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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. Rugged Olympus Mons

    Science.gov (United States)

    2005-01-01

    9 July 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a 1.5 meters per pixel (5 ft/pixel) view of a portion of the upper west flank of the giant martian volcano, Olympus Mons. Although considered to be young relative to much of Mars, at high resolution the Olympus Mons volcano turns out to have one of the most heavily cratered surfaces -- at the scale of small craters of tens of meters diameter and smaller -- on the planet. In other words, while the volcano may be a geologically young feature, it is still very ancient and inactive. A segment of a lava channel -- likely a collapsed lava tube -- is present in this scene. Location near: 17.9oN, 134.6oW Image width: 3 km (1.9 mi) Illumination from: lower left Season: Northern Autumn

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  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. PK-yrityksen tietohallintostrategia

    OpenAIRE

    Tuononen, Jani

    2016-01-01

    Opinnäytetyön tavoitteena oli luoda ohjeistus PK-yrityksen tietohallintostrategian tekemiseen. Opinnäytetyön PK-yrityksen tietohallintostrategiasta on tarkoitus auttaa PK-yritystä arvioimaan oman tietohallintonsa nykytilan ja muutosten tarpeet. Tutkielman tulos auttaa PK-yrityksen tietohallintostrategiaa suunniteltaessa, toteutettaessa ja päivittämisessä. Teoriaosuudessa kerrotaan, mitä on strategia ja mistä PK-yrityksen tietohallintostrategia koostuu. Strategian on tarkoitus edetä koh...

  11. 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,

  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. 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.

  15. 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.

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

    International Nuclear Information System (INIS)

    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.

  17. 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...

  18. 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.

  19. 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

  20. Subglacial birth of Olympus Mons and its aureoles

    International Nuclear Information System (INIS)

    The vast volcanic plains and shields of Mars, together with the thermal, spectrographic, and morphological evidence for water ice at the poles, for several percent water in Viking soil samples, for ground ice of permafrost over much of the planet, and for the existence of surface water at some time in the past, suggest that magma and water or ice may have interacted during evolution of the planet's landscape. Relatively small mesas and buttes, with and without summit craters, are remarkably similar to the table mountains of Iceland that formed by subglacial eruption during the late Quaternary period. Table mountains typically comprise foundations of pillow lava and palagonitized tuff breccias (moberg), overlain by subaerial lava flows that commonly culminated in a typical shield volcano; some table mountains, however, failed to reach the subaerial stage and thus lack the cap rock. Subglacial fissure eruptions produced ridges composed of pillow lava and moberg. Conical knobs on steep-sided Martian plateaus are reminiscent of the small Icelandic shield volcanoes atop moberg pedestals. Candidate table mountains on Mars are especially numerous in the region between latitude 40 0N and the margin of the north polar cap, and interaction of lava with a formerly more extensive ice cap may have occurred. More significant is the possibility that Olympus Mons and the broad lobate aureole deposits around its base may have had similar subglacial beginnings. This hypothesis requires an ice cap several kilometers thick in the vicinity of this enormous shield during its initial stages of eruption. The amounts of water ice required do not appear excessive, given the limits to present knowledge of the water budget throughout the planet's history. A mechanism for localizing such ice, however, is required

  1. 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).

  2. 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...

  3. Pk-yrityksen taloushallinnon ja asiakasrekisterin vaihtaminen

    OpenAIRE

    Hautamäki, Anne

    2010-01-01

    Pk-yritysten taloushallinnon nykyaikaiset tietokantapohjaiset ratkaisut tarjoavat joustavuutta ja tehokkuutta sekä säästävät työtä ja aikaa. Opinnäytetyön tarkoituk-sena oli tutkia kohdeyrityksen nykyisen taloushallinto-ohjelmiston uusimisvaihtoehtoja. Kohdeyritys on mainos- ja liikelahjoja tarjoava pk-yritys. Kohdeyrityksen markki-nointialueeseen kuuluu koko Suomi. Kohdeyrityksellä on tällä hetkellä kaksi myyntitoimipistettä, joista toisessa on myös tuotantoa. Työssä kuvataan kohdeyr...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Instagram-opas pk-yrityksille

    OpenAIRE

    Seppälä, Marjaana

    2016-01-01

    Tämän opinnäytetyön aihe on Instagram-opas pienille ja keskisuurille yrityksille. Tarkoituksena on luoda pk-yrityksille sopiva Instagram-opas, jonka sisältöä voidaan hyödyntää Instagram-palvelun käyttöönotossa ja markkinointia suunniteltaessa. Opas toteutetaan Business-to-Consumer (B2C)– kentällä toimivan yrityksen näkökulmasta. Oppaan tarkoituksena on laskea pk-yrityksen kynnystä lähteä mukaan Instagram-palveluun ja lisätä tietämystä palvelun käytöstä. Tässä opinnäytetyössä tarkastella...

  9. 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...

  10. 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...

  11. 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 ...

  12. 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...

  13. 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.

  14. 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.

  15. The Olympus Scandal: a documentary investigation inside a major Corporate Governance Scandal in Japan.

    OpenAIRE

    Sadet, Fabien

    2013-01-01

    Purpose / Research Problem – This dissertation aims at investigating the Corporate Governance scandal that occurred at Olympus Corporation in 2011. Drawing from its analysis and conclusions, the study arrives to a set of factors influencing such a scandal, such as corporate culture and poor Corporate Governance design. The research has not yet fully explored this scandal, although it appears important in order to enhance Corporate Governance designs around the world. Design / Methodology ...

  16. Modeling Recent Subsidence of Mars' Olympus Mons Using Lava Flows as Paleo-Slope Indicators

    Science.gov (United States)

    Simpson, M.; Reeves, A.; Chadwick, J.; McGovern, P. J.

    2013-12-01

    Olympus Mons is an enormous volcanic edifice on Mars with a basal diameter over 600 km and a height of 23 km. In spite of this size, no indications of subsidence, such as an obvious topographic moat, have previously been detected around the volcano. In this study, we mapped the orientations of long, thin lava flows on the plains to the south and southeast of Olympus Mons using 100m-resolution imagery from the Thermal Emission Imaging System (THEMIS) on Mars Odyssey, and topography using Mars Orbiter Laser Altimeter (MOLA) data from Mars Global Surveyor. The results show that the flows are no longer oriented in a downhill direction, consistently deviating from modern slope vectors in a counterclockwise direction by 21.4 × 10.8 degrees (n = 65). The configuration of this misalignment between modern and paleo-topography is consistent with subsidence centered on the volcano in the time since the flows were emplaced. Our preliminary geophysical modeling used a range of load volumes, load radii, and lithospheric thicknesses to identify the scenario required to best restore modern topography to match the paleo-topography present when the lava flows were emplaced (i.e. 'uplift' Olympus Mons until the lava flows on the surrounding plains are restored to a downhill direction). The results show that lithospheric subsidence of about 1.2 km due to the magmatic addition of 3.8x10^5 km^3 best fits the observed topographic changes. Load center heights of 1 to 8 km were considered, with best fits generally in the 3-5 km range. Best-fit elastic lithosphere thickness (Te) values were generally 100 km or greater, consistent with estimates for Te from loading models [1,2] and gravity-topography relationships [3,4,5]. Our new crater size-density measurements of the plains in the study area show that the observed subsidence occurred within the past 229 × 26 my. Previous crater counts for Olympus Mons calderas and lower flank flows [6] reveal volcanic activity clustered around 100

  17. 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).

  18. 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

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

    International Nuclear Information System (INIS)

    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

  20. 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.

  1. 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...

  2. 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...

  3. 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…

  4. 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

  5. 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....

  6. 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.

  7. Canadian EHF (28/19 GHz) satellite communication terminals for the Olympus program

    Science.gov (United States)

    Pike, C. J.; Bradley, D. R.; Hindson, D. J. M.

    Researchers at the Communications Research Center (CRC) are actively developing extremely high frequency (EHF) technology for the development of the Olympus satellite terminals. The specifications and performance evaluation of the terminals are presented from the radio frequency (RF) perspective as well as the digital approach using 70 MHz modems. Terminals constructed at CRC will be used to conduct experiments in the areas of rain fade countermeasures using an adaptive data rate transmission technique, in on-board processing (OBP) that will be demonstrated in a double-hop configuration using a surface acoustic wave demodulator, and in other user trials related to tele-education, and tele-medicine. Phase shift keyed (PSK) modems will be used for the rain fade countermeasures experiment. Terminals will also be used for demonstrations of point-to-point communications applicable to private business, tele-education and tele-medicine networks.

  8. 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

  9. PK-yrityksen johtaminen ja budjetoinnin kehittäminen

    OpenAIRE

    Penttinen, Petri

    2007-01-01

    Tämän opinnäytetyön tarkoituksena on kuvata budjetoinnin ja rullaavan ennustamisen merkitystä case-yrityksissä. Case-yritysten perusliiketoiminnat ovat täysin erilaisia, joten opinnäytetyössä ei verrata yritysten talousohjausta. Opinnäytetyön teoriaosuudessa esitellään pk- yrityksen johtamisen, budjetoinnin ja rullaavan ennustamisen teoriaa. Haastattelemalla kootussa empiirisessä osuudessa kuvataan, kuinka kahdessa erilaisessa pk- yrityksessä käytännössä toteutetaan näitä. Teoriaosuus on...

  10. MIDAS/PK code development using point kinetics model

    International Nuclear Information System (INIS)

    In this study, a MIDAS/PK code has been developed for analyzing the ATWS (Anticipated Transients Without Scram) which can be one of severe accident initiating events. The MIDAS is an integrated computer code based on the MELCOR code to develop a severe accident risk reduction strategy by Korea Atomic Energy Research Institute. In the mean time, the Chexal-Layman correlation in the current MELCOR, which was developed under a BWR condition, is appeared to be inappropriate for a PWR. So as to provide ATWS analysis capability to the MIDAS code, a point kinetics module, PKINETIC, has first been developed as a stand-alone code whose reference model was selected from the current accident analysis codes. In the next step, the MIDAS/PK code has been developed via coupling PKINETIC with the MIDAS code by inter-connecting several thermal hydraulic parameters between the two codes. Since the major concern in the ATWS analysis is the primary peak pressure during the early few minutes into the accident, the peak pressure from the PKINETIC module and the MIDAS/PK are compared with the RETRAN calculations showing a good agreement between them. The MIDAS/PK code is considered to be valuable for analyzing the plant response during ATWS deterministically, especially for the early domestic Westinghouse plants which rely on the operator procedure instead of an AMSAC (ATWS Mitigating System Actuation Circuitry) against ATWS. This capability of ATWS analysis is also important from the view point of accident management and mitigation

  11. MIDAS/PK code development using point kinetics model

    Energy Technology Data Exchange (ETDEWEB)

    Song, Y. M.; Park, S. H. [KAERI, Taejon (Korea, Republic of)

    1999-05-01

    In this study, a MIDAS/PK code has been developed for analyzing the ATWS (Anticipated Transients Without Scram) which can be one of severe accident initiating events. The MIDAS is an integrated computer code based on the MELCOR code to develop a severe accident risk reduction strategy by Korea Atomic Energy Research Institute. In the mean time, the Chexal-Layman correlation in the current MELCOR, which was developed under a BWR condition, is appeared to be inappropriate for a PWR. So as to provide ATWS analysis capability to the MIDAS code, a point kinetics module, PKINETIC, has first been developed as a stand-alone code whose reference model was selected from the current accident analysis codes. In the next step, the MIDAS/PK code has been developed via coupling PKINETIC with the MIDAS code by inter-connecting several thermal hydraulic parameters between the two codes. Since the major concern in the ATWS analysis is the primary peak pressure during the early few minutes into the accident, the peak pressure from the PKINETIC module and the MIDAS/PK are compared with the RETRAN calculations showing a good agreement between them. The MIDAS/PK code is considered to be valuable for analyzing the plant response during ATWS deterministically, especially for the early domestic Westinghouse plants which rely on the operator procedure instead of an AMSAC (ATWS Mitigating System Actuation Circuitry) against ATWS. This capability of ATWS analysis is also important from the view point of accident management and mitigation.

  12. 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.

  13. 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

  14. Genetic Diversity, Natural Selection and Haplotype Grouping of Plasmodium knowlesi Gamma Protein Region II (PkγRII): Comparison with the Duffy Binding Protein (PkDBPαRII)

    Science.gov (United States)

    Fong, Mun Yik; Rashdi, Sarah A. A.; Yusof, Ruhani; Lau, Yee Ling

    2016-01-01

    Background Plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in Southeast Asia. This parasite invades the erythrocytes of humans and of its natural host, the macaque Macaca fascicularis, via interaction between the Duffy binding protein region II (PkDBPαRII) and the Duffy antigen receptor on the host erythrocytes. In contrast, the P. knowlesi gamma protein region II (PkγRII) is not involved in the invasion of P. knowlesi into humans. PkγRII, however, mediates the invasion of P. knowlesi into the erythrocytes of M. mulata, a non-natural host of P. knowlesi via a hitherto unknown receptor. The haplotypes of PkDBPαRII in P. knowlesi isolates from Peninsular Malaysia and North Borneo have been shown to be genetically distinct and geographically clustered. Also, the PkDBPαRII was observed to be undergoing purifying (negative) selection. The present study aimed to determine whether similar phenomena occur in PkγRII. Methods Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkγRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00) programmes. Genetic differentiation between the PkγRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright’s FST fixation index in DnaSP (version 5.10.00). Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3). Results A total of 78 PkγRII sequences was obtained. Comparative analysis showed that the PkγRII have similar range of haplotype (Hd) and nucleotide diversity (π) with that of PkDBPαRII. Other similarities between PkγRII and PkDBPαRII include undergoing purifying (negative) selection, geographical

  15. Black Carbon and Dust in Snow and Ice on Snow Dome, Mt. Olympus

    Science.gov (United States)

    Kaspari, S.; Delaney, I.; Skiles, M.; Dixon, D. A.

    2012-12-01

    Deposition of black carbon (BC) and dust on highly reflective snow and glacier ice causes darkening of the surface, resulting in greater absorption of solar energy, heating of the snow/ice, and accelerated snow and glacier melt. The deposition of BC and dust may be affecting the timing and availability of water resources in the Pacific Northwest where the majority of runoff comes from snow and glacier melt, but minimal related research has taken place in this region. A recent modeling study suggested that BC deposition is causing a decrease in spring snow water equivalent and a shift to earlier peak runoff in the spring in the Western United States. Additionally, limited observations made in the early 1980s in Washington State determined that light absorbing impurities (e.g., BC and dust) were reducing the snow albedo. Since 2009, we have collected snow and ice samples from glaciers and the seasonal snowpack from spatially distributed sites in Washington State to determine impurity content, and to assess how impurity concentrations vary in relation to emission source proximity. Here we present results from the summer 2012 fieldwork on Snow Dome, Mt. Olympus in Washington State. Mt. Olympus is located upwind from major regional sources of BC and dust, but may receive BC from ocean shipping and trans-Pacific transport of BC and dust from large Asian sources. We used a field spectrometer to measure spectral albedo on Snow Dome, and analyzed surface snow samples and shallow ice cores to characterize the spatial and temporal variability of impurity deposition. Total impurity load was determined gravimetrically. Dust concentrations are inferred from ICPMS analyses and BC concentrations are determined using a Single Particle Soot Photometer (SP2), with select samples also analyzed for BC using a Sunset EC-OC to facilitate method inter-comparison. We assess the role that absorbing impurities may play in accelerating melt at Snow Dome, and briefly compare our results to

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. Pk-yrityksen messuosallistuminen : Mekalasi Oy Lapsi 2009 -messuilla

    OpenAIRE

    Puttonen, Sari; Kajander, Satu

    2009-01-01

    Opinnäytetyö toteutettiin työelämälähtöisenä kehittämishankkeena, jonka kohdeorganisaationa oli Mekalasi Oy. Kehittämishankkeen tarkoituksena oli perehtyä pk-yrityksen messuosallistumiseen kansainvälisillä messuilla ja tuottaa messusuunnitelma Lapsi 2009 -messuille. Tavoitteena oli koota kohdeorganisaatiolle teoreettiseen tietoon perustuva, käytännöllinen ja myöhemmin muillekin messuille sovellettavissa oleva messusuunnitelma. Kehittämishanke toteutettiin toimintakeskeisenä hankkeen...

  2. 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...

  3. 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...

  4. 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…

  5. 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.

  6. 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.

  7. 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...

  8. Cellular response to DNA damage. Link between p53 and DNA-PK

    International Nuclear Information System (INIS)

    Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to ionizing radiation and display an inability to repair double-strand DNA breaks. DNA-PK is a member of a protein kinase family that includes ATR and ATM which have strong homology in their carboxy-terminal kinase domain with Pl-3 kinase. ATM has been proposed to act upstream of p53 in cellular response to ionizing radiation. DNA-PK may similarly interact with p53 in cellular growth control and in mediation of the response to ionizing radiation. (author)

  9. Analytiikan hyödyntäminen pk-yritysten liiketoiminnassa

    OpenAIRE

    Lehtinen, Jaakko

    2014-01-01

    Opinnäytetyö tehtiin osana tuotantotalouden insinööritutkintoa Metropolia Ammattikorkeakoulussa. Työn tarkoitus oli selvittää Suomen pk-yritysten valmius analytiikan hyödyntämiseen maturiteettitasojen avulla. Työssä selvitettiin myös, miten pk-yrityksen tulisi nähdä edistyneempien tiedonhallinnan ilmiöt ja miten pk-yritys voisi nostaa maturiteettitasoaan analytiikan hyödyntämisessä ja kilpailla käyttämällä analytiikkaa liiketoimintaprosessissaan. Opinnäytetyössä käytettiin laadullista...

  10. Multiscale Reactive Molecular Dynamics for Absolute pK a Predictions and Amino Acid Deprotonation.

    Science.gov (United States)

    Nelson, J Gard; Peng, Yuxing; Silverstein, Daniel W; Swanson, Jessica M J

    2014-07-01

    Accurately calculating a weak acid's pK a from simulations remains a challenging task. We report a multiscale theoretical approach to calculate the free energy profile for acid ionization, resulting in accurate absolute pK a values in addition to insights into the underlying mechanism. Importantly, our approach minimizes empiricism by mapping electronic structure data (QM/MM forces) into a reactive molecular dynamics model capable of extensive sampling. Consequently, the bulk property of interest (the absolute pK a) is the natural consequence of the model, not a parameter used to fit it. This approach is applied to create reactive models of aspartic and glutamic acids. We show that these models predict the correct pK a values and provide ample statistics to probe the molecular mechanism of dissociation. This analysis shows changes in the solvation structure and Zundel-dominated transitions between the protonated acid, contact ion pair, and bulk solvated excess proton. PMID:25061442

  11. Pk-ifrs:n vaikutukset tilitoimistojen työhön Suomessa

    OpenAIRE

    Ylipekkala, Kaisa

    2011-01-01

    Tutkimuksen tavoitteet Tutkimuksen tavoitteena oli selvittää, miten pk-ifrs vaikuttaa tilitoimistojen työhön Suomessa, mikäli pienet ja keskisuuret yritykset alkavat soveltaa kyseistä normistoa. Tavoitteena oli tutkia pk-ifrs:n vaikutuksia tilitoimistojen liiketoimintaan, henkilöstöön ja kirjanpitojärjestelmiin. Lähdeaineisto Tutkimus toteutettiin kvalitatiivisena tutkimuksena. Teoreettisen osuuden aineistona käytettiin sekä kotimaista että ulkomaista ammattikirjallisuutta, lehtia...

  12. 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.

  13. 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

  14. 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

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

    International Nuclear Information System (INIS)

    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

  16. 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.

  17. 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

  18. 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.

  19. 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)

  20. 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.

  1. Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme

    International Nuclear Information System (INIS)

    Purpose: To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy. Materials and methods: Thirty four patients with GBM received postoperative radiotherapy. Tumor sections were examined for poly-ADP ribose polymerase-1 (PARP-1) and DNA protein kinase (DNA-PK) expression. Immunohistochemical staining intensities of PARP-1 and DNA-PK were determined (score 0–3) and expression levels were correlated with patients overall survival. Results: Median survival time of the whole study group was 10.0 months (95% CI 8.1–11.9). Median survival of patients with high and low (⩾median and < median) tumor PARP-1 levels were 10.0 months (95% CI 7.9–12.1) and 12.0 months (95% CI 8.3–15.7), respectively (p = 0.93). In contrast, median survival of patients with high and low tumor DNA-PK levels were 9.0 months (95% CI 7.2–10.8) and 13.0 months (95% CI 10.7–15.3), respectively (p = 0.02). In multivariate analysis, DNA-PK expression emerged as a significant independent predictor for overall survival (HR 3.9, 95% CI 1.5–10.7, p = 0.01). Conclusion: This hypothesis generating study showed that high tumor levels of DNA-PK correlate with poor survival of GBM patients. Further studies are needed to confirm these results and to clarify whether DNA-PK inhibitors might have a potential to radiosensitize GBM and improve the treatment outcome of this devastating disease.

  2. Sum Peak Measurements for ICC and PK Determination in the Decay of 152,154 Eu

    International Nuclear Information System (INIS)

    The X and gamma rays energies and intensities from decay of 152 Eu were measured accurately using high resolution HPGe detector. The sum peak technique is used to determine the internal conversion coefficients (K) for the first excited states in 152 Sm, 152 Gd and 154 Gd and the K-capture probability (Pk). The Experimental results indicate for (K) a good agreement with the experimental and theoretical values for pure E2 transitions. Also the Pk values show an agreement with the experimental and theoretical values. 3 figs., 5 tabs

  3. Pk-yritysten automaatiosuunnittelu ja automaation käyttö

    OpenAIRE

    Vuorenmaa, Esa

    2014-01-01

    Opinnäytetyön aiheena oli: Pk-yritysten automaatiosuunnittelu ja automaation käyttö. Työllä ei ollut erillistä toimeksiantajaa, vaan se perustui henkilökohtaiseen mielenkiintoon aiheesta. Työn tuloksilla saan alustavaa tietoa automaation ja automaatiosuunnittelun tarjoamisen kannattavuudesta ja mahdollisuuksista oman toiminimen perustamisen näkökannalta. Työn tavoitteena oli selvittää pk-yritysten suhtautumista automaation käytöstä, automaatiosuunnittelusta, sekä heidän yleisiä mielipite...

  4. Studies on the genetic basis of Pk, P and P1 blood group antigen expression

    OpenAIRE

    Hellberg, Åsa

    2007-01-01

    The clinically important carbohydrate P/GLOB blood group systems and collection give rise to both common (P1, P2) and rare (p, P1k, P2k) blood group phenotypes. The associated antibodies are implicated in severe transfusion reactions and recurrent spontaneous abortions. The aim of this study was to explore the molecular genetic basis of Pk, P and P1 antigen expression. Sequence analysis of the A4GALT and B3GALNT1 genes proposed to synthesize the related Pk (Gb3) and P (Gb4) antigens, r...

  5. 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...

  6. Crecimiento celular de cultivos PK-15 inoculados con la cepa Aranjuez del virus de la enfermedad de Newcastle (NDV)

    OpenAIRE

    González Zapatero, M.ª A.; De Santiago Redel, Enrique

    1984-01-01

    [EN]The effect produced by the Aranjuez strain of Newcastle disease virus (NDV), over the growth of PK-15 cell cultures, is studied in the present paper. The PK-15 cell cultures non-inoculated were compared with the cell cultures inoculated in different serial passages of the virus. The mitotic index of this cell culture is, also established.

  7. Seizing the Opportunity: Building PK3 Systems in New Jersey's School Districts. Policy Brief

    Science.gov (United States)

    Rice, Cynthia

    2008-01-01

    This policy brief discusses how the implementation of high quality preschool required by the expansion initiative can set the stage for a more expansive view of the first stage of children's education: the development of a preschool-through third-grade (PK3) system. By adopting a broader view of early childhood education as a period extending from…

  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:: The...

  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. 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

  11. 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

  12. 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.

  13. 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

  14. 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.)

  15. Pharmacokinetic (PK) drug interaction studies of cabozantinib: Effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK.

    Science.gov (United States)

    Nguyen, Linh; Holland, Jaymes; Miles, Dale; Engel, Caroline; Benrimoh, Natacha; O'Reilly, Terry; Lacy, Steven

    2015-09-01

    Cabozantinib is a small-molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with progressive, metastatic medullary thyroid cancer. In vitro data indicate that (1) cytochrome P450 (CYP) 3A4 is the primary CYP isoenzyme involved in the metabolism of cabozantinib, and (2) CYP2C8 is the CYP isoenzyme most potently inhibited by cabozantinib with potential for in vivo inhibition at clinically relevant plasma exposures. Pharmacokinetic (PK) drug-drug interactions (DDIs) were evaluated clinically between cabozantinib and (1) a CYP3A inducer (rifampin) in healthy volunteers, (2) a CYP3A inhibitor (ketoconazole) in healthy volunteers, and (3) a CYP2C8 substrate (rosiglitazone) in patients with solid tumors. Compared with cabozantinib given alone, coadministration with rifampin resulted in a 4.3-fold higher plasma clearance (CL/F) of cabozantinib and a 77% decrease in cabozantinib plasma AUC0-inf , whereas coadministration with ketoconazole decreased cabozantinib CL/F by 29% and increased cabozantinib AUC0-inf by 38%. Chronic coadministration with cabozantinib resulted in no significant effect on rosiglitazone plasma Cmax , AUC0-24 , or AUC0-inf . In summary, chronic use of strong CYP3A inducers and inhibitors should be avoided when cabozantinib is administered, and cabozantinib at clinically relevant exposures is not anticipated to markedly affect the PK of concomitant medications via CYP enzyme inhibition. PMID:25854986

  16. 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.

  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. 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

  19. 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.

  20. Onko verotus esteenä Pk-IFRS:n etenemiselle Euroopassa? Case: Suomi, Saksa, Ruotsi ja Iso-Britannia

    OpenAIRE

    Lehtiniemi, Minna

    2012-01-01

    TUTKIELMAN TAVOITTEET Tutkielman tavoitteena on tutkia Suomen, Ruotsin, Saksan ja Iso-Britannian ve-rotuskäytäntöjä ja verrata verotuksen yhteensopivuutta Pk-IFRS – standardin kirjauskäytäntöihin. Tutkielmassa pyrittiin selvittämään toimiiko verotus esteenä Pk-IFRS:n soveltamiselle edellä mainituissa maissa. Samalla etsittiin mahdollista esimerkkiä Suomessa vallitsevaan kirjanpidon ja verotuksen kytkösongelmaan. Tutkielmassa on lisäksi tuotu EU:ssa sekä maailmalla meneillään olevia Pk-IFR...

  1. 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.

  2. Pk-yrityksen lyhyen aikavälin talouden suunnittelu ja hallinta

    OpenAIRE

    Hannula, Jukka

    2012-01-01

    Opinnäytetyössä käsitellään pk-yrityksen talouden suunnittelua ja hallintaa. Tarkasteluajanjakso on nykyhetkestä seuraavan vuoden loppuun. Talouden suunnittelua lähestytään sekä budjetoinnin että laskentatoimen yritysjohdolle tuottamien raporttien kautta. Budjetoinnissa käydään läpi erilaiset budjetin laatimisen mahdollisuudet sekä osabudjettien laatimisen perusperiaatteet. Laskentatoimen raportoinnin osalta tarkastellaan erityisesti johdon laskentatoimen mahdollisuuksia tukea yrityksen johto...

  3. Responses of Bog Vegetation and CO2 Exchange to Experimental N and PK Addition

    Science.gov (United States)

    Juutinen, S.; Bubier, J. L.; Shrestha, P.; Smith, R.; Moore, T.

    2008-12-01

    Atmospheric nitrogen (N) deposition has the potential to alter the structure and functioning of nutrient poor wetland ecosystems. It is important to quantify the effect of N input on ecosystem carbon (C) sequestration in these globally important C storages. We address this issue at the temperate Mer Bleue bog, ON, Canada. After 6 years of experimental fertilization, we saw that high N deposition can change mixed Sphagnum and dwarf shrub dominated communities to taller and denser dwarf shrub communities that are losing moss cover, and which might have even lower net C uptake. Now, after 8 years of fertilization and with new treatments we quantify the relationship between the plant community structure and ecosystem CO2 exchange. Three levels of N fertilization were applied with or without phosphorus and potassium (PK) into triplicate plots. We measured light saturated net ecosystem CO2 exchange (NEE), and its components ecosystem respiration and gross photosynthesis using clear and dark chambers (May-August). Vegetation characteristics were quantified by measuring foliage cover (LAI), amount of woody and foliar biomass, and abundance of moss species (point interception technique), moss growth (cranked wires) and green area of vascular leaves and moss. Addition of PK fertilizer did not alter NEE or its components relative to the control. The 8-year low N addition alone and with PK, and the 4-year fertilization with high N levels resulted in the highest net ecosystem CO2 uptake relative to the control. The ecosystem respiration increased with increasing N input rate. All levels of N fertilization resulted in higher gross photosynthesis than the control, but there was no increasing trend with increasing N input. Vascular foliage increased, while moss cover drastically decreased with increasing levels of N fertilization. At the highest level of N (and PK) addition woody biomass increased at the expense of leaf increment. Dependencies of ecosystem CO2 exchange on the

  4. 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.

  5. 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

  6. 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 ...

  7. 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.

  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. Návrh optimálního modelu e-komunikace pro divizi mikroskopů a průmyslových endoskopů společnosti Olympus

    OpenAIRE

    Dobiášová, Olga

    2008-01-01

    The graduatin thesis is devoted to implementation of the new model of e-communication for the division of microscopes and industrial endoscopes of the Olympus company. The first part includes theoretical essentials for the elaboration. The terms concerning marketing and commerial communications are explained in it, such as the differences between the purchasing process of the consumer and the companies, the topic of brand management is also mentioned and situation analysis and in the end gene...

  10. 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

  11. 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...

  12. 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...

  13. 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...

  14. Opas digitaalisten palveluiden hyödyntämiseksi matkailualan pk-yrityksissä

    OpenAIRE

    Kaitala, Ilona

    2013-01-01

    Digitaalisista palveluista on tullut merkittävä osa nykypäivän markkinointia. Myös matkailualan yritysten ja asiakkaiden digitaalisten palveluiden käyttö on yleistynyt. Tämän opinnäytetyön tavoitteina on tuottaa digitaalisen markkinoinnin opas sekä selvittää, millaisia digitaalisia palveluita voidaan käyttää matkailualan pk-yritysten markkinoinnissa, sekä miten digitaalista markkinointia käytetään matkailualalla. Opinnäytetyön toimeksiantajana on Hämeen Ammattikorkeakoulun eTour– hank...

  15. A Comparison of Decision Methods for C pk When Data are Autocorrelated

    DEFF Research Database (Denmark)

    Lundkvist, Peder; Vannman, Kerstin; Kulahci, Murat

    2012-01-01

    In many industrial applications, autocorrelated data are becoming increasingly common due to, for example, on-line data collection systems with high-frequency sampling. Therefore, the basic assumption of independent observations for process capability analysis is not valid. The purpose of this...... article is to compare decision methods using the process capability index C-pk when data are autocorrelated. This is done through a case study followed by a simulation study. In the simulation study the actual significance level and power of the decision methods are investigated. The outcome of the...

  16. 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...

  17. Ict-toimintojen johtamismallin kehittäminen pk-yrityksessä

    OpenAIRE

    Sarvi, Juha

    2013-01-01

    Tämä opinnäytetyö on tehty Kesla Oyj:n toimeksiannosta. Työn tavoitteena oli luoda liiketoimintastrategiaa tukeva johtamismalli pk-yrityksen tietohallinnosta vastaavalle organisaatiolle. Yrityksessä on käytössä ISO 9001 laatujärjestelmä, jossa on kuvattu yrityksen ydinprosessit, mutta ei tukiprosesseja. Johtamismalli haluttiin luoda siten, että sen perustana on strategia- ja prosessijohtamismalli. Työ aloitettiin keräämällä tietoa kokouskäytäntöjen nykytilanteesta haastattelemalla yrityks...

  18. 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。

  19. 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...

  20. LLC-PK1 cells express Na+-lactate cotransport in apical membranes after confluency

    International Nuclear Information System (INIS)

    L-[3H]lactate uptake was characterized in LLC-PK1 cell apical membrane vesicles obtained by intensive culture on microcarrier beads. The apical membrane preparation technique involved MgCl2 precipitation. Na+-dependent L-[3H]lactate uptake was present only after confluency; its appearance paralleled the subcellular localization of aminopeptidase in apical membranes. L-[3H]lactate uptake was Na+-dependent and electrogenic. Only the Na+-dependent component of L[3H]lactate uptake was saturable with one family of independent carriers. The apparent affinity constant was 1.1 ± 0.25 mM and the apparent maximal velocity was 29 ± 3 nmol·mg-1·min-1. The Na+-lactate cotransport stoichiometry was 2 Na+ for 1 lactate. The specificity of the L-lactate transport system was compatible with that of the monocarboxylic acid pathway described previously brush-border membranes of kidney cortex and discrete from the tricarboxylic acid carrier, the D-glucose transporter, and the general pathway for anions. The LLC-PK1 cell line appears to be a useful tool for study of the regulation of L-lactate uptake and biosynthesis of the renal monocarboxylic acid transporter

  1. 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....

  2. 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

  3. pkDACLASS: Open source software for analyzing MALDI-TOF data

    Science.gov (United States)

    Ndukum, Juliet; Atlas, Mourad; Datta, Susmita

    2011-01-01

    In recent years, mass spectrometry has become one of the core technologies for high throughput proteomic profiling in biomedical research. However, reproducibility of the results using this technology was in question. It has been realized that sophisticated automatic signal processing algorithms using advanced statistical procedures are needed to analyze high resolution and high dimensional proteomic data, e.g., Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) data. In this paper we present a software package-pkDACLASS based on R which provides a complete data analysis solution for users of MALDITOF raw data. Complete data analysis comprises data preprocessing, monoisotopic peak detection through statistical model fitting and testing, alignment of the monoisotopic peaks for multiple samples and classification of the normal and diseased samples through the detected peaks. The software provides flexibility to the users to accomplish the complete and integrated analysis in one step or conduct analysis as a flexible platform and reveal the results at each and every step of the analysis. Availability The database is available for free at http://cran.r-project.org/web/packages/pkDACLASS/index.html PMID:21464846

  4. 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

  5. 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

  6. A possible role of repair proteins BRCA1 and DNA-PK in the processing of oxidative DNA damage

    Directory of Open Access Journals (Sweden)

    Alexandros G Georgakilas

    2008-08-01

    Full Text Available BRCA1 and DNA-PK are two significant multifunctional proteins involved primarily in the processing of double strand breaks (DSBs. BRCA1 participates actively in homologous recombination (HR while DNA-PK in non-homologous end joining (NHEJ. In this mini review, we discuss all recent evidence for a possible involvement of these repair proteins also in the processing of oxidatively-induced DNA damage.Keyword: DNA damage, BRCA1, DNA-PKReceived: 6 June 2008, Accepted: 10 August 2008 Published online: 18 August 2008

  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. PK-PD modelling of norfloxacin after oral administration in rabbits

    Directory of Open Access Journals (Sweden)

    B.H. Pavithra

    Full Text Available Norfloxacin posses a wide spectrum of activity, excellent tissue penetration and is rapidly bactericidal at low concentrations and hence an attempt was made to integrate reported pharmacodynamic data with pharmacokinetic data of norfloxacin after oral administration in rabbits to determine its effectiveness against common bacterial pathogens infecting rabbits. Pharmacokinetic data were obtained after a single per oral administration of norfloxacin @ 100mg per kg. Plasma drug concentrations were determined using high performance liquid chromatography (HPLC. From PK-PD integration, it is observed that norfloxacin is highly effective against gram negative infections caused by Pasteurella multocida (AUC/MIC and Cmax/MIC ratio of 133.5 and 111.5 respectively, its efficacy against Salmonella spp., E. Coli, Shigella spp. and Haemophilus influenza is moderate. However, per-oral administration of norfloxacin is not suitable to contain tested gram positive bacterial pathogens infecting rabbits. [Veterinary World 2010; 3(12.000: 546-548

  9. 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...

  10. Pharmacokinetics, bioavailability and PK/PD relationship of cefquinome for Escherichia coli in Beagle dogs.

    Science.gov (United States)

    Zhou, Y F; Zhao, D H; Yu, Y; Yang, X; Shi, W; Peng, Y B; Liu, Y H

    2015-12-01

    The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration-time curve of cefquinome was analyzed using a two-compartmental model, and the mean values of t1/2α (h), t1/2β (h), Vss (L/kg), ClB (L/kg/h) and AUC (μg·h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one-compartmental model with first-order absorption. The mean values of t1/2Kel , t1/2Ka , tmax (h), Cmax (μg/mL) and AUC (μg·h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC90 (0.125 μg/mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study. PMID:25776615

  11. 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.

  12. Contribution of reactive oxygen species to para-aminophenol toxicity in LLC-PK1 cells

    International Nuclear Information System (INIS)

    para-aminophenol (PAP) causes nephrotoxicity by biochemical mechanisms that have not been fully elucidated. PAP can undergo enzymatic or non-enzymatic oxidation to form reactive intermediates. Using modulators of reactive oxygen species (ROS), the role of ROS in PAP toxicity in LLC-PK1 cells was investigated. ROS formation was determined using a fluorescein derivative and viability using alamarBlue. Following treatment of cells with PAP, ROS formation occurred prior to loss of cell viability. Several modulators of ROS were used to identify the pathways involved in PAP toxicity. Viability was improved with catalase treatment, while viability was decreased when cells were treated with superoxide dismutase (SOD). Both catalase and SOD exert their effects outside of cells in the incubation medium, since there was no evidence of uptake of these enzymes in LLC-PK1 cells. In cell-free incubations, hydrogen peroxide (H2O2) was produced when 0.5 mM PAP was included in the incubation medium. Further, SOD greatly increased and catalase greatly decreased H2O2 production in these cell-free incubations. These data suggest that H2O2 formed in the incubation medium contributes to loss of viability following PAP treatment. When cells were coincubated with 0.5 mM PAP and tiron, pyruvate, bathocuproine, 1, 10-phenanthroline, or dimethylthiourea (DMTU), ROS formation was decreased. However, there was minimal improvement in cell viability. Paradoxically, DMTU exacerbated PAP-induced loss of viability. These data suggest that ROS are generated in cells exposed to PAP but these species are not the predominant cause of cellular injury

  13. 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

  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. An amphiphilic, PK-PBAN analog is a selective pheromonotropic antagonist that penetrates the cuticle of a heliothine insect

    Science.gov (United States)

    A linear pyrokinin(PK)/pheromone biosynthesis activating neuropeptide (PBAN) lead antagonist was structurally modified to impart amphiphilic properties to enhance its ability to transmigrate the hydrophobic cuticle of noctuid moth species and yet retain aqueous solubility in the hemolymph to reach t...

  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. Accelerated glacier melt on Snow Dome, Mount Olympus, Washington, USA, due to deposition of black carbon and mineral dust from wildfire

    Science.gov (United States)

    Kaspari, Susan; McKenzie Skiles, S.; Delaney, Ian; Dixon, Daniel; Painter, Thomas H.

    2015-04-01

    Assessing the potential for black carbon (BC) and dust deposition to reduce albedo and accelerate glacier melt is of interest in Washington because snow and glacier melt are an important source of water resources, and glaciers are retreating. In August 2012 on Snow Dome, Mount Olympus, Washington, we measured snow surface spectral albedo and collected surface snow samples and a 7 m ice core. The snow and ice samples were analyzed for iron (Fe, used as a dust proxy) via inductively coupled plasma sector field mass spectrometry, total impurity content gravimetrically, BC using a single-particle soot photometer (SP2), and charcoal through microscopy. In the 2012 summer surface snow, BC (54 ± 50 µg/L), Fe (367±236 µg/L) and gravimetric impurity (35 ± 18 mg/L) concentrations were spatially variable, and measured broadband albedo varied between 0.67-0.74. BC and dust concentrations in the ice core 2011 summer horizon were a magnitude higher (BC = 3120 µg/L, Fe = 22000 µg/L, and gravimetric impurity = 1870 mg/L), corresponding to a modeled broadband albedo of 0.45 based on the measured BC and gravimetric impurity concentrations. The Big Hump forest fire is the likely source for the higher concentrations. Modeling constrained by measurements indicates that the all-sky 12 h daily mean radiative forcings in summer 2012 and 2011 range between 37-53 W m-2 and 112-149 W m-2, respectively, with the greater forcings in 2011 corresponding to a 29-38 mm/d enhancement in snowmelt. The timing of the forest fire impurity deposition is coincident with an increase in observed discharge in the Hoh River, highlighting the potential for BC and dust deposition on glaciers from forest fires to accelerate melt.

  20. The pK0Σ+ final state in proton-proton collisions

    International Nuclear Information System (INIS)

    This paper reports results from a study of the reaction pp → pK0Σ+ at beam momenta of pbeam = 2950, 3059, and 3200 MeV/c (excess energies of ε = 126, 161, and 206 MeV). Total cross-sections were determined for all energies; a set of differential cross-sections (Dalitz plots; invariant-mass spectra of all two-body subsystems; angular distributions of all final-state particles; distributions in helicity and Jackson frames) are presented for ε = 161 MeV. The total cross-sections are proportional to the volume of available three-body phase space indicating that the transition matrix element does not change significantly in this range of excess energies. It is concluded from the differential data that the reaction proceeds dominantly via the N(1710)P11- and/or N(1720)P13-resonance(s); N(1650)S11 and Δ(1600)P33 could also contribute. (orig.)

  1. 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.

  2. 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-...

  3. 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.

  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. 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

    BACKGROUND: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic......-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical...... patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps. METHODS: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple d...

  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. Effects on field- and bottom-layer species in an experiment with repeated PK- and NPK-fertilization

    International Nuclear Information System (INIS)

    Long-term changes in forest ground vegetation because of repeated PK- and NPK-fertilization were examined in an old field experiment, located in a 85-year-old Pinus sylvestris stand in northern Sweden. Fertilizers were added at 5-(PK, NPK) or 10-(PK) year intervals, beginning 26 years prior to the study. The treatments were tested in two replicates on plots sized 40 x 40 m. The total doses added were N 720 kg/ha, P 222-380 kg/ha and K 318-620 kg/ha. N was given as ammonium nitrate, P as superphosphate and K as potassium chloride. The vegetation on control plots was of the Vaccinium vitis-idaea type. The field layer was dominated by V.vitis-idaea and V.myrtillus, and the bottom layer by Pleurozium schreberi. The effect of fertilization was quantified by examining the areal cover of individual species. This was done in 25 0.25 m2 frames systematically placed in a grid over each treatment plot. The only pronounced effect in the field layer was on V.myrtillus. The cover was strongly reduced by fertilization with PK. The reduction was 70% for the 5-year interval and 34% for the 10-year interval. The cover more than doubled after NPK-fertilization. Among the cryptogams, a reduction in cover was indicated for Cladina arbuscula and C.rangiferina because of fertilization with NPK. NPK reduced the number of species that were found, totally depending on negative effects on several lichen species. For species absent in the examined frame areas but present somewhere else on the treatment plots, it was seen that Deschampsia flexuosa increased after NPK-fertilization, while Peltigera apthosa and Steroecaulon tomentosum decreased. Hylocomium splendens occurred on both control plots, but only on one fertilized plot. 30 refs, 1 fig, 5 tabs

  9. Dual Identification and Analysis of Differentially Expressed Transcripts of Porcine PK-15 Cells and Toxoplasma gondii during in vitro Infection

    Science.gov (United States)

    Zhou, Chun-Xue; Elsheikha, Hany M.; Zhou, Dong-Hui; Liu, Qing; Zhu, Xing-Quan; Suo, Xun

    2016-01-01

    Toxoplasma gondii is responsible for causing toxoplasmosis, one of the most prevalent zoonotic parasitoses worldwide. The mechanisms that mediate T. gondii infection of pigs (the most common source of human infection) and renal tissues are still unknown. To identify the critical alterations that take place in the transcriptome of both porcine kidney (PK-15) cells and T. gondii following infection, infected cell samples were collected at 1, 3, 6, 9, 12, 18, and 24 h post infection and RNA-Seq data were acquired using Illumina Deep Sequencing. Differential Expression of Genes (DEGs) analysis was performed to study the concomitant gene-specific temporal patterns of induction of mRNA expression of PK-15 cells and T. gondii. High sequence coverage enabled us to thoroughly characterize T. gondii transcriptome and identify the activated molecular pathways in host cells. More than 6G clean bases/sample, including >40 million clean reads were obtained. These were aligned to the reference genome of T. gondii and wild boar (Sus scrofa). DEGs involved in metabolic activities of T. gondii showed time-dependent down-regulation. However, DEGs involved in immune or disease related pathways of PK-15 cells peaked at 6 h PI, and were highly enriched as evidenced by KEGG analysis. Protein-protein interaction analysis revealed that TGME49_120110 (PCNA), TGME49_049180 (DHFR-TS), TGME49_055320, and TGME49_002300 (ITPase) are the four hub genes with most interactions with T. gondii at the onset of infection. These results reveal altered profiles of gene expressed by PK-15 cells and T. gondii during infection and provide the groundwork for future virulence studies to uncover the mechanisms of T. gondii interaction with porcine renal tissue by functional analysis of these DEGs. PMID:27242740

  10. 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

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

    OpenAIRE

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

    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 kin...

  12. 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.

  13. Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

    International Nuclear Information System (INIS)

    Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.

  14. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity

    International Nuclear Information System (INIS)

    Background and purpose: Inhibition of EGFR-function can induce radiosensitization in tumor cells. Purpose of our investigation was to identify the possible molecular mechanism of radiosensitization following treatment with anti-EGFR-antibody C225 (Cetuximab). Materials and methods: The effect of C225 on radiation response was determined in human cell lines of bronchial carcinoma (A549) and breast adenoma cells (MDA MB 231). The molecular effects of C225 on EGFR-function after irradiation were analyzed applying western blotting, immune-precipitation and kinase assays. Effects on DNA-repair were detected by quantification of γ-H2AX positive foci 24 h after irradiation. Results: The EGFR specific antibody C225 induced radiosensitization in A549 and also in MDA MB 231 cells. Radiosensitization in A549 was associated with blockage of radiation-induced EGFR transport into the nucleus, and immobilized the complex of EGFR with DNA-dependent protein kinase (DNA-PK) in the cytoplasm. As a consequence radiation-induced DNA-PK activation was abolished, a process that is essential for DNA-repair after radiation exposure. Likewise C225 treatment increased the residual amount of γ-H2AX-positive foci 24 h after irradiation in A549 and in MDA MB 231 cells. Conclusions: Our results suggest that irradiation induced DNA-PK activation-essential for DNA repair-may be hampered specifically by use of the anti-EGFR-antibody C225. This process is associated with radiosensitization

  15. PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-ε-caprolactone nanoparticles.

    Science.gov (United States)

    Ahmed, Iman S; El-Hosary, Rania; Shalaby, Samia; Abd-Rabo, Marwa M; G Elkhateeb, Dalia; Nour, Samia

    2016-05-17

    In this work lyophilized poly-ε-caprolactone nanoparticles (NPs) loaded with atorvastatin calcium (AC) were developed in an attempt to improve the in-vivo performance of AC following oral administration. The individual and combined effects of several formulation variables were previously investigated using step-wise full factorial designs in order to produce optimized AC-NPs with predetermined characteristics including particle size, drug loading capacity, drug release profile and physical stability. Four optimized formulations were further subjected in this work to lyophilization to promote their long-term physical stability and were fully characterized. The pharmacodynamics (PD)/pharmacokinetics (PK) properties of two optimized freeze-dried AC-NPs formulations showing acceptable long-term stability were determined and compared to a marketed AC immediate release tablet (Lipitor(®)) in albino rats. PD results revealed that the two tested formulations were equally effective in reducing low density lipoproteins (LDL) and triglycerides (TG) levels when given in reduced doses compared to Lipitor(®) and showed no adverse effects. PK results, on the other hand, revealed that the two freeze-dried AC-NPs formulations were of significantly lower bioavailability compared to Lipitor(®). Taken together the PD and PK results demonstrate that the improved efficacy obtained at reduced doses from the freeze-dried AC-NPs could be due to increased concentration of AC in the liver rather than in the plasma. PMID:27021467

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

    Science.gov (United States)

    Zhang, Hongling; Huang, Yong; Du, Qian; Luo, Xiaomao; Zhang, Liang; Zhao, Xiaomin; Tong, Dewen

    2015-01-01

    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. PMID:25499817

  17. 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

  18. 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, ...

  19. Preclinical evaluation of [18F]PK-209, a new PET ligand for imaging the ion-channel site of NMDA receptors

    International Nuclear Information System (INIS)

    Introduction: The present study was designed to assess whether [18F]PK-209 (3-(2-chloro-5-(methylthio)phenyl)-1-(3-([18F]fluoromethoxy) phenyl)-1-methylguanidine) is a suitable ligand for imaging the ion-channel site of N-methyl-D-aspartate receptors (NMDArs) using positron emission tomography (PET). Methods: Dynamic PET scans were acquired from male rhesus monkeys over 120 min, at baseline and after the acute administration of dizocilpine (MK-801, 0.3 mg/kg; n = 3/condition). Continuous and discrete arterial blood samples were manually obtained, to generate metabolite-corrected input functions. Parametric volume-of-distribution (VT) images were obtained using Logan analysis. The selectivity profile of PK-209 was assessed in vitro, on a broad screen of 79 targets. Results: PK-209 was at least 50-fold more selective for NMDArs over all other targets examined. At baseline, prolonged retention of radioactivity was observed in NMDAr-rich cortical regions relative to the cerebellum. Pretreatment with MK-801 reduced the VT of [18F]PK-209 compared with baseline in two of three subjects. The rate of radioligand metabolism was high, both at baseline and after MK-801 administration. Conclusions: PK-209 targets the intrachannel site with high selectivity. Imaging of the NMDAr is feasible with [18F]PK-209, despite its fast metabolism. Further in vivo evaluation in humans is warranted

  20. DNA-activated protein kinase (DNA-PK) and significance in its responses to radiation. The end is the beginning of the story

    International Nuclear Information System (INIS)

    This review described findings hitherto and future perspective on the DNA-PK. The enzyme was activated by double-strand DNA, required the end of the DNA and was the major component of p350 protein. Ku-antigen (an autoimmune antigen) was found a subunit. It phosphorylated p53, c-Myc, RPAp34, DNA ligase I, DNA topoisomerase I and II. Therefore DNA-PK can be a trigger factor which recognizes DNA break induced by radiation, and phosphorylates proteins participating in the DNA repair, cell cycle regulation and cell death. Recently p350 was found to be a responsible gene product to SCID syndrome of mice hypersensitive to ionizing radiation. The review included; On the DNA-PK: Discovery, relation to Ku antigen and molecular properties. On the DNA-PK and radiation sensitivity, and V(D)J recombination: Ku80 was the product of X-ray repair cross-complementing (XRCC). p350 was found the gene product whose lack causing SCID syndrome of radiosensitive mice. On the significance of phosphorylation of DNA-PK and the substrate: p53. RPA (replication protein A, alias RF-A or SSB). P1/MCM3, a possible substrate. On the other properties of DNA-PK: DNA-helicase activity. Suppression of transcription by RNA polymerase. DNA-PKp350 and ATM (ataxia-telangiectasia). Family molecules of p53 and ATM (MEI-41, Tel1p and Mec1p, and Rad3). (H.O). 70 refs

  1. Novel enzymatic synthesis of spacer-linked P(k) trisaccharide targeting for neutralization of Shiga toxin.

    Science.gov (United States)

    Kato, Tatsuya; Oizumi, Takahiro; Ogata, Makoto; Murakawa, Akiko; Usui, Taichi; Park, Enoch Y

    2015-09-10

    A novel alkyl spacer-conjugated derivative of P(k) trisaccharide (P(k)), one of the active receptors of Shiga toxins (Stxs; Stx1 and Stx2) produced by pathogenic Escherichia coli (STEC), was designed and synthesized by a combination of cellulase-mediated condensation from Trichoderma reesei and α1,4-galactosyltransferase (LgtC) from Neisseria gonorrhoeae. The specific activity of N. gonorrhoeae LgtC was 66U/mg, which was 13-fold higher than that from N. meningitidis expressed in E. coli. 5-trifluoroacetamidopentyl-β-P(k) (TFAP-P(k)) was synthesized (yield of 86%, based on the amount of TFAP-lactose added) and its binding to Stx1a-B and Stx2a-B was evaluated. The dissociation constants (KDs) of Stx1a-B and Stx2a-B to the spacer-linked P(k), immobilized on a CM5 sensor chip, were 6.8×10(-6) M (kon=4.1×10(1)M(-1)S(-1), koff=2.8×10(-4)S(-1)) and 2.2×10(-5)M (kon=3.9×10(2)M(-1)S(-1), koff=8.6×10(-3)S(-1)), respectively. This result suggests that the monovalent P(k)-derivative, conjugated to a pentylamino group, represents a promising Stx-neutralizing agent. This cellulase-mediated condensation using cellulase and glycosyltransferase is a valuable tool for the synthesis of spacer-linked oligosaccharide. PMID:26102632

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. Fissured Rocks and Water Reservoirs in Eastern Thessaly Mountain Range, Greece (Olympus, Ossa, Maurovouni and Pelion): The Role of Tectonic Deformation

    Science.gov (United States)

    Papanikolaou, I.; Migiros, G.; Stamatis, G.; Yoxas, G.

    2009-04-01

    The storage capacity of fractured hard rocks is lower than porous media and karst formations, though they can yield groundwater of sufficiently good quality for drinking purposes and may host important water resources, even if they are often of low permeability. In particular, for countries like Greece, where water needs for the local population and the tourist industry are excessive and waterfall limited, these reservoirs are of strategic importance. The mountain Range in Eastern Thessaly comprises an extensive nappe of metamorphic rocks, consisting of schists, gneisses, involving partly some ophiolithic rocks and marble intercalations. The thickness of the nappe exceeds 600 m in Ossa, whereas in the area of Pelion is estimated up to 3.000 m. This nappe rests on top of the Autochthonous Olympus- Ossa unit, which forms a massive Mesozoic carbonate sequence. Extensive fieldwork data supported by the analysis of the physical and chemical properties of a large number of springs and combined by the study of the geological structure both local and regional, resulted in important outcomes regarding the fissured rocks permeability, water flow and springs distribution. Schists are characterized by heterogeneity regarding their permeability features. They are divided into hard-rocks where quartz, epidote and amphiboles prevail, displaying higher permeability and soft-rocks where clay minerals prevail, exhibiting low permeability features, because the presence of clay blocks the fissures and prevent any infiltration process. The marbles are of high permeability, but are of limited extent. A few springs are located in marbles, but the vast majority of the springs are associated to the hard-rock schists, are scattered and characterized by high seasonal discharges. In the area of Ossa in particular, the most important reservoirs exist at the bordering zones of the metamorphic and the post-alpine formations due to the enrichment of the sedimentary post-alpine formations. In the

  7. 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

  8. 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.

  9. 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.

  10. 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 Ca(2+) via inositol 1,4,5-trisphosphate receptor (IP3R). Elevation of cytosolic calcium ion (Ca(2+)) 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 Ca(2+) both in PK-15 cells and PCV2-targeted primary cells from pigs. PMID:27213427

  11. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant α1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker

    International Nuclear Information System (INIS)

    The peripheral benzodiazepine receptor ligand PK11195 has been used as an in vivo marker of neuroinflammation in positron emission tomography studies in man. One of the methodological issues surrounding the use of the ligand in these studies is the highly variable kinetic behavior of [11C]PK11195 in plasma. We therefore undertook a study to measure the binding of [3H]PK11195 to whole human blood and found a low level of binding to blood cells but extensive binding to plasma proteins. Binding assays using [3H]PK11195 and purified human plasma proteins demonstrated a strong binding to α1-acid glycoprotein (AGP) and a much weaker interaction with albumin. Immunodepletion of AGP from plasma resulted in the loss of plasma [3H]PK11195 binding demonstrating: (i) the specificity of the interaction and (ii) that AGP is the major plasma protein to which PK11195 binds with high affinity. PK11195 was able to displace fluorescein-dexamethasone from AGP with IC50 of 11C]PK11195 to the brain parenchyma in diseases with blood brain barrier breakdown. Finally, local synthesis of AGP at the site of brain injury may contribute the pattern of [11C]PK11195 binding observed in neuroinflammatory diseases

  12. 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)

  13. 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.

  14. Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography

    International Nuclear Information System (INIS)

    Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration

  15. 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.)

  16. 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.)

  17. 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...

  18. 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

  19. {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

  20. A modification of the generalized Born theory for improved estimates of solvation energies and pK shifts

    Science.gov (United States)

    Jayaram, B.; Liu, Y.; Beveridge, D. L.

    1998-07-01

    We present herein an appraisal on the performance of the generalized Born (GB) model in estimating the solvation energies of small molecules and pKa shifts of dicarboxylic acids. The quality of the solvation energy results obtained with the GB model was exceedingly good as already reported in the literature but the pKa shift estimates fell short of expectations. Analysis of the problem on a simple prototype system revealed that with the GB model, the estimates of the two components, viz. the shielding and the self-energy terms, to be somewhat in error. These errors compensate each other in the calculation of solvation energies but affect the intramolecular interaction energies and hence pK shifts differently. We examine here the feasibility of introducing modifications to the GB model for a simultaneous evaluation of both solvation and intramolecular interaction energies.

  1. Incorporation of mineral phosphorus and potassium on leather waste (collagen): A new NcollagenPK-fertilizer with slow liberation

    International Nuclear Information System (INIS)

    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 NcollagenPK formulations, as a source of nutrients for the growth of rice plants, showed promising agronomic results.

  2. PkANN - II. A non-linear matter power spectrum interpolator developed using artificial neural networks

    CERN Document Server

    Agarwal, Shankar; Feldman, Hume A; Lahav, Ofer; Thomas, Shaun A

    2013-01-01

    In this paper we introduce PkANN, a freely available software package for interpolating the non-linear matter power spectrum, constructed using Artificial Neural Networks (ANNs). Previously, using Halofit to calculate matter power spectrum, we demonstrated that ANNs can make extremely quick and accurate predictions of the power spectrum. Now, using a suite of 6380 N-body simulations spanning 580 cosmologies, we train ANNs to predict the power spectrum over the cosmological parameter space spanning $3\\sigma$ confidence level (CL) around the concordance cosmology. When presented with a set of cosmological parameters ($\\Omega_{\\rm m} h^2, \\Omega_{\\rm b} h^2, n_s, w, \\sigma_8, \\sum m_\

  3. Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death

    International Nuclear Information System (INIS)

    Exposure to ionizing radiation and hyperthermia results in important biological consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand breaks. There is good evidence that the nucleus, specifically cellular DNA, is the principal target for radiation-induced cell lethality. DNA double-strand breaks (DSBs) are considered to be the most serious type of DNA damage induced by ionizing radiation. On the other hand, verifiable mechanisms which can lead to heat-induced cell death are damage to the plasma membrane and/or inactivation of heat-labile proteins caused by protein denaturation and subsequent aggregation. Recently, several reports have suggested that DSBs can be induced after hyperthermia because heat-induced phosphorylated histone H2AX (γ-H2AX) foci formation can be observed in several mammalian cell lines. In mammalian cells, DSBs are repaired primarily through two distinct and complementary mechanisms: non-homologous end joining (NHEJ), and homologous recombination (HR) or homology-directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) are key players in the initiation of DSB repair and phosphorylate and/or activate many substrates, including themselves. These phosphorylated substrates have important roles in the functioning of cell cycle checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is a crucial cell suicide mechanism during development and in the defense of homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important system which can protect an organism against carcinogenesis. This paper reviews recently obtained results and current topics concerning the role of DNA-PK and ATM in heat- or radiation-induced apoptotic cell death. (author)

  4. 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

  5. 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

  6. Differential effect of detergents on [3H]Ro 5-4864 and [3H]PK 11195 binding to peripheral-type benzodiazepine-binding sites

    International Nuclear Information System (INIS)

    The present study demonstrates a differential effect of various detergent treatments on [3H]Ro 5-4864 and [3H]PK 11195 binding to peripheral benzodiazepine binding sites (PBS). Triton X-100 caused a decrease of about 70% in [3H]Ro 5-4864 binding to membranes from various peripheral tissues of rat, but had only a negligible effect on [3H]PK 11195 binding. A similar effect of Triton X-100 was observed on guinea pig and rabbit kidney membranes. The decrease in [3H]Ro 5-4864 binding after treatment with Triton X-100 was apparently due to a decrease in the density of PBS, since the affinity remained unaltered. The detergents 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS), Tween 20, deoxycholic acid, or digitonin (0.0125%) caused only a minor change in [3H]Ro 5-4864 and [3H]PK 11195 binding to rat kidney membranes; but when concentrations were substantially increased (0.1%), all detergents caused a decrease of at least 50% in [3H]Ro 5-4864 binding, while [3H]PK 11195 binding to rat kidney membranes remained unaffected by the first three detergents, with only a minor decrease (15%) after treatment with digitonin

  7. Cadmium is more toxic to LLC-PK1 cells than to MDCK cells acting on the cadherin-catenin complex.

    Science.gov (United States)

    Zimmerhackl, L B; Momm, F; Wiegele, G; Brandis, M

    1998-07-01

    Cadmium toxicity to renal cells was investigated in Madin-Darby canine kidney (MDCK) and LLC-PK1 cells as models of the distal tubule/collecting duct and proximal tubule, respectively. Cells were grown on two-compartment filters and exposed to 0.1-50 microM Cd2+. In MDCK cells, Cd2+ was more toxic from the basolateral than from the apical side and dependent on the extracellular Ca2+ concentration. Toxicity was evident within 24 h, as shown by a decrease in transepithelial resistance (TER), reduced proliferation (bromodeoxyuridine incorporation), reduction in ATP concentration, and morphological changes. On confocal microscopy, E-cadherin and alpha-catenin staining patterns indicated interference with the cadherin-catenin complex. LLC-PK1 cells showed a similar toxicity pattern, which was evident at lower Cd2+ concentrations. An increase of E-cadherin and alpha-catenin molecules in the Triton X-100-insoluble fraction was detectable at high Cd2+ concentrations in LLC-PK1 cells but not in MDCK cells. Lactate dehydrogenase release indicated membrane leakage in LLC-PK1 cells. Rhodamine-phalloidin staining, a probe for F-actin filaments, demonstrated alterations of the actin cytoskeleton in both cell lines. In conclusion, cadmium caused ATP depletion and interfered with the cadherin-catenin complex and probably the tight junctions changing renal cell morphology and function. PMID:9689016

  8. 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

  9. 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...

  10. 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

  11. Tilinpäätösraportoinnin muutoksen yhteys olennaisen virheellisyyden esiintymiseen - Pk-IFRS:n käyttö Suomen kirjanpitolainsäädännön sijaan tilintarkastajan näkökulmasta

    OpenAIRE

    Chan, Kwun Chuen

    2014-01-01

    TUTKIMUKSEN TAVOITTEET: Tutkielman tavoitteena on tutkia pk-IFRS:n käyttöönoton arvioituja vaikutuksia olennaisen virheellisyyden riskiin Suomessa. Tutkimus tarkastelee erityisesti pk-IFRS:n ja FAS:n välisiä eroja ja pyrkii selvittämään tilintarkastajan näkökulmasta, vaikuttaisiko pk-IFRS:n käyttö FAS:n sijaan olennaisen virheellisyyden esiintymiseen. Lisäksi tutkimuksessa pyritään selvittämään, voisiko pk-IFRS:n käyttöönottavilla yrityksillä olla muita tekijöitä, kuin pk-IFRS:n ja Suomen...

  12. Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195.

    Science.gov (United States)

    Parente, Andrea; Feltes, Paula Kopschina; Vállez García, David; Sijbesma, Jurgen W A; Moriguchi Jeckel, Cristina M; Dierckx, Rudi A J O; de Vries, Erik F J; Doorduin, Janine

    2016-05-01

    (11)C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-(11)C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of (11)C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate (11)C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-(11)C-PK11195. The herpes simplex encephalitis (HSE) model was used for induction of neuroinflammation in male Wistar rats. Six or 7 d after virus inoculation, a dynamic (11)C-PBR28 or (R)-(11)C-PK11195 PET scan with arterial blood sampling was obtained. Pharmacokinetic modeling was performed on the PET data and analyzed using volumes of interest and a voxel-based approach. Volume-of-interest- and voxel-based analysis of (11)C-PBR28 images showed overexpression of TSPO in brain regions known to be affected in the HSE rat model. (11)C-PBR28 was metabolized faster than (R)-(11)C-PK11195, with a metabolic half-life in plasma of 5 and 21 min, respectively. Overall, (11)C-PBR28 was more sensitive than (R)-(11)C-PK11195 in detecting neuroinflammation. The binding potential (BPND) of (11)C-PBR28 was significantly higher (P < 0.05) in the medulla (176%), pons (146%), midbrain (101%), hippocampus (85%), thalamus (73%), cerebellum (54%), and hypothalamus (49%) in HSE rats than in control rats, whereas (R)-(11)C-PK11195 showed a higher BPND only in the medulla (32%). The BPND in control animals was not significantly different between tracers, suggesting that the nonspecific binding of both tracers is similar. (11)C-PBR28 was more sensitive than (R)-(11)C-PK11195 in the detection of TSPO overexpression in the HSE rat model, because more brain regions with significantly increased tracer uptake could be found, irrespective of the data

  13. [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

  14. Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT in DNA repair, apoptosis and necrosis after cisplatin

    Directory of Open Access Journals (Sweden)

    Calkins Anne S

    2011-06-01

    Full Text Available Abstract Background Platinum-containing chemotherapy produces specific DNA damage and is used to treat several human solid tumors. Tumors initially sensitive to platinum-based drugs frequently become resistant. Inhibition of DNA repair is a potential strategy to enhance cisplatin effectiveness. After cisplatin treatment, a balance between repair and apoptosis determines whether cancer cells proliferate or die. DNA-dependent protein kinase (DNA-PK binds to DNA double strand breaks (DSBs through its Ku subunits and initiates non-homologous end joining. Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity. Results Silencing the expression of the catalytic subunit of DNA-PK (DNA-PKcs increased sensitivity to cisplatin and decreased the appearance of γH2AX after cisplatin treatment. We purified DNA-PK by its Ku86 subunit and identified interactors by tandem mass spectrometry before and after cisplatin treatment. The structure specific recognition protein 1 (SSRP1, Spt16 and γH2AX appeared in the Ku86 complex 5 hours after cisplatin treatment. SSRP1 and Spt16 form the facilitator of chromatin transcription (FACT. The cisplatin-induced association of FACT with Ku86 and γH2AX was abrogated by DNase treatment. In living cells, SSRP1 and Ku86 were recruited at sites of DSBs induced by laser beams. Silencing SSRP1 expression increased sensitivity to cisplatin and decreased γH2AX appearance. However, while silencing SSRP1 in cisplatin-treated cells increased both apoptosis and necrosis, DNA-PKcs silencing, in contrast, favored necrosis over apoptosis. Conclusions DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. Since DNA-PK regulates apoptosis, silencing DNA-PKcs redirects cells treated with cisplatin toward necrosis. Silencing FACT however, allows both apoptosis and

  15. Quantitative imaging of subcellular calcium stores in mammalian LLC-PK1 epithelial cells undergoing mitosis by SIMS ion microscopy.

    Science.gov (United States)

    Chandra, Subhash

    2005-09-01

    Quantitative 3-D total calcium gradients, representing subcellular stored calcium, were imaged with a CAMECA IMS-3f SIMS ion microscope in cryogenically prepared frozen freeze-dried LLC-PK1 cells captured in interphase and various stages of mitosis. 39K and 23Na concentrations were also measured in the same cells. Correlative optical (or SEM) and SIMS analysis of cells revealed a redistribution of the interphase Golgi calcium store in prophase and prometaphase cells. In metaphase cells, simultaneous SIMS imaging of total calcium in both the spindle and the non-spindle cytoplasm of individual cells revealed a gradual and dynamic alignment of calcium stores in both half-spindles prior to the onset of anaphase. The anaphase cells revealed the highest local total calcium concentrations in the spindle regions behind the daughter chromosomes and the lowest in the central spindle region. The pericentriolar material in telophase cells contained calcium stores. Quantitatively, a typical metaphase cell with well-aligned calcium stores in the spindle region contained 1.1 mM total calcium in each half-spindle, 0.8 mM total calcium in the non-spindle cytoplasm, and 0.5mM total calcium in the chromosomes. At the submicron scale, the distribution of total calcium was heterogeneous in the chromosomes, metaphase spindle, and non-spindle cytoplasm. An increased binding of calcium to chromosomes is not a physiological requirement for chromosomal condensation in mitosis, since interphase nuclei and mitotic chromosomes contained comparable total calcium concentrations measured per unit volume. A significant reduction of total calcium in the non-spindle cytoplasm was observed in the metaphase, anaphase, and telophase cells, which is indicative of the limited storage of the releasable calcium pool in these specific stages of mitosis. Direct total calcium measurements in subcellular regions confirmed that both the spindle and the non-spindle cytoplasm of metaphase cells contained inositol

  16. 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

  17. 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.

  18. Conductive Na+ transport in an epithelial cell line (LLC-PK1) with characteristics of proximal tubular cells

    International Nuclear Information System (INIS)

    22Na influx and efflux from confluent monolayers of an epithelial cell line with multiple differentiated characteristics of the straight segment of the renal proximal tubule were studied in the presence and absence of a pH gradient. The results show that 22Na+ influx in the absence of a pH gradient is inhibited by amiloride as well as by complete replacement of Cl- by an impermeable anion, such as isethionate. Dissipation of cell membrane potential by increasing the potassium concentration of the extracellular medium in the presence of valinomycin also inhibited Na+ influx, whereas sodium influx induced by an H+ gradient was not affected. Inhibition of Na+ influx by different maneuvers produced hyperpolarization of the plasma cell membrane, as would be expected if the sodium movement involved net displacement of charges. Calcium and other divalent and trivalent cations also inhibited Na+ influx measured in the absence of an H+ gradient. Na+ influx induced by a pH gradient, however, was not affected. Like the Na+-H+-exchange system, the conductive Na+ pathway is localized in the apical membrane of the epithelial cells. From these results, the authors conclude that at least a fraction of transepithelial Na+ transport in LLC-PK1 monolayers occurs through a simple rheogenic transport system

  19. 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...

  20. Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets

    OpenAIRE

    Davda, Jasmine P; Hansen, Ryan J.

    2010-01-01

    Antibodies that target endogenous soluble ligands are an important class of biotherapeutic agents. While much focus has been placed on characterization of antibody pharmacokinetics, less emphasis has been given to characterization of antibody effects on their soluble targets. We describe here the properties of a generalized mechanism-based PK/PD model used to characterize the in vivo interaction of an antibody and an endogenous soluble ligand. The assumptions and properties of the model are e...

  1. In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand. [11C]PK-11195 and animal PET following ethanol injury in rat striatum

    International Nuclear Information System (INIS)

    To investigate whether [11C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model. On day 1, ethanol was injected into the rat's right striatum (ST) using a stereotaxic operative procedure. On day 3, head magnetic resonance imaging (MRI) scans for surgically treated rats were performed to evaluate ethanol injury morphologically. On day 4, dynamic PET scans (17 injured rats and 7 non-injured controls) were performed for 60 min with an animal PET scanner under chloral hydrate anesthesia following a bolus injection of [11C]PK-11195 through tail vein. Because PBRs are present throughout the brain, there is no suitable receptor-free reference region. The reference tissue model may not be applicable because of low target to back-ground ratio for low affinity of [11C]PK-11195 to PBRs. We evaluated the PBRs binding with regions of interest (ROIs)-based approach to estimate total distribution volume (V). We used an integral from 0 min to 60 min (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 ratios between lesioned and unlesioned control rats were compared using unpaired t tests. Immunohistochemical staining was performed for confirming the presence of activated microglia following decapitation on the PET experiment day. The right/left ST V60 ratios in lesioned rats (1.07±0.08) were significantly higher than those in unlesioned control rats (1.00±0.06, P11C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model. (author)

  2. Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Red Cell Pathology Group of the Spanish Society of Haematology (AEHH).

    Science.gov (United States)

    Zarza, R; Alvarez, R; Pujades, A; Nomdedeu, B; Carrera, A; Estella, J; Remacha, A; Sánchez, J M; Morey, M; Cortes, T; Pérez Lungmus, G; Bureo, E; Vives Corrons, J L

    1998-11-01

    The PK-LR gene has been studied in 12 unrelated patients with red cell pyruvate kinase deficiency and hereditary nonspherocytic haemolytic anaemia (CNSHA). The entire codifying region of the R-type PK gene and the flanking intronic regions were analysed by single-stranded conformation polymorphism (SSCP) followed by direct sequencing of abnormal DNA. 10 different mutations were identified in 22/24 alleles at risk. Eight of these were missense mutations that caused the following single amino acid changes: G514C (172Glu-Gln), G1010A (337Arg-Gln), G1015C (339Asp-Gln), T1070C (357Ile-Thr), C1223T (408Thr-Ile), G1291A (431Ala-Thr), C1456T (486Arg-Trp) and G1595A (532Arg-Gln). Two were nonsense mutations: G721T (241Glu-Stop) and C1675T (559Arg-Stop). 7/22 alleles demonstrated the same C1456 --> T mutation. The study of the polymorphic site at nucleotide (nt) 1705 performed in all cases disclosed a 1705 C/C mutation in 10 and a 1705 A/C mutation in three. This is the first report on the presence of several different L-type PK gene mutations within Spanish population. Furthermore, from the PK gene mutations found, six were unique and not previously described (1015C, 1070C, 1223T, 1291A, 1595A and 1675T) and one (C1456T) seems to be predominant in Spain. Interestingly, no case with the 1529A mutation commonly found in Northern European populations was present here. PMID:9827908

  3. 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

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

    OpenAIRE

    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 human cerebrospinal fluid (CSF) are used as a surrogate for human brainECF concentrations. Due to qualitative and quantitative differences in processes that govern the pharmacokinetics (PK) of drugs in...

  5. 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

  6. 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

  7. 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

  8. Chloride binding regulates the Schiff base pK in gecko P521 cone-type visual pigment.

    Science.gov (United States)

    Yuan, C; Kuwata, O; Liang, J; Misra, S; Balashov, S P; Ebrey, T G

    1999-04-01

    The binding of chloride is known to shift the absorption spectrum of most long-wavelength-absorbing cone-type visual pigments roughly 30 nm to the red. We determined that the chloride binding constant for this color shift in the gecko P521 visual pigment is 0.4 mM at pH 6.0. We found an additional effect of chloride on the P521 pigment: the apparent pKa of the Schiff base in P521 is greatly increased as the chloride concentration is increased. The apparent Schiff base pKa shifts from 8.4 for the chloride-free form to >10.4 for the chloride-bound form. We show that this shift is due to chloride binding to the pigment, not to the screening of the membrane surface charges by chloride ions. We also found that at high pH, the absorption maximum of the chloride-free pigment shifts from 495 to 475 nm. We suggest that the chloride-dependent shift of the apparent Schiff base pKa is due to the deprotonation of a residue in the chloride binding site with a pKa of ca. 8.5, roughly that of the Schiff base in the absence of chloride. The deprotonation of this site results in the formation of the 475 nm pigment and a 100-fold decrease in the pigment's ability to bind chloride. Increasing the concentration of chloride results in the stabilization of the protonated state of this residue in the chloride binding site and thus increased chloride binding with an accompanying increase in the Schiff base pK. PMID:10194387

  9. 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

  10. 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

  11. Radioactive Waste Characterization Strategies; Comparisons Between AK/PK, Dose to Curie Modeling, Gamma Spectroscopy, and Laboratory Analysis Methods- 12194

    International Nuclear Information System (INIS)

    In the coming fiscal years of potentially declining budgets, Department of Energy facilities such as the Los Alamos National Laboratory (LANL) will be looking to reduce the cost of radioactive waste characterization, management, and disposal processes. At the core of this cost reduction process will be choosing the most cost effective, efficient, and accurate methods of radioactive waste characterization. Central to every radioactive waste management program is an effective and accurate waste characterization program. Choosing between methods can determine what is classified as low level radioactive waste (LLRW), transuranic waste (TRU), waste that can be disposed of under an Authorized Release Limit (ARL), industrial waste, and waste that can be disposed of in municipal landfills. The cost benefits of an accurate radioactive waste characterization program cannot be overstated. In addition, inaccurate radioactive waste characterization of radioactive waste can result in the incorrect classification of radioactive waste leading to higher disposal costs, Department of Transportation (DOT) violations, Notice of Violations (NOVs) from Federal and State regulatory agencies, waste rejection from disposal facilities, loss of operational capabilities, and loss of disposal options. Any one of these events could result in the program that mischaracterized the waste losing its ability to perform it primary operational mission. Generators that produce radioactive waste have four characterization strategies at their disposal: - Acceptable Knowledge/Process Knowledge (AK/PK); - Indirect characterization using a software application or other dose to curie methodologies; - Non-Destructive Analysis (NDA) tools such as gamma spectroscopy; - Direct sampling (e.g. grab samples or Surface Contaminated Object smears) and laboratory analytical; Each method has specific advantages and disadvantages. This paper will evaluate each method detailing those advantages and disadvantages

  12. Anatomy of the pQCD approach to the baryonic decays {lambda}{sub b} {yields} p{pi}, pK

    Energy Technology Data Exchange (ETDEWEB)

    Lue, Cai-Dian; Wang, Yu-Ming; Zou, Hao [Chinese Acadamy of Sciences (China). Institute of High Energy Physics and Theoretical Physics Center for Science Facilities; Ali, Ahmed [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kramer, Gustav [Hamburg Univ. (Germany). II. Institut fuer Theoretische Physik

    2009-06-15

    We calculate the CP-averaged branching ratios and CP-violating asymmetries for the two-body charmless hadronic decays {lambda}{sub b} {yields} p{pi}, pK in the perturbative QCD (pQCD) approach to lowest order in {alpha}{sub s}. 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 {lambda}{sub b} {yields} p{pi}, pK decays are much smaller compared to the nonfactorizable diagrams in the conventional pQCD approach. We argue that this reflects the estimates of the {lambda}{sub b} {yields} p transition form factors in the k{sub T} 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 {lambda}{sub b} {yields} 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 {lambda}{sub b} {yields} p{pi}, and {lambda}{sub b} {yields} pK. The asymmetry parameter {alpha} relevant for the anisotropic angular distribution of the emitted proton in the polarized {lambda}{sub b} baryon decays is also calculated for the two decay modes. (orig.)

  13. DNA-PK and ATM phosphorylation sites in XLF/Cernunnos are not required for repair of DNA double strand breaks.

    Science.gov (United States)

    Yu, Yaping; Mahaney, Brandi L; Yano, Ken-Ichi; Ye, Ruiqiong; Fang, Shujuan; Douglas, Pauline; Chen, David J; Lees-Miller, Susan P

    2008-10-01

    Nonhomologous end joining (NHEJ) is the major pathway for the repair of DNA double strand breaks (DSBs) in human cells. NHEJ requires the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), Ku70, Ku80, XRCC4, DNA ligase IV and Artemis, as well as DNA polymerases mu and lambda and polynucleotide kinase. Recent studies have identified an additional participant, XLF, for XRCC4-like factor (also called Cernunnos), which interacts with the XRCC4-DNA ligase IV complex and stimulates its activity in vitro, however, its precise role in the DNA damage response is not fully understood. Since the protein kinase activity of DNA-PKcs is required for NHEJ, we asked whether XLF might be a physiological target of DNA-PK. Here, we have identified two major in vitro DNA-PK phosphorylation sites in the C-terminal region of XLF, serines 245 and 251. We show that these represent the major phosphorylation sites in XLF in vivo and that serine 245 is phosphorylated in vivo by DNA-PK, while serine 251 is phosphorylated by Ataxia-Telangiectasia Mutated (ATM). However, phosphorylation of XLF did not have a significant effect on the ability of XLF to interact with DNA in vitro or its recruitment to laser-induced DSBs in vivo. Similarly, XLF in which the identified in vivo phosphorylation sites were mutated to alanine was able to complement the DSB repair defect as well as radiation sensitivity in XLF-deficient 2BN cells. We conclude that phosphorylation of XLF at these sites does not play a major role in the repair of IR-induced DSBs in vivo. PMID:18644470

  14. 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.

  15. 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.)

  16. 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.

  17. 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...

  18. 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...

  19. Comportamiento farmacocinético de la marbofloxacina en bovinos de diferentes edades y relación PK-PD frente a mastitis estafilocócicas

    OpenAIRE

    Díaz David, Diego Carlos

    2012-01-01

    Durante las últimas décadas, el interés por la relación entre la farmacocinética (PK) y la farmacodinamia (PD) se ha incrementado. Las marbofloxacina es un antimicrobiano de uso veterinario perteneciente a la familia de las fluoroquinolonas. Está indicado para bovinos, porcinos, caninos y felinos. Las características farmacocinéticas que presenta en diversas especies permiten la administración por distintas vías con una buena biodisponibilidad, una amplia distribución tisular y una prolongada...

  20. Lisäresursseja pk-yritysten viestintään : Uuden viestintäpalvelun kehittäminen palvelumuotoilun keinoin

    OpenAIRE

    Jyrälä, Heta

    2016-01-01

    Opinnäytetyön toimeksiantajana toimi kuopiolainen Mainostoimisto Aihe Oy. Opinnäytetyön tavoitteena oli suunnitella uusi viestintäpalvelu pienten ja keskisuurten yritysten tarpeisiin. Uutta viestintäpalvelua haluttiin lähteä kehittämään, koska monilla yrityksillä sekä yhteisöillä voi olla paljon viestittävää asiakkailleen ja sidosryhmilleen, mutta ei resursseja viestinnän toteuttamiseen. Tehtävänä oli selvittää millaisella palvelukokonaisuudella pk-yritykset saisivat kaipaamiaan lisäresurssej...

  1. 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.

  2. Determining the pk(a) of N,N-dimethylsphingosine and the flip-flop rate of related compounds with deuterium nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Deuterium nuclear magnetic resonance (2H-NMR) spectroscopy was applied to determine the pk(a) of the protein kinase C (PKC) inhibitor, N,N-dimethylsphingosine (DMS), when bound to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. The quadrupolar splittings from deuterium labels at the α- and the β-positions of the POPC headgroup responded in a manner indicative of a positive surface charge density at pH 7.0. Conversely, at pH 10.0 DMS had virtually no influence on either quadrupolar splitting, an effect attributed to titration of the dimethylamino group of DMS to its neutral form. A DMS titration curve was obtained by quantifying the charge in the quadrupolar splittings as a function of pH. Simulation of this curve yielded a pk(a) of 8.8 of membrane-bound DMS. Using a similar approach, the dynamic process of flip-flop was examined in two DMS analogues. We discuss here the quantitative and the qualitative aspects as well as the limitations of this application. (author)

  3. 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

  4. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132

  6. 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

  7. Protective effects of methanolic extract form fruits of Lycium ruthenicum Murr on 2,2′-azobis (2-amidinopropane dihydrochloride-induced oxidative stress in LLC-PK1 cells

    Directory of Open Access Journals (Sweden)

    Jia-Le Song

    2014-01-01

    Full Text Available Background: Fruits of Lycium ruthenicum Murr is a health food and also used as a folk to treat heart disease, abnormal menstruation and menopause in Tibetan, China. However; whether L. ruthenicum Murr fruits methanolic extracts (LFME protect LLC-PK1 porcine renal tubules cells from AAPH-induced oxidative damage has not been investigated. Objective: To investigate the protective effects of L. ruthenicum Murr fruits methanolic extracts (LFME against 2, 2′- azobis (2-amidinopropane dihydrochloride (AAPH-induced oxidative damage in renal proximal tubule LLC-PK1 cells. Materials and Methods: LLC-PK1 cells were co-incubated with AAPH (1mM and different concentrations of LFMW together for 24 h. Cell viability was determined by MTT assay. Total intercellular reactive oxygen species (ROS levels and lipid peroxidation were measured using a fluorescent probe 2′, 7′-dichlorfluorescein-diacetate (DCFH-DA and the TBA reactive substance (TBARS assay, respectively. The endogenous antioxidant enzymes including catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-px and intercellular glutathione (GSH levels were determined using commercial assay kits according to the manufacturer′s instructions. Results: LFME did not show a significant cytotoxic effect and increased the viability of LLC-PK1 cells in a concentration-dependent manner. LFME also decreased the total intercellular levels of ROS, reduced lipid peroxidation and increased the GSH levels as well as the activities of endogenous antioxidant enzymes to protect LLC-PK1 cells against AAPH-induced oxidative damage. Conclusion: The results from the present study indicated that LFME is an effective ROS scavenger to protect LLC-PK1 cells against AAPH-induced oxidative damage through decreasing ROS generation, reducing lipid peroxidation and up-regulation of endogenous GSH levels and antioxidant enzymes.

  8. 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

  9. 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

  10. 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 by...... received two subcutaneous (SC) bolus injections of low and high doses of glucagon and ZP-GA-1 (20 and 120 nmol/kg). Results We report posterior probability distributions and correlations for all identifiable model parameters. Based on visual inspection and residual analysis, the PD model described data...... parameters given priors reported in the literature. We used profile likelihood analysis to investigate parameter identifiability and reduce the number of model variables. We estimated model parameters in pre-clinical data from one cross-over study with a total of 20 experiments in five dogs. The dogs...

  11. 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.

  12. Failure of the crossover pipes used in the PK-39-IIM boiler middle radiant part and a numerical analysis of the factors caused this failure

    Science.gov (United States)

    Baranov, V. N.; Gorb, A. A.; Nikolaev, S. F.

    2013-06-01

    The consequences resulting from an emergency failure of one subflow in the middle radiant part of a modernized PK-39-IIM boiler occurred during one of its first startups after the erection are presented. A numerical analysis of the factors that caused this failure is carried out. The calculation was carried out in accordance with the recommendations suggested in the standard method of hydraulic design. It is shown that at a load equal to 40% of its nominal value, increment of heat absorption in the subflow equal to 586 kJ/kg (140 kcal/kg), and heat absorption nonuniformity coefficient in the misaligned element equal to 1.5, the temperature of medium downstream of the subflow is equal to 670°C (operating conditions close to those under which the failure occurred).

  13. 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.

  14. 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.

  15. 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

  16. Effect of radiation on regulation of sodium-dependent glucose transport in LLC-PK1 epithelia: Possible model for gene expression

    International Nuclear Information System (INIS)

    Epithelia formed from plateau-phase cultures of porcine kidney cells (LLC-PK1) respond to low concentrations of glucose by synthesizing more glucose transport proteins. This induction, requiring 6 to 8 days for complete expression, has been shown to depend solely on the glucose concentration in the media. The authors are examining the radioresponse of this model system to determine its suitability for the study of radiation effects on gene expression. The inducible glucose transport system has several features that lend themselves to radiation studies. One of these features is that the transport of glucose in itself shows little or no decrement for radiation doses up to 200 Gy. At doses greater than 200 Gy glucose transport is inactivated by radiation with a D/sub o/ of approximately 400 Gy. In addition, the efflux of glucose is unaffected for doses up to 500 Gy. The induction of increased glucose transport, however, is inhibited by radiation in a dose-dependent manner for doses over 5 Gy. The time course of the induction process, the dependence on a specifically timed block in protein synthesis, and the kinetics of the radiation inhibition all support the notion that, prior to the protein synthesis step, radiation blocks the expression of this induced change

  17. Effect of radiation on the regulation of sodium-dependent glucose transport in LLC-PK1 epithelial cell line: possible model for gene expression

    International Nuclear Information System (INIS)

    Low concentrations of glucose induce cultured kidney epithelial cells (LLC-PK1) to produce hexose transport proteins. We have investigated the effects of ionizing radiation on this induction process in plateau-phase cultures. The induced production of hexose transporters, requiring approximately 6 to 9 days for complete expression, can be inhibited by irradiation during the first 4 days. After the fourth postinduction day, radiation sensitivity decreases with almost no radiation effect on the induction of hexose transport apparent by the sixth day of the induction period. The D0 value associated with the induction block is approximately 25 Gy, a value which is considerably greater than that necessary to inhibit cell replication. Hexose transport, itself resistant to ionizing radiation at doses in excess of 100 Gy, is sensitive to cycloheximide throughout the induction period. The sensitivity to cycloheximide decreases during the last 2 days of the induction period, approximately 1 day after the reduction in radiosensitivity. Based on these properties hexose transport may be a convenient model for the study of radiation effects upon gene expression in this cell line

  18. 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)

  19. 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。

  20. 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.

  1. 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.

  2. Update on the GRB universal scaling E$_{\\rm{X,iso}}$-E$_{\\rm{\\gamma,iso}}$-E$_{\\rm{pk}}$ with ten years of $Swift$ data

    CERN Document Server

    Zaninoni, Elena; Margutti, Raffaella; Amati, Lorenzo

    2015-01-01

    From a comprehensive statistical analysis of $Swift$ X-ray light-curves of gamma-ray bursts (GRBs) collected from December 2004 to the end of 2010, we found a three-parameter correlation between the isotropic energy emitted in the rest frame 1-10$^4$ keV energy band during the prompt emission (E$_{\\rm{\\gamma,iso}}$), the rest frame peak of the prompt emission energy spectrum (E$_{\\rm{pk}}$), and the X-ray energy emitted in the rest frame 0.3-30 keV observed energy band (E$_{\\rm{X,iso}}$), computed excluding the contribution of the flares. In this paper, we update this correlation with the data collected until June 2014, expanding the sample size with $\\sim$35% more objects, where the number of short GRBs doubled. With this larger sample we confirm the existence of a universal correlation that connects the prompt and afterglow properties of long and short GRBs. We show that this correlation does not depend on the X-ray light-curve morphology and that further analysis is necessary to firmly exclude possible bia...

  3. 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.

  4. 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

  5. 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;

    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...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... 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...

  6. 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...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... 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...

  7. 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

    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...

  8. 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.

  9. 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

  10. 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.

  11. Varmuuskopioinnin suunnittelu PK-yritykselle

    OpenAIRE

    Mäntysalo, Sampsa

    2011-01-01

    Tämän työn tarkoituksena on selvittää ja toteuttaa GeoUnion Oy:lle sopiva varmuuskopiointimenetelmä. GeoUnion Oy on yksityinen geodesia-, geologia- ja geotekniikkaalan yritys. Yrityksen palveluihin kuuluu mittaus-, maaperätutkimus- ja suunnittelupalvelut. Yrityksellä on asiakkaita niin Suomessa kuin ulkomaillakin. Työ aloitettiin selvittämällä yrityksen tarpeet ja vaatimukset varmuuskopiointimenetelmälle. Tämän jälkeen valittiin neljä näihin vaatimuksiin sopivaa varmistusmenetelmää, joita...

  12. 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...

  13. Yrityssaneerauskelpoisuus PK-yrityksissä

    OpenAIRE

    Kauppi, Riitta

    2010-01-01

    Opinnäytetyön aiheena oli yrityssaneeraus pienissä ja keskisuurissa yrityksissä. Opinnäytetyössä keskityttiin lähinnä tarkastelemaan yrityssaneerauksen hakeutumisen edellytyksiä sekä esteperusteita sekä yrityssaneerauksen aloittamisharkintaan liittyviä edellytyksiä yrityksen saneerauskelpoisuutta ajatellen. Laki yrityksen saneerauksesta on tullut voimaan 1993 ja uudistettu yrityssaneerauslaki on tullut voimaan 2007. Opinnäytetyön teoriaosassa käsiteltiin lainsäädännön pohjalta yrityssane...

  14. 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 ...

  15. Yritysturvallisuuskoulutuksen tuotteistaminen PK-yrityksille

    OpenAIRE

    Rosenqvist, Päivi

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli kehittää toimeksiantajayrityksen yritysturvallisuuteen ja riskienhallintaan liittyvää koulutustarjontaa ja luoda uusi koulutustuote. Kyseessä oli konstruktiivinen tutkimus jossa käytettiin olemassa olevaa teoreettista tietoa sekä uutta, käytännöstä kerättyä tietoa. Teoriatieto osoittaa, että kaikkeen yrittämiseen liittyy riskejä ja niihin varautuminen muodostaa yhden yrittäjyyden suurimmista haasteista. Yrityksissä tarvitaan riskien tunnistamiseen ja hall...

  16. 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

  17. 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

  18. 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

  19. 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。

  20. 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。

  1. Backward scattering in π-p → pπ-,anti pp → π+π-,K-p → pK- and anti pp → panti p at 8 and 12 GeV/c

    International Nuclear Information System (INIS)

    Data on the reactions π-p → pπ-, anti pp → π+π-, K-p → pK- and anti pp → panti p at 8 and 12 GeV/c are presented. Our results agree with line reversal symmetry (between π-p → pπ- and anti pp → π+π-), Regge pole behaviour of non-exotic reactions (π-p → pπ-, anti pp → π+π-), and universal behaviour for exotic reactions (anti pp → panti p) K-p → K-) with dσ/dυvertical strokeυ=0∝s-10 excluding the existence of a ''glory'' mechanism in anti pp elastic backward scattering in our energy range. (orig.)

  2. 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...

  3. 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......)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a...... sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-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...

  4. ÜRETİM SÜRECİNDE İSTATİSTİKSEL PROSES KONTROL (İPK UYGULAMALARI VE ELEKTRONİK SEKTÖRÜNDE BİR İNCELEME

    Directory of Open Access Journals (Sweden)

    Hakan YILDIRIM

    2013-01-01

    Full Text Available ÜRETİM SÜRECİNDE İSTATİSTİKSEL PROSES KONTROL (İPK UYGULAMALARI VE ELEKTRONİK SEKTÖRÜNDE BİR İNCELEMEÖzet: İstatistiksel Proses Kontrol (İPK prosesin izlenip değişkenliğin kontrol altına alınması ve kontrol altına alınan proseste iyileştirme faaliyetlerinin yapılmasına imkan tanır. Süreçteki problemlerin belirlenip çözüme kavuşturulması için “Yedi Kalite Aracı” olarak bilinen; sınıflandırma, çetele, histogram, pareto analizi, neden-sonuç diyagramı, serpilme diyagramları ve kontrol grafiklerinden yararlanılır. Bu çalışmada, elektronik sektöründe yangın ve gaz algılama sistemlerinin üretimini yapan bir işletmede İstatistiksel Proses Kontrol tekniklerinin uygulaması yapılmıştır. Üretim sürecindeki arıza türleri, kaynakları ve sebeplerinin incelenmesi amacıyla düzenli veri toplanması için çetele tablosu oluşturulmuştur. En önemli arıza sebeplerine yönelmek için Pareto Analizi yapılmıştır. İşletmede, arızaların oluşmasındaki en büyük etken ile ilgili nedenlerin belirlenmesi için neden-sonuç diyagramı oluşturulmuştur. Prosesin kontrol altında olma durumunun belirlenmesi için kalite kontrol kısmından alınan veriler ile kontrol diyagramları oluşturulmuştur.STATISTICAL PROCESS CONTROL (SPC APPLICATIONS IN THE PRODUCTION PROCESS AND A STUDY IN THE ELECTRONIC INDUSTRYAbstract: Statistical Process Control is used for monitor the process and to control variability and making improvement activities. To solve the problems, stratification, check sheet, histogram, pareto chart, cause-effect diagrams, scatter diagram and control charts are used. These are also known as Seven Quality Tools. In this study, a company in the electronics industry which is producing fire and gas detection system was applied to statistical process control techniques. To examine of fault types, sources and causes in the production process check sheet was made. Pareto Analysis is made

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Rahoituksen suunnittelu pk-yrityksessä

    OpenAIRE

    Fabritius, Juha

    2012-01-01

    Osakeyhtiön rahoitus suunnitellaan sekä pitkälle että lyhyelle aikavälille. Osakeyhtiötä rahoitetaan omalla tai vieraalla pääomalla. Oma pääoma tulee omistajilta ja ulkopuolisilta sijoittajilta. Se perustuu tuottoon ja siitä halutaan osakkeen omistajille osinkoja voitetusta pääomasta. Vieraalla pääomalla maksetaan investoinnit tuotteisiin ja koneisiin. Sen jälkeen tuotolla maksetaan takaisin lainattu pääoma luotonantajille. Tämän tutkimuksen tavoite oli selvittää rahoituksen suunnittelua lyhy...

  10. 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…

  11. 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

  12. 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

    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......-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...

  13. 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

  14. 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

  15. 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.

  16. 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…

  17. Laadunhallinta pk-yrityksissä : ISO 9001:2008

    OpenAIRE

    Lester, Päivi

    2011-01-01

    Tämän opinnäytetyön tavoitteena oli selvittää hyötyvätkö pienet ja keskisuuret yritykset laatustandardi ISO 9001:2008:n avulla kehitetystä laadunhallintajärjestelmästä ja millä lailla. Tutkimuskysymyksenä oli miten yritykset ovat kokeneet standardin ISO 9001:2008 käyttöönoton, ylläpidon ja sen tuomat hyödyt. Laatu on nykypäivän markkinoilla yrityksille tärkeä kilpailukeino, ja sen hallintaan käytettäviä työkaluja on paljon. Yksi tunnetuimmista laadunhallintajärjestelmistä on standardi ISO 900...

  18. 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

  19. Dosing of colistin – back to basic PK/PD

    OpenAIRE

    Bergen, Phillip J.; Jian LI; Nation, Roger L

    2011-01-01

    The increasing prevalence of multidrug-resistant Gram-negative bacteria worldwide has led to a re-evaluation of the previously discarded antibiotic, colistin. Despite its important role as salvage therapy for otherwise untreatable infections, dosage guidelines for the prodrug colistin methanesulfonate (CMS) are not scientifically based and have led to treatment failure and increased colistin resistance. In this review we summarise the recent progress made in the understanding of the pharmacok...

  20. 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 ...

  1. 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...

  2. 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...

  3. Www-sivuston suunnittelu ja toteutus pk-yritykselle

    OpenAIRE

    Rauhala, Antti

    2012-01-01

    Tämän opinnäytetyön toimeksiantaja on Rakennus Takalahti Oy ja työn tavoitteena oli rakentaa toimeksiantajayritykselle toimivat ja yrityksen asiakkaita palvelevat www-sivut, joiden kautta potentiaaliset asiakkaat pystyvät tutustumaan yritykseen tarkemmin ja tarvittaessa ottamaan yhteyttä. Lisäksi sivujen tulisi olla toimeksiantajayrityksen näköinen ja sen brändiä tukeva. Rakennus Takalahti Oy on vuonna 1988 perustettu oulunsalolainen rakennusalan yritys, jonka toimialaan kuuluvat muun muassa ...

  4. The PK/PD Interactions of Doxycycline against Mycoplasma gallisepticum

    Science.gov (United States)

    Zhang, Nan; Gu, Xiaoyan; Ye, Xiaomei; Wu, Xun; Zhang, Bingxu; Zhang, Longfei; Shen, Xiangguang; Jiang, Hongxia; Ding, Huanzhong

    2016-01-01

    Mycoplasma gallisepticum is one of the most important pathogens that cause chronic respiratory disease in chicken. This study investigated the antibacterial activity of doxycycline against M. gallisepticum strain S6. In static time–killing studies with constant antibiotic concentrations [0–64 minimum inhibitory concentration (MIC)], M. gallisepticum colonies were quantified and kill rates were calculated to estimate the drug effect. The half-life of doxycycline in chicken was 6.51 ± 0.63 h. An in vitro dynamic model (the drug concentrations are fluctuant) was also established and two half-lives of 6.51 and 12 h were simulated. The samples were collected for drug concentration determination and viable counting of M. gallisepticum. In static time–killing studies, doxycycline produced a maximum antimycoplasmal effect of 5.62log10 (CFU/mL) reduction and the maximum kill rate was 0.11 h−1. In the in vitro dynamic model, doxycycline had a mycoplasmacidal activity in the two regimens, and the maximum antimycoplasmal effects were 4.1 and 4.75log10 (CFU/mL) reduction, respectively. Furthermore, the cumulative percentage of time over a 48-h period that the drug concentration exceeds the MIC (%T > MIC) was the pharmacokinetic–pharmacodynamic index that best correlated with antimicrobial efficacy (R2 = 0.986, compared with 0.897 for the peak level divided by the MIC and 0.953 for the area under the concentration–time curve over 48 h divided by the MIC). The estimated %T > MIC values for 0log10 (CFU/mL) reduction, 2log10 (CFU/mL) reduction and 3log10 (CFU/mL) reduction were 32.48, 45.68, and 54.36%, respectively, during 48 h treatment period of doxycycline. In conclusion, doxycycline shows excellent effectiveness and time-dependent characteristics against M. gallisepticum strain S6 in vitro. Additionally, these results will guide optimal dosing strategies of doxycycline in M. gallisepticum infection. PMID:27199972

  5. 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.)

  6. Pk-matkailuyritysten verkostoituminen : Case: Lohjan matkailupalvelukeskuksen toiminta-alue

    OpenAIRE

    Ahtela, Anu

    2011-01-01

    Kansallisen aluepolitiikan tavoitteena on mm. alueiden kansallisen ja kansainvälisen kilpailukyvyn kehittyminen sekä alueiden erityishaasteisiin vastaaminen. Globaali kilpailutilanne kiristyy ja matkailualan yritysten tulisi pitää puoliaan kiristyvässä kilpailussa. Pienille ja keskisuurille matkailualanyrityksille verkostoituminen tarjoaa tähän erinomaisen, toisiaan jopa ainoan, mahdollisuuden. Ennen kuin verkostoitumista alueella voidaan kehittää ja tarjota siihen uusia mahdollisuuksia, on s...

  7. 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.

  8. 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 ...

  9. 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...

  10. 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. ...

  11. 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

  12. Markkinointiviestinnän kanavien kartoitus PK-yritykselle

    OpenAIRE

    Laiho, Leena

    2013-01-01

    Opinnäytteen tarkoitus oli vertailla markkinoinnin keinoja ja mahdollisuuksia. Opinnäyte pyrki nostamaan esiin niitä mainonnan menetelmiä, joilla markkinointi saadaan toteutettua menestyksekkäästi taloudelliset resurssit huomioonottaen. Tutkimuksen tavoitteena oli mainonnan tehokkuuden mittaaminen markkinointitutkimuksen keinoja soveltamalla. Tutkimuksen avulla pyrittiin saamaan informaatiota siitä, miten asiakkaat seuraavat eri mainontakanavia, minkä tyyppiset mainokset herättävät mielenkiin...

  13. 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.

  14. 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.

  15. 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 (...

  16. 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...

  17. 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...

  18. 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...

  19. ISO 9001:2008 -laadunhallintajärjestelmä pk-yritykseen

    OpenAIRE

    Vanhatalo, Tuomas

    2010-01-01

    Tämä opinnäyte toteuttaa ISO 9001 -laadunhallintastandardin mukaisen laadunhallintajärjestelmän rakentamisen pienikokoiseen konepajayritykseen. Opinnäytetyössä käytetään pohjatietona standardeja: ISO 9000, ISO 9001, ISO 9004, ISO 19011 ja teknistä tiedotetta ISO/TR 10013. Lisäksi aineistossa on merkittäviä teoksia laadunhallintajärjestelmän rakentamisesta ja laadunhallinnan kehittämisestä. Opinnäytetyö jakaa ISO 9001 -standardin mukaisen laadunhallintajärjestelmän rakentamisen ...

  20. 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。

  1. 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.

  2. 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...

  3. 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 ...

  4. 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…

  5. 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...

  6. 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。

  7. 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

  8. 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

  9. Materiaalinhallinnan kehittäminen teollisuuseristykseen keskittyvässä PK-yrityksessä

    OpenAIRE

    Salmi, Ville

    2014-01-01

    Opinnäytetyön tavoitteena oli hankinnan portfolioanalyysin teko ABC-analyysia avuksi käyttäen. Tutkimuksen avulla pyrittiin kehittämään yrityksen hankintojen suunnittelua. Lisäksi varastojen järjestystä, toimivuutta ja siisteyttä oli parannettava. Tutkimuksen toteuttamista varten selvitettiin ensin yrityksen nykytila ja ongelmat. Materiaalinhallinnassa oli useita epäkohtia, kuten hankintojen ajoitus. Varastot olivat sekavat, epäjärjestelmälliset ja epäsiistit. Inventaarion suorittaminen oli v...

  10. 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

  11. Immunogenicity to Therapeutic Proteins: Impact on PK/PD and Efficacy

    OpenAIRE

    Chirmule, Narendra; Jawa, Vibha; Meibohm, Bernd

    2012-01-01

    The development of therapeutic proteins requires the understanding of the relationship between the dose, exposure, efficacy, and toxicity of these molecules. Several intrinsic and extrinsic factors contribute to the challenges for measuring therapeutic proteins in a precise and accurate manner. In addition, induction of an immune response to therapeutic protein results in additional complexities in the analysis of the pharmacokinetic profile, toxicity, safety, and efficacy of this class of mo...

  12. The effects of Mycoplasma hyopneumoniae on porcine circovirus type 2 replication in vitro PK-15 cells.

    Science.gov (United States)

    Wang, Haiyan; Feng, Zhixin; Wu, Yuzi; Wei, Yanna; Gan, Yuan; Hua, Lizhong; Li, Bin; Wang, Xiaomin; Liu, Maojun; Xiong, Qiyan; Shao, Guoqing

    2016-04-01

    Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome (PMWS). Mycoplasma hyopneumoniae (Mhp) is a very well-known co-factor that potentially enhances PCV2 replication and thus the development of PMWS. However, co-infection with Mhp and PCV2 in vivo under different conditions can produce divergent clinical signs and lesions. In this study, PCV2 replication could be enhanced by subsequent co-inoculation with Mhp (PCV2+Mhp) in a time and dose dependent method, but not by prior (Mhp+PCV2) or simultaneous (Mhp/PCV2) co-inoculation. Furthermore, different magnitudes of PCV2-infected cells, varying from 150%±14% to 351%±28%, were detected when co-infected with different Mhp strains. The relative percentage of PCV2-infected cells greatly decreased from 351%±28 to 141%±18 when the Mhp strain was treated with UV light for 12h. These results offer the evidences to better understand the complex clinical syndromes in Mhp/PCV2 co-infection cases, and the occurrence of PMWS. PMID:27033909

  13. 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.

  14. DNA-PK contributes to the phosphorylation of AIRE: Importance in transcriptional activity

    OpenAIRE

    Liiv, Ingrid; Rebane, Ana; Org, Tõnis; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Juronen, Erkki; Valmu, Leena; Bottomley, Matthew James; Kalkkinen, Nisse; Peterson, Pärt

    2008-01-01

    The autoimmune regulator (AIRE) protein is a key mediator of the central tolerance for tissue specific antigens and is involved in transcriptional control of many antigens in thymic medullary epithelial cells (mTEC). Mutations in the AIRE gene cause a rare disease named autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Here we report using GST pull-down assay, mass-spectrometry and co-immunoprecipitation that a heterotrimeric complex of DNA-Dependent Protein Kinase (DNA...

  15. 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 ...

  16. How to integrate in vitro PK/PD information for toxicity prediction

    OpenAIRE

    2009-01-01

    Predicting drugs' in vivo effects from in vitro testing requires modelling processes that are not reproduced by in vitro systems. The most obvious difference between the two situations is the absence of the absorption, distribution, metabolism, and excretion (ADME) processes that govern target tissue exposure in vivo. For identical input doses, the concentrations to which in vitro systems are exposed may not correspond to those found in vivo. The partners of Predict-IV work package 5 will dev...

  17. Radiobiological and PK assays at advance Centre for Training Research and Education in Cancer (ACTREC)

    International Nuclear Information System (INIS)

    Radiobiological, pharmacokinetic and biodistribution studies are of paramount importance for drug development and more so in the development of newer radiation modulators. Radiobiological studies have now graduated from simple cell survival and viability assays to more complex molecular and imaging studies to study radiation modulation both in in-vitro and in-vivo models. Tata Memorial Centre and its research centre (ACTREC) is a premiere cancer centre in India dedicated to cancer research. The Department of Radiation Oncology treats approximately 7000 new patients in a year and is uniquely placed to do both translational radiation and clinical research in the field of drug development. The Clinical Biology Lab of the Department of Radiation Oncology at ACTREC in collaboration with other labs at ACTREC has standardized cell survival assays, DNA damage assays such as Gamma H2AX assay (by flow as well as confocal microscopy), Micronuclei assay and COMET assays using CASP software for quantification. We have also done apoptotic assays. These assays have been conducted for development newer drug formulations (for e.g liposomal radiosensitizers). We also have a strong imaging division having sophisticated microscopes (confocal and single molecule super resolution microscopes) for in-vitro optical imaging and a dedicated preclinical PET/CT/SPECT for in-vivo imaging. The clinical 3T MRI and PET/CT is being used to study the effect of hypoxia in various cancers

  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. 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.

  20. 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.

  1. 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...

  2. Anti-TJa alloimmunization (anti-PP1Pk): two consecutive pregnancies of an anti-TJa-carrying patient.

    Science.gov (United States)

    Haentjens-Verbeke, K; Dufour, P h; Vinatier, D; Tordjeman, N; Monnier, J C; Manessier, L

    1996-01-01

    Anti-TJa alloimmunization is an extremely rare condition which can cause miscarriages during the first and second terms of pregnancy. At 20-year-old female patient, an anti-TJa carrier, was given plasma transfusions in the course of her first two pregnancies. The cordocentesis, which was the main follow-up test during the first pregnancy, could not be carried out during the second pregnancy due to the presence of a huge subchorionic hematoma. Both pregnancies were characterized by fetal growth retardation, which was particularly considerable in one. Due to chronic fetal distress, both infants were delivered prematurely by cesarean section. The immunohematological data concerning anti-TJa alloimmunization and the different palliative treatments available to date are reviewed. PMID:8838768

  3. 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...

  4. 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.

  5. 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...

  6. 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...

  7. Johtamisjärjestelmän kehittäminen kiinteistöhuoltoalan pk-yritykseen

    OpenAIRE

    Råberg, Susan

    2013-01-01

    Opinnäytetyössäni kehitin yritykseemme sopivan ja toimivan johtamisjärjestelmän. Yritys on aloittanut toimintansa vuonna 1982 ja kasvanut vuosien saatossa. Organisaation johtaminen ja johtamiskulttuuri olivat jääneet vähemmälle huomiolle kun kaikki aika ja näkemys on panostettu yrityksen kasvuun. Nyt oli otollinen aika panostaa johtamisen kehittämiseen yrityksessä ja johtamiskulttuurin luomiseen. Tärkeimmät kehittämisen tavoitteet olivat saada työn johtaminen ja organisointi sujumaan arje...

  8. 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.

  9. 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…

  10. 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...

  11. 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-

  12. 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

  13. 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.

  14. 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...

  15. Revitalizing the Field of Educational Foundations and PK-20 Educators' Commitment to Social Justice and Issues of Equity in an Age of Neoliberalism

    Science.gov (United States)

    Hartlep, Nicholas D.; Porfilio, Bradley J.

    2015-01-01

    In this article, we situate the imminent extinction of educational foundations within larger macro contexts, including the corporate control of knowledge production, the marginalization of critical academics who challenge the social, economic, and political status quos, and the global (United States in particular) economic recession. We also…

  16. 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…

  17. 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...

  18. 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

  19. Lihan mikrobiologiseen ja aistittavaan laatuun vaikuttavia tekijöitä pienimuotoisen liha-alan laitoksen naudanlihan raakakypsytysprosessissa : elintarvikealan pk-yrityksen laadun varmentaminen

    OpenAIRE

    Haikarainen, Leena

    2011-01-01

    Tämä työ on tehty Kangasniemen kunnan ja paikallisten liha-alan pienyritysten yhteistyönä. Työn tavoitteena oli löytää liha-alan pienyritykselle sopiva varastointiaika ja lämpötila naudanlihan raakakypsyttämiseen eli mureuttamiseen. Samalla oli tarkoitus arvioida raakakypsytyksen jälkeen pakastetun lihan säilyvyysaika. Tarkoituksena oli myös vastata lainsäädännön (MMMa 37/EEO/2006) vaatimukseen ”varastointia varten pakastettavaksi tarkoitetut elintarvikkeet on pakastettava viipymättä jää...

  20. 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.

  1. 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。

  2. 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...

  3. 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...

  4. Expression and phosphorylation state analysis of intracellular protein kinases using Multi-PK antibody and Phos-tag SDS-PAGE

    OpenAIRE

    Yasunori Sugiyama; Syouichi Katayama; Isamu Kameshita; Keiko Morisawa; Takuma Higuchi; Hiroshi Todaka; Eiji Kinoshita; Emiko Kinoshita-Kikuta; Tohru Koike; Taketoshi Taniguchi; Shuji Sakamoto

    2015-01-01

    Protein kinase expression and activity play important roles in diverse cellular functions through regulation of phosphorylation signaling. The most commonly used tools for detecting the protein kinase are protein kinase-specific antibodies, and phosphorylation site-specific antibodies were used for detecting activated protein kinase. Using these antibodies, only one kinase was analyzed at a time, however, a method for analyzing the expression and activation of a panel of protein kinases in ce...

  5. 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 $\\...

  6. 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

    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...... maximal triptorelin stimulation of the basal LH pool release was 1330 times above basal concentrations, with a potency of 0.047 ng ml-1. The LH pool release was decreased by a maximum of 94.2% by degarelix with an estimated potency of 1.49 ng ml-1. Conclusions Our model of the HPG axis was able to account...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  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. 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, J.

    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

  9. 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...

  10. [18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

    OpenAIRE

    Boutin, Hervé; Prenant, Christian; Maroy, Renaud; Galea, James; Greenhalgh, Andrew D; Smigova, Alison; Cawthorne, Christopher; Julyan, Peter; Wilkinson, Shane M.; Banister, Samuel D; Brown, Gavin; Herholz, Karl; Kassiou, Michael; Rothwell, Nancy J

    2013-01-01

    Purpose: Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. 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 neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to&nb...

  11. In Vivo Detection of Diffuse Inflammation in Secondary Progressive Multiple Sclerosis Using PET Imaging and the Radioligand 11C-PK11195.

    OpenAIRE

    Rissanen, E.; Tuisku, J.; Rokka, J.; Paavilainen, T.; Parkkola, R.; Rinne, J O.; Airas, L

    2014-01-01

    Patients with secondary progressive multiple sclerosis (SPMS) are lacking efficient medication to slow down the progression of their disease. PET imaging holds promise as a method to study, at the molecular level and in vivo, the central nervous system pathology of SPMS. PET might thus help to elucidate potential therapeutic targets and be useful as an imaging biomarker in future treatment trials of progressive multiple sclerosis. The objective of this study was to evaluate whether translocat...

  12. Cross-Culture Influences on Interpersonal Relationship in Communication Management A Case Study: Foreign Supervisors PK Chinese Employees inForeign-Invested Enterprises

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zhang

    2013-05-01

    Full Text Available China has taken a gradual reform in the enterprise system and human resources management has been changedday by day in foreign-invested enterprises. A subsequent challenge of this globalization is the managerialinfluences of multicultural management. This paper is to clarify and analyze the problems which stem fromcultural conflicts between foreign supervisors and Chinese subordinators in Chinese foreign-investedenterprises. Other than that, this paper also tries to find some feasible ways to improve the current situation. Aqualitative approach with a single case study of “Email Gate” in China is employed in the study.

  13. Aplicación de fluoroquinolonas en Medicina Veterinaria: criterios farmacocinéticos y farmacocinéticos/farmacodinámicos (PK/PD

    OpenAIRE

    Marín Carrillo, Pedro

    2008-01-01

    La tesis doctoral esta compuesta por 10 artículos, con sus correspondientes 10 resúmenes. En todos los casos que fue posible, se realizó un estudio cruzado y el método de determinación de todas las quinolonas fue cromatografía liquida de alta resolución (HPLC) con un detector de fluorescencia: 1. El objetivo fue estudiar la farmacocinética de difloxacino (5 mg/kg) en el caballo (n=6). Difloxacino puede ser efectivo para el tratamiento de infecciones por bacterias sensibles en caballos. ...

  14. Optimization of gas path aerodynamics for PK-39 boiler of power generating unit No. 4 of Troitskaya SDPP using numerical simulation of gas flows

    Science.gov (United States)

    Prokhorov, V. B.; Grigorev, I. V.; Fomenko, M. V.; Kaverin, A. A.

    2015-12-01

    Power generating unit no. 4 of Troitskaya State District Power Plant (SDPP) is incapable of operating with a nominal load of 278 MW because of high aerodynamic drag of the gas path. At present, the maximum load of the two-boiler single-turbine unit is 210 MW practically without a possibility of adjustment. The results of numerical simulation of the gas flow for the existing gas path from the electrostatic precipitator (EP) to the smoke exhausts (SEs) and two flue designs proposed for renovation of this section are presented. The results of simulation show that the existing flue section has high aerodynamic drag, which is explained by poor, as regards aerodynamics, design. The local loss coefficient, in terms of the dynamic pressure in the sucker pocket of the smoke exhaust is equal to 4.57. The local aerodynamic loss coefficient after renovation at the considered section according to the first version would make 1.48, and according to the second version 1.325, which would reduce losses at this section by more than a factor of three, and ensure the power unit operation with the rated load.

  15. Triple Regge analysis of the fragmentation processes K-p → Σ+ and pk- → Σ+ at 4.2 GeV/c, ch. 4

    International Nuclear Information System (INIS)

    The inclusive production of Σ+ in K-p interactions at 4.2 GeV/c has been studied. Both the target fragmentation of the proton into Σ+ and the beam fragmentation of the kaon into Σ+ have been analyzed with a triple-Regge model. In the p(anti sigma)+-channel, an effective exchange trajectory has been obtained which lies between the K and K(890) trajectories. For the K(anti sigma)+-channel, a trajectory is found which may be interpreted as a Δ-tracjectory lowered by one half

  16. 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...

  17. 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.

  18. 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 ...

  19. Partial wave analysis of the reaction p(3.5 GeV) + p -> pK(+) Lambda to search for the "ppK(-)" bound state

    Czech Academy of Sciences Publication Activity Database

    Agakishiev, G.; Arnold, O.; Belver, D.; Belyaev, A.; Krása, Antonín; Křížek, Filip; Kugler, Andrej; Sobolev, Yuri, G.; Tlustý, Pavel; Wagner, Vladimír

    2015-01-01

    Roč. 742, MAR (2015), s. 242-248. ISSN 0370-2693 R&D Projects: GA MŠk LG12007; GA ČR GA13-06759S Institutional support: RVO:61389005 Keywords : kaonic nuclei * anti-kaon-nucleon physics * ppK(-) * low energy * QCD * partial wave analysis Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 6.131, year: 2014

  20. 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.

  1. 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.

  2. 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。

  3. Estudio de Soluciones Cimentación de un Edificio Industrial, antiguas instalaciones "Pikolin", en la carretera de Logroño-Zaragoza, en el P.K. 6+500, T.M. Zaragoza.

    OpenAIRE

    MOYA MAÑES, IGNACIO

    2015-01-01

    [EN] The object of the present study is the solution of the foundations of an Industrial building in the sector H-61-5, old industries Pikolin, highway Logroño Km 6.5 Zaragoza. In this environment are known problems of subsidence and collapse by Karst land. Raises a study and analysis of the foundations of the industrial building located in the environment of Zaragoza. In recent years there has been an increase in damage to structures from the effects of karst terrain, havin...

  4. 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.

  5. Turnaround Insights from the Organizational Sciences: A Review of the Empirical Evidence and the Development of a Staged Model of Recovery with Potential Implications for the PK-12 Education Sector

    Science.gov (United States)

    Murphy, Joseph

    2008-01-01

    In this article, we review research from the organizational sciences to develop lessons for educators and policy makers. The approach is an integrative review of the literature. We employ a comprehensive process to unpack and make sense of the turnaround literature from the organizational sciences. We rely on strategies appropriate for document…

  6. Development of new generation tools for introduction and enhanced use of advanced nuclear fuel types in Czech nuclear reactors. Czech Ministry of Trade and Industry Project 1H-PK2/07 within the POKROK programme. Final report

    International Nuclear Information System (INIS)

    The following topics were studied: (1) Stationary and quasi-stationary models and modules of neutron physics of the reactor core; (2) Preparation and processing of spectrally dependent effective cross section data and libraries; (3) Stationary and quasi-stationary models of thermal technology of the fuel and reactor core; (4) Dynamic models of physics and thermal technology of the fuel and reactor core; (5) Technological and user interface of the complex; and (6) Standardization of the methods. (P.A.)

  7. Budist dönemi Türk şiiri üzerine incelemeler: An-Tsang’a ait bir şiir metni (metin, tercüme, notlar, dizin, tıpkıbasım)

    OpenAIRE

    KILIÇ, Ayşe

    2012-01-01

    An-tsang tarafından çevirisi yapılan Buddhavataṃsaka Sÿtra’dan alınan veDoğu Türkistan seferleri sırasında ele geçirilmiş olan bu eser, British Museum Or.8212/ 108 numaralı mecmuada kayıtlı olup aynı mecmuanın 54. sayfasından 62.sayfasının sonuna kadar 151 satır, 200 mısra ve 50 dörtlükten meydana gelmektedir.Eserde MahayÀnÀ Buddhizminin felsefesi, Buddhist öğretileri, Buddha veBodhisattvaların evreni algılayış biçimleri açıklanır. Uygur dönemine ait zengin birkelime hazinesi ve özel...

  8. 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。

  9. 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 ...

  10. 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 ...

  11. 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...

  12. 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 ...

  13. What Is a Colonoscopy

    Medline Plus

    Full Text Available ... less than 1 mm. We have the high definition colonoscope by Olympus. This also has a filter ... south Florida, it’s called narrowband image and high definition colonoscope. The colonoscope also can augment the size, ...

  14. 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...

  15. 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...

  16. Piperidine-Substituted Perylene Sensitizer for Dye-Sensitized Solar Cells

    OpenAIRE

    Ashraful Islam; Surya Prakash Singh; Palanisamy Kalimuthu; Daichi Takahashi; Yusho Takaguchi; Joe Otsuki; Liyuan Han

    2011-01-01

    We have prepared a novel piperidine-donor-substituted perylene sensitizer, PK0002, and studied the photovoltaic performance in dye-sensitized solar cells (DSSCs). Physical properties and photovoltaic performance of this new perylene derivative PK0002 are reported and compared with those of unsubstituted perylene sensitizer, PK0003. PK0002, when anchored to nanocrystalline TiO2 films, achieves very efficient sensitization across the whole visible range extending up to 800 nm. The incident phot...

  17. A pragmatic approach to the design of population pharmacokinetic studies

    OpenAIRE

    Roy, Amit; Ette, Ene I.

    2005-01-01

    The publication of a seminal article on nonlinear mixed-effect modeling led to a revolution in pharmacokinetics (PKs) with the introduction of the population approach. Since then, interest in obtaining accurate and precise estimates of population PK parameters has led to work on population PK study design that extended previous work on optimal sampling designs for individual PK parameter estimation. The issues and developments in the design of population PK studies are reviewed as a prelude t...

  18. Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

    OpenAIRE

    Xi-Qing Yan; Zhi-Gang Chen; Rong-Liang Wang; Jun Yang; Fang Ai; Yan-Juan Pan; Pei-Yong Qiu; Da-Xin Wang

    2013-01-01

    The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK paramete...

  19. Quantification and diversity in the black seeds (nigella sativa L.) gene stock of pakistan for their composition of mineral nutrients

    International Nuclear Information System (INIS)

    Nigella saliva (L.) a member of family Ranunculaceae is an annual herbaceous plant indigenous to the Mediterranean region that contains more than 100 nutrients and had been used for edible and medicinal purposes in major parts of the world since long. Present study is on the analysis of thirty four accessions with two check genotypes for genetic diversity based on thirteen mineral nutrients. High variation for Fe, Ca, Cu, Mg, Pb, Zn, Co, Mn, Na, P, B, K and N indicated the scope of sample selection for these characters. Coefficient of correlation studies revealed that Cu had significantly positive correlation with Ca, whereas Mg was significantly correlated with Ca and Cu. Linkages of desirable traits are suggested to be broken through novel techniques for maximum exploitation of genomic diversity for valuable phyto-chemicals. Based on principal component analysis, first four factors contributed 62 percent of the variability amongst genotypes for mineral nutrients. Eigen value> I exhibited 23.57 % of variation for component I, 17.28 % for component 2 and 12.43 % of variation for component 3, respectively. Moreover, it also reflects the potential of improvement, through building broad based gene pool by acquiring more samples from diverse geographical areas. These principal components could be selected individually for the improvement of specific mineral nutrients for multipurpose use and applications. Six clusters were observed for 36 genotypes based on mineral nutrients. The genotypes Pk-020877, Pk-020749, Pk-020876, Pk-020545, Pk-020561, Pk-020781 and Pk-020729, Pk-020620, Pk-020561, Pk-020631, Pk-020879, Pk-020868 produced the highest N (5.56), Fe (0.74), Ca (10.83), Mg (11.56), Pb (0.09), Zn (0.09), Na (0.68), P (0.66), B (39.58), and K (0.99), whereas Pk-020873 produced lowest N (1.67), Pk-020766 Fe (0.10), Pk-020576 Ca (7.38), Pk-020585 Mg (9.40), check-2 Pb (0.02), Pk-020872 Zn (0.01), Pk-020781 and Pk-020877 Na (0.17), check-2 P (0.50), Pk-020585 B (13

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. 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 .

  7. 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?

  8. 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.

  9. 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

  10. American College of Gastroenterology

    Science.gov (United States)

    ... gMed, MD-Reports, and Olympus EndoWorks, Pentax EndoPro IQ, ProVation, and Summit Imaging Instill in patients your ... content on the ACG Education Universe. Self-Assessment Test Take the ACG Self-Assessment Test. Produced annually ...

  11. 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.

  12. Unigene BLAST: CBRC-GGAL-18-0005 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-18-0005 gnl|UG|Gga#S6727767 pgp1n.pk007.f2 Normalized Chicken Pituitary/Hypothalamus/P ... cDNA clone pgp1n.pk007.f2 5' similar to sp|O57340|TSH B_CHICK THYROTROPIN BETA CHAIN PRECURSOR (THYROID-S ... TIMULATING HORMONE BETA SUBUNIT) (TSH -BETA) (TSH -B) gb|AAB88127> /clone=pgp1n.pk007.f2 / ...

  13. Thermal degradation kinetics of polyketone based on styrene and carbon monoxide

    International Nuclear Information System (INIS)

    Highlights: • The PK were synthesized from carbon monoxide and styrene in the presence of PANI-PdCl2 catalyst and PdCl2 catalyst. • The structures and thermal behaviors of PK prepared by homogenous and the supported catalyst were investigated. • The microstructures of PK were changed in the supported catalyst system. • The alternating PK copolymer (PANI-PdCl2 catalyst) was more thermally stable than PK (PdCl2 catalyst). • The degradation activation energy values were estimated by Flynn–Wall–Ozawa method and Kissinger method. - Abstract: Copolymerization of styrene with carbon monoxide to give polyketones (PK) was carried out under homogeneous palladium catalyst and polyaniline (PANI) supported palladium(II) catalyst, respectively. The copolymers were characterized by 1H NMR, 13C NMR and GPC. The results indicated that the PK catalyzed by the supported catalyst has narrow molecular weight distribution (PDI = 1.18). For comparison purpose of thermal behaviors of PK prepared by the homogeneous and the supported catalyst, thermogravimetric (TG) analysis and derivative thermogravimetric (DTG) were conducted at different heating rates. The peak temperatures (396–402 °C) for PK prepared by the supported catalyst are higher than those (387–395 °C) of PK prepared by the homogeneous catalyst. The degradation activation energy (Ek) values were estimated by Flynn–Wall–Ozawa method and Kissinger method, respectively. The Ek values, as determined by two methods, were found to be in the range 270.72 ± 0.03–297.55 ± 0.10 kJ mol−1. Structures analysis and thermal degradation analysis revealed that the supported catalyst changed the microstructures of PK, resulting in improving thermal stability of PK

  14. 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...

  15. Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Qiu Chun-Yu

    2012-05-01

    Full Text Available Abstract Background Prokineticin 2 (PK2 is a secreted protein and causes potent hyperalgesia in vivo, and is therefore considered to be a new pronociceptive mediator. However, the molecular targets responsible for the pronociceptive effects of PK2 are still poorly understood. Here, we have found that PK2 potentiates the activity of acid-sensing ion channels in the primary sensory neurons. Methods In the present study, experiments were performed on neurons freshly isolated from rat dorsal root ganglion by using whole-cell patch clamp and voltage-clamp recording techniques. Results PK2 dose-dependently enhanced proton-gated currents with an EC50 of 0.22 ± 0.06 nM. PK2 shifted the proton concentration-response curve upwards, with a 1.81 ± 0.11 fold increase of the maximal current response. PK2 enhancing effect on proton-gated currents was completely blocked by PK2 receptor antagonist. The potentiation was also abolished by intracellular dialysis of GF109203X, a protein kinase C inhibitor, or FSC-231, a protein interacting with C-kinase 1 inhibitor. Moreover, PK2 enhanced the acid-evoked membrane excitability of rat dorsal root ganglion neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, PK2 exacerbated nociceptive responses to the injection of acetic acid in rats. Conclusion These results suggest that PK2 increases the activity of acid-sensing ion channels via the PK2 receptor and protein kinase C-dependent signal pathways in rat primary sensory neurons. Our findings support that PK2 is a proalgesic factor and its signaling likely contributes to acidosis-evoked pain by sensitizing acid-sensing ion channels.

  16. 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 \

  17. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges

    OpenAIRE

    Yulia Vugmeyster; Xin Xu; Frank-Peter Theil; Khawli, Leslie A; Leach, Michael W.

    2012-01-01

    Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which w...

  18. 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

    K-depleted and control rats were anesthetized and infused with terbutalin. In controls, plasma K concentration (pK) decreased by 0.7 mm (P = 0.01). In moderate hypokalemia terbutalin-induced decrease in pK was reduced by 0.3 mm for each 1 mm decrease in pK (n = 8, R(2) = 0.82, P = 0.002) and by 0...

  19. 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...

  20. 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...

  1. Unigene BLAST: CBRC-GGAL-35-0059 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-35-0059 gnl|UG|Gga#S6695670 pat .pk0066.b10.f chicken activated T cell cDNA Gallus gall ... us cDNA clone pat .pk0066.b10.f 5' similar to transcription factor 4, ... mRNA sequence /clone=pat .pk0066.b10.f /clone_end=5' /gb=AI981816 /gi=588484 ...

  2. Measurements of some basic constants of 68Ga(BAT-TECH) as an imaging agent

    International Nuclear Information System (INIS)

    The kinetic properties of a new myocardial imaging agent 68Ga(BAT-TECH) are investigated and its thermodynamic constants are measured. The results are as follows: Citrate→BAT-TECH exchange reaction order is second-order; reaction rate k = 0.50 l/mol·s; activation energy Ea = 56.6 kJ/mol; the stability constant of 68Ga(BAT-TECH) lgβ = 14.9; the acid dissociation constants of BAT-TECH pK1 = 4.62, pK2 = 7.68, pK-3 = 8.68, pK4 = 11.2

  3. 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

  4. 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...

  5. Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.

    Science.gov (United States)

    Haija, Marwa Abu El; Qian, You-Wen; Muthukumar, Akila

    2014-08-01

    Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency. PMID:24481986

  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. Mechanisms of prickle1a function in zebrafish epilepsy and retinal neurogenesis

    Directory of Open Access Journals (Sweden)

    Xue Mei

    2013-05-01

    Epilepsy is a complex neurological disorder characterized by unprovoked seizures. The etiology is heterogeneous with both genetic and environmental causes. Genes that regulate neurotransmitters and ion channels in the central nervous system have been associated with epilepsy. However, a recent screening in human epilepsy patients identified mutations in the PRICKLE1 (PK1 locus, highlighting a potentially novel mechanism underlying seizures. PK1 is a core component of the planar cell polarity network that regulates tissue polarity. Zebrafish studies have shown that Pk1 coordinates cell movement, neuronal migration and axonal outgrowth during embryonic development. Yet how dysfunction of Pk1 relates to epilepsy is unknown. To address the mechanism underlying epileptogenesis, we used zebrafish to characterize Pk1a function and epilepsy-related mutant forms. We show that knockdown of pk1a activity sensitizes zebrafish larva to a convulsant drug. To model defects in the central nervous system, we used the retina and found that pk1a knockdown induces neurite outgrowth defects; yet visual function is maintained. Furthermore, we characterized the functional and biochemical properties of the PK1 mutant forms identified in human patients. Functional analyses demonstrate that the wild-type Pk1a partially suppresses the gene knockdown retinal defects but not the mutant forms. Biochemical analysis reveals increased ubiquitylation of one mutant form and decreased translational efficiency of another mutant form compared with the wild-type Pk1a. Taken together, our results indicate that mutation of human PK1 could lead to defects in neurodevelopment and signal processing, providing insight into seizure predisposition in these patients.

  8. 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...

  9. 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

  10. 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.

  11. 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

  12. 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...

  13. Grey-box modelling of pharmacokinetic/pharmacodynamic systems

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Jacobsen, Judith L; Pedersen, Oluf;

    2004-01-01

    Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling...

  14. AN ARTIFICIAL NEURAL NETWORK APPLICATIONS IN THE MANUFACTURING of CAST RESIN TRANSFORMERS

    Directory of Open Access Journals (Sweden)

    NEJAT YUMUŞAK

    1998-12-01

    Full Text Available In this study, prediction of deviation of calculated Pk, P0 and Uı.. values from the values to be measured is done by using neural nets. For this purpose three layer fe ed- forward ne ural ne ts us ing back propagation teaming algorithm is being used. We obtained an improv ement for Pk ,Po and Uk with ANN prediction.

  15. Gene : CBRC-GGAL-01-0073 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-01-0073 Novel 1 D UNKNOWN Y091_NPVOP 3e-04 28% ref|XP_001132857.1| PREDICTED: hypothet ... 28% gnl|UG|Gga#S6722311 pgf1n.pk003.g13 normalized chicken ... fat cDNA library Gallus gallus cDNA clone pgf1n.pk ...

  16. 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

  17. 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

  18. 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.

  19. 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…

  20. 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 $(4\\times10^{18})$.

  1. 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; Haunsø, Stig; Kjeldsen, Keld

    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...

  2. Identification of pyruvate kinase as an antigen associated with Tourette syndrome.

    Science.gov (United States)

    Kansy, Janice W; Katsovich, Liliya; McIver, Kevin S; Pick, Jennifer; Zabriskie, John B; Lombroso, Paul J; Leckman, James F; Bibb, James A

    2006-12-01

    Immune responses to beta-hemolytic streptococcal infections are hypothesized to trigger tic disorders and early-onset obsessive-compulsive disorder (OCD) in some pediatric populations. Here we identify the M1 isoform of the glycolytic enzyme, pyruvate kinase (PK) as an autoimmune target in Tourette syndrome and associated disorders. Antibodies to PK reacted strongly with surface antigens of infectious strains of streptococcus, and antibodies to streptococcal M proteins reacted with PK. Moreover, immunoreactivity to PK in patients with exacerbated symptoms who had recently acquired a streptococcal infection was 7-fold higher compared to patients with exacerbated symptoms and no evidence of a streptococcal infection. These data suggest that PK can function as an autoimmune target and that this immunoreactivity may be associated with Tourette syndrome, OCD, and associated disorders. PMID:17011640

  3. 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)

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Development of Compact Lenses for Micro Four-Thirds System

    Science.gov (United States)

    Koiwai, Tamotsu; Akita, Hidenori

    In 2010, "The micro SLR Olympus PEN" of Micro Four Thirds standard won double titles of CAMERA GRAND PRIX .The characteristics of Olympus PEN series are high-quality, compact, lightweight, no feeling of burden/stress and easy to take both still images and movies by SLR quality. Especially, the consciousness of compact and lightweight is taken into the series’ entire system including the body and interchangeable lenses. We have developed the interchangeable lenses by aiming ultimate miniaturization for optical and lens-barrel design along with making the miniaturizing compliance of Micro Four Thirds standard useful. In order to create compact and lightweight interchangeable lenses, a number of technical difficulties, such as realization of thinner design by adapting lens-barrel retraction system, lens-barrel with a high degree of accuracy, quick and silent AF, adaptation of special lenses, thorough trimming of weight, had to be overcome in the developmental process. Here we refer to these miniaturization technologies.

  9. Scanning acoustic microscopy study of human cortical and trabecular bone.

    Science.gov (United States)

    Bumrerraj, S; Katz, J L

    2001-12-01

    Scanning acoustic microscopy (SAM) has been used in the burst mode to study the properties of human cortical and trabecular bone. An Olympus UH3 SAM (Olympus Co., Tokyo, Japan) was used with a 400 MHz burst mode lens (120 degrees aperture, nominal lateral resolution 2.5 microm). The human cortical bone was from the midshaft of a femur from a 60+ male cadaver; the trabecular bone specimens were obtained from the distal femoral condyles of another 60+ human male cadaver. Elastic moduli for both trabecular and cortical bone were obtained by means of a series of calibration curves correlating SAM gray levels of known materials with their elastic moduli; specimens included: polypropylene, PMMA, Teflon, aluminum, Pyrex glass, titanium, and stainless steel. Values obtained by this method are in good agreement with those obtained by nanoindentation techniques. The three critical findings earlier by Katz and Meunier were observed here as well in both the cortical and trabecular bone samples. PMID:11853252

  10. 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

  11. 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...

  12. creative accounting

    OpenAIRE

    Horák, Matěj

    2010-01-01

    This bachelor thesis deals with the very actual issue, which is creative accounting. The main goal is to provide a comprehensive view on the issue of creative accounting and clarify this concept. The topic is characterized in detail in the introductory part, followed by a description of the most frequently used techniques with specific examples. The thesis continues with a description of the accounting scandals that are associated with creative accounting (e.g. Enron, Parmalat, Olympus). Part...

  13. 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".

  14. 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 ...

  15. Parasitic nematodes from turtles: New species and new record from Indonesia

    OpenAIRE

    Endang Purwaningsih; Mumpuni,

    2015-01-01

    Objective: To describe the morphological characteristics of some species of parasitic nematodes found in freshwater turtles from Sumatera (Amyda cartilaginea) and Kalimantan (Notochelys platynota). Methods: Specimens for light microscopy examination were fixed with warm 70% alcohol, cleared and mounted in lactophenol for stout specimens and glycerine for delicate specimens, prior to wet mounting. Drawings were made with the aid of a drawing tube attached to an Olympus compou...

  16. 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...

  17. 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-...

  18. Vybrané charakteristiky z biologie významných druhů z čeledi miříkovitých

    OpenAIRE

    Gregorová, Vladislava

    2014-01-01

    ABSTRACT The objective of this study was to compare the germination of cultural and weed variety of selected species of the family Apiceae. There were selected species: Daucus carota and Pastnaca sativa. For this research were selected three stocks of Carrot: Daucus carota -- wild, Daucus carota -- seeded from stored root in the garden - variety Olympus and Daucus carota -- originated from the propagation crop species -- variety Cider. For Pastinaca sativa were selected two populations: Pasti...

  19. hsCRP: Correlation between immunochemiluminescent and immunoturbidimetric method

    OpenAIRE

    Smokovska, Suzana; Ruskovska, Tatjana

    2008-01-01

    C-reactive protein (CRP) has been proposed as a sensitive inflammatory biomarker and an independent predictor for cardiovascular risk in healthy (inflammation and necrosis free) population. For this purpose a method with high sensitivity (hsCRP-high sensitivity CRP) that measures very precisely the values of this parameter from 0 to 10 mg/L has been used. The aim of our study was to determine the correlation between immunochemiluminescent (Immulite) and immunoturbidimetric (Olympus AU400)...

  20. 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...

  1. 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...

  2. 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)

  3. Small scale spatial heterogeneity of Normalized Difference Vegetation Indices (NDVIs) and hot spots of photosynthesis in biological soil crusts

    OpenAIRE

    T. Fischer; M. Veste; Andreas Eisele; Oliver Bens; W. Spyra; Reinhard F. J. Hüttl

    2012-01-01

    Normalized Difference Vegetation Indices (NDVIs) are typically determined using satellite or airborne remote sensing, or field portable spectrometers, which give an averaged signal on centimetre to metre scale plots. Biological soil crust (BSC) patches may have smaller sizes, and ecophysiological, hydrological as well as pedological processes may be heterogeneously distributed within this level of resolution. A ground-based NDVI imaging procedure using low-cost equipment (Olympus Camedia 5000...

  4. 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)

  5. Percutaneous transhepatic biliary biopsy using gastrofiberscopic biopsy forceps.

    OpenAIRE

    Kim, C. S.; Han, Y M; Song, H. Y.; Choi, K. C.; Kim, D. G.; B.H. Cho

    1992-01-01

    To obtain a histopathologic diagnosis at the site of a biliary obstruction, we recently have performed 24 cases of biliary biopsy using gastrofiberscopic biopsy forceps (Olympus, Tokyo, Japan) via transhepatic tracts provided in the course of the procedure of percutaneous biliary drainage. Histopathologic diagnosis was successfully made at the first attempt of biopsy procedure but a second trial was made a week later in 6 cases who were negative for malignant cells on the first attempt. The h...

  6. Production of dimethylsulphide during the seasonal anoxia off Goa

    Digital Repository Service at National Institute of Oceanography (India)

    Shenoy, D.M.; Sujith, K.B.; Gauns, M.; Patil, S.; Sarkar, Amit; Naik, H.; Narvekar, P.V.; Naqvi, S.W.A.

    microscope (Olympus IX 51; 400X). Phytoplankton taxa were identified following Tomas (1997), Subramanyan (1946, 1968), Lebour (1978). For carbon conversion, phytoplankton was broadly classified as diatoms and non-diatoms. Their bio-volumes were separately...-volume of dominant diatom and non-diatom taxa were then applied to other less dominant taxa (numerically contributing <5%) for carbon conversion. Since samples were analyzed immediately, effect of preservation and storage was not considered in this study. Wind...

  7. Computer simulation of lower-hybrid heating and current drive in tokamaks. Progress report, September 1, 1982-July 1, 1983

    International Nuclear Information System (INIS)

    A lower hybrid ray tracing package has been adapted for use in the PPPL 1-D tokamak transport code TRANSP. The code LHRAY has been written in OLYMPUS format and is suitable for use as a separate simulation program or in conjunction with TRANSP. The generality of the OLYMPUS conventions was chosen in order to make LHRAY easily transferable to other OLYMPUS style transport codes such as BALDUR. The details of LHRAY are described in this report. The physical model documented in our first progress report has been used with one major modification. Instead of solving the 1-D Fokker-Planck equations numerically to give the electron distribution function F/sub e/ in the presence of a background electric field, we have approximated F/sub e/ analytically using the theory of Liu et al for runaway electron distributions. The organization of LHRAY is given and the naming conventions are noted. Finally, preliminary results are presented. Program documentation and a listing of the code are included as appendices

  8. 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

  9. 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.

  10. 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.

  11. Human liver type pyruvate kinase: Complete amino acid sequence and the expression in mammalian cells

    International Nuclear Information System (INIS)

    Pyruvate kinase (PK) has four isozymes (L, R, M1, M2) that are encoded by two different genes. Among these isozymes, abnormalities of liver (L)-type PK is considered to be associated with hereditary nonspherocytic hemolytic anemia in humans. The authors isolated and determined the full-length sequence of human L-type PK cDNA. The cDNA contains 1,629 base pairs encoding 543 amino acids, 68 base pairs of 5'-noncoding sequence, and 734 base pairs of 3'-noncoding sequence. The similarity between human and rat L-type PK was 86.9% at the nucleotide sequence level and 92.4% at the amino acid sequence level. The full-length L-type PK cDNA was placed under the promoter of simian virus 40 and introduced into monkey COS cells. Human L-type PK activity was detected in the extract of COS cells by the classical PK electrophoresis method

  12. 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.

  13. Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy

    Directory of Open Access Journals (Sweden)

    J. G. Coen van Hasselt

    2014-01-01

    Full Text Available This work describes a first population pharmacokinetic (PK model for free and total cefazolin during pregnancy, which can be used for dose regimen optimization. Secondly, analysis of PK studies in pregnant patients is challenging due to study design limitations. We therefore developed a semiphysiological modeling approach, which leveraged gestation-induced changes in creatinine clearance (CrCL into a population PK model. This model was then compared to the conventional empirical covariate model. First, a base two-compartmental PK model with a linear protein binding was developed. The empirical covariate model for gestational changes consisted of a linear relationship between CL and gestational age. The semiphysiological model was based on the base population PK model and a separately developed mixed-effect model for gestation-induced change in CrCL. Estimates for baseline clearance (CL were 0.119 L/min (RSE 58% and 0.142 L/min (RSE 44% for the empirical and semiphysiological models, respectively. Both models described the available PK data comparably well. However, as the semiphysiological model was based on prior knowledge of gestation-induced changes in renal function, this model may have improved predictive performance. This work demonstrates how a hybrid semiphysiological population PK approach may be of relevance in order to derive more informative inferences.

  14. 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.

  15. 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...

  16. AcEST: BP912168 [AcEST

    Lifescience Database Archive (English)

    Full Text Available YMU001_000015_H05 554 Adiantum capillus-veneris mRNA. clone: YMU001_000015_H05. BP912168 - Show ... PQEDILEVEKERACLSGYEKMSNLGNS---SWLREEQLSTVSLKMMLACA*CSR ... 276 S Q +++E+ A + G+ ++ N + SW + Q+S + ++M+ CA C R ... +G L + ++ G + +S +T+ +L PK+ +L+I G Sbjct: 1415 LANQCSR SYKVRFEDIGRCLKCECSVSDVFGRSSELISIVTAPILPGKPKIEKLEIEG ... +G L + ++ G + +S +T+ +L PK+ +L+I G Sbjct: 1405 LANQCSR SYKARFEDIGRCLKCECSVSDVFGRSSELISIVTAPILPGKPKIEKLEIEG ... +G L + ++ G + +S +T+ +L PK+ +L+I G Sbjct: 1539 LANQCSR SYKVRFEDIGRCLKCECSVSDVFGRSSELISIVTAPILPGKPKIEKLEIEG ...

  17. 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...

  18. 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...

  19. 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...

  20. 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 ...

  1. The role of DNA dependent protein kinase in synapsis of DNA ends

    OpenAIRE

    2003-01-01

    DNA 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-PKCS) 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-PKCS, which we demonstrate to require synapsis of DNA ends. Interestingly, the presence of DNA-PK preve...

  2. 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...

  3. 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...

  4. 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.

  5. Hypoxia/oxidative stress alters the pharmacokinetics of CPU86017-RS through mitochondrial dysfunction and NADPH oxidase activation

    OpenAIRE

    Gao, Jie; Ding, Xuan-Sheng; Zhang, Yu-mao; Dai, De-zai; Liu, Mei; Zhang, Can; Dai, Yin

    2013-01-01

    Aim: Hypoxia/oxidative stress can alter the pharmacokinetics (PK) of CPU86017-RS, a novel antiarrhythmic agent. The aim of this study was to investigate the mechanisms underlying the alteration of PK of CPU86017-RS by hypoxia/oxidative stress. Methods: Male SD rats exposed to normal or intermittent hypoxia (10% O2) were administered CPU86017-RS (20, 40 or 80 mg/kg, ig) for 8 consecutive days. The PK parameters of CPU86017-RS were examined on d 8. In a separate set of experiments, female SD ra...

  6. Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level

    OpenAIRE

    Choi, Min-Koo; Song, Im-Sook

    2016-01-01

    This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2–75 μM) in LLC-PK1-Pgp, s...

  7. Retrospective serological survey of antibodies to porcine circovirus type 1 and type 2.

    OpenAIRE

    Magar, R; Müller, P; Larochelle, R

    2000-01-01

    A retrospective serological survey was performed to determine the presence of antibodies to porcine circovirus type 1 (PCV1) and porcine circovirus type 2 (PCV2) in serum samples collected from sows at slaughterhouses in Canada in 1985, 1989, and 1997. Each serum sample was tested by indirect immunofluorescence on PCV-free PK15 cells, on PCV1-infected PK15 cells and on PCV2-infected PK15 cells. For the 3 years studied, sera positive to PCV1 and PCV2 were identified and the number of sera posi...

  8. Two amino acid mutations in the capsid protein of type 2 porcine circovirus (PCV2) enhanced PCV2 replication in vitro and attenuated the virus in vivo

    OpenAIRE

    Fenaux, M.; Meng, X.J.; F Elvinger; Opriessnig, T.; Halbur, P. G.

    2004-01-01

    Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome (PMWS) in pigs. To identify potential genetic determinants for virulence and replication, we serially passaged a PCV2 isolate 120 times in PK-15 cells. The viruses harvested at virus passages 1 (VP1) and 120 (VP120) were biologically, genetically, and experimentally characterized. The PCV2 VP120 virus replicated in PK-15 cells to a titer similar to that of the PK-15 cell line-derived ...

  9. Two Amino Acid Mutations in the Capsid Protein of Type 2 Porcine Circovirus (PCV2) Enhanced PCV2 Replication In Vitro and Attenuated the Virus In Vivo

    OpenAIRE

    Fenaux, M.; Opriessnig, T.; Halbur, P. G.; F Elvinger; Meng, X.J.

    2004-01-01

    Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome (PMWS) in pigs. To identify potential genetic determinants for virulence and replication, we serially passaged a PCV2 isolate 120 times in PK-15 cells. The viruses harvested at virus passages 1 (VP1) and 120 (VP120) were biologically, genetically, and experimentally characterized. The PCV2 VP120 virus replicated in PK-15 cells to a titer similar to that of the PK-15 cell line-derived ...

  10. 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...

  11. Grape yield and quality of the grapevine cultivar limberger treated with plant growth regulators

    OpenAIRE

    Todić Slavica R.

    2004-01-01

    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 co...

  12. 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.

  13. The TURis System for Transurethral Resection of the Prostate: A NICE Medical Technology Guidance.

    Science.gov (United States)

    Cleves, Andrew; Dimmock, Paul; Hewitt, Neil; Carolan-Rees, Grace

    2016-06-01

    The transurethral resection in saline (TURis) system was notified by the company Olympus Medical to the National Institute of Health and Care Excellence's (NICE's) Medical Technologies Evaluation Programme. Following selection for medical technologies guidance, the company developed a submission of clinical and economic evidence for evaluation. TURis is a bipolar surgical system for treating men with lower urinary tract symptoms due to benign prostatic enlargement. The comparator is any monopolar transurethral resection of the prostate (mTURP) system. Cedar, a collaboration between Cardiff and Vale University Health Board, Cardiff University and Swansea University in the UK, acted as an External Assessment Centre (EAC) for NICE to independently critique the company's submission of evidence. Eight randomised trials provided evidence for TURis, demonstrating efficacy equivalent to that of mTURP for improvement of symptoms. The company presented meta-analyses of key outcome measures, and the EAC made methodological modifications in response to the heterogeneity of the trial data. The EAC analysis found that TURis substantially reduced the relative risks of transurethral resection syndrome (relative risk 0.18 [95 % confidence interval 0.05-0.62]) and blood transfusion (relative risk 0.35 [95 % confidence interval 0.19-0.65]). The company provided a de novo economic model comparing TURis with mTURP. The EAC critiqued the model methodology and made modifications. This found TURis to be cost saving at £70.55 per case for existing Olympus customers and cost incurring at £19.80 per case for non-Olympus customers. When an additional scenario based on the only available data on readmission (due to any cause) from a single trial was modelled, the estimated cost saving per case was £375.02 for existing users of Olympus electrosurgery equipment and £284.66 per case when new Olympus equipment would need to be purchased. Meta-analysis of eight randomised trials showed

  14. UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Kooy, M. van M.; Akkerman, J.W.N.; Asbeck, S. van; Borghuis, Lizette; Prooijen, H.C. van (Utrecht Univ. Hospital (Netherlands))

    1993-02-01

    In the present study the authors have further investigated the routes of platelet activation following UVB exposure. Evidence is provided that UVB radiation does not activate the platelets via the classical Phospholipase A[sub 2] and Phospholipase C routes. Despite this observation, UVB-induced fibrinogen binding was found to be correlated with a 40% increase in phosphorylated 47 kD protein. Both findings could be completely inhibited in the presence of staurosporine, a potent inhibitor of protein kinase C (PK-C). In efforts to explain the mechanism of PK-C activation by UV radiation they found that both UV-induced PK-C activation and platelet aggregation were significantly reduced in the presence of specific scavengers for reactive oxygen species including superoxide dismutase and catalase. It is concluded that exposure of platelets to UVB radiation can activate PK-C via oxygen radicals, resulting in exposure of fibrinogen binding sites and subsequent platelet aggregation. (Author).

  15. 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.

  16. 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 $_{-p}K$.

  17. 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.

  18. The role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Wegener, Gregers; Brink, Christiaan; Harvey, Brian

    2010-01-01

    Background Recently we reported on a novel antidepressant-like response following simultaneous administration of sildenafil (PDE5 inhibitor, thereby increasing cGMP levels), and atropine (muscarinic acetylcholine receptor antagonist) in the rat forced swim test (FST). It is unclear whether the...... antidepressant-like activity of sildenafil + atropine is mediated via the activation of PK-G, a downstream effector for cGMP, and whether this may target known pathways in antidepressant action. Purpose We investigated whether the antidepressant-like response of sildenafil ± atropine could be reversed by Rp-8-Br......-PET-cGMP, a PK-G inhibitor, and also whether a combination of 8-Br-cGMP (PK-G activator) ± atropine would likewise be active in the FST, and whether this combination could be attenuated by a PK-G inhibitor. Study methods The FST consisted of a 15 minute pre-conditioning swim session on the first day of the...

  19. NCTM's Standards for School Mathematics, K-12.

    Science.gov (United States)

    Thompson, Charles S.; Rathmell, Edward C.

    1988-01-01

    Provides a rationale and overview of the content of the working draft of the Curriculum and Evaluation Standards for School Mathematics, developed by the National Council of Teachers of Matematics. (PK)

  20. Is oral absorption of vigabatrin carrier-mediated?

    DEFF Research Database (Denmark)

    Nøhr, M. K.; Juul, R. V.; Thale, Z. I.; Holm, R.; Kreilgaard, M.; Nielsen, Carsten Uhd

    2015-01-01

    The aim of the study was to investigate the intestinal transport mechanisms responsible for vigabatrin absorption in rats by developing a population pharmacokinetic (PK) model of vigabatrin oral absorption. The PK model was used to investigate whether vigabatrin absorption was carrier-mediated and...... if the proton-coupled amino acid transporter 1 (PAT1) was involved in the absorption processes. Vigabatrin (0.3-300 mg/kg) was administered orally or intravenously to Sprague Dawley rats in the absence or presence of PAT1-ligands l-proline, l-tryptophan or sarcosine. The PK profiles of vigabatrin...... were described by mechanistic non-linear mixed effects modelling, evaluating PAT1-ligands as covariates on the PK parameters with a full covariate modelling approach. The oral absorption of vigabatrin was adequately described by a Michaelis-Menten type saturable absorption. Using a Michaelis constant...

  1. Impact of special patient populations on the pharmacokinetics of echinocandins.

    Science.gov (United States)

    Muilwijk, Eline W; Lempers, Vincent J C; Burger, David M; Warris, Adilia; Pickkers, Peter; Aarnoutse, Rob E; Brüggemann, Roger J M

    2015-06-01

    Echinocandins belong to the class of antifungal agents. Currently, three echinocandin drugs are licensed for intravenous treatment of invasive fungal infections: anidulafungin, caspofungin and micafungin. While their antifungal activity overlaps, there are substantial differences in pharmacokinetics (PK). Numerous factors may account for variability in PK of echinocandins including age (pediatrics vs adults), body surface area and body composition (normal weight vs obesity), disease status (e.g., critically ill and burn patients) and organ dysfunction (kidney and liver impairment). Subsequent effects of altered exposure might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal clinical utilization of echinocandin in a specific patient or patient population. This review provides up-to-date information on PK data of anidulafungin, caspofungin and micafungin in special patient populations. Patient populations addressed are neonates, children and adolescents, obese patients, patients with hepatic or renal impairment, critically ill patients (including burn patients) and patients with hematological diseases. PMID:25947367

  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. Using Writing Activities to Reinforce Mathematics Instruction.

    Science.gov (United States)

    Davison, David M.; Pearce, Daniel L.

    1988-01-01

    Presents writing activities appropriate in the mathematics classroom in the five categories of direct use of language, linguistic translation, summarizing, applied use of language, and creative use of language. (PK)

  4. 76 FR 19980 - Funding Priorities, Requirements, and Definitions

    Science.gov (United States)

    2011-04-11

    .... (2004). Impact of exposures to violence in school on child and adolescent mental health and behavior. Journal of Community Psychology. 32, 559-573. \\6\\ Smith, P.K. & Sharp, S. (1994). The problem of...

  5. 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

  6. 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.

  7. 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.)

  8. How to Spot Health Fraud

    Science.gov (United States)

    ... Bioterrorism and Drug Preparedness How to Spot Health Fraud Share Tweet Linkedin Pin it More sharing options ... health fraud. --P.K. Joining Forces to Fight Fraud Health fraud isn't confined to the United ...

  9. DINAMIKA PENDIDIKAN KEWIRAUSAHAAN: PEMETAAN SISTEMATIS TERHADAP PENDIDIKAN, PENGAJARAN DAN PEMBELAJARAN KEWIRAUSAHAAN

    Directory of Open Access Journals (Sweden)

    Margo Purnomo

    2015-03-01

    Full Text Available Saat ini belum ada kesepakatan diantara para ahli pendidikan kewirausahaan (PK tentang pendekatan terbaik dalam pembelajaran (BK dan pengajaran (AK kewirausahaan. Berdasarkan Systematic Mapping Study (SMS, ada empat fokus tema dalam PK yaitu kebijakan untuk pendidikan kewirausahaan, konteks pendidikan kewirausahaan, pengajaran kewirausahaan, dan pembelajaran kewirausahaan. Berdasarkan SMS diketahui juga bahwa permasalahannya bukan tentang metode apa yang terbaik dalam PK tetapi pengajar kewirausahaan dituntut untuk mampu mengenali fungsi dan keunggulan setiap metode pengajaran kewirausahaan. Hal ini mengindikasikan bahwa perkembangan kewirausahaan yang semakin kontekstual membutuhkan dukungan kebijakan PK yang terintegrasi baik pada ranah makro, mezzo, dan mikro. Dukungan demikian sangat penting agar pelaksanaan pembelajaran dan pengajaran kewirausahaan yang inovatif, efektif, dan efisien dapat diselenggarakan.

  10. 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 ...

  11. 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

  12. Integration of the 3D kinetics code QUABOX/CUBBOX in the GRS analysis simulator-ATLAS based on ATHLET

    International Nuclear Information System (INIS)

    The paper describes the successfully performed verification tests with the ATLAS simulator environment and the coupled QUABOX/CUBBOX-ATHLET code system with enhanced option of switching from point kinetics (PK) to 3D calculations. (authors)

  13. [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

  14. 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:

  15. In vivo imaging of ''neuroinflammation''. Principles and applications

    International Nuclear Information System (INIS)

    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 [11C], the R-enatiomer [11C] PK1195 has been used for positron emission tomography (PET) studies to demonstrate neuroinflammatory changes in vivo. [11C](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 [11C](R) PK11195 PET as a diagnostic tool and a surrogate marker of ''neuroinflammation'' in therapeutic trials. (orig.)

  16. 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)

  17. 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 ...

  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. 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

  20. Reference: GRAZMRAB17 [PLACE

    Lifescience Database Archive (English)

    Full Text Available GRAZMRAB17 Busk PK, Jensen AB, Pages M Regulatory elements in vivo in the promoter ...of the abscisic acid responsive gene rab17 from maize. Plant J 11:1258-1295 (1997) PubMed: 9225468; ...