate the applicability of recycling and sweeping antibodies over conventional antibodies, PK/PD analyses were performed. PK/PD parameters for antibody and antigen dynamics were estimated from the results of a pharmacokinetic study in human FcRn transgenic mice. A simulation study was performed using the estimated PK/PD parameters with various target antigen profiles. In comparison to conventional antibody, recycling antibody enhanced antibody-antigen complex clearance by 3 folds, while sweeping antibody accelerated antigen clearance by 10 folds in a pharmacokinetic study. Simulation results showed that recycling and sweeping antibodies can improve dosage frequency and reduce the required dose for target antigens with various clearances, plasma concentrations or binding kinetics. Moreover, importance of the association rate constant to enhance the beneficial effect of antibodies was shown. These results support the conclusion that recycling and sweeping antibodies can be applied to various target antigens with different profiles, and expand the number of antigens that antibodies can target. PMID:26944099

  19. PK/PD modelling of glucose-insulin-glucagon dynamics in healthy dogs after a subcutaneous bolus administration of native glucagon or a novel glucagon analogue

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Boye Knudsen, Carsten;

    Objective We aim to develop a simulation model of the complex glucose-insulin-glucagon dynamics based on physiology and data. Furthermore, we compare pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of marketed reconstituted glucagon with a stable liquid glucagon analogue invented...

  20. Cell nonhomologous end joining capacity controls SAF-A phosphorylation by DNA-PK in response to DNA double-strand breaks inducers.

    Science.gov (United States)

    Britton, Sébastien; Froment, Carine; Frit, Philippe; Monsarrat, Bernard; Salles, Bernard; Calsou, Patrick

    2009-11-15

    Aiming to identify novel phosphorylation sites in response to DNA double-strand breaks (DSB) inducers, we have isolated a phosphorylation site on KU70. Unexpectedly, a rabbit antiserum raised against this site cross-reacted with a 120 kDa protein in cells treated by DNA DSB inducers. We identified this protein as SAF-A/hnRNP U, an abundant and essential nuclear protein containing regions binding DNA or RNA. The phosphorylation site was mapped at S59 position in a sequence context favoring a "S-hydrophobic" consensus model for DNA-PK phosphorylation site in vivo. This site was exclusively phosphorylated by DNA-PK in response to DNA DSB inducers. In addition, the extent and duration of this phosphorylation was in inverse correlation with the capacity of the cells to repair DSB by Nonhomologous End Joining. These results bring a new link between the hnRNP family and the DNA damage response. Addtionaly, the mapped phospho-site on SAF-A might serve as a potential bio-marker for DNA-PK activity in academic studies and clinical analyses of DNA-PK activators or inhibitors. PMID:19844162

  1. Biodistribution and dosimetry of [I-123]iodo-PK 11195 : a potential agent for SPET imaging of the peripheral benzodiazepine receptor

    NARCIS (Netherlands)

    Versijpt, J; Dumont, F; Thierens, H; Jansen, H; De Vos, F; Slegers, G; Santens, P; Dierckx, RA; Korf, J

    2000-01-01

    The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PER has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PER. The aim of this stud

  2. Feline and canine coronaviruses are released from the basolateral side of polarized epithelial LLC-PK1 cells expressing the recombinant feline aminopeptidase-N cDNA

    NARCIS (Netherlands)

    Rossen, J W; Kouame, J; Goedheer, A J; Vennema, H; Rottier, P J

    2001-01-01

    In this study feline (FECV and FIPV) and canine (CCoV) coronavirus entry into and release from polarized porcine epithelial LLC-PK1 cells, stably expressing the recombinant feline aminopeptidase-N cDNA, were investigated. Virus entry appeared to occur preferentially through the apical membrane, simi

  3. Pharmacokinetic analysis of [11C]PBR28 in the rat model of herpes encephalitis: comparison with (R)-[11C]PK11195 for pre-clinical imaging

    NARCIS (Netherlands)

    Kopschina Feltes, Paula; Parente, Andrea; Vállez Garcia, David; Sijbesma, Jurgen; Moriguchi Jeckel, Cristina; Dierckx, Rudi; de Vries, Erik; Doorduin, Janine

    2015-01-01

    Aim: [11C]PBR28 is a second generation translocator protein (TSPO) ligand with supposedly better imaging characteristics than the most commonly used tracer [11C]PK11195. Surprisingly, only limited studies have evaluated the pharmacokinetic and binding profile of [11C]PBR28 in neuroinflammatory model

  4. Pharmacokinetic analysis of 11C-PBR28 in the rat model of herpes encephalitis (HSE): comparison with (R)-11C-PK11195

    NARCIS (Netherlands)

    Parente, Andrea; Kopschina Feltes, Paula; Vállez Garcia, David; Sijbesma, Jurgen; Moriguchi Jeckel, Cristina M; Dierckx, Rudi; de Vries, Erik F; Doorduin, Janine

    2016-01-01

    11C-PBR28 is a second generation TSPO tracer with supposedly superior characteristics than the most commonly used tracer for neuroinflammation, (R)-11C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of 11C-PBR28 in rodent models of ne

  5. De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology

    NARCIS (Netherlands)

    Nijkamp, J.F.; Broek, van den M.; Datema, E.; Kok, de S.; Bosman, L.; Luttik, M.A.; Daran-Lapujade, P.; Vongsangnak, W.; Nielsen, J.; Heijne, W.H.M.; Klaassen, P.; Paddon, C.J.; Platt, D.; Kotter, P.; Ham, van R.C.H.J.; Reinders, M.J.T.; Pronk, J.T.; Ridder, de D.; Daran, J.M.

    2012-01-01

    Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization

  6. MOLECULAR CLONING, CHARACTERIZATION, AND REGULATION OF A PSEUDOMONAS PICKETTII PK01 GENE IN ENCODING PHENOL HYDROXYLASE AND EXPRESSION OF THE GENE IN PSEUDOMONAS AERUGINOSA PA01C

    Science.gov (United States)

    A 26 kilobase BamHI restriction endonuclease DNA fragment has been cloned from Pseudomonas pickettii PK01, a strain isolated from a soil microcosm that had been amended with benzene, toluene, and xylene. This DNA fragment, cloned into vector plasmid pR0l727 and designated pR0l957...

  7. [18F]DPA-714: Direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats

    International Nuclear Information System (INIS)

    Neuro-inflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated micro-glia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuro-inflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats. Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [11C]PK11195 and/or [18F]DPA-714 under anaesthesia. Uptake of [11C]PK11195 vs [18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.8460.67 vs 2.2860.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [11C]PK11195 or with [18F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [11C]PK11195 and [18F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.3561.21 vs 4.6662.50 for [11C]PK11195 vs [18F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI) fold by linear regression) for [18F]DPA-714. In a clinically relevant model of neuro-inflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [18F]DPA-714 displayed a higher signal-to-noise ratio than [11C]PK11195. Our results suggest that, with the longer half-life of [18F] which facilitates distribution of

  8. 猪血凝性脑脊髓炎病毒在PK-15细胞中的增殖特性%Replicative kinetics of porcine hemagglutinating encephalomyelitis virus (HEV) in PK-15 cells

    Institute of Scientific and Technical Information of China (English)

    潘伟; 宋晗星; 赵传博; 丁宁; 陆慧君; 贺文琦; 高丰

    2012-01-01

    To study the replication characteristics of HEV-67N strain in porcine kidney PK 15 cell lines,indirect im- munofluorescent assay(IFA) ,real-time RT PCR assay and virus titration assay were used to detect HEV protein expression,virus genome RNA replication and assembly of matured virus particles, respectively. The monolayer cells were inoculated with HEV-67N strain at 400 TCID50 per well iri 24-well tissues culture plates. The results showed that the viral antige could be detected as early as 8h p. i,and the cells were fully infected at 32 h p. i. The virus genome RNA synthesized rapidly between 32-48 h p. i,reached its peak at 48 h p. i. The virus-infected cells exhibited obvious CPE at 56 h p. i. The result of virus titration assay and Rreal time RT PCR assay are consistent with each other.%利用光学显微镜观察、间接免疫荧光(IFA)、Real-time PCR和病毒感染滴度(TCID50)等测定方法,分别从病毒抗原分布、病毒基因组复制水平以及病毒感染滴度变化等方面对猪血凝性脑脊髓炎病毒(HEV-67N)在猪肾上皮传代细胞系(PK-15细胞)上的增殖特性进行了研究。使用HEV-67N株感染24孔细胞培养板内的PK-15细胞,接种剂量为400个TCID50(104.37)/孔,间接免疫荧光检测结果显示,在感染后8h即可检测到被荧光抗体标记的感染细胞,且随着感染时间的延长,出现荧光的细胞数量逐渐增多,至感染后32h,几乎所有的细胞均出现有荧光。Real-time PCR检测结果显示,病毒基因组RNA的复制在感染后32~48h呈快速上升趋势,其基因组拷贝数在感染后48h达到最高值,之后增殖速度减慢,至感染后56h细胞出现CPE。TCID50的测定结果显示,HEV感染滴度的变化趋势与基因组RNA含量的变化相一致,在感染后32~48h增殖速度最快,之后逐渐减缓,至72h病毒感染滴度达到最高。

  9. DNA double-strand break repair, DNA-PK, and DNA ligases in two human squamous carcinoma cell lines with different radiosensitivity

    International Nuclear Information System (INIS)

    Purpose: Variation in sensitivity to radiotherapy among tumors has been related to the capacity of cells to repair radiation-induced DNA double-strand breaks (DSBs). DNA-dependent protein kinase (DNA-PK) and DNA ligases may affect DNA dsb rejoining. This study was performed to compare rate of rejoining of radiation-induced DSBs, DNA-PK, and DNA ligase activities in two human squamous carcinoma cell lines with different sensitivity to ionizing radiation. Methods and Materials: Cell survival of two human squamous carcinoma cell lines, UM-SCC-1 and UM-SCC-14A, was determined by an in vitro clonogenic assay. DSB rejoining was studied using pulsed field gel electrophoresis (PFGE). DNA-PK activity was determined using BIOTRAK DNA-PK enzyme assay system (Amersham). DNA ligase activity in crude cell extracts was measured using [5'-33P] Poly (dA)·(oligo (dT) as a substrate. Proteolytic degradation of proteins was analyzed by means of Western blotting. Results: Applying the commonly used linear-quadratic equation to describe cell survival, S = e-αD-βD2, the two cell lines roughly have the same α value (∼0.40 Gy-1) whereas the β value was considerably higher in UM-SCC-14A (0.067 Gy-2 ± 0.007 Gy-2 [SEM]) as compared to UM-SCC-1 (0.013 Gy-2 ± 0.004 Gy-2 [SEM]). Furthermore, UM-SCC-1 was more proficient in rejoining of X-ray-induced DSBs as compared to UM-SCC-14A as quantified by PFGE. The constitutive level of DNA-PK activity was 1.6 times higher in UM-SCC-1 as compared to UM-SCC-14A (p < 0.05). The constitutive level of DNA ligase activity was similar in the two cell lines. Conclusions: The results suggest that the proficiency in rejoining of DSBs is associated with DNA-PK activity but not with total DNA ligase activity

  10. Identification and analysis of differential miRNAs in PK-15 cells after foot-and-mouth disease virus infection.

    Directory of Open Access Journals (Sweden)

    Ke-Shan Zhang

    Full Text Available The alterations of MicroRNAs(miRNAs in host cell after foot-and-mouth disease virus (FMDV infection is still obscure. To increase our understanding of the pathogenesis of FMDV at the post-transcriptional regulation level, Solexa high-throu MicroRNAs (miRNAs play an important role both in the post-transcriptional regulation of gene expression and host-virus interactions. Despite investigations of miRNA expression ghput sequencing and bioinformatic tools were used to identify differentially expressed miRNAs and analyze their functions during FMDV infection of PK-15 cells. Results indicated that 9,165,674 and 9,230,378 clean reads were obtained, with 172 known and 72 novel miRNAs differently expressed in infected and uninfected groups respectively. Some of differently expressed miRNAs were validated using stem-loop real-time quantitative RT-PCR. The GO annotation and KEGG pathway analysis for target genes revealed that differently expressed miRNAs were involved in immune response and cell death pathways.

  11. Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells

    Directory of Open Access Journals (Sweden)

    Yingshan Zhou

    2016-02-01

    Full Text Available Porcine circovirus type 2 (PCV2 infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following ER stress. Here, we demonstrate that PCV2 triggered unfolded protein response (UPR in PK-15 cells by activating the PERK/eIF2α pathway without concomitant activation of IRE1 or ATF6. Since ATF4 and CHOP were induced later than PERK/eIF2α, it is clear that persistent PCV2 infection could lead to selective activation of PERK via the PERK-eIF2α-ATF4-CHOP axis. Therefore, PERK activation could be part of the pro-apoptotic signaling via induced expression of CHOP by PCV2. Since PERK inhibition by GSK2606414 or RNA silencing or suppression of eIF2α dephosphorylation by salubrinal limited viral replication, we suppose that PCV2 deploys UPR to enhance its replication. Over-expression of GRP78 or treatment with tauroursodeoxycholic acid could enhance viral capsid expression and/or viral titers, indicating that these chaperones, endogenous or exogenous, could help correct folding of viral proteins. Our findings provide the first evidence that ER stress plays a role in the pathogenesis of PCV2 infection probably as part of autophagic and apoptotic responses.

  12. Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells.

    Science.gov (United States)

    Zhou, Yingshan; Qi, Baozhu; Gu, Yuanxing; Xu, Fei; Du, Huahua; Li, Xiaoliang; Fang, Weihuan

    2016-02-01

    Porcine circovirus type 2 (PCV2) infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER) stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following ER stress. Here, we demonstrate that PCV2 triggered unfolded protein response (UPR) in PK-15 cells by activating the PERK/eIF2α pathway without concomitant activation of IRE1 or ATF6. Since ATF4 and CHOP were induced later than PERK/eIF2α, it is clear that persistent PCV2 infection could lead to selective activation of PERK via the PERK-eIF2α-ATF4-CHOP axis. Therefore, PERK activation could be part of the pro-apoptotic signaling via induced expression of CHOP by PCV2. Since PERK inhibition by GSK2606414 or RNA silencing or suppression of eIF2α dephosphorylation by salubrinal limited viral replication, we suppose that PCV2 deploys UPR to enhance its replication. Over-expression of GRP78 or treatment with tauroursodeoxycholic acid could enhance viral capsid expression and/or viral titers, indicating that these chaperones, endogenous or exogenous, could help correct folding of viral proteins. Our findings provide the first evidence that ER stress plays a role in the pathogenesis of PCV2 infection probably as part of autophagic and apoptotic responses. PMID:26907328

  13. Light energy conversion into H{sub 2} by Anabaena variabilis mutant PK84 dense cultures exposed to nitrogen limitations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jianguo [Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071 (China); Bukatin, Vyacheslav E.; Tsygankov, Anatoly A. [Institute of Basic Biological Problem, Russia Academy of Sciences, Pushchino, Moscow Region 142292 (Russian Federation)

    2006-09-15

    Concentrated cultures (25-86mgChl al{sup -1}) of Anabaena variabilis PK84 were incubated under 99% Ar+1% CO{sub 2} atmosphere in the photobioreactor made of coaxial cylinders. Under illumination equal to 353{mu}Em{sup -2}s{sup -1} they produced hydrogen with the rate more than 20mll{sup -1}h{sup -1} for several days. The efficiency of light energy conversion into H{sub 2} was approx. 1% and did not depend significantly on initial Chl a concentration. H{sub 2}/O{sub 2} ratio reached 41.5% of theoretical value for water photolysis. Data indicate that dense cultures might be used for outdoor systems under direct sun light. Supra-optimal temperatures 36{sup |}C were not harmful for cultures even for 2 days period. Short-term incubation of cultures under 36{sup |}C even increased H{sub 2} production rate and efficiency of light energy bioconversion by 1.25 times. (author)

  14. Tekijänoikeudet ja niihin liittyvät sopimukset PK-yrittäjien näkökulmasta

    OpenAIRE

    Tallila, Emilia

    2016-01-01

    Tämä opinnäytetyö on tehty oppaaksi tekijänoikeuksista ja niihin liittyvistä sopimuksista pienille ja keskisuurille yrityksille eli PK-yrityksille kohdennettuna. Oppaan tarkoituksena on lisätä PK-yritysten tekijänoikeudellista tuntemusta ja neuvoa niihin liittyvien sopimusten tulkinnassa ja tekemisessä. Tästä syystä opinnäytetyössä on vahvassa roolissa myös sopimusoikeudellisten perusteiden käsittely. Aiheen rajauksen vuoksi tässä opinnäytetyössä keskitytään Suomen lainsäädäntöön. Opinnäy...

  15. Hormone interactions and regulation of Unifoliata, PsPK2, PsPIN1 and LE gene expression in pea (Pisum sativum) shoot tips.

    Science.gov (United States)

    Bai, Fang; DeMason, Darleen A

    2006-07-01

    The Unifoliata (Uni) gene plays a major role in development of the compound leaf in pea, but its regulation is unknown. In this study, we examined the effects of plant hormones on the expression of Uni, PsPK2 (the gene for a pea homolog of Arabidopsis PID, a regulator of PIN1 targeting), PsPIN1 (the major gene for a putative auxin efflux carrier) and LE (a gibberellin biosynthesis gene, GA3ox), and also examined mutual hormonal regulation of these genes, in pea shoot tips, including a number of mutants. The Uni promoter possessed putative auxin and gibberellin response elements. The PsPIN1 mRNA levels were increased in afila, which replaces leaflets with branched tendrils; and reduced in tendrilless, which replaces tendrils with leaflets, compared with the wild type (WT). In contrast, mRNA levels of LE were increased in uni and tendrilless and decreased in afila compared with the WT. Uni, PsPK2 and PsPIN1 are positively regulated by gibberellin and auxin, and were induced to higher levels by simultaneous application of auxin and gibberellin. Auxin induction of Uni, PsPK2 and PsPIN1 did not require de novo protein synthesis. LE was positively regulated by auxin and cytokinin. In conclusion, these results support the hypothesis that auxin and gibberellin positively regulate Uni, which controls pea compound leaf development. Also, Uni, PsPIN1, PsPK2 and LE are expressed differentially in the leaf mutants, suggesting that mutual regulation by auxin and gibberellin promotes compound leaf development. PMID:16760220

  16. Observation of narrow baryon resonance decaying into $pK^0_s$ in pA-interactions at $70 GeV/c$ with SVD-2 setup

    CERN Document Server

    Aleev, A; Ardashev, E; Balandin, V; Basiladze, Sergei G; Berezhnev, S; Bogdanova, G A; Boguslavsky, M; Egorov, N; Ejov, V; Ermakov, G; Ermolov, P; Furmanec, N; Golovnia, S; Golubkov, S; Gorkov, A; Gorokhov, S; Gramenitsky, I; Grishin, N; Grishkevich, Ya; Karmanov, D; Kholodenko, A; Kiriakov, A; Kosarev, I; Kouzmine, N; Kozlov, V; Kozlov, Yu; Kokoulina, E; Korotkov, N V; Kramarenko, V; Kubarovsky, A; Kurchaninov, L L; Kuzmin, V; Kuznetsov, E; Lanshikov, G; Larichev, A; Leflat, A; Levitsky, M; Lyutov, S; Maiorov, S; Merkin, M; Minaenko, A A; Mitrofanov, G Ya; Moiseev, A; Murzin, V; Nikitin, V; Nomokonov, V P; Oleinik, A; Orfanitsky, S V; Parakhin, V; Petrov, V; Pilavova, L; Pleskach, A; Popov, V; Riadovikov, V; Rudenko, R; Rufanov, I; Senko, V; Shafranov, M; Shalanda, N A; Sidorov, A; Soldatov, M; Tikhonova, L A; Topuria, T; Tsyupa, Yu; Vasilev, M; Vischnevskaya, A; Volkov, V; Vorobev, A; Voronin, A; Yakimchuk, V; Yukaev, A I; Zakamsky, L; Zapolskii, V N; Zhidkov, N; Zmushko, V V; Zotkin, S A; Zotkin, D S; Zverev, E

    2004-01-01

    SVD-2 experiment data have been analyzed to search for an exotic baryon state, the $\\Theta^+$-baryon, in a $pK^0_s$ decay mode at $70 GeV/c$ on IHEP accelerator. The reaction $pA \\to pK^0_s+X$ with a limited multiplicity was used in the analysis. The $pK^0_s$ invariant mass spectrum shows a resonant structure with $M=1526\\pm3(stat.)\\pm 3(syst.) MeV/c^2$ and $\\Gamma < 24 MeV/c^2$. The statistical significance of this peak was estimated to be of $5.6 \\sigma$. The mass and width of the resonance is compatible with the recently reported $\\Theta^+$- baryon with positive strangeness which was predicted as an exotic pentaquark ($uudd\\bar{s}$) baryon state. The total cross section for $\\Theta^+$ production in pN-interactions for $X_F\\ge 0$ was estimated to be $(30\\div120) \\mu b$ and no essential deviation from A-dependence for inelastic events $(\\sim A^{0.7})$ was found.

  17. Mechanistic Projection of First-in-Human Dose for Bispecific Immunomodulatory P-Cadherin LP-DART: An Integrated PK/PD Modeling Approach.

    Science.gov (United States)

    Chen, X; Haddish-Berhane, N; Moore, P; Clark, T; Yang, Y; Li, H; Xuan, D; Barton, H A; Betts, A M; Barletta, F

    2016-09-01

    A bispecific immunomodulatory biotherapeutic molecule (P-cadherin LP-DART) based on the Dual Affinity Re-Targeting (DART) scaffold has been developed as a potential antitumor treatment showing efficacy in preclinical testing. A minimal anticipated biological effect level (MABEL) approach was applied to project the first-in-human (FIH) dose, because of its immune agonistic properties following target engagement. The pharmacological activity of P-cadherin LP-DART is driven by binding to both P-cadherin on the tumor cells and CD3 on T cells. Therefore, the concentration of the tri-molecular synapse formed between drug, T cell, and tumor cell, rather than drug concentration, is responsible for efficacy. A mechanistic pharmacokinetic/pharmacodynamic (PK/PD)-driven approach was explored to understand the exposure-response relationship based on the synapse concentration to project the MABEL dose. Orthogonal approaches including PK-driven and receptor occupancy calculations were also investigated. This study showcases the application of PK/PD modeling in immune-oncology, and could potentially be implemented for other bispecific biotherapeutics. PMID:27170541

  18. High cell density culture with S. cerevisiae CEN.PK113-5D for IL-1β production: optimization, modeling, and physiological aspects.

    Science.gov (United States)

    Landi, Carmine; Paciello, Lucia; de Alteriis, Elisabetta; Brambilla, Luca; Parascandola, Palma

    2015-02-01

    Saccharomyces cerevisiae CEN.PK113-5D, a strain auxotrophic for uracil belonging to the CEN.PK family of the yeast S. cerevisiae, was cultured in aerated fed-batch reactor as such and once transformed to express human interleukin-1β (IL-1β), aiming at obtaining high cell densities and optimizing IL-1β production. Three different exponentially increasing glucose feeding profiles were tested, all of them "in theory" promoting respiratory metabolism to obtain high biomass/product yield. A non-structured non-segregated model was developed to describe the performance of S. cerevisiae CEN.PK113-5D during the fed-batch process and, in particular, its capability to metabolize simultaneously glucose and ethanol which derived from the precedent batch growth. Our study showed that the proliferative capacity of the yeast population declined along the fed-batch run, as shown by the exponentially decreasing specific growth rates on glucose. Further, a shift towards fermentative metabolism occurred. This shift took place earlier the higher was the feed rate and was more pronounced in the case of the recombinant strain. Determination of some physiological markers (acetate production, intracellular ROS accumulation, catalase activity and cell viability) showed that neither poor oxygenation nor oxidative stress was responsible for the decreased specific growth rate, nor for the shift to fermentative metabolism. PMID:25106469

  19. Study of pK values and effective dielectric constants of ionizable residues in pentapeptides and in staphylococcal nuclease (SNase) using a mean-field approach.

    Science.gov (United States)

    Bossa, Guilherme Volpe; Fahr, Alfred; Pereira de Souza, Tereza

    2014-04-17

    The determination of pK values of amino acid residues as a function of temperature and ionic concentration is crucial to understanding the dynamics of various biological processes such as adsorption of peptides and their interactions with active sites of enzymes. In this study we developed a mean-field model to calculate the position-dependent dielectric constants of ionizable groups and the mean electrostatic potential on the surface. Such potential, which takes into account the contributions exerted by neighboring groups and ions in solution, is responsible for the fine-tuning of the pK value of each residue. The proposed model was applied to the amino acids Asp, Glu, Lys, His, Tyr, and Cys, and since the results were consistent with experimentally obtained values, the model was extended and applied to computation of pK values of Gly and Ala pentapeptides and of ionizable residues of the enzyme staphylococcal nuclease (SNase). In this latter case, we used an approach similar to a first-neighbors approximation, and the results turned out to be in good agreement with previously reported data when considering only the interactions of charged groups located at distances of maximally 20 Å. These considerations and the little computational cost involved turn the suggested approach into a promising tool for the modeling of force fields in computational simulations.

  20. Comparative transcriptome analyses indicate enhanced cellular protection against FMDV in PK15 cells pretreated with IFN-γ.

    Science.gov (United States)

    Fu, Yin; Zhu, Zesen; Chang, Huiyun; Liu, Zaixin; Liu, Jing; Chen, Huiyong

    2016-07-25

    Interferon gamma (IFN-γ) can induce a host antiviral response to foot and mouth disease virus (FMDV) in vivo and in vitro. To elucidate the mechanism of IFN-γ anti FMDV infection in host cells, high-throughput RNA sequencing was analyzed for systemic changes in gene expression profiles in PK15 cells infected by FMDV with or without IFN-γ pretreatment. More than 25 million reads, covering 1.2-1.5 Gb, were analyzed from each experiment panel. FMDV challenge altered the transcription of genes involved in positively and negatively regulating cell death or apoptosis; however, the expected immune suppression response was not obvious. IFN-γ pretreatment combined with FMDV infection normalized the increase in apoptosis. Furthermore, the transcription factors required for IFN-γ functioning, STAT1 and IRF1 were up-regulated by IFN-γ pretreatment and stimulated downstream IFN-stimulated genes (ISGs). These induced ISGs are mainly responsible for antigen processing, antigen presentation or antiviral defense. Interestingly, a synergistic effect on some ISGs, including OAS1, OAS2, MX1, MX2, RIG-I and IFIT1, was observed in the combined treatment compared to the IFN-γ treatment alone. The suggested effects identified by RNA sequencing were consistent with cellular morphology changes and confirmed by related protein markers. This is the first report exploring transcriptome alterations introduced by FMDV infection with or without IFN-γ pretreatment. The identified key host genes that control cell survival in vitro broaden our comprehensive understanding of how IFN-γ inhibits FMDV infection and may shed light on developing improved FMD control approaches. PMID:27018244

  1. [{sup 11}C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches

    Energy Technology Data Exchange (ETDEWEB)

    Su, Zhangjie; Herholz, Karl; Gerhard, Alexander; Jackson, Alan; Hinz, Rainer [University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Roncaroli, Federico [Imperial College London, ' ' John Fulcher' ' Neuro-Oncology Lab, London (United Kingdom); Du Plessis, Daniel [Salford Royal NHS Foundation Trust, Neuropathology Unit, Salford (United Kingdom); Turkheimer, Federico [King' s College London, Centre for Neuroimaging, Institute of Psychiatry, London (United Kingdom)

    2013-09-15

    Translocator protein (TSPO) is a biomarker of neuroinflammation that can be imaged by PET using [{sup 11}C]-(R)PK11195. We sought to characterize the [{sup 11}C]-(R)PK11195 kinetics in gliomas of different histotypes and grades, and to compare two reference tissue input functions (supervised cluster analysis versus cerebellar grey matter) for the estimation of [{sup 11}C]-(R)PK11195 binding in gliomas and surrounding brain structures. Twenty-three glioma patients and ten age-matched controls underwent structural MRI and dynamic [{sup 11}C]-(R)PK11195 PET scans. Tissue time-activity curves (TACs) were extracted from tumour regions as well as grey matter (GM) and white matter (WM) of the brains. Parametric maps of binding potential (BP{sub ND}) were generated with the simplified reference tissue model using the two input functions, and were compared with each other. TSPO expression was assessed in tumour tissue sections by immunohistochemistry. Three types of regional kinetics were observed in individual tumour TACs: GM-like kinetics (n = 6, clearance of the tracer similar to that in cerebellar GM), WM-like kinetics (n = 8, clearance of the tracer similar to that in cerebral WM) and a form of mixed kinetics (n = 9, intermediate rate of clearance). Such kinetic patterns differed between low-grade astrocytomas (WM-like kinetics) and oligodendrogliomas (GM-like and mixed kinetics), but were independent of tumour grade. There was good agreement between parametric maps of BP{sub ND} derived from the two input functions in all controls and 10 of 23 glioma patients. In 13 of the 23 patients, BP{sub ND} values derived from the supervised cluster input were systematically smaller than those using the cerebellar input. Immunohistochemistry confirmed that TSPO expression increased with tumour grade. The three types of [{sup 11}C]-(R)PK11195 kinetics in gliomas are determined in part by tracer delivery, and indicated that kinetic analysis is a valuable tool in the study of

  2. In vivo imaging of ''neuroinflammation''. Principles and applications; In-vivo-Darstellung ''neuroinflammatorischer'' Veraenderungen mit [{sup 11}C] PK11195-PET. Grundlagen und Anwendung

    Energy Technology Data Exchange (ETDEWEB)

    Gerhard, A.; Banati, R.B. [MRC Clinical Sciences Centre and Div. of Neuroscience, Faculty of Medicine, Imperial Coll., London (United Kingdom)

    2002-09-01

    Microglia are the brains' resident immunocompetent cells that can be activated by acute as well as chronic pathological stimuli. When activated they express the peripheral benzodiazepine binding site to which the isoquinolin PK11195 binds with high specificity. Labelled with [{sup 11}C], the R-enatiomer [{sup 11}C] PK1195 has been used for positron emission tomography (PET) studies to demonstrate neuroinflammatory changes in vivo. [{sup 11}C](R) PK11195-PET has been successfully used to show in vivo microglial activation in ischemic (stroke), inflammatory (multiple sclerosis) and degenerative (Alzheimer's and Parkinson's disease). Longitudinal studies are in progress to help to clarify the relationship between localisation and extent of microglial activation and the clinical presentations in these disorders. This will help to determine the role of [{sup 11}C](R) PK11195 PET as a diagnostic tool and a surrogate marker of ''neuroinflammation'' in therapeutic trials. (orig.) [German] Mikroglia sind residente immunkompetente Zellen des Gehirns, die durch akute, aber auch langsam voranschreitende, chronische Schaedigungprozesse aktiviert werden. Im aktivierten Zustand exprimieren sie den peripheren Benzodiazepinrezeptor, an den das Isoquinolin PK11195 spezifisch bindet. Radioaktiv markiert kann das R-Enantiomer [{sup 11}C] PK11195 als Ligand in der Positronenemissionstomographie (PET) genutzt werden und ermoeglicht so die In-vivo-Darstellung aktiver ''neuroinflammatorischer'', d.h. die Mikroglia aktivierender, Veraenderungen. Mit der [{sup 11}C](R) PK11195-PET konnte bisher In-vivo-Mikrogliaaktivierung bei ischaemischen (Schlaganfall), entzuendlichen (multiple Sklerose) und degenerativen (Morbus Alzheimer- und Parkinson-Erkrankung) demonstriert werden. Laufende longitudinale Studien werden dazu beitragen, die Beziehung zwischen Lokalisation und Ausmass der Mikrogliaaktivierung und klinischer Krankheitsauspraegung

  3. Car PK Plane

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    私人飞机的价格在100万到1000万不等,大抵相当于一辆高级豪华轿车。以罗宾逊 R44直升机为例,每架售价400万元人民币左右,比之宾利或劳斯莱斯,还要便宜,而且可以分期付款。目前的国产轻型飞机中,最便宜的是北航生产的蜜蜂系列,价格在15万至32万元北京科源和厦门飞机有限公司生产的 AD200和 AD100飞机,价格都在20万元左右。南方多家航空俱乐部使用的赛斯纳飞机价格在100多万元。而国外的轻型飞机中,特别适合初学者的轻型飞机塞斯纳17R 价格大抵18万美元。停降在北京首都机场的私人飞机售价一般在100万至1000万元人民币,以300至400万的

  4. PK7300全自动血型分析仪测定ABO血型抗体效价的初步研究%A preliminary study on ABO blood type antibody titration by PK7300 automated blood typing analyzer

    Institute of Scientific and Technical Information of China (English)

    石绍川; 刘东; 李军; 田耘博; 陈鹏

    2014-01-01

    目的:探索使用PK7300全自动血型分析仪测定ABO血型抗体效价的方法,探讨献血者血型检测中与ABO血型抗体效价相关的影响因素及注意事项。方法仪器微板法测定抽样标本的ABO血型抗体效价;仪器微板法及手工试管法测定各血型混合血浆的ABO血型抗体效价;统计分析该中心2013年5~7月检测出的ABO血型抗体效价降低的情况。结果A型献血者与B型献血者的ABO血型抗体效价比较,差异无统计学意义(P>0.05),O型献血者的ABO血型抗体效价明显高于A型或B型献血者(P<0.05);手工试管法的灵敏度明显优于仪器微板法,而手工试管法二的灵敏度又明显优于手工试管法一(P<0.05);ABO血型抗体效价降低的A型献血者明显多于B型或O型(均P<0.01),ABO血型抗体效价降低的男性献血者明显多于女性(P<0.01)。结论仪器微板法测定ABO血型抗体效价操作简便、结果判读客观、重复性好,1∶1~1∶80的稀释比例范围能满足绝大多数标本的测定需要,采用梯度稀释有助于减小测定误差;血型、性别、年龄、亚型等因素可能与献血者ABO血型抗体效价降低相关。%Objective To explore the detection method of ABO blood type antibody titration by the PK7300 automated blood typing analyzer and to investigate the ABO blood type antibody titer‐related influencing factors and the matter needing attentions in blood typing test for blood donors .Methods The ABO blood type antibody titers of the samples were measured by the analyzer microplate method;the ABO blood type antibody titer of each mixed plas‐ma was respectively measured by the analyzer microplate method and by the manual tube method;the decrease situa‐tion of ABO blood type antibody titers detected in our center from May to July 2013 were statistically analyzed .Re‐sults There was no statistically significant difference in the ABO

  5. Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

    Directory of Open Access Journals (Sweden)

    E.A. Pessoa

    2009-07-01

    Full Text Available Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU. After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3% and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1% and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 µg/mg protein and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

  6. Anatomy of the pQCD approach to the baryonic decays Λb → pπ, pK

    International Nuclear Information System (INIS)

    We calculate the CP-averaged branching ratios and CP-violating asymmetries for the two-body charmless hadronic decays Λb → pπ, pK in the perturbative QCD (pQCD) approach to lowest order in αs. The baryon distribution amplitudes involved in the factorization formulae are considered to the leading twist accuracy and the distribution amplitudes of the proton are expanded to the next-to-leading conformal spin (i.e., ''P''-waves), the moments of which are determined from QCD sum rules. Our work shows that the contributions from the factorizable diagrams in Λb → pπ, pK decays are much smaller compared to the nonfactorizable diagrams in the conventional pQCD approach. We argue that this reflects the estimates of the Λb → p transition form factors in the kT factorization approach, which are found typically an order of magnitude smaller than those estimated in the light-cone sum rules and in the non-relativistic quark model. As an alternative, we adopt a hybrid pQCD approach, in which we compute the factorizable contributions with the Λb → p form factors taken from the light cone QCD sum rules. The non-factorizable diagrams are evaluated utilizing the conventional pQCD formalism which is free from the endpoint singularities. The predictions worked out here are confronted with the recently available data from the CDF collaboration on the branching ratios and the direct CP asymmetries for the decays Λb → pπ, and Λb → pK. The asymmetry parameter α relevant for the anisotropic angular distribution of the emitted proton in the polarized Λb baryon decays is also calculated for the two decay modes. (orig.)

  7. Cadmium chloride induced cell injury through oxidative stress%镉通过氧化应激机制诱导LLC-PK1细胞损伤

    Institute of Scientific and Technical Information of China (English)

    方鑫; 李海玲; 安彩艳

    2014-01-01

    目的:探讨镉诱导猪肾近曲小管上皮细胞(LLC-PK1)毒性及氧化应激在其中的作用。方法用不同浓度的氯化镉刺激细胞9h和25μmol/L的氯化镉刺激细胞不同时间,采用Formazan 分析细胞存活率反映镉对细胞的损伤程度;以还原型谷胱甘肽(GSH)为靶点,影响GSH浓度的两个试剂BSO和NAC,观察镉诱导细胞损伤中氧化应激的作用。结果随着氯化镉染毒时间延长,细胞存活率下降,同样,随着剂量的增加,细胞的存活率逐渐也下降。同时BSO加重镉诱导的细胞损伤,NAC完全抑制镉诱导的细胞损伤。结论氯化镉对LLC- PK1细胞具有明显的毒性,细胞损伤是通过氧化应激介导,且与细胞内的谷胱甘肽的水平有着密切关系。%Objective To investigate the possible mechanisms of cadmium chloride-induced LLC-PK1 cell toxicity and the role of oxidative stress during the progress. Methods LLC-PK1 cells were treated with different concentrations of cadmium chloride for 9h,and different times at the same dose of cadmium chloride (25μmol/L), respectively.Formazan was used to analyze the cells viability.GSH was taken as a target,and the role of oxidative stress in the progress of cadmium chloride-induced cell injury was assessed by BSO and NAC. Results With the increasing of treatment time and cadmium concentration,Cadmium-induced cell toxicity became more serious and the viability of cells decreased.The cell susceptibility to cadmium chloride could be substantially altered by glutathione (GSH)-modulating agents.Depletion of GSH with BSO increased, whereas supply of cells with NAC decreased subsequent cell injury. Conclusion Cadmium chloride induced cell injury through oxidative stress,which was closely associated with the expression level of intracellular GSH.

  8. Proyecto de aparcamiento anexo a la CV-122 (p.k. 1 + 300, margen izquierdo) en el término municipal de Todolella (Castellón).

    OpenAIRE

    MILIÁN SORRIBES, VÍCTOR ANTONIO

    2016-01-01

    [ES] Todolella es un pueblo del interior de Castellón que en la actualidad presenta problemas de estacionamiento. Para solucionarlo se construirá un parking en las afueras del pueblo al lado de la CV-122 (p.k. 1+300, margen izquierdo) y aprovechando las obras se construirá un paseo peatonal. Para confeccionar la explanada se va alzará un muro de contención de hormigón armado en ménsula y se forrará de piedra para imitar la tradicional construcción de "pedra en sec". A partir del levant...

  9. Dirac-Fock calculations of forbidden transitions within the 3pk and 3dk ground configurations of highly charged tungsten ions (W47+-W61+)

    International Nuclear Information System (INIS)

    Wavelengths and transition probabilities have been computed for forbidden lines within the 3pk and 3dk ground configurations of tungsten ions from W47+ to W61+. The fully relativistic multiconfiguration Dirac-Fock method was used for the calculations. They take into account the correlations within the n = 3 complex, some n = 3 → n' = 4 single excitations and quantum electrodynamics effects. The present results are compared to and agree very well with experimental wavelengths and theoretical transition probabilities previously published for a few lines.

  10. Differentiation-dependent expression of the Na+/glucose cotransporter (SGLT1) in LLC-PK1 cells: role of protein kinase C activation and ongoing transcription.

    OpenAIRE

    Shioda, T; Ohta, T.(Research Center for Nuclear Physics, Osaka University, Ibaraki, Osaka 567-0047, Japan); Isselbacher, K J; Rhoads, D B

    1994-01-01

    We examined changes in the mRNA level of SGLT1, a Na+/glucose cotransporter, by the differentiation status of LLC-PK1 renal epithelial cells. Proliferating (undifferentiated) cells revealed no detectable SGLT1 mRNA by Northern blot analysis. However, when cells became confluent and differentiated into polarized monolayers, there was an abrupt appearance of the SGLT1 mRNA. When confluent (differentiated) cells were dedifferentiated by reseeding at a subconfluent density, SGLT1 mRNA levels decr...

  11. Eficiência e efeito residual de biofertilizantes de rochas com PK e enxofre com Acidithiobacillus em alface Efficiency and residual effect of PK rock biofertilizers with sulfur and Acidithiobacillus on lettuce

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Matias de Lima

    2007-09-01

    PB2 and KB2 and 150% the recommended level PB3 and KB3 for SSP and KCl and a control treatment with no P and K (P0K0. The experimental design was a factorial 5² in the randomized block, with four replicates. There was similar performance of the PK rock biofertilizers compared to the mineral fertilizers, especially when the level BP2BK3 was applied. The consecutive crop showed residual effect on lettuce yield (fresh shoot biomass, height, number of leaves, commercial evaluation, and P and K accumulation on shoot dry biomass. The results suggest that P and K rock biofertilizers may be used as an alternative in mineral fertilization.

  12. Identification and Analysis of Differentially-Expressed microRNAs in Japanese Encephalitis Virus-Infected PK-15 Cells with Deep Sequencing

    Directory of Open Access Journals (Sweden)

    Yuhan Cai

    2015-01-01

    Full Text Available Japanese encephalitis virus (JEV, a mosquito-borne Flavivirus, causes acute viral encephalitis with high morbidity and mortality in humans and animals. MicroRNAs (miRNAs are small noncoding RNAs that are important modulators of the intricate host-pathogen interaction networks. However, our knowledge of the changes that occur in miRNAs in host cells after JEV infection is still limited. To understand the molecular pathogenesis of JEV at the level of posttranscriptional regulation, we used Illumina deep sequencing to sequence two small RNA libraries prepared from PK-15 cells before and after JEV infection. We identified 522 and 427 miRNAs in the infected and uninfected cells, respectively. Overall, 132 miRNAs were expressed significantly differently after challenge with JEV: 78 were upregulated and 54 downregulated. The sequencing results for selected miRNAs were confirmed with RT-qPCR. GO analysis of the host target genes revealed that these dysregulated miRNAs are involved in complex cellular pathways, including the metabolic pathway, inflammatory response and immune response. To our knowledge, this is the first report of the comparative expression of miRNAs in PK-15 cells after JEV infection. Our findings will underpin further studies of miRNAs’ roles in JEV replication and identify potential candidates for antiviral therapies against JEV.

  13. New analysis on narrow baryon resonance decaying into $pK^0_s$ in $pA$-interactions at $70 GeV/c$ with SVD-2 setup

    CERN Document Server

    Aleev, A; Balandin, V; Basiladze, S; Berezhnev, S; Bogdanova, G; Boguslavsky, I; Bychkov, V; Ejov, V; Ermakov, G; Ermolov, P; Furmanec, N; Golovkin, V; Golovnia, S; Gorokhov, S; Gramenitsky, I; Grishin, N; Grishkevich, Ya; Karmanov, D; Kholodenko, A; Kiriakov, A; Kouzmine, N; Kozlov, V; Kokoulina, E; Kramarenko, V; Kubarovsky, A; Kudryashov, I; Kuzmin, V; Kuznetsov, E; Lanshikov, G; Larichev, A; Leflat, A; Levitsky, M; Lyutov, S; Merkin, M; Minaenko, A; Mitrofanov, G; Nikitin, V; Orfanitsky, S; Parakhin, V; Petrov, V; Peshekhonov, V; Pleskach, A; Popov, V; Riadovikov, V; Ronjin, V; Rufanov, I; Savrina, D; Senko, V; Shalanda, N; Soldatov, M; Tikhonova, L; Topuria, T; Tsyupa, Yu; Uzbyakova, A; Vasilev, M; Vishnevskaya, A; Viriasov, K; Volkov, V; Vorobiev, A; Voronin, A; Yakimchuk, V; Yukaev, A; Zakamsky, L; Zapolsky, V; Zhidkov, N; Zotkin, D; Zotkin, S; Zverev, E

    2008-01-01

    The inclusive reaction $p A \\to pK^0_s + X$ was studied at IHEP accelerator with $70 GeV/c$ proton beam using SVD-2 detector. Two different samples of $K^0_s$, statistically independent and belonging to different phase space regions, were used in the analyses and a narrow baryon resonance with the mass $M=1523\\pm 2(stat.)\\pm 3(syst.) MeV/c^2$ was observed in both samples of the data. The combined statistical significance was estimated to be of 8.0 (392 signal over 1990 background events). Using the part of events reconstructed with better accuracy the width of resonance was constrained to $\\Gamma \\approx 0.1$}, that qualitatively agrees to a Regge-based model predictions. A new cross section estimate of $\\sigma \\cdot BR(\\Theta^+ \\to pK^0) = 4.9 \\pm 1.0(stat.) \\pm 1.5(syst.) \\mu b/nucleon$ for $x_F > 0$ was obtained.

  14. EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma.

    Science.gov (United States)

    Lu, Jingchen; Tang, Min; Li, Hongde; Xu, Zhijie; Weng, Xinxian; Li, Jiangjiang; Yu, Xinfang; Zhao, Luqing; Liu, Hongwei; Hu, Yongbin; Tan, Zheqiong; Yang, Lifang; Zhong, Meizuo; Zhou, Jian; Fan, Jia; Bode, Ann M; Yi, Wei; Gao, Jinghe; Sun, Lunquan; Cao, Ya

    2016-09-28

    We conducted this research to explore the role of latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) in modulating the DNA damage response (DDR) and its regulatory mechanisms in radioresistance. Our results revealed that LMP1 repressed the repair of DNA double strand breaks (DSBs) by inhibiting DNA-dependent protein kinase (DNA-PK) phosphorylation and activity. Moreover, LMP1 reduced the phosphorylation of AMP-activated protein kinase (AMPK) and changed its subcellular location after irradiation, which appeared to occur through a disruption of the physical interaction between AMPK and DNA-PK. The decrease in AMPK activity was associated with LMP1-mediated glycolysis and resistance to apoptosis induced by irradiation. The reactivation of AMPK significantly promoted radiosensitivity both in vivo and in vitro. The AMPKα (Thr172) reduction was associated with a poorer clinical outcome of radiation therapy in NPC patients. Our data revealed a new mechanism of LMP1-mediated radioresistance and provided a mechanistic rationale in support of the use of AMPK activators for facilitating NPC radiotherapy. PMID:27255972

  15. The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism

    Directory of Open Access Journals (Sweden)

    McBride William H

    2005-07-01

    Full Text Available Abstract Background By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. Methods Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay. Results Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity. Conclusion We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132.

  16. 逆转录病毒载体介导的T7RNA聚合酶在猪源细胞PK15及SK6中的稳定表达%Stable Expression of T7 RNA Polymerase Gene Mediated by Retroviral Vector in PK15 and SK6 Cells

    Institute of Scientific and Technical Information of China (English)

    吴锦艳; 田宏; 郑海学; 陈妍; 靳野; 尚佑军; 刘湘涛

    2011-01-01

    本研究旨在利用逆转录病毒载体系统将T7RNA聚合酶基因导入猪源细胞,并对该基因的遗传稳定性进行分析.作者克隆并构建含T7RNA聚合酶基因的逆转录病毒重组载体pBABEpuro/T7.将pBABEpuro/T7与水泡性口炎病毒载体pVSV-G共转染GP2-293细胞,收获重组病毒并用该病毒在Polybrene的介导下分别感染PK15和SK6细胞,用嘌呤霉素筛选阳性细胞克隆.对此阳性细胞进行传代,并对不同代次细胞中的T7RNA聚合酶基因进行扩增,确定其遗传稳定性.用直接荧光法和聚丙烯酰胺凝胶电泳检测细胞中T7RNA聚合酶基因的表达及其活性.结果表明T7RNA聚合酶能够被稳定地整合进靶细胞基因组内,细胞系内的T7RNA聚合酶具有较好的转录活性,其活性传代不减弱.免疫荧光检测发现所表达的T7 RNAP蛋白具有良好的反应原性.本研究表明T7RNA聚合酶基因稳定整合进猪源细胞,该基因的稳定整合为建立高效体内病毒拯救系统提供了良好的工具.%The experiment was conducted to insert T7 RNA polymerase (RNAP) gene into cells of swine by retroviral vector system, then to analyze its hereditary stability. The bacteriophage T7 RNAP gene was amplified via PCR from lysogen DE3, and the gene was cloned into pBABEpuro retrovial vector to construct a recombinant plasmid that named as pBABEpuro/T7. Then the pT7BABEpuro and pVSV-G plasmids were cotransfected into GP2-293 packaging cells by Lipfection 2000, some pseudotype viruses were ingathered and transfected into PK15 and SK6 cells under polybrene, respectively. The T7-PK15 and T7-SK6 cells were propagated in DMEM with puromycin respectively. The genome extraction from the cells transfected different times, and the T7 RNAP gene was amplified from the genome by PCR. Expression and activity of T7 RNAP gene in T7-PK15 and T7-SK6 cells were analyzed by immediate fluorescence and SDS-PAGE assay. Results showed that the T7 RNAP gene had been integrated into

  17. The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production.

    Science.gov (United States)

    Meng, Qiao; Hagemeier, Stacy R; Fingeroth, Joyce D; Gershburg, Edward; Pagano, Joseph S; Kenney, Shannon C

    2010-05-01

    Ganciclovir (GCV) and acyclovir (ACV) are guanine nucleoside analogues that inhibit lytic herpesvirus replication. GCV and ACV must be monophosphorylated by virally encoded enzymes to be converted into nucleotides and incorporated into viral DNA. However, whether GCV and/or ACV phosphorylation in Epstein-Barr virus (EBV)-infected cells is mediated primarily by the EBV-encoded protein kinase (EBV-PK), the EBV-encoded thymidine kinase (EBV-TK), or both is controversial. To examine this question, we constructed EBV mutants containing stop codons in either the EBV-PK or EBV-TK open reading frame and selected for stable 293T clones latently infected with wild-type EBV or each of the mutant viruses. Cells were induced to the lytic form of viral replication with a BZLF1 expression vector in the presence and absence of various doses of GCV and ACV, and infectious viral titers were determined by a green Raji cell assay. As expected, virus production in wild-type EBV-infected 293T cells was inhibited by both GCV (50% inhibitory concentration [IC(50)] = 1.5 microM) and ACV (IC(50) = 4.1 microM). However, the EBV-PK mutant (which replicates as well as the wild-type (WT) virus in 293T cells) was resistant to both GCV (IC(50) = 19.6 microM) and ACV (IC(50) = 36.4 microM). Expression of the EBV-PK protein in trans restored GCV and ACV sensitivity in cells infected with the PK mutant virus. In contrast, in 293T cells infected with the TK mutant virus, viral replication remained sensitive to both GCV (IC(50) = 1.2 microM) and ACV (IC(50) = 2.8 microM), although susceptibility to the thymine nucleoside analogue, bromodeoxyuridine, was reduced. Thus, EBV-PK but not EBV-TK mediates ACV and GCV susceptibilities.

  18. In vivo evaluation in mice and metabolism in blood of human volunteers of [123I]iodo-PK11195: a possible single-photon emission tomography tracer for visualization of inflammation

    International Nuclear Information System (INIS)

    We report the in vivo evaluation (biodistribution, displacement and metabolization in blood, brain and heart) in mice and the metabolism in blood of human volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide ([123I]iodo-PK11195), a potential radioligand for visualization of inflammation in humans by single-photon emission tomography. In three series of 18 white mice (NMRI, 20-25 g), the concentration of radioactivity was measured during 48 h. Blood samples were taken, organs and intestines were excised, excretion was collected and all tissues were weighed and counted for radioactivity. The tissue uptake of radioactivity was measured as % of the injected activity/g of tissue. The excretion was expressed as % of the injected activity. Selective tissue uptake was investigated by pretreatment of another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There was an inflow of [123I]iodo-PK11195 in the brain and among peripheral organs, heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After pretreatment with cold PK11195, there was a decrease in accumulation in the latter three organs, especially in heart (ca. 55%) and lungs (ca. 80%). Metabolite analysis was performed using high-performance liquid chromatography (HPLC). First, the extraction yield of [123I]iodo-PK11195 from blood and tissue was assessed, and found to be >90%. From blank blood samples and organs spiked with [123I]iodo-PK11195 it was concluded that no metabolization took place during the extraction procedure. Analysis of plasma, brain and heart of mice showed that 10 min p.i. [123I]iodo-PK11195 was the only significant (ca. 95%) radioactive compound in brain and heart where-as in plasma other radioactive products (>60%) appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37 and 50 min p.i. showed that [123I]iodo-PK11195 rapidly decomposes into two polar metabolites, which at these time

  19. In vivo evaluation in mice and metabolism in blood of human volunteers of [{sup 123}I]iodo-PK11195: a possible single-photon emission tomography tracer for visualization of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, F.; Vos, F. de; Slegers, G. [Department of Radiopharmacy, Univ. of Gent (Belgium); Versijpt, J. [Division of Nuclear Medicine, University Hospital Gent (Belgium)]|[Department of Biological Psychiatry, University Hospital Groningen (Netherlands); Jansen, H.M.L.; Dierckx, R.A. [Division of Nuclear Medicine, University Hospital Gent (Belgium); Korf, J. [Department of Biological Psychiatry, University Hospital Groningen (Netherlands)

    1999-03-01

    We report the in vivo evaluation (biodistribution, displacement and metabolization in blood, brain and heart) in mice and the metabolism in blood of human volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide ([{sup 123}I]iodo-PK11195), a potential radioligand for visualization of inflammation in humans by single-photon emission tomography. In three series of 18 white mice (NMRI, 20-25 g), the concentration of radioactivity was measured during 48 h. Blood samples were taken, organs and intestines were excised, excretion was collected and all tissues were weighed and counted for radioactivity. The tissue uptake of radioactivity was measured as % of the injected activity/g of tissue. The excretion was expressed as % of the injected activity. Selective tissue uptake was investigated by pretreatment of another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There was an inflow of [{sup 123}I]iodo-PK11195 in the brain and among peripheral organs, heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After pretreatment with cold PK11195, there was a decrease in accumulation in the latter three organs, especially in heart (ca. 55%) and lungs (ca. 80%). Metabolite analysis was performed using high-performance liquid chromatography (HPLC). First, the extraction yield of [{sup 123}I]iodo-PK11195 from blood and tissue was assessed, and found to be >90%. From blank blood samples and organs spiked with [{sup 123}I]iodo-PK11195 it was concluded that no metabolization took place during the extraction procedure. Analysis of plasma, brain and heart of mice showed that 10 min p.i. [{sup 123}I]iodo-PK11195 was the only significant (ca. 95%) radioactive compound in brain and heart where-as in plasma other radioactive products (>60%) appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37 and 50 min p.i. showed that [{sup 123}I]iodo-PK11195 rapidly decomposes into two polar

  20. EXPRESSION AND SUBCELLULAR LOCALIZATION OF DNA-PK IN NASOPHARYNGEAL CARCINOMA CELL LINES CNE1 AND CNE2 WITH DIFFERENT RADIOSENSITIVITY

    Institute of Scientific and Technical Information of China (English)

    ZHONG Ping-ping; HE Yu-xiang; XIA Yun-fei; YAN Shan-shan

    2006-01-01

    Objective: Radiosensitivity is mainly determined by the number of DNA double-strand breaks (DSBs) induced by ionizing radiation and the extent of its repair. The DNA-PK complex formation is one of the major pathways by which the mammalian cells respond to DSBs repairing. Our previous study suggested that CNE1 is more radioresistant than CNE2. This study was designed to answer whether the radiosensitive difference of Nasopharyngeal Carcinoma cell lines CNE 1/CNE2 was related to the expression and localization of Ku70/Ku80/DNA-PKcs. Methods: Immunohistochemistry was performed to detect the subcellular localization of Ku70/Ku80/DNA-PKcs in NPC cells lines CNE1 and CNE2. Western-blot was used to determine the expression of Ku protein in total extract of CNE1 and CNE2 and semi-quantitative assay of protein expression was performed to estimate the optic density (OD) value of each band using automatic image analysis system. Results:Ku70/Ku80/DNA-PKcs primarily located in the nuclei. A part of nucleolus in CNE1 and CNE2 showed positive dyeing of DNA-PKcs. Protein expression of Ku70/Ku80/DNA-PKcs was detected in CNE1 and CNE2, and the integral optical density (IOD) of Ku70 protein was 22.03 ± 7.56 and 19.98 ± 6.04 respectively (t=0.021, P>0.05), while the IODs of Ku80 protein in the two cell lines were 33.44 ± 12.87 and 28.98 ± 9.24 respectively (t=0.24, P>0.05), and the IODs of DNA-PKcs protein were 45.03 ± 1.77 and 40.87 ± 4.19 (t=1.58, P>0.05). The above results suggested that the basic expression of Ku70/Ku80/DNA-PKcs had no statistic difference between the different radiosensitive NPC cell lines CNE1 and CNE2.Conclusion: The variation of radiosensitivity in NPC cell lines CNE1 and CNE2 has no obviously correlation with the subcellular localization and basic expression of DNA-PK protein. So we presumed that the difference of radiosensitivity between CNE1 and CNE2 may be on account of some other factors than subcellular localization and basic expression of

  1. Incorporation of mineral phosphorus and potassium on leather waste (collagen): A new N{sub collagen}PK-fertilizer with slow liberation

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Francisco G.E.; Prado, Nayara T. do [Departamento de Quimica, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil); Oliveira, Luiz C.A., E-mail: luizoliveira@ufla.br [Departamento de Quimica, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil); Bastos, Ana R.R. [Departamento de Quimica, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil); Lopes, Joao H. [Departamento de Quimica, UNICAMP, CEP 13083-970, Campinas-SP (Brazil); Carvalho, Janice G. de [Departamento de Ciencia do Solo, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil)

    2010-04-15

    The feasibility of using a solid waste (rich in nitrogen) from the leather industry, after chromium extraction, as adsorbent for P and K, for possible utilization as NPK fertilizer was evaluated. The materials, with and without the addition of P and K, were characterized by chemical analyses, infrared spectroscopy, EDS (energy dispersive X-ray spectrometry) and SEM (scanning electronic microscopy). Langmuir and Freundlich equations were used for analyzing the experimental data, which showed a better fit to the Freundlich model, thus suggesting a multilayer adsorption process on the surface of the adsorbent. A preliminary test in greenhouse demonstrates that the P and K incorporation on the matrix rich in nitrogen (collagen) is a interesting alternative to use such material as NPK fertilizer. The application of N{sub collagen}PK formulations, as a source of nutrients for the growth of rice plants, showed promising agronomic results.

  2. Search for a narrow baryonic state decaying to ${pK^0_S}$ and ${\\overline{p}K^0_S}$ in deep inelastic scattering at HERA

    CERN Document Server

    Abramowicz, H; Adamczyk, L; Adamus, M; Antonelli, S; Aushev, V; Behnke, O; Behrens, U; Bertolin, A; Bhadra, S; Bloch, I; Boos, E G; Brock, I; Brook, N H; Brugnera, R; Bruni, A; Bussey, P J; Caldwell, A; Capua, M; Catterall, C D; Chwastowski, J; Ciborowski, J; Ciesielski, R; Cooper-Sarkar, A M; Corradi, M; Dementiev, R K; Devenish, R C E; Dusini, S; Foster, B; Gach, G; Gallo, E; Garfagnini, A; Geiser, A; Gizhko, A; Gladilin, L K; Golubkov, Yu A; Grzelak, G; Guzik, M; Gwenlan, C; Hain, W; Hlushchenko, O; Hochman, D; Hori, R; Ibrahim, Z A; Iga, Y; Ishitsuka, M; Januschek, F; Jomhari, N Z; Kadenko, I; Kananov, S; Karshon, U; Kaur, P; Kisielewska, D; Klanner, R; Klein, U; Korzhavina, I A; Kotanski, A; Koetz, U; Kovalchuk, N; Kowalski, H; Krupa, B; Kuprash, O; Kuze, M; Levchenko, B B; Levy, A; Limentani, S; Lisovyi, M; Lobodzinska, E; Loehr, B; Lohrmann, E; Longhin, A; Lontkovskyi, D; Lukina, O Yu; Makarenko, I; Malka, J; Mastroberardino, A; Idris, F Mohamad; Nasir, N Mohammad; Myronenko, V; Nagano, K; Nobe, T; Nowak, R J; Onishchuk, Yu; Paul, E; Perlanski, W; Pokrovskiy, N S; Polini, A; Przybycien, M; Roloff, P; Ruspa, M; Saxon, D H; Schioppa, M; Schneekloth, U; Schoerner-Sadenius, T; Shcheglova, L M; Shevchenko, R; Shkola, O; Shyrma, Yu; Singh, I; Skillicorn, I O; Slominski, W; Solano, A; Stanco, L; Stefaniuk, N; Stern, A; Stopa, P; Sztuk-Dambietz, J; Tassi, E; Tokushuku, K; Tomaszewska, J; Tsurugai, T; Turcato, M; Turkot, O; Tymieniecka, T; Verbytskyi, A; Abdullah, W A T Wan; Wichmann, K; Wing, M; Yamada, S; Yamazaki, Y; Zakharchuk, N; Zarnecki, A F; Zawiejski, L; Zenaiev, O; Zhautykov, B O; Zotkin, D S

    2016-01-01

    A search for a narrow baryonic state in the $pK^0_S$ and $\\overline{p}K^0_S$ system has been performed in $ep$ collisions at HERA with the ZEUS detector using an integrated luminosity of 358 pb$^{-1}$ taken in 2003-2007. The search was performed with deep inelastic scattering events at an $ep$ centre-of-mass energy of 318 GeV for exchanged photon virtuality, $Q^2$, between 20 and 100 $\\rm{} GeV^{2}$. Contrary to evidence presented for such a state around 1.52 GeV in a previous ZEUS analysis using a sample of 121 pb$^{-1}$ taken in 1996-2000, no resonance peak was found in the $p(\\overline{p})K^0_S$ invariant-mass distribution in the range 1.45-1.7 GeV. Upper limits on the production cross section are set.

  3. Erythropoietin suppresses epithelial to mesenchymal transition and intercepts Smad signal transduction through a MEK-dependent mechanism in pig kidney (LLC-PK1) cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chien-Liang; Chou, Kang-Ju; Lee, Po-Tsang [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Chen, Ying-Shou; Chang, Tsu-Yuan; Hsu, Chih-Yang; Huang, Wei-Chieh [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Chung, Hsiao-Min [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Fang, Hua-Chang, E-mail: hcfang@isca.vghks.gov.tw [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

    2010-04-15

    Purpose: Tumor growth factor-{beta}1 (TGF-{beta}1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-{beta}1-mediated EMT and fibrosis in kidney injury. Methods: We examined apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-{beta}1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-{beta}1 signal pathway proteins and EMT markers. Results: We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-{beta}1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-{beta}1-mediated apoptosis and also partially inhibited TGF-{beta}1-mediated EMT. We showed that EPO treatment suppressed TGF-{beta}1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-{beta}1-treated cells. Conclusions: EPO inhibited apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

  4. Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model.

    Directory of Open Access Journals (Sweden)

    Shamim H Rahman

    2015-05-01

    Full Text Available In vitro disease modeling based on induced pluripotent stem cells (iPSCs provides a powerful system to study cellular pathophysiology, especially in combination with targeted genome editing and protocols to differentiate iPSCs into affected cell types. In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID, a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK activity. Our results demonstrate that gene editing in RS-SCID fibroblasts rescued DNA-PK dependent signaling to overcome radiosensitivity. Furthermore, in vitro T-cell differentiation from iPSCs was employed to model the stage-specific T-cell maturation block induced by the disease causing mutation. Genetic correction of the RS-SCID iPSCs restored T-lymphocyte maturation, polyclonal V(DJ recombination of the T-cell receptor followed by successful beta-selection. In conclusion, we provide proof that iPSC-based in vitro T-cell differentiation is a valuable paradigm for SCID disease modeling, which can be utilized to investigate disorders of T-cell development and to validate gene therapy strategies for T-cell deficiencies. Moreover, this study emphasizes the significance of designer nucleases as a tool for generating isogenic disease models and their future role in producing autologous, genetically corrected transplants for various clinical applications.

  5. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model.

    Science.gov (United States)

    Bogdanović, Renée Marie; Syvänen, Stina; Michler, Christina; Russmann, Vera; Eriksson, Jonas; Windhorst, Albert D; Lammertsma, Adriaan A; de Lange, Elisabeth C; Voskuyl, Rob A; Potschka, Heidrun

    2014-10-01

    Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.

  6. Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair.

    Science.gov (United States)

    Sunada, Shigeaki; Kanai, Hideki; Lee, Younghyun; Yasuda, Takeshi; Hirakawa, Hirokazu; Liu, Cuihua; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi

    2016-09-01

    High-linear energy transfer (LET) heavy ions have been increasingly employed as a useful alternative to conventional photon radiotherapy. As recent studies suggested that high LET radiation mainly affects the nonhomologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair, we further investigated this concept by evaluating the combined effect of an NHEJ inhibitor (NU7441) at a non-toxic concentration and carbon ions. NU7441-treated non-small cell lung cancer (NSCLC) A549 and H1299 cells were irradiated with X-rays and carbon ions (290 MeV/n, 50 keV/μm). Cell survival was measured by clonogenic assay. DNA DSB repair, cell cycle distribution, DNA fragmentation and cellular senescence induction were studied using a flow cytometer. Senescence-associated protein p21 was detected by western blotting. In the present study, 0.3 μM of NU7441, nontoxic to both normal and tumor cells, caused a significant radio-sensitization in tumor cells exposed to X-rays and carbon ions. This concentration did not seem to cause inhibition of DNA DSB repair but induced a significant G2/M arrest, which was particularly emphasized in p53-null H1299 cells treated with NU7441 and carbon ions. In addition, the combined treatment induced more DNA fragmentation and a higher degree of senescence in H1299 cells than in A549 cells, indicating that DNA-PK inhibitor contributes to various modes of cell death in a p53-dependent manner. In summary, NSCLC cells irradiated with carbon ions were radio-sensitized by a low concentration of DNA-PK inhibitor NU7441 through a strong G2/M cell cycle arrest. Our findings may contribute to further effective radiotherapy using heavy ions. PMID:27341700

  7. 水稻丙酮酸激酶基因OsPK1的过表达转基因株系的获得与鉴定%Generation and Characterization of Overexpression Lines of a Rice Pyruvate Kinase Gene OsPK1

    Institute of Scientific and Technical Information of China (English)

    张艳; 庞金环; 吴家和; 何朝族

    2012-01-01

    We have reported that downregulation of OsPKl ,a rice pyruvate kinase, causes dwarfism, reduced seed set and so on. Therefore, the aim in this study is to explore the effect of the overexpression of OsPKl on rice. The construct containing a CaMV 35S-driven full-length CDS of OsPKl was introduced into the genome of wild-type ( WT) Nipponbare via an Agrobacterium-mediated method. Three overexpression lines were selected for further characterization and analysis. Statistics showed that these overexpression plants approach WT plants in plant height,tiller number,panicle length and thousand seed weight,while present slightly reduced seed set and significantly increased viable seed number per panicle. Quantitative RT-PCR results exhibited that the expressions of four metabolic enzymes were downregulated or upregulated in the young leaves of overexpression plants. The sugar contents were measured using GC-MS.and the results indicated that the contents of glucose,fructose,galactose and sucrose in OsPKl overexpression plants showed few differences compared with those of WT plants. Together,the characterization of OsPKl overexpression plants can help us better understand the role of OsPKl, and increased viable seed number per panicle should be a prospective application.%利用农杆菌介导的转化方法研究OsPK1过表达对水稻的影响.将CaMV 35S启动子驱动的OsPK1的全长CDS序列导入到日本晴基因组中.选择3个过表达转基因系作为代表进行鉴定和分析.结果显示,过表达植株在株高、分蘖数、穗长和千粒重四方面接近野生型水稻,结实率略下降,但每穗饱满种子数明显增加.通过定量RT-PCR分析,发现有4个代谢酶在过表达植株嫩叶中表达存在着上调或下调.用GC-MS方法检测糖含量,显示OsPK1过表达株系中葡萄糖、果糖、半乳糖和蔗糖的含量与野生型差异不大.总之,对OsPK1过表达株系的鉴定,有助于更好了解OsPK1的功能,并且每穗饱满种子

  8. Transcellular transport of radioiodinated 3-iodo-α-methyl-L-tyrosine across monolayers of kidney epithelial cell line LLC-PK1

    International Nuclear Information System (INIS)

    3-[123I]iodo-α-methyl-L-tyrosine ([123I]IMT) is an imaging agent for amino acid transport. In order to obtain fundamental data related to tumor imaging with [123I]IMT and renal physiological accumulation of [123I]IMT, we investigated the transport characteristics of [125I]IMT in porcine kidney epithelial cell line LLC-PK1 using cell monolayers grown on microporous membrane filters. LLC-PK1 monolayers were created on a collagen-coated microporous (3 μm) membrane (4.7 cm2). To examine transcellular transport (secretion and reabsorption) and accumulation, the monolayers were incubated for up to 90 min at 37 deg C with 18.5 kBq [125I]IMT in Dulbecco's phosphate-buffered saline (pH 7.4) as an uptake solution. After incubation, transcellular transport was assessed by quantifying the radioactivity of the solutions on each side of the monolayer. For the accumulation experiment, the cells were solubilized in NaOH solution, and the radioactivity was quantified. For the inhibition experiment, the inhibitor was added at a final concentration of 1 mM. For the pH dependence experiment, the pH of the apical-side uptake solution was varied from pH 5 to pH 8. Transport of [14C]Tyr was examined for comparison. Bi-directional transcellular transport of [125I]IMT was observed, corresponding to secretion and reabsorption in proximal tubule. Accumulation of [125I]IMT from the basolateral side (1.62±0.15%) and the apical side (2.62±0.35%) was observed at 90 min. 2-Amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L), L-Tyr (mother compound of [125I]IMT) and 2-aminoisobutyric acid (an inhibitor of system L and A) inhibited both directional transport (p125I]IMT from both sides (p125I]IMT transport is system L, rather than Na+-dependent transport, in both apical and basolateral membrane. [125I]IMT was transported by the system that transported L-Tyr, but the observed pH dependence of transport suggests that different mechanisms are involved in accumulation of

  9. Pre-Service Teachers Enhance Climate Literacy Through Writing Children's Books on Climate Literacy Concepts and Implementing Related Activities in the PK-12 Classroom

    Science.gov (United States)

    Walton-Jaggers, L. J.

    2014-12-01

    Grambling State University faculty participated in NICE workshops during 2011, 2012, and 2013 that were designed to help pre-service teachers increase their knowledge about global climate change through the use of NASA Earth observation sets. The faculty members were encouraged to infuse climate education projects and activities into their courses from information and resources provided during the workshops. As a result, pre-service teacher candidates in the Department of Curriculum and Instruction of the College of Education at Grambling State University have written Children's Literature that specifically focused on different climate change concepts. This project has served as the culminating Climate Change Signature Project that was designed to promote increased opportunities for PK-12 students to expand their knowledge and understanding of climate literacy concepts while enhancing Reading/Literacy skills. The pre-service teacher candidates completed several sequential steps in preparing for the culminating project. This paper will include the presentation ofseveral formal and informal assessments that were used to determine the impact of the project on the teacher candidates and their students.

  10. 宝刀百炼生玄光——PK900-HZ10A迷你高速球详评

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    PK900-HZ10A迷你高速球外形体积上比普通高速球更小.只有3.5寸,安装更方便.整机或内置摄像机旋转方向的隐蔽性更佳。另外,由于该机采用10倍自动聚集光学变倍镜头(3.8mm~38mm)+10倍数字变倍.共计100倍变倍:IRC双滤光片自动彩色转黑白切换和DSS帧积累功能,360度水平旋转、180度垂直自动翻转:速度从每秒1度到每秒360度可调等.其性能表现都会令用户关注,下面通过实测来验证其强大的功能表现。

  11. Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

    International Nuclear Information System (INIS)

    Carbon-11-labeled chromen-4-one derivatives were synthesized as new potential PET agents for imaging of DNA repair enzyme DNA-dependent protein kinase (DNA-PK) in cancer. The target tracers, X-[11C]methoxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; [11C]4a–d), were prepared from their corresponding precursors, X-hydroxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; 5a–d), with [11C]CH3OTf through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a C-18 Sep-Pak Plus cartridge. The radiochemical yields decay corrected to end of bombardment (EOB), from [11C]CO2, were 40–60%. The specific activity at end of synthesis (EOS) was 185–370 GBq/μmol. - Highlights: ► New chromen-4-one derivatives were synthesized. ► New carbon-11-labeled chromen-4-one derivatives were synthesized. ► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.

  12. The MLH1 c.1852_1853delinsGC (p.K618A variant in colorectal cancer: genetic association study in 18,723 individuals.

    Directory of Open Access Journals (Sweden)

    Anna Abulí

    Full Text Available Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

  13. A theoretical survey of atomic structure and forbidden transitions in the 4pk and 4dk ground configurations of tungsten ions W29+ through W43+

    International Nuclear Information System (INIS)

    Energy levels, wavelengths and radiative decay rates have been calculated for states within the 4pk (k = 1–5) and 4dk (k = 1–9) ground configurations in highly charged tungsten ions. Magnetic dipole (M1) and electric quadrupole (E2) transition probabilities have been obtained using the fully relativistic multiconfiguration Dirac–Fock (MCDF) approach including the correlations within the n = 4 complex, some n = 4 → n′ = 5 single excitations and quantum electrodynamics effects. The validity of the method is assessed through limited comparison with experimental and theoretical data previously published as well as with new relativistic Hartree–Fock calculations. The excellent agreement observed between our new MCDF A-values and those obtained using different theoretical approaches together with a detailed analysis of configuration interaction effects does not confirm the very recent GRASP2K calculations of Jonauskas et al (2012 At. Data Nucl. Data Tables 98 19) for M1 lines within the 4dk configurations, the latter results remaining in large disagreement with all other methods in many cases. (paper)

  14. H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations.

    Science.gov (United States)

    Anandakrishnan, Ramu; Aguilar, Boris; Onufriev, Alexey V

    2012-07-01

    The accuracy of atomistic biomolecular modeling and simulation studies depend on the accuracy of the input structures. Preparing these structures for an atomistic modeling task, such as molecular dynamics (MD) simulation, can involve the use of a variety of different tools for: correcting errors, adding missing atoms, filling valences with hydrogens, predicting pK values for titratable amino acids, assigning predefined partial charges and radii to all atoms, and generating force field parameter/topology files for MD. Identifying, installing and effectively using the appropriate tools for each of these tasks can be difficult for novice and time-consuming for experienced users. H++ (http://biophysics.cs.vt.edu/) is a free open-source web server that automates the above key steps in the preparation of biomolecular structures for molecular modeling and simulations. H++ also performs extensive error and consistency checking, providing error/warning messages together with the suggested corrections. In addition to numerous minor improvements, the latest version of H++ includes several new capabilities and options: fix erroneous (flipped) side chain conformations for HIS, GLN and ASN, include a ligand in the input structure, process nucleic acid structures and generate a solvent box with specified number of common ions for explicit solvent MD.

  15. Addition of ash and PK with or without N on a peatland in southern Sweden. Effects on tree growth and needle element concentrate; Tillfoersel av aska och PK med eller utan N paa en torvmark i soedra Sverige. Effekter paa traedtillvaext och aemneshalter i barr

    Energy Technology Data Exchange (ETDEWEB)

    Sikstroem, Ulf (Forestry Research Inst. of Sweden, Uppsala (Sweden))

    2008-04-15

    In Sweden, about 1.3 million tonnes of ash are produced annually. Out of that amount, 150 000 - 300 000 tonnes have been estimated to originate from forest fuels, i.e. ashes that potentially can be brought back to the forest. Apart from being a compensatory measure after intensive forest harvest (e.g. including tops and branches), the ash may be used to increase the tree growth on peat soils (ash fertilization). On peat soils, tree growth is generally increased after addition of ash or phosphorous (P) and potassium (K) fertilizers. However, in some cases also nitrogen (N) addition is required. On sparsely stocked mires, fertilization may promote the regeneration as well as increase the growth of the trees. Sufficient drainage and supply of plant-available N are some prerequisites for increasing tree growth by PK-addition. In 1982, Skogforsk established a field experiment (168 Perstorp) located in the province of Scania in a sparsely stocked Pinus Sylvestris (L.) sapling stand on a ditched mire where different nutrient regimes were tested. The experiment had a randomized block design including four blocks and seven treatments. Ash and different dozes of P (raw phosphate) and K (potassium chloride), with or without simultaneous N addition, were included as well as un untreated control. The aim of the present study was to evaluate the effects on tree growth and needle elemental concentrations 26 years after treatment. The addition of similar dozes of P (approx. 40 kg P/ha), as ash (2.5 tonnes/ha) or as PK-fertilizer rendered similar growth responses. The increase in stem-wood growth was in the order of 1,6 - 1,9 m3/ha/yr during the 26-year period. The N-addition had no additional effect. On the control plots, the growth was more or less negligible (approx. 0,04 m3sk/ha/yr). On average, the high dozes of raw-phosphate and potassium chloride (40 kg P/ha and 80 kg K/ha) gave a higher growth increase than the low dozes (20 kg P/ha and 40 kg K/ha), although this effect was

  16. Optimizing an online SPE-HPLC method for analysis of (R)-[{sup 11}C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)- 3-isoquinolinecarboxamide [(R)-[{sup 11}C]PK11195] and its metabolites in humans

    Energy Technology Data Exchange (ETDEWEB)

    Greuter, Henri N.J.M. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands)]. E-mail: hnjm.greuter@vumc.nl; van Ophemert, Patricia L.B. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Luurtsema, Gert [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); van Berckel, Bart N.M. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Franssen, Eric J.F. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Windhorst, Bert D. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Lammertsma, Adriaan A. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands)

    2005-04-01

    (R)-[{sup 11}C]PK11195 is used as a positron emission tomography tracer for activated microglia in several neurological disorders. Quantification of specific binding requires a metabolite-corrected plasma input function. In this study, a high-performance liquid chromatography (HPLC) procedure with online solid phase extraction was modified for analyzing (R)-[{sup 11}C]PK11195 plasma samples, yielding total sample recoveries of more than 98%. When applied to human studies, the use of two HPLC systems enabled analysis of up to seven plasma samples under regular conditions. Online radioactivity detection was compared with offline sample measurements of HPLC profiles. Offline measurements provided the most reliable results especially for late plasma samples. In 10 patients, an average decrease of parent compound from 94.6% at 2.5 min to 45.2% at 1 h after administration was observed.

  17. Study of the production of A(b)(0) and (B)over-bar(0) hadrons in pp collisions and first measurement of the A(b)(0)-> J/psi pK(-) branching fraction

    NARCIS (Netherlands)

    Aaij, R.; Adeva, B.; Adinoffi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Gutierrez, O. Aquines; Archilli, F.; d'Argent, P.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barsche, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediagal, I.; Be, L. J.; Bellee, V.; Belloli, N.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Bettler, M-O; Van Beuzekom, M.; Bien, A.; Bifani, S.; Billoir, P.; Bird, T.; Birnkraut, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britschl, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Buchanan, E.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Gomez, M. Calvo; Campana, P.; Perez, D. Campora; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Akiba, K. Carvalho; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch.; Cavallero, G.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S. -F.; Chiapolini, N.; Chrzaszcz, M.; Vida, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collazuo, G.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Torres, M. Cruz; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dall'Occo, E.; Dalseno, J.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Simone, P.; Dean, C. -T.; Decamp', D.; Deckenhoff, M.; Del Buono, L.; Deleage, N.; Demmer, M.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Ruscio, F.; Dijkstra, H.; Donleavy, S.; Dordeill, F.; Dorigo, M.; Suarez, A. Dosil; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farber, C.; Farley, N.; Farry, S.; Fay, R.; Ferguson, D.; Albor, V. Fernandez; Ferrari, F.; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Foh, K.; Fo, P.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Torreira, A. Gallas; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Pardinas, J. Garcia; Tico, J. Garra; Garrido, L.; Gascon, D.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeckil, E.; Gersabeck, M.; Gershon, T.; Chez, Ph.; Giani, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gligorov, V. V.; Gobel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Gandara, M. Grabalosa; Diaz, R. Graciani; Cardoso, L. A. Granado; Grauges, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grunberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hal, S.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Humair, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jane, E.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Keckell, M.; Kelsey, M.; Kenyon, I. R.; Kenzie, M.; Kete, T.; Khanji, B.; Khurewathanaku, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg', P.; Kozeiha, M.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lail, A.; Lambert, D.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; Van Leerdam, J.; Lees, J-P.; Lefevre, R.; Leflat, A.; Lefrancois, J.; Cid, E. Lemos; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Liu, X.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Martinez, M. Lucio; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Machefert, F.; Maciuc, F.; Maev, O.; Maguirem, K.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Manning, P.; Mapelli, A.; Maratas, J.; Marchand, J. F.; Marconi, U.; Benito, C. Maria; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Santos, D. Martinez; Vidal, F. Martinez; Tostes, D. Martins; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurin, B.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Meissner, M.; Melnychuk, D.; Merk, M.; Michielin, E.; Milanes, D. A.; Minard, M. -N.; Mitzel, D. S.; Rodriguez, J. Molina; Monroy, I. A.; Monteil, S.; Morandin, M.; Morawski, P.; Marda, A.; Moreollo, M. J.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Muller, D.; Muller, J.; Muller, K.; Muller, V.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Ninci, D.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, C. J. G.; Rodrigues, B. Osorio; Goicochea, J. M. Otalora; Otto, A.; Owen, P.; Oyanguren, A.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Pappenheimer, C.; Parkes, C.; Passaleval, G.; Pate, G. D.; Pate, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Altarelli, M. Pepe; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petruzzo, M.; Olloqui, E. Picatoste; Pietrzyk, B.; Pilar, T.; Pinci, D.; Pistone, A.; Piuccill, A.; Playfer, S.; Casasus, M. Plo; Poikela, T.; Polci, F.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Popov, A.; Popovi, D.; Popovici, B.; Potterat, C.; Price, E.; Price, J. D.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redi, F.; Reichert, S.; Reid, M. M.; Dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rih, M.; Rinnert, K.; Molina, V. Rives; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Lopez, J. A. Rodriguez; Perez, P. Rodriguez; Roiser, S.; Romanovsky, V.; Vida, A. Romero; Ronayne, J. W.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Vas, P. Ruiz; Silva, J. J. Saborido; Sagidova, N.; Sail, P.; Saitta, B.; Guimaraes, V. Salustino; Mayordomo, C. Sanchez; Sedes, B. Sanmartin; Santacesaria, R.; Rios, C. Santamarina; Santimaria, M.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmellingl, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schubiger, M.; Schune, M. -H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenkom, V.; Shires, A.; Siddi, B. G.; Coutinho, R. Silva; De Oliveira, L. Silva; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, E.; Smith, I. T.; Smith, J.; Smithm, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; De Paula, B. Souza; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stah, S.; Stefkova, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; Van Tilburg, J.; Tisserand, V.; Tobin, M.; Todd, J.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valenti, G.; Vallier, A.; Gomez, R. Vazquez; Regueiro, P. Vazquez; Sierra, C. Vazquez; Vecchi, S.; Velthuis, J. J.; Vetri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Diaz, M. Vieites; Vilasis-Cardona, X.; Volkov, V.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voss, C.; De Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wyllie, K.; Xie, Y.; Xu, Z.; Yang, Z.; Yu, J.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaevth, M.; Zhang, L.; Zhang, Y.; Zhelezovil, A.; Zhokhov, A.; Zhong, L.; Zucchelli, S.

    2016-01-01

    The product of the A(b)(0) ((B) over bar (0)) differential production cross-section and the branching fraction of the decay A(b)(0)-> J/psi pK(-) ((B) over bar (0)-> J/psi p (K) over bar*(892)(0)) is measured as a function of the beauty hadron transverse momentum, p(T), and rapidity, y. The kinemati

  18. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole Lehberg; Afzelius, Pia; Bender, Dirk;

    2014-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...... characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195...

  19. Study of the production of $\\Lambda_b^0$ and $\\overline{B}^0$ hadrons in $pp$ collisions and first measurement of the $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ branching fraction

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Buchanan, Emma; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fohl, Klaus; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Igancio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Ninci, Daniele; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Edmund; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavorima; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zucchelli, Stefano

    2016-01-01

    The product of the $\\Lambda_b^0$ ($\\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ ($\\overline{B}^0\\rightarrow J/\\psi\\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\\rm T}<20~{\\rm GeV}/c$ and $2.0 < y < 4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\\sqrt{s}=7~{\\rm TeV}$ in 2011 and $\\sqrt{s}=8~{\\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\\Lambda_B^0}/f_d$, the branching fraction of the decay $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ is measured to be \\begin{equation*} \\mathcal{B}(\\Lambda_b^0\\rightarrow J/\\psi pK^-)= (3.04\\pm0.04\\pm0.06\\pm0.33^{+0.43}_{-0.27})\\times10^{-4}, \\end{equation*} where the first uncertainty is st...

  20. Aldehyde tag coupled with HIPS chemistry enables the production of ADCs conjugated site-specifically to different antibody regions with distinct in vivo efficacy and PK outcomes.

    Science.gov (United States)

    Drake, Penelope M; Albers, Aaron E; Baker, Jeanne; Banas, Stefanie; Barfield, Robyn M; Bhat, Abhijit S; de Hart, Gregory W; Garofalo, Albert W; Holder, Patrick; Jones, Lesley C; Kudirka, Romas; McFarland, Jesse; Zmolek, Wes; Rabuka, David

    2014-07-16

    It is becoming increasingly clear that site-specific conjugation offers significant advantages over conventional conjugation chemistries used to make antibody-drug conjugates (ADCs). Site-specific payload placement allows for control over both the drug-to-antibody ratio (DAR) and the conjugation site, both of which play an important role in governing the pharmacokinetics (PK), disposition, and efficacy of the ADC. In addition to the DAR and site of conjugation, linker composition also plays an important role in the properties of an ADC. We have previously reported a novel site-specific conjugation platform comprising linker payloads designed to selectively react with site-specifically engineered aldehyde tags on an antibody backbone. This chemistry results in a stable C-C bond between the antibody and the cytotoxin payload, providing a uniquely stable connection with respect to the other linker chemistries used to generate ADCs. The flexibility and versatility of the aldehyde tag conjugation platform has enabled us to undertake a systematic evaluation of the impact of conjugation site and linker composition on ADC properties. Here, we describe the production and characterization of a panel of ADCs bearing the aldehyde tag at different locations on an IgG1 backbone conjugated using Hydrazino-iso-Pictet-Spengler (HIPS) chemistry. We demonstrate that in a panel of ADCs with aldehyde tags at different locations, the site of conjugation has a dramatic impact on in vivo efficacy and pharmacokinetic behavior in rodents; this advantage translates to an improved safety profile in rats as compared to a conventional lysine conjugate. PMID:24924618

  1. Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

    Science.gov (United States)

    Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

    2016-05-01

    In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26991506

  2. First observation of γγ-> p$\\bar{p}$K+K- and search for exotic baryons in pK systems

    Energy Technology Data Exchange (ETDEWEB)

    Shen, C. P.; Yuan, C. Z.; Adachi, I.; Aihara, H.; Asner, David M.; Aulchenko, V.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bakich, A. M.; Barberio, E.; Behera, P.; Bhardwaj, V.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bonvicini, Giovanni; Bozek, A.; Bracko, Marko; Browder, Thomas E.; Cervenkov, D.; Chang, P.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Chistov, R.; Cho, K.; Chobanova, V.; Choi, S-K.; Choi, Y.; Cinabro, David A.; Dalseno, J.; Danilov, M.; Dash, N.; Dolezal, Z.; Drasal, Z.; Dutta, D.; Eidelman, S.; Fang, Wenzheng; Fast, James E.; Ferber, T.; Fulsom, Bryan G.; Gaur, Vipin; Gabyshev, N.; Garmash, A.; Gillard, R.; Glattauer, R.; Goldenzweig, P.; Grzymkowska, O.; Haba, J.; Hayasaka, K.; Hayashii, H.; Hou, W. S.; Iijima, T.; Inami, K.; Inguglia, G.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jaegle, Igal; Jeon, H. B.; Joo, K. K.; Julius, T.; Kang, K. H.; Kato, E.; Kiesling, C.; Kim, D. Y.; Kim, J. B.; Kim, K. T.; Kim, S. H.; Kim, Y. J.; Kodys, P.; Korpar, S.; Kotchetkov, Dmitri V.; Krizan, P.; Krokovny, Pavel; Kuzmin, A.; Kwon, Y. J.; Lange, J. S.; Li, C. H.; Li, H.; Li, Y.; Li Gioi, L.; Libby, J.; Liventsev, D.; Lubej, M.; Luo, T.; Masuda, M.; Matsuda, T.; Matvienko, D.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, Subhashree; Moll, A.; Moon, H K.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Nath, K.; Natkaniec, Z.; Nishida, S.; Ogawa, S.; Olsen, Stephen L.; Ostrowicz, W.; Pakhlov, P.; Pakhlova, G.; Pal, Bilas K.; Park, C. S.; Park, H.; Pesantez, L.; Pestotnik, R.; Petric, M.; Piilonen, Leo E.; Pulvermacher, C.; Rauch, J.; Ritter, M.; Sakai, Y.; Sandilya, Saurabh; Santelj, L.; Sanuki, T.; Savinov, Vladimir; Schluter, T.; Schneider, O.; Schnell, G.; Schwanda, C.; Seino, Y.; Semmler, D.; Senyo, K.; Seong, Ilsoo; Sevior, ME; Shibata, T. A.; Shiu, Jing-Ge; Shwartz, B.; Simon, F.; Sokolov, A.; Solovieva, E.; Stanic, S.; Staric, M.; Strube, Jan F.; Stypula, J.; Sumihama, M.; Sumiyoshi, T.; Takizawa, M.; Tamponi, Umberto; Tanida, K.; Tenchini, F.; Trabelsi, K.; Uchida, M.; Uehara, S.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Varner, G.; Wang, C. H.; Wang, M. Z.; Wang, P.; Watanabe, M.; Watanabe, Y.; Williams, K. M.; Won, E.; Yamaoka, Jared AK; Yelton, John; Yook, Youngmin; Yusa, Y.; Zhang, C. C.; Zhang, Z. P.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Zupanc, A.

    2016-06-30

    The process γγ→p$\\bar{p}$K+K- and its intermediate processes are measured for the first time using a 980 fb-1 data sample collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The production of p$\\bar{p}$K+K- and a Λ(1520)0 ($\\bar{Λ}$(1520)0) signal in the pK- ($\\bar{p}$K+) invariant mass spectrum are clearly observed. However, no evidence for an exotic baryon near 1540 MeV/c2, denoted as Θ(1540)0 ($\\bar{Θ}$(1540)0) or Θ(1540)++ (Θ(1540)--), is seen in the pK- ($\\bar{p}$K+) or pK+ ($\\bar{p}$K-) invariant mass spectra. Cross sections for γγ→p$\\bar{p}$K+K-, Λ(1520)0$\\bar{p}$K++c.c. and the products σ(γγ→Θ(1540)0$\\bar{p}$K++c.c.)B(Θ(1540)0→pK-) and σ(γγ→Θ(1540)++$\\bar{p}$K-+c.c.)B(Θ(1540)++→pK+) are measured. We also determine upper limits on the products of the χc0 and χc2 two-photon decay widths and their branching fractions to p$\\bar{p}$K+K- at the 90% credibility level.

  3. Veromuutosten vaikutus pk-yrityksiin

    OpenAIRE

    Mäkitalo, Jani; Mursu, Kai

    2016-01-01

    Nykyisen taloustilanteen takia Suomen valtion menot ovat nousseet. Tämän takia hallitus on tehnyt leikkauksia valtion budjettiin sekä muuttanut verotusta. Työssä perehdytään Suomen vero-organisaatioon, veropolitiikkaan ja toteutettuihin veromuutoksiin. Työssä käydään läpi veromuutoksien osalta ansio- ja pääomatuloverotusta, kiinteistöverotusta ja edustusmenojen vähennyskelpoisuutta. Näiden muutosten vaikutuksia tutkitaan yritysesimerkein. Esimerkkiyritykset ovat yhtiömuodoiltaan toiminim...

  4. WDR-PK-AK-018

    Energy Technology Data Exchange (ETDEWEB)

    Hollister, R

    2009-08-26

    Method - CES SOP-HW-P556 'Field and Bulk Gamma Analysis'. Detector - High-purity germanium, 40% relative efficiency. Calibration - The detector was calibrated on February 8, 2006 using a NIST-traceable sealed source, and the calibration was verified using an independent sealed source. Count Time and Geometry - The sample was counted for 20 minutes at 72 inches from the detector. A lead collimator was used to limit the field-of-view to the region of the sample. The drum was rotated 180 degrees halfway through the count time. Date and Location of Scans - June 1,2006 in Building 235 Room 1136. Spectral Analysis Spectra were analyzed with ORTEC GammaVision software. Matrix and geometry corrections were calculated using OR TEC Isotopic software. A background spectrum was measured at the counting location. No man-made radioactivity was observed in the background. Results were determined from the sample spectra without background subtraction. Minimum detectable activities were calculated by the Nureg 4.16 method. Results - Detected Pu-238, Pu-239, Am-241 and Am-243.

  5. PK-yrityksen asiakkuusjohtamisen toimintamalli

    OpenAIRE

    Marjanen, Hannu

    2014-01-01

    Opinnäytetyön aiheena oli pienten ja keskisuurten yritysten asiakkuusjohtamisen kehittäminen. Tavoitteena oli luoda asiakkuusjohtamisen toimintamalli pienten ja keskisuurten yritysten kilpailukyvyn ja kannattavuuden parantamiseksi. Opinnäytetyön viitekehys muodostuu myynnin ja markkinoinnin sekä johtamisen kirjallisuuskatsauksesta. Tutkimus toteutettiin hyödyntämällä kehittämistutkimuksen menetelmää. Tutkimustietoa kerättiin sosiaalisen median kanavista että haastattelemalla pienten ...

  6. Analytical Performance of Olympus AU2700 Automatic Biochemical Analyzer in Detecting Electrolyte Proj ect%奥林巴斯AU2700全自动生化分析仪测定电解质项目的性能验证研究

    Institute of Scientific and Technical Information of China (English)

    韩学波; 唐秀英; 李莉; 于欣

    2014-01-01

    Objective:Evaluation the analysis performance of Olympus AU2700 automatic biochemical Analyzer determined electrolytes proj ect.Methods:In accordance with United States clinical laboratory standards organization (CLSI) guidance document and other documents related to the experimental program,analyzes the precision,accuracy,linear range of Olympus AU2700 automatic biochemical analyzer determination electrolyte project.Results:AU2700 automatic biochemical analyzer examines in the K+ batch coefficient of variation respectively is 1.84% and 0.89%,the K+ inter-assay coefficients of variation respectively is 2.08% and 4.20%.The Na+ batch coefficient of variation respectively is 0.05% and 0.94%,the K+ inter-assay coefficients of variation respectively is 0.64% and 0.81%.The Cl- batch coefficient of variation respectively is 0.88% and 0.75%,the Cl- inter-assay coefficients of variation respectively is 1.12% and 1.21%.These results satisfies the CLIA88 standard.Accuracy:the detection result in the EQA the permissible range.Linearity:The linear regression equation of Potassium is Y=1.0085X-0.0312.a is 1.0085 and correlation coefficient is 0.99.Reportable range is 0.68~11.8 mmol/L.The linear regression equation of Sodium ions is Y=9998X-0.0055.a is 0.9998 and correlation co-efficient is 1.Reportable range is 37~288.6 mmol/L.The linear regression equation of Chloride ion is Y=0.9895X+1.8413.a is 0.9895 and correlation coefficient is 0.99.Reportable range is 37.1~246.6 mmol/L.Conclusion:Olympus AU2700 automatic biochemical analyzer examination electrolyte project has met the requirements of biochemical assay laboratory in precision,accuracy,linear range and other aspects,may be used in the clinical specimen examination.%目的:评价奥林巴斯 AU2700全自动生化分析仪测定电解质项目的分析性能。方法:按照美国临床实验室标准化组织(CLSI)指南文件和其他相关文献的实验方案,分析奥林巴斯 AU2700全自动生化分析仪测定电

  7. Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg [Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore (Singapore); Zhu Congju; Wong Yinling; Gao Qiuhan; Ty, Albert; Wong, Meng Cheong [Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore (Singapore)

    2012-05-01

    Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub 2}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, {gamma}-H{sub 2}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G{sub 2}/M arrest and increased {gamma}-H{sub 2}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub 2}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are

  8. Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

    International Nuclear Information System (INIS)

    Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)–Akt-DNA–dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H2AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H2AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G2/M arrest and increased γ-H2AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H2AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G2/M

  9. Textural and structural features, composition and formation conditions of arenaceous rocks in PK1 horizon, Pokursk suite in south-eastern Pur-Tazovsk area (Yamalo-Nenets Autonomous Territory)

    Science.gov (United States)

    Nedolivko, N.; Perevertailo, T.; Barkalova, A.; Dolgaya, T.

    2015-02-01

    Terrigenous deposits of the productive PK1 horizon in Pokursk suite of Pur-Tazovsk area (Yamalo-Nenets Autonomous Territory) were studied to specify the structure and identify the formation features. Complex horizon structure of sequential silt, mudrock interbedding and alternation has been identified. Littoral-marine type of sedimentation (occurring during the total marine transgression increase) by the help of genetic rock features identified during the core sampling and by the granulometry and X-ray-phase results analysis has been determined.

  10. Textural and structural features, composition and formation conditions of arenaceous rocks in PK1 horizon, Pokursk suite in south-eastern Pur-Tazovsk area (Yamalo-Nenets Autonomous Territory)

    International Nuclear Information System (INIS)

    Terrigenous deposits of the productive PK1 horizon in Pokursk suite of Pur-Tazovsk area (Yamalo-Nenets Autonomous Territory) were studied to specify the structure and identify the formation features. Complex horizon structure of sequential silt, mudrock interbedding and alternation has been identified. Littoral-marine type of sedimentation (occurring during the total marine transgression increase) by the help of genetic rock features identified during the core sampling and by the granulometry and X-ray-phase results analysis has been determined

  11. 肿瘤 M2-PK、CEA、SCC、NSE 和 CYFRA21-1在人肺癌诊断中的比较%Comparison of tumor M2-PK, CEA, SCC, NSE and CYFRA21-1 in diagnosis of lung cancer

    Institute of Scientific and Technical Information of China (English)

    魏枫华; 齐川; 李满元

    2014-01-01

    Objective:To compare differences of tumor M2-PK, CEA, SCC, NSE and CYFRA21-1 in diagnosis of lung canc-er. Methods:142 cases with newly diagnosed lung cancer was recruited in the study. M2-PK was detected by an ELISA method. Re-sults: Through comparing tumor markers of human lung cancer with different histologic types, it found that M2-PK had a higher sensi-tivity (57% ) than those of CEA (38% ) and CYFRA 21-1 (43% ). In non-small cell lung cancer (NSCLC), M2-PK (59% ), CEA (39% ) and CYFRA21-1 (56% ) were more sensitive than others. However, for small cell lung cancer, NSE was more sensitive than the other tumor markers. Conclusions: M2-PK can be a better marker for the diagnosis of lung cancer.%目的:为了比较 M2-PK、CEA、CYFRA21-1、NSE 和 SCC 在人肺癌诊断中的差异。方法:142例新诊断的肺癌患者被纳入本次研究,M2-PK 是用一个灵敏的 ELISA 试剂盒来检测的。结果:通过比较不同组织类型人肺癌的肿瘤标志物,发现 M2-PK 灵敏度(灵敏度57%)比 CEA(灵敏度38%)和 CYFRA 21-1(灵敏度43%)高。在非小细胞肺癌中 M2-PK(灵敏度59%),CEA(灵敏度39%),CYFRA21-1(灵敏度56%)的灵敏度普遍较高。对于小细胞肺癌来说,NSE 比其他标志物更敏感。结论:M2-PK 可以作为检测肺癌的标志物。

  12. 肿瘤 M2-PK、CEA、SCC、NSE 和 CYFRA21-1在人肺癌诊断中的比较%Comparison of tumor M2-PK, CEA, SCC, NSE and CYFRA21-1 in diagnosis of lung cancer

    Institute of Scientific and Technical Information of China (English)

    魏枫华; 齐川; 李满元

    2014-01-01

    目的:为了比较 M2-PK、CEA、CYFRA21-1、NSE 和 SCC 在人肺癌诊断中的差异。方法:142例新诊断的肺癌患者被纳入本次研究,M2-PK 是用一个灵敏的 ELISA 试剂盒来检测的。结果:通过比较不同组织类型人肺癌的肿瘤标志物,发现 M2-PK 灵敏度(灵敏度57%)比 CEA(灵敏度38%)和 CYFRA 21-1(灵敏度43%)高。在非小细胞肺癌中 M2-PK(灵敏度59%),CEA(灵敏度39%),CYFRA21-1(灵敏度56%)的灵敏度普遍较高。对于小细胞肺癌来说,NSE 比其他标志物更敏感。结论:M2-PK 可以作为检测肺癌的标志物。%Objective:To compare differences of tumor M2-PK, CEA, SCC, NSE and CYFRA21-1 in diagnosis of lung canc-er. Methods:142 cases with newly diagnosed lung cancer was recruited in the study. M2-PK was detected by an ELISA method. Re-sults: Through comparing tumor markers of human lung cancer with different histologic types, it found that M2-PK had a higher sensi-tivity (57% ) than those of CEA (38% ) and CYFRA 21-1 (43% ). In non-small cell lung cancer (NSCLC), M2-PK (59% ), CEA (39% ) and CYFRA21-1 (56% ) were more sensitive than others. However, for small cell lung cancer, NSE was more sensitive than the other tumor markers. Conclusions: M2-PK can be a better marker for the diagnosis of lung cancer.

  13. 讽刺喜剧的印式述说--谈《外星人PK地球神》%An Indian Style of Satire---On Extraterrestrials PK God

    Institute of Scientific and Technical Information of China (English)

    段奕辰

    2016-01-01

    Indian comedy film Extraterrestrials PK God, through the earth course of extraterrestrials PK , humorously expresses the stick of truth, good and beauty , the ironically revealing of the fake religion , the warning the public blind psychology , and under the appear-ance of entertainment society , it contains philosophical thinking of culture and religious .This article mainly from three aspects com-ments on the film .%印度喜剧电影《外星人PK地球神》,通过外星人PK的地球历程,诙谐地表达了对“真”“善”“美”的坚守、对伪宗教的揭露讽刺、对大众盲从心理的警示,在娱乐外衣下包裹着对文化、宗教的理性思索。本文从三个方面详细解读该影片。

  14. At the foot of Mount Olympus: A theory on myth

    Directory of Open Access Journals (Sweden)

    Flip Schutte

    2006-09-01

    Full Text Available A cult normally develops around myths and rituals. In this article myth as phenomenon will be investigated. Different types and categories of myths will be listed, while research done in the past on myths will also be dealt with. Furthermore, the issue of ritual accompanying the myth will be briefly discussed. This article wants to promote the notion that one does not need any particular worldview, be it mythological, orthodox, fundamentalistic, or biblisistic, to use, understand, and appreciate myths. Even in a postmodern world the value of myths can be appreciated.

  15. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole L.; Afzelius, Pia; Bender, Dirk;

    characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195...... accumulated in only one lesion. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long...

  16. Reforçament del ferm i obres complementàries a la carretera C-150a, del PK 19+000 al 23+210. Tram: Banyoles – Serinyà

    OpenAIRE

    Samper Montero, Christian

    2010-01-01

    El present projecte de final de carrera te per objecte l’estudi per reforçar i millorar les obres complementàries de la antiga carretera de Girona a Ripoll, i actual C150a del PK 19+000 al 23+210, incloent els ramals d’accés a la carretera C-66 (actual carretera Girona – Olot - Ripoll). El projecte es divideix en els documents necessaris, que son una memòria amb el seus annexes, un document de plànols, el plec de prescripcions tècniques i una valoració econòmica que es troba di...

  17. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    DEFF Research Database (Denmark)

    Afzelius, Pia; Nielsen, Ole L; Alstrup, Aage Ko;

    2016-01-01

    with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga...

  18. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    DEFF Research Database (Denmark)

    Afzelius, Pia Maria Tullia; Nielsen, Ole L; Alstrup, Aage Ko;

    2016-01-01

    -FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs...... with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga......-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. (18)F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while (11)C-methionine...

  19. Interaction of GABA-mimetics with the taurine transporter (TauT, Slc6a6) in hyperosmotic treated Caco-2, LLC-PK1 and rat renal SKPT cells.

    Science.gov (United States)

    Rasmussen, Rune Nørgaard; Lagunas, Candela; Plum, Jakob; Holm, René; Nielsen, Carsten Uhd

    2016-01-20

    The aim of the present study was to investigate if basic GABA-mimetics interact with the taurine transporter (TauT, Slc6a6), and to find a suitable cell based model that is robust towards extracellular changes in osmolality during uptake studies. Taurine uptake was measured in human Caco-2 cells, porcine LLC-PK1 cells, and rat SKPT cells using radiolabelled taurine. Hyperosmotic conditions were obtained by incubation with raffinose (final osmolality of 500mOsm) for 24h prior to the uptake experiments. Expression of the taurine transporter, TauT, was investigated at the mRNA level by real-time PCR. Uptake of the GABA-mimetics gaboxadol and vigabatrin was investigated in SKPT cells, and quantified by liquid scintillation or HPLC-MS/MS analysis, respectively. The uptake rate of [(3)H]-taurine was Na(+) and Cl(-) and concentration dependent with taurine with an apparent Vmax of 6.3±1.6pmolcm(-2)min(-1) and a Km of 24.9±15.0μM. β-alanine, nipecotic acid, gaboxadol, GABA, vigabatrin, δ-ALA and guvacine inhibited the taurine uptake rate in a concentration dependent manner. The order of affinity for TauT was β-alanine>GABA>nipecotic acid>guvacine>δ-ALA>vigabatrin>gaboxadol with IC50-values of 0.04, 1.07, 2.02, 4.19, 4.94, 31.4 and 39.9mM, respectively. In conclusion, GABA mimetics inhibited taurine uptake in hyperosmotic rat renal SKPT cells. SKPT cells, which seem to be a useful model for investigating taurine transport in the short-term presence of high concentrations of osmolytes. Furthermore, analogues of β-alanine appear to have higher affinities for TauT than GABA-analogues.

  20. The influence of ATM, ATR, DNA-PK inhibitors on the cytotoxic and genotoxic effects of dibenzo[def,p]chrysene on human hepatocellular cancer cell line HepG2.

    Science.gov (United States)

    Spryszyńska, Sylwia; Smok-Pieniążek, Anna; Ferlińska, Magdalena; Roszak, Joanna; Nocuń, Marek; Stępnik, Maciej

    2015-09-01

    The effect of inhibitors of phosphatidylinositol-3-kinase related kinases (PIKK): ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) on the response of HepG2 human liver cancer cells to dibenzo[def,p]chrysene (DBC) was investigated. High cytotoxicity of DBC (IC50=0.1μM) was observed after 72h incubation. PIKK inhibitors: KU55933 (5μM), NU7026 (10μM) or caffeine (1 and 2mM) when used alone did not significantly influence the cytotoxicity. However, two combinations: KU55933/NU7026 and caffeine/NU7026 significantly increased HepG2 viability (by 25%) after treatment with DBC at 0.5μM. The cytoprotective effect was confirmed by cell cycle and apoptosis/necrosis analysis. DNA damage level after exposure to DBC assessed by comet assay (single strand breaks) showed a long persistence and significant decrease after incubation of the cells in the presence the inhibitors (the combination of KU55933+NU7026 showed the strongest effect). Weak induction of reactive oxygen species (ROS) by DBC (0.5μM) was observed. Although, KU55933 and NU7026 when used alone did not increase ROS levels in the cells, their combination induced the ROS increase and moderately enhanced ROS generation by DBC. We propose a mechanism how cells with damaged DNA after exposure to DBC and under the condition of PIKK inhibition, may be at higher risk of undergoing malignant transformation. PMID:26338538

  1. M2-PK和Cath-D在卵巢交界性浆液性囊腺瘤中的表达及意义%Expressions and significances of M2-PK and Cath-D in borderline ovarian serous cystadenoma

    Institute of Scientific and Technical Information of China (English)

    田园; 王淑丽; 张立会

    2014-01-01

    目的:探讨M2型丙酮酸激酶(M2-pyruvate kinase,M2-PK)和组织蛋白酶D(Cathepsin-D,Cath-D)在卵巢浆液性囊腺瘤和交界性浆液性肿瘤组织中的表达情况及临床意义.方法:采用免疫组化S-P法,分别检测40例卵巢浆液性囊腺瘤和38例卵巢交界性浆液性囊腺瘤中M2-PK和Cath-D的表达水平.结果:在卵巢浆液性囊腺瘤、交界性浆液性囊腺瘤组织中,M2-PK的阳性表达率分别为40.00%和76.32%;Cath-D的阳性表达率分别为25.00%和65.79%,两组间阳性表达率均有统计学差异(P<0.05).M2-PK和Cath-D在交界性卵巢浆液性肿瘤组织中的表达呈正相关(P<0.05).结论:M2-PK表达升高和Cath-D表达降低在卵巢交界性浆液性囊腺瘤的发生、发展过程中起重要作用,二者可为卵巢交界性肿瘤早期诊断及观察预后提供重要依据.

  2. Respostas do feijoeiro à aplicação de diversos tipos de matéria orgânica não decomposta, na presença de adubações minerais com P, PK, NPou NPK Responses of dry beans to applications of some undecomposed organic materials in the presence of mineral fertilizers containing, P, PK, NP or NPK

    Directory of Open Access Journals (Sweden)

    Shiro Miyasaka

    1967-01-01

    Full Text Available Experiências conduzidas em Campinas (solo Latosol Roxo e Pindorama (solo Podzolizado de Lins e Marília, variação Marília, para estudar os efeitos de diversos tipos de matéria orgânica não decomposta, na presença de adubações minerais com P, PK, NP ou NPK, mostraram que, dos adubos minerais, sòmente o nitrogênio aumentou substancialmente a produção do feijoeiro. Dos adubos orgânicos comparados - ramas de soja perene, capim-gordura, fôlhas de café e serapilheira - o primeiro foi o mais eficiente. Em Campinas, as ramas de soja aumentaram a produção, tanto na ausência como na presença do nitrogênio mineral, quer aplicadas em sulcos laterais aos destinados às sementes de feijão, quer em cobertura, após a emergência das plantas. Em Pindorama, porém, só atuaram favoravelmente quando empregadas em sulcos laterais, na ausência do nitrogênio mineral.Experiments were conducted at Campinas and Pindorama, State of São Paulo, to study the effects of the indicated treatments on dry beans (Phaseolus vulgarisL. Of the mineral fertilizers, only nitrogen increased the yields in both localities. Of the organic materials - Glycine javanica, Melinis minutiflora, coffee tree leaves and forest litter - the first mentioned was the most effective. In the Campinas experiment, G. javanica induced considerable yield increases, either when side placed or top dressed in the absence or in the presence of mineral nitrogen. At Pindorama, however, it was effective only when side placed in the absence of mineral nitrogen.

  3. Efeitos sõbre a produção do feijoeiro, da aplicação de diversos tipos de matéria orgânica, não decomposta, na presença de adubação mineral com P, NP, PK Responses of dry beans to the application of several undecomposed organic materials in the presence of mineral fertilizers with P, NP and PK

    Directory of Open Access Journals (Sweden)

    Shiro Miyasaka

    1967-01-01

    Full Text Available Numa experiência em que se estudou, na cultura do feijoeiro, o comportamento de diversos tipos de matéria orgânica, não decomposta, na presença de adubações minerais com P, NP ou PK, o nitrogênio foi o elemento que controlou a produção. Nas parcelas adubadas exclusivamente com P, os adubos orgânicos, aplicados em sulcos laterais aos destinados às sementes, aumentaram consideràvelmente a produção, crescendo os aumentos na seguinte ordem: bagaço de cana, capim-gordura, soja perene, fôlhas de cafeeiro, cascas de café e cascas de amendoim. Nas parcelas com NP, as produções foram geralmente maiores, e dos adubos orgânicos sòmente as cascas de amendoim, o capim-gordura e a dose dupla de fôlhas de café proporcionaram pequenos aumentos.Nitrogen was the element that limited the yield of dry beans. In the plots with P alone, the responses to the side-placed organic materials were very good and increased in the order: sugar cane thrash, Melinis minutiflora hay, Glycine javanica hay, coffee tree leaves, coffee fruit hulls and peanut hulls. In the NP plots, the yields were generally higher but only peanut hulls, M. minutiflora hay and the double dose of coffee tree leaves induced small increases.

  4. Inclusion in PK-12: An International Perspective

    Science.gov (United States)

    Curcic, Svjetlana

    2009-01-01

    With an aim to investigate inclusion across borders, quantitative and qualitative data were examined that came from 18 countries: Australia, Brazil, Canada, Cyprus, Finland, France, Iceland, India, Ireland, the Netherlands, Norway, Portugal, Slovenia, South Africa, Spain, Sweden, the UK, and the USA. Four themes emerged in this study: (1) concerns…

  5. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions.

    Science.gov (United States)

    Afzelius, Pia; Nielsen, Ole L; Alstrup, Aage Ko; Bender, Dirk; Leifsson, Páll S; Jensen, Svend B; Schønheyder, Henrik C

    2016-01-01

    Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for identification and localization of infection. These methods are, however, not always successful. Early identification and localization of infection is critical for the appropriate and timely selection of therapy. The aim of this study was thus; a head to head comparison of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. (18)F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while (11)C-methionine and particularly (11)C-PK11195 and (68)Ga-citrate accumulated to a lesser extent in infectious foci. (18)F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions. PMID:27069765

  6. Morphological and molecular imaging of hematogenously inoculated and disseminated Staphylococcus aureus lesions in domestic juvenile female pigs by PET/CT. The bio-distribution of the radionuclides 18F-FDG, 11C-methionine, 11C-PK11195, and 68Ga-citrate in pigs is presented

    DEFF Research Database (Denmark)

    Afzelius, Pia; Nielsen, Ole Lerberg; Alstrup, Aage Kristian Olsen;

    2016-01-01

    . Bacteremia may give rise to bacterial spread to different tissues such as e.g. heart, joints, spleen, bones, and skin/soft tissue. Staphylococcus aureus is a conditional pathogen: it is carried on many humans and animals without symptoms, but it is also able to cause serious diseases like osteomyelitis...... tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose 11C-methionine, 11C-PK11195, and 68Ga-citrate as tracers and validated their diagnostic utility in a porcine model. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra...

  7. Study on therapeutic effect of anti-TB drugs and regimens for tuberculosis meningitis and PK /PD of these drugs%抗结核药物及方案对结核性脑炎治疗作用及药物的药代动力学/药效学研究

    Institute of Scientific and Technical Information of China (English)

    赵伟杰; 付雷; 李破; 王彬; 徐建

    2011-01-01

    Objective To determinte the concentrations of three anti -TB drugs are increased in the brain tissue of health and TB meningitis( MTB) model mice , study the pharmacokinetics/pharmacodynamics ( PK/PD) parameters of them in plasma and brain tissue using healthy and MTB model mice , evaluate the activities of these drugs respectively and combinations of them , provide information for the treatment of MTB based on their activities and parameters . Methods MTB mice model was developed through injecting H 37Rv into the tail vein of mice. After administrated RFP . Lfx. Mfx for 5 days , the plasma and brain tissue of healthy and MTB mice were gotten at different time points and the concentrations of these drugs were determined by HPLC , and then obtain the PK and PK/PD parameters.The mice were given Lfx. Mfx and other drugs usually used to therapy TB alone or combination , CFU in lungs and brain tissues were obtained after treatment for 8 weeks and these data together with the PK and PK/PD parameters were analyzed to evaluate the efficiency of treating pulmonaiy TB and MTB. Results The AUC0-24 of RFP, Lfx, Mfx were increased by 56. 0% , 148. 5% , 80. 4% , AUC0-24/MIC were 445. 0, 16. 5, 7. 4 respectively ; after treatment for 8 weeks, except PZA , Lfx that the CFU were decreased more . For MTB , every groups except Lfx were effective and INH , RHPto, RHLfx, RHMfx were more effective. Conclusions The amounts of drugs entering into the brain tissue increase while the hrain was infected by H 37Rv when compared with that of healthy mice ; RHPto, RHLfx, RHMfx are effective combinations to therapy MTB , so all of them can be choosed as therapeutic remedy for different patients.%目的 测定三种抗结核药在健康和结核性脑膜炎小鼠脑组织中的浓度,评价几种单药和联合方案抗肺结核和结核性脑膜炎的活性;评价其药代动力学/药效学(PK/PD)参数.方法 通过小鼠静脉感染H37Rv 建立结核性脑膜炎模型,健康和结核

  8. Research progress of optimizing vancomycin individual administration with the PK/PD model%结合药代动力学/药效学模式优化儿童万古霉素个体给药方案研究进展

    Institute of Scientific and Technical Information of China (English)

    邹心(综述); 罗征秀(审校)

    2016-01-01

    万古霉素是从链霉菌中分离得到的糖肽类抗生素,至今仍是治疗耐甲氧西林葡萄球菌的首选药物。万古霉素代谢个体差异显著,仅通过药物说明书和医师经验性用药,对于重症及复杂感染患儿很难使血药浓度达到目标范围(15~20 mg/L),必须借助万古霉素血药浓度监测(TDM),利用群体药代动力学/药效学(PK/PD)模式,通过贝叶斯(Bayes)反馈获得个体PK/PD参数来实施精细调控。文章从万古霉素当前临床用药指南拓展到最新研究理论,充分显示肾功能、体质量、年龄、疾病状态是影响儿童万古霉素代谢效应的主要参数;且血药浓度-时间曲线下面积/最小抑菌浓度(AUC/MIC)≥400为更佳的监测效应值。%e: Vancomycin is a glycopeptide antibiotic separated from streptomycete, having been used as the ifrst choice to treat methicillin-resistant Staphylococcus aureus infection so far. The studies show that because of the individual difference in the metabolism of vancomycin, it is dififcult to get the trough concentration of pediatric patients severely ill or complicatedly in-fected to reach the target range (15—20 mg/L). However, with the help of therapeutic drug monitoring (TDM) of vancomycin and the pharmacokinetic/pharmacodynamic parameter (PK/PD) mode, the PK/PD parameters to achieve the precise control can be acquired by using the Bayes feedback. By a stretched review from clinical medication guide of vancomycin to the latest evidence from research, this paper fully demonstrates that renal function, weight, age, and disease state are the principal parameters to impact pediatric patient’s vancomycin metabolism and that the area under the concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC)≥400 is the better cut-off value to determine vancomycin efifcacy and toxicity.

  9. Die Checkliste PK "Professionelles ärztliches Kommunikationsverhalten" in Unterricht und Evaluation kommunikativer Fertigkeiten im Medizinstudium [Checklist "Professional Communication in Medicine" in teaching and assessing of anamnesis and communication skills in medical education

    Directory of Open Access Journals (Sweden)

    Pucher-Matzner, Ingeborg

    2006-11-01

    Full Text Available [english] Objectives: The checklist „Professional Communication in Medicine“ serves as a tool for teaching and training medical students in communication skills, it has also been developed in order to evaluate the students’ performance at the end of their second year at the Medical University of Vienna. The checklist consists of three parts: 26 items referring to the contents of the interview according to George Engel’s ten step model of anamnesis, 10 items referring to the style of communication and 12 items deal with the relationship established. Methods: Teachers of communication skills in medicine were asked to check the list for objectivity (interrater- reliability. In a first step (learning, after they got to know how to handle the list, they were trained in applying this checklist with the help of videos – each presenting a complete anamnesis. The testing that followed looked at the items in terms of their level of consensus. Results: On the whole it can be said that a good level of consensus – in around 75 percent of all items - was reached in assessing all three parts, i.e. style of communication, contents and relationship. The highest levels of consensus were observed in part B: style of communication, the lowest in section C: relationship. Conclusion: Results have turned out satisfactorily as far as they provide consistent forms of assessment for the major part of items. However, improvements need to be made in areas dealing with question-building, psychosocial aspects but also personal development. All in all, the checklist can be seen as an essential contribution to quality assurance in medical communication, involving both, students and teachers. [german] Zielsetzungen: Die Checkliste PK „Professionelles ärztliches Kommunikationsverhalten“ ist als Unterrichtsmittel, für gezieltes Training und die Evaluation kommunikativer Fertigkeiten, im medizinischen Unterricht an der Medizinischen Universität Wien (MUW

  10. Temporal changes in glial fibrillary acidic protein messenger RNA and [{sup 3}H]PK11195 binding in relation to imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Craven, J.A.; Gundlach, A.L.; Conway, E.L. [The University of Melbourne, Clinical Pharmacology and Therapeutics Unit (Australia); Department of Medicine, Austin and Repatriation Medical Centre (Australia)

    1997-10-24

    Immunohistochemical studies have demonstrated that following global forebrain ischaemia the selective neuronal loss that occurs in the CA1 pyramidal cell layer of the hippocampus is accompanied by a reactive astrocytosis, characterized by increases in glial fibrillary acidic protein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocampus have been mapped four, eight, 12, 16 and 20 days following 10 min of global forebrain ischaemia in the rat and related to changes in [{sup 3}H]PK11195 binding to peripheral benzodiazepine receptors, a putative marker of activated microglia. Recent studies have suggested that the imidazoline-I{sub 2}-receptor, one of a class of non-adrenergic receptors related to, but structurally and functionally distinct from {alpha}{sub 2}-adrenoceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding sites. Following transient ischaemia there was a marked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, peaking four days after ischaemia and then increasing gradually during the remainder of the study period. There was also a sustained increase in [{sup 3}H]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked four days after ischaemia the density of [{sup 3}H]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marked increase in glial fibrillary acidic protein messenger RNA levels there was no concomitant alteration in imidazoline-I{sub 2}-receptor binding sites detected using the specific radioligand, [{sup 3}H]2

  11. Interrelated Glacial, Volcanic and Hydrologic Processes on the Tharsis Montes, Olympus Mons and Hecates Tholus, Mars

    Science.gov (United States)

    Head, J. W.; Marchant, D. R.; Shean, D. E.; Fassett, C. I.; Wilson, L.

    2005-12-01

    Volcanic, hydrological and glacial processes are prominent in the geological history of Mars and assessment of areas where their relationships can be established provides important information on their nature and intensity. An effort to examine these interrelationships is motivated by the uncertainties that exist in atmospheric general circulation models concerning the homogeneous or heterogeneous distribution of water ice during periods of high obliquity and resulting transport of polar volatiles equatorward. Geological evidence for distinctive and very large tropical mountain glacial deposits on the NW flanks of the Tharsis Montes shows that the emplacement of ice in the equatorial regions is heterogeneous and is intimately linked to the presence of large volcanic edifices on the broad Tharsis rise. Accumulation of ice and formation of glaciers is likely caused by adiabatic cooling of water-laden polar air masses and precipitation and accumulation on the NW volcano flanks (F. Forget, personal communication). The resulting glacial deposits show interesting relationships to volcanic deposits formed prior to, during and subsequent to glaciation. Evidence that the glacial deposits formed from cold-based glaciation comes from the lack of modification of delicate structures associated with underlying lava flows (seen in detrended altimetry data). Evidence that volcanism occurred during glaciation is five-fold: 1) narrow linear ridges in the glacial deposits radial to the volcano are interpreted as dikes that were intruded into the glacier, rapidly melting the adjacent ice and collapsing, as has been proposed for englacial dike intrusions in Iceland; 2) broad, steep-sided, thick lobate flow-like features are interpreted to represent sill-like subglacial lava flows at the volcano-glacial interface; 3) circular donut-like annuli surround vent-like craters suggesting localized subglacial explosive eruptions; 4) steep asymmetric lava flows at glacial deposit margins are interpreted to be formed by the cooling and banking up of lava against the glacier terminus; 5) collapsed lava flows and local chaotic terrain are interpreted to be places where lava flows descended directly over glacial accumulation zones. Evidence for post-glacial volcanic emplacement is seen in: 1) edifice and flanking rift zone flows that invade and are superposed on the fan-shaped deposits, but show no evidence for associated melting and 2) the surface manifestation of a dike in excess of a hundred km in length that formed rows of tephra and spatter cones and localized lava flows a few to more than 10 km in length, all superposed on the Arsia fan-shaped glacial deposit. Emplacement of tropical mountain glacial deposits on the flanks of the Tharsis volcanoes suggests that there might be meltwater produced from one of several sources: 1) climate-induced (top-down) melting of surface snow in the tropics, 2) thickening of the ice sufficiently to produce basal melting, 3) conduction of magmatic heat to the glacier on the edifice flanks, 4) direct contact of the magma/lava with glacial ice. We find only limited evidence for meltwater processes at the Tharsis Montes, most likely related to dike emplacement and subglacial intrusion/flow events. In contrast, Hecates Tholus may provide an example of a volcanic edifice where summit ice accumulating occurred and basal melting was sufficient to produce the radial valleys that are observed. Thus, comparison of closely associated volcanic, fluvial and glacial deposits can be synergistic and provide new insight into the processes shaping the surface of Mars.

  12. 78 FR 42902 - Safety Zone; Olympus Tension Leg Platform, Mississippi Canyon Block 807, Outer Continental Shelf...

    Science.gov (United States)

    2013-07-18

    ... natural gas, and thereby protect the safety of life, property, and the environment. The authority for this... releases of natural gas and increase the safety of life, property, and the environment in the Gulf of... will significantly reduce the threat of allisions, oil spills, and releases of natural gas, and...

  13. 重回长焦市场Olympus SP-500 UZ

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    很久以前,Olympus在长焦相机市场上可谓一枝独秀,但是不知为什么,后来却逐渐退出了,而这次其新推出的这款10倍光学变焦相机不但提供了全手动操控功能,而且还提供了直接输出为RAW格式文件的功能,并提供了21种场景模式和143区AF功能,功能之强大令人咋舌。

  14. PK-PD integration and modeling of marbofloxacin in sheep.

    Science.gov (United States)

    Sidhu, P K; Landoni, M F; Aliabadi, F S; Lees, P

    2010-02-01

    The fluoroquinolone antimicrobial drug, marbofloxacin, was administered intravenously (IV) and intramuscularly (IM) to sheep at a dose rate of 2 mg kg(-1) in a 2-period cross-over study. Using a tissue cage model of inflammation, the pharmacokinetic properties of marbofloxacin were established for serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). For serum, after IV dosing, mean values for pharmacokinetic parameters were: clearance 0.48 L kg(-1) h(-1); elimination half-life 3.96 h and volumes of distribution 2.77 and 1.96 L kg(-1), respectively, for V(darea) and V(ss). After IM dosing mean values for pharmacokinetic variables were: absorption half-time 0.112 h, time of maximum concentration 0.57 h, terminal half-life (T(1/2)el) 3.65 h and bioavailability 106%. For exudate, mean T(1/2)el values were 12.38 and 13.25 h, respectively, after IV and IM dosing and for transudate means were 13.39 h (IV) and 12.55 h (IM). The in vitro minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and ex vivo time-kill curves for marbofloxacin in serum, exudate and transudate were established against a pathogenic strain of Mannheimia haemolytica. Integration of in vivo pharmacokinetic data with MIC determined in vitro provided mean values of area under curve (AUC)/MIC ratio for serum, exudate and transudate of 120.2, 156.0 and 156.6 h after IV dosing and 135.5, 165.3 and 146.2 h after IM dosing, respectively. After IM administration maximum concentration (C(max))/MIC ratios were 21.1, 6.76 and 5.91, respectively, for serum, exudate and transudate. The ex vivo growth inhibition data after IM administration were fitted to the sigmoid E(max) (Hill) equation to provide values for serum of AUC(24h)/MIC producing, bactericidal activity (22.51 h) and virtual eradication of bacteria (35.31 h). It is proposed that these findings might be used with MIC(50) or MIC(90) data to provide a rational approach to the design of dosage schedules which optimise efficacy in respect of bacteriological as well as clinical cures.

  15. OKO tarjoaa pk-yrityksille toimivat pankkiyhteydet Baltiassa / Matti Niiranen

    Index Scriptorium Estoniae

    Niiranen, Matti

    2005-01-01

    Soome finantsrühma OP kohast Eesti ja Baltimaade turul, OKO panga ühistööst Hansapangaga. Vt samas: Viron 3. suurin vakuutusyhtiö OP-ryhmälle Pohjola-kaupan myötä; OP-ryhmä vahvistaa asemiaan

  16. Rahoitusselvitys aloittelevalle pk-yritykselle : Case: Pets Cooler

    OpenAIRE

    Uotinen, Emmi

    2013-01-01

    Tarkoituksena oli selvittää erilaisia rahoitusvaihtoehtoja aloittelevalle pienelle ja keskisuurelle yritykselle. Opinnäytetyön tavoite oli helpottaa toimeksiantajayrityksen Pets Cooler rahoituslähteiden valintaa. Yritystoiminnan on tarkoitus käynnistyä mahdollisimman nopeasti, ja selvitys on tukena aloituksessa. Toimeksiantaja halusi käsiteltävän myös kansainvälisen liiketoiminnan rahoitusta. Vienti ja mahdollisesti myös ulkomailla tapahtuva tuotanto on yrityksen haaveena tulevaisuudessa. ...

  17. Varastonhallinnan kehittäminen pk-yrityksessä

    OpenAIRE

    Salminen, Heidi

    2014-01-01

    Tässä opinnäytetyössä selvitettiin miten varastonhallintaa voitaisiin parantaa pienyrityksessä. Samalla selvitettiin myös nykyisen kassajärjestelmän mahdollisuuksia, sekä tilausprosessikäytäntöä. Työn tilaajana oli Kosmetologipalvelu Liisa Tuominen. Kehitysprojektissa haluttiin selvittää, voisiko nykyiseen kassajärjestelmään saada lisättyä toisenlainen hälytysraja -menetelmä auttamaan ammattituotteiden varastonhallinnassa ja tilausprosessissa. Tilausprosessia tutkittiin myös myyntituotteiden ...

  18. Liiketoiminnan strateginen kehittäminen : viherrakennusalan pk-yritys

    OpenAIRE

    Saarinen, Johanna

    2010-01-01

    Tutkimuksen teoreettisen osan tavoitteena oli kartoittaa strategia-ajattelua ja olemassa olevia strategisen ajattelun koulukuntien keskeisiä teemoja ja perehtyä tarkemmin liikeidea-ajattelumallin sisältöön. Keskeisenä teemana oli liikeidean neljän peruselementin, markkinoiden, tuotteiden tai palveluiden, toimintatavan ja imagon välinen yhteensopivuus. Lisäksi tavoitteena oli perehtyä viherrakennusalan yrittäjyyteen analysoimalla toimialaa Porterin viiden voiman mallin ja SWOT-analyysin avulla...

  19. Project+ study guide exam PK0-002

    CERN Document Server

    Heldman, William

    2006-01-01

    Here's the book you need to prepare for the latest version of CompTIA's Project+ exam. This Study Guide was developed to meet the exacting requirements of today's certification candidates. In addition to the consistent and accessible instructional approach that has earned Sybex the ""Best Study Guide"" designation in the 2003 CertCities Readers Choice Awards, this book provides: Clear and concise information on project management Practical examples and insights drawn from real-world experience Leading-edge exam preparation software, including a test engine and electronic flashcards You'll a

  20. Google与 Yahoo企业文化之间的PK

    Institute of Scientific and Technical Information of China (English)

    王海选

    2008-01-01

    @@ 在美国硅谷Yahoo公司办公室的墙上贴着一些获得了专利的古怪发明的草图,比如说便携式的鸟笼.其用意就是告诉Yahoo的员工:只要花些心思,我们一定能够创造出一些更大的发明来.

  1. Vakuutusyhtiö pk-yritysten turvallisuusinvestointien rahoittajana

    OpenAIRE

    Palotie, Turo

    2012-01-01

    Opinnäytetyön tarkoituksena oli tutkia vakuutusyhtiön tarjoaman turvallisuusinvestointituen vaikutusta yrityksissä. Tutkimuskohteena olivat kuusi If Vahinkovakuutus Oy:n asiakasyritystä, joista haastateltiin sellaisia henkilöitä, joilla on päätäntävaltaa yrityksen rahoitukseen tai turvallisuuteen liittyvissä asioissa. Tein opinnäytetyön toimeksiantona If Vahinkovakuutus Oy:lle. Tutkimuksen tavoitteena on antaa vakuutusyhtiölle kehittämisideoita turvallisuusinvestointitukitoimintaan. Tut...

  2. Yritysvastuuraportointi pk-yrityksissä, Case: Yhtyneet Medix laboratoriot Oy

    OpenAIRE

    Pitkänen, Tomi

    2016-01-01

    Yhteiskuntavastuu on tärkeä aihepiiri, jonka merkitys on kasvanut niin liikeelämässä kuin myös kuluttajapuolella. Aiheena yhteiskuntavastuu on jo aika vanha, mutta 2000-luvulle tultaessa vaatimukset eettisemmästä yritystoiminnasta ovat koventuneet. Tämän opinnäytetyön tarkoituksena on kartoittaa, miltä pienen tai keskisuuren yrityksen yritysvastuuraportti voisi mahdollisesti näyttää. Tätä varten opinnäytetyöhön kerättiin runsaasti teoriapohjaa, tutkittiin erilaisia ohjeita ja raportteja sekä ...

  3. PK-yrityksen markkinoinnin ja verkkosivujen suunnittelu : case Rapurallaa

    OpenAIRE

    Alanto, Maria

    2013-01-01

    Tässä opinnäytetyössä suunniteltiin pienyrityksen sivuelinkeinolle verkkosivut. Yrittäjä on yksityinen elinkeinoharjoittaja, ja yrityksen toimiala on maatalous ja sivuelinkeinona on rapujen kasvatus. Yritys toimii Salon seudulla, mutta potentiaalinen markkina-alue on koko Suomi. Opinnäytetyö on toiminnallinen työ. Verkkosivun suunnittelun myötä tavoitteena oli yrityksen tunnettuuden ja näkyvyyden lisääminen digitaalisen markkinoinnin keinoilla. Digitaalisella markkinointiviestinnällä yrit...

  4. Top 20 Psychological Principles for PK-12 Education

    Science.gov (United States)

    Lucariello, Joan M.; Nastasi, Bonnie K.; Dwyer, Carol; Skiba, Russell; DeMarie, Darlene; Anderman, Eric M.

    2016-01-01

    This article describes an initiative undertaken by a coalition of psychologists (Coalition for Psychology in Schools and Education) from the American Psychological Association (APA) to identify the top 20 principles from psychological science relevant to teaching and learning in the classroom. This article identifies these principles and their…

  5. PK-12 Public Educational Facilities Master Plan Evaluation Guide

    Science.gov (United States)

    21st Century School Fund, 2011

    2011-01-01

    Proper planning of school facilities is critical for all school districts no matter how large or small, whether major construction is in the works or the district is managing enrollment declines. When school districts properly plan for their school facilities they have better schools, more public use and higher value for public spending. This…

  6. Energy instructions for SMEs; Energiaohjeistus pk-yrityksille

    Energy Technology Data Exchange (ETDEWEB)

    Inkinen, R. [Polstop Oy, Helsinki (Finland)

    2006-12-19

    The most common environmental aspects for SMEs are energy consumption, material effectiveness and waste handling. High material effectiveness reduces direct energy consumption and amount and cost of waste. Waste management is quite well instructed in environmental managing systems but effectiveness of material and energy saving are instructed inadequate. Especially SMEs would need clear and brief, perhaps branch-specific instructions for energy saving. Energy instructions for SMEs is a project where instructions and monitoring forms for SMEs are created. These tools will be easily used as a part of environmental management systems in different branches. It helps companies to make energy savings and this way diminish greenhouse gases. (orig.)

  7. Solvability of the Diophantine equations xp + 22m y4 = pk z2 and xp + y2 = pk z4

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    We study the solvability of two classes of Diophantine equations by using some new methods and new results in this paper.Letp be an odd prime and Bn denote nth Bernoulli number.We prove that ifp ≡ 1(mod 4)andp |B(p-1)/2,then the equationxp +22mn4 = pky2,m,n,k ∈ N ,k > 1,gcd(x,py)= 1,and the equationxp +y2 =pkz4,k ∈ N,gcd(x,y)= 1,k > 1,21 y have no integral solutions respectively.

  8. Tezkire-i Buğra Han’ın Çağatayca Yazılmış Bir Nüshası Metin- Dil İncelemesi- Tıpkıbasım A Manuscript Of Tazkira-i Bughra Khan Written In Chagatay Turkısh Texte- Grammar Notes- Facsimile

    Directory of Open Access Journals (Sweden)

    B. Erdem DAĞISTANLIOĞLU

    2012-12-01

    ındaki bilgiler oldukça sınırlıdır. Bu dönem hakkındaki bilinmezliklerin benzeri, İslamiyet’in Türkler arasında yayılmasında büyük bir yeri bulunan ve efsanevi özellikler taşıyan Satuk Buğra Han için de geçerlidir.Bu makale, Türklerin İslamiyeti kitle hâlinde kabul edişlerini ve ilk Müslüman Türk hükümdarının efsanevi hayatını anlatan Tezkire-i Buğra Han kitabının 19. yüzyılda Çağatayca olarak kaleme alınmış bir nüshasının çeviri yazı ve dil incelemesini içermektedir.Çalışmamıza konu olan eser, Klasik Çağataycanın dil özelliklerini taşımakla beraber, Özbekçe ve Çağdaş Uygurcanın ses ve şekil bilgisi özelliklerini de barındırmaktadır. Tezkire-i Buğra Han kitabı gerek ses gerekse şekil bilgisi bakımından Çağatayca öncesi arkaik örnekleri de içermektedir. Eser bu özellikleriyle, hem Çağataycadan çağdaş Türk lehçelerine geçişi yansıtmakta hem de içerdiği arkaik yapılarla dikkat çekmektedir.Yazmanın Çağatayca dışında en çok Çağdaş Uygurcanın dil özelliklerini barındırdığı görülmektedir. Kitabın ilk sayfasındaki karışık bir hâlde yazılmış ifadelerin içinden tespit edebildiğimiz tārįħķa bir min g iki yüz yėtmiş1 ….. inal aķsuluķ taĥrįri āħir boldı cümlesi eserin Çağdaş Uygurcayla olan bağını da açıklar niteliktedir.Bu makalede söz konusu yazma eserin bütünü hakkında, yazarı, yazıldığı yüzyıl, diğer nüshaları vb. özellikleri bakımından bilgi verilmiş olup yalnızca Satuk Buğra Han menkabesinin geçtiği kısmın çeviri yazılı metni sunulmuştur. Ayrıca incelenen kısmın tıpkıbasımı da makalenin sonuna eklenmiştir.Bu yazıda, British Library’deki Or. 8161 numaralı metnin 83a-102b varakları arasındaki Satuk Buğra Han menkabesini esas almakla birlikte, dil incelemesinde gerek duyuldukça yazmanın bütünü göz önünde bulundurularak açıklamalar yapılmıştır.

  9. Electronic Customer Relationship Management (eCRM) from the Perspective of Two Banks with Online Marketing in Pakistan : case of HSBC PK and Standard Chartered Bank PK

    OpenAIRE

    Abdul, Shakoor

    2011-01-01

    This study observes an approach which is known as explorative because it aims to evaluate and examine online media as a tool for e-CRM. In addition, this involves the approach known as iterative also depends on the data, which is qualitative in congestion with observational information. This study builds on the existing literature and theories within customer relationship marketing (CRM). The subfield to CRM, called e-CRM, is further studied the phenomenon of online marketing and online CRM (...

  10. Brand duel: Yi li VS Mengniu%品牌PK:伊利VS蒙牛

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    如今营销领域炒得红红火火的“体验营销”是什么?--很多人一定认为是:让消费者体验到产品!错!到位的“体验营销”,用最通俗的话说就是:从产品的核心利益(物质利益和情感利益)出发,最简单,最直接的让消费者体验到本品牌所具有的差异化特色。

  11. PK-PD Modeling of Fluoroquinolones and ABC Transporters in Poultry

    NARCIS (Netherlands)

    Haritova, A.M.

    2006-01-01

    In the first part of this thesis advance pharmacokinetic models, based on an integration of pharmacokinetic and pharmacodynamic data for selected fluotoquinolones, are presented. The comparative investigations with danofloxacin mesylate and marbofloxacin indicated that with both fluoroquinolones a c

  12. Budjetoinnin ja kassavirran hallinnan parantaminen pk-yrityksessä - Case Pohjan Taimi Oy

    OpenAIRE

    Mannermaa, Jaana

    2015-01-01

    Tämän opinnäytetyön tarkoituksena on kuvata kohdeyrityksenä toimivan Pohjan Taimi Oy:n budjetointia ja punnita yritykselle uutta tapaa hoitaa budjetointi, jotta talous ja kassavirran hallinta olisi paremmin ennustettavissa. Yrityksen talouden suunnittelu edellyttää tulevaisuutta koskevia talouden ennusteita sekä lyhyellä että pitkällä aikavälillä. Case-yrityksellä on käytössään vuosibudjetti ja kuukausibudjetit talouden seurantaan. Suurimpana ongelmana on talouden ennustamisen vaikeus ja heil...

  13. Neutron experiments on nuclear order in silver at pK temperatures

    DEFF Research Database (Denmark)

    Nummila, K.K.; Tuoriniemi, J.T.; Vuorinen, R.T.;

    1996-01-01

    Spontaneous long range antiferromagnetic order in the spin-1/2 s ystem of silver nuclei has been observed by neutron diffraction on a single crystal of Ag The observed antiferromagnetic state had a simple 1-k structure and no field induced phase transitions within the ordered state could be inden...

  14. Search for a new baryonic state decaying to $pK^0_S$

    CERN Document Server

    Bussey, P J

    2016-01-01

    We report on a new ZEUS search for a narrow state decaying into $p(\\bar{p})K^0_S$, which was previously claimed by the ZEUS collaboration. In the present search, which uses much increased statistics, no evidence for this state is found. Limits on the cross section for such a state are given.

  15. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.

    Science.gov (United States)

    Bienert, Agnieszka; Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

    2010-06-01

    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

  16. Analisa Waktu Simpan Air Terhadap Kinerja AC Split 1 PK dengan Alat Penukar Kalor Tipe Serpentine

    OpenAIRE

    Tambunan, Tulus H

    2015-01-01

    About three-quarters of the world's energy use is still with fossil fuels. The amount of exhaust gases produced by major industries that use fossil fuels causes global warming is getting worse. The consumption of most fossil fuels is the use of electricity. Given the climate in Indonesia is quite hot, almost every house uses air conditioning to create a comfortable temperature for humans who live in them. Additionally began heating needs air.Dengan utilize waste heat for heating water conditi...

  17. Rancang Bangun Kondesor Untuk Mesin Pengering Pakaian Sistem Pompa Kalor Dengan Daya 1PK

    OpenAIRE

    Nainggolan, Ricardo

    2014-01-01

    This design aims to address the problems faced by businesses loundry on providing for washing machines and dryers that can work quickly. Therefore, to design that aims to produce a unit of portable clothes dryer with AC disa-oriented home on electrical energy efficiency measures that can be applied to small and large scale. The design of all components of the physical models of clothes dryers in the units is based on the results of theoretical calculations and the use of heat ...

  18. Oseltamivir PK/PD Modeling and Simulation to Evaluate Treatment Strategies against Influenza-Pneumococcus Coinfection

    Science.gov (United States)

    Boianelli, Alessandro; Sharma-Chawla, Niharika; Bruder, Dunja; Hernandez-Vargas, Esteban A.

    2016-01-01

    Influenza pandemics and seasonal outbreaks have shown the potential of Influenza A virus (IAV) to enhance susceptibility to a secondary infection with the bacterial pathogen Streptococcus pneumoniae (Sp). The high morbidity and mortality rate revealed the poor efficacy of antiviral drugs and vaccines to fight IAV infections. Currently, the most effective treatment for IAV is by antiviral neuraminidase inhibitors. Among them, the most frequently stockpiled is Oseltamivir which reduces viral release and transmission. However, effectiveness of Oseltamivir is compromised by the emergence of resistant IAV strains and secondary bacterial infections. To date, little attention has been given to evaluate how Oseltamivir treatment strategies alter Influenza viral infection in presence of Sp coinfection and a resistant IAV strain emergence. In this paper we investigate the efficacy of current approved Oseltamivir treatment regimens using a computational approach. Our numerical results suggest that the curative regimen (75 mg) may yield 47% of antiviral efficacy and 9% of antibacterial efficacy. An increment in dose to 150 mg (pandemic regimen) may increase the antiviral efficacy to 49% and the antibacterial efficacy to 16%. The choice to decrease the intake frequency to once per day is not recommended due to a significant reduction in both antiviral and antibacterial efficacy. We also observe that the treatment duration of 10 days may not provide a clear improvement on the antiviral and antibacterial efficacy compared to 5 days. All together, our in silico study reveals the success and pitfalls of Oseltamivir treatment strategies within IAV-Sp coinfection and calls for testing the validity in clinical trials. PMID:27379214

  19. ITIL V3:n hyödyntäminen pk-yrityksen strategisessa suunnittelussa

    OpenAIRE

    Heikkonen, Pekka

    2013-01-01

    Opinnäytetyön aiheena oli tutkia olemassa olevia käytäntöjä ja kehittää uusia strategioita Suomen IT-Ratkaisut Oy:lle. Strategiat perustuvat IT-palveluiden hallinnassa ja johtamisessa käytettävään ITIL (Information Technology Infrastructure Library)-viitekehykseen. ITIL tarjoaa paljon hyviä käytänteitä IT-palveluja tarjoavan yrityksen strategian suunnitteluun. Tavoitteena opinnäytetyössä oli luoda yritykselle IT-strategiat, jotka sopivat pienelle yritykselle, jolla on suunnitelmat kasvattaa t...

  20. Evaluierung des Tumormarkers (TU M2-PK) bei Lungenkrebspatienten und Anwendung in der arbeitsmedizinischen Berufskrebsforschung

    OpenAIRE

    Neu, Kathleen

    2005-01-01

    Inzidenz- und Mortalitätszahlen belegen, daß sich der Lungenkrebs mit ca. 40.000 Neuererkrankungen jährlich zu einem bedeutsamen Krankheitsbild entwickelt. Ätiologisch gilt der Zigarettenrauch als wichtigster Risikofaktor für den Lungenkrebs. Bestätigend lagen in unserem Bronchialkarzinom-Kollektiv (n = 53 Patienten; 43 männlich, 10 weiblich; Alter zwischen 34 und 77 Jahren) ohne Ausnahme Raucher oder ehemalige Raucher vor. Zusätzlich ließen sich bei ca. 23 % der Patienten beruflich bedingte ...

  1. Grandmother Song——祖孙两代的观念PK

    Institute of Scientific and Technical Information of China (English)

    王旭

    2010-01-01

    Vienna Teng是来自美国旧金山的华人.她有个优雅的中国名字叫史逸欣。出于对音乐的热爱,Vienna Teng放弃了电脑工程师的工作,全身心投身于音乐创作。她有着地道的美国腔,但是她的歌词里处处洋溢着中国式诗意,不经意间泄露出她骨子里的中国文化基因。

  2. http://www.se.org.pk/File-Download.aspx?publishedid=218

    Directory of Open Access Journals (Sweden)

    Syed Saqlain Hussain, Muhammad Jamil, Muhammad Sadiq and Shahzada Munawar Mehdi

    2012-05-01

    Full Text Available It is an established fact that temporary waterlogging occurs at first irrigation to wheat crop in rice-wheat cropping system. This is also true in saline sodic soils. Wheat crop becomes pale yellow just after first irrigation resulting in severe reduction in growth and yield. This study was planned to address this problem by various management strategies like irrigation at 25 days after sowing (DAS without fertilizer, irrigation at 25 DAS + 120-110-70 NPK kg ha-1, irrigation at 25 DAS + 120-110-70 NPK kg ha-1 + 25 kg sulphuric acid per hectare, irrigation at 25 DAS+ 120-110-70 NPK kg ha-1 +12 kg sulphuric acid per hectare and irrigation at 40 DAS +120-110-70 NPK kg ha-1. A saline sodic field {pHs =8.92, ECe =5.70 (dS m-1 and SAR=23.71 (mmol L-11/2} was selected. Maximum grain yield (3.01 t ha-1, number of tillers (437 m-2, 1000-grain weight (35.43 g and number of grains spike-1 (40 were produced with the application of 120-110-70 NPK kg ha-1 + 25 kg ha -1 sulphuric acid at first irrigation applied 25 days after sowing in saline sodic soil.

  3. PÄÄOMARAKENNE JA VELKAANTUNEISUUS : – CASE KAINUULAISET PK-YRITYKSET

    OpenAIRE

    Pyykkönen, Henna

    2009-01-01

    Tämän opinnäytetyön tarkoituksena oli tutkia pääomarakenteeseen vaikuttavia tekijöitä kainuulaisissa pkyrityksissä. Selittäviksi tekijöiksi valittiin yrityksen ikä, koko, toimiala, aineellinen ja aineeton omaisuus aiempien tutkimusten ja teorioiden perusteella. Työn teoriataustassa kerrotaan oman ja vieraan pääomanehtoisista rahoitusvaihtoehdoista ja vertaillaan niitä keskenään. Pääomarakenneteorioista on valittu kaksi tähän työhön selittämään pääomarakennetta. Valitut teoriat ...

  4. PK-YRITYKSEN VERKKOSIVUJEN UUDISTAMINEN MARKKINOINNIN NÄKÖKULMASTA : CASE: PIHAKIVI OY PORI

    OpenAIRE

    Suominen, Mika

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli uudistaa Porissa toimivan betoni- ja luonnonkiviä myyvän Pihakivi Oy Porin verkkosivut. Ensijaisena tavoitteena oli tehdä yritykselle nykyaikaiset ja myös mobiililaitteilla toimivat internet-sivut. Sivujen sisällön suhteen tarkoituksena oli hyödyntää aiemmilta internet sivuilta kerättyä Google Analytics dataa sekä ottaa markkinoinnillinen näkökulma paremmin huomioon. Opinnäytetyön teoriassa paneuduttiin markkinoinnin kilpailukeinoihin, markkinoin...

  5. Oseltamivir PK/PD Modeling and Simulation to Evaluate Treatment Strategies against Influenza-Pneumococcus Coinfection.

    Science.gov (United States)

    Boianelli, Alessandro; Sharma-Chawla, Niharika; Bruder, Dunja; Hernandez-Vargas, Esteban A

    2016-01-01

    Influenza pandemics and seasonal outbreaks have shown the potential of Influenza A virus (IAV) to enhance susceptibility to a secondary infection with the bacterial pathogen Streptococcus pneumoniae (Sp). The high morbidity and mortality rate revealed the poor efficacy of antiviral drugs and vaccines to fight IAV infections. Currently, the most effective treatment for IAV is by antiviral neuraminidase inhibitors. Among them, the most frequently stockpiled is Oseltamivir which reduces viral release and transmission. However, effectiveness of Oseltamivir is compromised by the emergence of resistant IAV strains and secondary bacterial infections. To date, little attention has been given to evaluate how Oseltamivir treatment strategies alter Influenza viral infection in presence of Sp coinfection and a resistant IAV strain emergence. In this paper we investigate the efficacy of current approved Oseltamivir treatment regimens using a computational approach. Our numerical results suggest that the curative regimen (75 mg) may yield 47% of antiviral efficacy and 9% of antibacterial efficacy. An increment in dose to 150 mg (pandemic regimen) may increase the antiviral efficacy to 49% and the antibacterial efficacy to 16%. The choice to decrease the intake frequency to once per day is not recommended due to a significant reduction in both antiviral and antibacterial efficacy. We also observe that the treatment duration of 10 days may not provide a clear improvement on the antiviral and antibacterial efficacy compared to 5 days. All together, our in silico study reveals the success and pitfalls of Oseltamivir treatment strategies within IAV-Sp coinfection and calls for testing the validity in clinical trials. PMID:27379214

  6. A Descriptive Study of Wisconsin PK-12 Virtual Public School Program Operations and Management

    Science.gov (United States)

    Banker, Margaret M.

    2012-01-01

    E-Learning as it pertains to public education is in its infancy in America. There is limited research on what operational design, development, and management attributes of virtual school programs foster student achievement. The Wisconsin Department of Instruction has not developed or adopted program standards for E-Learning programs. The purpose…

  7. Strategic Planning for Educational Technology Initiatives in PK-12 Lutheran Schools

    Science.gov (United States)

    Muth, Nicole

    2012-01-01

    Technology rich learning environments provide the potential for engaging, relevant, and personalized curricula that prepare students for 21st century careers. However, a lack of strategic planning by educators results in available technology not being used to its fullest potential. Several educational organizations have published guidelines for…

  8. Experience of attaining high labor productivity in a stoping face using mechanized complex 110PK-70

    Energy Technology Data Exchange (ETDEWEB)

    Reshetnikov, M.N.

    1982-01-01

    In 1979 when the first 1 million T of coal was produced at the mine ''Zyryanovskaya'' high volumes of coal extraction were attained in individual months: in January 102,300 T, in July 122,200 T. In 1980, high results were also attained. In January 106,000 T were extracted and in November 108,500 T of coal. The brigade has accumulated experience for introducing scientific organization of labor and improving labor productivity. In 1977 labor productivity of the workers in the stoping face was 31.5 T per shift, in 1978 variable productivity was elevated to 48.2 T. In 1979 labor productivity reached 67.3 T per shift. The best results for productivity was reached in June 1979, 90 T at the outlet, in February 1980--81.1 T per shift. The success of the brigade is formed of many factors, technical, organizational, economic. The basis for high labor productivity of the workers is timely preparation of new longwalls, normal production conditions for fulfillment of plans and the adopted socialist commitments. An important factor in the work of the extraction brigade is the type and condition of mining equipment. The level of work organization as a whole depends on the brigade, directly on the miners and the section leaders themselves. High conscientiousness of all the brigade members also is important for improving labor productivity. The majority of workers in the brigade (about 70%) are members of the party. Mass technical creativity of all the brigade members is also a great reserve for improving labor efficiency. The brigade has 24 efficiency experts who annually introduce 20-30 suggestions each aimed at improving work efficiency.

  9. Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx((R)))

    NARCIS (Netherlands)

    Boers-Sonderen, M.J.; Herpen, C.M. van; Graaf, W.T. van der; Desar, I.M.; Logt, M.G. van der; Beer, Y.M. de; Ottevanger, P.B.; Erp, N. van

    2014-01-01

    PURPOSE: Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD. METHODS: Seventeen patients treated with PLD 30 or 40 mg/m(2) underwent phar

  10. Evolution from a hinge actuator mechanism to an antenna deployment mechanism for use on the European large communications satellite (L-SAT/OLYMPUS)

    Science.gov (United States)

    Death, M. D.

    1984-01-01

    The evolution of an Antenna Deployment Mechanism (ADM) from a Hinge Actuator Mechanism (HAM) is described as it pertains to the deployment of large satellite antennas. Design analysis and mechanical tests are examined in detail.

  11. 浅析OLYMPUS AU 640测试过程中异常数据标志出现原因及处理方法

    Institute of Scientific and Technical Information of China (English)

    李彦伟

    2011-01-01

    @@ OLYMUPS AU640全自动生化分析仪(AU640 AUTOMATED CHIMISTRY ANALYZER)是日本 OLYMPUS公司研制生产的大型全自动生化分析仪.该机操作简单、检测速度快、自动化程度高、精确度高、故障率低,机内有完善的自检和故障报警系统以及完备的质控系统,其结果稳定可靠.

  12. Application and Improvement for the Lamp Base of the Olympus Microscope%OLYMPUS显微镜光源灯座的改进与应用

    Institute of Scientific and Technical Information of China (English)

    熊光星; 刘雅克; 贾红岩; 黄红梅

    2011-01-01

    目的 通过对显微镜光源部分灯座的改进,解决最微镜灯泡损坏后必须更换整个光源部分的问题.方法 利用普通照明米泡的灯座替换原有特殊光源,从而利用米泡进行照明,并达到灯泡损坏后容易更换的目的,结果临床使用后效果满意,能够达到原有的照明效果,并可轻易更换灯泡.结论 该方法简单易行,设计合理,能够为医院节约一定的成本,具有很好的推广应用价值.%Objective To avoid replacing the whole light source when the lamp burned-out hy improving the lamp base nf the microscope.Methods Replaeed the original light source by the rice bulb holder, so we could use the rice bulb to illuminate for the microscope, and replace the burned-out easily. Results It is improved in clinical application that the improvement is reasonable and effective, and it is esay to replace the lamp of the microscope by users. Conclusion The method is simple, practical and designed resonable, and could save the cost for hospitals and is worth being promoted.

  13. Aineeton palkitseminen pk-yritysten työntekijöiden sitouttamisen ja motivoinnin välineenä

    OpenAIRE

    Lundstedt, Timo

    2013-01-01

    Tämän opinnäytetyön tarkoituksena oli kartoittaa aineettoman palkitsemisen mahdollisuuksia pienten ja keskisuurten yritysten työntekijöiden sitouttamisen ja motivoinnin välineenä. Pääasiallisena tavoitteena oli kehittää työntekijöiden työpaikkasitoutuneisuutta ja työmotivaatiota aineettoman palkitsemisen keinoin. Aineeton palkitseminen on ajankohtainen kokonaisuus, jota Suomessa ei ole vielä täysin osattu hyödyntää. Yrityksen johdolle se on myös mahdollisuus, jonka motivoivaan vaikutukseen er...

  14. Bridging the Gap between Engineering Design and PK-12 Curriculum Development through the Use of the STEM Education Quality Framework

    Science.gov (United States)

    Pinnell, Margaret; Rowly, James; Preiss, Sandi; Franco, Suzanne; Blust, Rebecca; Beach, Renee

    2013-01-01

    This paper will describe a unique partnership among the Department of Teacher Education and School of Engineering at the University of Dayton (UD) and the Dayton Regional STEM Center (DRSC). This partnership resulted in the development of the STEM Education Quality Framework (SQF), a tool to guide educators in teaching, learning and refining STEM…

  15. Asiakkuudenhallintaohjelmiston käyttöönotto ja vaikutus pk-yrityksen toiminnassa : case FirstView Digital Signage

    OpenAIRE

    Aalto, Ritva

    2013-01-01

    Tämän opinnäytetyön toimeksiantaja on turkulainen osakeyhtiö FirstView Digital Signage. Yritys otti uuden asiakkuudenhallintaohjelmiston käyttöönsä keväällä 2013 ja käyttöönotto saatettiin päätökseen toimeksiannon muodossa. Projektin aikana tutustutaan CRM (Customer Relationship Management) -asiakkuudenhallintaan, palvelukulttuuriin sekä siihen liittyvän tiedon hallintaan. Nämä muodostavat työn teoreettisen viitekehyksen. Työn toiminnallisen osan muodostaa tuotettu käyttöopas uuden asiakku...

  16. Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

    DEFF Research Database (Denmark)

    Bodenlenz, Manfred; Höfferer, Christian; Magnes, Christoph;

    2012-01-01

    OFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis. RESULTS: dOFM was well tolerated...

  17. The effect of isoflavone supplementation on cardiovascular disease parameters in men undergoing 80% VO2pk exercise.

    OpenAIRE

    Hart, Vanessa Lynn Rogowsky

    2002-01-01

    Atherosclerosis, one of the major causative factors of cardiovascular diseases (CVD), is thought to be initiated by oxidative stress. Particular attention has been paid to the atherogenic effects of oxidative damage on low density lipoproteins (LDL). Current research shows that dietary antioxidant supplementation protects against oxidative stress, and therefore may present preventative measures and treatments for patients with diseases influenced by oxidative stress. Isoflavones found in s...

  18. 中石油收购PK石油公司的SWOT分析%SWOT analysis of CNPC purchased PK Company.

    Institute of Scientific and Technical Information of China (English)

    蔡茜

    2007-01-01

    近年来,越来越多的中国企业加快了海外并购的步伐,特别是由于全球范围内战略性资源的严重匮乏,使得各国的石油石化公司纷纷寻求海外市场,中石油正是在这样的背景下完成了对哈萨克斯坦石油公司的收购.本文通过对此案进行SWOT分析,详细阐述中石油收购的优劣势、机遇和挑战,为公司的制订进一步的战略计划提供信息,并且为更多的即将加入海外并购行列的中国企业提出建议.

  19. Intel CULV双核PK AMD Congo——超轻薄笔记本性能提速

    Institute of Scientific and Technical Information of China (English)

    Marshall

    2010-01-01

    消费级超低功耗移动平台的出现让超轻薄笔记本成为了2009年下半年市场的新兴热点,成功细分市场的同时成为传统笔记本和上网本产品最具威胁的竞争对手。轻薄的机身和超长续航时间带来了优秀的便携性,而2009年末~2010年初性能的提升则让超轻薄笔记本美丽蝶变!

  20. [PK/PD Modeling as a Tool for Predicting Bacterial Resistance to Antibiotics: Alternative Analyses of Experimental Data].

    Science.gov (United States)

    Golikova, M V; Strukova, E N; Portnoy, Y A; Firsov, A A

    2015-01-01

    Postexposure number of mutants (NM) is a conventional endpoint in bacterial resistance studies using in vitro dynamic models that simulate antibiotic pharmacokinetics. To compare NM with a recently introduced integral parameter AUBC(M), the area under the time course of resistance mutants, the enrichment of resistant Staphylococcus aureus was studied in vitro by simulation of mono(daptomycin, doxycycline) and combined treatments (daptomycin + rifampicin, rifampicin + linezolid). Differences in the time courses of resistant S. aureus could be reflected by AUBC(M) but not N(M). Moreover, unlike AUBC(M), N(M) did not reflect the pronounced differences in the time courses of S. aureus mutants resistant to 2x, 4x, 8x and 16xMIC of doxycycline and rifampicin. The findings suggested that AUBC(M) was a more appropriate endpoint of the amplification of resistant mutants than N(M).

  1. Ekologisen ja sosiaalisen kestävyyden toteutuminen pk-yrityksessä : Case: Café Alegria

    OpenAIRE

    Naarminen, Mirva

    2012-01-01

    Työn tarkoituksena on selvittää, millä tavoin toimeksiantajayritys ilmentää toiminnassaan sosiaalista ja ekologista kestävää kehitystä. Tavoitteena on myös tarkastella, kuinka yrityksen pieni koko mahdollisesti vaikuttaa sen eettiseen toimintaan. Toimeksiantajana ja esimerkkiyrityksenä toimii savonlinnalainen ekokahvila Café Alegria. Kestävän kehityksen trendi on vahva hotelli- ja ravintola-alalla ja kuluttajien vaateet vihreälle toiminnalle yleistyvät. Ympäristötoimien tarkkaileminen ja...

  2. Pengaruh Penambahan Cake Terhadap Oil Content PKM (Palm Kernel Meal) Di Pk Crushing Plant PT. Multimas Nabati Asahan

    OpenAIRE

    Yusup, Muhammad

    2012-01-01

    Effect of Oil Content Of Cake addition of PKM (Palm Kernel Meal) is done by mixing the PKM and Cake through the process of solvent extraction using N- hexane with PKM and Cake variation ratio of 50:1; 50:0.9; 50:0.8; 50:0.7; 50:0.6, and 50:0.5. Research has been done shows that the effect of the addition of cake on PKM can increase oil content in samples and cake mass is added to produce the oil content of the standard is 0.6 g.

  3. A case of linear porokeratosis with penile localization

    OpenAIRE

    Turna İlknur; Sevgi Akarsu; Uğur Pabuççuoğlu; Emel Fetil

    2014-01-01

    Porokeratosis (PK), a disorder of epidermal keratinization with a unique clinical appearance, is characterized histopathologically by the presence of cornoid lamella. Many different clinical forms of PK have been described i.e., classical plaque-type PK of Mibelli, disseminated superficial actinic PK, linear PK, PK palmaris et plantaris disseminata, and punctate PK. Linear PK is a rare variant of PK presenting with slightly scaly atrophic papules following Blaschko’s lines. Additionally, PK c...

  4. Multilateral nonproliferation cooperation: US-led effort to remove HEU/LEU fresh and spent fuel from the Republic of Georgia to Dounreay, Scotland (Auburn Endeavor/Project Olympus)

    International Nuclear Information System (INIS)

    In early March 1998, the United States government approved a plan in cooperation with the United Kingdom and Georgian governments to rapidly retrieve and transport about 4.3 kilograms of enriched uranium. This material consisted largely of highly enriched uranium and a small amount of low-enriched uranium fresh fuel, as well as about 800 grams of HEU/LEU-based spent fuel from a shutdown IRT-M research reactor on the outskirts of Tbilisi in Georgia, a former Soviet republic. A technical team led by DOE consisted of HEU handling, packing and transportation experts from the Oak Ridge Y-12 Plant, managed and operated by Lockheed Martin Energy Systems, and spent fuel handling and transportation experts from NAC International in Norcross, Georgia, U.S.A. The team was part of an interagency task force formed with Department of Defense military personnel under US European Command and headed by a senior official from the Department of State. The operation was executed in full cooperation with the government of the Republic of Georgia and the staff at the institute of Physics. In April of 1998, the fresh fuel was repacked in US-supplied 6M-2R containers [USA/0002/B(U)F] and the spent fuel was repacked in the NAC-LWT cask [USA/9225/B(U)F-85]. All the containers were then transported in one US Air Force C-5B cargo aircraft via air-to-air refueling from Tbilisi, Georgia, to Kinloss Royal Air Force Base outside Inverness, Scotland. In Scotland the fresh and spent fuel was transported north to the Dounreay Nuclear Complex west of Thurso, Caithness, Scotland, for interim storage and final disposition. This successful national security project was the first time the United States teamed with a NATO partner to remove nuclear material from a site of proliferation concern

  5. The World Under a Microscope

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Olympus sponsors the first national confocal microscopic-image competition The Olympus Cup National Confocal Microscopic-image Competition, the first of its kind in China,lifted its curtain in Beijing on November 1. Olympus (China) Co. Ltd. is the competition’s sole spon-

  6. Analisis Hukum Perlindungan Merek Asing Terhadap Tindakan Pendaftaran Secara Itikad Tidak Baik (Studi Putusan No. 108/PK/PDT.SUS/2011)

    OpenAIRE

    Horison, Andy

    2015-01-01

    A brand is an important element which is adhered to goods and services. Generally, it is a brand and not a product which makes goods interested and its price high. The more well-known a brand is, the more it is interested by people. However, its fame also causes it to be the violating target, and what usually occurs is bad faith in registering the brand. This condition has made the researcher conduct a research on the protection of foreign brands toward bad faith in registering...

  7. Online Retailers' PK, Verbal Duels or Real Benefits?%电商PK,口水战还是真实惠?

    Institute of Scientific and Technical Information of China (English)

    张晓(撰文); 尹延冰(绘图)

    2012-01-01

    Ms. Wu living in Jinan wants to buy a TV set for her new home. On August 14th, she was excited by the news of the .verbal duels between online retailers, She was disappointedto find that some price reductions were already in short supply when the price war kicked off on August 15th at 9 a.m. Meanwhile, a TV brand increased the price of one product that was sold only in 360buy. com. When she turned to Suning and Gome for bargain opportunities, this lady was genuinely surprised that the websites of these two online retailers both crashed.%济南的吴女士近期正打算为新家添置一台电视机。8月14日,各电商间的微博口水战无疑让她兴奋不已。8月15日上午9点,电商大战正式打响,吴女士迫不及待地进入各电商网站寻找时机。可她发现,京东商城上不少降价商品在价格战刚开始就已缺货,与此同时某品牌电视竟连夜涨价,而这款电视只有京东一家销售。

  8. PK-yritysten ympäristövastuu : ympäristölainsäädännön ja yhteiskuntavastuun ohjaavuus liiketoiminnassa

    OpenAIRE

    Liljeqvist, Suvi

    2014-01-01

    Ympäristönsuojelun ja ympäristöoikeuden merkitys yhteiskunnassa kasvaa jatkuvasti. Kestävä kehitys on yhä tärkeämpää, sillä ympäristön saastuminen, luonnonvarojen ehtyminen ja maapallon väestönkasvu näkyy kaikkialla. Erilaiset sosiaaliset ja ympäristöä koskevat ongelmat ovat osa tätä päivää. Yritysten vastuu ekologisten ja sosiaalisten ongelmien ratkaisemisessa on merkittävä. Yhteiskuntavastuusta on muodostunut vähitellen osa normaalia yritystoimintaa. Yrityksen yhteiskuntavastuu muodostuu va...

  9. Experience gained from shifting a PK-19 boiler to operate with increased superheating and with a load higher than its rated value

    Science.gov (United States)

    Kholshchev, V. V.

    2011-08-01

    Failures of steam superheater tubes occurred after the boiler was shifted to operate with a steam temperature of 540°C. The operation of the steam superheater became more reliable after it had been subjected to retrofitting. The modernization scheme is described. An estimate is given to the temperature operating conditions of tubes taking into account the thermal-hydraulic nonuniformity of their heating.

  10. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Vowinckel, E; Reutens, D; Becher, B;

    1997-01-01

    Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We exa...

  11. Penentuan Kadar Minyak Pada Palm Pernel (PK)dan Palm Kernel Meal(PKM) dengan Metode Ekstraksi Sokletasi di PKCrushing Plan PTMultimas Nabati Asahan

    OpenAIRE

    Hakiki, Iman

    2016-01-01

    To maximize production of palm kernel oil, should be determined in advance oil content contained in palm kernel and the rest of the discharge results in the form of waste which still contains oil. Have analyzed the oil content in palm kernel and palm kernel meal with soxhletation extraction method. From the analysis conducted on 14-25 February 2015 obtained results palm kernel oil content in each - each amounting to 50.97%; 51.49%; 50.24%; while on the analysis of the oil content in palm kern...

  12. Search for the deeply bound $K^-pp$ state via the $^3$He($K^-,n)$ reaction at $p_{K^-}$=1 GeV/$c$

    CERN Document Server

    Hashimoto, Tadashi; Beer, George; Bhang, Hyoungchan; Bragadireanu, Mario; Buehler, Paul; Busso, Luigi; Cargnelli, Michael; Choi, Seonho; Curceanu, Catalina; Enomoto, Shun; Faso, Diego; Fujioka, Hiroyuki; Fujiwara, Yuya; Fukuda, Tomokazu; Guaraldo, Carlo; Hayano, Ryugo S; Hiraiwa, Toshihiko; Iio, Masami; Iliescu, Mihai; Inoue, Kentaro; Ishiguro, Yosuke; Ishikawa, Takashi; Ishimoto, Shigeru; Ishiwatari, Tomoichi; Itahashi, Kenta; Iwai, Masaaki; Iwasaki, Masahiko; Kato, Yuko; Kawasaki, Shingo; Kienle, Paul; Kou, Hiroshi; Ma, Yue; Marton, Johann; Matsuda, Yasuyuki; Mizoi, Yutaka; Morra, Ombretta; Nagae, Tomofumi; Noumi, Hiroyuki; Ohnishi, Hiroaki; Okada, Shinji; Outa, Haruhiko; Piscicchia, Kristian; Lener, Marco Poli; Vidal, Antonio Romero; Sada, Yuta; Sakaguchi, Atsushi; Sakuma, Fuminori; Sato, Masaharu; Scordo, Alessandro; Sekimoto, Michiko; Shi, Hexi; Sirghi, Diana; Sirghi, Florin; Suzuki, Ken; Suzuki, Shoji; Suzuki, Takatoshi; Tanida, Kiyoshi; Tatsuno, Hideyuki; Tokuda, Makoto; Tomono, Dai; Toyoda, Akihisa; Tsukada, Kyo; Doce, Oton Vazquez; Widmann, Eberhard; Wunschek, Barbara K; Yamaga, Takumi; Yamazaki, Toshimitsu; Yim, Heejoong; Zhang, Qi; Zmeskal, Johann

    2014-01-01

    An experiment to search for the $K^-pp$ bound state was performed via the in-flight $^3$He($K^-,n)$ reaction at $\\theta_{n}^{lab}=0^\\circ$ using 5.3 $\\times$ $10^9$ kaons at 1 GeV/$c$ at the J-PARC hadron experimental facility. In the neutron missing-mass spectrum, no significant peak was observed in the region corresponding to $K^-pp$ binding energy larger than 80 MeV, where a bump structure was reported in the $\\Lambda p$ final state in different reactions. Mass-dependent upper limits of the production cross section for the state isotropically decaying into $\\Lambda p$ were determined at 95% confidence level to be (30--180), (70--250), and (100--270) $\\mu$b/sr, for the natural widths of 20, 60, and 100 MeV, respectively.

  13. PK/PD Modelling of the QT Interval: a Step Towards Defining the Translational Relationship Between In Vitro, Awake Beagle Dogs, and Humans.

    Science.gov (United States)

    Marostica, Eleonora; Van Ammel, Karel; Teisman, Ard; Gallacher, David; Van Bocxlaer, Jan; De Ridder, Filip; Boussery, Koen; Vermeulen, An

    2016-07-01

    Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a 1. Overall, dogs were more sensitive than humans to QT-interval change, an a 1 of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.

  14. Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK

    Directory of Open Access Journals (Sweden)

    Hyun-moon Back

    2015-01-01

    Full Text Available KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life and Tmax of matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively. Cmax and AUCinf of matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.

  15. Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair

    Institute of Scientific and Technical Information of China (English)

    Longhou Fang; YiGuo Wang; Dan Du; Guang Yang; Tim Tak Kwok; Siu Kai Kong; Benjamin Chen; David J Chen; Zhengjun chen

    2007-01-01

    @@ The author affiliations were mixed up in the previous published version. The third fund number of National Natural Science Foundation of China in the Acknowledgments was wrong, it should be "30270335".

  16. Prediction of brain target site concentrations on the basis of CSF PK : impact of mechanisms of blood-to-brain transport and within brain distribution

    NARCIS (Netherlands)

    Westerhout, Joost

    2014-01-01

    In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Direct measurement of brain extracellular fluid (brainECF) concentrations is highly restricted in human. Therefore, unbound drug concentrations in huma

  17. Guanine and 7-methylguanine amino proton exchange rates as a function of buffer pK: implications for the exchange mechanism.

    OpenAIRE

    Hartmann, B.; Lavery, R.; Ramstein, J

    1986-01-01

    Using the stopped-flow kinetic method we have measured the deuteration rate of the amino protons in 2'deoxyguanosine 5'monophosphate and 7-methylguanosine 5'monophosphate. For both compounds the exchange rates are accelerated with increasing concentration of a large number of buffers with widely differing pKs. The results obtained, in conjunction with a theoretical model study, give rise to serious doubts concerning the normally accepted mechanism of amino proton exchange involving a pre-prot...

  18. Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients.

    Science.gov (United States)

    Hénin, Emilie; Meille, Christophe; Barbolosi, Dominique; You, Benoit; Guitton, Jérôme; Iliadis, Athanassios; Freyer, Gilles

    2016-04-01

    The MODEL1 trial is the first model-driven phase I/II dose-escalation study of densified docetaxel plus epirubicin administration in metastatic breast cancer patients, a regimen previously known to induce unacceptable life-threatening toxicities. The primary objective was to determine the maximum tolerated dose of this densified regimen. Study of the efficacy was a secondary objective. Her2-negative, hormone-resistant metastatic breast cancer patients were treated with escalating doses of docetaxel plus epirubicin every 2 weeks for six cycles with granulocyte colony stimulating factor support. A total of 16 patients were treated with total doses ranging from 85 to 110 mg of docetaxel plus epirubicin per cycle. Dose escalation was controlled by a non-hematological toxicity model. Dose densification was guided by a model of neutrophil kinetics, able to optimize docetaxel plus epirubicin dosing with respect to pre-defined acceptable levels of hematological toxicity while ensuring maximal efficacy. The densified treatment was safe since hematological toxicity was much lower compared to previous findings, and other adverse events were consistent with those observed with this regimen. The maximal tolerated dose was 100 mg given every 2 weeks. The response rate was 45 %; median progression-free survival was 10.4 months, whereas 54.6 months of median overall survival was achieved. The optimized docetaxel plus epirubicin dosing regimen led to fewer toxicities associated with higher efficacy as compared with standard or empirical densified dosing. This study suggests that model-driven dosage adjustment can lead to improved efficacy-toxicity balance in patients with cancer when several anticancer drugs are combined.

  19. Kinetics of an acid-base catalyzed reaction (aspartame degradation) as affected by polyol-induced changes in buffer pH and pK values.

    Science.gov (United States)

    Chuy, S; Bell, L N

    2009-01-01

    The kinetics of an acid-base catalyzed reaction, aspartame degradation, were examined as affected by the changes in pH and pK(a) values caused by adding polyols (sucrose, glycerol) to phosphate buffer. Sucrose-containing phosphate buffer solutions had a lower pH than that of phosphate buffer alone, which contributed, in part, to reduced aspartame reactivity. A kinetic model was introduced for aspartame degradation that encompassed pH and buffer salt concentrations, both of which change with a shift in the apparent pK(a) value. Aspartame degradation rate constants in sucrose-containing solutions were successfully predicted using this model when corrections (that is, lower pH, lower apparent pK(a) value, buffer dilution from the polyol) were applied. The change in buffer properties (pH, pK(a)) from adding sucrose to phosphate buffer does impact food chemical stability. These effects can be successfully incorporated into predictive kinetic models. Therefore, pH and pK(a) changes from adding polyols to buffer should be considered during food product development.

  20. Viennin rahoitus- ja tukimuodot sekä projektit vienninedistämistoiminnassa : Case: Ilmasilta pk-yrityksille Keski-Pohjanmaalta -hanke

    OpenAIRE

    Laitinen, Jonna

    2013-01-01

    Viennin aloittamiseen tarvitaan usein monia työkaluja, joista rahoitus on yksi tärkeä osa. Useat kotimaiset sekä myös ulkomaiset pankit tarjoavat laajan valikoiman työkaluja viennin rahoittamiseen. Yritysten vientiä myös tuetaan hyvin Suomessa ja edistetään monin eri tavoin. Tässä opinnäytetyössä tutkitaan erilaisia viennin rahoitusmahdollisuuksia sekä tukimuotoja. Tämän lisäksi havainnollistetaan kuinka viennin edistämistoiminta voidaan hoitaa projektina. Työn tarkoituksena on luo...

  1. A long trail behind the planetary nebula HFG1 (PK 136+05) and its precataclysmic binary central star V664 Cas

    CERN Document Server

    Boumis, P; Lloyd, M; Akras, S

    2009-01-01

    A deep wide-field image in the light of the Halpha+[N II] emission lines, of the planetary nebula HFG1 which surrounds the precataclysmic binary system V664 Cas, has revealed a tail of emission at least 20' long, at a position angle of 316deg. Evidence is presented which suggests that this is an ~10^5 y old trail of shocked material, left behind V664 Cas as it ejects matter whilst ploughing through its local interstellar media at anywhere between 29 and 59 km/s depending on its distance from the Sun.

  2. Descriptive Indicators of Future Teachers' Technology Integration in the PK-12 Classroom: Trends from a Laptop-Infused Teacher Education Program

    Science.gov (United States)

    Hughes, Joan E.

    2013-01-01

    This research examined preservice teacher graduates' positioning toward integrating technology in future teaching. Participants included 115 preservice teachers across three cohorts in 2008-2009 who graduated from a laptop-infused teacher education program. The study implemented a case study methodology that included a survey administered upon…

  3. Associated strangeness production in the pp to pK^+K^-p and pp to pK^+ pi^0 Sigma^0 reactions

    CERN Document Server

    Xie, Ju-Jun

    2010-01-01

    The total and differential cross sections for associated strangeness production in the $pp \\to pK^+K^-p$ and $pp \\to pK^+\\pi^0\\Sigma^0$ reactions have been studied in a unified approach using an effective Lagrangian model. It is assumed that both the $K^-p$ and $\\pi^0\\Sigma^0$ final states originate from the decay of the $\\Lambda(1405)$ resonance which was formed in the production chain $pp\\to p(N^*(1535)\\to K^+\\Lambda(1405))$. The available experimental data are well reproduced, especially the ratio of the two total cross sections, which is much less sensitive to the particular model of the entrance channel. The significant coupling of the $N^*(1535)$ resonance to $\\Lambda(1405) K$ is further evidence for large $s \\bar{s}$ components in the quark wave function of the $N^*(1535)$ resonance.

  4. The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer : Genetic Association Study in 18,723 Individuals

    NARCIS (Netherlands)

    Abuli, Anna; Bujanda, Luis; Munoz, Jenifer; Buch, Stephan; Schafmayer, Clemens; Maiorana, Maria Valeria; Veneroni, Silvia; van Wezel, Tom; Liu, Tao; Westers, Helga; Esteban-Jurado, Clara; Ocana, Teresa; Pique, Josep M.; Andreu, Montserrat; Jover, Rodrigo; Carracedo, Angel; Xicola, Rosa M.; Llor, Xavier; Castells, Antoni; Dunlop, Malcolm; Hofstra, Robert; Lindblom, Annika; Wijnen, Juul; Peterlongo, Paolo; Hampe, Jochen; Ruiz-Ponte, Clara; Castellvi-Bel, Sergi

    2014-01-01

    Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly

  5. The Development of Models Based on Linear and Nonlinear Multivariate Methods to Predict ADME/PK Properties Using Physicochemical Properties of Kinase, Protease Inhibitors, and GPCR Antagonists

    Directory of Open Access Journals (Sweden)

    Deepu Bakasta

    2013-01-01

    Full Text Available Oral bioavailability of a drug compound is the significant property for potential drug candidates. Measuring this property can be costly and time-consuming. Quantitative structure-property relationships (QSPRs are used to estimate the percentage of oral bioavailability, and they are an attractive alternative to experimental measurements. A data set of 217 drug and drug-like compounds with measured values of the percentage of oral bioavailability taken from the small molecule ChemBioBase database was used to develop and test a QSPR model. Descriptors were calculated for the compounds using Codessa 2.1 tool. Nonlinear general regression neural network model was generated using the DTREG predictive modeling program software. The calculated percentage of oral bioavailability model performs well, with root-mean-square (rms errors of 4.55% oral bioavailability units for the training set, 14.32% oral bioavailability units for the test set, and 19.12% oral bioavailability units for the external prediction set. Given the structural diversity and bias of the data set, this is a good first attempt at modeling oral bioavailability using QSPR methods. The model can be used as a potential virtual screen or property estimator. With a larger data supply less biased toward the high end values of the percentage of oral bioavailability, a more successful model could likely be developed.

  6. First observation of $\\gamma \\gamma \\to p \\bar{p} K^+ K^-$ and search for exotic baryons in $pK$ systems

    CERN Document Server

    Shen, C P; Adachi, I; Aihara, H; Asner, D M; Aulchenko, V; Aushev, T; Ayad, R; Babu, V; Badhrees, I; Bakich, A M; Barberio, E; Behera, P; Bhardwaj, V; Bhuyan, B; Biswal, J; Bobrov, A; Bonvicini, G; Bozek, A; Bračko, M; Browder, T E; Červenkov, D; Chang, P; Chekelian, V; Chen, A; Cheon, B G; Chilikin, K; Chistov, R; Cho, K; Chobanova, V; Choi, S -K; Choi, Y; Cinabro, D; Dalseno, J; Danilov, M; Dash, N; Doležal, Z; Drásal, Z; Dutta, D; Eidelman, S; Fang, W X; Fast, J E; Ferber, T; Fulsom, B G; Gaur, V; Gabyshev, N; Garmash, A; Gillard, R; Glattauer, R; Goldenzweig, P; Grzymkowska, O; Haba, J; Hayasaka, K; Hayashii, H; Hou, W -S; Iijima, T; Inami, K; Inguglia, G; Ishikawa, A; Itoh, R; Iwasaki, Y; Jaegle, I; Jeon, H B; Joo, K K; Julius, T; Kang, K H; Kato, E; Kiesling, C; Kim, D Y; Kim, J B; Kim, K T; Kim, S H; Kim, Y J; Kodyš, P; Korpar, S; Kotchetkov, D; Križan, P; Krokovny, P; Kuzmin, A; Kwon, Y -J; Lange, J S; Li, C H; Li, H; Li, L; Li, Y; Gioi, L Li; Libby, J; Liventsev, D; Lubej, M; Luo, T; Masuda, M; Matsuda, T; Matvienko, D; Miyabayashi, K; Miyata, H; Mizuk, R; Mohanty, G B; Mohanty, S; Moll, A; Moon, H K; Mussa, R; Nakano, E; Nakao, M; Nanut, T; Nath, K J; Natkaniec, Z; Nishida, S; Ogawa, S; Olsen, S L; Ostrowicz, W; Pakhlov, P; Pakhlova, G; Pal, B; Park, C -S; Park, H; Pesántez, L; Pestotnik, R; Petrič, M; Piilonen, L E; Pulvermacher, C; Rauch, J; Ritter, M; Sakai, Y; Sandilya, S; Santelj, L; Sanuki, T; Savinov, V; Schlüter, T; Schneider, O; Schnell, G; Schwanda, C; Seino, Y; Semmler, D; Senyo, K; Seong, I S; Sevior, M E; Shibata, T -A; Shiu, J -G; Shwartz, B; Simon, F; Sokolov, A; Solovieva, E; Stanič, S; Starič, M; Strube, J F; Stypula, J; Sumihama, M; Sumiyoshi, T; Takizawa, M; Tamponi, U; Tanida, K; Tenchini, F; Trabelsi, K; Uchida, M; Uehara, S; Uglov, T; Unno, Y; Uno, S; Urquijo, P; Usov, Y; Van Hulse, C; Varner, G; Wang, C H; Wang, M -Z; Wang, P; Watanabe, M; Watanabe, Y; Williams, K M; Won, E; Yamaoka, J; Yelton, J; Yook, Y; Yusa, Y; Zhang, C C; Zhang, Z P; Zhilich, V; Zhukova, V; Zhulanov, V; Zupanc, A

    2016-01-01

    The process $\\gamma \\gamma \\to p \\bar{p} K^+ K^-$ and its intermediate processes are measured for the first time using a 980~fb$^{-1}$ data sample collected with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. The production of $p \\bar{p} K^+ K^-$ and a $\\Lambda(1520)^0~(\\bar{\\Lambda}(1520)^0)$ signal in the $pK^-$~($\\bar{p} K^+$) invariant mass spectrum are clearly observed. However, no evidence for an exotic baryon near 1540~MeV/$c^2$, denoted as $\\Theta(1540)^0$~($\\bar{\\Theta}~(1540)^0$) or $\\Theta(1540)^{++}$~($\\Theta(1540)^{--}$), is seen in the $p K^-$~($\\bar{p}K^+$) or $pK^+$~($\\bar{p} K^-$) invariant mass spectra. Cross sections for $\\gamma \\gamma \\to p \\bar{p} K^+ K^-$, $\\Lambda(1520)^0 \\bar{p} K^+ +c.c.$ and the products $\\sigma(\\gamma \\gamma \\to \\Theta(1540)^0 \\bar{p} K^+ +c.c.)\\BR(\\Theta(1540)^0 \\to p K^{-})$ and $\\sigma(\\gamma \\gamma \\to \\Theta(1540)^{++} \\bar{p} K^- +c.c.)\\BR(\\Theta(1540)^{++}\\to p K^{+})$ are measured. We also determine upper limits on the products of the $\\...

  7. Measurement of $K^- p$ radiative capture to $\\gamma \\Lambda$ and $\\gamma \\Sigma^0$ for $p_{K^-}$ between 514 and 750 MeV/$c$

    CERN Document Server

    Prakhov, S; Phaisangittisakul, N; Nefkens, B M K; Allgower, C E; Bekrenev, V; Briscoe, W J; De Cruz, L; Isenhower, D; Knecht, N; Koulbardis, A; Kozlenko, N; Kruglov, S; Lolos, G; Lopatin, I; Manley, D M; Marušić, A; McDonald, S; Olmsted, J; Papandreou, Z; Peaslee, D; Price, J W; Ryckebusch, J; Sadler, M; Shafi, A; Starostin, A; Staudenmaier, H M; Strakovsky, I I; Supek, I; Van Cauteren, T

    2009-01-01

    Differential cross sections for $K^-$ radiative capture in flight on the proton, leading to the $\\gamma\\Lambda$ and $\\gamma\\Sigma^0$ final states, have been measured at eight $K^-$ momenta between 514 and 750 MeV/$c$. The data were obtained with the Crystal Ball multiphoton spectrometer installed at the separated $K/\\pi$ beam line C6 of the BNL Alternating Gradient Synchrotron. The results substantially improve the existing experimental data available for studying radiative decays of excited hyperon states. An exploratory theoretical analysis is performed within the Regge-plus-resonance approach. According to this analysis, the $\\gamma\\Sigma^0$ final state is dominated by hyperonresonance exchange and hints at an important role for a resonance in the mass region of 1700 MeV. In the $\\gamma\\Lambda$ final state, on the other hand, the resonant contributions account for only half the strength, and the data suggest the importance of a resonance in the mass region of 1550 MeV.

  8. Internetin ilmaisten kirjanpito-ohjelmien soveltuvuus pk-yritysten käyttöön. Kolmen Internetin ilmaisen kirjanpito-ohjelman vertailua.

    OpenAIRE

    Hulkkonen, Tiia

    2014-01-01

    Tässä opinnäytetyössä tutkitaan Internetistä löytyvien ilmaisten kirjanpito-ohjelmien soveltuvuutta pienten ja keskisuurten yritysten käyttöön. Tehdyn tutkimustyön tavoitteena on tuoda vasta toimintaansa aloittelevien sekä mahdollista kirjanpito-ohjelman vaihtoa suunnittelevien pienten ja keskisuurten yritysten tietoon vaihtoehtoja maksullisille, lisenssin vaativille kirjanpito-ohjelmille. Internetistä löytyvistä kirjanpito-ohjelmista tutkimuksen kohteeksi valikoitui sattumanvaraisesti kolme ...

  9. Design and construction of a rockfill spur dyke on the Rupert River (PK 85) under the Eastmain1-A/LaSarcelle/Rupert diversion project; Conception et construction d'un epi en enrochement sur la riviere Rupert (PK 85) dans le cadre du projet Eastmain-1-A/LaSarcell/derivation Rupert

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, Pierre; Fecteau Sebastien, Thibodeau; Patrick [GENIVAR, Quebec, (Canada); Cote, Pierre; Grenon, Alain [Societe d' Energie de la Baie James, Montreal, (Canada)

    2010-07-01

    The Eastmain-1-A/Sarcelle plants and Rupert diversion project involved the partial diversion of the Rupert River in the direction of the La Grande complex. This diversion point on the Rupert River is located at the 314th kilometre, where a dam with a regulation works was constructed. A network of nine hydraulic works was designed and constructed to maintain the water levels in the slow flow section of the river to limit the environmental impact. A rockfill spur dyke was constructed at the 85th kilometre of the Rupert River, for control of the water levels over a distance of 10.8 kilometres. This paper presented the challenges facing the construction operation of this hydraulic work on the Rupert River. The design of this structure was first simulated by 2-D hydrodynamic models. A scale model built at the 1:40 scale was used to assess the stability of the temporary piers created for shelter during the construction process.

  10. A case of linear porokeratosis with penile localization

    Directory of Open Access Journals (Sweden)

    Turna İlknur

    2014-09-01

    Full Text Available Porokeratosis (PK, a disorder of epidermal keratinization with a unique clinical appearance, is characterized histopathologically by the presence of cornoid lamella. Many different clinical forms of PK have been described i.e., classical plaque-type PK of Mibelli, disseminated superficial actinic PK, linear PK, PK palmaris et plantaris disseminata, and punctate PK. Linear PK is a rare variant of PK presenting with slightly scaly atrophic papules following Blaschko’s lines. Additionally, PK confined to the genital area is also an uncommon condition. Both genital and linear PK are extremely rare and only one case of genital linear PK has been reported in the literature. Here, we report the case of a patient with penile linear PK who was treated with diclofenac sodium gel and imiquimod cream but did not recover.

  11. Dicty_cDB: AFK592 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available rgahti vitnnstlakhiahdtilipsngiltallaaiplqlla*kgnl*kydpdrpkn*pk Translated Amino Acid sequence (All Frames) ...ieqdtpiiliilddsnsplmrvaaeevkargahti vitnnstlakhiahdtilipsngiltallaaiplqlla*kgnl*kydpdrpkn*pk Homology vs CSM

  12. Optimization of the phenylurea moiety in a phosphoinositide 3-kinase (PI3K) inhibitor to improve water solubility and the PK profile by introducing a solubilizing group and ortho substituents.

    Science.gov (United States)

    Kawada, Hatsuo; Ebiike, Hirosato; Tsukazaki, Masao; Yamamoto, Shun; Koyama, Kohei; Nakamura, Mitsuaki; Morikami, Kenji; Yoshinari, Kiyoshi; Yoshida, Miyuki; Ogawa, Kotaro; Shimma, Nobuo; Tsukuda, Takuo; Ohwada, Jun

    2016-07-01

    Phosphoinositide 3-kinase (PI3K) is a promising anti-cancer target, because various mutations and amplifications are observed in human tumors isolated from cancer patients. Our dihydropyrrolopyrimidine derivative with a phenylurea moiety showed strong PI3K enzyme inhibitory activity, but its pharmacokinetic property was poor because of lack of solubility. Herein, we report how we improved the solubility of our PI3K inhibitors by introducing a solubilizing group and ortho substituents to break molecular planarity. PMID:27189888

  13. 美国牛仔——Maisto(玛莎图)版Jeep牧马人PK The Franklin Mint(富兰克林)版Jeep牧马人

    Institute of Scientific and Technical Information of China (English)

    刘洋

    2008-01-01

    首先要说明的是虽然全球模型生产商众多,但因为外观造型的版权问题,故各款车型在全球也很难找到一款模型生产商不同、车款完全相同的两台模型车来。此次我们对比的是车型相同,但车款不同、模型生产商不同、比例不同的两台Jeep牧马人模型。一款是Maisto(玛莎图)版本的1:18比例Jeep牧马人消防救护车;另一款是1:24比例TheFranklinMint(富兰克林)版本的基本型Jeep牧马人CJ7。

  14. A quimiometria nos cursos de graduação em química: proposta do uso da análise multivariada na determinação de pkª

    Directory of Open Access Journals (Sweden)

    Paulo Cesar de Souza Pereira

    2014-01-01

    Full Text Available An experiment was proposed applying the Chemometric approach of Multivariate Analysis for inclusion in undergraduate Chemistry courses to promote and expand the use of this analytical-statistical tool. The experiment entails the determination of the acid dissociation constant of dyes via UV-Vis electronic spectrophotometry. The dyes used show from simple equilibrium to very complex systems involving up to four protolytic species with high spectral overlap. The Chemometric methodology was more efficient than univariate methods. For use in classes, it is up to the teacher to decide which systems should be utilized given the time constraints and laboratory conditions.

  15. Growth responses of Lycoris longituba to application of soybean meal and P-K fertilizers%豆饼和磷钾肥对长筒石蒜生长的影响

    Institute of Scientific and Technical Information of China (English)

    鲍淳松; 张鹏翀; 江燕

    2015-01-01

    A furrow fertilizer application method was carried out, in which bulb of Lycoris longituba was planted on the top of casing soil over the applied fertilizer, soybean meal fertilizer at the bottom and superphosphate and potassium chloride fertilizer on the upper layer, to study the fertilizing effects of different usages of soybean meal and chemical fertilizer on the leaf growth and bulb biomass. Results showed that relative leaf biomass decreased with the fertilization amount at the late stage of the first growth season. The fertilization did not significantly increase average leaf count, leaf length and bulb biomass in the following 2 years. Bulb of L. longituba grew slowly, and the average annual compound growth rate of fresh bulb weight was only about 41%. It is suggested that relative fertile soil be selected to plant Lycoris longituba, and the principal of multiple and light fertilizations were suggested to follow.%试验采用先施豆饼肥、上面施化肥后覆土,再在上面种植鳞茎的沟施方法,探讨不同用量的豆饼肥和化肥(过磷酸钙+氯化钾)对长筒石蒜生长的影响。结果表明:施肥未显著增加叶生长量和鳞茎生物量。施肥后首季表现出用量越多叶量越小的趋势,表现出施肥的负面效应,但随后年份负面影响减小。长筒石蒜生长缓慢,鳞茎鲜重平均年复合增长率仅41%。建议选择相对肥沃的土壤种植,施肥则宜多次薄施。

  16. Identification of Hemagglutinating encephalomyelitis virus Receptor in PK Cells Membrane%猪血凝性脑脊髓炎病毒PK细胞膜受体的鉴定

    Institute of Scientific and Technical Information of China (English)

    陆慧君; 贺文琦; 宋德光; 刘立国; 常灵竹; 李志萍; 陈克研; 高丰

    2008-01-01

    在毕赤酵母(Pichia pastoris)中表达猪血凝性脑脊髓炎病毒(Hemagglutinating encephalomyelitis virus,HEV)67N株S蛋白片段,纯化后免疫家兔,获得兔抗HEV-S蛋白特异性抗体;提取PK细胞膜蛋白,SDS-PAGE电泳后,转印NC膜,以纯化的S1蛋白代替病毒,利用改进的病毒铺覆蛋白结合试验(COPBA)对PK细胞膜受体进行鉴定.结果扩增获得1 797 bp的S1目的基因片段,用S1特异性引物和AOX1通用引物PCR鉴定结果表明,实验成功地构建了重组酵母表达质粒,重组酵母菌经1%甲醇诱导,在培养基上清中检测到73 kD目的蛋白.Western blot分析发现,该重组蛋白可与HEV多克隆抗体发生特异性血清反应;提取的PK细胞膜蛋白转膜后与纯化的S1目的蛋白结合,DAB显色发现在90 kD处有清晰的蛋白带.

  17. What Is a Colonoscopy

    Medline Plus

    Full Text Available ... cancer from forming. So, we have become a standard. We are in a beautiful suite at Broward ... less than 1 mm. We have the high definition colonoscope by Olympus. This also has a filter ...

  18. What Is a Colonoscopy

    Medline Plus

    Full Text Available ... your hospital is how many years the nurses has been working with the doctors in the same ... the high definition colonoscope by Olympus. This also has a filter that allows us to see and ...

  19. The Red Dress: Getting to the Heart of Women's Health

    Science.gov (United States)

    ... of The Heart Truth's Red Dress Collection 2006 Fashion Show on the runway at Olympus Fashion Week. Those wearing red dresses designed by America's top fashion houses included Amerie for Tommy Hilfiger (far left), ...

  20. What Is a Colonoscopy

    Medline Plus

    Full Text Available ... definition colonoscope by Olympus. This also has a filter that allows us to see and pick up ... just a fold. I can turn on my filter, and make sure that we are dealing with ...

  1. Extravehicular Activity Fact Sheet: An EVA Chronology

    Data.gov (United States)

    National Aeronautics and Space Administration — Walking to Olympus: An EVA Chronology chronicles the 154 EVAs conducted from March 1965 to April 1997. It is intended to make clear the crucial role played by EVA...

  2. Schools K-12 - MDC_ElementaryAttendanceBoundary

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — Polygon feature class of Miami-Dade County, Public Schools attendance zones for Elementary schools (PK-5) and K-8 Centers (PK-8) schools. K-8 Centers are elementary...

  3. THE RELATIONSHIP BETWEEN QUANTITY AND LEVEL OF COMPETITION, AND COGNITIVE EXPERTISE IN SPANISH TENNIS PLAYERS

    OpenAIRE

    García-González, Luis; Moreno, Alberto; Moreno, Perla; Gil, Alexander; del-Villar, Fernando

    2015-01-01

    This work evaluates the relationship between quantity and level of competition, and cognitive expertise. To this end, cognitive expertise has been evaluated in Spanish tennis players (N=150) by means of declarative knowledge (DK) and procedural knowledge (PK) levels. DK and PK were assessed through a specific questionnaire (DK/PK-QT; García-González, Moreno, Moreno, Iglesias, & Del Villar, 2008). ANOVAs showed significant differences in both DK and PK with regard to the quantity of competi...

  4. Protection against β adrenoceptor agonist reduction of plasma potassium in severe but not in moderate hypokalemia

    DEFF Research Database (Denmark)

    Tran, Cao Thach Tran; Kjeldsen, Keld

    2011-01-01

    and terbutalin showed no additive effect. Normalization of pK by KCl infusion in severe hypokalemia immediately abolished protection against terbutalin induced further pK reduction. Hence, terbutalin clamped pK at around 4 mm, whereas it continued to increase to around 5 mm without terbutalin infusion. Major new...... findings are: Protection against terbutalin induced further reduction in pK in severe pre-existing hypokalemia (...

  5. The effect of gamma irradiation of seeds on germination - growth - mineral content and yield of two barley varieties grown under saline conditions

    International Nuclear Information System (INIS)

    Seeds of two barley varieties [Arabi Abiad (AA) and Pakistani PK 30163 (PK)] were irradiated with 0 and 15 Gy doses of gamma irradiation. Then, they were sown on salty soil (16.8-18 dS/m) and irrigated with salty water (7-8 dS/m). Gamma irradiation significantly increased the % of seedling emergence of PK only. At the heading stage, gamma irradiation decreased the % of total N of PK and increased shoot dry weight, Mg++ and P content and the % of total N of AA. K+ content of PK was lower than that of AA. At harvest stage, gamma irradiation increased total and grain yields and harvest index of PK; however, straw yield and 1,000 grain weight of AA were higher than those of PK

  6. Improving the Accuracy of Predicting Maximal Oxygen Consumption (VO2peak)

    Science.gov (United States)

    Downs, Meghan E.; Lee, Stuart M. C.; Ploutz-Snyder, Lori; Feiveson, Alan

    2016-01-01

    Maximal oxygen (VO2pk) is the maximum amount of oxygen that the body can use during intense exercise and is used for benchmarking endurance exercise capacity. The most accurate method to determineVO2pk requires continuous measurements of ventilation and gas exchange during an exercise test to maximal effort, which necessitates expensive equipment, a trained staff, and time to set-up the equipment. For astronauts, accurate VO2pk measures are important to assess mission critical task performance capabilities and to prescribe exercise intensities to optimize performance. Currently, astronauts perform submaximal exercise tests during flight to predict VO2pk; however, while submaximal VO2pk prediction equations provide reliable estimates of mean VO2pk for populations, they can be unacceptably inaccurate for a given individual. The error in current predictions and logistical limitations of measuring VO2pk, particularly during spaceflight, highlights the need for improved estimation methods.

  7. 百万像素数码相机专辑(下)

    Institute of Scientific and Technical Information of China (English)

    HHH

    2001-01-01

    Olympus和富士在数码相机市场上是死敌。在中低档市场上,OlympusD-4xx、D-3XX系列相机因“侧移动式镜头盖”的设计而大受消费者欢迎,同时富士的旧有相机线有面临更新换代的压力,因而有MX-1200的替代品FinePix 1300与OlympusD-360正面对决,而Finepix1400的对手则是D-460。富士在Finepix1400上采用与OlympusD-460类似的镜头盖设计,来个“师夷长技以制夷”。

  8. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole Lerberg; Afzelius, Pia; Bender, Dirk;

    2015-01-01

    The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11...

  9. Diagnostic Value of Three Tumor Markers (Tumor M2-PK, CEA, CYFRA21-1) as Analyzed with Application of Logistic Regression and ROC Curve in Patients with Non-Small-Cell Lung Cancer%Logistic回归和ROC曲线综合分析三种肿瘤标志物对非小细胞肺癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘小琴; 赵红霞; 时静; 丁志祥

    2008-01-01

    目的:探讨Logistic回归和ROC曲线综合分析三种肿瘤标志物对非小细胞肺癌的诊断价值.方法:采用酶联免疫吸附法和电化学发光免疫分析仪(Elecsys2010)分别检测70例非小细胞肺癌(NSCLC)患者及50例肺良性疾病患者外周血中Tumor M2-PK、CEA和CYFRA 21-1的含量. Logistic回归筛选相关指标,并建立相应回归方程,ROC曲线分析临床性能.结果:NSCLC患者Tumor M2-PK、CEA、CYFRA21-1水平明显高于肺良性疾病患者,差异有统计学意义(P<0.01).NSCLC患者三种肿瘤标志物水平与TNM分期密切相关,TNM分期越晚,三种标志物水平也越高.建立回归方程Y=1/[1+EXP(2.256-0.132X1-0.303X2)],新变量Y诊断NSCLC的敏感性、特异性和准确性分别为72.9%、96%和80.8%.结论:Tumor M2-PK可作为NSCLC的一个诊断标志物.运用Logistic回归和ROC曲线综合分析可提高NSCLC诊断的准确性.

  10. Astragalus polysaccharides improve chronic heart failure by promoting myocardial FFA metabolism via AMPK pathway%黄芪多糖对慢性心衰大鼠心肌 AM PK 活性和FFA 代谢的影响

    Institute of Scientific and Technical Information of China (English)

    宋杰; 胡阳黔; 刘坚; 李静

    2015-01-01

    目的:探讨黄芪多糖( APS)对慢性心力衰竭( CHF)大鼠心肌腺苷酸活化蛋白激酶( AMPK)活性和游离脂肪酸( FFA)代谢的影响。方法:32只雄性SD大鼠随机分为4组:正常对照组、假手术组、模型组和APS组,每组8只。采用大鼠左侧冠状动脉结扎术建立心肌梗死后心衰模型。造模成功后, APS 组大鼠给予 APS (3 g· kg-1· d-1)连续灌胃6周。采用心脏超声检测左心室舒张期内径( LVD)、左心室收缩期内径( LVS)、左心室射血分数(LVEF)和短轴缩短率(FS);HE染色观察心肌病理形态学改变;乙酰辅酶A合成酶-乙酰辅酶A氧化酶法( ACS-ACOD)检测血清及心肌FFA浓度;Western blotting法测大鼠心肌总AMPK、磷酸化AMPK( p-AMPK)、脂肪酸转位酶(FAT/CD36)和肉毒碱软脂酰转移酶-1(CPT-1)的蛋白表达情况。结果:假手术组与对照组比较各项指标无显著差异。模型组较对照组LVEF和FS显著降低( P<0.05)而LVD和LVS显著增加( P<0.05)。 APS组LVEF和FS较模型组明显改善(P<0.05)并且LVD和LVS较模型组明显减小(P<0.05)。 HE染色显示模型组较对照组心肌坏死灶增加,残余心肌细胞减少;而APS组较模型组心肌坏死灶减少,残余心肌细胞增多。模型组血清及心肌FFA浓度较对照组明显增加(P<0.05);APS组血清及心肌FFA浓度较模型组明显减少(P<0.05)。模型组p-AMPK、CPT-1和细胞膜FAT/CD36表达较对照组显著减少(P<0.05);而与模型组相比APS组p-AMPK、CPT-1和细胞膜FAT/CD36表达明显增加( P<0.05)。结论:APS可能通过激活慢性心衰大鼠AMPK相关通路促进心肌摄取利用FFA,从而改善慢性心衰。%AIM:To investigate the effect of Astragalus polysaccharides ( APS) on chronic heart failure and its mechanism.METHODS:Male SD rats (n=32) were randomly divided into control group , sham group, model group and APS group (8 rats in each group).The left coronary artery ligation in the rats was conducted to establish myocardial infarc -tion heart failure model.After modeling, the rats in APS group were given APS (3 g· kg-1· d-1) by intragastric adminis-tration for 6 weeks.Left ventricular diastolic diameter (LVD), left ventricular systolic diameter (LVS), left ventricular ejection fraction ( LVEF) and fractional shortening ( FS) were detected by echocardiography .HE staining was used to ob-serve the pathological changes .The concentrations of free fatty acid ( FFA) in the serum and myocardium were observed by the method of acetyl coenzyme A synthetase and acetyl coenzyme A oxidase ( ACS-ACOD ) .The protein levels of total AMP-activated protein kinase (AMPK), phosphorylated AMP-activated protein kinase (p-AMPK), fatty acid translocase (FAT/CD36) and carnitine palmitoyltransferase I (CPT-1) were measured by Western blotting.RESULTS: No signifi-cant difference in each index between sham group and control group was observed .Compared with control group , LVEF and FS in model group was significantly decreased , while LVD and LVS was significantly increased ( P<0.05 ) .The LVEF and FS in APS group were significantly improved compared with model group ( P<0.05 ) , and there was no significant difference between APS group and control group .LVD and LVS in APS group were obviously improved compared with mo-del group (P<0.05), and the difference was significant compared with control group (P<0.05).Compared with control group, focal myocardial necrosis increased , and residual myocardial cells reduced in model group , while those was much better in APS group as compared with model group (P<0.05).The FFA concentrations in the serum and myocardium in model group increased significantly compared with control group ( P<0.05 ) , while those decreased significantly in APS group as compared with model group (P<0.05).The protein levels of p-AMPK, CPT-1, and cell membrane FAT/CD36 in model group decreased significantly compared with control group (P<0.05), and those in APS group increased obvious-ly compared with control group (P<0.05).CONCLUSION:APS improves chronic heart failure by activating the AMPK pathway and promoting myocardial ingestion and utiliation of FFA .

  11. Surgeons' vision rewarded.

    Science.gov (United States)

    Baillie, Jonathan

    2010-08-01

    Surgeons and clinical staff, theatre circulation and scrub personnel, and anaesthetists, as well as the estates and facilities team at Kent's Maidstone Hospital, have worked with specialist supplier of integrated audio, video, and instrumentation systems for the operating room, Olympus Medical, to develop what is claimed is among the UK's most advanced operating theatres yet built for laparoscopic and endoscopic surgery. HEJ editor Jonathan Baillie discussed the project with Amir Nisar, the surgeon who championed efforts to get the facility built, and Olympus Medical national sales manager, systems integration, James Watts. PMID:20839526

  12. MOLA Global roughness map of Mars

    Science.gov (United States)

    2000-01-01

    The median of slopes in 35-km windows indicate the typical roughness on 300-meter baselines. The rougher nature of the heavily cratered terrain in the Southern Hemisphere is apparent, as well as that of Valles Marineris (12S, 289E) canyon walls and the Olympus Mons (18N, 227E) aureole deposits. The Northern Lowlands are smooth, especially Amazonis Planitia (16N, 202E), a region to the west of Olympus Mons, were typical median slopes on these baselines are often smaller than 0.1 degree. A shaded relief map of the topography is overlaid is monochrome.

  13. Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration

    Science.gov (United States)

    Gordon, Richard; Neal, Matthew L.; Luo, Jie; Langley, Monica R.; Harischandra, Dilshan S.; Panicker, Nikhil; Charli, Adhithiya; Jin, Huajun; Anantharam, Vellareddy; Woodruff, Trent M.; Zhou, Qun-Yong; Kanthasamy, Anumantha G.; Kanthasamy, Arthi

    2016-01-01

    Prokineticin-2 (PK2), a recently discovered secreted protein, regulates important physiological functions including olfactory biogenesis and circadian rhythms in the CNS. Interestingly, although PK2 expression is low in the nigral system, its receptors are constitutively expressed on nigrostriatal neurons. Herein, we demonstrate that PK2 expression is highly induced in nigral dopaminergic neurons during early stages of degeneration in multiple models of Parkinson's disease (PD), including PK2 reporter mice and MitoPark mice. Functional studies demonstrate that PK2 promotes mitochondrial biogenesis and activates ERK and Akt survival signalling pathways, thereby driving neuroprotection. Importantly, PK2 overexpression is protective whereas PK2 receptor antagonism exacerbates dopaminergic degeneration in experimental PD. Furthermore, PK2 expression increased in surviving nigral dopaminergic neurons from PD brains, indicating that PK2 upregulation is clinically relevant to human PD. Collectively, our results identify a paradigm for compensatory neuroprotective PK2 signalling in nigral dopaminergic neurons that could have important therapeutic implications for PD. PMID:27703142

  14. THE MAXIMUM AND MINIMUM DEGREES OF RANDOM BIPARTITE MULTIGRAPHS

    Institute of Scientific and Technical Information of China (English)

    Chen Ailian; Zhang Fuji; Li Hao

    2011-01-01

    In this paper the authors generalize the classic random bipartite graph model, and define a model of the random bipartite multigraphs as follows: let m=m(n) be a positive integer-valued function on n and (n, m; {pk}) the probability space consisting of all the labeled bipartite multigraphs with two vertex sets A={a1,a2,...,an} and B= {b1, b2,..., bm}, in which the numbers taibj of the edges between any two vertices ai∈A and bj∈B are identically distributed independent random variables with distribution P{taibj}=k}=pk, k=0, 1, 2,..., where pk≥0 and ∑ pk=1. They obtain that Xc,d,A, the number of vertices in A with degree between c and d of Gn,m∈ (n, m;{Pk}) has asymptotically Poisson distribution, and answer the following two questions about the space (n,m; {pk}) with {pk} having geometric distribution, binomial distribution and Poisson distribution, respectively. Under which condition for {Pk} can there be a function D(n) such that almost every random multigraph Gnm∈ (n, m; {pk}) has maximum degree D(n) in A? under which condition for {pk} has almost every multigraph Gn,m∈ (n,m;{pk}) a unique vertex of maximum degree in A?

  15. Prokineticin 2 facilitates mechanical allodynia induced by α,β-methylene ATP in rats.

    Science.gov (United States)

    Ren, Cuixia; Qiu, Chun-Yu; Gan, Xiong; Liu, Ting-Ting; Qu, Zu-Wei; Rao, Zhiguo; Hu, Wang-Ping

    2015-11-15

    Prokineticin 2 (PK2), a new chemokine, causes mechanical hypersensitivity in the rat hind paw, but little is known about the molecular mechanism. Here, we have found that ionotropic P2X receptor is essential to mechanical allodynia induced by PK2. First, intraplantar injection of high dose (3 or 10 pmol) of PK2 significantly increased paw withdrawal response frequency (%) to innocuous mechanical stimuli (mechanical allodynia). And the mechanical allodynia induced by PK2 was prevented by co-administration of TNP-ATP, a selective P2X receptor antagonist. Second, although low dose (0.3 or 1 pmol) of PK2 itself did not produce an allodynic response, it significantly facilitated the mechanical allodynia evoked by intraplantar injection of α,β-methylene ATP (α,β-meATP). Third, PK2 concentration-dependently potentiated α,β-meATP-activated currents in rat dorsal root ganglion (DRG) neurons. Finally, PK2 receptors and intracellular signal transduction were involved in PK2 potentiation of α,β-meATP-induced mechanical allodynia and α,β-meATP-activated currents, since the potentiation were blocked by PK2 receptor antagonist PKRA and selective PKC inhibitor GF 109203X. These results suggested that PK2 facilitated mechanical allodynia induced by α,β-meATP through a mechanism involved in sensitization of cutaneous P2X receptors expressed by nociceptive nerve endings.

  16. Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To study the implication of prokineticin 1 (PK1/EG VEGF) and prokineticin 2 (PK2/Bv8) in hepatocellular carcinoma angiogenesis. METHODS: The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF (an angiogenesis marker), vWF (an endothelial cell marker) and to CD68 (a monocyte/macrophage marker). Furthermore, the mRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochemistry and immunocytochemistry.RESULTS:PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/Bv8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC, as expected. In addition, out of all isolated liver cells examined, only Kupffer cells (liver resident macrophages) express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.CONCLUSION:In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.

  17. Image-driven pharmacokinetics: nanomedicine concentration across space and time.

    Science.gov (United States)

    Brill, Dab A; MacKay, J Andrew

    2015-01-01

    Clinical pharmacokinetics (PK) primarily measures the concentration of drugs in the blood. For nanomedicines it may be more relevant to determine concentration within a target tissue. The emerging field of image-driven PK, which utilizes clinically accepted molecular imaging technology, empirically and noninvasively, measures concentration in multiple tissues. Image-driven PK represents the intersection of PK and biodistribution, combining to provide models of concentration across space and time. Image-driven PK can be used both as a research tool and in the clinic. This review explores the history of pharmacokinetics, technologies used in molecular imaging (especially positron emission tomography) and research using image-driven pharmacokinetic analysis. When standardized, image-driven PK may have significant implications in preclinical development as well as clinical optimization of targeted nanomedicines.

  18. The clinical application value of glycosylated hemoglobin(HbA1c) plus fasting plasma glucose in diagnosing diabetes

    Institute of Scientific and Technical Information of China (English)

    程多智

    2012-01-01

    Objective To evaluate clinical application value of HbA1c plus fasting plasma glucose(FPG) in diagnosing diabetes mellitus(DM).Methods 681 patients with DM were enrolled in this study. The level of HbA1c by Bio-RAD-10 glycated hemoglobin analyzer,FPG by OLYMPUS

  19. Training and transfer of colonoscopy skills: a multinational, randomized, blinded, controlled trial of simulator versus bedside training

    NARCIS (Netherlands)

    A. Haycock; A.D. Koch; P. Familiari; F. van Delft; E. Dekker; L. Petruzziello; J. Haringsma; S. Thomas-Gibson

    2010-01-01

    Background: The Olympus colonoscopy simulator provides I high-fidelity training platform designed to develop knowledge and skills in colonoscopy it has the potential to shorten the learning process to competency. Objective: To investigate the efficacy of the simulator in training novices in colonosc

  20. Olympus’s Share in Building a Harmonious Society

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In February,Olympus (Beijing) Sales & Services Co. Ltd. (OCM) was awarded the "Excellent Working Unit in Promoting the Building of a Harmonious Society" by the Beijing Chaoyang District Government. Among more than 100,000 enterprises in Chaoyang District, only 200 won this prize. OCM was awarded this prize for its great contribution to building a harmonious society.

  1. Literature Mining on Pharmacokinetics Numerical Data: A Feasibility Study

    OpenAIRE

    Wang, Zhiping; Kim, Seongho; Quinney, Sara K.; Guo, Yingying; Hall, Stephen D.; Rocha, Luis M; Li, Lang

    2009-01-01

    A feasibility study of literature mining is conducted on drug PK parameter numerical data with a sequential mining strategy. Firstly, an entity template library is built to retrieve pharmacokinetics relevant articles. Then a set of tagging and extraction rules are applied to retrieve PK data from the article abstracts. To estimate the PK parameter population-average mean and between-study variance, a linear mixed meta-analysis model and an E-M algorithm are developed to describe the probabili...

  2. Coaggregation of Prevotella intermedia with oral Actinomyces species.

    OpenAIRE

    Nesbitt, W E; Fukushima, H.; Leung, K P; Clark, W B

    1993-01-01

    Five strains of Prevotella intermedia were examined for their ability to coaggregate with various gram-positive and gram-negative species of oral bacteria. Two of the P. intermedia strains coaggregated with selected Actinomyces species, P. intermedia 27 with Actinomyces viscosus T14V and Actinomyces naeslundii ATCC 12104, PK606, PK984, and PK947, and P. intermedia 113 with Actinomyces odontolyticus WVU 1546 and Actinomyces israelii WVU 838. Exposure of both Prevotella strains but not the Acti...

  3. A Physiologically Based Pharmacokinetic Model to Predict Disposition of CYP2D6 and CYP1A2 Metabolized Drugs in Pregnant Women

    OpenAIRE

    Ke, Alice Ban; Nallani, Srikanth C.; Zhao, Ping; Rostami-Hodjegan, Amin; Isoherranen, Nina; Unadkat, Jashvant D.

    2013-01-01

    Conducting pharmacokinetic (PK) studies in pregnant women is challenging. Therefore, we asked if a physiologically based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women. We refined and verified our previously published pregnancy PBPK model by incorporating cytochrome P450 CYP1A2 suppression (based on caffeine PK) and CYP2D6 induction (based on metoprolol PK) into the model. This model accounts for gestational age–dependent changes in materna...

  4. On malnormal peripheral subgroups in fundamental groups of 3-manifolds

    CERN Document Server

    de la Harpe, Pierre

    2011-01-01

    Let $K$ be a non-trivial knot in the 3-sphere, $E_K$ its exterior, $G_K = \\pi_1(E_K)$ its group, and $P_K = \\pi_1(\\partial E_K) \\subset G_K$ its peripheral subgroup. We show that $P_K$ is malnormal in $G_K$, namely that $gP_Kg^{-1} \\cap P_K = \\{e\\}$ for any $g \\in G_K$ with $g \

  5. Identification of a cAMP-dependent protein kinase in bovine and human follicular fluids.

    Science.gov (United States)

    Yang, L S; Kadam, A L; Koide, S S

    1993-11-01

    A soluble protein kinase (PK) was purified from bovine and human follicular fluids (FF) by ultrafiltration through a PM-10 membrane followed by chromatography on heparin-agarose, DEAE-cellulose and cellulose phosphate columns. The PK phosphorylated calf thymus histones and endogenous FF proteins having estimated Mrs of 40, 62, 128 and 180 KD. cAMP enhanced PK activity; whereas protein kinase A (PKA)-inhibitor peptide blocked the activity. The present findings suggest that the enzyme is a cAMP-dependent PK. PMID:8118427

  6. Calculation of constants of acid-base equilibria at the oxide-electrolyte interface from electrokinetic potential dependence on pH

    International Nuclear Information System (INIS)

    Method is proposed for calculating the constants of acid-base equilibria at the oxide-electrolyte interface. The method is based on the electrokinetic potential dependence on ph value at different electrolyte concentrations. It is shown that the calculated constant values for La2O3 and ZrO2 equal correspondingly 7.3 and 3.9 (pK10); 11.9 and 9.1 (pK20); 9.2 and 5.8 (pK30); 10.0 and 7.2 (pK40) agree well with literature data. 21 refs.; 3 figs.; 3 tabs

  7. The role of DNA dependent protein kinase in synapsis of DNA ends

    OpenAIRE

    Weterings, Eric; Verkaik, Nicole; Brüggenwirth, Hennie; Gent, Dik; Hoeijmakers, Jan

    2010-01-01

    textabstractDNA dependent protein kinase (DNA-PK) plays a central role in the non-homologous end-joining pathway of DNA double strand break repair. Its catalytic subunit (DNA-PK(CS)) functions as a serine/threonine protein kinase. We show that DNA-PK forms a stable complex at DNA termini that blocks the action of exonucleases and ligases. The DNA termini become accessible after autophosphorylation of DNA-PK(CS), which we demonstrate to require synapsis of DNA ends. Interestingly, the presence...

  8. Zero-Knowledge Proofs with Low Amortized Communication from Lattice Assumptions

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; López-Alt, Adriana

    2012-01-01

    We construct zero-knowledge proofs of plaintext knowledge (PoPK) and correct multiplication (PoPC) for the Regev encryption scheme with low amortized communication complexity. Previous constructions of both PoPK and PoPC had communication cost linear in the size of the public key (roughly quadrat...

  9. Verification of the Firoozbakht conjecture for primes up to four quintillion

    OpenAIRE

    Kourbatov, Alexei

    2015-01-01

    If $p_k$ is the k-th prime, the Firoozbakht conjecture states that the sequence $(p_k)^{1/k}$ is strictly decreasing. We use the table of first-occurrence prime gaps in combination with known bounds for the prime-counting function to verify the Firoozbakht conjecture for primes up to four quintillion $(4\\times10^{18})$.

  10. Effects of lead nitrate on the activity of metabolic enzymes during early developmental stages of the African catfish, Clarias gariepinus (Burchell, 1822)

    NARCIS (Netherlands)

    Osman, A.G.M.; Mekkawy, Imam A.; Verreth, J.A.J.; Kirschbaum, Frank

    2007-01-01

    Glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase (LDH) and pyruvate kinase (PK) are key metabolic enzymes. G6PDH has been used as a biomarker of pollution-induced carcinogenesis in fish. LDH has been used as marker of lesions in toxicology and clinical chemistry, and PK catalyses the

  11. Assessment of in vitro high throughput pharmacokinetic data to predict in vivo pharmacokinetic data of environmental chemicals

    Science.gov (United States)

    Assessing the health risks of the thousands of chemicals in use requires both toxicology and pharmacokinetic (PK) data that can be generated more quickly. For PK, in vitro clearance assays with hepatocytes and serum protein binding assays provide a means to generate high throughp...

  12. Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

    Science.gov (United States)

    Despite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7(MK-7) on the rate of bone loss in o...

  13. Pharmacokinetic-pharmacodynamic modeling of activity of ceftazidime during continuous and intermittent infusion

    NARCIS (Netherlands)

    J.W. Mouton (Johan); A.A. Vinks; N.C. Punt

    1997-01-01

    textabstractWe developed and applied pharmacokinetic-pharmacodynamic (PK-PD) models to characterize in vitro bacterial rate of killing as a function of ceftazidime concentrations over time. For PK-PD modeling, data obtained during continuous and intermittent infusion of

  14. Individualized conditioning regimes in cord blood transplantation : Towards improved and predictable safety and efficacy

    NARCIS (Netherlands)

    Admiraal, R; Boelens, J J

    2016-01-01

    INTRODUCTION: The conditioning regimen used in cord blood transplantation (CBT) may significantly impact the outcomes. Variable pharmacokinetics (PK) of drugs used may further influence outcome. Individualized dosing takes inter-patient differences in PK into account, tailoring drug dose for each in

  15. Influence of Erroneous Patient Records on Population Pharmacokinetic Modeling and Individual Bayesian Estimation

    NARCIS (Netherlands)

    van der Meer, Aize Franciscus; Touw, Daniel J.; Marcus, Marco A. E.; Neef, Cornelis; Proost, Johannes H.

    2012-01-01

    Background: Observational data sets can be used for population pharmacokinetic (PK) modeling. However, these data sets are generally less precisely recorded than experimental data sets. This article aims to investigate the influence of erroneous records on population PK modeling and individual maxim

  16. Bounds for Eigenvalues of the Fan Product of Matrices%矩阵Fan积特征值的界

    Institute of Scientific and Technical Information of China (English)

    朱雪芳

    2012-01-01

    设Zn为非对角元素都为非正实数的n阶方阵的集合,令Ak∈Zn,k∈{1,…,m),给出矩阵Fan积最小特征值的一个新下界,τ(A1★…★Am)≥min1≤i≤n{m∏ k=1Ak(i,i)-m∏k=1 [Ak(i,.i)pk -τ(A[pk]k)]1/pk}其中pk >0且m∑k=11/pk≥1,这个下界改进了文献中的相关结果.%Denote by Zn the class of all n x n real matrices all of whose off-diagonal entries are nonpositive.Let Ak ∈Zn, where k ∈{1, …, m}.We present a new bound for the minimum eigenvalue of Fan product of matrices.T(A1 ★ …★Am)≥min/1≤I≤n{m/II/k=1/Ak(I,I)-m/II/k=1[Ak(I,I)Pk-T(A[Pk]/k)1/Pk}where pk>0 and m∑k=1/1/Pk≥1. This bound improve the corresponding results in the literature.

  17. Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

    Science.gov (United States)

    Schell, Ryan F.; Sidone, Brian J.; Caron, Whitney P.; Walsh, Mark D.; Zamboni, Beth A.; Ramanathan, Ramesh K.; Zamboni, William C.

    2013-01-01

    Purpose A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Methods Inter-patient PK variability of 9 liposomal and SM formulations of the same drug were evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). Results CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R2 = 0.39). PK variability of liposomal agents was greater when evaluated from 0–336 h compared with 0–24 h. Conclusion PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents needs to be evaluated. PMID:23891988

  18. Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

    Science.gov (United States)

    Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

    2014-08-01

    Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.

  19. Latanoprost systemic exposure in pediatric and adult patients with glaucoma

    DEFF Research Database (Denmark)

    Raber, Susan; Courtney, Rachel; Maeda-Chubachi, Tomoko;

    2011-01-01

    To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose.......To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose....

  20. Evaluation of [C-11]-DAA1106 for imaging and quantification of neuro inflammation in a rat model of herpes encephalitis

    NARCIS (Netherlands)

    Doorduin, Janine; Klein, Hans C.; de Jong, Johan R.; Dierckx, Rudi A.; de Vries, Erik. F. J.

    2010-01-01

    Introduction: Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [C-11]-PK11195 can be used to study neuroinflammation in these disorders. However; [C-11]-PK11195 may not be sensitive enough to visualize mild neuroinflammation.

  1. Unigene BLAST: CBRC-GGAL-09-0012 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-09-0012 gnl|UG|Gga#S6698203 pnl1s.pk003.f8 chicken liver cDNA library Gallus gallus cDNA clone pnl...1s.pk003.f8 5' similar to histidine-rich glycoprotein - bovine (fragments), mRNA sequence /clone=pnl

  2. PRKDC mutations associated with immunodeficiency, granuloma, and autoimmune regulator-dependent autoimmunity

    NARCIS (Netherlands)

    A.-L. Mathieu (Anne-Laure); E. Verronese (Estelle); G.I. Rice (Gillian I.); F. Fouyssac (Fanny); Y. Bertrand (Yves); C. Picard (Capucine); M. Chansel (Marie); J.E. Walter (Jolan E.); L.D. Notarangelo (Luigi Daniele); M.J. Butte (Manish J.); K.C. Nadeau (Kari Christine); K. Csomos (Krisztian); D.J. Chen (David); K. Chen (Karin); A. Delgado (Ana); C. Rigal (Chantal); C. Bardin (Christine); C. Schuetz (Catharina); D. Moshous (Despina); H. Reumaux (Héloïse); F. Plenat (François); A. Phan (Alice); M.-T. Zabot (Marie-Thérèse); B. Balme (Brigitte); S. Viel (Sébastien); J. Bienvenu (Jacques); P. Cochat (Pierre); M. van der Burg (Mirjam); C. Caux (Christophe); E.H. Kemp (E. Helen); I. Rouvet (Isabelle); C. Malcus (Christophe); J.-F. Méritet (Jean-Francois); A. Lim (Annick); Y.J. Crow (Yanick J.); N. Fabien (Nicole); C. Ménétrier-Caux (Christine); J.-P. De Villartay (Jean-Pierre); T. Walzer (Thierry); A. Belot (Alexandre)

    2015-01-01

    textabstractBackground PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription f

  3. Moxifloxacin dosing in post-bariatric surgery patients

    NARCIS (Netherlands)

    Colin, Pieter; Eleveld, Douglas J.; Struys, Michel M. R. F.; T'Jollyn, Huybrecht; Van Bortel, Luc M.; Ruige, Johannes; De Waele, Jan; Van Bocxlaer, Jan; Boussery, Koen

    2014-01-01

    Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin

  4. Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Nekka Fahima

    2009-06-01

    Full Text Available Abstract Background Pharmacokinetic and pharmacodynamic (PK/PD indices are increasingly being used in the microbiological field to assess the efficacy of a dosing regimen. In contrast to methods using MIC, PK/PD-based methods reflect in vivo conditions and are more predictive of efficacy. Unfortunately, they entail the use of one PK-derived value such as AUC or Cmax and may thus lead to biased efficiency information when the variability is large. The aim of the present work was to evaluate the efficacy of a treatment by adjusting classical breakpoint estimation methods to the situation of variable PK profiles. Methods and results We propose a logical generalisation of the usual AUC methods by introducing the concept of "efficiency" for a PK profile, which involves the efficacy function as a weight. We formulated these methods for both classes of concentration- and time-dependent antibiotics. Using drug models and in silico approaches, we provide a theoretical basis for characterizing the efficiency of a PK profile under in vivo conditions. We also used the particular case of variable drug intake to assess the effect of the variable PK profiles generated and to analyse the implications for breakpoint estimation. Conclusion Compared to traditional methods, our weighted AUC approach gives a more powerful PK/PD link and reveals, through examples, interesting issues about the uniqueness of therapeutic outcome indices and antibiotic resistance problems.

  5. Loss asymptotics for the single-server queue with complete rejection

    NARCIS (Netherlands)

    Zwart, A.P.

    2015-01-01

    Consider the single-server queue in which customers are rejected if their total sojourn time would exceed a certain level K. A basic performance measure of this system is the probability PK that a customer gets rejected in steady state. This paper presents asymptotic expansions for PK as K ... If

  6. Dose individualization in PharmDIS-e

    NARCIS (Netherlands)

    Proost, JH; Punt, NC

    2003-01-01

    Individualized dosage regimen calculations require knowledge on the pharmacokinetic and pharmacodynamic properties of the drug and the characteristics of the patient. A PK-PD-based dosage regimen is not easily and generally applicable, mainly because the combination of available PK parameters and th

  7. Mass Spectrometric Approaches to Detecting and Quantifying Prions

    Science.gov (United States)

    Prions are infectious proteins that replicate by converting a normal cellular protein (PrPC)into a prion. Although prions and PrPC are isoforms, they have dramatically different physicochemical properties. Prions are resistant to proteinase K (PK) degradation, while PrPC is completely degraded by PK...

  8. Isolation and characterization of a proteinase K sensitive PrPSc fraction

    Science.gov (United States)

    Recent studies have shown that a sizeable fraction of PrPSc present in prion-infected tissues is,contrary to previous conceptions, sensitive to digestion by proteinase K (PK). This finding has important implications in the context of diagnosis of prion disease, as PK has been extensively used in att...

  9. The Prospect of an "A" in STEM Education

    Science.gov (United States)

    Daugherty, Michael K.

    2013-01-01

    STEM education has since become perhaps the largest reform movement in PK-12 education over the last decade. The rationale for increased emphasis in STEM education is driven largely by lackluster national assessments of PK-12 students over the last decade or two. These assessments continue to indicate that the United States is failing to compete…

  10. Pediatric Clinical Pharmacology of Voriconazole: Role of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacotherapy.

    Science.gov (United States)

    Kadam, Rajendra S; Van Den Anker, Johannes N

    2016-09-01

    Voriconazole is a potent antifungal agent used for the treatment of invasive fungal infections caused by Aspergillus and Candida species in adult and pediatric patients. Voriconazole has a narrow therapeutic index and a large intra- and inter-individual pharmacokinetics (PK) variability. Several factors including non-linear PK, age, body weight, cytochrome P450 2C19 genotype, concomitant drugs, liver function, and food are responsible for the large variability in voriconazole PK. A combination of a narrow therapeutic index with a large PK variability results in treatment failure in many patients at clinically recommended doses. There is an urgent need to establish an optimal dosing regimen for pediatric patients 60 %) treatment failure rates. Therapeutic drug monitoring is commonly used in clinical practice to optimize the voriconazole dosing regimens in pediatric patients, but it is associated with several practical limitations. Implementation of a PK model-guided individualized dose selection will help in reducing the PK variability and will improve therapeutic outcomes. In this review, we have summarized the covariates influencing the PK of voriconazole in adult and pediatric patients, emphasizing that the clearance of voriconazole is significantly different between adult and pediatric patients owing to developmental changes in the major clearance pathways. Moreover, we have provided the limitations of the current dosing regimens and have proposed a new dosing method using a PK model-guided dose individualization of voriconazole in pediatric patients.

  11. PET Centre and Centre for Functionally Integrative Neuroscience, Aarhus University

    DEFF Research Database (Denmark)

    Cumming, Paul; Pedersen, Mads Damgaard; Minuzzi, Luciano;

    2006-01-01

    The cerebral distribution of peripheral-type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 bin...

  12. Gamma irradiation of barley seeds and its effect on ionic contents in plants differing in salt tolerance

    International Nuclear Information System (INIS)

    In a field experiment, seeds of two barley varieties Arabi Abiad (AA) and Pakistani PK 30163 (PK) were irradiated with a 15 Gy dose of gamma irradiation, and sown on a saline soil (16.4-18.7 dS/m) and irrigated with a saline water (7.8 dS/m). At physiological maturity stage, gamma irradiation increased shoots dry weight of AA variety. Dose of 15 Gy had a negative effect on k+ and Na+ contents in plants of the PK variety; however, Mg++ and K+ contents of AA variety were increased. Gamma irradiation decreased the Σ cations and the Σ cations-Na+ in plants of the PK variety, and increased the Σ cations-Na+ of the AA variety. Moreover, it has positively affected both Ca++/Na+ ratio of PK variety and K+/Na+ ratio of AA variety. Ratio of Na+/Cl- of both varieties was smaller than one. (author)

  13. Potassium dynamics are attenuated in hyperkalemia and a determinant of QT adaptation in exercising hemodialysis patients

    DEFF Research Database (Denmark)

    Tran, Cao Thach; Bundgaard, Henning; Ladefoged, Søren Daustrand;

    2013-01-01

    Disturbances in plasma potassium concentration (pK) are well known risk factors for the development of cardiac arrhythmia. The aims of the present study were to evaluate the effect of hemodialysis on exercise pK dynamics and QT hysteresis, and whether QT hysteresis is associated with the p......K decrease following exercise. Twenty-two end-stage renal disease patients exercised on a cycle ergometer with incremental work load before and after hemodialysis. ECG was recorded and pK was measured during exercise and recovery. During exercise, pK increased from 5.1 ± 0.2 to 6.1 ± 0.2 mM (mean ± SE; P...

  14. Detection of prominent left anterior descending coronary artery stenosis for patients with stable angina using Doppler tissue echocardiography.

    Science.gov (United States)

    Veyrat, Colette; Larrazet, Fabrice; Cohen, Laurent; Laborde, François; Pellerin, Denis

    2005-08-01

    The midseptum has an elective left anterior descending coronary artery (LAD) supply. Septal peak velocity (PkV) and myocardial velocity gradient (MVG) were studied at rest with M-mode Doppler tissue echocardiography during the cardiac cycle including the septal active relaxation (SAR) outward wall motion preceding isovolumic relaxation. In all, 33 patients had significant multivessel coronary artery disease. Group A (15 patients) had prominent LAD stenosis. Group B (18 patients) had prominent circumflex (15) or right (3) coronary artery stenoses. The goal was to detect a prominent LAD stenosis. During SAR, sensitivity to detect a prominent LAD stenosis was 86% for PkV PkV PkV and 0.80 for MVG during systole. In multivessel coronary artery disease, SAR variables better identified a prominent LAD stenosis than systolic variables. Moreover, SAR PkVs were informative per se, whereas systole required MVG calculation. PMID:16084334

  15. Purification and characterization of a Ca2+ -dependent/calmodulin-stimulated protein kinase from moss chloronema cells

    Indian Academy of Sciences (India)

    Jacinta S D’souza; Man Mohan Johri

    2003-03-01

    We have demonstrated the presence of a Ca2+-dependent/calmodulin-stimulated protein kinase (PK) in chloronema cells of the moss Funaria hygrometrica. The kinase, with a molecular mass of 70,000 daltons (PK70), was purified to homogeneity using ammonium sulphate fractionation, DEAE-cellulose chromatography, and calmodulin (CaM)-agarose affinity chromatography. The kinase activity was stimulated at a concentration of 50 M free Ca2+, and was further enhanced 3–5-fold with exogenously added 3–1000 nm moss calmodulin (CaM). Autophosphorylation was also stimulated with Ca2+ and CaM. Under in vitro conditions, PK70 phosphorylated preferentially lysine-rich substrates such as HIIIS and HVS. This PK shares epitopes with the maize Ca2+-dependent/calmodulin-stimulated PK (CCaMK) and also exhibits biochemical properties similar to the maize, lily, and tobacco CCaMK. We have characterized it as a moss CCaMK.

  16. Functional analysis of the kinome of the wheat scab fungus Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Chenfang Wang

    2011-12-01

    Full Text Available As in other eukaryotes, protein kinases play major regulatory roles in filamentous fungi. Although the genomes of many plant pathogenic fungi have been sequenced, systematic characterization of their kinomes has not been reported. The wheat scab fungus Fusarium graminearum has 116 protein kinases (PK genes. Although twenty of them appeared to be essential, we generated deletion mutants for the other 96 PK genes, including 12 orthologs of essential genes in yeast. All of the PK mutants were assayed for changes in 17 phenotypes, including growth, conidiation, pathogenesis, stress responses, and sexual reproduction. Overall, deletion of 64 PK genes resulted in at least one of the phenotypes examined, including three mutants blocked in conidiation and five mutants with increased tolerance to hyperosmotic stress. In total, 42 PK mutants were significantly reduced in virulence or non-pathogenic, including mutants deleted of key components of the cAMP signaling and three MAPK pathways. A number of these PK genes, including Fg03146 and Fg04770 that are unique to filamentous fungi, are dispensable for hyphal growth and likely encode novel fungal virulence factors. Ascospores play a critical role in the initiation of wheat scab. Twenty-six PK mutants were blocked in perithecia formation or aborted in ascosporogenesis. Additional 19 mutants were defective in ascospore release or morphology. Interestingly, F. graminearum contains two aurora kinase genes with distinct functions, which has not been reported in fungi. In addition, we used the interlog approach to predict the PK-PK and PK-protein interaction networks of F. graminearum. Several predicted interactions were verified with yeast two-hybrid or co-immunoprecipitation assays. To our knowledge, this is the first functional characterization of the kinome in plant pathogenic fungi. Protein kinase genes important for various aspects of growth, developmental, and infection processes in F. graminearum were

  17. Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Saleh, Soundos; Becker, Corina; Frey, Reiner; Mück, Wolfgang

    2016-03-01

    This analysis aimed to characterize the pharmacokinetics (PK) and PK/pharmacodynamic (PK/PD) relationship of riociguat and its metabolite M1 in patients with chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH). Blood samples were collected in two phase 3 studies-PATENT-1 (Pulmonary Arterial Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1; 12 weeks; PAH) and CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1; 16 weeks; CTEPH)-and long-term extensions. Patients were initially randomized to receive placebo or riociguat, and they received riociguat in the extensions. Nonlinear mixed-effects modeling was used to develop a population PK model describing riociguat PK. PK/PD relationships were investigated by comparing derived PK parameters with changes in PD parameters. Covariate analyses included smoking status, bosentan comedication, bilirubin levels, and baseline creatinine clearance. The PK of riociguat/M1 was described by a one-compartment model. Mean population estimates for riociguat absorption rate constant, clearance, and volume of distribution were 2.17/h, 1.81 L/h, and 32.3 L, respectively; for M1 they were 0.258/h, 3.16 L/h, and 124 L. Interindividual variability was moderate for riociguat and moderate to high for M1. There was no evidence of time- or dose-dependent changes in riociguat/M1 PK. Riociguat clearance was higher in smokers (120% increase) and bosentan-treated patients (36% increase) than in nonsmokers and those not receiving bosentan. There was an inverse correlation between bilirubin and riociguat clearance. In PK/PD analyses, 6-minute walk distance was related to hemodynamic parameters, particularly pulmonary vascular resistance. Riociguat PK were described by a one-compartment model. Effects of covariates on riociguat and M1 PK were established, and a PK/PD relationship was demonstrated. (ClinicalTrials.gov identifiers: PATENT-1, NCT00810693

  18. Subcellular localization of PS1 based on PS1/GFP fusing protein

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Mutations in presenilin 1 (PS1) gene are closely associated with the early onset of familial Alzheimer's disease (EOFAD). The fusion genes, GFP-PS1 (recombinant plasmid pEGFP-C1-PS1) and PS1-GFP (recombinant plasmid pEGFP-N2-PS1) were constructed to study the subcellular localization of PS1 holoprotein. Recombinant plasmids were transiently transfected into two cell lines, HEK293 and CHO, respectively, using the green fluorescence from GFP (green fluorescence protein) as the PS1 localization signal. Then, we observed green fluorescence with a SPOT Ⅱ (Olympus, BH2) and CONFOCAL microscope (Olympus, FV300) under 488 nm. The results show that PS1 located on the nuclear envelope. A few can be found on the cellular membrane and in the cytosol in a non-homogeneous distribution.

  19. Impact of dredging on water quality and group diversity of marine zooplankton during construction and reclaimation activities of new berths at Mormugao Harbour, Goa.

    Digital Repository Service at National Institute of Oceanography (India)

    Snigdha

    ) profiler Plate 5 : Collection of Water Samples By Niskin Water Sampler Plate 6 : Heron Trantor Net Plate 7 : Turner Designs Fluorometer Plate 8 : Chlorophyll Analysis Plate 9 : Folsom Splitter Plate 10 : Splitting the samples Plate 11 : Olympus Research... ?animal? food. Phytoplankton functions best, it seems, only as ?baby food? for many zooplankton species, therefore a vigorous population growth cannot be expected if that is the only food that is provided in abundance. The density of an organism depends...

  20. The relationship between volatile halocarbons and phytoplankton pigments during a Trichodesmium bloom in the coastal eastern Arabian Sea

    Digital Repository Service at National Institute of Oceanography (India)

    Roy, R.; Pratihary, A.; Narvenkar, G.; Mochemadkar, S.; Gauns, M.; Naqvi, S.W.A.

    chamber and examining through an Olympus inverted microscope (magnification 100-200X). Generic and species identifications were done according to various taxonomic keys following Subrahmanyam (1959), Lebour (1978) and Tomas (1996). 3. Result 3... hydrocarbons in the ocean, Journal of Geophysical Research 97, 12683-12687. Kononen, K., Leppänen, J-M., 1997. Patchiness, scales and controlling mechanisms of cyanobacterial blooms in the Baltic Sea: Application of a multiscale research strategy. In...

  1. Apply Web-based Analytic Tool and Eye Tracking to Study The Consumer Preferences of DSLR Cameras

    OpenAIRE

    Jih-Syongh Lin; Shih-Yen Huang

    2013-01-01

    Consumer’s preferences and purchase motivation of products often lie in the purchasing behaviors generated by the synthetic evaluation of form features, color, function, and price of products. If an enterprise can bring these criteria under control, they can grasp the opportunities in the market place. In this study, the product form, brand, and prices of five DSLR digital cameras of Nikon, Lumix, Pentax, Sony, and Olympus were investigated from the image evaluation and eye tracking. The web-...

  2. Biomarkers of environmental contaminants in field population of green mussel (Perna viridis) from Karnataka-Kerala coast (South West coast of India).

    OpenAIRE

    Krishnakumar, P.K.; Sasikumar, Geetha; Bhat, G. S.; Asokan, D.P.K.

    2006-01-01

    Biomarker: sister chromatid exchange (SCE); chromosomal aberration; micronucleus (MN); hemic neoplasia (HN), mutagenic activity; comet cells. Exposure/effect represented: exposure to trace metals (Fe, Cu, Ni, Cd, Cr, Zn, Pb, Mn) / DNA damage. Analytical technique: Toxic and essential elements in tissues were determined using AAS; metaphase chromosomes were viewed using light microscope (Olympus BX50) with image analysis facility; hemolymph was stained using the Schiff Feulgen-picromethyl blu...

  3. DESY. Scientific annual report 2009; DESY. Wissenschaftlicher Jahresbericht 2009

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-15

    The following topics are dealt with: Research with HERA and LHC, developments for the ILC, elementary-particle theory, astroparticle physics, the DESY Grid center, the ALPS experiment for the search for very light unknown particles decaying into {gamma}{gamma}, the OLYMPUS experiment, experiments with synchrotron radiation at DORIS III and PETRA III, developments of FLASH and the European XFEL, the DESY accelerators, national and international collaboration, electronics development, speeches and publications. (HSI)

  4. DESY. Scientific annual report 2009

    International Nuclear Information System (INIS)

    The following topics are dealt with: Research with HERA and LHC, developments for the ILC, elementary-particle theory, astroparticle physics, the DESY Grid center, the ALPS experiment for the search for very light unknown particles decaying into γγ, the OLYMPUS experiment, experiments with synchrotron radiation at DORIS III and PETRA III, developments of FLASH and the European XFEL, the DESY accelerators, national and international collaboration, electronics development, speeches and publications. (HSI)

  5. Transumbilical laparoendoscopic single-site total mesorectal excision for rectal carcinoma

    OpenAIRE

    Michalik, Maciej; Bobowicz, Maciej; Frask, Agata; Orlowski, Michał

    2012-01-01

    In recent years, multiple studies have proved laparoscopic total mesorectal excision (TME) to be as safe and as effective in rectal cancer treatment as open surgery, with the undeniable benefit of perioperative trauma reduction. Decreasing the number of incisions and performing single-port surgery could have further reduced the trauma. A new access device, QuadPort™ Olympus, enables operations from just one small transumbilical incision, leaving a barely visible scar afterwards. This is one o...

  6. Nye metoder ved gastrointestinal endoskopi

    DEFF Research Database (Denmark)

    Stigaard, Trine; Meisner, Søren

    2010-01-01

    The development of diagnostic and therapeutic flexible endoscopy is vivid. This article describes some of the most recent diagnostic techniques: Narrow Band Imaging, Fujinon Intelligent Color Enhancement, Autofluorescence Imaging, Optical Coherence Tomography, Confocal Laser Endomicroscopy....... Literature was found through searches on PUBMED and written information from Olympus, Fujinon and Pentax. Which techniques will be used in the future? Will optical biopsy soon be possible? We need more controlled studies....

  7. Design and Performance of a Lead Fluoride Detector as a Luminosity Monitor

    OpenAIRE

    Benito, Roberto Pérez; Khaneft, Dmitry; O'Connor, Colton; Capozza, Luigi; Diefenbach, Jürgen; Gläser, Boris; Ma, Yue; Maas, Frank; Piñeiro, David Rodríguez

    2016-01-01

    Precise luminosity measurements for the OLYMPUS two-photon exchange experiment at DESY were performed by counting scattering events with alternating beams of electrons and positrons incident on atomic electrons in a gaseous hydrogen target. Final products of M{\\o}ller, Bhabha, and pair annihilation interactions were observed using a pair of lead fluoride Cherenkov calorimeters with custom housings and electronics, adapted from a system used by the A4 parity violation experiment at MAMI. This ...

  8. Концепція системи оздоровчого (функціонального) харчування у фітнесі

    OpenAIRE

    Tsyganenko O.I.

    2011-01-01

    The literature analysis on the organization of an improving food in fitness is carried out. The concept of system of an improving (functional) food in fitness is developed. The concept includes the purpose and problems of system of an improving food in fitness, principles of its organization, conceptual approaches to the organization of an improving food in fitness. For information support of work of system it is recommended to use the computer program "Olympus".

  9. M-scope Endoscope is Superior to Traditional Endoscope for NOTES Procedures

    Institute of Scientific and Technical Information of China (English)

    LI Wen; SUN Gang; WANG Xiang-dong; XIAO Jian-guo; SUN Guo-hui; HUANG Xue-fei; Kantsevoy,Sergey V.

    2008-01-01

    @@ Background:Currently used regular dual channel endoscope was designed only for intralumenal Use inside the GI tract.Recently developed M-scope endoscope(GIF一2TQ260M,Olympus Optical LTD,Tokyo,Japan)has advantage of multibending option of its distal tip,which may be very useful for Natural Orifice Translumenal Endoscopic Surgery (NOTES) procedures inside the peritoneal cavity.

  10. Editorial: Supply Chain Management

    OpenAIRE

    Aidonis, D.; Folinas, D.; Triantafillou, D.

    2012-01-01

    This special issue has followed up the 2nd Olympus International Conference on Supply Chains held on October 5-6, 2012, in Katerini, Greece. The Conference was organized by the Department of Logistics of Alexander Technological Educational Institution (ATEI) of Thessaloniki, in collaboration with the Laboratory of Quantitative Analysis, Logistics and Supply Chain Management of the Department of Mechanical Engineering, Aristotle University of Thessaloniki (AUTH). During the 2-Days Conference m...

  11. Comparison between distributed and centralized demand assignment TDMA satellite access schemes

    OpenAIRE

    Celandroni, Nedo; Ferro, Erina; Potort?, Francesco

    1996-01-01

    This paper presents the performance measurements from a comparison between FODAIIBEA and two other satellite access schemes, FEEDERS and DRIFS. The three schemes differ in terms of the scheduling of the channel capacity: Le. centralized control in FODA/IBEA and distributed in the other two. All these access schemes were designed at CNUCE, where the simulation tool used for the comparison was also developed. FODA/IBEA was developed and tested on several satellites (Olympus, Eutelsat and Italsa...

  12. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply

    Energy Technology Data Exchange (ETDEWEB)

    Spoden, Gilles A. [Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck (Austria); Tumorvirology Research Group, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innrain 66, 6020 Innsbruck (Austria); Rostek, Ursula; Lechner, Stefan; Mitterberger, Maria [Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck (Austria); Mazurek, Sybille [Department for Biochemistry and Endocrinology, Veterinary Faculty, University of Giessen, 35392 Giessen (Germany); ScheBo Biotech AG, Netanyastrasse 3, 35394 Giessen (Germany); Zwerschke, Werner, E-mail: werner.zwerschke@oeaw.ac.at [Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck (Austria); Tumorvirology Research Group, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innrain 66, 6020 Innsbruck (Austria)

    2009-10-01

    The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) can switch between a highly active tetrameric and an inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells. We developed specific M2-PK-binding peptide aptamers which inhibit M2-PK, but not the 96% homologous M1-PK isoenzyme. In this study we demonstrate that, at normal blood glucose concentrations, peptide aptamer-mediated inhibition of M2-PK induces a significant decrease of the population doubling (PDL rate) and cell proliferation rate as well as an increase in cell size, whereas under glucose restriction an increase in PDL and cell proliferation rates but a decrease in cell size was observed. Moreover, M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity. These findings suggest that M2-PK is a metabolic sensor which regulates cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner.

  13. Individual Variability in Aerobic Fitness Adaptations to 70-d of Bed Rest and Exercise Training

    Science.gov (United States)

    Downs, Meghan; Buxton, Roxanne; Goetchius, Elizabeth; DeWitt, John; Ploutz-Snyder, Lori

    2016-01-01

    Change in maximal aerobic capacity (VO2pk) in response to exercise training and disuse is highly variable among individuals. Factors that could contribute to the observed variability (lean mass, daily activity, diet, sleep, stress) are not routinely controlled in studies. The NASA bed rest (BR) studies use a highly controlled hospital based model as an analog of spaceflight. In this study, diet, hydration, physical activity and light/dark cycles were precisely controlled and provided the opportunity to investigate individual variability. PURPOSE. Evaluate the contribution of exercise intensity and lean mass on change in VO2pk during 70-d of BR or BR + exercise. METHODS. Subjects completed 70-d of BR alone (CON, N=9) or BR + exercise (EX, N=17). The exercise prescription included 6 d/wk of aerobic exercise at 70 - 100% of max and 3 d/wk of lower body resistance exercise. Subjects were monitored 24 hr/d. VO2pk and lean mass (iDXA) were measured pre and post BR. ANOVA was used to evaluate changes in VO2pk pre to post BR. Subjects were retrospectively divided into high and low responders based on change in VO2pk (CON > 20% loss, n=5; EX >10% loss, n=4, or 5% gain, n=4) to further understand individual variability. RESULTS. VO2pk decreased from pre to post BR in CON (Ptraining induced gains in VO2pk appear unrelated to lean mass or exercise intensity.

  14. The pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus

    Science.gov (United States)

    Chamberlain, James M.; Capparelli, Edmund V.; Brown, Kathleen M.; Vance, Cheryl W.; Lillis, Kathleen; Mahajan, Prashant; Lichenstein, Richard; Stanley, Rachel M.; Davis, Colleen O.; Gordon, Stephen; Baren, Jill M.; van den Anker, John N.

    2011-01-01

    Objective[mh2] To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE. Study design Ten hospitals in the Pediatric Emergency Care Applied Research Network (PECARN) enlisted patients 3 months to 17 years with convulsive SE (STATUS) or for a traditional PK study (ELECTIVE). Sparse sampling was used for STATUS and intensive sampling for ELECTIVE. Noncompartmental analyses were performed on ELECTIVE, and served to nest compartmental population PK analysis for both cohorts. Results 48 STATUS and 15 ELECTIVE patients were enrolled. Median age was 7 years, 2 months. The population PK parameters were: clearance 1.2 mL/min/kg, half-life 16.8 hours, volume of distribution 1.5 L/kg. Based on the PK model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations above 30–50 ng/mL for 6–12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg. Conclusions Lorazepam PK in convulsive status epilepticus is similar to previous PK measured in pediatric patients with cancer, except for longer half-life and similar to adult PK parameters except for increased clearance. PMID:22050870

  15. Pitted keratolysis, erythromycin, and hyperhidrosis.

    Science.gov (United States)

    Pranteda, Guglielmo; Carlesimo, Marta; Pranteda, Giulia; Abruzzese, Claudia; Grimaldi, Miriam; De Micco, Sabrina; Muscianese, Marta; Bottoni, Ugo

    2014-01-01

    Pitted keratolysis (PK) is a plantar skin disorder mainly caused by coryneform bacteria. A common treatment consists of the topical use of erythromycin. Hyperhidrosis is considered a predisposing factor for bacterial proliferation and, consequently, for the onset of PK. The aim of this study was to evaluate the relationship between PK erythromycin and hyperhidrosis. All patients with PK seen in Sant'Andrea Hospital, between January 2009 and December 2011, were collected. PK was clinically and microscopically diagnosed. All patients underwent only topical treatment with erythromycin 3% gel twice daily. At the beginning of the study and after 5 and 10 days of treatment, a clinical evaluation and a gravimetric measurement of plantar sweating were assessed. A total of 97 patients were diagnosed as PK and were included in the study. Gravimetric measurements showed that in 94 of 97 examined patients (96.90%) at the time of the diagnosis, there was a bilateral excessive sweating occurring specifically in the areas affected by PK. After 10 days of antibiotic therapy, hyperhidrosis regressed together with the clinical manifestations. According to these data, we hypothesize that hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection. PMID:24703267

  16. A comparative, retrospective, observational study of the clinical and microbiological profiles of post-penetrating keratoplasty keratitis

    Science.gov (United States)

    Lin, I.-Huang; Chang, Yi-Sheng; Tseng, Sung-Huei; Huang, Yi-Hsun

    2016-09-01

    Infectious keratitis after penetrating keratoplasty (PK) is a devastating condition that may result in graft failure and poor visual outcome. In this study, we retrospectively reviewed the medical records of patients who underwent PK between 2009 and 2014, and recorded those who developed infectious keratitis. We compared the predisposing factors and organisms isolated to those identified in our previous study, conducted between 1989 and 1994. The incidence of post-PK infectious keratitis decreased from 11.6% (41 out of 354 cases, 1989-1994) to 6.5% (9 out of 138 cases, 2009-2014). Graft epithelial defect and suture-related problems remained the leading two risk factors of infectious keratitis after PK. Gram-positive and Gram-negative bacterial infection decreased from 58.5% and 46.3% to 11.1% and 22.2%, respectively (P = 0.023 and P = 0.271). In contrast, fungus infection increased from 9.8% to 66.7% (P = 0.001) fungi have become the major pathogen for post-PK infectious keratitis. In conclusion, while the incidence of post-PK infectious keratitis has decreased over time, the number and frequency of fungal infections have significantly increased in the recent study period. Clinicians should be aware of the shifting trend in pathogens involved in post-PK infectious keratitis.

  17. Proteinase K and the structure of PrPSc: The good, the bad and the ugly.

    Science.gov (United States)

    Silva, Christopher J; Vázquez-Fernández, Ester; Onisko, Bruce; Requena, Jesús R

    2015-09-01

    Infectious proteins (prions) are, ironically, defined by their resistance to proteolytic digestion. A defining characteristic of the transmissible isoform of the prion protein (PrP(Sc)) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrP(Sc) by Western blot, ELISA or immunohistochemical detection. PK digestion has also been used to detect differences in prion strains. Thus, PK has been a crucial tool to detect and, thereby, control the spread of prions. PK has also been used as a tool to probe the structure of PrP(Sc). Mass spectrometry and antibodies have been used to identify PK cleavage sites in PrP(Sc). These results have been used to identify the more accessible, flexible stretches connecting the β-strand components in PrP(Sc). These data, combined with physical constraints imposed by spectroscopic results, were used to propose a qualitative model for the structure of PrP(Sc). Assuming that PrP(Sc) is a four rung β-solenoid, we have threaded the PrP sequence to satisfy the PK proteolysis data and other experimental constraints.

  18. Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice.

    Science.gov (United States)

    Serrano, A; Menéndez, J; Casarejos, M J; Solano, R M; Gallego, E; Sánchez, M; Mena, M A; García de Yebenes, J

    2005-08-01

    Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT) controls. PK-KO mice have high striatal dopamine levels and increased dopamine metabolism in spite of low reduced tyrosine hydroxylase protein. Cinnarizine, which blocks dopamine receptors and increases dopamine release, further increased dopamine metabolism. PK-KO mice increased GSH levels as a compensatory mechanism against enhanced free radical production related to acceleration of dopamine turnover. Neuronal markers, such as beta-tubulin slightly increased in PK-KO and furthermore with cinnarizine. Astroglial markers were decreased in PK-KO mice, and this effect was potentiated by cinnarizine, suggesting abnormal glia in these animals. Microglia was hyperactivated in PK-KO midbrain, suggesting inflammation in these animals. Proapoptotic proteins were increased by cinnarizine and, to a lesser extent, in PK-KO mice. Our data indicate that mutation of parkin is a risk factor for drug-induced parkinsonism. PMID:15993444

  19. EVALUATION OF CO-PRODUCT OF VERMICULITE AS SUBSTRATE IN SEEDLINGS PRODUCTION OF NIM

    Directory of Open Access Journals (Sweden)

    G. H. Silva

    2014-09-01

    Full Text Available This study evaluated the effect of different doses of organic matter and fertilizer PK neem seedlings grown in co-product of vermiculite. At the end of the experiment, the seedlings were separated into root, stem and leaves, then the material was placed in an oven and subsequent weighing. The parameters evaluated were: height, diameter, number of leaves, root length, IQD (Dickson quality index and TDM (total dry mass. The design used in the experiment was the DIC with seven levels of organic matter (OM (0, 5, 10, 15, 20, 25, 30% and three fertilization PK (Phosphorus and Potassium (PK0, PK100, PK300 with four replications. For doses of OM and fertilization was applied polynomial regression grade 2 at 5% of probability. The results of the analysis of variance showed that there were significant positive quadratic effect among all levels of treatment with OM on all variables. However, all variables were not statistically different for PK and PK + OM in all parameters evaluated. Thus the species under study shows no demand of chemical fertilizer in their early growth stages. The IQD values at a dose of 20% of OM indicate higher rates of development. The dose of 5% of OM in co-product of vermiculite is enough to produce seedlings of nem of good quality.

  20. Recent and episodic volcanic and glacial activity on Mars revealed by the High Resolution Stereo Camera.

    Science.gov (United States)

    Neukum, G; Jaumann, R; Hoffmann, H; Hauber, E; Head, J W; Basilevsky, A T; Ivanov, B A; Werner, S C; van Gasselt, S; Murray, J B; McCord, T

    2004-12-23

    The large-area coverage at a resolution of 10-20 metres per pixel in colour and three dimensions with the High Resolution Stereo Camera Experiment on the European Space Agency Mars Express Mission has made it possible to study the time-stratigraphic relationships of volcanic and glacial structures in unprecedented detail and give insight into the geological evolution of Mars. Here we show that calderas on five major volcanoes on Mars have undergone repeated activation and resurfacing during the last 20 per cent of martian history, with phases of activity as young as two million years, suggesting that the volcanoes are potentially still active today. Glacial deposits at the base of the Olympus Mons escarpment show evidence for repeated phases of activity as recently as about four million years ago. Morphological evidence is found that snow and ice deposition on the Olympus construct at elevations of more than 7,000 metres led to episodes of glacial activity at this height. Even now, water ice protected by an insulating layer of dust may be present at high altitudes on Olympus Mons.

  1. A new Agraecina spider species from the Balkan Peninsula (FYR Macedonia) (Araneae: Liocranidae).

    Science.gov (United States)

    Deltshev, Christo; Wang, Chunxia

    2016-01-01

            Specimens were collected using pitfall traps. Coloration is described from alcohol-preserved specimens. Specimens were examined and measured using a Wild M5A stereomicroscope. Further details were studied and measured under an Olympus BX41 compound microscope. All drawings were made using a drawing apparatus attached to a Leica stereomicroscope. Male palps and female genitalia were examined and illustrated after they were dissected from the spiders' bodies. Photos were taken with an Olympus C7070 wide zoom digital camera mounted on an Olympus SZX12 stereomicroscope. The images were montaged using Helicon Focus image stacking software. Measurements of the legs are taken from the dorsal side. Total length of the body includes the chelicerae. All measurements were taken in mm. Abbreviations used in text include: AME, anterior median eyes; ALE, anterior lateral eyes; EM, embolus; MA, median apophysis; CD, copulatory duct; ST, spermatheca; fe, femur; pa, patella; ti, tibia; mt, metatarsus; p, prolateral; d, dorsal; r, retrolateral; v, ventral. Type specimens are deposited in the National Museum of Natural History (NMNHS), Sofia, Bulgaria. PMID:27395163

  2. Poly(ADP-Ribose) Polymerase-1 and DNA-Dependent Protein Kinase Have Equivalent Roles in Double Strand Break Repair Following Ionizing Radiation

    International Nuclear Information System (INIS)

    Purpose: Radiation-induced DNA double strand breaks (DSBs) are predominantly repaired by nonhomologous end joining (NHEJ), involving DNA-dependent protein kinase (DNA-PK). Poly(ADP-ribose) polymerase-1 (PARP-1), well characterized for its role in single strand break repair, may also facilitate DSB repair. We investigated the activation of these enzymes by differing DNA ends and their interaction in the cellular response to ionizing radiation (IR). Methods and Materials: The effect of PARP and DNA-PK inhibitors (KU-0058684 and NU7441) on repair of IR-induced DSBs was investigated in DNA-PK and PARP-1 proficient and deficient cells by measuring γH2AX foci and neutral comets. Complementary in vitro enzyme kinetics assays demonstrated the affinities of DNA-PK and PARP-1 for DSBs with varying DNA termini. Results: DNA-PK and PARP-1 both promoted the fast phase of resolution of IR-induced DSBs in cells. Inactivation of both enzymes was not additive, suggesting that PARP-1 and DNA-PK cooperate within the same pathway to promote DSB repair. The affinities of the two enzymes for oligonucleotides with blunt, 3' GGG or 5' GGG overhanging termini were similar and overlapping (Kdapp = 2.6-6.4nM for DNA-PK; 1.7-4.5nM for PARP-1). DNA-PK showed a slightly greater affinity for overhanging DNA and was significantly more efficient when activated by a 5' GGG overhang. PARP-1 had a preference for blunt-ended DNA and required a separate factor for efficient stimulation by a 5' GGG overhang. Conclusion: DNA-PK and PARP-1 are both required in a pathway facilitating the fast phase of DNA DSB repair.

  3. Interaction of DNA-dependent protein kinase with DNA and with Ku: biochemical and atomic-force microscopy studies.

    OpenAIRE

    Yaneva, M.; Kowalewski, T; Lieber, M R

    1997-01-01

    DNA-dependent protein kinase (DNA-PK or the scid factor) and Ku are critical for DNA end-joining in V(D)J recombination and in general non-homologous double-strand break repair. One model for the function of DNA-PK is that it forms a complex with Ku70/86, and this complex then binds to DNA ends, with Ku serving as the DNA-binding subunit. We find that DNA-PK can itself bind to linear DNA fragments ranging in size from 18 to 841 bp double-stranded (ds) DNA, as indicated by: (i) mobility shifts...

  4. Mutability of prions

    OpenAIRE

    Li, Jiali; Mahal, Sukhvir P.; Demczyk, Cheryl A.; Weissmann, Charles

    2011-01-01

    Murine prions transferred from brain to cultured cells gradually adapt to the new environment. Brain-derived 22L prions can infect neuroblastoma-derived PK1 cells in the presence of swainsonine (swa); that is, they are ‘swa resistant'. PK1 cell-adapted 22L prions are swa sensitive; however, propagation in swa results in selection of swa-resistant substrains. Cloned, PK1 cell-adapted 22L prions were initially unable to develop swa resistance (‘swa incompetent'); however, after serial propagati...

  5. Regulating mineralization rates of Tithonia diversifolia and Lantana camara prunings to improve phosphorus availability in calcareous soils

    OpenAIRE

    Y. Nuraini; N. Sukmawatie

    2014-01-01

    The effect of mixing of Tithonia diversifolia and Lantana camara prunings to improve synchronization between P released from the prunings with crop demand for P was studied in a laboratory and in a glasshouse. Tithonia diversifolia prunings (Td), Lantana camara prunings (Lc), and farmyard manure (Pk) were thoroughly mixed with the proportion (% of dry weight) of; 25Td +75 Lc ; 50Td +50 Lc ; 75Td +25 Lc ; 90Lc +10 Pk ; 45Td +45 +10 Lc Pk ; 100Td and 100Lc, and then mixed with 100 g of air-drie...

  6. Comparison of fecal pyruvate kinase isoform M2 and calprotectin in acute diarrhea in hospitalized children

    OpenAIRE

    Czub, Elzbieta; Jan K. Nowak; Moczko, Jerzy; Lisowska, Aleksandra; Banaszkiewicz, Aleksandra; Banasiewicz, Tomasz; Walkowiak, Jaroslaw

    2014-01-01

    Fecal concentrations of pyruvate kinase isoform M2 (M2-PK) and calprotectin (FC) serve as biomarkers of inflammation of gastrointestinal mucosa. The value of M2-PK in discriminating between patients with viral and bacterial acute diarrhea (AD) is currently unknown. We analyzed M2-PK and FC concentrations in fifty hospitalized children with AD (29 of which were caused by rotavirus and 21 by Salmonella enteritidis) as well as 32 healthy subjects. There was no difference in the areas under the r...

  7. Grape yield and quality of the grapevine cultivar limberger treated with plant growth regulators

    Directory of Open Access Journals (Sweden)

    Todić Slavica R.

    2004-01-01

    Full Text Available The effects of foliar application of paclobutrasol (PK, chlorcholinechloride (CC and gibberellic acid (GA3 on grape yield and quality of the grapevine cultivar Limberger were studied. PK and CC strongly inhibited shoot growth. The number of berries per bunch, bunch weight and grape yield per m2 were increased. At the same time, sugar content of must was either reduced (CC2000 or retained at the level of control (PK1000, CC1000. The GA150 treatment resulted in lower grape yield. At the concentration of GA3 100mg/l no significant increase in yield was found, whilst sugar content of must was significantly increased.

  8. EFFECT OF PANCHAKAVYA ON SOIL ENZYME ACTIVITY IN ASHWAGANDHA

    OpenAIRE

    B Vajantha; M. Umadevi; Patnaik, M C; M.Rajkumar

    2015-01-01

    The study was carried out to investigate the effect of panchakavya made from cow (PK-C) and buffalo (PK-B) products on urease and dehydrogenase activity and root yield of Ashwagandha and it revealed that soil application of PK-C @ 15% recorded the highest urease activity at both the stages of crop (85.24, 44.56 at flowering and harvest during rabi 2007-08 and 81.07, 35.50 μg of NH4 + released g-1 soil h-1 at flowering and harvest in kharif 2008). The highest dehydrogenase activity also notice...

  9. [Paradoxical kinesis phenomenon in focal hand dystonia--writer's cramp].

    Science.gov (United States)

    Shavlovskaia, O A; Orlova, O R; Golubev, V L

    2005-01-01

    Paradoxical kinesis (PK) phenomenon and its variants, exerting a beneficial influence on dystonia dynamics, are described using self clinical examination of 57 writer's cramp patients. PK was found in all the patients independently of writer's cramp variant, duration and severity. The most frequent writing maneuvers were as follows: hand printed (100%), proximal arm muscles writing (82.5%), individually selected writing instrument (67.5-80%), unusual means (67.5-75%), writing imitation with unlike-pen object (70%), marked papers (52.5%). The beneficial influence of PK phenomenon on dystonia expression may be considered as one of the directions of writer's cramp rehabilitation.

  10. Additive structure of Z(.) mod m_k (squarefree) and Goldbach's Conjecture

    OpenAIRE

    Benschop, N. F.

    2001-01-01

    The product m_k of the first k primes (2..p_k) has neighbours m_k +/- 1 with all prime divisors beyond p_k, implying there are infinitely many primes [Euclid]. All primes between p_k and m_k are in the group G_1 of units in semigroup Z_{m_k}(.) of mutiplication mod m_k. Due to the squarefree modulus Z_{m_k} is a disjoint union of 2^k groups, with as many idempotents - one per divisor of m_k, which form a Boolean lattice BL. The generators of Z_{m_k} and the additive properties of its lattice ...

  11. On structure of small contractions of odd dimensional projective varieties

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Let X be a smooth projective variety of dimension 2k-1 (k≥3) over the complex number field. Assume that fR: X→Y is a small contraction such that every irreducible component Ei of the exceptional locus of fR is a smooth subvariety of dimension k. It is shown that each Ei is isomorphic to the k-dimensional projective space Pk, the k-dimensional hyperquadric surface Qk in Pk+1, or a linear Pk-1-bundle over a smooth curve.

  12. Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics

    OpenAIRE

    Nekka Fahima; Li Jun; Bi Goue

    2009-01-01

    Abstract Background Pharmacokinetic and pharmacodynamic (PK/PD) indices are increasingly being used in the microbiological field to assess the efficacy of a dosing regimen. In contrast to methods using MIC, PK/PD-based methods reflect in vivo conditions and are more predictive of efficacy. Unfortunately, they entail the use of one PK-derived value such as AUC or Cmax and may thus lead to biased efficiency information when the variability is large. The aim of the present work was to evaluate t...

  13. Recognition of DNA Termini by the C-Terminal Region of the Ku80 and the DNA-Dependent Protein Kinase Catalytic Subunit

    OpenAIRE

    Woods, Derek S.; Catherine R Sears; Turchi, John J.

    2015-01-01

    DNA double strand breaks (DSBs) can be generated by endogenous cellular processes or exogenous agents in mammalian cells. These breaks are highly variable with respect to DNA sequence and structure and all are recognized in some context by the DNA-dependent protein kinase (DNA-PK). DNA-PK is a critical component necessary for the recognition and repair of DSBs via non-homologous end joining (NHEJ). Previously studies have shown that DNA-PK responds differentially to variations in DSB structur...

  14. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    Science.gov (United States)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  15. Insulin-like growth factor-I receptor in proliferation and motility of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Minoru; Tomizawa; Fuminobu; Shinozaki; Takao; Sugiyama; Shigenori; Yamamoto; Makoto; Sueishi; Takanobu; Yoshida

    2010-01-01

    AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol3 kinase (PI3K), and PD980...

  16. Moving from basic toward systems pharmacodynamic models.

    Science.gov (United States)

    Jusko, William J

    2013-09-01

    Building upon many classical foundations of pharmacology, a diverse array of mechanistic pharmacokinetic-pharmacodynamic (PK/PD) models have emerged based on mechanisms of drug action and primary rate-limiting or turnover processes in physiology. An array of basic models can be extended to handle various complexities including tolerance and can readily be employed as building blocks in assembling enhanced PK/PD or small systems models. Our corticosteroid models demonstrate these concepts as well as elements of horizontal and vertical integration of molecular to whole-body processes. The potential advantages and challenges in moving PK/PD toward systems models are described.

  17. Pharmacokinetics and tolerability of cediranib, a potent VEGF signalling inhibitor, in cancer patients with hepatic impairment

    DEFF Research Database (Denmark)

    van Herpen, Carla M L; Lassen, Ulrik; Desar, Ingrid M E;

    2013-01-01

    tumours received a single 45 mg dose of cediranib, followed by 30 mg continuous once-daily oral dosing for 21 days after a 7-day washout period (clinicaltrials.gov identifier NCT00621725). The primary objective was to compare the single-dose pharmacokinetics (PK) of cediranib in patients with different...... levels of hepatic impairment classified according to the bilirubin level. Safety, tolerability, multiple-dose PK and PK stratified according to the Child-Pugh criteria were also assessed. Thirty patients received cediranib: 18 with normal-mild hepatic impairment and 12 with moderate hepatic impairment...... not influence PK results in multiple dosing. After continuous once-daily dosing, the geometric least square means ratio was 0.72 (90% CI 0.51-1.03) for AUCSS and 0.67 (90% CI 0.47-0.94) for CSS,max. Similar results were obtained when patients were classified for hepatic impairment according to the...

  18. Feasibility of bioethanol production from tubers of Dioscorea sansibarensis and Pyrenacantha kaurabassana.

    Science.gov (United States)

    Moshi, Anselm P; Nyandele, Jane P; Ndossi, Humphrey P; Eva, Sosovele M; Hosea, Ken M

    2015-11-01

    Inedible tubers from Dioscorea sansibarensis (DS) and Pyrenacantha kaurabassana (PK) were found to be suitable feedstock for bioethanol production. Important composition parameters for bioethanol production for DS and PK are dry matter (% fresh tubers) ca. 20 and 6, total carbohydrates % dry weight base (db) ca. 68 and 47 and total protein (% db) ca. 16 and 10, respectively. DS and PK were found to contain inulin and galactomannan as principal polysaccharides (% of total carbohydrate) ca. 90 and 70, respectively. Diluted acid hydrolysis yielded ca. 100% of total reducing sugars. Ethanol yield ca. 56 and 35g/L was obtained at high efficiency through batch fermentation of acid hydrolysate (25% w/v) of DS and PK, respectively. A simple technique of recording and monitoring ethanol through CO2 generated during fermentation correlated strongly with HPLC measurement R(2)=0.99. Thus, tubers from these plants are potential feedstocks for bioethanol production with no competing uses. PMID:26298406

  19. Evidence of tetraphenylporphyrin monoacids by ion-transfer voltammetry at polarized liquid|liquid interfaces

    OpenAIRE

    Su, Bin; Li, Fei; Partovi-Nia, Raheleh; Gros, Claude; Barbe, Jean-Michel; Samec, Zdenek; Girault, Hubert H.

    2008-01-01

    We present a simple methodology to illustrate the existence of tetraphenylporphyrin monoacid based on ion-transfer voltammetry at a polarized water|1,2-dichloroethane interface and organic pK values are also estimated.

  20. In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Benavides, J.; Guilloux, F.; Rufat, P.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Gueremy, C.; Le Fur, G. (Pharmuka Laboratoires, 92 - Gennevilliers (France))

    1984-03-16

    'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of (/sup 3/H)PK 11195 and (/sup 3/H)RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make (/sup 3/H)PK 11195 the most suitable ligand for this kind of studies.

  1. EPA National Center for Computational Toxicology UPDATE (ICCVAM public forum)

    Science.gov (United States)

    A presentation to the ICCVAM Public Forum on several new and exciting activities at NCCT, including Chemical library update, Chemistry Dashboard, Retrofitting in vitro assays with metabolic competence and In vitro PK.

  2. Isaac Newton: Man, Myth, and Mathematics.

    Science.gov (United States)

    Rickey, V. Frederick

    1987-01-01

    This article was written in part to celebrate the anniversaries of landmark mathematical works by Newton and Descartes. It's other purpose is to dispel some myths about Sir Isaac Newton and to encourage readers to read Newton's works. (PK)

  3. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

    NARCIS (Netherlands)

    C.M.L. Herpen, C.M.L. (Carla); F.A.L.M. Eskens (Ferry); M.J.A. de Jonge (Maja); I. Desar; L. Hooftman (Leon); E. Bone (Elisabeth); J.N.H. Timmerbonte (Johanna); J. Verweij (Jaap)

    2010-01-01

    textabstractBackground: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxe

  4. Prior knowledge and reading comprehension ability of deaf adolescents.

    Science.gov (United States)

    Jackson, D; Paul, P; Smith, J

    1997-01-01

    Fifty-one severely to profoundly deaf students (mean dB hearing loss = 89) were randomly assigned to two groups that differed by the type of probes (short or long) used to elicit prior knowledge (PK). PK scores were used to predict reading comprehension (RC), which was assessed by students' responses to three types of questions: test-explicit (TE), text-implicit (TI), and script-implicit (SI). Multiple regression models with PK scores and scores from a standardized achievement test (Stanford Achievement Test - Hearing Impaired Version, reading subtest) were also used to predict RC. The regression model showed that, for the group pretested with an in-depth, or long, probe of PK, the best predictor of RC was the ability to answer TE and SI questions. We present discussions of the observed differences in comprehension as a function of long and short knowledge probes and the use of three question types, together with implications for instruction.

  5. Potential role of DNA-dependent protein kinase in cellular resistance to ionizing radiation

    Institute of Scientific and Technical Information of China (English)

    LI Ning; ZHANG Hong; WANG Yanling; WANG Xiaohu; HAO Jifang

    2009-01-01

    In this paper, we study the ability of DNA-PK-deficient (M059J) and -proficient (M059K) cells to undergo the rate of cellular proliferation, cell cycle distribution and apoptosis after 10 Gy X-ray irradiation, and the role of DNA-PK in radiosensitivity. The results showed that M059J cells exhibited hyper-radiosensitivity compared with M059K cells. A strong G2 phase arrest was observed in M059J cells post irradiation. Significant accumulation in the G2 phase in M059J cells was accompanied by apoptosis at 12 h. Altogether, the data suggested that DNA-PK may have two roles in mammalian cells after DNA damage, a role in DNA DSB repair and a second role in DNA-damaged cells to traverse a G2 checkpoint, by which DNA-PK may affect cellular sensitivity to ionizing radiation.

  6. The origin of the logarithmic integral in the prime number theorem

    OpenAIRE

    Tunstrøm, Kolbjørn

    2013-01-01

    We establish why li(x) outperforms x/log x as an estimate for the prime counting function pi(x). The result follows from subdividing the natural numbers into the intervals s_k :={p_k^2,..., p_{k+1}^2-1}, k>=1, each being fully sieved by the k first primes {p_1,..., p_k}. Denoting the number of primes in s_k by pi_k, we show that pi_k |s_k|/log p_{k+1}^2 and that pi(x) li(x) originates as a continuum approximation of the sum sum_k pi_k. In contrast, pi(x) x/log x stems from sieving repeatedly ...

  7. Optimizing anticancer drug treatment in pregnant cancer patients : pharmacokinetic analysis of gestation-induced changes for doxorubicin, epirubicin, docetaxel and paclitaxel

    NARCIS (Netherlands)

    van Hasselt, J G C; van Calsteren, K; Heyns, L; Han, S; Mhallem Gziri, M; Schellens, J H M; Beijnen, J H; Huitema, A D R; Amant, F

    2014-01-01

    BACKGROUND: Pregnant patients with cancer are increasingly treated with anticancer drugs, although the specific impact of pregnancy-induced physiological changes on the pharmacokinetics (PK) of anticancer drugs and associated implications for optimal dose regimens remains unclear. Our objectives wer

  8. In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

    International Nuclear Information System (INIS)

    'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of [3H]PK 11195 and [3H]RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make [3H]PK 11195 the most suitable ligand for this kind of studies. (Auth.)

  9. Thermally reversible thermoset materials based on the chemical modification of alternating aliphatic polyketones

    NARCIS (Netherlands)

    Araya Hermosilla, Rodrigo Andrés

    2016-01-01

    This thesis focused on the synthesis and characterization of different kinds of reversible thermosets and thermoset nanocomposite materials by using alternating aliphatic polyketone (PK) as raw material. Fundamental knowledge was generated regarding the molecular design of new polymers via chemical

  10. Combined HLA matched limbal stem cells allograft with amniotic membrane transplantation as a prophylactic surgical procedure to prevent corneal graft rejection after penetrating keratoplasty: case report

    Directory of Open Access Journals (Sweden)

    Paolo Capozzi

    2014-09-01

    Full Text Available Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK. Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.

  11. On the Affine Isoperimetric Inequalities

    Indian Academy of Sciences (India)

    Wuyang Yu; Gangsong Leng

    2011-11-01

    We obtain an isoperimetric inequality which estimate the affine invariant -surface area measure on convex bodies. We also establish the reverse version of -Petty projection inequality and an affine isoperimetric inequality of $_{-p}K$.

  12. Prions, proteinase K and infectivity.

    Science.gov (United States)

    Sajnani, Gustavo; Requena, Jesús R

    2012-01-01

    It has been described that the breakdown of β-sheets in PrP (Sc) by denaturation results in loss of infectivity and PK-sensitivity, suggesting a relationship between the structure and PK-resistance. It is also known that an important fraction of total PrP (Sc) is PK-sensitive and can be isolated by the method we already described. Consequently, we decided to employ the PK-sensitive fraction of PrP (Sc) as a potential and useful tool for structural studies. Thus, two essential questions were addressed in our recent article. First, the difference in the infectivity between the sensitive and resistant fractions and second, whether sensitive and resistant PrP (Sc) shared the same conformation or were only different size multimers with the same basic conformation. Here we discuss our latest data in light of recent infectivity studies and their possible implications on the conformation of the prion.

  13. The pyruvate kinase of Stigmatella aurantiaca is an indole binding protein and essential for development.

    Science.gov (United States)

    Stamm, Irmela; Lottspeich, Friedrich; Plaga, Wulf

    2005-06-01

    Myxospore formation of the myxobacterium Stigmatella aurantiaca can be uncoupled from the cooperative development i.e. fruiting body formation, by low concentrations of indole. Two putative indole receptor proteins were isolated by their capacity to bind indole and identified as pyruvate kinase (PK) and aldehyde dehydrogenase. The PK activity of Stigmatella crude extracts was stimulated by indole. Cloning of the PK gene (pykA) and the construction of a pykA disruption mutant strikingly revealed that PK is essential for multicellular development: Fruiting body formation was abolished in the mutant strain and indole-induced spore formation was delayed. The developmental defects could be complemented by insertion of the pykA gene at the mtaB locus of the Stigmatella genome excluding any polar effects of the pykA disruption. PMID:15882428

  14. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin;

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  15. AcEST: DK947046 [AcEST

    Lifescience Database Archive (English)

    Full Text Available PK+H+ETTGPEI Sbjct: 170 RVILKAFGAELVLTDPAKGMKGAVSKAEEILNNTPDAYILQQFDNPANPKIHYETTGPEI 229 Query: 182 WEDTAGKIDILISXXXXXXXXXXXXRF...KAEEIRDKTPNSYILQQFENPANPKVHYETTGPEI 168 Query: 182 WEDTAGKIDILISXXXXXXXXXXXXRFLXXXXXXXXXXXXEPTESSVLAGGKPGPHK...7 Query: 182 WEDTAGKIDILISXXXXXXXXXXXXRFLXXXXXXXXXXXXEPTESSVLAGGKPGPHKIQG 361 WED...FGAELVLTDPARGMKGAVQKAEEIKAKTPNSYILQQFENPANPKIHYETTGPEI 168 Query: 182 WEDTAGKIDILISXXXXXXXXXXXXRFLXXXXXXXXXX...Query: 182 WEDTAGKIDILISXXXXXXXXXXXXRFLXXXXXXXXXXXXEPTESSVLAGGKPGPHKIQG 361 W+ TA

  16. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.

    NARCIS (Netherlands)

    Herpen, C.M.L. van; Eskens, F.A.; Jonge, M. de; Desar, I.M.E.; Hooftman, L.; Bone, E.A.; Timmer-Bonte, J.N.H.; Verweij, J.

    2010-01-01

    BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:

  17. [Mortui vivos docent?--experienced burdens of medical students in the gross anatomy course].

    Science.gov (United States)

    Limbrecht, Kerstin; Brinkmann, Anke; Lamp, Christoph; Böckers, Anja; Böckers, Tobias; Traue, Harald C; Jerg-Bretzke, Lucia

    2013-08-01

    The dissection course (here abbreviated: PK) is still an obligatory part of medical schools in Germany. In this study we investigated the experiences and burdens of medical students in gross anatomy, especially "distancing from the human body".This study was carried out three times with the self-composed questionnaire BF-PK: before, while and after PK. In total 371 students participated in the PK. 297 students participated at measurement 1. In advance 25-30% of the medical students reported anxiety and emotional inhibition, during the course only 7-10%. The coping strategy "distancing from the human body" was prominent. Anxiety, emotional inhibition and disgust remained for 5-10% of the participants.The gross anatomy course causes emotional stress for a considerable amount of medical students. For those students that were not able to overcome the mental stress themselves service offers should be implemented. PMID:23468367

  18. THE EFFECT OF UNFAVOURABLE FACTORS ON PERUVATE KINASE ACTIVITY IN BRAIN CORTEX OF WHITE RATS IN POSTNATAL ONTOGENESIS

    Directory of Open Access Journals (Sweden)

    L. M. Guseynova

    2012-12-01

    Full Text Available The effect of unionizated electromagnetic radiation (EMI of different intensity and hypoxia on pyruvate kinase activity (PK; EC 2.7.1.40 in the tissues of right and left hemispheres of white rats has been studied during postnatal ontogenesis. The highest hyperactivity of PK was revealed in the left hemisphere of brain cortex both in the control animals and after the influence of extremal environmental factors. It was stated that hypoxia induces higher changes in the dynamics of changes in the dynamics of changes in the PK-activity in the tissues of brain cortex than EMI, which leads to changes in energy supply of brain. The changes in the PK-activity are supposed to be caused by involving decay products and activation of biosynthetic processes into energy supply of cells.

  19. Fibonacci Numbers and Computer Algorithms.

    Science.gov (United States)

    Atkins, John; Geist, Robert

    1987-01-01

    The Fibonacci Sequence describes a vast array of phenomena from nature. Computer scientists have discovered and used many algorithms which can be classified as applications of Fibonacci's sequence. In this article, several of these applications are considered. (PK)

  20. 过程能力分析在制造业中的实际应用%Research on application of process capability analysis in manufacturing

    Institute of Scientific and Technical Information of China (English)

    窦智

    2009-01-01

    The paper researches the application of process capability in manufacturing, introduces the method of process capability analysis, and how to implement C_(pk) evaluation and procedure in manufacturing, find out where are the root causes, and uses C_(pk) analysis to improve capability of process.%探讨过程能力分析(C_(pk))在生产制造业中的实际应用.介绍过程能力分析方法,简述如何在生产制造业中实施C_(pk)评价的实践和流程,指出存在的问题,以及如何提高过程能力.

  1. Large-Amplitude Electrostatic Waves Observed at a Supercritical Interplanetary Shock

    Science.gov (United States)

    Wilson, L. B., III; Cattell, C. A.; Kellogg, P. J.; Goetz, K.; Kersten, K.; Kasper, J. C.; Szabo, A.; Wilber, M.

    2010-01-01

    We present the first observations at an interplanetary shock of large-amplitude (> 100 mV/m pk-pk) solitary waves and large-amplitude (approx.30 mV/m pk-pk) waves exhibiting characteristics consistent with electron Bernstein waves. The Bernstein-like waves show enhanced power at integer and half-integer harmonics of the cyclotron frequency with a broadened power spectrum at higher frequencies, consistent with the electron cyclotron drift instability. The Bernstein-like waves are obliquely polarized with respect to the magnetic field but parallel to the shock normal direction. Strong particle heating is observed in both the electrons and ions. The observed heating and waveforms are likely due to instabilities driven by the free energy provided by reflected ions at this supercritical interplanetary shock. These results offer new insights into collisionless shock dissipation and wave-particle interactions in the solar wind.

  2. Parathyroid biopsy

    Science.gov (United States)

    ... Feel The test feels like a quick needle jab or stick. You may feel a sting as ... activities the same day. Alternative Names Biopsy - parathyroid Images Endocrine glands Parathyroid biopsy References Pellitteri PK, Sofferman ...

  3. Crop Yield, N Uptake and Nitrates in a Fluvo-Aquic Soil Profile

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shu-Xiang; LI Xiu-Ying; LI Xiao-Ping; YUAN Feng-Ming; YAO Zhao-Hua; SUN Yong-Lin; ZHANG Fu-Dao

    2004-01-01

    The effects of different chemical fertilizer combinations (N, P and K) on crop yield, N uptake and nitrate distribution and accumulation to a depth of 100 cm were studied in a cinnamon fiuvo-aquic soil profile (Beijing) with a continuous winter wheat-summer maize cropping system for nine years. The experiment consisted of 7 treatments: no fertilizer control (CK); N alone, N in combination with K (NK), P (NP), and P and K (NPK and N1PK); and P and K in combination without N (PK). The rate of N was 150 kg ha-1 for the N treatments except Treatment N1PK with higher N rate (195 kg ha-1), and the rates of P (P2O5) and K (K2O) were 75 and 37.5 kg ha-1, respectively. The applications of N combined with P and K (NK, NP and NPK) resulted in higher crop yields than a single application of N. The yields followed the order: NPK >NP > N1PKPK > NK > N > CK for winter wheat, and NPK > N1PK > NP > NK > N > PK > CK for summer maize. Supplement of N with P or K, or both P and K resulted in a higher average N uptake of the two crops, which was in a decreasing order NPK > NP > N1PK > NK > N > PK > CK. The combinations also increased apparent N recovery more than N alone and CK. The nitrate content in the profile was thus reduced more in the combination treatments. The nitrate accumulation in the soil profiles followed the order:N > NK > N1PK > NPK > NP > CK > PK. Higher N uptake by the adequately fertilized crops (Treatment NPK) reduced nitrate accumulation in the profile and thus reduced nitrate leaching. The optimum N:P:K ratio was thus of paramount importance in increasing yields and N uptake of crops and reducing nitrate leaching losses.

  4. Upper bounds for prime gaps related to Firoozbakht's conjecture

    OpenAIRE

    Kourbatov, Alexei

    2015-01-01

    We study two kinds of conjectural bounds for the prime gap after the k-th prime $p_k$: (A) $p_{k+1} 9$. The upper bound (A) is equivalent to Firoozbakht's conjecture. We prove that (A) implies (B) with $b=1$; on the other hand, (B) with $b=1.17$ implies (A). We also give other sufficient conditions for (A) that have the form (B) with $b\\to1$ as $p_k\\to\\infty$.

  5. Change in Erythropoietin Pharmacokinetics Following Hematopoietic Transplantation

    OpenAIRE

    Widness, JA; Schmidt, RL; Hohl, RJ; Goldman, FD; Al-Huniti, NH; Freise, KJ; Veng-Pedersen, P.

    2007-01-01

    Pre-clinical studies have demonstrated that bone marrow ablation has a profound effect in decreasing erythropoietin (EPO) elimination. The study’s objective was to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61 years, undergoing fully myeloablative hematopoietic stem cell transplantation. Serial PK studies using intravenous injection of recombinant human EPO (92±2.0 U/kg) (mean±SEM) ...

  6. Evaluation of human pharmacokinetics, therapeutic dose and exposure predictions using marketed oral drugs.

    Science.gov (United States)

    McGinnity, D F; Collington, J; Austin, R P; Riley, R J

    2007-06-01

    In this article approaches to predict human pharmacokinetics (PK) are discussed and the capability of the exemplified methodologies to estimate individual PK parameters and therapeutic dose for a set of marketed oral drugs has been assessed. For a set of 63 drugs where the minimum efficacious concentration (MEC) and human PK were known, the clinical dose was shown to be well predicted or in some cases over-estimated using a simple one-compartment oral PK model. For a subset of these drugs, in vitro potency against the primary human targets was gathered, and compared to the observed MEC. When corrected for plasma protein binding, the MEC of the majority of compounds was GFR. For approximately 90% of compounds studied, the predicted CL using in vitro-in vivo (IVIV) extrapolation together with a CL(renal) estimate, where appropriate, was within 2-fold of that observed clinically. Encouragingly volume of distribution at steady state (V(ss)) estimated in preclinical species (rat and dog) when corrected for plasma protein binding, predicted human V(ss) successfully on the majority of occasions--73% of compounds within 2-fold. In this laboratory, absorption estimated from oral rat PK studies was lower than the observed human absorption for most drugs, even when solubility and permeability appeared not to be limiting. Preliminary data indicate absorption in the dog may be more representative of human for compounds absorbed via the transcellular pathway. Using predicted PK and MEC values estimated from in vitro potency assays there was a good correlation between predicted and observed dose. This analysis suggests that for oral therapies, human PK parameters and clinical dose can be estimated from a consideration of data obtained from in vitro screens using human derived material and in vivo animal studies. The benefits and limitations of this holistic approach to PK and dose prediction within the drug discovery process are exemplified and discussed.

  7. ロクロニウム単回投与から得られた薬物動態モデル6種類の単回・持続投与時における予測性能

    OpenAIRE

    笹川, 智貴

    2016-01-01

    PURPOSE:Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion.METHODS:Rocuronium Cp values from 19 health...

  8. Elucidation of the Pharmacokinetic/Pharmacodynamic Determinant of Colistin Activity against Pseudomonas aeruginosa in Murine Thigh and Lung Infection Models▿

    OpenAIRE

    Dudhani, Rajesh V.; Turnidge, John D.; Coulthard, Kingsley; Milne, Robert W.; Rayner, Craig R.; Li, Jian; Nation, Roger L.

    2009-01-01

    Colistin is increasingly used as last-line therapy against Gram-negative pathogens. The pharmacokinetic (PK)/pharmacodynamic (PD) index that best correlates with the efficacy of colistin remains undefined. The activity of colistin against three strains of Pseudomonas aeruginosa was studied in neutropenic mouse thigh and lung infection models. The PKs of unbound colistin were determined from single-dose PK studies together with extensive plasma protein binding analyses. Dose-fractionation stud...

  9. Pharmacokinetic-Pharmacodynamic Analysis of Spiroindolone Analogs and KAE609 in a Murine Malaria Model

    OpenAIRE

    Lakshminarayana, Suresh B.; Freymond, Céline; Fischli, Christoph; Yu, Jing; Weber, Sebastian; Goh, Anne; Yeung, Bryan K. S.; Ho, Paul C.; Dartois, Véronique; Diagana, Thierry T.; Rottmann, Matthias; Blasco, Francesca

    2014-01-01

    Limited information is available on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters driving the efficacy of antimalarial drugs. Our objective in this study was to determine dose-response relationships of a panel of related spiroindolone analogs and identify the PK-PD index that correlates best with the efficacy of KAE609, a selected class representative. The dose-response efficacy studies were conducted in the Plasmodium berghei murine malaria model, and the relationship between ...

  10. A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach.

    Science.gov (United States)

    Weber, Benjamin; Hochhaus, Guenther

    2015-07-01

    The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) and reference (R) inhaled fluticasone propionate (FP) products. PK bioequivalence trials for inhaled FP were simulated based on this PK model for a varying number of subjects and T products. The statistical power to conclude bioequivalence when T and R products are identical was demonstrated to be 90% for approximately 50 subjects. Furthermore, the simulations demonstrated that PK metrics (area under the concentration time curve (AUC) and C max) are capable of detecting differences between T and R formulations of inhaled FP products when the products differ by more than 20%, 30%, and 25% for total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics, respectively. These results were derived using a rather conservative risk assessment approach with an error rate of <10%. The simulations thus indicated that PK studies might be a viable alternative to clinical studies comparing pulmonary efficacy biomarkers for slowly dissolving inhaled drugs. PK trials for pulmonary efficacy equivalence testing should be complemented by in vitro studies to avoid false positive bioequivalence assessments that are theoretically possible for some specific scenarios. Moreover, a user-friendly web application for simulating such PK equivalence trials with inhaled FP is provided.

  11. Development of a novel tricyclic class of potent and selective FIXa inhibitors.

    Science.gov (United States)

    Meng, Dongfang; Andre, Patrick; Bateman, Thomas J; Berger, Richard; Chen, Yi-Heng; Desai, Kunal; Dewnani, Sunita; Ellsworth, Kenneth; Feng, Daming; Geissler, Wayne M; Guo, Liangqin; Hruza, Alan; Jian, Tianying; Li, Hong; Metzger, Joe; Parker, Dann L; Reichert, Paul; Sherer, Edward C; Smith, Cameron J; Sonatore, Lisa M; Tschirret-Guth, Richard; Wu, Jane; Xu, Jiayi; Zhang, Ting; Campeau, Louis-Charles; Orr, Robert; Poirier, Marc; McCabe-Dunn, Jamie; Araki, Kazuto; Nishimura, Teruyuki; Sakurada, Isao; Hirabayashi, Tomokazu; Wood, Harold B

    2015-11-15

    Using structure based drug design, a novel class of potent coagulation factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds were evaluated in rat IV/PO pharmacokinetic (PK) studies and demonstrated desirable oral PK profiles. Finally, the pharmacodynamics (PD) of this class of molecules were evaluated in thrombin generation assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor. PMID:26318999

  12. Scaling Pharmacodynamics from In Vitro and Preclinical Animal Studies to Humans

    OpenAIRE

    Mager, Donald E.; Woo, Sukyung; Jusko, William J.

    2009-01-01

    An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks...

  13. A pharmacokinetic/pharmacodynamic mathematical model accurately describes the activity of voriconazole against Candida spp. in vitro

    OpenAIRE

    Li, Yanjun; Nguyen, M. Hong; Cheng, Shaoji; Schmidt, Stephan; Zhong, Li; Derendorf, Hartmut; Clancy, Cornelius J.

    2008-01-01

    We developed a pharmacokinetic/pharmacodynamic (PK/PD) mathematical model that fits voriconazole time–kill data against Candida isolates in vitro and used the model to simulate the expected kill curves for typical intravenous and oral dosing regimens. A series of Emax mathematical models were used to fit time–kill data for two isolates each of Candida albicans, Candida glabrata and Candida parapsilosis. PK parameters extracted from human data sets were used in the model to simulate kill curve...

  14. Pharmacokinetics and pharmacodynamics of antibiotics in biofilm infections of Pseudomonas aeruginosa in vitro and in vivo

    DEFF Research Database (Denmark)

    Hengzhuang, Wang; Høiby, Niels; Ciofu, Oana

    2014-01-01

    Although progress on biofilm research has been obtained during the past decades, the treatment of biofilm infections with antibiotics remains a riddle. The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of an antimicrobial agent provide important information helping to establish an effici......Although progress on biofilm research has been obtained during the past decades, the treatment of biofilm infections with antibiotics remains a riddle. The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of an antimicrobial agent provide important information helping to establish...

  15. Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

    OpenAIRE

    Malfatti, Michael A.; Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

    2014-01-01

    Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study ...

  16. Dermoscopy of Pitted Keratolysis

    Directory of Open Access Journals (Sweden)

    Lauren L. Lockwood

    2010-08-01

    Full Text Available Irritated hyperhidrotic soles with multiple small pits are pathognomonic for pitted keratolysis (PK. Here we show the dermatoscopic view of typical pits that can ensure the diagnosis. PK is a plantar infection caused by Gram-positive bacteria, particularly Corynebacterium. Increases in skin surface pH, hyperhidrosis, and prolonged occlusion allow these bacteria to proliferate. The diagnosis is fundamentally clinical and treatment generally consists of a combination of hygienic measures, correcting plantar hyperhidrosis and topical antimicrobials.

  17. Study of the cepheid distribution in the LMC by the Meads method

    International Nuclear Information System (INIS)

    The distribution of the cepheids in the LMC was studied by the Meads analysis. All cepheids and the group of stars with lgP=0.4-0.69 have the scale of non-uniformity about 700-1400 pk. The cepheids in the regions of the bar have the scale of non-uniformity ≅200pk. This scale was also obtained by the correlation analysis

  18. Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats.

    Science.gov (United States)

    Ryu, Sung Ha; Kim, Yong Soon; Jang, Hyun-Jun; Kim, Kyu-Bong

    2015-01-01

    Red ginseng (RG) is one of the top selling herbal medicines in Korea, but is not recommended in hypertensive patients. In this study, the pharmacokinetic (PK) interaction between RG and losartan, an antihypertensive drug, was examined. RG was orally administered for 2 wk to male Sprague-Dawley (S-D) rats at either control (0), 0.5, 1, or 2 g/kg/d for 2 wk. After the last administration of RG and 30 min later, all animals were treated with 10 mg/kg losartan by oral route. In addition, some S-D rats were administered RG orally for 21 d at 2 g/kg followed by losartan intravenously (iv) at 10 mg/kg/d. Post losartan administration, plasma samples were collected at 5, 15, and 30 min and 1, 1.5, 2, 3, 6, 12, and 24 h. Plasma concentrations of losartan and E-3174, the active metabolite of losartan, were analyzed by a high-pressure liquid chromatography-tandem mass spectrometer system (LC-MS/MS). Oral losartan administration showed dose-dependent pharmacokinetics (PK) increase with time to maximum plasma, but this was not significant between different groups. There was no significant change in tmax with E-3174 PK. With iv losartan, pharmacokinetics showed elevation of area under the plasma concentration-time curve from time zero extrapolated to infinitity. There was not a significant change in AUCinf with E-3174 PK. Therefore, RG appeared to interfere with biotransformation of losartan, as RG exerted no marked effect on E-3174 PK in S-D rats. Data demonstrated that oral or iv treatment with losartan in rats pretreated with RG for 2 wk showed that losartan PK was affected but E-3174 PK remained unchanged among different dose groups. These results suggested that RG induces negligible influence on losartan and E-3174 PK in rats.

  19. Comparison the post operative refractive errors in same size corneal transplantation through deep lamellar keratoplasty and penetrating keratoplasty methods after sutures removing in keratoconus patients

    OpenAIRE

    Hasan Razmjoo; Seyed Mohammad Ghoreishi; Alireza Ashtari; Iman Ghafouri; Bashir Mamousi

    2016-01-01

    Background: Corneal transplantation is a surgery in which cornea is replaced by a donated one and can be completely penetrating keratoplasty (PK) or included a part of cornea deep lamellar keratoplasty (DLK). Although the functional results are limited by some complications, it is considered as one of the most successful surgeries. This study aimed to compare the refractive errors after same size corneal transplantation through DLK and PK methods in keratoconus patients over 20 years. Mat...

  20. Omistusrakenteen vaikutus pienten ja keskisuurten yritysten rahoituslähteiden valintaan

    OpenAIRE

    Korhonen, Mikko

    2014-01-01

    Opinnäytetyön tarkoitus on selvittää omistusrakenteen vaikutusta pienten ja keskisuurten yritysten rahoituslähtei-den valintaan. Tutkielmassa tarkastellaan pk-yritysten rahoitusasenteita. Tavoitteena tutkielmassa on saada vastaukset seuraaviin kysymyksiin: Vaikuttaako toimitusjohtajan, pankin omis-tus, pääomasijoitusyhtiöomistus ja keskittynyt omistusrakenne rahoituslähteen valintaan pk-yrityksessä. Yrityksen koon vaikutusta rahoituslähdevalintoihin tutkitaan liikevaihdon suuruudella mita...