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Sample records for grammatik kurs a2

  1. Ny forskning i grammatik. Fællespublikation 9

    Artikler over grammatik der er blevet til i forlængelse af foredrag holdt på et fællesseminar på Sandbjerg Gods den 11.-13. oktober 2001. Artiklerne omhandler grammatikforskning inden for dansk, fransk, italiensk og spansk...

  2. Turgi rahvad Krimmis / Ott Kurs

    Kurs, Ott, 1939-

    2002-01-01

    Illustreeritud geograafilise kaardiga ; ka krimtsakidest ehk krõmtsakidest ning krimmitatarlaste naasmisest kodumaale alates 1980-ndate II poolest. Sama ilmunud ka : Kurs, Ott. Rajamaade rahvaid. - Tartu : Ilmamaa, 2006, lk. 212-223

  3. Regarding KUR Reactivity Measurement System

    Nakamori, Akira; Hasegawa, Kei; Tsuchiyama, Tatsuo; Yamamoto, Toshihiro; Okumura, Ryo; Sano, Tadafumi

    2012-01-01

    This article reported: (1) the outline of the reactivity measurement system of Kyoto University Research Reactor (KUR), (2) the calibration data of control rod, (3) the problems and the countermeasures for range switching of linear output meter. For the laptop PC for the reactivity measurement system, there are four input signals: (1) linear output meter, (2) logarithmic output meter, (3) core temperature gauge, and (4) control rod position. The hardware of reactivity measurement system is controlled with Labview installed on the laptop. Output, reactivity, reactor period, and the change in reactivity due to temperature effect or Xenon effect are internally calculated and displayed in real-time with Labview based on the four signals above. Calculation results are recorded in the form of a spreadsheet. At KUR, the reactor core arrangement was changed, so the control rod was re-calibrated. At this time, calculated and experimental values of reactivity based on the reactivity measurement system were compared, and it was confirmed that the reactivity calculation by Labview was accurate. The range switching of linear output meter in the nuclear instrumentation should automatically change within the laptop, however sometimes this did not function properly in the early stage. It was speculated that undefined percent values during the transition of percent value were included in the calculation and caused calculation errors. The range switching started working properly after fixing this issue. (S.K.)

  4. ANALISIS PARITAS DAYA BELI KURS RUPIAH TERHADAP DOLLAR AMERIKA SERIKAT

    Elysa Pernika Simanjuntak

    2017-06-01

    Full Text Available Penelitian ini bertujuan untuk menganalisis bagaimana penerapan teori paritas daya beli kurs Rupiah terhadap Dollar AS dalam jangka panjang maupun jangka pendek dan pengaruh tingkat inflasi, produk domestik bruto, jumlah uang beredar, dan cadangan devisa terhadap kurs Rp/USD dengan menggunakan alat analisis Error Correction Model Engle-Granger. Variabel dependen dalam penelitian ini adalah kurs, sedangkan variabel independennya adalah inflasi, produk domesti bruto, jumlah uang beredar, dan cadangan devisa. Hasil penelitian ini menunjukkan bahwa dalam jangka panjang maupun jangka pendek, teori paritas daya beli berlaku pada kurs Rupiah terhadap Dollar Amerika Serikat. Variabel independen secara bersama-sama berpengaruh terhadap kurs Rupiah dalam jangka pendek maupun jangka panjang kecuali variabel jumlah uang beredar tidak berpengaruh dalam jangka panjang dan cadangan devisa tidak berpengaruh terhadap kurs dalam jangka pendek. Rekomendasi dari penelitian ini adalah Bank Indonesia selaku bank sentral Republik Indonesia diharapkan lebih berhati- hati dalam mengambil kebijakan yang tepat demi menjaga kestabilan nilai tukar Rupiah. Salah satunya tetap mengawasi kebijakan yang ditetapkan pemerintah mengenai pemakaian Rupiah untuk seluruh transaksi dalam negeri.  This research aims to analyze how the application of the theory of purchasing power parity exchange rate of the Rupiah against the US Dollar in the long term and short term and influence the rate of inflation, GDP, money supply, and the foreign exchange reserves of the exchange rate of Rp/USD by using analytical tools Error Correction Model Engle-Granger. Dependent variable in this study is the exchange rate, while the independent variables are inflation, gross domestic product, money supply, and the foreign exchange reserves. The results of this study indicated that in the long term and short term, the theory of purchasing power parity exchange rate prevailing at the Rupiah against the US

  5. Ultracold and very cold neutron facility in KUR

    Kawabata, Yuji; Utsuro, Masahiko

    1992-01-01

    The present status of the ultracold and very cold neutron facility installed in the Kyoto University Reactor (KUR) is described in this presentation. It consists of a VCN (very cold neutrons) guide tube, a VCN bender and a supermirror neutron turbine. The guide tube extracts VCN from a liquid deuterium cold neutron source in a graphite thermal column and the neutron turbine converts VCN to UCN (ultracold neutrons). As for the utilization of the present facility, VCN radiography and an UCN gravity spectrometer are shown for the practical examples of the research with VCN and UCN. (author)

  6. Future plans on the Kyoto University Research Reactor (KUR)

    Shibata, Seiichi

    2000-01-01

    The Research Reactor Institute (RRI), Kyoto University, for aiming at performing the 'Experiments using a reactor and its related research', was established in Showa 38 (1963) as a cooperative research institute for universities and so on in allover Japan. Operation using KUR of one of main facilities in RRI was started by 1 MW of its rated output in 1964, and converted to 5 MW in 1968, after which through development , addition and modification of various research apparatus it has been proposed to the cooperative application researches with universities and so on in allover Japan, hitherto. Among these periods, its research organization is improved to six departments containing twenty divisions and two attached research facilities to progress some investigations on future plans at RRI for response to new researching trends. Here were described on present state of research on use of low concentrated uranium fuels at research reactor, and future plans on neutron factory and hybrid reactor. The former aims at establishment of a new research facility capable of alternating to KUR for future academic research on research reactor containing high quality and high degree application of neutron field and safety management and feature upgrading of nuclear energy. And, the latter aims at development on an accelerator drive uncritical reactor combined an accelerator neutron source and an uncritical reactor. (G.K.)

  7. Thermal neutron standard fields with the KUR heavy water facility

    Kanda, K.; Kobayashi, K.; Shibata, T.

    1978-01-01

    A heavy water facility attached to the KUR (Kyoto University Reactor, swimming pool type, 5 MW) yields pure thermal neutrons in the Maxwellian distribution. The facility is faced to the core of KUR and it contains about 2 tons of heavy water. The thickness of the layer is about 140 cm. The neutron spectrum was measured with the time of flight technique using a fast chopper. The measured spectrum was in good agreement with the Maxwellian distribution in all energy region for thermal neutrons. The neutron temperature was slightly higher than the heavy water temperature. The contamination of epithermal and fast neutrons caused by photo-neutrons of the γ-n reaction of heavy water was very small. The maximum intensity of thermal neutrons is 3x10 11 n/cm 2 sec. When the bismuth scatterer is attached, the gamma rays contamination is eliminated by the ratio of 0.05 of gamma rays to neutrons in rem. This standard neutron field has been used for such experiments as thermal neutron cross section measurement, detector calibration, activation analysis, biomedical purposes etc. (author)

  8. Sprachbewusstheit und Fremdsprachenlernen. Inwiefern fördert die Grammatik in skandinavischen DaF-Lehrwerken die Sprachbewusstheit der Lernenden?

    Åsta Haukås

    2016-10-01

    Full Text Available Dieser Artikel untersucht, inwiefern einige skandinavische Lehrwerke für junge DaF-AnfängerInnen das Potenzial haben, die Sprachbewusstheit der Lernenden zu fördern. Vor dem Hintergrund einer kurzen Übersicht zur für die Studie relevanten Forschung im Bereich Fremdsprachendidaktik und der jeweiligen Lehrpläne für die Schule werden Grammatikerklärungen und -übungen analysiert. Obwohl die Lehrpläne in Norwegen und Schweden große Ähnlichkeiten aufweisen, ist das Vorkommen von expliziten Grammatikerläuterungen und Grammatikübungen in den norwegischen Lehrwerken viel höher als in den schwedischen. In sämtlichen Lehrwerken werden die Lernenden jedoch nur vereinzelt dazu aufgefordert, Sprache zu beobachten, über Sprache zu sprechen und eigene Schlüsse zu ziehen. Die Schlussfolgerung ist demnach, dass die Lehrwerke nur begrenzt zur Förderung der Sprachbewusstheit der Lernenden beitragen.  This article studies to what extent a sample of Scandinavian textbooks for young learners of German as a foreign language have the potential to promote language awareness. Using a short overview of relevant aspects of research on foreign language learning as well as descriptions of national curricula for compulsory school as background, grammar descriptions and exercises are analysed. Even though there are many similarities between the Norwegian and Swedish curricula, the number of explicit grammar descriptions and exercises is extensively higher in the Norwegian textbooks. However, in all textbooks the learners are only rarely asked to observe language, talk about language and draw their own conclusions. The main result is therefore that the textbooks contribute to promoting language awareness to a very limited extent.

  9. Theoretical and experimental notes on noise phenomena of KUR

    Kishida, Kuniharu

    1980-01-01

    The classification of global or local noise is important in reactor noise analysis. The term of ''global'' or ''local'' corresponds to that of ''system size'' or ''cell size'' in statistical physics. On the other hand, point model or phase space description is used in time series analysis. If a time series model describing spatial behavior is established, it will serve to reactor diagnosis. The noise phenomena of KUR are discussed from these points of view. In other words, from experimental results, the point reactor picture is reasonable to neutronic aspect but quantitative problem remains in coolant temperature fluctuations. By taking into account a diffusion type model, the spatial dependence is discussed for the problem remaining in coolant temperature fluctuations. It is pointed out that the time-space picture is a crucial idea of reactor noise phenomena. (author)

  10. Record of radiation management inside KUR facilities, no. 13 (1976)

    Katsurayama, Kosuke; Tsujimoto, Tadashi; Saito, Masahiro; Tsuruta, Takao; Fukui, Masami.

    1979-01-01

    The record of radiation management inside the KUR buildings in 1976 is reported. Relating to the routine radiation management inside the facilities, the spatial dose rate has been always monitored, utilizing the area monitors which are composed of GM survey meters and BF 3 neutron survey meters, inside the reactor building, the hot laboratory, the tracer building, the waste treatment building, the linear accelerator building, the gamma irradiation building, the solid waste storage and the research building. The measured dose rate at 5000 kW power level was about 2 mrem/h in the reactor building and about 4 mrem/h in the hot laboratory at maximum. Inside the other buildings, the dose rates were almost background level. The cumulative dose was measured utilizing film badges, and the measured maximum value was about 450 mrem in one month in the spent fuel storage pool. The surface contamination was monitored, and about 10 -7 μCi/cm 2 was obtained on the reactor top and in several places in the hot laboratory. The monitoring of radioactivity concentration in water was conducted, and the concentration almost exceeded 1 x 10 -5 μCi/cm 3 in low level water. The monitoring was conducted for radioactive dust concentration, and about 100 x 10 -11 μCi/cm 3 was obtained at maximum in the hot cave. The gas concentration in the reactor room showed about 6 x 10 -7 μCi/cm 3 as the mean value of a month. The external exposure dose around the site was about 2 mrem in one year as the mean value. The status of operation of the KUR, the radiation monitoring systems for spatial dose rate, the cumulative spatial dose, the surface contamination and so on, the monitoring equipments and the regular inspection are explained. (Nakai, Y.)

  11. Present state of the modification project of KUR

    Utsuro, Masahiko

    1991-01-01

    The Kyoto University research reactor attained the initial criticality and started the operation at the rated thermal output of 1 MW in 1964. Since then, it has been utilized for the very wide fields of research for more than a quarter century as the first full scale research reactor for the main purpose of common utilization by universities and others. With the remarkable advance of scientific research during this period, the demand for heightening the performance of the facilities has become strong. The subcommittee on examination of KUR remodeling has advanced the examination aiming at the improvement of safety and performance, the strengthening of the features as research reactor, and the improvement of reliability and rate of operation. In particular, the method of inserting a core tank has been analyzed and examined in detail. The way of thinking on research reactor was summarized in 'Concrete image of MW class research reactor attached to university: Neutron spectrum factory'. Its contents are described. The subjects to be examined hereafter are pointed out. The research on precise neutron utilization, the neutron utilization of special condition are the future objective. (K.I.)

  12. Proceedings of the 2nd KUR symposium on hyperfine interactions

    Mekata, M.; Minamisono, T.; Kawase, Y.

    1991-10-01

    Hyperfine interactions between a nuclear spin and an electronic spin discovered from hyperfine splitting in atomic optical spectra have been utilized not only for the determination of nuclear parameters in nuclear physics but also for novel experimental techniques in many fields such as solid state physics, chemistry, biology, mineralogy and for diagnostic methods in medical science. Experimental techniques based on hyperfine interactions yield information about microscopic states of matter so that they are important in material science. Probes for material research using hyperfine interactions have been nuclei in the ground state and radioactive isotopes prepared with nuclear reactors or particle accelerators. But utilization of muons generated from accelerators is recently growing. Such wide spread application of hyperfine interaction techniques gives rise to some difficulty in collaboration among various research fields. In these circumstances, the present workshop was planned after four years since the last KUR symposium on the same subject. This report summarizes the contributions to the workshop in order to be available for the studies of hyperfine interactions. (J.P.N.)

  13. Low temperature irradiation facility at Kyoto University Reactor (KUR)

    Atobe, Kozo; Okada, Moritami; Yoshida, Hiroyuki; Kodaka, Hisao; Miyata, Kiyomi.

    1977-01-01

    A new refrigeration system has been substituted to the low temperature irradiation facility at KUR instead of the previous one, since April in 1975. The model 1204 CTi He liquifier was designed to be modified for the refrigerator with the capacity of 30 watts at 10 K. The refrigeration capacity of 38 watts at 10 K was defined using a special cryostat and transfer-tubes, and the lowest temperature of about 18 K was measured using the irradiation loop without reactor operation. The reconstructed facility enables us to hold the many specimens simultaneously in the sample chamber of the irradiation loop at about 25 K during reactor operation of 5 MW. The irradiation dose has been reached about 6.6 x 10 16 n sub(f)/cm 2 and 6.1 x 10 17 n sub(th)/cm 2 with the normal reactor operation cycle of up to 77 hours. The stable operation condition of the machine and the special safety system for the refrigeration system enable us to maintain easily the facility with a constant operation condition for such a long time irradiation. Many kinds of low temperature neutron irradiation experiments are carried out using the facility, which techniques are partially reported. (auth.)

  14. Status and future plan of KUR-ISOL for new isotope search

    Taniguchi, Akihiro [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.

    1997-07-01

    He gas-jet type ISOL (KUR-ISOL: Kyoto University Reactor-Isotope Separator On-Line) was set up in Kyoto University Reactor in 1979. The thema of researches using KUR-ISOL are investigation of new isotope elements, study of nuclear structure of neutron-enrich nucleide in the neighborhood of 150 of mass number, development of unstable nuclide production unit and research of physical properties using unstable nuclide as probe. By KUR-ISOL, four kinds of new isotopes such as {sup 156}Pm, {sup 155}Nd, {sup 154}Pr and {sup 152}Ce and {beta}-decay of {sup 150}La had been identified. {beta}-decay of {sup 150}La as a sample of them was explained in this report. Today, the experiment of {sup 153}Pr, {sup 152}Pr and {sup 149,150}Ce are proceeding. For future plans, new beam line and new target used transuranic elements will be developed. (S.Y.)

  15. Educational use of research reactor (KUR) and critical assembly (KUCA) at Kyoto University

    Misawa, Tsuyoshi; Unesaki, Hironobu; Ichihara, Chihiro; Pyeon, Cheol Ho; Shiroya, Seiji

    2005-01-01

    At Kyoto University Research Reactor Institute, a research reactor of 5MW (KUR) and a critical assembly (KUCA) have been used for educational purpose to train undergraduate or graduate students. Using KUR, basic experiments for neutron applications have been carried out, and KUCA has been used for the education of nuclear engineering and technology. Especially, using KUCA, a joint reactor laboratory course of graduate level is offered every summer since 1975 by nine associated Japanese universities, and more than 2200 students attended this course

  16. Direct radiocarbon dating and DNA analysis of the Darra-i-Kur (Afghanistan) human temporal bone.

    Douka, Katerina; Slon, Viviane; Stringer, Chris; Potts, Richard; Hübner, Alexander; Meyer, Matthias; Spoor, Fred; Pääbo, Svante; Higham, Tom

    2017-06-01

    The temporal bone discovered in the 1960s from the Darra-i-Kur cave in Afghanistan is often cited as one of the very few Pleistocene human fossils from Central Asia. Here we report the first direct radiocarbon date for the specimen and the genetic analyses of DNA extracted and sequenced from two areas of the bone. The new radiocarbon determination places the find to ∼4500 cal BP (∼2500 BCE) contradicting an assumed Palaeolithic age of ∼30,000 years, as originally suggested. The DNA retrieved from the specimen originates from a male individual who carried mitochondrial DNA of the modern human type. The petrous part yielded more endogenous ancient DNA molecules than the squamous part of the same bone. Molecular dating of the Darra-i-Kur mitochondrial DNA sequence corroborates the radiocarbon date and suggests that the specimen is younger than previously thought. Taken together, the results consolidate the fact that the human bone is not associated with the Pleistocene-age deposits of Darra-i-Kur; instead it is intrusive, possibly re-deposited from upper levels dating to much later periods (Neolithic). Despite its Holocene age, the Darra-i-Kur specimen is, so far, the first and only ancient human from Afghanistan whose DNA has been sequenced. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. REAKSI PASAR MODAL TERHADAP PELAPORAN SELISIH KURS PERSPEKTIF FOREIGN CURRENCY FORWARD EXCHANGE-IFRS (STUDI EMPIRIS DI BURSA EFEK INDONESIA

    R. Anastasia Endang Susilawati

    2011-02-01

    Full Text Available Penelitian ini bertujuan memberikan bukti empiris mengenai pelaporan selisih kurs terhadap reaksi pasar modal dengan menggunakan return saham sebagai proxy. Sampel penelitian diperoleh 31 perusahaan dari Bursa Efek Indonesia pada periode pengamatan antara tahun 2007-2010 menggunakan metode purposive sampling. Temuan penelitian ini mendukung hipotesis satu dan hipotesis dua bahwa terdapat hubungan signifikan antara pelaporan rugi selisih kurs yang diakui sebagai pendapatan/biaya dengan return saham. Return saham tidak berkorelasi secara signifikan dengan perubahan pendapatan bersih atau revenue. Return saham berkorelasi negatif dan signifikan dengan perubahan cash flow dibagi dengan total assets. Return saham tidak berkorelasi secara signifikan dengan pelaporan rugi selisih kurs. Dari uji beda, investor merespon tidak berbeda dengan melihat return saham terhadap dua metode pelaporan akuntansi atas laba/rugi selisih kurs yaitu yang mengakui sebagai pendapatan/biaya dan yang mengkapitalisasi laba/rugi selisih kurs tersebut. Penelitian selanjutnya diharapkan memasukkan perusahaan yang mengkapitalisasi laba/rugi selisih kurs sebagian pada seluruh jenis industri dan membandingkan ketiga metode pelaporan selisih kurs 

  18. Weiterentwicklung Gruppenleiter/innen-Kurs: Ein Projekt in der Freiwilligenarbeit des CVJM/CVJF Regionalverband Basels: Projektbericht

    Fankhauser, Miriam

    2016-01-01

    Im folgenden Bericht geht es um das Projekt «Weiterentwicklung Gruppenleiter/innen-Kurs – Ein Pro- jekt in der Freiwilligenarbeit des CVJM/CVJF Regionalverband Basels». Dieses Projekt wurde von der Studentin Miriam Fankhauser im Rahmen der Praxisausbildung an der Hochschule Luzern für Soziale Arbeit durchgeführt. In Auftrag gegeben wurde das Projekt vom CVJM/CVJF Regionalverband Basel. Beim eben genannten Projekt ging es darum, den Gruppenleiter/innen-Kurs weiterzuentwickeln. Der Kurs rich...

  19. Measurements of neutron intensity from liquid deuterium moderator of the cold neutron source of KUR

    Kawai, Takeshi; Ebisawa, Toru; Akiyoshi, Tsunekazu; Tasaki, Seiji

    1990-01-01

    The neutron spectra from the liquid deuterium moderator of the cold neutron source of KUR were measured by the time of flight (TOF) method similar to the previous measurements for the liquid hydrogen moderator. The cold neutron gain factor is found to be about 20 ∼ 28 times for the wavelength longer than 6 A. Cold neutron intensities from the liquid deuterium moderator and from the liquid hydrogen moderator are compared and discussed. (author)

  20. Analisis Pemanfaatan Kredit Usaha Rakyat (KUR) Bagi Pengembangan Usaha Kecil Menengah (UKM) di Kecamatan Medan Johor

    Dalimunthe, Mhd Hidayat

    2017-01-01

    This study entitled "Utilization Analysis Business Credit (KUR) For the Development of Small and Medium Enterprises (SMEs) in the district of Medan Johor". The purpose of this study was to determine the effect of financing provided business credit against business development. This research is qualitative descriptive. The population is all Small and Medium Enterprises (UKM), which receives funding from the People's Business Credit Medan Johor. Determination of the sample using random sampling...

  1. Kuranishi spaces as a 2-category

    Joyce, Dominic

    2015-01-01

    This is a survey of the author's in-progress book arXiv:1409.6908. 'Kuranishi spaces' were introduced in the work of Fukaya, Oh, Ohta and Ono in symplectic geometry (see e.g. arXiv:1503.07631), as the geometric structure on moduli spaces of $J$-holomorphic curves. We propose a new definition of Kuranishi space, which has the nice property that they form a 2-category $\\bf Kur$. Thus the homotopy category Ho$({\\bf Kur})$ is an ordinary category of Kuranishi spaces. Any Fukaya-Oh-Ohta-Ono (FOOO)...

  2. ANALISIS KURS, TCPI DAN KEBIJAKAN TAX REFUND TERHADAP JUMLAH WISMAN DI INDONESIA

    Rif’atin Nabilah

    2017-06-01

    Full Text Available Industri pariwisata merupakan suatu sektor yang memegang peranan penting dalam perekonomian Indonesia, salah satunya sebagai sumber penerimaan devisa. Hal ini  disebabkan karena pertumbuhan pariwisata Indonesia yang terus meningkat dan berdampak positif terhadap penerimaan devisa Indonesia. Jumlah wisman yang datang ke Indonesia merupakan faktor yang berpengaruh secara langsung terhadap penerimaan devisa tersebut. Penelitian ini bertujuan untuk mengetahui seberapa besar pengaruh kurs, TCPI dan kebijakan Tax Refund sebagai variabel ekonomi makro terhadap jumlah wisman Singapura yang datang ke Indonesia periode 2009-2013. Metode analisis yang digunakan adalah OLS (Ordinary Least Square menggunakan bantuan program E-views. Hasil menunjukkan bahwa kurs dan kebijakan Tax Refund mempengaruhi jumlah wisman Singapura yang datang ke Indonesia secara signifikan, sedangkan TCPI tidak. Jumlah kunjungan wisman dapat ditingkatkan dengan upaya Pemerintah dalam memaksimalkan pelaksanaan kebijakan Tax Refund, mengendalikan laju inflasi di Indonesia serta mengupayakan agar rupiah tidak selalu terdepresiasi. Dengan upaya tersebut,  wisatawan  global akan semakin tertarik untuk berwisata ke Indonesia.  Tourism is one of sector that have an important effect in economy of Indonesia, one of them as a source of foreign exchange earnings. That’s not caused due to the growth of Indonesian tourism that has a positive impact to foreign exchange earnings in Indonesia. The number of tourists in Indonesia is the factor that directly affects the foreign exchange earnings. This study aims to determine how much kurs, TCPI and Tax Refund as a macro economic variables to the number of  Singapore tourists in Indonesia at 2009-2013. Analysis metode used in this study is OLS (Ordinary Least Square using  E-views program assistance. Research show that kurs and Tax Refund affects significantly to the number of Singapore tourists in Indonesia and TCPI didn’t make it. The

  3. Kurşunun Cyprinus carpio Kas Dokusunda İyon Paremetrelerine Etkisi

    Hikmet Yeter ÇOĞUN

    2011-10-01

    Full Text Available Bu araştırmada, C. carpio’nun kas dokusunda kurşun (Pb etkisinde iyon parametrelerdeki (Na+, K+, Ca++ ve Mg++ değişimleri Atomik Absorbsiyon Spektrometrik yöntemle belirlenmiştir.Araştırmada kurşunun 0.1 ve 1.0 mg/L derişimleri 10 ve 20 günlük sürelerde, C. carpio kas dokusundaki metal etkisinde kas dokusundaki iyon parametreler (Na+, K+, Ca++ ve Mg++ incelenmiştir. Yapılan çalışmada C. carpio kas dokusunda kurşun her iki derişimde de etki kalma süresinin uzamasıyla arttığı saptanmıştır. C. carpio balıkların kas dokusunda kurşun etkisinde iyon değerleri incelendiğinde, sodyum ve potasyum iyonlarında her iki derişimde ve etkide kalınan süreye bağlı olarak azalmaya, kalsiyum ve magnezyum düzeylerinde ise bir artmaya neden olmuştur.Sodyum ve potasyum iyonlarındaki azalma her iki süre sonunda kontrol grubuna göre yaklaşık %33 ve %93 oranlarında olmuştur. Kalsiyum iyon düzeyi kontrol balıkları ile karşılaştırıldığında 10. günde yaklaşık 4 katlık bir artış, 20. günde ise bu artış yaklaşık 10 kat kadar olduğu gözlenmiştir. Magnezyum iyonunda her iki sürede de artma olmuştur, fakat bu artış her iki sürenin 0.1 mg L-1Pb derişiminde kontrol grubuna göre istatistiksel bir ayrıma neden olmazken, 20. günde ise tüm derişimlerde %30 bir artış olarak istatistiksel bir ayrıma neden olmuştur

  4. Research of magnetism by neutron diffraction About 30 years with KUR-TAS

    Kawano, Shinji

    2005-01-01

    The author started his researches in KUR in 1969. This paper includes development of devices and his works. Development of the high pressure cell, the high magnetic field system, the high pressure and magnetic field and low temperature system and software, improvement and maintenance of these systems are reported. Some examples of works such as the magnetic structure and the magnetic phase diagram of Er-Y-La alloy, the helifan structure of Ho, the magnetic structure of Er under high pressure, the magnon measurement of Tb under high pressure, and the magnetic structure of DyNiSn are stated. (S.Y.)

  5. Present status of operation and utilization of Kyoto University Reactor, KUR

    Kimura, Itsuro

    1988-01-01

    The Research Reactor Institute was established as an inter-university research institute in 1963. The main installation of the Institute is the KUR, a light water moderated, tank type reactor of 5,000 kW. In addition, a 46 MeV electron linear accelerator and a gamma ray irradiation facility with 10,000 Ci Co-60 are actively used for research. In 1974, Kyoto University Critical Assembly (KUCA) was constructed, and it has been used for research and education. The Reactor Utilization Center and the Fundamental Research Laboratory for Neutron Therapy were established in 1975 and 1976, respectively. Approximately 200 people work there, of them, some 80 do research and education, including 13 professors and 12 associate professors. All the experimental facilities of the Institute are available for the cooperative research projects of other universities and public research institutions in the fields of natural science and engineering, medical science, agriculture and forestry, fishery and stock-raising, environment science, cultural science and others. As a rule, the KUR is operated for about 70 hours from Tuesday morning to Friday evening every week. The annual examination by the government is carried out in spring. The total operation time was about 45,000 hours as of the end of 1987. The recent topics are reported. (Kako, I.)

  6. Modulbaserte kurs for PhD-studentar ved Matematisk-naturvitskapleg fakultet, UiB

    Hege Folkestad

    2010-07-01

    Full Text Available Universitetsbiblioteket i Bergen har utarbeidd eit modulbasert kurs for PhD-studentar ved Matematisk-naturvitskapleg fakultet. Biblioteket har samarbeidd med fakultetet om innhald, tidspunkt og annonsering, for i størst mogeleg grad å nå studentane og tilpasse til deira behov. Kurset er ikkje obligatorisk, men anbefalast sterkt av fakultetet, som vektlegg overførbare ferdigheiter hjå doktorandane. Evalueringane så langt er svært gode, og kurset vidareførast derfor i noverande form. Generell teori er skilt ut, og presentert i tre plenumssesjonar over til saman 5 timar: 1 Strukturelle trekk ved vitskapleg litteratur, generell søketeknikk, reiskapar for søk og gjenfinning, oppdateringstenester og evaluering av skriftleg materiale 2 Siteringsstatistikk 3 Publisering, inklusive opphavsrettslege problemstillingar, Open Access, sjølvarkivering og institusjonelle arkiv. Stoff som knyttast til praktiske ferdigheiter vert presentert i workshop-form for mindre grupper i kursrom med PC-tilgang. Vi tilbyr såleis valfrie, separate, 1-2 t workshops i databasesøking, inndelt etter plattform (i.e. alle Thomson-Reutersbasane samla, alle CSA-basane samla osb.. Vidare tilbyr vi 2 t workshops i referansehandtering (EndNote. For nye brukarar vektleggast innlegging av referansar, val av stil, generering av referanselister og bruk av EndNote med Word, for erfarne brukarar vektleggast fulltekstnedlasting, oppretting av bibliografi frå fleire dokument, samarbeid om EN-bibliotek og oppretting av nye stilar. Med modulbasert kurs står studentane fritt til å stå over kjent stoff, kombinere databasekurs eller EndNote-nivå, eller kome tilbake for modular som er meir relevante seinare i løpet. I denne presentasjonen leggast vekta på plenumssesjon 1 og workshop-modulane.

  7. De tékhne grammatiké van Dionysius Thrax: de oudste spraakunst in het westen (übersetzt und eingeleitet von Pierre Swiggers und Alfons Wouters; Leuven-Paris 1998, Peeters, Orbis Linguarum 2

    Matjaž Babič

    1999-12-01

    Full Text Available Wie der Untertitel des Buches mit Recht andeutet, handelt es sich bei der Tekhne grammatike um ein Werk, das für die Geschichte der Abendländischen Sprachwissen­ schaft, der Literaturwissenschaft und nicht zuletzt der Sprachdidaktik von ungeheurer Bedeutung ist. Da jedoch die klassischen Sprachen in der heutigen Schule immer mehr den modernen Sprachen weichen müssen, reicht bei manchen Sprachwissen­ schaftlern, die sich nicht speziell mit der Antike befassen, das Gymnasialgriechisch nicht aus, um ein terminologisch beladenes Buch wie dieses im Original zu lesen. Es sind demzufolge Übersetzungen angesagt, die jedoch zweien nicht immer leicht ver­ einbaren Ansprüchen genligen müssen: sie müssen auch in einer modernen Sprache lesbar, zugleich jedoch terminologisch nicht zu weit vom Original entfernt sein. P. Swiggers und A. Wouters, zwei auf diesem Feld bekannte Fachleute, haben sich eine Übersetzung ins Niederländische vorgenommen.

  8. Development of a filtered neutron field in KUR. In behalf of biological irradiation experiments

    Sato, Takashi; Utsuro, Masahiko; Utsumi, Hiroshi

    1995-07-01

    Very little direct measurements have been made of the biological effects of neutrons below 100keV. Recently, an iron-filtered 24keV neutron beam of Harwell Materials Testing Reactor, PLUTO, was reported to be highly efficient in inducing chromosome aberrations; the efficiency being comparable to that of fission neutrons. This results could have serious repercussions for radiation protection standards as the ICRP assume a decrease in neutron RBE below 100keV. The investigations reported here have as their primary purpose the production of neutron beams at the 24keV iron window energy, using the B-1 experimental facility of the Kyoto University Research Reactor (KUR) at the Research Reactor Institute, Kyoto University (KURRI). The filtered neutron filed for biomedical applications is designed to maximized the contributions of neutrons with other energies and gamma-rays. The characteristics of the radiation field were obtained by the simple transmission calculations for Fe(45cm) and Al(35cm) filters, by using the Monte Carlo code MCN P, and by the measurement of nuclear heating for Fe and Al filter pieces. The 24keV neutron flux and gamma-ray dose rate were measured using a proton recoil counter and TLDs, respectively. The measured findings are as follows: The 24keV neutron flux at the irradiation field was approximately 1x10 6 n/cm 2 /s, and the gamma-ray dose rate was 1.0Gy/h at the surface of the B-1 plug. Nuclear heating of the filter materials was 5.2mW/g for Fe and 4mW/g for Al, in maximum. (author)

  9. Decays of 143La and 145Ce using KUR-ISOL

    Ukon, Hiroe; Shibata, Michihiro; Kawade, Kiyoshi; Yamamoto, Hiroshi; Katoh, Toshiro; Kawase, Yoichi; Okano, Kotoyuki; Ruan, J.Z.

    1987-01-01

    Accurate measurements of beta- and gamma-rays resulting from the decay of 143 La and 145 Ce are made with KUR-ISOL to develop their decay diagram. First, gamma-singles spectrometry is performed to determine the energy and intensity of gamma-rays resulting from the decay of 143 La and 145 Ce. About 30 and 7 peaks are newly identified for 143 La and 145 Ce, respectively, in their gamma-ray spectra. Another gamma-singles spectrometry is carried out using 60 cm 3 Ge(Li) and LEPS detectors to determine 620 keV gamma-ray emission rate in the decay of 143 La. The emission rate is calculated at 4.23 and 4.62 percent from measurements made with Ge(Li) and LEPS, respectively. Gamma-gamma coincidence spectrometry is performed using a 60 cm 3 Ge(Li)-142 cm 3 Ge(Li) or a 60 cm 3 Ge(Li)-LEPS detector. LEPS is then applied to beta-singles spectrometry to determine the maximum energy of the gamma-rays from 143 La and 145 Ce within an error of about 20 keV. The beta-ray end point is determined from the measurements. Decay diagrams of 143 La and 145 Ce are constructed based on these results. The intensity and multipolarity of 18.9, 23.4 and 42.3 keV gamma-rays in the decay of 143 La are determined. Energy and intensity of gamma-rays of 2.8 MeV or above are also determined for 143 La. Three low energy levels of 145 Ce is examined in comparison to the decay diagram of 143 La. 143 Ce is found to have an energy level structure similar to that of other nuclides of N = 85. (Nogami, K.)

  10. Thermal-hydraulic analysis for core conversion to the use of low-enriched uranium fuels in the KUR

    Mishima, Kaichiro; Kanda, Keiji; Shibata, Toshikazu

    1985-01-01

    A feasibility study has been performed on the core conversion to the use of low-enriched uranium (LEU) fuels in the KUR. Five fuel element geometries are studied. For each fuel element, the relation between the pressure drop and the flow rate, critical heat flux, and heat fluxes for the onset of flow instability and the onset of nucleate boiling are calculated using the computer code PLTEMP3.MOD1 which has been developed for this analysis. The effect of fuel material (UAl x -Al, U 3 O 8 -Al and U 3 Si 2 -Al) on the peak fuel temperatures is also studied. A particular interest in the mixed core which may be constructed on the way to the use of LEU fuels, the change in the bypass flow rate due to the change in the gap between different fuel elements is investigated. (author)

  11. Resumption of transport of KUR spent fuel from Japan to USA - Very long-term storage and public acceptance for transport

    Nakagome, Yoshihiro; Nishimaki, Kenzo; Kanda, Keiji

    1999-01-01

    The Research Reactor Institute, Kyoto University (KURRI) has more than 250 MTR-type HEU spent fuel elements. They have been stored in water pools after irradiation in the Kyoto University Research Reactor (KUR) core. The longest pool residence time is 25 years. In accordance with the Foreign Research Reactor Spent Nuclear Fuel Receipt Program of the United States, sixty KUR spent fuel elements were shipped from KURRI to the Savannah River Site of the USDOE in August, 1999. This shipment was done successfully through a public port in Osaka Prefecture, Japan. This is the first shipment in the past twenty-six years after the last shipment through the Yokohama Port. Concerning the use of a public port, we had to solve many issues for public acceptance. In this paper, we describe how we have stored the spent fuels for a long time with high integrity and how we have obtained public acceptance for the transport. (author)

  12. Pengaruh Literasi Keuangan Dan Faktor Demografi Terhadap Proses Keputusan Pengambilan Kredit Usaha Rakyat (KUR Pada Bank Rakyat Indonesia (BRI Kantor Unit Mantingan, Kabupaten Ngawi Jawa Timur.

    Farida Fajar Hidayati

    2017-04-01

    Full Text Available Financial institutions such as banks are often chosen by the people as a financial institution that provides funds or capital. Bank Rakyat Indonesia (BRI through Kredit Usaha Rakyat (KUR program help people in providing lending capital. Therefore, financial literacy or personal financial knowledge of the people is really needed to become guidelines the people in decision-making process of credits. This research aims to determine the effect of financial literacy and demographic factors to the decision- making process Kredit Usaha Rakyat (KUR at Bank Rakyat Indonesia Unit Office Mantingan, Ngawi, East Java. This research is quantitative desciptive data and causal analysis, respondents surveyed in this research amounted to 251 customers of Bank Rakyat Indonesia (BRI which took the capital loan business credit or Kredit Usaha Rakyat (KUR. The result showed the financial literacy in the position 84,1% with a number of very good category and demographic factor at the 71,8% with good category. Based on the coefficienr of determination is obtained that the influence of financial literacy and demographic factor to the decision-making process of credit is 25,19% and 74,81% of rest is affected by other factors such as intenal factor like life style, and psychologi factor. External factor like family effect and co-workers.

  13. Analisis Pengaruh Kurs Rupiah, Laju Inflasi, Jumlah Uang Beredar dan Pertumbuhan Ekspor terhadap Total Pembiayaan Perbankan Syariah dengan Dana Pihak Ketiga sebagai Variabel Moderating

    Syukuri Ahmad Rifai

    2017-06-01

    Full Text Available The purpose of this study was to determine the effect of the rupiah exchange rate, inflation, money supply and the growth of exports to total Islamic banking financing by using third party funds as a moderating variable. The population in this study is all Islamic banking in Indonesia both Islamic Banks or Business Unit of Sharia in 2007-2015. The sample is the entire population with time series data as much as 108 of data. The method used is multiple regression analysis. The results of this study showed that simultaneous variable rupiah exchange rate, inflation, the money supply and export growth significantly influence the total financing of Islamic banking in Indonesia. Meanwhile, third-party funds moderating influences the rupiah exchange rate, inflation and export growth to the total financing of Islamic banking in Indonesia Tujuan dari penelitian ini untuk mengetahui pengaruh kurs rupiah, inflasi, jumlah uang beredar dan pertumbuhan ekspor terhadap total pembiayaan perbankan syariah dengan menggunakan dana pihak ketiga sebagai variabel moderasi. Populasi dalam penelitian ini adalah seluruh perbankan syariah di Indonesia baik Bank Umum Syariah atau pun Unit Usaha Syariah tahun 2007-2015. Sampelnya adalah seluruh populasi dengan data time series sejumlah 108. Metode yang digunakan adalah analisis regresi berganda. Hasil penelitian ini menunjukkan bahwa secara simultan variabel kurs rupiah, inflasi, jumlah uang yang beredar dan pertumbuhan ekspor berpengaruh signifikan terhadap total pembiayaan perbankan syariah di Indonesia. Sedangkan, dana pihak ketiga memoderasi pengaruh kurs rupiah, inflasi dan pertumbuhan ekspor terhadap total pembiayaan perbankan syariah di Indonesia

  14. Proceedings of the specialist research meeting on 'the latest study on analysis of trace amount of elements using activation analysis and the results and future prospects of activation analysis using KUR'

    Ebihara, Mitsuru; Shibata, Seiichi; Sekimoto, Shun

    2014-01-01

    This Specialist Research Meeting report is the summary of the lectures that were delivered at the Specialist Research Meeting of Kyoto University Reactor Research Institute on January 25, 2013 and October 30, 2013. These meetings were held under the subtitles of 'Current state of trace element analysis using activation analysis' and 'Achievements and future prospects of activation analysis using Kyoto University research reactor (KUR)', respectively. At the former meeting, 14 speeches were delivered including the following: (1) introduction of Australia Nuclear Science and Technology Organisation (ANSTO), (2) determination of element concentration in the hairs in frequent ALS (amyotrophic lateral sclerosis) occurrence zones, (3) effects of vegetation on the acid neutralizing capacity of soil, (4) activation analysis of geological samples, and (5) current situation of KUR. At the latter meeting, 15 speeches were delivered including the following: (1) neutron activation analysis of iron meteorites and Chinese herbal medicines / herbs, (2) neutron activation analysis at KUR using IAEA-k0 method, (3) current state of KUR, (4) development and applications of automatic prompt gamma-ray analysis equipment. (A.O.)

  15. Nuclear physics with use of KUR. Reviews of 30 years studies on short-lived nuclei and perspectives for the future

    Kawase, Yoichi

    1995-01-01

    The research works which were carried out over the past 30 years on nuclear structure study have been reviewed with emphasis on the technical developments of experimental apparatus for the studies of very short-lived isotopes produced by the Kyoto University reactor(KUR). In the first chapter, nuclear structure studies of neutron-rich nuclei with use of the on-line irradiation apparatus and the on-line isotope separator(ISOL) for fission products have been described. In the second chapter, applications of nuclear methods to solid state physics by the perturbed angular correlation(PAC) technique have been examined to investigate the local electromagnetic fields in metals and compounds through the hyperfine interactions. Perspectives for the future of related research fields are given aiming at the advanced uses of short-lived radioisotopes. (author)

  16. Fresh old news from Ferenczi about the function of dreams: the dream as a Kur, as a treatment and as a Gyógyászat.

    Canesin Dal Molin, Eugênio

    2012-10-01

    This article discusses a text on the function of dreams and their relation to trauma. Ferenczi intended to present this material as a talk at the 12th International Congress of Psychoanalysis, which was to take place in Interlaken, Switzerland the same year that he wrote it (1931). The entire conference, however, was postponed, and parts of this communication's content appeared in other texts in which Ferenczi rethinks the concept of trauma and its clinical significance. In the present article the author makes use of the Freud/Ferenczi correspondence to contextualize Freud's Hungarian follower's originality regarding his theorizations about different aspects of the function of dreams. In the 1931 speech, as well as in this article, Ferenczi used a patient's dream work as a clinical example of a process in which traumatic experiences and unmastered sensory impressions can be repeated to achieve a better working-through for the dreamer. The process Ferenczi describes resembles an effort of self-treatment, of self-Kur. Copyright © 2012 Institute of Psychoanalysis.

  17. Analysis of migration trends and functions of areas inhabited by Roma: Example of Međimurje county (Croatia and the settlement of Kuršanec

    Kliček Slaven

    2016-01-01

    Full Text Available Međimurje County stands out as a developed and densely populated county of Central Croatia. Demographic and socio-economic developmental trends of Međimurje indicate the referred-to status: age structure, birth rates, population activity rates and share of jobs are significantly higher than the Croatian average. At the same time, Međimurje is home to one of the largest Croatian Roma communities, ethnically homogeneous and spatially isolated, whose predominantly unfavourable geographical features make the opposite developmental pole of previously described developed areas inhabited by the majority population. Development indicators at county level have omitted concrete living conditions of Roma. They inhabit the rural periphery characterized by social and spatial segregation, unemployment and existence on the margins of society and settlements. This paper provides an analysis of housing, economic and social functions of areas inhabited by Roma, as well as migratory trends and main functional orientation of these areas in Međimurje County. In so, the settlement of Kuršanec will be emphasized as a representative example of areas inhabited by Roma in Međimurje County.

  18. Ein altes Problem: Partikeln in der Grammatik - ja, aber wie?

    Kärnä, Aino

    2005-01-01

    Full Text Available This article deals with the concept 'particle', specifically with the German notion of 'Abtönungspartikel'. These pragmatic or modal particles were first discussed in contemporary German grammars by Harald Weydt. Although the concept itself is clear, it is difficult to include such a category in existing grammars, as is shown by the treatment of such inflexible words in different editions of the standard German grammar, Der Duden. It seems difficult to formulate a description of the word class 'particle' in such a way that it includes pragmatic particles as well as other kinds of particles, such as focus particles. This problem is not new, and I also discuss parallels from the history of linguistics.

  19. Grammatik in bilingualen Wörterbüchern

    Bergenholtz, Henning

    1995-01-01

    Almensproglige ordbøger indeholder - i modsætning til fagordbøger - traditionelt mange grammatiske oplysninger. De er dog ikke altid indarbejdet optimalt. Der kan dels foreslås mere hensigtsmæssige leksikografiske koncepter, dels er de foreliggende grammatiske informationer ikke sjældent unøjagtige...

  20. Vanast maailmast uude / Ott Kurs

    Kurs, Ott, 1939-

    2010-01-01

    Inimasustuse arenguloost arheoloogia, antropoloogia ja geneetika uurimistulemustele toetuvalt. Nüüdisinimese muistsetest rännuteedest väljakujunemispaigast Aafrikas Euraasiasse ja Ameerikasse, lühidalt hilisematest rahvarännetest (kuni 16. sajandini). Põlisrahvaste olukorrast tänapäeva Ameerika riikides

  1. ANALISIS PERUBAHAN KURS RUPIAH TERHADAP DOLLAR AMERIKA

    Triyono Triyono

    2008-12-01

    Full Text Available This research analyse influence of money supply, inflation, SBI rate of interest, and import to Indonesia Rupiah exchange rate to US Dollar. In analysis, used multiple regression analysis instrument with model Error Correction Model (ECM. With this method obtained equation of regression in long-run and short-run equilibrium. In the long run equilibrium model, covered series of adjustment process that bringing every shock to equilibrium. In other word, in the long run very possibly performed full adjustment to every changes in arising out. Estimation result from regression ECM and long-run analysis indicate that inflation variable, SBI rate of interest, and import have significant influence with positive direction to exchange rate. While variable JUB have influence with negative direction to exchange rate.

  2. Installation of foundation fieldbus to KUR

    Ishihara, Shinji; Fujita, Yoshiaki

    1999-11-01

    The instrumentation and control system for the research reactor in Research Reactor Institute, Kyoto University has been used for the safe and steady operation since the initial critical attainment in 1964. It has been modified and added many devices in the chance of increasing the reactor power from 1 MW to 5 MW, installing new experimental facilities or fitting to modified nuclear regulations. In order to avoid the unscheduled shutdown of the research reactor by cause the failure of the devices, most of instrumentation system was renewed in 1999. Operating the research reactor more safely and reliably, Supervisory Control Automation and Data Acquisition System which employed personal computers with the Windows NT operating system was added to the conventional instrumentation system, and the fieldbus system called Foundation Fieldbus was installed. Compared with conventional instrumentation system, each fieldbus system has some advantages. Many kinds of fieldbus systems have been developed and sold on the markets in some countries. Foundation Fieldbus standardizing international, which was able to use the devices made by multi-vendor was tentatively installed to study particular techniques about Foundation Fieldbus. The primary coolant flow rate, the temperature difference between the reactor tank inlet and outlet temperatures, the calorimetric power and the reactor power in nuclear instrumentation are monitored on human-machine interface devices on the fieldbus. The programmable logic controller is employed to control the information system for the reactor. This paper introduces Foundation Fieldbus installed. (author)

  3. Kaks turgi eepost eesti keeles / Ott Kurs

    Kurs, Ott, 1939-

    2013-01-01

    Arvustus: Manas : pärimus kangelasest : kirgiisi rahva eepos / [ümberjutustus ja runod: Peeter Ilus ; toimetaja ja järelsõna: Artur Laast ; illustraator Kristina Viin ; kujundaja Mart Anderson]. Ikla : Penikoorem, 2012

  4. Analisis Kurs dan Money Supply di Indonesia

    Oktavia, Adek Laksmi; Sentosa, Sri Ulfa; Aimon, Hasdi

    2013-01-01

    This article focused on analyze (1) Effect of the money supply, income, domestic interest rates, inflation and the trade balance to the exchange rate in Indonesia. (2) The influence of domestic interest rates, output and the exchange rate on the money supply in Indonesia. Data used time series of (I year kuartal 2000 – IV year kuartal 2010). This article use analyzer model equation of simultaneous with method of Two Stage Least Squared (TSLS). The result of research concludes that (1) the ...

  5. PENGARUH KURS SPOT DAN KURS FORWARD DALAM MEMPREDIKSI FUTURE SPOT PADA PASAR VALAS KAWASAN ASIA TENGGARA

    I Gusti Ayu Kade Diana Yanthi

    2013-10-01

    Full Text Available The importance of the activity in foreign exchange occur as the result of the development of international trading and increased international money and capital movement. The vast development of international economic  caused  economic relationship  among  countries  will  be  linked  to  each other  and  subsequently improve trading activities in their goods, money and capital flows. The variables used in this study are spot, forward  and future  spot. Based  on  the result  of Regression  Estimation  applied in  hypothesis on foreign currencies exchange which done simultaneously are proven able to predict future spot. The investor and international economic  actor could use spot  exchange rate and forward  exchange rate as a  short terms predictor for the next trimester in 2011.

  6. Faktor - Faktor Determinan Kurs Rupiah Terhadap Dollar Amer

    elys fauziyah

    2017-03-01

    Full Text Available Indonesia is a developing country that is often affected by fluctuations in foreign exchange rates, especially US Dollar. This condition is the effect of the government policies that implement the floating exchange rate system since August 14, 1977. The aims of this study are to know the development and to analyze the effect of macroeconomic variables on the Rupiah exchange rate against US Dollar in 2008-2014. The method which used in this study is descriptive statistics and multiple linear regression. The results of the study show that during 2008-2014, the variables of inflation, interest rate (BI rate of Indonesia’s balance of payments, and exports fluctuated, while the variable of PDB tended to increase. Other results show that interest rates and gross domestic product have a positive effect on the exchange rate of Rupiah against US Dollar, whereas the inflation and exports have a negative effect. Meanwhile, Indonesia’s balance of payments does not significantly affect the Rupiah against US Dollar.

  7. Valuable cure for cold plugs; Verdifull kur mot kalde plugger

    Toenseth, Svein

    2010-07-01

    Direct electric pipeline heating (DEH) has replaced the 'anti-freeze' when cold constipation should be prevented in the oil's 'veins' on the seabed. It has saved billions for Statoil. (AG)

  8. Läänemerest Musta mereni / Ott Kurs

    Kurs, Ott, 1939-

    2006-01-01

    Põhja-Euroopa ja Baltimaade ühendusest Baltoscandia, Krimmi poolsaare ajaloost ja elanikest ning Balti riikide huvist Krimmis. Artikkel on lühendatud tõlge ettekandest "The Black sea region, the Crimea and the Baltics" konverentsil Academia Baltoscandia's Paneve̓ysises Leedus 9. novembril 2002

  9. Bibliotekāru loma bibliotēkas un bibliotekāra tēla veidošanā Tīmekļa 2.0 resursos

    Moskina, Viktorija

    2010-01-01

    Tīmeklis 2.0 sniedz lielākas iespējas nekā vienkārši meklēt, lasīt un pārvietoties informācijas telpā. Tas ir interaktīvs: virtuālās sarunas, personalizācija, individuālisms. Uzsvars uz cilvēku mijiedarbību raksturo Tīmekli 2.0 kā izteikti sociālu tīmekli, kurš pirmajā plāna izvirza indivīdu prasmi socializēties. Pētījuma mērķis ir noskaidrot, cik veiksmīgi bibliotekāri tiek galā ar bibliotēkas un bibliotekāru tēla veidošanu Tīmekļa 2.0 resursos un sniegt ieteikumus Latvijas bibliotekārie...

  10. Annexin A2 and cancer

    Christensen, Maria V; Høgdall, Claus K; Jochumsen, Kirsten M

    2018-01-01

    Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using Pub......Med. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma......, prostate cancer and urothelial carcinoma were evaluated. Annexin A2 expression correlates with resistance to treatment, binding to the bone marrow, histological grade and type, TNM-stage and shortened overall survival. The regulation of Annexin A2 is of interest due to its potential as target for a more...

  11. HEAO A-2 extragalactic results

    Boldt, E. A.

    1979-01-01

    The all-sky surveys made with the A-2 instrument aboard HEAO-1 involved spectroscopy over a broad enough band width, with sufficient resolution, to obtain the basic spectral characteristics for two extreme aspects of the extragalactic X-ray sky. The overall spectrum (above 3 KeV) is remarkably well decribed by a thermal model. At the other extreme, the detailed broad-band observations of individual sources are restricted to objects within the present epoch. The objects include several individual active galaxies studied in detail for the first time as well as clusters of galaxies. Relating these results to the vast spatially unresolved hard X-ray flux measured with this instruments as well as the softer X-rays (at less than 3 keV) spatially resolved to high redshifts with the Einstein Observatory remains a challenge.

  12. Grammatisches Wissen, Fremdsprachenunterricht und Lehrwerke – Zur Qualität von Grammatikübungen in zwei kroatischen DaF-Lehrwerken

    Leonard Pon

    2014-12-01

    In the third part, the results of the analysis of the two Croatian textbooks are presented. Both quantitative and qualitative data are commented on. This part also includes some information regarding the Croatian teaching situation so that potential readers not acquainted with it can better understand comments and suggestions provided by the author. On one side, the paper points to the strengths and weaknesses of the teaching materials in question. On the other side, the author provides some general comments on what a good text-book should contain in order to help foreign language learners develop their grammar compe-tence.

  13. Nuclear phase-out a part of the German Constitution? On the political grammar of constitutional changes; Atomausstieg ins Grundgesetz? Zur politischen Grammatik von Verfassungsaenderungen

    Gaerditz, Klaus Ferdinand

    2016-07-01

    The study examines whether and to what extent the simple legal effected nuclear phase-out could be safeguarded in the Basic Law, which regulatory methods would be available, the advantages and disadvantages of these and how their effects would be assessed. In addition to political and practical consequences, this also includes considerations of democracy and constitutional theory in an overall consideration, which ultimately touches the question of the regulatory function of constitutional changes. [German] Die Studie untersucht, ob bzw. inwiefern der einfachgesetzlich erfolgte Atomausstieg im Grundgesetz abgesichert werden koennte, welche Regelungstechniken hierzu zur Verfuegung stuenden, welche Vor- bzw. Nachteile diese haetten und wie deren Wirkungen zu bewerten waeren. Hierbei sind neben politisch-praktischen Folgen auch demokratie- und verfassungstheoretische Erwaegungen in eine Gesamtbetrachtung einzubeziehen, die letztlich die Frage nach der Regelungsfunktion von Verfassungsaenderungen beruehren.

  14. The Professorial Chair (kursī ‘ilmī or kursī li-l-wa‘ẓ wa-l-irshād in Morocco

    Erzini, Nadia

    2013-06-01

    Full Text Available Moroccan congregational mosques are equipped with a minbar (pulpit which is used for the Friday sermon. Many mosques in Morocco are also equipped with one or more smaller chairs, which differ in their form and function from the minbar. These chairs are used by professors to give regular lectures to students of traditional education, and by scholars to give occasional lectures to the general public. This tradition of the professorial chair was probably introduced to Morocco from the Middle East in the thirteenth century. Most of the existing chairs in Morocco seem to date from the nineteenth and twentieth centuries, and they continue to be made and used today. The chairs always have two steps, a seat, a backrest and armrests. This form probably evokes the original minbar of the Prophet in Medina, which had two steps and a seat, and this is one of many aspects of the conservatism and se parate evolution of Moroccan Malikism.Las mezquitas congregacionales en Marruecos suelen tener un almimbar (p?lpito que se utiliza durante el sermón de los viernes. Muchas mezquitas de Marruecos cuentan también con una o más sillas, diferenciadas del almimbar en su forma y su función ya que son utilizadas por los profesores para ensenar a los estudiantes de la educación tradicional, y por eruditos que dan conferencias ocasionales al p?blico en general. Esta tradición de cátedras se introduce probablemente en Marruecos desde Próximo Oriente en el siglo XIII. La mayoría de las cátedras existentes parecen datar de los siglos XIX y XX, manteniéndose hasta nuestros días la fabricación y utilización de estas sillas. Las cátedras siempre tienen dos peldanos, un asiento, un respaldo y apoyabrazos. La forma de las sillas parece evocar el almimbar original del Profeta en Medina, tradición que se muestra como uno de los muchos aspectos del conservadurismo y de la evolución distinta del Malikismo marroquí.

  15. 18 CFR 3a.2 - Authority.

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Authority. 3a.2 Section 3a.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.2 Authority. Official information or...

  16. Kur'an'daki İnfak Kavramının Anlam Yelpazesi

    Ali Rıza Gül

    2015-11-01

    Full Text Available The conception of infâq conveys a wide range of meanings embracing many different conceptions elaborated within the Koran. Infâq is attributed both to Allah -in its metaphorical meaning- and the human beings. The meaning attributed to Allah is understood as granting mankind material subservience. However the meaning attributed to human beings is understood as disposing of the possessed thing and spending them both for themselves and the others, helping the other, based on its lexical meaning. As for the infâq done by the Muslims, together with this lexical meaning is named as zakât (obligatory alms, alms, helping, material contribution to war (provided that it is in the path to Allah, nafaqah, teberru. In addition to all these, the material support provided by the disbelievers in order to destroy Islam and the Muslims, the helps and contributions made by hypocrites (munâfiqûn to Islam’s army -though they are not good intentions- are assessed in the Koran within the work of infâq

  17. Analisis Pengaruh Indeks Bursa Saham Asing Dan Kurs Dolar Amerika Serikat Terhadap Indeks Bursa Efek Indonesia

    Siregar, Adlin Syahputra Angkasa

    2011-01-01

    Examining the development of the Indonesia Stock Exchange is an interesting and challenging since the government removed the foreign ownership limit on the Indonesia Stock Exchange September 1997. In relative terms, the amount of factors influence the foreign stock market indices of the development of a stock shows the stock level of integration with world capital markets. Stock markets are more integrated with world capital markets, which are more influenced by foreign factors, the potential...

  18. DAMPAK PENERAPAN PSAK 10 (REVISI 2010 MENGENAI PENGARUH PERUBAHAN KURS VALUTA ASING TERHADAP DAYA INFORMATIF LABA

    Dianwicaksih Arieftiara

    2017-06-01

    Full Text Available This study aims to examine the consequences of the implementation of PSAK No. 10 (2010 regarding The Effect of Changes in Foreign Exchange Rates on the informativeness of earnings. Our research sample consists of companies listed on Indonesia Stock Exchange (IDX from 2010 until 2013. Using panel least square linear regression, this study finds that the implementation of PSAK No. 10 (2010 improves the informativeness of earnings which is measured by Earnings Response Coefficient (ERC. This is the first study that investigates the impact of the implementation of PSAK No. 10 (2010 on ERC, therefore this study contributes on providing evidence of the impact of accounting standard revision implementation on capital market aspect.

  19. Rahvusvaheline üldharidus ja võõrkeelsed õppekavad - milleks ja kellele? / Kalmar Kurs

    Kurs, Kalmar

    2010-01-01

    Rahvusvahelisest üldharidusest, mille all peetakse silmas õppetööd üldhariduse tasemel, mida korraldatakse võõrkeeles ning mille alusdokumendiks ei ole Eesti põhikooli ja gümnaasiumi riiklikud õppekavad

  20. PERAMALAN KUNJUNGAN WISATAWAN MENGGUNAKAN MODEL ARMAX DENGAN NILAI KURS DAN EKSPOR-IMPOR SEBAGAI FAKTOR EKSOGEN

    PUTU IKA OKTIYARI LAKSMI

    2015-02-01

    Full Text Available Forecasting is science to estimate occurrence of the future. This matter can be conducted by entangling intake of past data and place to the next period with a mathematical form. This research aims to estimate the number of foreign tourists visiting Bali models using autoregressive moving average exogenous (ARMAX. The data used in this study is the number of tourists in Australia and the number of tourists in the RRC as a variable Y, and foreign currency exchange rate AUD, Chinese Yuan, and Export Import as the X factor from the period July 2009 to July 2014. In the analysis can be obtained in the best ARMAX models of the number of tourists in Australia is ARMAX(1,2,2 and the best model of the number of tourists in the RRC does not exist because the data for the ARMAX model parameters tourists no significant RRC.

  1. PERAMALAN KUNJUNGAN WISATAWAN MENGGUNAKAN MODEL ARMAX DENGAN NILAI KURS DAN EKSPOR-IMPOR SEBAGAI FAKTOR EKSOGEN

    PUTU IKA OKTIYARI LAKSMI

    2014-11-01

    Full Text Available Forecasting is science to estimate occurrence of the future. This matter can be conducted by entangling intake of past data and place to the next period with a mathematical form. This research aims to estimate the number of foreign tourists visiting Bali models using autoregressive moving average exogenous (ARMAX. The data used in this study is the number of tourists in Australia and the number of tourists in the RRC as a variable Y, and foreign currency exchange rate AUD, Chinese Yuan, and Export Import as the X factor from the period July 2009 to July 2014. In the analysis can be obtained in the best ARMAX models of the number of tourists in Australia is ARMAX(1,2,2 and the best model of the number of tourists in the RRC does not exist because the data for the ARMAX model parameters tourists no significant RRC.

  2. FLUKTUASI KURS RUPIAH TERHADAP DOLLAR AMERIKA SERIKAT PADA PERIODE TAHUN 1997.I – 2004.IV

    Anggyatika Mahda Kurnia

    2009-12-01

    Full Text Available This study aimed to analyze the fluctuation of the rupiah against the U.S. dollar. The data used in this study are quarterly time series data between the 1997.I to 2004.IV. Analysis tool used in this study is multiple linear regressions using the Error Correction Model (ECM. The results of this study concluded that variables such as exchange rates, inflation, SBI rate and the value of imports is stationary, only money supply variable that is not stationary. Based on the classical assumption was not found problem. Normality test showed normal distribution of Ut, tests of model specification with the Ramsey Reset test indicates the model used is linear. The coefficient of determination (R2 showed that approximately 90.5813 percent of the value of the rupiah against the U.S. dollar be explained by variables in the model. Result analysis by t test found that a significant variable is the money supply, inflation, and the value of imports.

  3. MEMBANGUN EARLY WARNING INDICATORS PERGERAKAN KURS DI INDONESIA: PENGEMBANGAN BUSINESS CYCLE ANALYSIS

    Andra Devi Benazir

    2011-08-01

    Full Text Available The economic crisis in 1997/1998 that was signed by depreciation rupiah almost destroyed the pillars of the economy. This exchange rate shock possibly will happen in the future like that happened in August 2007. At the same time, rupiah falled to the lowest level Rp. 9.410 per dollar (the exchange rate use the last month in August 2007. The exchange rate of its daily until above Rp 9.500 per dollar (Sadewa, 2007. Therefore, it was needed indicator of theearly detection with build leading indicators the movement of the exchange rate in Indonesia. The purpose of this research is building leading indicators the movement of the exchangerate in Indonesia. It could give the capacity forecasting of the Indonesian economy of the movement direction in a manner the aggregate with the Business Cycle Analysis method andIts development. Empirical results showed that is received by four leading indicators and four coincident indicators. The real export, the real import, foreign currency deposit, and forexbanks demand deposits in foreign currency became the moving indicator preceded the exchange rate. Whereas, there are four indicators to coincident was foreign assets, interbank call money rate 1 day, the German share index (DAX, and the USA share index (Nasdaq. This condition indicated that the exchange rate rupiah really was affected by the external factor.

  4. KUR'N'DA TEŞBİHLİ ANLATIM ÜSLÛBU

    Muhammed Aydın

    2001-12-01

    Full Text Available There are various stylistic features in the Qur'an These featurescontribute greatly to the understanding and the clarification of theQur'an. One of the most significant stylistic features is certainly thesimilitude. The similitude is a very helpful way for the remembranceof the Qur'anic data. In this article we concentrate on theimportance of this stylistic device in the Qur'an. In addition, we tryto show that the similitude plays a very important role in theunderstanding of the Glories Qur'an.

  5. Kur'an'ı Nesnel Okuma Çabalarına Bir Katkı

    Yusuf Çelik

    2015-11-01

    Full Text Available The question, which whether similarly to objectivity which was obtained in positive science could be obtained in social science, will be tried to answer in our article. It will be given knowledge about two concepts were brought forward with the name of objectivity cultural and absouletly cultural objectivity in the subjectivity and objectivity context. As it was known, either divine welded texts or human welded texts, of which abilities adress to age and future are due to the interpretation of these texts

  6. Mere kulstof i jorden er en kur mod våde marker

    Gislum, René

    2018-01-01

    Kulstof: Jordens evne til at afdræne jordprofilen afhænger bl.a. af jordens indhold af organisk materiale. Frøgræs og græs generelt øger både organisk materiale og vandinfiltration samt evnen til at modstå jordpakning....

  7. Kur'an'a Göre Boşanma Prosedürü

    Hamza Aktan

    2015-11-01

    Full Text Available If we investigate The Qur’an carefully as a source of lslamic Law to have knowledge on the rules of divorce we see that divorce is a final solution of friction between husband and wife. There are some verses in The Qur’an that order married couple under any circumstances to try hard to cotinue the conjugal community. First of all The Qur’an orders the couple to be upon each other’s behaviour (Qur’an, Al Nisa 4/19; and see also Al Baqarah 2/231, Al Talaq 65/2}. In case the wife is obstinately disobidant (naashiz the husband have to strive for getting on well together (Qur’an, Al Nisa’ 4/34. On the cotrary if the husband goes beyond the rulles of marriage then the wife tries to come to an agreement to keep the peace (Qur’an, Al Nisa 4/ 128. In any case if the striving of couple to keep the peace doesn’t give a result then the relatives have to be interested the problem. So they choose an arbitrator (hakam from the family of the wife and an arbitrator from the family of the husband. The two or more chosen arbitrators try to makepeace among the husband and wife (Qur’an, Al Nisa 4/35. If arbitrators not meet with succes of making peace among the couple then the divorce may be considered as a solution of the problem. When the husband decided to divorce his wife he must do it in the period of divorce. Because The Qur’an determined a period for divorce (Qur’an, Al Talaq 65/1. And the Prophet Mohammad (peace be upon him declared this concise (mujmal period. According to declaration of the Prophet (peace be upon him the period of divorce begins with the end of menstruation and finish with coition (Azimabadİ, Avn Al Ma’bud, VI, 227-228. In another word the husband can divorce only in the period of canonical cleannes of his wife but before the coition. If he has a sexual intercours with his wife then he can not divorce until the next period. From these Qur’anic verses and the declaration of the Prophet (peace be upon him we may deduce that the divorce is the fi

  8. Nuotolinio mokymosi kursų rengimo sistemų lyginamoji analizė

    Konrads, Egils

    2008-01-01

    E-learning can give you the freedom and flexibility to learn something new and useful whenever you want at your own place. E-learning is an ideal solution if the subject you are interested in is not available nearby. You can study a wide range of subjects at any level without going out from your place. The main goal of the project is to choose a distant learning system for organization. Deep system analysis describes and compares functions of several systems. This project will help the or...

  9. Annexin A2 in Proliferative Vitreoretinopathy

    2017-10-01

    that breaches the blood-retinal barrier, leakage of plasma proteins and circulating blood cells, possibly together with local hypoxia, conspire to...immunofluorescence staining to document the migration of A2-positive cells from the RPE to the surface of the retina in PVR (Fig. 3). We have also detected a few...readily detected (Fig. 9B, 9C). Cells in both groups were also positive for A2. These data indicate that expression of A2 in both RPE cells and

  10. 7 CFR 15a.2 - Definitions.

    2010-01-01

    ... FINANCIAL ASSISTANCE Introduction § 15a.2 Definitions. As used in this part, the term: (a) Title IX means... political subdivision thereof, of any instrumentality of a State or political subdivision thereof, any...) Offers academic study beyond the bachelor of arts or bachelor of science degree, whether or not leading...

  11. 42 CFR 51a.2 - Definitions.

    2010-10-01

    ... CHILD HEALTH § 51a.2 Definitions. Act means the Social Security Act, as amended. Genetic diseases means... accredited school of medicine and a full-time academic medical staff holding faculty status in such school of medicine. Secretary means the Secretary of Health and Human Services or his or her designee. ...

  12. VOA: a 2-d plasma physics code

    Eltgroth, P.G.

    1975-12-01

    A 2-dimensional relativistic plasma physics code was written and tested. The non-thermal components of the particle distribution functions are represented by expansion into moments in momentum space. These moments are computed directly from numerical equations. Currently three species are included - electrons, ions and ''beam electrons''. The computer code runs on either the 7600 or STAR machines at LLL. Both the physics and the operation of the code are discussed

  13. Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2 among Emiratis.

    Mohammad M Al-Ahmad

    Full Text Available Cytochrome P450 1A2 (CYP1A2 is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.

  14. UPWIND 1A2 Metrology. Final Report

    Eecen, P.J.; Wagenaar, J.W.; Stefanatos, N.

    . Since this problem covers many areas of wind energy, the work package is defined as a crosscutting activity. The objectives of the metrology work package are to develop metrology tools in wind energy to significantly enhance the quality of measurement and testing techniques. The first deliverable...... is a valuable tool for the further assessment and interest has been shown from other work packages, such as Training. This report describes the activities that have been carried out in the Work Package 1A2 Metrology of the UpWind project. Activities from Risø are described in a separate report: T.F. Pedersen...... was to perform a state of the art assessment to identify all relevant measurands. The required accuracies and required sampling frequencies have been identified from the perspective of the users of the data (the other work packages in UpWind). This work led to the definition of the Metrology Database, which...

  15. Hardware upgrade for A2 data acquisition

    Ostrick, Michael; Gradl, Wolfgang; Otte, Peter-Bernd; Neiser, Andreas; Steffen, Oliver; Wolfes, Martin; Koerner, Tito [Institut fuer Kernphysik, Mainz (Germany); Collaboration: A2-Collaboration

    2014-07-01

    The A2 Collaboration uses an energy tagged photon beam which is produced via bremsstrahlung off the MAMI electron beam. The detector system consists of Crystal Ball and TAPS and covers almost the whole solid angle. A frozen-spin polarized target allows to perform high precision measurements of polarization observables in meson photo-production. During the last summer, a major upgrade of the data acquisition system was performed, both on the hardware and the software side. The goal of this upgrade was increased reliability of the system and an improvement in the data rate to disk. By doubling the number of readout CPUs and employing special VME crates with a split backplane, the number of bus accesses per readout cycle and crate was cut by a factor of two, giving almost a factor of two gain in the readout rate. In the course of the upgrade, we also switched most of the detector control system to using the distributed control system EPICS. For the upgraded control system, some new tools were developed to make full use of the capabilities of this decentralised slow control and monitoring system. The poster presents some of the major contributions to this project.

  16. Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.

    Jian, Tun-Yu; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Li, Hong-Liang; Bai, Min; Xu, Gui-Li

    2012-08-01

    Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Supplement to hydrogeochemical and stream-sediment reconnaissance basic data reports K/UR-445 through K/UR-457 [GJBX-165(82) through GJBX-177(82)]. National Uranium Resource Evaluation Program

    1982-01-01

    The objective of the Hydrogeochemical and Stream Sediment Reconnaissance (HSSR) Program was to provide information to be used in accomplishing the overall National Uranium Resource Evaluation (NURE) Program objectives. This was accomplished by a reconnaissance of surface water, groundwater, stream sediment, and lake sediment. The survey was conducted by Los Alamos National Laboratory, Oak Ridge Gaseous Diffusion Plant, and Savannah River Laboratory. The samples in the reports were collected by SRL and analyzed by the Uranium Resource Evaluation Project in Oak Ridge, Tennessee. Laboratory analyses were completed in August 1982. The following quadrangles located in the states of California, Nevada, Oregon, Arizona, Maine, Washington, and South Carolina are covered in this report: Adel, Bangor, Bath, Boise, Challis, Caliente, Death Valley, Elko, Ely, Fresno, Hailey, Idaho Falls, Jordan Valley, Lund, Mariposa, Phoenix, San Luis Obispo, Sacramento, Santa Cruz, Twin Falls, and Vya

  18. Analisis Perilaku Kurs Rupiah (Idr) terhadap Dollar Amerika (Usd) pada Sistem Kurs Mengambang Bebas di Indonesia Periode 1997.3 – 2011.4 (Aplikasi Pendekatan Keynesian Sticky Price Model)

    Pratiwi, Tara Eka; Santosa, H. Purbayu Budi Santosa

    2012-01-01

    Currency stability is an important issue to boost economic activity and create economic growth of a country. Trade between countries resulting in currency exchange rates between countries are reflected in the exchange rate. The importance of the role of exchange rates for both developed and developing countries, encourage efforts to keep the exchange rate of a country is in a relatively stable state. The stability of the currency exchange rate is also affected by the exchange rate system adop...

  19. Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors

    Hatano, Manabu; Kuwashima, Naruo; Tatsumi, Tomohide; Dusak, Jill E; Nishimura, Fumihiko; Reilly, Karlyne M; Storkus, Walter J; Okada, Hideho

    2004-01-01

    Background A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. Methods C57BL/6 mice received subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides recognized by CD8+ (mEphA2671–679, mEphA2682–689) and CD4+ (mEphA230–44) T cells. Splenocytes (SPCs) were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6) establishment/progression was then assessed. Results Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. Conclusions These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells. PMID:15563374

  20. Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors

    Hatano Manabu

    2004-11-01

    Full Text Available Abstract Background A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. Methods C57BL/6 mice received subcutaneous (s.c. vaccinations with bone marrow-derived dendritic cells (DCs pulsed with synthetic peptides recognized by CD8+ (mEphA2671–679, mEphA2682–689 and CD4+ (mEphA230–44 T cells. Splenocytes (SPCs were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6 establishment/progression was then assessed. Results Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. Conclusions These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells.

  1. Kitâb-ı Mukaddes ve Kur'an'ın Sevgi Anlayışı

    Atilla Yargıcı

    2015-11-01

    Full Text Available The Bible and The Kor’an says basically the same thing about God’s Love, neigbourhood and brotherhood love, whereas they mentione different ideas about sexual love. Firstly, they announce that man should love God more than the other loved objects like parents, husband-wife and children.The most important manifestation of God’s Love is to obey his rules and to love each other. Secondly, they also indicate brotherhood and neighbourhood love. According to them, God has created entire food and favour for everyone. There is no discrimination between the believer in God or unbeliever in him. So, man should love man without considering who he/she is. Thirdly, while Old Testament mentions sexual love very much, New Testament doesn’t tell us anything about that. However, The Kur’an has expressed that sexual love is a reality of man and it should occur within the marriage

  2. Kitâb-ı Mukaddes ve Kur'an'ın Sevgi Anlayışı

    Atilla Yargıcı

    2015-01-01

    The Bible and The Kor’an says basically the same thing about God’s Love, neigbourhood and brotherhood love, whereas they mentione different ideas about sexual love. Firstly, they announce that man should love God more than the other loved objects like parents, husband-wife and children.The most important manifestation of God’s Love is to obey his rules and to love each other. Secondly, they also indicate brotherhood and neighbourhood love. According to them, God has created entire food and fa...

  3. PENGARUH INFLASI, KURS DAN TINGKAT SUKU BUNGA TERHADAP NON PERFORMING LOAN PADA PT. BANK TABUNGAN NEGARA (PERSERO Tbk CABANG PADANG

    Muthia Roza Linda

    2015-11-01

    Full Text Available This study aimed to get empirical evidence of the effects of inflation, exchange rate, and interest rates on non-performing loans At the State Savings Bank (Persero Tbk Branch Padang. In this research used observation period ranging from 2008 - 2013. Data used is secondary data obtained from the financial statements of the State Savings Bank (Persero Tbk Branch Padang. For testing the hypothesis used multiple linear regression model to see the value of t-statistic. Based on the results of hypothesis testing found that inflation, and interest rates are individually significant effect on non-performing loans at the State Savings Bank (Persero Branch Padang, whereas no significant effect on the rate of non-performing loans at the State Savings Bank (Persero Branch Padang ,

  4. Doing religion im Phowa-Kurs: Praxeologische und reflexionslogische Studien zum "bewussten Sterben" im Diamantweg-Buddhismus

    Werner Vogd

    2015-07-01

    Full Text Available Im Sinne einer pragmatistischen Perspektive, wie sie zuerst John DEWEY (1987 [1934] in Anschluss an William JAMES formulierte, ist das Religiöse weniger als eine spezifische Art von experience zu verstehen, denn als ein adjustment hin zu einer epistemischen Perspektive, die alle Erfahrungen in einem veränderten Licht erscheinen lässt. Religiosität zielt damit auf ein besonderes Selbst- und Weltverhältnis, in dem die Beziehung zwischen Selbst und Welt aus einer ganzheitlichen Perspektive betrachtet wird. Wie aber können fremde, auf den ersten Blick in ihrer Genese unwahrscheinliche und unter modernen Verhältnissen zudem anzweifelbare religiöse Haltungen und Sinnsysteme etabliert werden? Am Beispiel der im tibetischen Buddhismus verbreiteten Phowa-Meditation des "bewussten Sterbens" wird untersucht, wie für westliche Adept/innen auf den ersten Blick befremdlich und esoterisch anmutende spirituelle Lehren mit zunehmender Praxis an Evidenz und Sinnhaftigkeit gewinnen können, indem sich Gruppenprozesse, Visualisierungen, körperorientierte Übungen und psychisches Erleben zu einem übergreifenden Arrangement verschränken. Die empirische Datengrundlage für die Untersuchung liefern narrative Interviews mit westlich sozialisierten Schüler/innen und Lehrer/innen des Diamantweg-Buddhismus, der derzeit größten buddhistischen Gemeinschaft des tibetischen Buddhismus in Deutschland. Die Auswertung der Interviews erfolgte angelehnt an die dokumentarische Methode, erweitert durch eine Kontexturanalyse, um den Reflexionsverhältnissen gerecht zu werden, die den religiösen Selbst- und Weltbezug aufspannen. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1503179

  5. Analisis Perbandingan Risiko Nilai Tukar Kurs Dinar (Emas, Dolar AS, Euro dan Yuan (Periode 2010 – 2015

    Andi Triyawan

    2017-12-01

    Full Text Available Money is a tool intermediary humans to perform the transaction  payment  is national or international. In its development money undergoes several changes. Similarly, in the development of the world economy, there has been a financial crisis that hit in various countries, such as the global economic crisis. Crisis economic global is the crisis that occurred as a result of the problems of economic markets in the whole world who make entire sectors of the economy markets experienced a collapse and the impact on other sectors . Which becomes a problem in terms of this is the risk of the value of the exchange currency money and the occurrence of fluctuations in the value of exchange currency money internationally which led to a decrease in the value of the exchange currency for money in countries developing. That is, because the use of fiat money system based only on the belief of its value without any intrinsic value in fiat money form . The purpose of this research is to know how big is the risk of the value of exchange and volatility that is generated in the use of value exchange currency currency exchange rate of Dinar ( Gold , Dollars USA, Euro and Yuan as the eyes of money internationally. This research is a study of Library Research with quantitative research type, by obtaining secondary data from site Internet. By taking samples as much as 60 months of each exchange Dinar Gold, Dollars USA, Euro and Yuan by way of purposive sampling and using the Analysis Time Series with Eviews 7.2. The results of the research of this is that the volatility of the value of the exchange currency for money top is Dinar Emas with value of 0.036590, while the volatility of most small is the value of the exchange currency Yuan with a value of 0.018472. Dinar Gold has a value of volatility and risk value of the exchange of the most high , so that when the dinar gold is used in terms of trade internationally and the company would have borne the risk of market which is bigger than use with US Dollars, and more. Suggestions of researchers is hopefully the research further more better and get the data the price of the commodity of gold that is more clear and accurate between the value of the price of gold that with the availability of a form of gold.

  6. ER SØKING I GOOGLE NOK? PH.D.-KURS VED NTNU UNIVERSITETSBIBLIOTEKET – EN UTVIKLINGSHISTORIE

    Hege Charlotte Faber

    2011-09-01

    Full Text Available This paper presents an overview of how the university library at the Norwegian University of Science and Technology (NTNU participates in the education and support of Ph.D. candidates.  NTNU has a broad academic scope, the range of subjects are from engineering and technology to humanities, psychology, medicine and fine arts.  The courses given by the NTNU university library reflects the different cultures, traditions, contents and developments. This paper also discusses various aspects in connection with the need for information literacy at doctoral level, integration of the courses as well as the need for further development in this field which is both connected to technological developments (such as Google as well as implementation of the Norwegian Qualification Framework.

  7. Specjalistyczny język medyczny a multimedialny kurs języka zawodowego dla pielęgniarek

    Magajewska, Mirosława

    2016-01-01

    In the age of the widespread globalization, intensive international economic, scientific and technical cooperation, there are promising prospects for those specialists who aim at improving their professional qualifications or taking up employment abroad. A fundamental conditio which is to be met in order to fulfil those plans is to achieve the command of professional language of the target country or professional English. The need of skilful verbal communication is connected with the occupati...

  8. 26 CFR 31.3401(a)-2 - Exclusions from wages.

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Exclusions from wages. 31.3401(a)-2 Section 31... Collection of Income Tax at Source § 31.3401(a)-2 Exclusions from wages. (a) In general. (1) The term “wages... specifically excepted from wages under section 3401(a). (2) The exception attaches to the remuneration for...

  9. Point of Grammar

    Hjulmand, Lise-Lotte

    2013-01-01

    Anglo Files har i dette nummer valgt at sætte fokus på grammatik, bl.a. fordi grammatik og sprogbrug nu indgår i den skriftlige eksamen i engelsk. Jeg håber imidlertid også, at dette initiativ er et tegn på, at grammatik, der i mange år var en forkætret disciplin, som man i hvert fald i dansk og ...

  10. Adenosine A2A receptors and A2A receptor heteromers as key players in striatal function

    Sergi eFerre

    2011-06-01

    Full Text Available A very significant density of adenosine adenosine A2A receptors (A2ARs is present in the striatum, where they are preferentially localized postsynaptically in striatopallidal medium spiny neurons (MSNs. In this localization A2ARs establish reciprocal antagonistic interactions with dopamine D2 receptors (D2Rs. In one type of interaction, A2AR and D2R are forming heteromers and, by means of an allosteric interaction, A2AR counteracts D2R-mediated inhibitory modulation of the effects of NMDA receptor stimulation in the striato-pallidal neuron. This interaction is probably mostly responsible for the locomotor depressant and activating effects of A2AR agonist and antagonists, respectively. The second type of interaction involves A2AR and D2R that do not form heteromers and takes place at the level of adenylyl-cyclase (AC. Due to a strong tonic effect of endogenous dopamine on striatal D2R, this interaction keeps A2AR from signaling through AC. However, under conditions of dopamine depletion or with blockade of D2R, A2AR-mediated AC activation is unleashed with an increased gene expression and activity of the striato-pallidal neuron and with a consequent motor depression. This interaction is probably the main mechanism responsible for the locomotor depression induced by D2R antagonists. Finally, striatal A2ARs are also localized presynaptically, in cortico-striatal glutamatergic terminals that contact the striato-nigral MSN. These presynaptic A2ARs heteromerize with A1 receptors (A1Rs and their activation facilitates glutamate release. These three different types of A2ARs can be pharmacologically dissected by their ability to bind ligands with different affinity and can therefore provide selective targets for drug development in different basal ganglia disorders.

  11. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    Holmes, Michael V; Simon, Tabassome; Exeter, Holly J

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.......This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease....

  12. Purification of phospholipase A2 from Bothrops atrox venom

    B. Quevedo

    1999-01-01

    Full Text Available Phospholipase A2 (PLA2 from Bothrops atrox (Sensu lato venom, from Chiriguaná (Colombia was purified using exclusión chromatography on Sephadex G-75, obtaining five fractions one of which showed phospholipase A2 activity. After further purification on Mono S cationic exchange column, eight fractions with PLA2 activity, measured using the hemolytic method, were obtained.

  13. Quercetin modulates activities of Taiwan cobra phospholipase A 2 ...

    Home; Journals; Journal of Biosciences; Volume 37; Issue 2. Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects on membrane structure and membrane-bound mode of phospholipase A2. Yi-Ling Chiou Shinne-Ren Lin Wan-Ping Hu Long-Sen Chang. Articles Volume 37 Issue 2 June 2012 pp ...

  14. 21 CFR 864.7400 - Hemoglobin A2 assay.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin A2...

  15. 15 CFR 4a.2 - Deputy Assistant Secretary for Security.

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Deputy Assistant Secretary for Security. 4a.2 Section 4a.2 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION... Security. The Deputy Assistant Secretary for Security (DAS) is responsible for implementing E.O. 12958 and...

  16. 40 CFR 721.4585 - Lecithins, phospholipase A2-hydrolyzed.

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Lecithins, phospholipase A2-hydrolyzed... Substances § 721.4585 Lecithins, phospholipase A2-hydrolyzed. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as lecithins...

  17. [Bernt Ahrenholz : Verweise mit Demonstrativa im Gesprochenen Deutsch...] / Klaus Geyer

    Geyer, Klaus

    2008-01-01

    Arvustus: Ahrenholz, Bernt. Verweise mit Demonstrativa im gesprochenen Deutsch : Grammatik, Zweitspracherwerb und Deutsch als Fremdsprache. Berlin ; New York : de Gruyter, 2007. (Linguistik - Impulse & Tendenzen ; 17)

  18. Secretory Phospholipase A(2) Activity toward Diverse Substrates

    Madsen, Jesper Jonasson; Linderoth, Lars; Subramanian, Arun Kumar

    2011-01-01

    We have studied secretory phospholipase A(2)-IIA (sPLA(2)) activity toward different phospholipid analogues by performing biophysical 1 characterizations and molecular dynamics simulations. The phospholipids were natural substrates, triple alkyl phospholipids, a prodrug anticancer etherlipid, and...

  19. Motor pathway excitability in ATP13A2 mutation carriers

    Zittel, S; Kroeger, J; van der Vegt, J P M

    2012-01-01

    OBJECTIVE: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). METHODS: Five members of a Chilean family...... with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval....... RESULTS: CSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC. CONCLUSION: A compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical...

  20. Evaluation the COL9A2 gene with high myopia

    Zhang, Dingding; Huang, Maomin

    2017-11-01

    This paper investigates the association of the COL9A2 gene between high myopia and normal controls in the Han Chinese population. It shows that the frameshift mutation (D281fs) in the COL9A2 gene is not associated with high myopia in the Han Chinese population, and the two novel variants(c.143G>C and c.884G>A) may contribute to the development of high myopia.

  1. The Role of Adenosine A2BR in Metastatic Melanoma

    2017-07-01

    burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense...would like to interrogate the role of adenosine receptor (A2BR) in regulating primary tumor growth and metastasis in experimental models of melanoma...The positive control was a triple negative breast cancer cell line, E0771. To interrogate the role of A2BR in aiding tumor metastasis, we used VeCad

  2. Novel approaches for targeting the adenosine A2A receptor.

    Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

    2015-01-01

    The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

  3. Interaction between EGFR and EphA2

    Larsen, Alice Bjerregaard

    2010-01-01

    Enhanced or altered epidermal growth factor receptor (EGFR) activity has been reported in many human cancers and several molecular targeting therapies has been developed. However, despite intense research, therapies targeting EGFR have shown conflicting results in clinical studies, indicating...... the involvement of other important molecular players. Several different EGFR mutations have been reported in cancer, one of which is the cancer specific type III EGFR deletion mutant (EGFRvIII, de2-7EGFR, ΔEGFR). In a global search for EGFR and EGFRvIII regulated genes we identified the receptor tyrosine kinase...... (RTK) EphA2. EphA2 belongs to the large Eph-receptor family, which has mainly been associated with neuronal development. More recently, expression of several Eph-receptors has been detected in many different cancer types. Elevated EphA2 expression has been reported in a broad range of human cancer...

  4. Interaction between EGFR and EphA2

    Larsen, Alice Bjerregaard

    2010-01-01

    Enhanced or altered epidermal growth factor receptor (EGFR) activity has been reported in many human cancers and several molecular targeting therapies has been developed. However, despite intense research, therapies targeting EGFR have shown conflicting results in clinical studies, indicating...... the involvement of other important molecular players. Several different EGFR mutations have been reported in cancer, one of which is the cancer specific type III EGFR deletion mutant (EGFRvIII, de2-7EGFR, ¿EGFR). In a global search for EGFR and EGFRvIII regulated genes we identified the receptor tyrosine kinase...... (RTK) EphA2. EphA2 belongs to the large Eph-receptor family, which has mainly been associated with neuronal development. More recently, expression of several Eph-receptors has been detected in many different cancer types. Elevated EphA2 expression has been reported in a broad range of human cancer...

  5. 17 CFR 270.3a-2 - Transient investment companies.

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Transient investment companies... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-2 Transient investment companies... which an issuer owns or proposes to acquire investment securities (as defined in section 3(a) of the Act...

  6. 26 CFR 1.103A-2 - Qualified mortgage bond.

    2010-04-01

    ... information and reasonable expectations determined as of the date of issue, submit on Form 8038 the... elected under § 6a.103A-2(i)(4)(v) to pay arbitrage to the United States, (J) In the case of an issue of... monthly gross pay, any additional income from investments, pensions, Veterans Administration (VA...

  7. PET imaging of adenosine A2A receptors

    Zhou, Xiaoyun

    2017-01-01

    This thesis describes the development and evaluation of [11C]preladenant as a novel radioligand for in vivo imaging of adenosine A2A receptors in the brain with positron-emission tomography (PET). The 11C-labeled drug [11C]preladenant was produced with high radiochemical yield and specific activity.

  8. Secretory Phospholipase A(2)-IIA and Cardiovascular Disease

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; Van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, Andre G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Pare, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not

  9. Phospholipases A2 in ocular homeostasis and diseases

    Wang, Jinmei; Kolko, Miriam; Kolko, Miriam

    2010-01-01

    Phospholipases A(2) (PLA(2)s) and its generation of second messengers play an important role in signal transduction, cell proliferation, cell survival and gene expression. At low concentrations mediators of PLA(2) activity have a variety of physiological effects whereas high levels of PLA(2) and ...

  10. Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

    Lohse, M.J.; Klotz, K.N.; Schwabe, U.

    1991-01-01

    It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine [(R)-AHPIA] into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling

  11. Solute Carrier Family 26 Member a2 (slc26a2 Regulates Otic Development and Hair Cell Survival in Zebrafish.

    Fei Liu

    Full Text Available Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by-association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO, and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment.

  12. A 2 MW, CW, 170 GHz gyrotron for ITER

    Piosczyk, B.; Arnold, A.; Alberti, S.

    2003-01-01

    A 140 GHz gyrotron for CW operation is under development for the stellarator W7-X. With a prototype tube a microwave output power of about 0.9 MW has been obtained in pulses up to 180 s, limited by the capability of the high voltage power supply. The development work on coaxial cavity gyrotrons has demonstrated the feasibility of manufacturing of a 2 MW, CW 170 GHz tube that could be used for ITER. The problems specific to the coaxial arrangement have been investigated and all relevant information needed for an industrial realization of a coaxial gyrotron have been obtained in short pulse experiments (up to 17 ms). The suitability of critical components for a 2 MW, CW coaxial gyrotron has been studied and a first integrated design has been done. (author)

  13. Irradiation creep induced anisotropy in a/2 dislocation populations

    Gelles, D.S.

    1984-05-01

    The contribution of anisotropy in Burgers vector distribution to irradiation creep behavior has been largely ignored in irradiation creep models. However, findings on Frank loops suggest that it may be very important. Procedures are defined to identify the orientations of a/2 Burgers vectors for dislocations in face-centered cubic crystals. By means of these procedures the anisotropy in Burgers vector populations was determined for three Nimonic PE16 pressurized tube specimens irradiated under stress. Considerable anisotropy in Burgers vector population develops during irradiation creep. It is inferred that dislocation motion during irradiation creep is restricted primarily to a climb of a/2 dislocations on 100 planes. Effect of these results on irradiation creep modeling and deformation induced irradiation growth is considered

  14. A2e High Fidelity Modeling: Strategic Planning Meetings

    Hammond, Steven W. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sprague, Michael A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Womble, David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Barone, Matt [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    Atmosphere to electrons (A2e) is a multi-year U.S. Department of Energy (DOE) research initiative targeting significant reductions in the cost of wind energy through an improved understanding of the complex physics governing wind flow into and through whole wind farms. Better insight into the flow physics of large multi-turbine arrays will address the plant-level energy losses, is likely to reduce annual operational costs by hundreds of millions of dollars, and will improve project financing terms to more closely resemble traditional capital projects. In support of this initiative, two planning meetings were convened, bringing together professionals from universities, national laboratories, and industry to discuss wind plant modeling challenges, requirements, best practices, and priorities. This report documents the combined work of the two meetings and serves as a key part of the foundation for the A2e/HFM effort for predictive modeling of whole wind plant physics.

  15. A 2:1 MUX Based on Multiple MEMS Resonators

    Hafiz, Md Abdullah Al

    2017-01-09

    Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. This paper reports a realization of a 2:1 MUX, a concatenable digital logic element, based on electrothermal frequency tuning of electrically connected multiple arch resonators. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

  16. A 2:1 MUX Based on Multiple MEMS Resonators

    Hafiz, Md Abdullah Al; Kosuru, Lakshmoji; Younis, Mohammad I.; Fariborzi, Hossein

    2017-01-01

    Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. This paper reports a realization of a 2:1 MUX, a concatenable digital logic element, based on electrothermal frequency tuning of electrically connected multiple arch resonators. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

  17. Optical Properties of Some A2BCl4 Type Chlorides

    D. H. Gahane; B. M. Bahirwar; S. V. Moharil

    2013-01-01

    Efficient luminescence is reported for the first time in Eu2+ activated double Chlorides A2BCl4 (A=Alkali metal, B=Alkaline earth element). A simple wet-chemical preparation is described. Emission intensities are comparable to that of the commercial phosphor. Excitation covers near UV region. These phosphors may be useful for applications like solid state lighting, scintillation detectors and X-ray storage using photo-stimulable phosphors.

  18. 17 CFR 240.10A-2 - Auditor independence.

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Auditor independence. 240.10A... Exchange Act of 1934 Reports Under Section 10a § 240.10A-2 Auditor independence. It shall be unlawful for an auditor not to be independent under § 210.2-01(c)(2)(iii)(B), (c)(4), (c)(6), (c)(7), and § 210.2...

  19. Origin of photoluminescence in β -G a2O3

    Ho, Quoc Duy; Frauenheim, Thomas; Deák, Peter

    2018-03-01

    β -G a2O3 , a candidate material for power electronics and UV optoelectronics, shows strong room-temperature photoluminescence (PL). In addition to the three well-known bands of as-grown samples in the UV, blue, and green, also red PL was observed upon nitrogen doping. This raises the possibility of applying β -G a2O3 nanostructures as white phosphors. Using an optimized, Koopmans-compliant hybrid functional, we show that most intrinsic point defects, as well as substitutional nitrogen, act as deep acceptors, and each of the observed PL bands can be explained by electron recombination with a hole trapped in one of them. We suggest this mechanism to be general in wide-band-gap semiconductors which can only be doped n -type. Calculations on the nitrogen acceptor reproduce the observed red luminescence accurately. Earlier we have shown that not only the energy, but the polarization properties of the UV band can be explained by self-trapped hole states. Here we find that the blue band has its origin mainly in singly negative Ga-O divacancies, and the green band is caused dominantly by interstitial O atoms (with minor contribution of Ga vacancies to both). These assignments can explain the experimentally observed dependence of the PL bands on free-electron concentration and stoichiometry. The information provided here paves the way for the conscious tuning of light emission from β -G a2O3 .

  20. Ballpoint pen ingestion in a 2-year-old child.

    Rameau, Anaïs; Anand, Sumeet M; Nguyen, Lily H

    2011-07-01

    A 2-year-old girl ingested a ballpoint pen, which was found on chest x-ray to have lodged in the lower esophagus and stomach. The pen, which measured nearly 15 cm in length, was removed via rigid esophagoscopy without complication. To the best of our knowledge, this is the longest nonflexible foreign body ingested by a young child ever reported in the English-language literature. We describe the presentation of this case and the current guidelines for safety as enumerated in the Small Parts Regulations established by the U.S. Consumer Product Safety Commission.

  1. Spansk basisgrammatik

    Jensen, Kjær

    Det er en grammatik over moderne spansk sprog bestående af tre dele: Del 1 indeholder den fundamentale grammatik der gør rede for syntaktiske regler og relationer. Del 2, Analyser og definitioner viser opbygningen af syntagmer og sætninger. Del 3 er en alfabetisk ordliste der indholder grammatiske...

  2. Reversible photocapture of a [2]rotaxane harnessing a barbiturate template.

    Tron, Arnaud; Thornton, Peter J; Lincheneau, Christophe; Desvergne, Jean-Pierre; Spencer, Neil; Tucker, James H R; McClenaghan, Nathan D

    2015-01-16

    Photoirradiation of a hydrogen-bonded molecular complex comprising acyclic components, namely, a stoppered thread (1) with a central barbiturate motif and an optimized doubly anthracene-terminated acyclic Hamilton-like receptor (2b), leads to an interlocked architecture, which was isolated and fully characterized. The sole isolated interlocked photoproduct (Φ = 0.06) is a [2]rotaxane, with the dimerized anthracenes assuming a head-to-tail geometry, as evidenced by NMR spectroscopy and consistent with molecular modeling (PM6). A different behavior was observed on irradiating homologous molecular complexes 1⊂2a, 1⊂2b, and 1⊂2c, where the spacers of 2a, 2b, and 2c incorporated 3, 6, and 9 methylene units, respectively. While no evidence of interlocked structure formation was observed following irradiation of 1⊂2a, a kinetically labile rotaxane was obtained on irradiating the complex 1⊂2c, and ring slippage was revealed. A more stable [2]rotaxane was formed on irradiating 1⊂2b, whose capture is found to be fully reversible upon heating, thereby resetting the system, with some fatigue (38%) after four irradiation–thermal reversion cycles.

  3. The End Point Tagger physics program at A2@MAMI

    Steffen, Oliver

    2017-04-01

    The A2-Collaboration uses a beam of real photons from the tagged photon facility at the electron accelerator MAMI in Mainz, Germany, to study photo-produced mesons. A new tagging device allows access to the higher photon beam energy range of 1.4 to 1.6 GeV. A large dataset containing more than 6 million η' and roughly 29 million ω decays has been obtained. Analyses are ongoing, including a study of the cusp effect and Dalitz plot in η' → ηπ0π0, giving insight to the ππ scattering length and the structure of the ηππ system, as well as the measurement of the electromagnetic transition form factor in η' → e+e-γ, a cross section measurement of γp → 3π0, and branching ratio analyses of η' → ωγ and ω → ηγ.

  4. Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2.

    Lister, M D; Hancock, A J

    1988-10-01

    Six isomers of dipalmitoylcyclopentanetriol phosphocholine (cyclopentano-lecithin) were tested as potential substrates for phospholipase A2. Since each of these analogs possesses a configuration that mimics a narrow range of conformations of a glycerophospholipid molecule, the analogs were used to assess the enzyme's conformational requirements. Studies showed that all of the analogs containing the phosphocholine at the C-1 (or C-3) position could be hydrolyzed, while only one of the three analogs that contains the polar head group at the C-2 position was susceptible. Kinetic studies, however, revealed that only the all-trans-(1,3/2-1P)-cyclopentano-lecithin gave initial rates of hydrolysis that were measurable by pH-stat. Acyl group specificity of the enzyme towards the all-trans isomer was determined with an analog was acyl groups were distinguishable. The synthesis of this mixed-acid-cyclopentano-PC is described herein. When this analog was enzymatically assayed, results unequivocally showed the enzyme to be specific for C-2 acyl hydrolysis. This specificity, and data showing that the all-trans analog is stereospecifically hydrolyzed, indicate that it is acted on in an analogous manner to dipalmitoylphosphatidylcholine. These studies indicate that although the configuration of the analog is not necessarily a prerequisite for hydrolysis, there does appear to be an optimal spatial orientation for enzymatic activity. The analogy between the susceptibilities of all-trans-(1,3/2-1P)-cyclopentano-lecithin and glycero-lecithin suggests that the conformation of the glycero-lecithin during phospholipase A2-mediated hydrolysis may be best simulated by the all-trans orientation of C-O bonds in the artificial substrate.

  5. Inhibitory effects of Swietenia macrophylla on myotoxic phospholipases A2

    Jaime A. Pereañez

    Full Text Available Activity-guided fractionation of an ethanol-soluble extract of the leaves of Swietenia macrophylla King, Meliaceae, led to several fractions. As a result, sample Sm13-16, 23 had the most promising activity against phospholipases A2 (PLA2, Asp49 and Lys49 types. This fraction inhibited PLA2 activity of the Asp49 PLA2, when aggregated substrate was used. On the other hand, this activity was weakly neutralized when monodispersed substrate was used. In addition, Sm13-16, 23 inhibited, in a dose dependent manner, the cytotoxicity, myotoxicity and edema induced by PLA2s, as well as the anticoagulant activity of Asp49 PLA2. Overall, this fraction exhibited a better inhibition of the toxic activities induced by the Lys49 PLA2than those caused by the Asp49 PLA2. The spectral data of Sm13-16, 23 suggested the presence of aromatic compounds (UV λ max (nm 655, 266, and 219; IR λ max KBr (cm-1: ~ 3600-3000 (OH, 2923.07 and 1438.90 (C-H, 1656.69 (C = O, 1618.63 and 1607.67 (C-O, 1285.47772.60. We suggest that phenolic compounds could interact and inhibit the toxins by several mechanisms. Further analysis of the compounds present in the active fraction could be a relevant contribution in the treatment of accidents caused by snake envenomation.

  6. Bootstrapping the (A1, A2) Argyres-Douglas theory

    Cornagliotto, Martina; Lemos, Madalena; Liendo, Pedro

    2018-03-01

    We apply bootstrap techniques in order to constrain the CFT data of the ( A 1 , A 2) Argyres-Douglas theory, which is arguably the simplest of the Argyres-Douglas models. We study the four-point function of its single Coulomb branch chiral ring generator and put numerical bounds on the low-lying spectrum of the theory. Of particular interest is an infinite family of semi-short multiplets labeled by the spin ℓ. Although the conformal dimensions of these multiplets are protected, their three-point functions are not. Using the numerical bootstrap we impose rigorous upper and lower bounds on their values for spins up to ℓ = 20. Through a recently obtained inversion formula, we also estimate them for sufficiently large ℓ, and the comparison of both approaches shows consistent results. We also give a rigorous numerical range for the OPE coefficient of the next operator in the chiral ring, and estimates for the dimension of the first R-symmetry neutral non-protected multiplet for small spin.

  7. Magnetic gating of a 2D topological insulator

    Dang, Xiaoqian; Burton, J. D.; Tsymbal, Evgeny Y.

    2016-09-01

    Deterministic control of transport properties through manipulation of spin states is one of the paradigms of spintronics. Topological insulators offer a new playground for exploring interesting spin-dependent phenomena. Here, we consider a ferromagnetic ‘gate’ representing a magnetic adatom coupled to the topologically protected edge state of a two-dimensional (2D) topological insulator to modulate the electron transmission of the edge state. Due to the locked spin and wave vector of the transport electrons the transmission across the magnetic gate depends on the mutual orientation of the adatom magnetic moment and the current. If the Fermi energy matches an exchange-split bound state of the adatom, the electron transmission can be blocked due to the full back scattering of the incident wave. This antiresonance behavior is controlled by the adatom magnetic moment orientation so that the transmission of the edge state can be changed from 1 to 0. Expanding this consideration to a ferromagnetic gate representing a 1D chain of atoms shows a possibility to control the spin-dependent current of a strip of a 2D topological insulator by magnetization orientation of the ferromagnetic gate.

  8. Bee Venom Phospholipase A2: Yesterday's Enemy Becomes Today's Friend.

    Lee, Gihyun; Bae, Hyunsu

    2016-02-22

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson's disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes.

  9. Development and Evaluation of a 2KVA Inverter

    Ajayi Adedayo

    2013-09-01

    Full Text Available A 2KV inverter was designed, developed and tested for household applications. It consists of a heavy duty (24 V, 80 AH, oscillator unit, PWM (Pulse-width modulation controller unit, driver unit, amplifier unit, center-tap step up transformer and battery charger unit. The battery powered the circuitry and the oscillator section generates the drive signal that is amplified and set up the transformer to produce 240 V supply at the secondary winding connected to the output socket of inverter. The feedback control circuit uses discrete components such as: full wave rectifier, pulse width modulator (IC, diodes and other components to sense the output voltage (or load current. When the feedback senses that the load on the inverter output has increased, the inverter control circuitry acts by increasing the width of the switching pulse in the oscillator section which turn on the MOSFETS. MOSFETS turns on for longer time each cycle, automatically correcting the R.M.S value of the output to compensate for any drop in peak-peak output voltage as well as continuous charging of battery, consequently, maintaining a steady output voltage level in inverter irrespective of the load characteristics. The outputs of the tests carried on the unit shows that that instrument performs satisfactory well.

  10. A 2D nonlinear inversion of well-seismic data

    Métivier, Ludovic; Lailly, Patrick; Delprat-Jannaud, Florence; Halpern, Laurence

    2011-01-01

    Well-seismic data such as vertical seismic profiles are supposed to provide detailed information about the elastic properties of the subsurface at the vicinity of the well. Heterogeneity of sedimentary terrains can lead to far from negligible multiple scattering, one of the manifestations of the nonlinearity involved in the mapping between elastic parameters and seismic data. We present a 2D extension of an existing 1D nonlinear inversion technique in the context of acoustic wave propagation. In the case of a subsurface with gentle lateral variations, we propose a regularization technique which aims at ensuring the stability of the inversion in a context where the recorded seismic waves provide a very poor illumination of the subsurface. We deal with a huge size inverse problem. Special care has been taken for its numerical solution, regarding both the choice of the algorithms and the implementation on a cluster-based supercomputer. Our tests on synthetic data show the effectiveness of our regularization. They also show that our efforts in accounting for the nonlinearities are rewarded by an exceptional seismic resolution at distances of about 100 m from the well. They also show that the result is not very sensitive to errors in the estimation of the velocity distribution, as far as these errors remain realistic in the context of a medium with gentle lateral variations

  11. Difluorothromboxane A2 and stereoisomers: Stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels

    Morinelli, T.A.; Okwu, A.K.; Mais, D.E.; Halushka, P.V.; John, V.; Chen, Chienkuang; Fried, J.

    1989-01-01

    The present study reports on the selective effects on human platelets and canine saphenous veins of four stable difluorinated analogues and thromboxane A 2 (TXA 2 ), in which the characteristic 2,6-dioxa[3.1.1]bicycloheptane structure of TXA 2 has been retained. The four compounds differ in their stereochemistry of the 5,6 double bond and/or the 15-hydroxyl group. Only 10,10-difluoro-TXA 2 (compound I) with the natural stereochemistry of TXA 2 was an agonist in both platelets and canine saphenous veins. (15R)-10,10-Difluoro-TXA 2 (compound II), (5E)-10,10-difluoro-TXA 2 (compound III), and (5E,15R)-10,10-difluoro-TXA 2 (compound IV) were antagonists of platelet aggregation stimulated by compound I. However, compounds II, III, and IV stimulated contraction of canine saphenous veins. All four compounds could displace the TXA 2 /prostaglandin H 2 antagonist 9,11-dimethylmethano-11,12-methano-16-(3- 125 I-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-ω-tetranor-TXA 2 from its platelet receptor. These results support the existence of two subtypes of TXA 2 /prostaglandin H 2 receptors and emphasize the importance of the stereochemical requirements of these TXA 2 analogues for interaction with these receptors. These stable fluorinated TXA 2 analogues should prove useful tools for the further characterization of these and other TXA 2 /prostaglandin H 2 receptors

  12. A 2PI/sub u/ state of N2+

    Wu, H.H.

    1975-01-01

    The N 2 + Meinel (N 2 + M) system (A 2 PI/sub u/ - X 2 Σ + /sub g/) was examined through steady state and transient electron excitation of pure N 2 in a semi-static system by 80-eV electrons in the pressure range from 0.5 mTorr to 50 mTorr, and at wave lengths in the 1800 to 9200 A region. Examination of the rotational structure of the (2,0) band indicates that the A state is inverted and that the rotational distribution is never in thermal equilibrium under any experimental condition in pure N 2 . The variation of electronic transition moment was estimated from the relative emission rates within the N 2 + M system, and can be described by a quadratic function of r-centroid, anti r, as R/sub e/(anti r)/R/sub e/(1.0) = 33.28 (1.0 - 1.8 anti r + 0.8 anti r 2 ), in the interval 1.02A less than anti r less than 1.14A. Two measurable decay components are detected in the transient observations. The shorter lived component with relative intensity greater than or equal to % of the total is believed to be from direct excitation-ionization. This component has a lifetime of 5.1 to +- 0.8 μsec, and a quenching coefficient of 7.9 x 10 -10 cm 3 /sec. The damping constant of the longer lived component is dominated by diffusion or drift loss and has an estimated zero pressure radiative probability of less than or equal to 0.05 μsec -1 . The quenching coefficient of the long lived component is estimated to be 3.7 x 10 -11 cm 3 /sec. Intersystem cascade among the high vibrational levels of the N 2 + X and N 2 + A state to explain the observed longer lived component. The variation is relative intensity of the two components in the 1 mTorr less than P less than 15 mTorr region can be described within experimental uncertainty by this model, with assumed1/tau = 0.06 μsec -1 and quenching coefficient of 1.2 x 10 -9 cm 3 sec -1 for the high vibrational levels of the A state

  13. Data of evolutionary structure change: 1QQ4A-2SFAA [Confc[Archive

    Full Text Available 1QQ4A-2SFAA 1QQ4 2SFA A A ANIVGGIEYSINNASLCSVGFSVTR-GATKGFVTAGHCGTVNATARIG---GAVVGTFAA...ID>2SFA A 2SFAA 2SFA A 2SFAA...A 2SFAA VNYGGGDIVSG E EEE ... A 2SFAA GALFA-GSTAL

  14. [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain

    Jarvis, M.F.; Schulz, R.; Hutchison, A.J.; Do, U.H.; Sills, M.A.; Williams, M.

    1989-01-01

    In the present study, the binding of a highly A2-selective agonist radioligand, [3H]CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine) is described. [3H]CGS 21680 specific binding to rat striatal membranes was saturable, reversible and dependent upon protein concentration. Saturation studies revealed that [3H]CGS 21680 bound with high affinity (Kd = 15.5 nM) and limited capacity (apparent Bmax = 375 fmol/mg of protein) to a single class of recognition sites. Estimates of ligand affinity (16 nM) determined from association and dissociation kinetic experiments were in close agreement with the results from the saturation studies. [3H]CGS 21680 binding was greatest in striatal membranes with negligible specific binding obtained in rat cortical membranes. Adenosine agonists ligands competed for the binding of 5 nM [3H]CGS 21680 to striatal membranes with the following order of activity; CGS 21680 = 5'-N-ethylcarboxamidoadenosine greater than 2-phenylaminoadenosine (CV-1808) = 5'-N-methylcarboxamidoadenosine = 2-chloroadenosine greater than R-phenylisopropyladenosine greater than N6-cyclohexyladenosine greater than N6cyclopentyltheophylline greater than S-phenylisopropyladenosine. The nonxanthine adenosine antagonist, CGS 15943A, was the most active compound in inhibiting the binding of [3H]CGS 21680. Other adenosine antagonists inhibited binding in the following order; xanthine amine congener = 1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine greater than 1,3-dipropyl-8-cyclopentylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than 8-phenyltheophylline greater than 8-cyclopentyltheophylline = xanthine carboxylic acid congener greater than 8-parasulfophenyltheophylline greater than theophylline greater than caffeine

  15. Two-step Purification Method for Aging Pigments A2E and Iso-A2E Using Medium Pressure Liquid Chromatography

    Park, Sang Il; Park, Sang Cheol; Kim, So Ra; Jang, Young Pyo

    2016-01-01

    A newly modified method for the efficient purification of A2E and iso-A2E using reverse phase silica gel resin with medium pressure liquid chromatography (MPLC) was suggested. MPLC is one of the various preparative column chromatography techniques and separation under pressure renders the use of smaller particle size resins possible and increases the diversity of available stationary phases. A simplified two-step purification method was developed for the purification of aging pigments in eye, A2E and iso-A2E. With simple two-step elution of mobile phase in reverse phase MPLC, A2E and iso-A2E were successfully purified with great efficiency compare with previous column chromatography and HPLC method. This method provides more simple, convenient, cost-effective, and less time-consuming procedure for mass purification of aging pigments A2E and iso-A2E

  16. Two-step Purification Method for Aging Pigments A2E and Iso-A2E Using Medium Pressure Liquid Chromatography

    Park, Sang Il; Park, Sang Cheol [Kyunghee Univ., Seoul (Korea, Republic of); Kim, So Ra; Jang, Young Pyo [Seoul National Univ., Seoul (Korea, Republic of)

    2016-09-15

    A newly modified method for the efficient purification of A2E and iso-A2E using reverse phase silica gel resin with medium pressure liquid chromatography (MPLC) was suggested. MPLC is one of the various preparative column chromatography techniques and separation under pressure renders the use of smaller particle size resins possible and increases the diversity of available stationary phases. A simplified two-step purification method was developed for the purification of aging pigments in eye, A2E and iso-A2E. With simple two-step elution of mobile phase in reverse phase MPLC, A2E and iso-A2E were successfully purified with great efficiency compare with previous column chromatography and HPLC method. This method provides more simple, convenient, cost-effective, and less time-consuming procedure for mass purification of aging pigments A2E and iso-A2E.

  17. PENGARUH GROSS DOMESTIC PRODUCT, INFLASI, SUKU BUNGA, MONEY SUPPLY, CURRENT ACCOUNT DAN CAPITAL ACCOUNT TERHADAP NILAI KURS RUPIAH INDONESIA – DOLLAR AMERIKA

    Yunika Murdayanti

    2012-03-01

    Full Text Available Since free-floating exchange rate system has been applied in Indonesia on August 1998, the accumulation of depreciation of rupiah against the US dollar has been about 48,7% until December 2001. This condition brings many argumentation about the reasons behind the exchange rate instability faced by Indonesia among many experts whether it is caused by economic factors or by non-economic factors. By recognizing the causes, it will be easier for the experts and government of Indonesia to formulate the solution. This research is intended to analyze the influence of economic variables, i.e. Gross Domestic Product, money supply, interest rate, inflation rate, Current Account & Capital Account in both Indonesia and The United State of America, as well as the position of the balance of international payment of Indonesia to the exchange rate movement in order to give contributions to solve the problem. Based on the result money supply becomes the only variable which has a multicollinearity and excluded from the regression linear. Also only current account is not significant influence on the exchange rate movement, instead of the other variables. Coefficient of determination of the research model is 84.4 %, means that other factors, not accommodated in this research, give 15.6 % influence to the exchange rate movement. These other factors can be categorized as other economic factors or non-economic factors.

  18. 1) rheuma: komplementare therapien hoch im kurs; 2) ist der Ruckenschmerz magnetisch? 3) morbus alzheimer: unkonventionelle therapeutische Wundertute; 4) homocystein: Im westen nichts neues

    Resch

    2000-08-01

    Wahrend in akademischen Kreisen noch ausgiebig diskutiert wird, wie Naturheilkunde, Komplementarmedizin und Alternativmedizin begrifflich fassbar gemacht, sprich definiert werden konnen, hat sich langst ein Parallelmarkt entwickelt, auf dem seriose und obskure Anbieter eine breite Palette von vermeintlich hilfreichen diagnostischen Massnahmen und Therapien feilbieten. Ohne kassenarztliche Vereinigung, ohne wissenschaftliche Fachgesellschaften, ohne amtlichen Segen. Der Markt boomt, wie das Beispiel rheumatische Erkrankungen zeigt. Das hat seine Grunde, von denen S. Hill in ihrem Kommentar einige nennt. Abstrahiert konnte man sagen, dass es offensichtlich einen grossen Bedarf in Bereichen gibt, fur die die konventionelle Medizin zu wenig zu bieten hat. Die daraus resultierende Tatsache, dass Patienten immer mehr bereit sind, zusatzlich und erganzend Leistungen einzukaufen, musste nicht weiter schrecken (und ware parteienubergreifend sogar ganz im Sinne unserer Gesundheitspolitiker), wenn man unterstellen konnte, Patienten hatten eine einigermassen verlassliche Moglichkeit, seriose Angebote von denen von Quacksalbern, Scharlatanen und miesen Geschaftemachern zu unterscheiden. Das haben Sie aber nicht. Die Beispiele in diesem Journal Club sollen aufzeigen, wie schwer es manchmal selbst dort ist, Stellung zu beziehen, wo bereits Versuche vorliegen, bestimmte Angebote zu hinterfragen. Das liegt nicht zuletzt an den ziemlich durchgangigen Defiziten, was die Forschungsqualitat in diesem Bereich anbelangt. Es scheint hochste Zeit, dass sich die akademische Medizin ihrer Verantwortung in diesem Bereich bewusst wird und sich seiner annimmt. Wer sonst sollte das tun? Copyright 2000 S. Karger GmbH, Freiburg

  19. CRED Subsurface Temperature Recorder (STR); NWHI, KUR; Long: -178.34317, Lat: 28.41816 (WGS84); Sensor Depth: 9.75m; Data Range: 20090916-20100918.

    National Oceanic and Atmospheric Administration, Department of Commerce — Data from Coral Reef Ecosystem Division (CRED), NOAA Pacific Islands Fisheries Science Center (PIFSC) Subsurface Temperature Recorders (STR) provide a time series of...

  20. CRED Subsurface Temperature Recorder (STR); NWHI, KUR; Long: -178.32575, Lat: 28.38175 (WGS84); Sensor Depth: 12.50m; Data Range: 20090915-20100519.

    National Oceanic and Atmospheric Administration, Department of Commerce — Data from Coral Reef Ecosystem Division (CRED), NOAA Pacific Islands Fisheries Science Center (PIFSC) Subsurface Temperature Recorders (STR) provide a time series of...

  1. CRED Subsurface Temperature Recorder (STR); NWHI, KUR; Long: -178.28268, Lat: 28.39066 (WGS84); Sensor Depth: 19.20m; Data Range: 20060918-20080111.

    National Oceanic and Atmospheric Administration, Department of Commerce — Data from Coral Reef Ecosystem Division (CRED), NOAA Pacific Islands Fisheries Science Center (PIFSC) Subsurface Temperature Recorders (STR) provide a time series of...

  2. CRED Subsurface Temperature Recorder (STR); NWHI, KUR; Long: -178.34457, Lat: 28.41858 (WGS84); Sensor Depth: 9.75m; Data Range: 20041024-20060917.

    National Oceanic and Atmospheric Administration, Department of Commerce — Data from Coral Reef Ecosystem Division (CRED), NOAA Pacific Islands Fisheries Science Center (PIFSC) Subsurface Temperature Recorders (STR) provide a time series of...

  3. CRED Subsurface Temperature Recorder (STR); NWHI, KUR; Long: -178.35620, Lat: 28.45155 (WGS84); Sensor Depth: 20.12m; Data Range: 20081001-20100918.

    National Oceanic and Atmospheric Administration, Department of Commerce — Data from Coral Reef Ecosystem Division (CRED), NOAA Pacific Islands Fisheries Science Center (PIFSC) Subsurface Temperature Recorders (STR) provide a time series of...

  4. Measurement of the neutron flux distributions, epithermal index, Westcott thermal neutron flux in the irradiation capsules of hydraulic conveyer (Hyd) and pneumatic tubes (Pn) facilities of the KUR

    Chatani, Hiroshi

    2001-05-01

    The reactions of Au(n, γ) 198 Au and Ti(n, p) 47 or 48 Sc were used for the measurements of the thermal and epithermal (thermal + epithermal) and the fast neutron flux distributions, respectively. In the case of Hyd (Hydraulic conveyer), the thermal + epithermal and fast neutron flux distributions in the horizontal direction in the capsule are especially flat; the distortion of the fluxes are 0.6% and 5.4%, respectively. However, these neutron fluxes in the vertical direction are low at the top and high at the bottom of the capsule. These differences between the top and bottom are 14% for both distributions. On the other hand, in polyethylene capsules of Pn-1, 2, 3 (Pneumatic tubes Nos. 1, 2, 3), in contrast with Hyd, these neutron flux distributions in the horizontal direction have gradients of 8 - 18% per 2.5 cm diameter, and those on the vertical axis have a distortion of approximately 5%. The strength of the epithermal dE/E component relative to the neutron density including both thermal and epithermal neutrons, i.e., the epithermal index, for the hydraulic conveyer (Hyd) and pneumatic tube No.2 (Pn-2), in which the irradiation experiments can be achieved, are determined by the multiple foil activation method using the reactions of Au(n, γ) 198 Au and Co(n, γ) 60(m+g) Co. The epithermal index observed in an aluminum capsule of Hyd is 0.034-0.04, and the Westcott thermal neutron flux is 1.2x10 14 cm -2 sec -1 at approximately 1 cm above the bottom. The epithermal index in a Pn-2 polyethylene capsule was measured by not only the multiple foil activation method but also the Cd-ratio method in which the Au(n, γ) 198 Au reaction in a cadmium cover is also used. The epithermal index is 0.045 - 0.055, and the thermal neutron flux is 1.8x10 13 cm -2 sec -1 . (J.P.N.)

  5. Analisis Pengaruh Fluktuasi Kurs Valuta Asing dan Kebijakan Harga Bahan Bakar Minyak dalam Periode 2000-2008 terhadap Kinerja PT Astra Internasional di Indonesia

    Mohamad Heykal

    2011-05-01

    Full Text Available The fourth quarter in 2008 is the peak of Global Monetary Crisis, which is the decreasing of liquidity in companies around the world. The crisis also affected towards fluctuation of world petroleum price. Automotive industry in Indonesia was also affected towards cost of foreign exchange fluctuation and petroleum price due to the crisis. PT Astra International, Tbk. is assumed to represent automotive industry in Indonesia. The research is done through literature research and financial and sales report analysis in 2000-2008. The performance reduction is directly connected by the decreasing of earnings, especially in motor vehicle and parts sale in those years and also the increasing of cost of production, due to the increasing of import fee and transportation cost. Foreign exchange fluctuation and petroleum price directly affects the work performance of PT Astra Internasional.

  6. Data of evolutionary structure change: 1AQ7A-2FODA [Confc[Archive

    Full Text Available 1AQ7A-2FODA 1AQ7 2FOD A A IVGGYTCGANTVPYQVSLNSG-----YHFCGGSLINSQW...pdbChain>A 2FODA SLQYRSGSSWAHTCG 2FOD A 2FODA PLHCLVNGQYAVHG 2FOD A 2FODA...pdbChain> 2FODA TRTNG-QLAQT -

  7. Data of evolutionary structure change: 2QU0A-2HHED [Confc[Archive

    Full Text Available ID> 0 2QU0 A 2QU0A ...ne> 2QU0 A 2QU0A ...2QU0A-2HHED 2QU0 2HHE A D VLSAADKSNVKAAWGKVGGNAGAYGAEALERMFLSFPTT...ence>HGSAQ-----VKGHGence> HH-----HHHHH D 2HHED ence>TPDAVMGNPKVKAHGence>

  8. Casein Kinase 2 Is a Novel Regulator of the Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2) Trafficking.

    Chan, Ting; Cheung, Florence Shin Gee; Zheng, Jian; Lu, Xiaoxi; Zhu, Ling; Grewal, Thomas; Murray, Michael; Zhou, Fanfan

    2016-01-04

    Human organic anion transporting polypeptides (OATPs) mediate the influx of many important drugs into cells. Casein kinase 2 (CK2) is a critical protein kinase that phosphorylates >300 protein substrates and is dysregulated in a number of disease states. Among the CK2 substrates are several transporters, although whether this includes human OATPs has not been evaluated. The current study was undertaken to evaluate the regulation of human OATP1A2 by CK2. HEK-239T cells in which OATP1A2 was overexpressed were treated with CK2 specific inhibitors or transfected with CK2 specific siRNA, and the activity, expression, and subcellular trafficking of OATP1A2 was evaluated. CK2 inhibition decreased the uptake of the prototypic OATP1A2 substrate estrone-3-sulfate (E3S). Kinetic studies revealed that this was due to a decrease in the maximum velocity (Vmax) of E3S uptake, while the Michaelis constant was unchanged. The cell surface expression, but not the total cellular expression of OATP1A2, was impaired by CK2 inhibition and knockdown of the catalytic α-subunits of CK2. CK2 inhibition decreased the internalization of OATP1A2 via a clathrin-dependent pathway, decreased OATP1A2 recycling, and likely impaired OATP1A2 targeting to the cell surface. Consistent with these findings, CK2 inhibition also disrupted the colocalization of OATP1A2 and Rab GTPase (Rab)4-, Rab8-, and Rab9-positive endosomal and secretory vesicles. Taken together, CK2 has emerged as a novel regulator of the subcellular trafficking and stability of OATP1A2. Because OATP1A2 transports many molecules of physiological and pharmacological importance, the present data may inform drug selection in patients with diseases in which CK2 and OATP1A2 are dysregulated.

  9. Rapid purification method for vitamin A-derived aging pigments A2E and iso-A2E using cation exchange resin.

    Jee, Eun Hye; Kim, So Ra; Jang, Young Pyo

    2012-08-17

    A2E, known to be involved in the pathogenesis of age-related macular degeneration (AMD), is one of the major compounds that accumulate as fluorescent pigments in retinal pigment epithelial (RPE) cells with age and in some retinal disorders. While the biomimetic synthesis of A2E and its cis-isomer, iso-A2E is as simple as 'one-pot' reaction, the purification of these amphiphillic compounds has been a bottleneck for the mass production of these pathophysiologically important eye pigments. In order to provide a new method of rapid purification of A2E and iso-A2E, we employed a cation exchange resin for the separation of these pigments from crude reaction mixture. The reaction mixture was loaded on a weak acid resin and was eluted with 80% methanol with sodium hydroxide (pH 12), 100% methanol, and 100% methanol with 0.1% trifluoroacetic acid (TFA) in sequence. A2E and isoA2E were eluted only with 100% methanol solution containing TFA. Most of unreacted starting materials and intermediates were removed with 80% methanol containing sodium hydroxide. The new method can be used as a relatively simple and economic way to purify A2E and iso-A2E compared to conventional HPLC technique. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Foci of cyclin A2 interact with actin and RhoA in mitosis.

    Loukil, Abdelhalim; Izard, Fanny; Georgieva, Mariya; Mashayekhan, Shaereh; Blanchard, Jean-Marie; Parmeggiani, Andrea; Peter, Marion

    2016-06-09

    Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis depends primarily on the ubiquitin-proteasome system (UPS), while autophagy also contributes. However, a fraction of cyclin A2 persists beyond metaphase. In this work, we focus on cyclin A2-rich foci detected in mitosis by high resolution imaging and analyse their movements. We demonstrate that cyclin A2 interacts with actin and RhoA during mitosis, and that cyclin A2 depletion induces a dramatic decrease in active RhoA in mitosis. Our data suggest cyclin A2 participation in RhoA activation in late mitosis.

  11. Svært ved grammatikken - del 2

    Kristensen, Line Burholt; Boye, Kasper

    2016-01-01

    Denne artikel er anden del af en artikelserie om baggrunden for grammatiske vanskeligheder. Den første artikel (bragt i Logos nr. 75) forklarede hvorfor grammatik er vigtigt for mennesker, og hvorfor det er vigtigt at have en teori om grammatik når man skal afgrænse, undersøge og behandle...... grammatiske vanskeligheder. Artiklen viste også at en klar og praktisk anvendelig definition er nødvendig, men at eksisterende traditionelle teorier giver uklare kriterier for forskellen på grammatik og leksikon. I denne anden del af artikelserien præsenterer vi en ny teori om grammatisk status (Boye & Harder...

  12. 26 CFR 20.2056A-2 - Requirements for qualified domestic trust.

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Requirements for qualified domestic trust. 20.2056A-2 Section 20.2056A-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Taxable Estate § 20.2056A-2 Requirements for qualified...

  13. 26 CFR 20.6166A-2 - Definition of an interest in a closely held business.

    2010-04-01

    ... Procedure and Administration § 20.6166A-2 Definition of an interest in a closely held business. (a) In... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Definition of an interest in a closely held business. 20.6166A-2 Section 20.6166A-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  14. 29 CFR 2550.404a-2 - Safe harbor for automatic rollovers to individual retirement plans.

    2010-07-01

    ... retirement plans. 2550.404a-2 Section 2550.404a-2 Labor Regulations Relating to Labor (Continued) EMPLOYEE... RETIREMENT INCOME SECURITY ACT OF 1974 RULES AND REGULATIONS FOR FIDUCIARY RESPONSIBILITY § 2550.404a-2 Safe..., whether or not such return is guaranteed, consistent with liquidity; (ii) For purposes of paragraph (c)(3...

  15. 26 CFR 1.691(a)-2 - Inclusion in gross income by recipients.

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Inclusion in gross income by recipients. 1.691(a)-2 Section 1.691(a)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Income in Respect of Decedents § 1.691(a)-2 Inclusion in...

  16. Identifying low density lipoprotein cholesterol associated variants in the Annexin A2 (ANXA2) gene

    Fairoozy, Roaa Hani; Cooper, Jackie; White, Jon

    2017-01-01

    Background and aims: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulat...

  17. Site-specific epsilon-NH2 monoacylation of pancreatic phospholipase A2. 2. Transformation of soluble phospholipase A2 into a highly penetrating "membrane-bound" form.

    Van der Wiele, F C; Atsma, W; Roelofsen, B; van Linde, M; Van Binsbergen, J; Radvanyi, F; Raykova, D; Slotboom, A J; De Haas, G H

    1988-03-08

    Long-chain lecithins present in bilayer structures like vesicles or membranes are only very poor substrates for pancreatic phospholipases A2. This is probably due to the fact that pancreatic phospholipases A2 cannot penetrate into the densely packed bilayer structures. To improve the weak penetrating properties of pancreatic phospholipases A2, we prepared and characterized a number of pancreatic phospholipase A2 mutants that have various long acyl chains linked covalently to Lys116 in porcine and to Lys10 in bovine phospholipase A2 [Van der Wiele, F.C., Atsma, W., Dijkman, R., Schreurs, A.M.M., Slotboom, A.J., & De Haas, G.H. (1988) Biochemistry (preceding paper in this issue)]. When monomolecular surface layers of L- and D-didecanoyllecithin were used, it was found that the introduction of caprinic, lauric, palmitic, and oleic acid at Lys116 in the porcine enzyme increases its penetrating power from 13 to about 17, 20, 32, and 22 dyn/cm, respectively, before long lag periods were obtained. Incorporation of a palmitoyl moiety at Lys10 in the bovine enzyme shifted the penetrating power from 11 to about 25 dyn/cm. Only the best penetrating mutant, viz., porcine phospholipase A2 having a palmitoyl moiety at Lys116, was able to cause complete leakage of 6-carboxyfluorescein entrapped in small unilamellar vesicles of egg lecithin under nonhydrolytic conditions. Similarly, only this latter palmitoylphospholipase A2 completely hydrolyzed all lecithin in the outer monolayer of the human erythrocyte at a rate much faster than Naja naja phospholipase A2, the most powerful penetrating snake venom enzyme presently known.

  18. Gambaran Populasi Golongan Darah Subgroup A (A1, A2 di PMI Kulon Progo

    Hieronymus Rayi Prasetya

    2017-08-01

    Full Text Available Subgroup A1 and A2 are the most important in the blood group A. Subgroup A1 has the A antigen more than A2 subgroup, the A2 subgroup can cause misidentification of blood group due to poor A antigen and genetic variation possessed. Misidentification of the blood group will increase the risk of transfusion reactions. This research aims to describe the A1 and A2 subgroup population in Kulon Progo district. This study was conducted with a cross sectional sampling technique. The sample in this study were taken from donors of blood group A in Kulon Progo Red Cross. Identification of A1 and A2 subgroup is done by using lectin (Dolichos biflorus extract. The result of the examination of 53 samples showed that 96,2% was A1 subgroup and 3,8% was A2 subgroup. Key words : Subgroup A1, Subgroup A2, Population, Kulon Progo

  19. The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

    Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

    2013-01-01

    Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

  20. Procyanidin A2 and Its Degradation Products in Raw, Fermented, and Roasted Cocoa.

    De Taeye, Cédric; Caullet, Gilles; Eyamo Evina, Victor Jos; Collin, Sonia

    2017-03-01

    Cocoa is known as an important source of flavan-3-ols, but their fate "from the bean to the bar" is not yet clear. Here, procyanidin A2 found in native cocoa beans (9-13 mg/kg) appeared partially epimerized into A2 E1 through fermentation, whereas a second epimer (A2 E2 ) emerged after roasting. At m/z 575, dehydrodiepicatechin A was revealed to be the major HPLC peak before fermentation, whereas F1, a marker of well-conducted fermentations, becomes the most intense after roasting. RP-HPLC-ESI(-)-HRMS/MS analysis performed on a procyanidin A2 model medium after 12 h at 90 °C revealed many more degradation products than those identified in fermented cocoa, including the last epimer of A2, A2 open structure intermediates (m/z 577), and oxidized A-type dimers (m/z 573).

  1. A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase.

    Gracia, Eduard; Pérez-Capote, Kamil; Moreno, Estefanía; Barkešová, Jana; Mallol, Josefa; Lluís, Carme; Franco, Rafael; Cortés, Antoni; Casadó, Vicent; Canela, Enric I

    2011-05-01

    A2ARs (adenosine A2A receptors) are highly enriched in the striatum, which is the main motor control CNS (central nervous system) area. BRET (bioluminescence resonance energy transfer) assays showed that A2AR homomers may act as cell-surface ADA (adenosine deaminase; EC 3.5.4.4)-binding proteins. ADA binding affected the quaternary structure of A2ARs present on the cell surface. ADA binding to adenosine A2ARs increased both agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Collectively, the results of the present study show that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal A2ARs.

  2. Adenosine A2B receptor: from cell biology to human diseases

    Sun, Ying; Huang, Pingbo

    2016-08-01

    Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR’s functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

  3. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    Senior, B; Dunlop, JI; Batten, MR

    2000-01-01

    , Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided...... by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition....

  4. HLA-A2 reactive antibodies in a patient who types as HLA-A2: The importance of high resolution typing and epitope-based antibody analysis.

    Hahn, A B; Bravo-Egana, V; Jackstadt, J L; Conti, D J; Duquesnoy, R J

    2015-06-01

    This report describes a case of a highly sensitized patient who had serum antibodies reacting with HLA-A2 but whose phenotype included HLA-A2. The determination of HLA mismatch acceptability at the antigen level was problematic, but high-resolution HLA typing information and epitope-based antibody specificity analysis based on the nonself-self paradigm of HLA epitope immunogenicity have provided a solution. This case supports the concept that HLA typing at the allele level offers a better approach to identifying suitable donors for sensitized patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland.

    Miyano, Yuki; Tahara, Shigeyuki; Sakata, Ichiro; Sakai, Takafumi; Abe, Hiroyuki; Kimura, Shioko; Kurotani, Reiko

    2014-04-01

    Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

  6. Data of evolutionary structure change: 1BZ1A-2ZLWD [Confc[Archive

    Full Text Available 1BZ1A-2ZLWD 1BZ1 2ZLW A D MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPT...R VQLSGEEKAAVLALWDKVN--EEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL...> 2ZLW D 2ZLWD WDKVN

  7. Data of evolutionary structure change: 1AJ9A-2ZLWD [Confc[Archive

    Full Text Available 1AJ9A-2ZLWD 1AJ9 2ZLW A D -VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPT...R VQLSGEEKAAVLALWDKVN--EEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL... 2ZLW D 2ZLWD

  8. Adenosine A(2A) receptor dynamics studied with the novel fluorescent agonist Alexa488-APEC.

    Brand, Frank; Klutz, Athena M; Jacobson, Kenneth A; Fredholm, Bertil B; Schulte, Gunnar

    2008-08-20

    G protein-coupled receptors, such as the adenosine A(2A) receptor, are dynamic proteins, which undergo agonist-dependent redistribution from the cell surface to intracellular membranous compartments, such as endosomes. In order to study the kinetics of adenosine A(2A) receptor redistribution in living cells, we synthesized a novel fluorescent agonist, Alexa488-APEC. Alexa488-APEC binds to adenosine A(2A) (K(i)=149+/-27 nM) as well as A(3) receptors (K(i)=240+/-160 nM) but not to adenosine A(1) receptors. Further, we characterized the dose-dependent increase in Alexa488-APEC-induced cAMP production as well as cAMP response element binding (CREB) protein phosphorylation, verifying the ligand's functionality at adenosine A(2A) but not A(2B) receptors. In live-cell imaging studies, Alexa488-APEC-induced adenosine A(2A) receptor internalization, which was blocked by the competitive reversible antagonist ZM 241385 and hyperosmolaric sucrose. Further, internalized adenosine A(2A) receptors co-localized with clathrin and Rab5, indicating that agonist stimulation promotes adenosine A(2A) receptor uptake through a clathrin-dependent mechanism to Rab5-positive endosomes. The basic characterization of Alexa488-APEC described here showed that it provides a useful tool for tracing adenosine A(2A) receptors in vitro.

  9. Should A2 be a diagnostic requirement for posttraumatic stress disorder in DSM-V?

    O'Donnell, Meaghan L; Creamer, Mark; McFarlane, Alexander C; Silove, Derrick; Bryant, Richard A

    2010-04-30

    The requirement that trauma survivors experience fear, helplessness or horror (Criterion A2) as a part of their posttraumatic stress disorder (PTSD) diagnosis was introduced into DSM-IV. The imminent re-definition of PTSD in DSM-V highlights the need for empirical studies to validate the utility of the A2 requirement. We aimed to identify (i) how often A2 was associated with PTSD (B-F criteria) at 3 months after trauma and (ii) what was the peritraumatic emotional experience for those who met PTSD criteria but were A2 negative. In a prospective design cohort study we assessed the peritraumatic emotional experience of 535 injury patients in four Australian hospitals. These patients were followed up 3 months later and assessed for PTSD using a structured clinical interview. The majority of those who developed PTSD (B-F criterion) at 3 months met A2 criteria. A substantial minority, however (23%), did not meet A2 criteria. Those PTSD patients who were A2 negative fell into three groups: (i) those who experienced subthreshold levels of A2; (ii) those who experienced intense peritrauma emotional responses other than fear, helplessness or horror; and (iii) those who were amnesic to their peritrauma emotional experience. These findings do not support the inclusion of A2 as diagnostic requirement for DSM-V. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  10. Inhibition of [3H]nitrendipine binding by phospholipase A2

    Goldman, M.E.; Pisano, J.J.

    1985-01-01

    Phospholipase A 2 from several sources inhibited [ 3 H]nitrendipine binding to membranes from brain, heart and ileal longitudinal muscle. The enzymes from bee venom and Russell's viper venom were most potent, having IC 50 values of approximately 5 and 14 ng/ml, respectively, in all three membrane preparations. Inhibition of binding by bee venom phospholipase A 2 was time- and dose-dependent. Mastoparan, a known facilitator of phospholipase A 2 enzymatic activity, shifted the bee venom phospholipase A 2 dose-response curve to the left. Pretreatment of brain membranes with bee venom phospholipase A 2 (10 ng/ml) for 15 min caused a 2-fold increase in the K/sub d/ without changing the B/sub max/ compared with untreated membranes. Extension of the preincubation period to 30 min caused no further increase in the K/sub d/ but significantly decreased the B/sub max/ to 71% the value for untreated membranes. [ 3 H]Nitrendipine, preincubated with bee venom phospholipase A 2 , was recovered and found to be fully active, indicating that the phospholipase A 2 did not modify the ligand. It is concluded that phospholipase A 2 acts on the membrane at or near the [ 3 H]nitrendipine binding site and that phospholipids play a key role in the interactions of 1,4 dihydropyridine calcium channel antagonists with the dihydropyridine binding site. 33 references, 3 figures, 1 table

  11. Secretoglobin Superfamily Protein SCGB3A2 Deficiency Potentiates Ovalbumin-Induced Allergic Pulmonary Inflammation

    Taketomo Kido

    2014-01-01

    Full Text Available Secretoglobin (SCGB 3A2, a cytokine-like secretory protein of small molecular weight, which may play a role in lung inflammation, is predominantly expressed in airway epithelial cells. In order to understand the physiological role of SCGB3A2, Scgb3a2−/− mice were generated and characterized. Scgb3a2−/− mice did not exhibit any overt phenotypes. In ovalbumin- (OVA- induced airway allergy inflammation model, Scgb3a2−/− mice in mixed background showed a decreased OVA-induced airway inflammation, while six times C57BL/6NCr backcrossed congenic Scgb3a2−/− mice showed a slight exacerbation of OVA-induced airway inflammation as compared to wild-type littermates. These results indicate that the loss of SCGB3A2 function was influenced by a modifier gene(s in mixed genetic background and suggest that SCGB3A2 has anti-inflammatory property. The results further suggest the possible use of recombinant human SCGB3A2 as an anti-inflammatory agent.

  12. Functional interaction of TRPV4 channel protein with annexin A2 in DRG.

    Ning, Liping; Wang, Chuanwei; Ding, Xinli; Zhang, Yang; Wang, Xuping; Yue, Shouwei

    2012-09-01

    Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable, non-selective cation channel that is involved in the transmission of pain signals mediated by dorsal root ganglion (DRG). Annexin A2 belongs to a class of membrane-binding proteins that plays an important role in the regulation of ion channels. Nevertheless, little is known about the interaction between them in DRG. In this paper, we evaluated the functional interaction of TRPV4 with annexin A2 in DRG. We have used immunocytochemistry and co-immunoprecipitation assays to investigate the interaction between annexin A2 and TRPV4 in DRG. The role of annexin A2 in the regulation of TRPV4 activity in DRG was further verified by measurement of intracellular free calcium concentrations ([Ca(2+)](i)) and substance P (SP) release. First, annexin A2 was showed partial co-localization with TRPV4 in DRG neurons. Then, annexin A2 and TRPV4 were co-precipitated with each other in DRG lysates. Furthermore, the downregulation of annexin A2 using specific small interfering RNA significantly inhibited Ca(2+) influx and SP mediated by TRPV4. Our results provide evidence that annexin A2 is associated with TRPV4 and regulates TRPV4-mediated Ca(2+) influx and SP release in DRG neurons. The objective of this work is to determine the influence of annexin A2 on TRPV4 in DRG neurons, which may be the basis for treatment of pain relief.

  13. Cell adhesion and EGFR activation regulate EphA2 expression in cancer

    Larsen, Alice Bjerregaard; Stockhausen, Marie-Thérése; Poulsen, Hans Skovgaard

    2010-01-01

    family kinases (SRC). Moreover, the results show that adhesion-induced EGFR activation and EphA2 expression is affected by interactions with extracellular matrix (ECM) proteins working as integrin ligands. Stimulation with the EphA2 ligand, ephrinA1 inhibited ERK phosphorylation and cancer cell viability...... largely unknown. Here we show that the expression of EphA2 in in vitro cultured cells, is restricted to cells growing adherently and that adhesion-induced EphA2 expression is dependent upon activation of the epidermal growth factor receptor (EGFR), mitogen activated protein kinase kinase (MEK) and Src...

  14. Satisfaction with a 2-day communication skills course culturally tailored for medical specialists in Qatar

    Carma L Bylund

    2017-01-01

    CONCLUSION: Physicians in Qatar positively evaluated a 2-day communication skills course, though the majority of participants did not have any previous exposure to experiential communication skills training.

  15. Teorien om alt og andre artikler om sprog og filosofi

    Artikelsamling i anledning af Peter Widells 60-års fødselsdag, med emnerne: 1. Stilistik og litteraturvidenskab  (7 artikler), 2. Leksikografi, semantik og grammatik (10 artikler), 3. Sprogfilosofi, sprogpsykologi og metaforteori (10 artikler)....

  16. O sallingmo'l

    Hansen, Inger Schoonderbeek

    2005-01-01

    Anmeldelsen har til formål kort at beskrive Jens Ejsings nyeste bog, som beskriver sallingmålets grammatik meget detaljeret. Anmeldelsen er informativ snarere end kritisk. Udgivelsesdato: december...

  17. Brug af faste vendinger

    Bergenholtz, Henning; Bjærge, Esben

    Ordbogen indelholder tekstproduktionsangivelser til ca. 17.000 idiomer, ordsprog, bevingede ord og andre faste vendinger. Det drejer sig bl.a. om angivelser til betydningen, grammatik, kollokationer, eksempler, synonymer og antonymer....

  18. Clinical and prognostic role of annexin A2 in adamantinomatous craniopharyngioma.

    Wang, Yuelong; Deng, Jiaojiao; Guo, Gang; Tong, Aiping; Peng, Xirui; Chen, Haifeng; Xu, Jianguo; Liu, Yi; You, Chao; Zhou, Liangxue

    2017-01-01

    Annexin A2 (AnxA2) is a highly conserved Ca2 + -regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis. Potential prognostic biomarkers were further validated in a large cohort of 65 AdaCPs by immunohistochemistry. The effects of AnxA2 on AdaCP cells proliferation and migration were analyzed in vitro with isolated primary AdaCP cells as well as SV40T-immortalized cells. Finally, the gefitinib sensitivity of AdaCPs with differentially expressed AnxA2 and the potential molecular mechanisms were examined by flow cytometric analysis, Real-time PCR and immunoblot assays. Proteomic analysis indicated that AnxA2 was the protein spot with the most elevated expression in AdaCP samples. Immunohistochemistry assays indicated the expression level of AnxA2 was significantly higher in recurrent AdaCPs compared with primary ones. Moreover, AnxA2 + AdaCP cells exhibited enhanced proliferation and migration ability compared with AnxA2 - AdaCP cells in vitro. Further, we show that AnxA2 + AdaCP cells exhibited elevated expression of EGFR and downstream p-AKT (S308) and p-AKT (S473), and were more sensitive to tyrosine kinase inhibitor gefitinib. Our data suggest that AnxA2 may serve as a promising biomarker for AdaCP progression, recurrence and drug susceptibility. Our data support potential clinical implications for the follow-up treatment of AdaCP patients with high AnxA2 expression.

  19. The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.

    Hillary Johnston-Cox

    Full Text Available High fat diet (HFD-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR, an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance. As the A2bAR is expressed in different tissues, here, we provide the first lead to cellular mechanism by demonstrating that the receptor's influence on tissue insulin sensitivity is mediated via its expression in macrophages. This was shown using a newly generated transgenic mouse model expressing the A2bAR gene in the macrophage lineage on an otherwise A2bAR null background. Reinstatement of macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance and tissue insulin signaling to the level of control mice. The molecular mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine monophosphate in macrophages, reducing the expression and release of inflammatory cytokines, which downregulate insulin receptor-2. Thus, our results illustrate that macrophage A2bAR signaling is needed and sufficient for relaying the protective effect of the A2bAR against HFD-induced tissue inflammation and insulin resistance in mice.

  20. Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection.

    Woodham, Andrew W; Taylor, Julia R; Jimenez, Andrew I; Skeate, Joseph G; Schmidt, Thomas; Brand, Heike E; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro. A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry. A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding. These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Enzymatic Comparisons of Aspergillus niger PhyA and Escherichia coli AppA2 Phytases

    This study was to compare three phytase activity assays and kinetics of Aspergillus niger PhyA and Escherichia coli AppA2 phytases expressed in Pichia pastoris at the observed stomach pH of 3.5. In Experiment 1, equivalent phytase activities in the crude preparations of PhyA and AppA2 were tested ...

  2. 29 CFR 779.382 - May qualify as exempt 13(a)(2) establishments.

    2010-07-01

    ... STANDARDS ACT AS APPLIED TO RETAILERS OF GOODS OR SERVICES Exemptions for Certain Retail or Service Establishments Hotels and Motels § 779.382 May qualify as exempt 13(a)(2) establishments. A hotel or motel establishment may qualify as an exempt retail or service establishment under section 13(a)(2) of the Act...

  3. 29 CFR 779.386 - Restaurants may qualify as exempt 13(a)(2) establishments.

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Restaurants may qualify as exempt 13(a)(2) establishments... Service Establishments Restaurants and Establishments Providing Food and Beverage Service § 779.386 Restaurants may qualify as exempt 13(a)(2) establishments. (a) A restaurant may qualify as an exempt retail or...

  4. Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila

    Igaki, Tatsushi; Suzuki, Yasuyuki; Tokushige, Naoko; Aonuma, Hiroka; Takahashi, Ryosuke; Miura, Masayuki

    2007-01-01

    Despite the essential role of mitochondria in a variety of mammalian cell death processes, the involvement of mitochondrial pathway in Drosophila cell death has remained unclear. To address this, we cloned and characterized DmHtrA2, a Drosophila homolog of a mitochondrial serine protease HtrA2/Omi. We show that DmHtrA2 normally resides in mitochondria and is up-regulated by UV-irradiation. Upon receipt of apoptotic stimuli, DmHtrA2 is translocated to extramitochondrial compartment; however, unlike its mammalian counterpart, the extramitochondrial DmHtrA2 does not diffuse throughout the cytosol but stays near the mitochondria. RNAi-mediated knock-down of DmHtrA2 in larvae or adult flies results in a resistance to stress stimuli. DmHtrA2 specifically cleaves Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), a cellular caspase inhibitor, and induces cell death both in vitro and in vivo as potent as other fly cell death proteins. Our observations suggest that DmHtrA2 promotes cell death through a cleavage of DIAP1 in the vicinity of mitochondria, which may represent a prototype of mitochondrial cell death pathway in evolution

  5. A2A Receptor Antagonism and Dyskinesia in Parkinson’s Disease

    Micaela Morelli

    2012-01-01

    Full Text Available Dyskinesia, a major complication of treatment of Parkinson’s disease (PD, involves two phases: induction, which is responsible for dyskinesia onset, and expression, which underlies its clinical manifestation. The unique cellular and regional distribution of adenosine A2A receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned A2A receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of A2A receptors and the effects of adenosine A2A antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant biomarker studies. We also review clinical trials of A2A antagonists as adjuncts to L-DOPA in PD patients with motor fluctuations. These studies have generally demonstrated that the addition of an A2A antagonist to a stable L-DOPA regimen reduces OFF time and mildly increases dyskinesia. However, limited clinical data suggest that the addition of an A2A antagonist along with a reduction of L-DOPA might maintain anti-Parkinsonian benefit and reduce dyskinesia. Whether A2A antagonists might reduce the development of dyskinesia has not yet been tested clinically.

  6. The Role of Protein Elongation Factor EEF1A2 in Breast Cancer

    Lee, Jonathan M

    2004-01-01

    ... overexpression can be used as a breast cancer prognostic factor. In addition, we proposed to test the idea that EEF1A2 expression modulates sensitivity to cisplatin and taxol and that EEF1A2-inactivation could be used as a treatment for breast cancer...

  7. Data of evolutionary structure change: 2QU0A-2DN1B [Confc[Archive

    Full Text Available >A 2QU0A WGKVGGNAGAYGence> HHHH...2QU0A-2DN1B 2QU0 2DN1 A B VLSAADKSNVKAAWGKVGGNAGAYGAEALERMFLSFPTT...index>0 2DN1 B 2DN1B ...ence>WGKVN--VDEVGence> GGG --HHHHH VAL CA 367 GLY CA 400 2QU0

  8. Data of evolutionary structure change: 2QU0A-2HHBD [Confc[Archive

    Full Text Available 0 A 2QU0A ence>WGKVGGNAGAYG...2QU0A-2HHBD 2QU0 2HHB A D -VLSAADKSNVKAAWGKVGGNAGAYGAEALERMFLSFPT... 0 2HHB D 2HHBD ...ence>WGKVN--VDEVGence> GGG --HHHHH ... GLU CA 293 VAL CA 366 GLY CA 390 2QU

  9. Data of evolutionary structure change: 2QU0A-2HCOB [Confc[Archive

    Full Text Available 2QU0A-2HCOB 2QU0 2HCO A B -VLSAADKSNVKAAWGKVGGNAGAYGAEALERMFLSFPT...ryChain> 2HCO B 2HCOB ence>WGKVN--VDEVG...ne> GLY CA 388 2QU0 A 2QU...0A ence>WGKVGGNAGAYGence> HHHHGGGHHHHH

  10. Data of evolutionary structure change: 2QU0A-2DXMB [Confc[Archive

    Full Text Available n>A 2QU0A WGKVGGNAGAYGence> HHH...2QU0A-2DXMB 2QU0 2DXM A B -VLSAADKSNVKAAWGKVGGNAGAYGAEALERMFLSFPT...ID> 0 2DXM B 2DXMB ...ence>WGKVN--VDEVGence> GGG --HHHHH VAL CA 716 GLY CA 753 2QU0

  11. Some aspects of rat platelet and serum phospholipase A2 activities

    Aarsman, A.J.; Roosenboom, C.F.P.; Geffen, G.E.W. van; Bosch, H. van den

    1985-01-01

    Rat platelet lysate contained appreciable phospholipase A2 activity. In agreement with literature data this enzymatic activity eluted in the void volume of a Sephadex G-100 column. When the void volume peak was chromatographed over a Matrex gel blue A column, part of the phospholipase A2 activity

  12. A2BR Adenosine Receptor Modulates Sweet Taste in Circumvallate Taste Buds

    Yang, Dan; Shultz, Nicole; Vandenbeuch, Aurelie; Ravid, Katya; Kinnamon, Sue C.; Finger, Thomas E.

    2012-01-01

    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields. PMID:22253866

  13. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    Shinji Kataoka

    Full Text Available In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3 on taste nerves as well as metabotropic (P2Y purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate, but not anterior (fungiform, palate taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  14. Data of evolutionary structure change: 1A2IA-1WADA [Confc[Archive

    Full Text Available 1A2IA-1WADA 1A2I 1WAD A A APKAPADGLKMEATK-----QPVVFNHSTHKSVKCGDCH...HPVNGKEDYRKCGTAGCHDSMDKKDKSAKGYYHVMHDKN-TKFKSCVGCHVEVAGADAAKKKDLTGCKKSKCHE -VDVPADGAKIDFIAGGEKN... 1WAD A 1WADA IDFIAG...D A 1WADA VHDAKGGAKPT A 1WADA HHDPG-DKQYA - <

  15. 40 CFR Table A-2 to Subpart A of... - Units of Measure Conversions

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Units of Measure Conversions A Table A-2 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... A-2 to Subpart A of Part 98—Units of Measure Conversions To convert from To Multiply by Kilograms...

  16. 26 CFR 31.3401(a)(2)-1 - Agricultural labor.

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Agricultural labor. 31.3401(a)(2)-1 Section 31... SOURCE Collection of Income Tax at Source § 31.3401(a)(2)-1 Agricultural labor. The term “wages” does not include remuneration for services which constitute agricultural labor as defined in section 3121(g). For...

  17. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    Kataoka, Shinji; Baquero, Arian; Yang, Dan; Shultz, Nicole; Vandenbeuch, Aurelie; Ravid, Katya; Kinnamon, Sue C; Finger, Thomas E

    2012-01-01

    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  18. Cell adhesion and EGFR activation regulate EphA2 expression in cancer

    Larsen, Alice Bjerregaard; Stockhausen, Marie-Thérése; Poulsen, Hans Skovgaard

    2010-01-01

    largely unknown. Here we show that the expression of EphA2 in in vitro cultured cells, is restricted to cells growing adherently and that adhesion-induced EphA2 expression is dependent upon activation of the epidermal growth factor receptor (EGFR), mitogen activated protein kinase kinase (MEK) and Src...... family kinases (SRC). Moreover, the results show that adhesion-induced EGFR activation and EphA2 expression is affected by interactions with extracellular matrix (ECM) proteins working as integrin ligands. Stimulation with the EphA2 ligand, ephrinA1 inhibited ERK phosphorylation and cancer cell viability....... These effects were however abolished by activation of the EGF-receptor ligand system favoring Ras/MAPK signaling and cell proliferation. Based on our results, we propose a regulatory mechanism where cell adhesion induces EGFR kinase activation and EphA2 expression; and where the effect of ephrinA1 mediated...

  19. Overexpression of adenosine A2A receptors in rats: effects on depression, locomotion and anxiety

    Joana E Coelho

    2014-06-01

    Full Text Available Adenosine A2A receptors (A2AR are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer’s disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR] and aged-matched wild-types (WT of the same strain (Sprague-Dawley were studied. The forced swimming test (FST, sucrose preference test (SPT and the open-field test (OFT were performed to evaluate behavioral despair, anhedonia, locomotion and anxiety. Tg(CaMKII-hA2AR animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR rats exhibit depressive-like behavior, hyperlocomotion and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress and Alzheimer’s disease.

  20. Overexpression of Adenosine A2A Receptors in Rats: Effects on Depression, Locomotion, and Anxiety.

    Coelho, Joana E; Alves, Pedro; Canas, Paula M; Valadas, Jorge S; Shmidt, Tatiana; Batalha, Vânia L; Ferreira, Diana G; Ribeiro, Joaquim A; Bader, Michael; Cunha, Rodrigo A; do Couto, Frederico Simões; Lopes, Luísa V

    2014-01-01

    Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease.

  1. Yeast Derived LysA2 Can Control Bacterial Contamination in Ethanol Fermentation

    Jun-Seob Kim

    2018-05-01

    Full Text Available Contamination of fuel-ethanol fermentations continues to be a significant problem for the corn and sugarcane-based ethanol industries. In particular, members of the Lactobacillaceae family are the primary bacteria of concern. Currently, antibiotics and acid washing are two major means of controlling contaminants. However, antibiotic use could lead to increased antibiotic resistance, and the acid wash step stresses the fermenting yeast and has limited effectiveness. Bacteriophage endolysins such as LysA2 are lytic enzymes with the potential to contribute as antimicrobials to the fuel ethanol industries. Our goal was to evaluate the potential of yeast-derived LysA2 as a means of controlling Lactobacillaceae contamination. LysA2 intracellularly produced by Pichia pastoris showed activity comparable to Escherichia coli produced LysA2. Lactic Acid Bacteria (LAB with the A4α peptidoglycan chemotype (L-Lys-D-Asp crosslinkage were the most sensitive to LysA2, though a few from that chemotype were insensitive. Pichia-expressed LysA2, both secreted and intracellularly produced, successfully improved ethanol productivity and yields in glucose (YPD60 and sucrose-based (sugarcane juice ethanol fermentations in the presence of a LysA2 susceptible LAB contaminant. LysA2 secreting Sacharomyces cerevisiae did not notably improve production in sugarcane juice, but it did control bacterial contamination during fermentation in YPD60. Secretion of LysA2 by the fermenting yeast, or adding it in purified form, are promising alternative tools to control LAB contamination during ethanol fermentation. Endolysins with much broader lytic spectrums than LysA2 could supplement or replace the currently used antibiotics or the acidic wash.

  2. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer

    Ferré, Sergi; Bonaventura, Jordi; Tomasi, Dardo; Navarro, Gemma; Moreno, Estefanía; Cortés, Antonio; Lluís, Carme; Casadó, Vicent; Volkow, Nora D.

    2017-01-01

    The structure constituted by a G protein coupled receptor (GPCR) homodimer and a G protein provides a main functional unit and oligomeric entities can be viewed as multiples of dimers. For GPCR heteromers, experimental evidence supports a tetrameric structure, comprised of two different homodimers, each able to signal with its preferred G protein. GPCR homomers and heteromers can act as the conduit of allosteric interactions between orthosteric ligands. The well-known agonist/agonist allosteric interaction in the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer, by which A2AR agonists decrease the affinity of D2R agonists, gave the first rationale for the use of A2AR antagonists in Parkinson’s disease. We review new pharmacological findings that can be explained in the frame of a tetrameric structure of the A2AR-D2R heteromer: first, ligand-independent allosteric modulations by the D2R that result in changes of the binding properties of A2AR ligands; second, differential modulation of the intrinsic efficacy of D2R ligands for G protein-dependent and independent signaling; third, the canonical antagonistic Gs-Gi interaction within the frame of the heteromer; and fourth, the ability of A2AR antagonists, including caffeine, to also exert the same allosteric modulations of D2R ligands than A2AR agonists, while A2AR agonists and antagonists counteract each other’s effects. These findings can have important clinical implications when evaluating the use of A2AR antagonists. They also call for the need of monitoring caffeine intake when evaluating the effect of D2R ligands, when used as therapeutic agents in neuropsychiatric disorders or as probes in imaging studies. PMID:26051403

  3. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

    Nabil G Seidah

    Full Text Available Proprotein convertase subtilisin/kexin-9 (PCSK9 enhances the degradation of hepatic low-density lipoprotein receptor (LDLR. Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2 as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/- mice revealed: i a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/- tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

  4. Ethanol disrupts chondrification of the neurocranial cartilages in medaka embryos without affecting aldehyde dehydrogenase 1A2 (Aldh1A2) promoter methylation

    Hu, Yuhui; Willett, Kristine L.; Khan, Ikhlas A.; Scheffler, Brian E.; Dasmahapatra, Asok K.

    2009-01-01

    Medaka (Oryzias latipes) embryos at different developmental stages were exposed to ethanol for 48 h, then allowed to hatch. Teratogenic effects were evaluated in hatchlings after examining chondrocranial cartilage deformities. Ethanol disrupted cartilage development in medaka in a dose and developmental stage-specific manner. Compared to controls, the linear length of the neurocranium and other cartilages were reduced in ethanol-treated groups. Moreover, the chondrification in cartilages, specifically trabeculae and polar cartilages, were inhibited by ethanol. To understand the mechanism of ethanol teratogenesis, NAD+: NADH status during embryogenesis and the methylation pattern of Aldh1A2 promoter in whole embryos and adult tissues (brain, eye, heart and liver) were analyzed. Embryos 6 dpf had higher NAD+ than embryos 0 or 2 dpf. Ethanol (200 or 400 mM) was able to reduce NAD+ content in 2 and 6 dpf embryos. However, in both cases reductions were not significantly different from the controls. Moreover, no significant difference in either NADH content or in NAD+: NADH status of the ethanol-treated embryos, with regard to controls, was observed. The promoter of Aldh1A2 contains 31 CpG dinucleotides (-705 to +154, ATG = +1); none of which were methylated. Compared to controls, embryonic ethanol exposure (100 and 400 mM) was unable to alter Aldh1A2 promoter methylation in embryos or in the tissues of adults (breeding) developmentally exposed to ethanol (300 mM, 48 hpf). From these data we conclude that ethanol teratogenesis in medaka does not induce alteration in the methylation pattern of Aldh1A2 promoter, but does change cartilage development. PMID:19651241

  5. Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

    Hui-Ling Diao

    2017-11-01

    Full Text Available The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

  6. Design and synthesis of small molecule agonists of EphA2 receptor.

    Petty, Aaron; Idippily, Nethrie; Bobba, Viharika; Geldenhuys, Werner J; Zhong, Bo; Su, Bin; Wang, Bingcheng

    2018-01-01

    Ligand-independent activation of EphA2 receptor kinase promotes cancer metastasis and invasion. Activating EphA2 receptor tyrosine kinase with small molecule agonist is a novel strategy to treat EphA2 overexpressing cancer. In this study, we performed a lead optimization of a small molecule Doxazosin that was identified as an EphA2 receptor agonist. 33 new analogs were developed and evaluated; a structure-activity relationship was summarized based on the EphA2 activation of these derivatives. Two new derivative compounds 24 and 27 showed much improved activity compared to Doxazosin. Compound 24 possesses a bulky amide moiety, and compound 27 has a dimeric structure that is very different to the parental compound. Compound 27 with a twelve-carbon linker of the dimer activated the kinase and induced receptor internalization and cell death with the best potency. Another dimer with a six-carbon linker has significantly reduced potency compared to the dimer with a longer linker, suggesting that the length of the linker is critical for the activity of the dimeric agonist. To explore the receptor binding characteristics of the new molecules, we applied a docking study to examine how the small molecule binds to the EphA2 receptor. The results reveal that compounds 24 and 27 form more hydrogen bonds to EphA2 than Doxazosin, suggesting that they may have higher binding affinity to the receptor. Published by Elsevier Masson SAS.

  7. Cyclin A2 promotes DNA repair in the brain during both development and aging.

    Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

    2016-07-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.

  8. Adenosine A2B and A3 receptor location at the mouse neuromuscular junction.

    Garcia, Neus; Priego, Mercedes; Hurtado, Erica; Obis, Teresa; Santafe, Manel M; Tomàs, Marta; Lanuza, Maria Angel; Tomàs, Josep

    2014-07-01

    To date, four subtypes of adenosine receptors have been cloned (A(1)R, A(2A)R, A(2B)R, and A(3)R). In a previous study we used confocal immunocytochemistry to identify A(1)R and A(2A)R receptors at mouse neuromuscular junctions (NMJs). The data shows that these receptors are localized differently in the three cells (muscle, nerve and glia) that configure the NMJs. A(1)R localizes in the terminal teloglial Schwann cell and nerve terminal, whereas A(2A)R localizes in the postsynaptic muscle and in the axon and nerve terminal. Here, we use Western blotting to investigate the presence of A(2B)R and A(3)R receptors in striated muscle and immunohistochemistry to localize them in the three cells of the adult neuromuscular synapse. The data show that A(2B)R and A(3)R receptors are present in the nerve terminal and muscle cells at the NMJs. Neither A(2B)R nor A(3)R receptors are localized in the Schwann cells. Thus, the four subtypes of adenosine receptors are present in the motor endings. The presence of these receptors in the neuromuscular synapse allows the receptors to be involved in the modulation of transmitter release. © 2014 Anatomical Society.

  9. Tackling amyloidogenesis in Alzheimer's disease with A2V variants of Amyloid-β.

    Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Morbin, Michela; Moda, Fabio; Colombo, Laura; Rossi, Alessandro; Cagnotto, Alfredo; Virgilio, Tommaso; Palamara, Luisa; Ruggerone, Margherita; Giaccone, Giorgio; Campagnani, Ilaria; Costanza, Massimo; Pedotti, Rosetta; Salvalaglio, Matteo; Salmona, Mario; Tagliavini, Fabrizio

    2016-02-11

    We developed a novel therapeutic strategy for Alzheimer's disease (AD) exploiting the properties of a natural variant of Amyloid-β (Aβ) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Aβ1-6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Aβ1-6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Aβ toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Aβ1-6A2VTAT(D) inhibits Aβ aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AβA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Aβ1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Aβ production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics.

  10. Tackling amyloidogenesis in Alzheimer’s disease with A2V variants of Amyloid-β

    Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Morbin, Michela; Moda, Fabio; Colombo, Laura; Rossi, Alessandro; Cagnotto, Alfredo; Virgilio, Tommaso; Palamara, Luisa; Ruggerone, Margherita; Giaccone, Giorgio; Campagnani, Ilaria; Costanza, Massimo; Pedotti, Rosetta; Salvalaglio, Matteo; Salmona, Mario; Tagliavini, Fabrizio

    2016-01-01

    We developed a novel therapeutic strategy for Alzheimer’s disease (AD) exploiting the properties of a natural variant of Amyloid-β (Aβ) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Aβ1-6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Aβ1-6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Aβ toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Aβ1-6A2VTAT(D) inhibits Aβ aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AβA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Aβ1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Aβ production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics. PMID:26864599

  11. Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice.

    Adén, Ulrika; Halldner, Linda; Lagercrantz, Hugo; Dalmau, Ishar; Ledent, Catherine; Fredholm, Bertil B

    2003-03-01

    Cerebral hypoxic ischemia (HI) is an important cause of brain injury in the newborn infant. Adenosine is believed to protect against HI brain damage. However, the roles of the different adenosine receptors are unclear, particularly in young animals. We examined the role of adenosine A2A receptors (A2AR) using 7-day-old A2A knockout (A2AR(-/-)) mice in a model of HI. HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated with the use of histopathological scoring and measurements of residual brain areas at 5 days, 3 weeks, and 3 months after HI. Behavioral evaluation of brain injury by locomotor activity, rotarod, and beam-walking test was made 3 weeks and 3 months after HI. Cortical cerebral blood flow, assessed by laser-Doppler flowmetry, and rectal temperature were measured during HI. Reduction in cortical cerebral blood flow during HI and rectal temperature did not differ between wild-type (A2AR(+/+)) and knockout mice. In the A2AR(-/-) animals, brain injury was aggravated compared with wild-type mice. The A2AR(-/-) mice subjected to HI displayed increased forward locomotion and impaired rotarod performance in adulthood compared with A2AR(+/+) mice subjected to HI, whereas beam-walking performance was similarly defective in both groups. These results suggest that, in contrast to the situation in adult animals, A2AR play an important protective role in neonatal HI brain injury.

  12. Behavioral control by striatal adenosine A2A -dopamine D2 receptor heteromers.

    Taura, J; Valle-León, M; Sahlholm, K; Watanabe, M; Van Craenenbroeck, K; Fernández-Dueñas, V; Ferré, S; Ciruela, F

    2018-04-01

    G protein-coupled receptors (GPCR) exhibit the ability to form receptor complexes that include molecularly different GPCR (ie, GPCR heteromers), which endow them with singular functional and pharmacological characteristics. The relative expression of GPCR heteromers remains a matter of intense debate. Recent studies support that adenosine A 2A receptors (A 2A R) and dopamine D 2 receptors (D 2 R) predominantly form A 2A R-D 2 R heteromers in the striatum. The aim of the present study was evaluating the behavioral effects of pharmacological manipulation and genetic blockade of A 2A R and D 2 R within the frame of such a predominant striatal heteromeric population. First, in order to avoid possible strain-related differences, a new D 2 R-deficient mouse with the same genetic background (CD-1) than the A 2A R knock-out mouse was generated. Locomotor activity, pre-pulse inhibition (PPI) and drug-induced catalepsy were then evaluated in wild-type, A 2A R and D 2 R knock-out mice, with and without the concomitant administration of either the D 2 R agonist sumanirole or the A 2A R antagonist SCH442416. SCH442416-mediated locomotor effects were demonstrated to be dependent on D 2 R signaling. Similarly, a significant dependence on A 2A R signaling was observed for PPI and for haloperidol-induced catalepsy. The results could be explained by the existence of one main population of striatal postsynaptic A 2A R-D 2 R heteromers, which may constitute a relevant target for the treatment of Parkinson's disease and other neuropsychiatric disorders. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  13. Identification of the A2 adenosine receptor binding subunit by photoaffinity crosslinking

    Barrington, W.W.; Jacobson, K.A.; Hutchison, A.J.; Williams, M.; Stiles, G.L.

    1989-01-01

    A high-affinity iodinated agonist radioligand for the A2 adenosine receptor has been synthesized to facilitate studies of the A2 adenosine receptor binding subunit. The radioligand 125I-labeled PAPA-APEC (125I-labeled 2-[4-(2-[2-[(4- aminophenyl)methylcarbonylamino]ethylaminocarbonyl]- ethyl)phenyl]ethylamino-5'-N-ethylcarboxamidoadenosine) was synthesized and found to bind to the A2 adenosine receptor in bovine striatal membranes with high affinity (Kd = 1.5 nM) and A2 receptor selectivity. Competitive binding studies reveal the appropriate A2 receptor pharmacologic potency order with 5'-N-ethylcarboxamidoadenosine (NECA) greater than (-)-N6-[(R)-1-methyl- 2-phenylethyl]adenosine (R-PIA) greater than (+)-N6-[(S)-1-methyl-2- phenylethyl]adenosine (S-PIA). Adenylate cyclase assays, in human platelet membranes, demonstrate a dose-dependent stimulation of cAMP production. PAPA-APEC (1 microM) produces a 43% increase in cAMP production, which is essentially the same degree of increase produced by 5'-N- ethylcarboxamidoadenosine (the prototypic A2 receptor agonist). These findings combined with the observed guanine nucleotide-mediated decrease in binding suggest that PAPA-APEC is a full A2 agonist. The A2 receptor binding subunit was identified by photoaffinity-crosslinking studies using 125I-labeled PAPA-APEC and the heterobifunctional crosslinking agent N-succinimidyl 6-(4'-azido-2'-nitrophenylamino)hexanoate (SANPAH). After covalent incorporation, a single specifically radiolabeled protein with an apparent molecular mass of 45 kDa was observed on NaDodSO4/PAGE/autoradiography. Incorporation of 125I-labeled PAPA-APEC into this polypeptide is blocked by agonists and antagonists with the expected potency for A2 receptors and is decreased in the presence of 10(-4) M guanosine 5'-[beta, gamma-imido]triphosphate

  14. Evidence that the EphA2 receptor exacerbates ischemic brain injury.

    John Thundyil

    Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

  15. Regulatory effects of adenosine A2A receptors on psychomotor ability and mood behavior of mice

    Li JIANG

    2011-07-01

    Full Text Available Objective To explore the effects of gene knock-out,agonist or inhibitor of adenosine A2A receptor on the locomotor activity,and anxiety-or depression-like behavior of mice.Methods Male C57BL/6 mice,comprising those underwent gene knock-out of adenosine A2A receptor(A2AKO and their wild-type(WT littermates,were assigned into A2AKO group and WT group.Another batch of male C57BL/6,specific-pathogen-free(SPF mice,were assigned into SCH58261 group,CGS21680 group and control group.Mice of aforesaid 3 groups were transperitoneally administered with SCH58261,a specific inhibitor of adenosine A2A receptor at a dose of 2mg/kg,CGS21680,a specific agonist of adenosine A2A receptor at a dose of 0.5mg/kg,and vehicle(0.25ml,comprising DMSO and saline,respectively.Ten minutes after injection,mice of the 3 groups underwent open-field test,elevated plus-maze test and forced swimming test to detect their locomotor activity,anxiety-and depression-like behavior.Results a Compared with WT group,the total movement distance decreased(P 0.05.b Compared with control group,the total movement distance decreased and the stay time in the peripheral area increased significantly in the open field test(P 0.05.Conclusions The agonist of adenosine A2A receptor may depress the spontaneous motility and exploratory behavior,and exacerbate the anxiety and depression,and it simulates the effect induced by knock-out of A2A receptor gene,but it is opposite to the effect induced by A2A receptor inhibitor.

  16. Annexin A2 Mediates the Localization of Measles Virus Matrix Protein at the Plasma Membrane.

    Koga, Ritsuko; Kubota, Marie; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji

    2018-02-28

    Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca 2+ -dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca 2+ -binding protein S100A10. Measles virus (MV), a member of the family Paramyxoviridae , is an enveloped virus with a nonsegmented negative strand RNA genome. Knockdown of AnxA2 greatly reduced MV growth in cells, without affecting its entry and viral RNA production. In MV-infected, AnxA2-knockdown cells, the expression level of the matrix (M) protein, but not other viral proteins, was reduced compared with that in control cells, and the distribution of the M protein at the plasma membrane was decreased. The M protein lines the inner surface of the envelope and plays an important role in virus assembly by connecting the nucleocapsid to the envelope proteins. The M protein bound to AnxA2 independently of AnxA2's phosphorylation or its association with S100A10, and was co-localized with AnxA2 within cells. Truncation of the N-terminal 10 amino acid residues, but not the N-terminal 5 residues, compromised the ability of the M protein to interact with AnxA2 and localize at the plasma membrane. These results indicate that AnxA2 mediates the localization of the MV M protein at the plasma membrane by interacting with its N-terminal region (especially residues at positions 6-10), thereby aiding in MV assembly. IMPORTANCE Measles virus (MV) is an important human pathogen, still claiming ∼ 100,000 lives per year despite the presence of effective vaccines, and causes occasional outbreaks even in developed countries. Replication of viruses largely relies on the functions of host cells. Our study revealed that the reduction of the host protein annexin A2 compromises the replication of

  17. A rapid phospholipase A2 bioassay using 14C-oleate-labelled E. coli bacterias.

    Meyer, T; von Wichert, P; Weins, D

    1989-02-01

    Two methods of phospholipase A2 determination using 14C-labelled E. coli bacterias as substrate were compared. One method works with a filter membrane for separation of cleaved 14C-oleate from remaining phospholipids, the other uses the well-known thin-layer chromatography for lipid analysis. Some features of human serum phospholipase A2 regarding pH and Ca2+ dependency were investigated. Possible sources of errors were discussed. It was shown that either method can differentiate between normal and pathologically elevated phospholipase A2 levels, but that the filter method is superior in terms of sensitivity and workload.

  18. Rare A2ML1 variants confer susceptibility to otitis media

    Santos-Cortez, Regie Lyn P.; Chiong, Charlotte M.; Reyes-Quintos, Ma. Rina T.; Tantoco, Ma. Leah C.; Wang, Xin; Acharya, Anushree; Abbe, Izoduwa; Giese, Arnaud P.; Smith, Joshua D.; Allen, E. Kaitlynn; Li, Biao; Cutiongco-de la Paz, Eva Maria; Garcia, Marieflor Cristy; Llanes, Erasmo Gonzalo D.V.; Labra, Patrick John; Gloria-Cruz, Teresa Luisa I.; Chan, Abner L.; Wang, Gao T.; Daly, Kathleen A.; Shendure, Jay; Bamshad, Michael J.; Nickerson, Deborah A.; Patel, Janak A.; Riazuddin, Saima; Sale, Michele M.; Chonmaitree, Tasnee; Ahmed, Zubair M.; Abes, Generoso T.; Leal, Suzanne M.

    2015-01-01

    A duplication variant within middle-ear-specific gene A2ML1 co-segregates with otitis media in an indigenous Filipino pedigree (LOD score=7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by three otitis-prone European- and Hispanic-American children, but is absent in non-otitis-prone children and >62,000 next-generation sequences. Seven additional A2ML1 variants were identified in six otitis-prone children. Collectively our studies support a role for A2ML1 in the pathophysiology of otitis media. PMID:26121085

  19. Ab-Initio Simulation of a/2 Screw Dislocations Gamma-TiAl

    Woodward, C; Rao, S. I

    2004-01-01

    ...The equilibrium core structure of an isolated a/2screw dislocations is calculated using a first-principles pseudopotential-planewave method within the Local Density Approximation of Density Functional Theory...

  20. Adding A2K Principles to the UN Guidelines for Consumer Protection

    Adding A2K Principles to the UN Guidelines for Consumer Protection ... of standards for good practices in consumer protection, particularly for developing countries. ... IWRA/IDRC webinar on climate change and adaptive water management.

  1. Data of evolutionary structure change: 1LA6A-2ZLWD [Confc[Archive

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  2. Data of evolutionary structure change: 1A01A-2ZLWD [Confc[Archive

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  3. Data of evolutionary structure change: 1BZ0A-2ZLWD [Confc[Archive

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  4. Data of evolutionary structure change: 1A00A-2ZLWD [Confc[Archive

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  5. Data of evolutionary structure change: 1C40A-2ZLWD [Confc[Archive

    Full Text Available 1C40A-2ZLWD 1C40 2ZLW A D -VLSAADKTNVKGVFSKISGHAEEYGAETLERMFTAYPQ...R VQLSGEEKAAVLALWDKV--NEEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL...dex> 2ZLW D 2ZLWD LWD

  6. EphA2 is a functional receptor for the growth factor progranulin.

    Neill, Thomas; Buraschi, Simone; Goyal, Atul; Sharpe, Catherine; Natkanski, Elizabeth; Schaefer, Liliana; Morrione, Andrea; Iozzo, Renato V

    2016-12-05

    Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases. © 2016 Neill et al.

  7. Wave failure at strong coupling in intracellular C a2 + signaling system with clustered channels

    Li, Xiang; Wu, Yuning; Gao, Xuejuan; Cai, Meichun; Shuai, Jianwei

    2018-01-01

    As an important intracellular signal, C a2 + ions control diverse cellular functions. In this paper, we discuss the C a2 + signaling with a two-dimensional model in which the inositol 1,4,5-trisphosphate (I P3 ) receptor channels are distributed in clusters on the endoplasmic reticulum membrane. The wave failure at large C a2 + diffusion coupling is discussed in detail in the model. We show that with varying model parameters the wave failure is a robust behavior with either deterministic or stochastic channel dynamics. We suggest that the wave failure should be a general behavior in inhomogeneous diffusing systems with clustered excitable regions and may occur in biological C a2 + signaling systems.

  8. Prediction of new ground-state crystal structure of T a2O5

    Yang, Yong; Kawazoe, Yoshiyuki

    2018-03-01

    Tantalum pentoxide (T a2O5 ) is a wide-gap semiconductor which has important technological applications. Despite the enormous efforts from both experimental and theoretical studies, the ground-state crystal structure of T a2O5 is not yet uniquely determined. Based on first-principles calculations in combination with evolutionary algorithm, we identify a triclinic phase of T a2O5 , which is energetically much more stable than any phases or structural models reported previously. Characterization of the static and dynamical properties of the phase reveals the common features shared with previous metastable phases of T a2O5 . In particular, we show that the d spacing of ˜3.8 Å found in the x-ray diffraction patterns of many previous experimental works is actually the radius of the second Ta-Ta coordination shell as defined by radial distribution functions.

  9. Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma

    Zhang, Hai-Jian; Yao, Deng-Fu; Yao, Min; Huang, Hua; Wu, Wei; Yan, Mei-Juan; Yan, Xiao-Di; Chen, Jie

    2012-01-01

    AIM: To investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

  10. Pervasive Technologies: Access to Knowledge (A2K)in the ...

    Pervasive networked communication technologies are transforming the way in ... These Third World mass-marketing commercial technology players have been ... The A2K movement advocates a commons approach to cyberspace, media ...

  11. Procurement of Gun Mounts for the M1A2 Tank

    1997-01-01

    .... The inquiry resulted from constituent allegations that the Program Executive Officer for Armored Systems Modernization improperly communicated Government information on Army procurement of gun mounts for the MlA2 tank...

  12. Striatal pre- and postsynaptic profile of adenosine A(2A receptor antagonists.

    Marco Orru

    2011-01-01

    Full Text Available Striatal adenosine A(2A receptors (A(2ARs are highly expressed in medium spiny neurons (MSNs of the indirect efferent pathway, where they heteromerize with dopamine D(2 receptors (D(2Rs. A(2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1 receptors (A(1Rs. It has been hypothesized that postsynaptic A(2AR antagonists should be useful in Parkinson's disease, while presynaptic A(2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A(2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261 showed no clear preference. Radioligand-binding experiments were performed in cells expressing A(2AR-D(2R and A(1R-A(2AR heteromers to determine possible differences in the affinity of these compounds for different A(2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A(2AR when co-expressed with D(2R than with A(1R. KW-6002 showed the best relative affinity for A(2AR co-expressed with D(2R than co-expressed with A(1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile

  13. 26 CFR 31.3121(a)-2 - Wages; when paid and received.

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Wages; when paid and received. 31.3121(a)-2... § 31.3121(a)-2 Wages; when paid and received. (a) In general, wages are received by an employee at the time that they are paid by the employer to the employee. Wages are paid by an employer at the time that...

  14. Ganglion of the Flexor Tendon Sheath at the A2 Pulley - Case Report

    P Gunaseelan

    2015-03-01

    Full Text Available There are few reported cases of flexor tendon sheath ganglion arising from the A2 pulley. We report a case of a flexor tendon sheath ganglion in a 17-year old female who presented with pain, triggering and a swelling at the base of her right ring finger. During the excision biopsy, a ganglion measuring 0.5×0.8×0.4 cm in size was removed from the A2 pulley area.

  15. Progranulin and the receptor tyrosine kinase EphA2, partners in crime?

    Chitramuthu, Babykumari; Bateman, Andrew

    2016-01-01

    Progranulin is a secreted protein with roles in tumorigenesis, inflammation, and neurobiology, but its signaling receptors have remained unclear. In this issue, Neill et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201603079) identify the tyrosine kinase EphA2 as a strong candidate for such a receptor, providing insight into progranulin and EphA2 signaling. PMID:27903608

  16. Hexachlorobenzene stimulates uroporphyria in low affinity AHR mice without increasing CYP1A2

    Gorman, Nadia; Trask, Heidi S.; Robinson, Susan W.; Sinclair, Jacqueline F.; Gerhard, Glenn S.; Smith, Andrew G.; Sinclair, Peter R.

    2007-01-01

    Hexachlorobenzene (HCB), a weak ligand of the aryl hydrocarbon receptor (AHR), causes hepatic uroporphyrin (URO) accumulation (uroporphyria) in humans and animals. CYP1A2 has been shown to be necessary in the development of uroporphyria in mice. Using mice expressing the low affinity form of the AH receptor (AHRd), we investigated whether the enhancement of uroporphyria by HCB involves an obligatory increase in CYP1A2 as measured by specific enzyme assays and immunoblotting. We compared the ability of HCB, in combination with iron dextran and the porphyrin precursor, 5-aminolevulinate (ALA), to cause uroporphyria in a strain of mice (C57BL/6) which expresses the high affinity form of the receptor (AHRb 1 ), with three strains of mice (SWR and two 129 sublines) expressing the low affinity AHRd. In C57BL/6 mice, HCB-enhanced uroporphyria was associated with a doubling of CYP1A2. HCB treatment produced uroporphyria in iron-loaded mice expressing AHRd, even though there was little or no increase in CYP1A2. Cyp1a2(-/-) mice in a 129 background were completely resistant to HCB-induced uroporphyria, and female Hfe(-/-) 129 mice, in which the levels of hepatic CYP1A2 were half of those of the male levels, responded poorly. The effect of exogenous iron, administered in the form of iron dextran, on HCB enhancement of uroporphryia could be replicated utilizing the endogenous hepatic iron accumulated in 129 Hfe(-/-) mice. In conclusion, some minimal basal expression of CYP1A2 is essential for HCB-mediated enhancement of uroporphyria, but increases in CYP1A2 above that level are not essential

  17. Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen; Hansen, Johnni; Lassen, Christina F; Bertram, Lars; Greene, Naomi; Sinsheimer, Janet S; Ritz, Beate

    2016-01-01

    Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases. © 2017 S. Karger AG, Basel.

  18. SCGB3A2 Inhibits Acrolein-Induced Apoptosis through Decreased p53 Phosphorylation.

    Kurotani, Reiko; Shima, Reika; Miyano, Yuki; Sakahara, Satoshi; Matsumoto, Yoshie; Shibata, Yoko; Abe, Hiroyuki; Kimura, Shioko

    2015-04-28

    Chronic obstructive pulmonary disease (COPD), a major global health problem with increasing morbidity and mortality rates, is anticipated to become the third leading cause of death worldwide by 2020. COPD arises from exposure to cigarette smoke. Acrolein, which is contained in cigarette smoke, is the most important risk factor for COPD. It causes lung injury through altering apoptosis and causes inflammation by augmenting p53 phosphorylation and producing reactive oxygen species (ROS). Secretoglobin (SCGB) 3A2, a secretory protein predominantly present in the epithelial cells of the lungs and trachea, is a cytokine-like small molecule having anti-inflammatory, antifibrotic, and growth factor activities. In this study, the effect of SCGB3A2 on acrolein-related apoptosis was investigated using the mouse fibroblast cell line MLg as the first step in determining the possible therapeutic value of SCGB3A2 in COPD. Acrolein increased the production of ROS and phosphorylation of p53 and induced apoptosis in MLg cells. While the extent of ROS production induced by acrolein was not affected by SCGB3A2, p53 phosphorylation was significantly decreased by SCGB3A2. These results demonstrate that SCGB3A2 inhibited acrolein-induced apoptosis through decreased p53 phosphorylation, not altered ROS levels.

  19. SCGB3A2 Inhibits Acrolein-Induced Apoptosis through Decreased p53 Phosphorylation

    Kurotani, Reiko; Shima, Reika; Miyano, Yuki; Sakahara, Satoshi; Matsumoto, Yoshie; Shibata, Yoko; Abe, Hiroyuki; Kimura, Shioko

    2015-01-01

    Chronic obstructive pulmonary disease (COPD), a major global health problem with increasing morbidity and mortality rates, is anticipated to become the third leading cause of death worldwide by 2020. COPD arises from exposure to cigarette smoke. Acrolein, which is contained in cigarette smoke, is the most important risk factor for COPD. It causes lung injury through altering apoptosis and causes inflammation by augmenting p53 phosphorylation and producing reactive oxygen species (ROS). Secretoglobin (SCGB) 3A2, a secretory protein predominantly present in the epithelial cells of the lungs and trachea, is a cytokine-like small molecule having anti-inflammatory, antifibrotic, and growth factor activities. In this study, the effect of SCGB3A2 on acrolein-related apoptosis was investigated using the mouse fibroblast cell line MLg as the first step in determining the possible therapeutic value of SCGB3A2 in COPD. Acrolein increased the production of ROS and phosphorylation of p53 and induced apoptosis in MLg cells. While the extent of ROS production induced by acrolein was not affected by SCGB3A2, p53 phosphorylation was significantly decreased by SCGB3A2. These results demonstrate that SCGB3A2 inhibited acrolein-induced apoptosis through decreased p53 phosphorylation, not altered ROS levels

  20. Informative gene selection using Adaptive Analytic Hierarchy Process (A2HP

    Abhishek Bhola

    2017-12-01

    Full Text Available Gene expression dataset derived from microarray experiments are marked by large number of genes, which contains the gene expression values at different sample conditions/time-points. Selection of informative genes from these large datasets is an issue of major concern for various researchers and biologists. In this study, we propose a gene selection and dimensionality reduction method called Adaptive Analytic Hierarchy Process (A2HP. Traditional analytic hierarchy process is a multiple-criteria based decision analysis method whose result depends upon the expert knowledge or decision makers. It is mainly used to solve the decision problems in different fields. On the other hand, A2HP is a fused method that combines the outcomes of five individual gene selection ranking methods t-test, chi-square variance test, z-test, wilcoxon test and signal-to-noise ratio (SNR. At first, the preprocessing of gene expression dataset is done and then the reduced number of genes obtained, will be fed as input for A2HP. A2HP utilizes both quantitative and qualitative factors to select the informative genes. Results demonstrate that A2HP selects efficient number of genes as compared to the individual gene selection methods. The percentage of deduction in number of genes and time complexity are taken as the performance measure for the proposed method. And it is shown that A2HP outperforms individual gene selection methods.

  1. Functional interaction between Cerebratulus lacteus cytolysin A-III and phospholipase A2

    Liu, J.; Blumenthal, K.M.

    1988-01-01

    A study on the interaction between bee venom phospholipase A 2 and Cerebratulus lacteus cytolysin A-III, a major hemolysin secreted by this organism has been carried out. The hemolytic activity of A-III in phosphate-buffered saline is increased 5-fold in the presence of phospholipase A 2 from bee venom. Dansylphosphatidylethanolamine (DPE) labeled, phosphatidylcholine-containing liposomes and human erythrocyte membranes were employed to study the interaction between these two proteins. In DPE-liposomes, A-III alone had no effect on DPE fluorescence nor did it enhance either the phospholipase A 2 -dependent fluorescence increase or blue shift in emission maximum, indicating that the cytolysis is not a major phospholipase A 2 -activator. However, when DPE was incorporated into erythrocyte membranes, A-III alone induced a 40% fluorescence increase and a 5 nm blue shift, implying a transient activation of an endogenous phospholipase A 2 . Further studies using synthetic lysophosphatidylcholine and free fatty acids demonstrated that the hemolytic activity of A-III is potentiated by free fatty acids, a product of phospholipid degradation catalyzed by phospholipase A 2 . Subsequent analysis of this phenomenon by gel filtration chromatography, analytical ultracentrifugation, chemical cross-linking, and measurement of [ 14 C]oleic acid binding by the cytolysin demonstrated that binding of oleic acid to A-III causes aggregation of the toxin molecules to a tetrameric form which has a higher α-helix content and a greater activity than the monomer

  2. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  3. Recognition of acidic phospholipase A2 activity in plasma membranes of resident peritoneal macrophages

    Shibata, Y.; Abiko, Y.; Ohno, H.; Araki, T.; Takiguchi, H.

    1988-01-01

    Phospholipase (PLase) activities in the plasma membrane of guinea pig peritoneal macrophages were studied, as these enzymes having such activity may be candidates for the release of arachidonic acid (AA) from phosphatidylcholine (PC). An AA release system operating at acidic pH was identified in the macrophage plasma membrane and characterized. This membrane-bound acidic PLase A 2 had an optimum pH at 4.5, and enzyme activation was observed in Ca ++ -free medium; but the maximum activity was found at 0.5 mM Ca ++ concentration. The Km value for PC of acidic PLase A 2 was 4.2 μM, and a Michaelis-Menten relationship was evident. Calcium might act as a cofactor at some intermediate step during the activation of acidic PLase A 2 in light of the uncompetitive manner of Ca ++ action. Furthermore, the release of [ 3 H]-AA from preradiolabelled macrophage plasma membranes occurred with the addition of Ca ++ at pH 4.5. These data suggest that the acid PLase A 2 is a component of the plasma membrane and is not due to lysosomal contamination since membrane-bound acidic PLase A 2 properties are opposite to those found for lysosomal PLase A 2

  4. Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2

    Joshua P. Klopper

    2010-01-01

    Full Text Available Nuclear hormone receptors, including RXR and PPARγ, represent novel therapeutic targets in melanoma. We have previously shown that the DRO subline of the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD treatment in vitro and in vivo. We performed microarray analysis of A375(DRO after TZD and combination rexinoid/TZD treatment in which the calcium binding protein S100A2 had increased expression after rexinoid or TZD treatment and a synergistic increase to combination treatment. Increased S100A2 expression is dependent on an intact PPARγ receptor, but it is not sufficient to mediate the antiproliferative effects of rexinoid/TZD treatment. Over expression of S100A2 enhanced the effect of rexinoid and TZD treatment while inhibition of S100A2 expression attenuated the response to rexinoid/TZD treatment, suggesting that S100A2 is necessary for optimal response to RXR and PPARγ activation by respective ligands. In summary, we have identified potential downstream mediators of rexinoid and TZD treatment in a poorly differentiated melanoma and found that alterations in S100A2 expression affect RXR and PPARγ signaling in A375(DRO cells. These studies provide insight into potential mechanisms of tumor response or resistance to these novel therapies.

  5. Differential effects of phorbol 12-myristate 13-acetate and diacylglycerols on thromboxane A2-independent phospholipase A2 activation in collage-stimulated human platelets.

    Reddy, S; Rao, G H; Murthy, M

    1994-04-01

    We investigated the priming effects of protein kinase C (PKC) activators such as phorbol 12-myristate 13-acetate (PMA), 1,2-DiC8 and OAG, and 1,3-DiC8 (a poor activator of PKC) on thromboxane A2 (TxA2)-independent phospholipase A2 (PLA2) activation in human platelets using collagen and A23187 as agonists. We measured PLA2 activation in collagen-stimulated platelets in the presence of BW755C, which abolished TxA2 synthesis, rise in cytosolic Ca2+, and aggregation. In the presence of PMA (50 nM), the amount of arachidonic acid (AA) released in platelets stimulated with collagen and A23187 represented 300% (13.85 nmol versus 4.5 nmol) and 400% (28 nmol versus 7 nmol) of controls (without PMA), respectively, while 1,2-DiC8, OAG, and 1,3-DiC8 increased TxA2-independent AA release by 50% in A23187-stimulated platelets and had no effect on the release of AA in collagen-stimulated platelets. Interestingly, 1,3-DiC8, which is a poor activator of PKC, was as effective as the other two DAGs (OAG and 1,2-DiC8) in priming TxA2-independent PLA2 activation, but was less effective than PMA in platelets stimulated with A23187. These results suggest that the TXA2-dependent IP3-mediated rise in cytosolic Ca2+ may not be obligatory for priming PLA2 activation in the presence of PMA in collagen-stimulated platelets. In contrast, 1,2-DiC8, OAG, and 1,3-DiC8 likely enhanced PLA2 activation via intracellular Ca2+ as they selectively affect this enzyme only in A23187-stimulated platelets. We also observed a significant increase in both saturated (palmitic and stearic acids) and unsaturated fatty acids (oleic and linoleic acids) in platelets stimulated by collagen or A23187 in the presence of PMA (50 nM), but not in the presence of DAGs. These findings imply that PMA may also affect the activation of DAG/MAG lipases, PLA1, or nonspecific PLA2. Since both 1,2-DiC8 and OAG exert no significant effect on the release of these fatty acids, the effects observed with PMA on DAG lipase/PLA1 may not

  6. High pressure studies of A2Mo3O12 negative thermal expansion materials (A2=Al2, Fe2, FeAl, AlGa)

    Young, Lindsay; Gadient, Jennifer; Gao, Xiaodong; Lind, Cora

    2016-01-01

    High pressure powder X-ray diffraction studies of several A 2 Mo 3 O 12 materials (A 2 =Al 2 , Fe 2 , FeAl, and AlGa) were conducted up to 6–7 GPa. All materials adopted a monoclinic structure under ambient conditions, and displayed similar phase transition behavior upon compression. The initial isotropic compressibility first became anisotropic, followed by a small but distinct drop in cell volume. These patterns could be described by a distorted variant of the ambient pressure polymorph. At higher pressures, a distinct high pressure phase formed. Indexing results confirmed that all materials adopted the same high pressure phase. All changes were reversible on decompression, although some hysteresis was observed. The similarity of the high pressure cells to previously reported Ga 2 Mo 3 O 12 suggested that this material undergoes the same sequence of transitions as all materials investigated in this paper. It was found that the transition pressures for all phase changes increased with decreasing radius of the A-site cations. - Graphical abstract: Overlay of variable pressure X-ray diffraction data of Al 2 Mo 3 O 12 collected in a diamond anvil cell. Both subtle and discontinuous phase transitions are clearly observed. - Highlights: • The high pressure behavior of A 2 Mo 3 O 12 (A=Al, Fe, (AlGa), (AlFe)) was studied. • All compounds undergo the same sequence of pressure-induced phase transitions. • The phase transition pressures correlate with the average size of the A-site cation. • All transitions were reversible with hysteresis. • Previously studied Ga 2 Mo 3 O 12 undergoes the same sequence of transitions.

  7. Human Adenosine A2A Receptor: Molecular Mechanism of Ligand Binding and Activation

    Byron Carpenter

    2017-12-01

    Full Text Available Adenosine receptors (ARs comprise the P1 class of purinergic receptors and belong to the largest family of integral membrane proteins in the human genome, the G protein-coupled receptors (GPCRs. ARs are classified into four subtypes, A1, A2A, A2B, and A3, which are all activated by extracellular adenosine, and play central roles in a broad range of physiological processes, including sleep regulation, angiogenesis and modulation of the immune system. ARs are potential therapeutic targets in a variety of pathophysiological conditions, including sleep disorders, cancer, and dementia, which has made them important targets for structural biology. Over a decade of research and innovation has culminated with the publication of more than 30 crystal structures of the human adenosine A2A receptor (A2AR, making it one of the best structurally characterized GPCRs at the atomic level. In this review we analyze the structural data reported for A2AR that described for the first time the binding of mode of antagonists, including newly developed drug candidates, synthetic and endogenous agonists, sodium ions and an engineered G protein. These structures have revealed the key conformational changes induced upon agonist and G protein binding that are central to signal transduction by A2AR, and have highlighted both similarities and differences in the activation mechanism of this receptor compared to other class A GPCRs. Finally, comparison of A2AR with the recently solved structures of A1R has provided the first structural insight into the molecular determinants of ligand binding specificity in different AR subtypes.

  8. Meteorology Research in DOE's Atmosphere to Electrons (A2e) Program

    Cline, J.; Haupt, S. E.; Shaw, W. J.

    2017-12-01

    DOE's Atmosphere to electrons (A2e) program is performing cutting edge research to allow optimization of wind plants. This talk will summarize the atmospheric science portion of A2e, with an overview of recent and planned observation and modeling projects designed to bridge the terra incognita between the mesoscale and the microscales that affect wind plants. Introduction A2e is a major focus of the Wind Energy Technologies Office (WETO) within the Office of Energy Efficiency & Renewable Energy (EERE) at the DOE. The overall objective of A2e is to optimize wind power production and integrates improved knowledge of atmospheric inflow (fuel), turbine and plant aerodynamics, and control systems. The atmospheric component of the work addresses both the need for improved forecasting of hub-height winds and the need for improved turbulence characterization for turbine inflows under realistic atmospheric conditions and terrain. Several projects will be discussed to address observations of meteorological variables in regions not typically observed. The modelling needs are addressed through major multi-institutional integrated studies comprising both theoretical and numerical advances to improve models and field observations for physical insight. Model improvements are subjected to formal verification and validation, and numerical and observational data are archived and disseminated to the public through the A2e Data Archive and Portal (DAP; http://a2e.energy.gov). The overall outcome of this work will be increased annual energy production from wind plants and improved turbine lifetimes through a better understanding of atmospheric loading. We will briefly describe major components of the atmospheric part of the A2e strategy and work being done and planned.

  9. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

    Mirjam Frischknecht

    Full Text Available We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2. It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA and collagen alpha-2(XI chain gene (COL11A2, respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

  10. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

    Frischknecht, Mirjam; Niehof-Oellers, Helena; Jagannathan, Vidhya; Owczarek-Lipska, Marta; Drögemüller, Cord; Dietschi, Elisabeth; Dolf, Gaudenz; Tellhelm, Bernd; Lang, Johann; Tiira, Katriina; Lohi, Hannes; Leeb, Tosso

    2013-01-01

    We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

  11. Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

    Hsu, Sandy Chan; Sears, Renee L.; Lemos, Roberta R.; Quintáns, Beatriz; Huang, Alden; Spiteri, Elizabeth; Nevarez, Lisette; Mamah, Catherine; Zatz, Mayana; Pierce, Kerrie D.; Fullerton, Janice M.; Adair, John C.; Berner, Jon E.; Bower, Matthew; Brodaty, Henry; Carmona, Olga; Dobricić, Valerija; Fogel, Brent L.; García-Estevez, Daniel; Goldman, Jill; Goudreau, John L.; Hopfer, Suellen; Janković, Milena; Jaumà, Serge; Jen, Joanna C.; Kirdlarp, Suppachok; Klepper, Joerg; Kostić, Vladimir; Lang, Anthony E.; Linglart, Agnès; Maisenbacher, Melissa K.; Manyam, Bala V.; Mazzoni, Pietro; Miedzybrodzka, Zofia; Mitarnun, Witoon; Mitchell, Philip B.; Mueller, Jennifer; Novaković, Ivana; Paucar, Martin; Paulson, Henry; Simpson, Sheila A.; Svenningsson, Per; Tuite, Paul; Vitek, Jerrold; Wetchaphanphesat, Suppachok; Williams, Charles; Yang, Michele; Schofield, Peter R.; de Oliveira, João R. M.; Sobrido, María-Jesús

    2014-01-01

    Familial idiopathic basal ganglia calcification (IBGC) or Fahr’s disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient’s disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation. PMID:23334463

  12. Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein

    Zolnierowicz, S.; Work, C.; Hutchison, K.; Fox, I.H.

    1990-01-01

    The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-[ 3 H]ethylcarboxamidoadenosine [( 3 H]NECA). To solve this problem, we developed a rapid and simple method to separate adenosine receptors from the adenosine A2-like binding protein. Human platelet and placental membranes were solubilized with 1% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. The soluble platelet extract was precipitated with polyethylene glycol and the fraction enriched in adenosine receptors was isolated from the precipitate by differential centrifugation. The adenosine A2-like binding protein was removed from the soluble placental extract with hydroxylapatite and adenosine receptors were precipitated with polyethylene glycol. The specificity of the [ 3 H]NECA binding is typical of an adenosine A2 receptor for platelets and an adenosine A1 receptor for placenta. This method leads to enrichment of adenosine A2 receptors for platelets and adenosine A1 receptors for placenta. This provides a useful preparation technique for pharmacologic studies of adenosine receptors

  13. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

  14. A2A Adenosine Receptor Antagonists as Therapeutic Candidates: are they still an interesting challenge?

    Cacciari, Barbara; Federico, Stephanie; Spalluto, Giampiero

    2018-04-22

    In the past decades, many efforts were done to develope ligands for the adenosine receptors, with the purpose to individuate agonists and antagonists affine and selective for each subtypes , named A1, A2A, A2B, and A3. These intense studies allowed a deeper and deeper knowledge of the nature and, moreover, of the pathophysiological roles of all the adenosine receptor subtypes. In particular, the involvment of the A2A adenosine receptor subtype in some physiological mechanisms in the brain, that could be related to important diseases such as the Parkinson's disease, encouraged the research in this field. Particular attention was given to the antagonists endowed with high affinity and selectivity since they could have a real employment in the treatment of Parkinson's disease, and some compounds, such as istradefylline, preladenant and tozadenant, are already studied in clinical trials. Actually, the role of A2A antagonists in Parkinson's disease is becoming contradictory due to contrasting results in the last studies, but, at the same time, new possible employments are emerging for this class of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of A2A ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Ranked solutions of the matric equation A1X1=A2X2

    A. Duane Porter

    1980-01-01

    Full Text Available Let GF(pz denote the finite field of pz elements. Let A1 be s×m of rank r1 and A2 be s×n of rank r2 with elements from GF(pz. In this paper, formulas are given for finding the number of X1,X2 over GF(pz which satisfy the matric equation A1X1=A2X2, where X1 is m×t of rank k1, and X2 is n×t of rank k2. These results are then used to find the number of solutions X1,…,Xn, Y1,…,Ym, m,n>1, of the matric equation A1X1…Xn=A2Y1…Ym.

  16. Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetry A2

    Perry Anthony; Arnold, R.G.; Todd Averett; Band, H.R.; Berisso, M.C.; Borel, H.; Peter Bosted; Stephen Bueltmann; M. Buenerd; T. Chupp; Steve Churchwell; G.R. Court; Donald Crabb; Donal Day; Piotr Decowski; P. DePietro; Robin D. Erbacher; R. Erickson; Andrew Feltham; Helene Fonvieille; Emil Frlez; R. Gearhart; V. Ghazikhanian; Javier Gomez; Keith Griffioen; C. Harris; M.A. Houlden; E.W. Hughes; Charles Hyde-Wright; G. Igo; Sebastien Incerti; John Jensen; J.K. Johnson; Paul King; Yu.G. Kolomensky; Sebastian Kuhn; Richard Lindgren; R.M. Lombard-Nelsen; Jacques Marroncle; James Mccarthy; Paul McKee; W. Meyer; Gregory Mitchell; Joseph Mitchell; Michael Olson; S. Penttila; Gerald Peterson; Gerassimos Petratos; R. Pitthan; Dinko Pocanic; R. Prepost; C. Prescott; Liming Qin; Brian Raue; D. Reyna; L.S. Rochester; Stephen Rock; Oscar Rondon-Aramayo; Franck Sabatie; Ingo Sick; T. Smith; L. Sorrell; F. Staley; S. St. Lorant; L.M. Stuart; Z. Szalata; Y. Terrien; William Tobias; Luminita Todor; T. Toole; S. Trentalange; Dieter Walz; Robert Welsh; Frank Wesselmann; T.R. Wright; C.C. Young; Markus Zeier; Hong Guo Zhu; Benedikt Zihlmann

    1999-01-01

    We have measured the spin structure functions g 2 p and g 2 d and the virtual photon asymmetries A 2 p and A 2 d over the kinematic range 0.02 2 (le) 30(GeV/c) 2 by scattering 38.8 GeV longitudinally polarized electrons from transversely polarized NH 3 and 6 LiD targets.The absolute value of A 2 is significantly smaller than the √R positivity limit over the measured range, while g 2 is consistent with the twist-2 Wandzura-Wilczek calculation. We obtain results for the twist-3 reduced matrix elements d 2 p , d 2 d and d 2 n . The Burkhardt-Cottingham sum rule integral (g 2 (x)dx) is reported for the range 0.02 (le) x (le) 0.8

  17. Data package addendum for COBRA-1A2 life extension to 400 EFPD

    Hecht, S.L.; Ermi, A.M.

    1994-01-01

    The COBRA-1A experiment was originally designed for irradiations up to 350 effective full power days (EFPD) in EBR-II. Three of the seven B7A test capsules were discharged after 88.6 EFPD (COBRA-1A1; EBR-II designation X516), while the remaining four capsules continued to be irradiated to a goal exposure of 300 EFPD (COBRA-1A2; EBR-II designation X516A). However, it was recently decided that COBRA-1A2 was to remain in the reactor during Run 170, giving and nominal end-of-life (EOL) exposure of 375 EFPD. Since the revised test exposure exceeds the design basis given in supporting analyses, amended analyses are provided herein, giving the technical bases for the extended irradiation. This report describes the safety analysis for the extension of the COBRA-1A2 test (X516A) to 400 effective full power days in FBR-II

  18. A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.

    Lemieux, Bruno; Blanchette, Marco; Monette, Anne; Mouland, Andrew J; Wellinger, Raymund J; Chabot, Benoit

    2015-01-01

    The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.

  19. A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.

    Bruno Lemieux

    Full Text Available The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.

  20. Effects of heparin on platelet aggregation and release and thromboxane A2 production

    Mohammad, S.F.; Anderson, W.H.; Smith, J.B.; Chuang, H.Y.; Mason, R.G.

    1981-01-01

    Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with 3 H-arachidonic acid and 14 C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of 14 C-serotonin and 3 H-arachidonic acid metabolites, it appeared that either release of 14 C and 3 H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both 14 C and 3 H

  1. Dual regulatory switch confers tighter control on HtrA2 proteolytic activity.

    Singh, Nitu; D'Souza, Areetha; Cholleti, Anuradha; Sastry, G Madhavi; Bose, Kakoli

    2014-05-01

    High-temperature requirement protease A2 (HtrA2), a multitasking serine protease that is involved in critical biological functions and pathogenicity, such as apoptosis and cancer, is a potent therapeutic target. It is established that the C-terminal post-synaptic density protein, Drosophila disc large tumor suppressor, zonula occludens-1 protein (PDZ) domain of HtrA2 plays pivotal role in allosteric modulation, substrate binding and activation, as commonly reported in other members of this family. Interestingly, HtrA2 exhibits an additional level of functional modulation through its unique N-terminus, as is evident from 'inhibitor of apoptosis proteins' binding and cleavage. This phenomenon emphasizes multiple activation mechanisms, which so far remain elusive. Using conformational dynamics, binding kinetics and enzymology studies, we addressed this complex behavior with respect to defining its global mode of regulation and activity. Our findings distinctly demonstrate a novel N-terminal ligand-mediated triggering of an allosteric switch essential for transforming HtrA2 to a proteolytically competent state in a PDZ-independent yet synergistic activation process. Dynamic analyses suggested that it occurs through a series of coordinated structural reorganizations at distal regulatory loops (L3, LD, L1), leading to a population shift towards the relaxed conformer. This precise synergistic coordination among different domains might be physiologically relevant to enable tighter control upon HtrA2 activation for fostering its diverse cellular functions. Understanding this complex rheostatic dual switch mechanism offers an opportunity for targeting various disease conditions with tailored site-specific effector molecules. © 2014 FEBS.

  2. Resistance irrelevant CYP417A2v2 was found degrading insecticide in Laodelphax striatellus.

    Miah, Mohammad Asaduzzaman; Elzaki, Mohammed Esmail Abdalla; Han, Zhaojun

    2017-07-01

    Cytochrome P450 monooxygenases (CYPs) usually overexpressed in resistant strain were found involved in oxidative detoxification of insecticides. In this study, an investigation was conducted to confirm if resistance irrelevant CYPs which were not overexpressed in resistant strain before, were capable of degrading insecticides. Three resistance irrelevant CYPs viz. CYP417A2v2, CYP425A1v2, and CYP4DJ1 from CYP4 family of Laodelphax striatellus were randomly selected for experiments. CYP417A2v2 and CYP425A1v2 were found expressed successfully in Sf9 cell line while CYP4DJ1 was not expressed successfully and out of two expressed CYPs, only CYP417A2v2 showed its efficient catalytic activity. For catalytic activity, three traditional model probe substrates and five insecticides were assayed. For the probe substrates screened, p -nitroanisole and ethoxycoumarin were preferentially metabolized by CYP417A2v2 (specific activity 3.76 ± 1.22 and 1.63 ± 0.37 nmol min -1  mg protein -1 , respectively) and they may be potential diagnostic probes for this enzyme. Among insecticides, only imidacloprid was efficiently degraded by CYP417A2v2. Incubation of imidacloprid with CYP417A2v2 of L. striatellus and subsequent HPLC, LC-MS, and MS/MS analysis revealed the formation of imidacloprid metabolites, that is, 4' or 5'hydroxy-imidacloprid by hydroxylation. This result implies the exemption of CYPs character that it is not always, all the CYPs degrading insecticides being selected and overexpressed in resistant strains and the degrading CYPs without mutations to upregulate could be candidates during insecticide resistance evolution. This characterization of individual insect CYPs in insecticide degradation can provide insight for better understand of insecticide resistance development.

  3. Rapid transfer of short-lived radioisotopes via a 2. 4 km rabbit system

    Burgerjon, J J; Gelbart, Z; Lau, V; Lehnart, D; Lenz, J; Pate, B D; Ruth, T J; Sprenger, H P; van Oers, N S.C.

    1984-09-01

    A 2.4 km long pipeline between a cyclotron and a hospital is used for the rapid transfer of short-lived radiopharmaceuticals. The vials containing the pharmaceuticals are placed inside capsules (rabbits) that are blown through a tube by means of compressed air. Travel times as short as 2 min are achieved, which makes the system suitable for the transfer of /sup 15/O, which has a 2 min half-life. The construction and test results of the system are described along with a computer model, developed to explain some properties of the system. 7 references, 15 figures, 2 tables.

  4. Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema

    Staurenghi, Giovanni; Ye, Li; Magee, Mindy H

    2015-01-01

    PURPOSE: To investigate the potential of lipoprotein-associated phospholipase A2 inhibition as a novel mechanism to reduce edema and improve vision in center-involved diabetic macular edema (DME). DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled phase IIa study...... (AEs) and nonocular AEs were similar between treatment groups. CONCLUSIONS: Once-daily oral darapladib administered for 3 months demonstrated modest improvements in vision and macular edema that warrant additional investigation of this novel lipoprotein-associated phospholipase A2 inhibitory mechanism...

  5. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    Beulens, J.W.J.; Berg, R. van den; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims: To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results: Eleven lean (BMI: 18.5-25 kg/m2) and 9 overweight (BMI

  6. Textbook Evaluation: An Analysis of Listening Comprehension Parts in Top Notch 2A & 2B

    Soori, Afshin; Haghani, Elham

    2015-01-01

    Textbooks are the instruments that assist both teachers and learners in process of second language learning. With respect to the importance of textbooks in a language course, evaluation of course books is a significant issue for most researchers. The present study investigated and analyzed Listening Comprehension parts in Top Notch 2A & 2B 2nd…

  7. Glass formation via structural fragmentation of a 2D coordination network.

    Umeyama, D; Funnell, N P; Cliffe, M J; Hill, J A; Goodwin, A L; Hijikata, Y; Itakura, T; Okubo, T; Horike, S; Kitagawa, S

    2015-08-18

    The structure of a glass obtained by the melt quenching of a two-dimensional (2D) coordination network was examined. X-ray analyses disclosed a 2D-to-0D structural transformation before and after glass formation. The mechanism is unique to coordination compounds, as it is characterized by labile and flexible coordination bonds.

  8. Cn(1), Dn(1) and A2n-1(2) reflection K-matrices

    Lima-Santos, A.; Malara, R.

    2003-01-01

    We investigate the possible regular solutions of the boundary Yang-Baxter equation for the vertex models associated with the C n (1) , D n (1) and A 2n-1 (2) affine Lie algebras. We find three types of solutions with n, n-1 and 1 free parameters, respectively. Special cases and all diagonal solutions are presented separately

  9. Data of evolutionary structure change: 1DR8A-2DHTB [Confc[Archive

    Full Text Available 1DR8A-2DHTB 1DR8 2DHT A B ------------------------MKVAVLPGDGIGPEV...Chain> 2DHT B 2DHT...50 VAL CA 456 VAL CA 489 SER CA 527 2DHT... B 2DHTB AIEHKRKKVTI GLY CA 352 GLU CA 281 PHE CA 327

  10. Data of evolutionary structure change: 1DR0A-2DHTB [Confc[Archive

    Full Text Available 1DR0A-2DHTB 1DR0 2DHT A B ------------------------MKVAVLPGDGIGPEV...tryChain> 2DHT B 2DHT...95 HIS CA 348 VAL CA 450 VAL CA 478 2DHT... B 2DHTB YAIEHKRKKVT GLY CA 354 GLU CA 281 PHE CA 323 2DHT

  11. Optimizing EphA2-CAR T Cells for the Adoptive Immunotherapy of Glioma

    Zhongzhen Yi

    2018-06-01

    Full Text Available Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28.ζ and 41BB.ζ CARs with short spacers had similar effector function, resulting in potent antitumor activity. In addition, incorporating the 41BB signaling domain into CD28.ζ CARs did not improve CAR T cell function. While we could not determine functional differences between CD28.ζ, 41BB.ζ, and CD28.41BB.ζ CAR T cells, we selected CD28.ζ CAR T cells for further clinical development based on safety consideration. Keywords: GBM, CAR T cells, EphA2, brain tumor

  12. Mulig terapeutisk intervention med haemmere og fremmere af fosfolipase A 2 -subtyper

    Kolko, Miriam; Zhan, Chen; Andreasen, Jens Rovelt

    2007-01-01

    Phospholipase A2 (PLA2) is a group of enzymes discovered more than a century ago in insect and snake poison. Not more than 20 years ago they were identified in vertebrates, and during the last five years, research has accelerated in relation to isolating and cloning several members of this super...

  13. 26 CFR 1.1402(a)-2 - Computation of net earnings from self-employment.

    2010-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(a)-2 Computation of net earnings from self-employment. (a) General rule. In general, the gross income and... ascertaining his net earnings from self-employment, are to be determined by reference to the provisions of law...

  14. NCS-1 associates with adenosine A2A receptors and modulates receptor function

    Gemma eNavarro

    2012-04-01

    Full Text Available Modulation of G protein-coupled receptor (GPCR signalling by local changes in intracellular calcium concentration is an established function of Calmodulin which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca2+-sensor proteins that frequently associate with calmodulin targets with different functional outcome. In the present study we aimed to investigate if a target of calmodulin – the A2A adenosine receptor, is able to associate with two other neuronal calcium binding proteins, namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer and co-immunoprecipitation experiments we show the existence of A2A - NCS-1 complexes in living cells whereas caldendrin did not associate with A2A receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A2A receptor intracellular signalling in a Ca2+-dependent manner. Taken together this study provides further evidence that neuronal Ca2+-sensor proteins play an important role in modulation of GPCR signalling.

  15. Data of evolutionary structure change: 1CG8A-2ZLWD [Confc[Archive

    Full Text Available 1CG8A-2ZLWD 1CG8 2ZLW A D -VLSSQNKKAIEELGNLIKANAEAWGADALARLFELHPQ...R VQLSGEEKAAVLALWDKV--NEEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL...> 2ZLW D 2ZLWD ARHFG...fEVID> 2 2ZLW D 2ZLWD LWD... CA 218 GLN CA 251 2ZLW D

  16. Data of evolutionary structure change: 1CG5A-2ZLWD [Confc[Archive

    Full Text Available 1CG5A-2ZLWD 1CG5 2ZLW A D -VLSSQNKKAIEELGNLIKANAEAWGADALARLFELHPQ...R VQLSGEEKAAVLALWDKV--NEEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL...ne> GLN CA 254 2ZLW D 2ZLWD...ain> 2ZLW D 2ZLWD AR...fEVID> 2 2ZLW D 2ZLWD

  17. Numerical simulations in granular matter: The discharge of a 2D silo

    ... short and elementary review of numerical simulations in granular assemblies, giving the process of discharge of a 2D silo as an example. The strengths and limitations of different approaches are discussed, together with some comments on the specific issues related to the numerics of discontinuous dissipative collisions.

  18. HbA2 measurements in β-thalassemia and in other conditions

    Giovanni Ivaldi

    2014-09-01

    Full Text Available Quite a few papers have been written on the significance of elevated hemoglobin (Hb A2 as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing or elevating the expression of HbA2 and last but not least on the need for reliable measurement methods and precise calibrations with accurate standards. However, little has been published on the causes that elevate or reduce the HbA2 levels in β- and a-thalassemia and in other conditions. For a better understanding of the value of a precise measurement of this parameter we summarize and elucidate in this review the direct and indirect mechanisms that cause the variations in HbA2 expression and that influence the value of this parameter in particular conditions. We conclude by explaining the advantages and disadvantages of trusting on a precise measurement in the complete diagnostic contest.

  19. Technologies omniprésentes et accès au savoir (A2K) | CRDI ...

    ... à la commercialisation de masse ont eu une influence majeure sur l'accès au savoir (A2K). ... Le mouvement pour l'accès au savoir cherche à promouvoir de nouvelles ... [President] for and on behalf of Centre For Internet And Society.

  20. Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes

    Lynch Vincent J

    2007-01-01

    Full Text Available Abstract Background Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Convincing examples of neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, thus they are excellent models to study the emergence of novel functions after gene duplications. Results Here, I show that positive Darwinian selection and neofunctionalization is common in snake venom phospholipase A2 genes. The pattern of gene duplication and positive selection indicates that adaptive molecular evolution occurs immediately after duplication events as novel functions emerge and continues as gene families diversify and are refined. Surprisingly, adaptive evolution of group-I phospholipases in elapids is also associated with speciation events, suggesting adaptation of the phospholipase arsenal to novel prey species after niche shifts. Mapping the location of sites under positive selection onto the crystal structure of phospholipase A2 identified regions evolving under diversifying selection are located on the molecular surface and are likely protein-protein interactions sites essential for toxin functions. Conclusion These data show that increases in genomic complexity (through gene duplications can lead to phenotypic complexity (venom composition and that positive Darwinian selection is a common evolutionary force in snake venoms. Finally, regions identified under selection on the surface of phospholipase A2 enzymes are potential candidate sites for structure based antivenin design.

  1. Enhanced Activity and Altered Specificity of Phospholipase A2 by Deletion of a Surface Loop

    Kuipers, Oscar P.; Thunnissen, Marjolein M.G.M.; Geus, Pieter de; Dijkstra, Bauke W.; Drenth, Jan; Verheij, Hubertus M.; Haas, Gerard H. de

    1989-01-01

    Protein engineering and x-ray crystallography have been used to study the role of a surface loop that is present in pancreatic phospholipases but is absent in snake venom phospholipases. Removal of residues 62 to 66 from porcine pancreatic phospholipase A2 does not change the binding constant for

  2. The action of cobra venom phospholipase A2 isoenzymes towards intact human erythrocytes

    Roelofsen, B.; Sibenius Trip, M.; Verheij, H.M.; Zevenbergen, J.L.

    1980-01-01

    1. 1. Cobra venom phospholipase A2 from three different sources has been fractionated into different isoenzymes by DEAE ion-exchange chromatography. 2. 2. Treatment of intact human erythrocytes with the various isoenzymes revealed significant differences in the degree of phosphatidylcholine

  3. Prevalence and gene frequencies of A1A2BO and Rh(D) blood ...

    Ruqaiya Hussain

    2012-08-03

    Aug 3, 2012 ... Human Genetics and Toxicology Lab, Section of Genetics, Department of Zoology ... alence and gene frequencies of A1A2BO and Rh(D) blood groups among the Muslim populations of ..... The principal bio-clinical significance of the erythrocytic ... (CST), UP, which funded the major project, titled '' Genomic.

  4. Characterization of the association of radiolabeled bleomycin A2 with HeLa cells

    Roy, S.N.; Horwitz, S.B.

    1984-01-01

    The association of [ 3 H]bleomycin A2 and Cu(II):[ 3 H]bleomycin A2 with HeLa cells has been characterized. Under the conditions of our experiments, approximately 0.1% of the total drug in the medium associates with HeLa cells. Both forms of the drug bind to HeLa cells in a specific and saturable manner, with a Km of 20 microM and a Vmax of 2.5 pmol/min/10(6) cells. Scatchard analysis of the specific binding data demonstrates a single set of high-affinity binding sites. Cytotoxic activities of both forms of the drug are similar, with a 50% lethal dose of 0.5 microM at 48 hr. The specific binding in HeLa cells of either the labeled metal-free drug or its copper complex is reversible by a 100-fold excess of either unlabeled drug. Interaction of the drug with cells is temperature sensitive but is unaffected by metabolic poisons, suggesting that this process is not energy dependent. Isolation of DNA from HeLa cells incubated with the drug indicates that 1 mol of either [ 3 H]bleomycin A2 or Cu(II):[ 3 H]bleomycin A2 binds per 10(8) nucleotides. Further studies with the radiolabeled drug are required to define precisely the mechanisms involved in bleomycin uptake and compartmentalization within the cell

  5. Megaloblastic anaemia, diabetes and deafness in a 2-year-old child ...

    Megaloblastic anaemia in childhood usually occurs as a result of dietary folate deficiency or, rarely, congenital disorders of vitamin B12 metabolism. We present a 2-year-old girl with megaloblastic anaemia and insulin-dependent diabetes mellitus, both of which proved responsive to pharmacological doses of thiamine.

  6. Phase locking of a 2.7 THz quantum cascade laser to a microwave reference

    Khosropanah, P.; Baryshev, A.; Zhang, W.; Jellema, W.; Hovenier, J.N.; Gao, J.R.; Klapwijk, T.M.; Paveliev, D.G.; Williams, B.S.; Kumar, S.; Hu, Q.; Reno, J.L.; Klein, B.; Hesler, J.L.

    2009-01-01

    We demonstrate the phase locking of a 2.7 THz metal–metal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier chain

  7. Phase locking of a 2.7 THz quantum cascade laser to a microwave reference

    Khosropanah, P.; Baryshev, A.; Zhang, W.; Jellema, W.; Hovenier, J. N.; Gao, J. R.; Klapwijk, T. M.; Paveliev, D. G.; Williams, B. S.; Kumar, S.; Hu, Q.; Reno, J. L.; Klein, B.; Hesler, J. L.

    2009-01-01

    We demonstrate the phase locking of a 2.7 THz metal-metal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier chain

  8. 26 CFR 1.263(a)-2 - Examples of capital expenditures.

    2010-04-01

    ...) INCOME TAX (CONTINUED) INCOME TAXES Items Not Deductible § 1.263(a)-2 Examples of capital expenditures... subsidiary and increasing the value of its stockholdings in the subsidiary shall not deduct amounts paid in... be added to the cost of its stock in the subsidiary. (h) The cost of good will in connection with the...

  9. Complete paroxysmal atrioventricular block in a 2-year-old girl

    Holst, Line Marie; Dixen, Ulrik; Jeppesen, Dorthe L

    2015-01-01

    We present a case of atypical syncope in a 2-year-old, otherwise healthy girl. The patient presented with three episodes of syncope without any precipitating factors and no family history of sudden unexpected death. Holter monitoring revealed 24 events of complete atrioventricular block lasting up...

  10. "Nonclassical" secretion of annexin A2 to the lumenal side of the enterocyte brush border membrane

    Danielsen, E Michael; van Deurs, Bo; Hansen, Gert H

    2003-01-01

    side of the microvilli, showing an apical secretion by a "nonclassical" mechanism. In addition, annexin A2 was associated with surface-connected, deep apical tubules in the apical terminal web region and with an underlying pleiomorphic, tubulo-vesicular compartment (subapical compartment...

  11. A MIDGUT DIGESTIVE PHOSPHOLIPASE A2 IN LARVAL MOSQUITOES, AEDES ALBOPICTUS AND CULEX QUINQUEFASCIATUS

    Phospholipase A2 (PLA2) is a secretory digestive enzyme that hydrolyzes ester bond at sn-2 position of dietary phospholipids, creating free fatty acid and lysophopholipid. The free fatty acids (arachidonic acid) are absorbed into midgut cells. Aedes albopictus and Culex quinquefasciatus digestive PL...

  12. Data of evolutionary structure change: 1VL8A-2UVDE [Confc[Archive

    Full Text Available 1VL8A-2UVDE 1VL8 2UVD A E FDLRGRVALVTGGSRGLGFGIAQGLAEAGCSVVVASRN-...eq1> -MLKGKVALVTGASRGIGRAIAIDLAKQGANVVVNYAGNEQKANEVVDEIKKL-GSDAIAVRADVANAED...>E 2UVDE VNYAGNEQKAN EEE H...in>E 2UVDE EIKKL-GSDAI HHH...yChain> 2UVD E 2UVDE VGVTG-NPGQA<

  13. Overexpression of porcine lipoprotein-associated phospholipase A2 in swine

    Tang, Xiaochun; Wang, Gangqi; Liu, Xingxing; Han, Xiaolei; Li, Zhuang; Ran, Guangyao; Li, Zhanjun; Song, Qi; Ji, Y; Wang, Haijun; Wang, Yuhui; Ouyang, Hongsheng; Pang, Daxin

    2015-01-01

    Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is associated with the risk of vascular disease. It circulates in human blood predominantly in association with low-density lipoprotein cholesterol (LDL-C) and hydrolyses oxidized phospholipids into pro-inflammatory products. However, in the mouse

  14. 26 CFR 48.6420(a)-2 - Gasoline includible in claim.

    2010-04-01

    ...) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Refunds and Other Administrative Provisions of Special Application to Retailers and Manufacturers Taxes § 48.6420(a)-2 Gasoline includible in... which was “used on a farm for farming purposes” as defined in paragraph (a) of § 48.6420(c)-1. The type...

  15. Secretory Phospholipase A2-IIA and Cardiovascular Disease: A Mendelian Randomization Study

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, André G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Paré, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is

  16. Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa

    Zheng, Zhaojun; Tharmalingam, Nagendran; Liu, Qingzhong; Kim, Wooseong; Fuchs, Beth Burgwyn; Zhang, Rijun; Vilcinskas, Andreas

    2017-01-01

    ABSTRACT The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrug-resistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36-residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pathogen Pseudomonas aeruginosa. The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical P. aeruginosa isolates were 32 to 64 μg/ml, and its MICs versus other Gram-negative bacteria were 2 to 32 μg/ml. Importantly, cecropin A2 demonstrated synergistic activity against P. aeruginosa when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective in vivo in the P. aeruginosa/Galleria mellonella model (P < 0.001). We found that cecropin A2 bound to P. aeruginosa lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against P. aeruginosa in vitro and in vivo, offering an alternative approach for the treatment of P. aeruginosa infections. PMID:28483966

  17. Data of evolutionary structure change: 1CG8A-2QU0A [Confc[Archive

    Full Text Available /pdbChain> 2QU0A ence>YFPHF-DLSHGence> G - 0 A A VLSSQNKKAIEELGNLIKANAEAWGADALARLFELHPQT...hain> 1CG8 A 1CG8A ence>VNLQA-FTPVT...ine>THR CA 278 2QU0 A 2QU...0A ence>CHLPNDFTPAV HH HHHH HHH

  18. Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting.

    Staquicini, Daniela I; Rangel, Roberto; Guzman-Rojas, Liliana; Staquicini, Fernanda I; Dobroff, Andrey S; Tarleton, Christy A; Ozbun, Michelle A; Kolonin, Mikhail G; Gelovani, Juri G; Marchiò, Serena; Sidman, Richard L; Hajjar, Katherine A; Arap, Wadih; Pasqualini, Renata

    2017-06-26

    Cytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAASG as a cytosol-targeting peptide. By affinity purification and mass spectrometry, intracellular annexin A2 was identified as the corresponding binding protein. Consistently, annexin A2 and a cell-internalizing, penetratin-fused version of the selected peptide (LGRFYAASG-pen) co-localized and specifically accumulated in the cytoplasm at the cell edges and cell-cell contacts. Functionally, tumor cells incubated with LGRFYAASG-pen showed disruption of filamentous actin, focal adhesions and caveolae-mediated membrane trafficking, resulting in impaired cell adhesion and migration in vitro. These effects were paralleled by a decrease in the phosphorylation of both focal adhesion kinase (Fak) and protein kinase B (Akt). Likewise, tumor cells pretreated with LGRFYAASG-pen exhibited an impaired capacity to colonize the lungs in vivo in several mouse models. Together, our findings demonstrate an unrecognized functional link between intracellular annexin A2 and tumor cell adhesion, migration and in vivo grafting. Moreover, this work uncovers a new peptide motif that binds to and inhibits intracellular annexin A2 as a candidate therapeutic lead for potential translation into clinical applications.

  19. MRI findings of an intermuscular lipoma in a 2-year-old

    Grandbois, Lindsey; Vade, Aruna; Lim-Dunham, Jennifer [Loyola University Medical Center, Department of Radiology, Maywood, IL (United States); Al-Masri, Hytham [Mount Sinai Hospital, Department of Pathology, Chicago, IL (United States)

    2006-09-15

    We report the MRI findings of a large deep intermuscular lipoma in a 2-year-old child with a painless palpable shoulder mass, and its differentiation from liposarcoma and other soft-tissue masses. To our knowledge, the imaging features of deep lipomas in children have not been reported. (orig.)

  20. Fluctuations in the cosmic microwave background on a 2.3 deg angular scale

    Calzolari, P.; Cortiglioni, S.; Mandolesi, N.

    1982-01-01

    The study of fluctuations in the temperature of the cosmic microwave background may provide important information on the origin of the large scale structures in the Universe. An experiment is in operation at Medicina (Bologna) for studying such temperature fluctuations on a 2 deg 3 angular scale at lambda=2.8 cm. Preliminary results seem to indicate ΔT/T -4

  1. ATP13A2 variants in early-onset Parkinson's disease patients and controls

    Djarmati, Ana; Hagenah, Johann; Reetz, Kathrin

    2009-01-01

    Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exo...

  2. Mesenteric teratoma associated with acute perforated appendicitis in a 2-year-old girl

    Jihoon Jang

    2016-07-01

    Full Text Available Mesenteric teratoma is a rare tumor, with few cases reported in the literature. Because mesenteric teratomas have no specific signs or symptoms, their clinical manifestations depend on their size and location. This report describes a mesenteric teratoma associated with acute perforated appendicitis in a 2-year-old girl who presented with abdominal pain and high grade fever.

  3. Meeting the EU recycling targets by introducing a 2-compartment bin to households

    Jensen, Morten Bang; Scheutz, Charlotte; Møller, Jacob

    A Danish municipality has introduced a 2-compartment bin in the waste collection scheme, this bin should increase recycling of dry household recyclables. An excessive waste sorting campaign was conducted and the efficiency of the bin assessed. The waste sorting campaign yielded a full waste...... targets can be fulfilled, there is still room for improvement (increase source separation), especially for hard plastic and metals....

  4. Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers.

    Muscat, Joshua E; Pittman, Brian; Kleinman, Wayne; Lazarus, Philip; Stellman, Steven D; Richie, John P

    2008-10-01

    The lower incidence rate of transitional cell carcinoma of the urinary bladder in blacks than in whites may be due to racial differences in the catalytic activity of enzymes that metabolize carcinogenic arylamines in tobacco smoke. To examine this, we compared cytochrome P4501A2 (CYP1A2) and N-acetyltransferase-2 activities (NAT2) in black and white smokers using urinary caffeine metabolites as a probe for enzyme activity in a community-based study of 165 black and 183 white cigarette smokers. The paraxanthine (1,7-dimethylxanthine, 17X)/caffeine (trimethylxanthine, 137X) ratio or [17X+1,7-dimethyluric acid (17U)]/137X ratio was used as an indicator of CYP1A2 activity. The 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU)/1-methylxanthine (1X) ratio indicated NAT2 activity. The odds ratio for the slow NAT2 phenotype associated with black race was 0.4; 95% confidence intervals 0.2-0.7. The putative combined low risk phenotype (slow CYP1A2/rapid NAT2) was more common in blacks than in whites (25% vs. 15%, Pwhites.

  5. A novel ATP1A2 gene mutation in an Irish familial hemiplegic migraine kindred.

    Fernandez, Desiree M

    2012-02-03

    OBJECTIVE: We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation. BACKGROUND: FHM is a rare autosomal-dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible for hemiplegic migraine have been described in the CACNA1A gene (chromosome 19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24). METHODS: We performed linkage analyses in this family for chromosome 1q23 and performed mutation analysis of the ATP1A2 gene. RESULTS: Linkage to the FHM2 locus on chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G to C substitution in exon 22 resulting in a novel protein variant, D999H, which co-segregates with FHM within this pedigree and is absent in 50 unaffected individuals. This residue is also highly conserved across species. CONCLUSIONS: We propose that D999H is a novel FHM ATP1A2 mutation.

  6. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors

    Gnad, Thorsten; Scheibler, Saskia; von Kügelgen, Ivar

    2014-01-01

    hamster or rat. However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A2A...

  7. The moderating effect of haemoglobin A2 on morbidity in sickle cell

    Administrator

    ion-exchange-HbS interference free technique using the. BiosystemR S.A. kit with ISO 9001 certificate registration no. 091006696. HbA2 percentage was .... factors. Understanding causes of anaemia and potential mechanisms are crucial to our ability to intervene to reduce this burden (Tolentino and Friedman, 2007).

  8. Measurement of radiative widths of a(2)(1320) and pi(2)(1670)

    Adolph, C.; Akhunzyanov, R.; Alekseev, M.; Alexeev, G. D.; Amoroso, A.; Andrieux, V.; Anosov, V. A.; Austregisilio, A.; Badelek, B.; Balestra, F.; Barth, J.; Baum, G.; Beck, R.; Bedfer, Y.; Berlin, A.; Bernhard, J.; Bicker, K.; Bieling, J.; Birsa, R.; Bisplinghoff, J.; Bodlak, M.; Boer, M.; Bordalo, P.; Bradamante, F.; Braun, C.; Bressan, A.; Büchele, M.; Burtin, E.; Capozza, L.; Chiosso, M.; Chung, S.U.; Cicuttin, A.; Crespo, M.; Curiel, Q.; Dalla Torre, S.; Dasgupta, S. S.; Dasgupta, S.; Denisov, O.; Donskov, S.; Doshita, N.; Duic, V.; Dünnweber, W.; Dziewiecki, M.; Efremov, A.V.; Elia, C.; Eversheim, P.; Eyrich, W.; Faessler, M.; Ferrero, A.; Filin, A.; Finger, M.; Finger jr., M.; Fischer, H.; Franco, C.; Fresne von Hohenesche, N.; Friedrich, J.; Frolov, V.; Gautheron, F.; Gavrichtchouk, O.; Gerassimov, S.; Geyer, R.; Gnesi, I.; Gobbo, B.; Goertz, S.; Gorzellik, M.; Grabmüller, S.; Grasso, A.; Grube, B.; Guskov, A.; Guthörl, T.; Haas, F.; von Harrach, D.; Hahne, D.; Hashimoto, R.; Heinsius, F.; Herrmann, F.; Hinterberger, F.; Höppner, Ch.; Horikawa, N.; d'Hose, N.; Huber, S.; Ishimoto, S.; Ivanov, A.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jary, V.; Jasinski, P.; Joerg, P.; Joosten, R.; Kabuss, E.; Ketzer, B.; Khaustov, G.; Khokhlov, Y.; Kisselev, Y.; Klein, F.; Klimaszewski, K.; Koivuniemi, J.; Kolosov, V.; Kondo, K.; Königsmann, K.; Konorov, I.; Konstantinov, V.; Kotzinian, A.; Kouznetsov, O.; Král, Z.; Krämer, M.; Kroumchtein, Z.; Kuchinski, N.; Kunne, F.; Kurek, K.; Kurjata, R. P.; Lednev, A.; Lehmann, A.; Levorato, S.; Lichtenstadt, J.; Maggiora, A.; Magnon, A.; Makke, N.; Mallot, G.; Marchand, C.; Martin, A.; Marzec, J.; Matoušek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.; Meyer, W.; Michigami, T.; Mikhailov, Y.; Miyachi, Y.; Nagaytsev, A.; Nagel, T.; Nerling, F.; Neubert, S.; Neyret, D.; Nikolaenko, V.; Nový, J.; Nowak, W. D.; Nunes, A.S.; Orlov, I.; Olshevsky, A.; Ostrick, M.; Panknin, R.; Panzieri, D.; Parsamyan, B.; Paul, S.; Pešek, M.; Platchkov, S.; Pochodzalla, J.; Polyakov, V.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Reicherz, G.; Rocco, E.; Rychter, A.; Rossiyskaya, N. S.; Ryabchikov, D.; Samoylenko, V.; Sandacz, A.; Sarkar, S.; Savin, I.; Sbrizzai, G.; Schiavon, P.; Schill, C.; Schlütter, T.; Schmidt, A.; Schmidt, K.; Schmiden, H.; Schönning, K.; Schopferer, S.; Schott, M.; Shevchenko, O.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Sosio, S.; Sozzi, F.; Srnka, Aleš; Steiger, L.; Stolarski, M.; Sulc, M.; Sulej, R.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Takekawa, S.; Ter Wolbeek, J.; Tessaro, S.; Tessarotto, F.; Thibaud, F.; Uhl, S.; Uman, I.; Vandenbroucke, M.; Virius, M.; Vondra, J.; Wang, L.; Weisrock, T.; Wilfert, M.; Windmolders, R.; Wollny, H.; Zaremba, K.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.

    2014-01-01

    Roč. 50, č. 4 (2014), 79:1-19 ISSN 1434-6001 R&D Projects: GA MŠk(CZ) LO1212 Keywords : radiative width * a(2)(1320) meson * (pi2)(1670) meson * Primakoff reaction Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.736, year: 2014

  9. Infantile Amnesia across the Years: A 2-Year Follow-Up of Children's Earliest Memories

    Peterson, Carole; Warren, Kelly L.; Short, Megan M.

    2011-01-01

    Although infantile amnesia has been investigated for many years in adults, only recently has it been investigated in children. This study was a 2-year follow-up and extension of an earlier study. Children (4-13 years old) were asked initially and 2 years later for their earliest 3 memories. At follow-up, their age at the time of these memories…

  10. Water-ice-driven activity on main-belt Comet P/2010 A2 (LINEAR)?

    Moreno, Fernando; Licandro, Javier; Tozzi, Gian-Paolo

    2010-01-01

    The dust ejecta of Main-Belt Comet P/2010 A2 (LINEAR) have been observed with several telescopes at the Observatorio del Roque de los Muchachos on La Palma, Spain. Application of an inverse dust tail Monte Carlo method to the images of the dust ejecta from the object indicates that a sustained, l...

  11. Draft genome sequence of the white-rot fungus Obba rivulosa 3A-2

    Otto Miettinen; Robert Riley; Kerrie Barry; Daniel Cullen; Ronald P. de Vries; Matthieu Hainaut; Annele Hatakka; Bernard Henrissat; Kristiina Hilden; Rita Kuo; Kurt LaButti; Anna Lipzen; Miia R. Makela; Laura Sandor; Joseph W. Spatafora; Igor V. Grigoriev; David S. Hibbett

    2016-01-01

    We report here the first genome sequence of the white-rot fungus Obba rivulsa (Polyporales, Basidiomycota), a polypore known for its lignin-decomposing ability. The genome is based on the homokaryon 3A-2 originating in Finland. The genome is typical in size and carbohydrate active enzyme (CAZy) content for wood-decomposing basidiomycetes.

  12. Regulation of cytosolic Phospholipase A2 activity plays a central role in cell responses

    Rossum, Gerarda Sophia Agnes Theodora van

    2001-01-01

    Phospholipases A2 are enzymes that hydrolyse fatty acids from the sn-2 position of phospholipids, resulting in the release of free fatty acids and lysophospholipids. The sn-2 position of phospholipids in mammalian cells is enriched with arachidonic acid, which is a substrate for cyclooxygenases,

  13. Aural Myiasis in A 2-Week Old Neonate - Case Report | Adegboye ...

    Aural myiasis, particularly in neonate, is rare, and the average practitioner of pediatrics is less likely to see a case. We present a 2- week old male neonate seen at Federal Medical Centre, Azare, Bauchi State of Nigeria with four days history of left ear chocolate – colour discharge and inconsolable cry before presentation.

  14. Subarachnoid hemorrhage induces enhanced expression of thromboxane A2 receptors in rat cerebral arteries

    Ansar, Saema; Larsen, Carl; Maddahi, Aida

    2010-01-01

    Cerebral ischemia remains the key cause of morbidity and mortality after subarachnoid hemorrhage (SAH) with a pathogenesis that is still poorly understood. The aim of the present study was to examine the involvement of thromboxane A(2) receptors (TP) in the pathophysiology of cerebral ischemia...

  15. Structures of the a2 ions of Ala-Ala-Ala and Phe-Phe-Phe

    Verkerk, U.H.; Zhao, J.; Lau, J.K.-C.; Lam, T.-W.; Hao, Q.; Steill, J.D.; Siu, C.K.; Oomens, J.; Hopkinson, A.C.; Siu, K.W.M.

    2012-01-01

    IRMPD spectra are reported for a2 ions derived from trialanine (AAA) and triphenylalanine (FFF) and compared with spectra calculated by density functional theory at the B3LYP/6-311++G(d,p) level of theory. At low collision energies the cyclic N1-protonated imidazolidinone ion C1 is dominant, but at

  16. Synthesis of structured phospholipids by immobilized phospholipase A2 catalyzed acidolysis

    Vikbjerg, Anders Falk; Vikbjerg, Anders Falk; Xu, Xuebing

    2007-01-01

    Acyl modification of the sn-2 position in phospholipids (PLs) was conducted by acidolysis reaction using immobilized phospholipase A2 (PLA2) as the catalyst. In the first stage we screened different carriers for their ability to immobilize PLA2. Several carriers were able to fix the enzyme...

  17. Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease.

    Popat, R A; Van Den Eeden, S K; Tanner, C M; Kamel, F; Umbach, D M; Marder, K; Mayeux, R; Ritz, B; Ross, G W; Petrovitch, H; Topol, B; McGuire, V; Costello, S; Manthripragada, A D; Southwick, A; Myers, R M; Nelson, L M

    2011-05-01

    In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04). In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  18. Thermo-hydro-geochemical modelling of the bentonite buffer. LOT A2 experiment

    Sena, Clara; Salas, Joaquin; Arcos, David (Amphos 21 Consulting S.L., Barcelona (Spain))

    2010-12-15

    The Swedish Nuclear Fuel and waste management company (SKB) is conducting a series of long term buffer material (LOT) tests at the Aespoe Hard Rock Laboratory (HRL) to test the behaviour of the bentonite buffer under conditions similar to those expected in a KBS-3 deep geological repository for high level nuclear waste (HLNW). In the present work a numerical model is developed to simulate (i) the thermo-hydraulic, (ii) transport and (iii) geochemical processes that have been observed in the LOT A2 test parcel. The LOT A2 test lasted approximately 6 years, and consists of a 4 m long vertical borehole drilled in diorite rock, from the ground of the Aespoe HRL tunnel. The borehole is composed of a central heater, maintained at 130 deg C in the lower 2 m of the borehole, a copper tube surrounding the heater and a 100 mm thick ring of pre-compacted Wyoming MX-80 bentonite around the copper tube /Karnland et al. 2009/. The numerical model developed here is a 1D axis-symmetric model that simulates the water saturation of the bentonite under a constant thermal gradient; the transport of solutes; and, the geochemical reactions observed in the bentonite blocks. Two cases have been modelled, one considering the highest temperature reached by the bentonite (at 3 m depth in the borehole, where temperatures of 130 and 85 deg C have been recorded near the copper tube and near the granitic host rock, respectively) and the other case assuming a constant temperature of 25 deg C, representing the upper part of borehole, where the bentonite has not been heated. In the LOT A2 test, the initial partially saturated bentonite becomes progressively water saturated, due to the injection of Aespoe granitic groundwater at granite - bentonite interface. The transport of solutes during the bentonite water saturation stage is believed to be controlled by water uptake from the surrounding groundwater to the wetting front and, additionally, in the case of heated bentonite, by a cyclic evaporation

  19. Thermo-hydro-geochemical modelling of the bentonite buffer. LOT A2 experiment

    Sena, Clara; Salas, Joaquin; Arcos, David

    2010-12-01

    The Swedish Nuclear Fuel and waste management company (SKB) is conducting a series of long term buffer material (LOT) tests at the Aespoe Hard Rock Laboratory (HRL) to test the behaviour of the bentonite buffer under conditions similar to those expected in a KBS-3 deep geological repository for high level nuclear waste (HLNW). In the present work a numerical model is developed to simulate (i) the thermo-hydraulic, (ii) transport and (iii) geochemical processes that have been observed in the LOT A2 test parcel. The LOT A2 test lasted approximately 6 years, and consists of a 4 m long vertical borehole drilled in diorite rock, from the ground of the Aespoe HRL tunnel. The borehole is composed of a central heater, maintained at 130 deg C in the lower 2 m of the borehole, a copper tube surrounding the heater and a 100 mm thick ring of pre-compacted Wyoming MX-80 bentonite around the copper tube /Karnland et al. 2009/. The numerical model developed here is a 1D axis-symmetric model that simulates the water saturation of the bentonite under a constant thermal gradient; the transport of solutes; and, the geochemical reactions observed in the bentonite blocks. Two cases have been modelled, one considering the highest temperature reached by the bentonite (at 3 m depth in the borehole, where temperatures of 130 and 85 deg C have been recorded near the copper tube and near the granitic host rock, respectively) and the other case assuming a constant temperature of 25 deg C, representing the upper part of borehole, where the bentonite has not been heated. In the LOT A2 test, the initial partially saturated bentonite becomes progressively water saturated, due to the injection of Aespoe granitic groundwater at granite - bentonite interface. The transport of solutes during the bentonite water saturation stage is believed to be controlled by water uptake from the surrounding groundwater to the wetting front and, additionally, in the case of heated bentonite, by a cyclic evaporation

  20. Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins.

    Moreno, Estefanía; Canet, Júlia; Gracia, Eduard; Lluís, Carme; Mallol, Josefa; Canela, Enric I; Cortés, Antoni; Casadó, Vicent

    2018-01-01

    Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26) and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A 2A R present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A 2A R and a modification of the bioluminescence resonance energy transfer (BRET) technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET), we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A 2A R involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A 2A R-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26) and dendritic cells (expressing A 2A R). This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector) without partitioning these functions in different subunits.

  1. Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins

    Estefanía Moreno

    2018-02-01

    Full Text Available Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26 and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A2AR present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A2AR and a modification of the bioluminescence resonance energy transfer (BRET technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET, we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A2AR involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A2AR-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26 and dendritic cells (expressing A2AR. This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector without partitioning these functions in different subunits.

  2. A Family with γ-Thalassemia and High Hb A2 Levels.

    Parmeggiani, Giulia; Gualandi, Francesca; Selvatici, Rita; Rimessi, Paola; Bigoni, Stefania; Taddei Masieri, Marina; Dolcini, Bernadetta; Venturoli, Anna; Cappabianca, Maria P; Ferlini, Alessandra; Ravani, Anna

    2016-06-01

    We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the (G)γ gene and (G)γ-(A)γ intergenic region, whereas the 3' region of the (A)γ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid (GA)γ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels.

  3. Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice.

    Pagnussat, N; Almeida, A S; Marques, D M; Nunes, F; Chenet, G C; Botton, P H S; Mioranzza, S; Loss, C M; Cunha, R A; Porciúncula, L O

    2015-08-01

    Caffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by adenosine A2 A receptor, but not A1 receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice. We determined whether A2 A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A2 A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. Scopolamine (1.0 mg·kg(-1) , i.p.) impaired short-term memory performance in all three tests and this scopolamine-induced amnesia was prevented by the A2 A receptor antagonist (SCH 58261, 0.1-1.0 mg·kg(-1) , i.p.) and by the A1 receptor antagonist (DPCPX, 0.2-5.0 mg·kg(-1) , i.p.), except in the modified Y-maze where only SCH58261 was effective. Both antagonists were devoid of effects on memory or locomotion in naïve rats. Notably, the activation of A2 A receptors with CGS 21680 (0.1-0.5 mg·kg(-1) , i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg(-1) , i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. These results show that A2 A receptors are necessary and sufficient to trigger memory impairment and further suggest that A1 receptors might also be selectively engaged to control the cholinergic-driven memory impairment. © 2015 The British Pharmacological Society.

  4. Conceptual design of a linac-stretcher ring to obtain a 2-gev continuous electron beam

    Cho, Y.; Holt, R.J.; Jackson, H.E.; Khoe, T.K.; Mavrogenes, G.S.

    1981-01-01

    In order to obtain a high duty factor, >100 /mu/A 2-Gev electron beam, a linac-stretcher ring system was designed. The system is an attractive option because it draws heavily on the existing accelerator technology. The linac-stretcher ring consists of a 2-Gev SLAC-type pulsed linac which injects into a storage ring. In between linac pulses, the stored electron beam is to extract resonantly. This design differs from those discussed recently in several important respects. The storage ring includes an rf system whose purpose is to control the beam orbit and rate of extraction from the ring. With an rf system in the ring, the injection scheme consists of a few turns of synchronous transfers of beam between the linac and storage ring. 4 refs

  5. Cross-reactivity and phospholipase A2 neutralization of anti-irradiated Bothrops jararaca venom antibodies

    Spencer, P.J.; Nascimento, N. do; Paula, R.A. de; Cardi, B.A.; Rogero, J.R.

    1995-01-01

    The detoxified Bothrops jararaca venom, immunized rabbits with the toxoid obtained and investigated cross-reactivity of the antibodies obtained against autologous and heterelogous venoms was presented. It was also investigated the ability of the IgGs, purified by affinity chromatography, from those sera to neutralize phospholipase. A 2 , an ubiquous enzyme in animal venoms. Results indicate that venom irradiation leads to an attenuation of toxicity of 84%. Cross-reactivity was investigated by ELISA and Western blot and all venoms were reactive to the antibodies. On what refers to phospholipase A 2 activity neutralization, the antibodies neutralized autologous venoms efficiently and, curiously, other venoms from the same genus were not neutralized, while Lachesis muta venom, a remote related specier, was neutralized by this serum. These data suggest that irradiation preserve important epitopes for induction of neutralizing antibodies and that these epitopes are not shared by all venoms assayed. (author). 8 refs, 2 figs, 3 tabs

  6. Multifactorial control of water and saline intake: role of a2-adrenoceptors

    L.A. De-Luca Jr.

    1997-04-01

    Full Text Available Water and saline intake is controlled by several mechanisms activated during dehydration. Some mechanisms, such as the production of angiotensin II and unloading of cardiovascular receptors, activate both behaviors, while others, such as the increase in blood osmolality or sodium concentration, activate water, but inhibit saline intake. Aldosterone probably activates only saline intake. Clonidine, an a2-adrenergic agonist, inhibits water and saline intake induced by these mechanisms. One model to describe the interactions between these multiple mechanisms is a wire-block diagram, where the brain circuit that controls each intake is represented by a summing point of its respective inhibiting and activating factors. The a2-adrenoceptors constitute an inhibitory factor common to both summing points

  7. A case of ocular thelaziasis in a 2.5 years old Holstein heifer

    Mousa Daradka

    2014-09-01

    Full Text Available A 2.5-years-old, Holstein lactating dairy cow was presented to the Veterinary Health Center with severe conjunctivitis and exuberant granulation tissue formation of the left eye. Upon close examination of the eye, a 2-cm long slender-shaped nematode was found in the conjunctival sac. The nematode was examined by a veterinary parasitologist and determined to be Thelazia species. The exuberant granulation tissue was surgically removed and a total of 0.5 mL of 1% levamisole was injected subconjunctivally. Levamesole was also injected subcutaneously at a dose of 10 mg/kg of body weight and repeated after 15 days. The cow made a complete recovery within 25 days following treatment. This is the first case report of ocular thelaziasis in dairy cattle in Jordan.

  8. PRE-DISCOVERY OBSERVATIONS OF DISRUPTING ASTEROID P/2010 A2

    Jewitt, David; Stuart, Joseph S.; Li Jing

    2011-01-01

    Solar system object P/2010 A2 is the first-noticed example of the aftermath of a recently disrupted asteroid, probably resulting from a collision. Nearly a year elapsed between its inferred initiation in early 2009 and its eventual detection in early 2010. Here, we use new observations to assess the factors underlying the visibility, especially to understand the delayed discovery. We present pre-discovery observations from the LINEAR telescope and set limits to the early-time brightness from SOHO and STEREO satellite coronagraphic images. Consideration of the circumstances of discovery of P/2010 A2 suggests that similar objects must be common, and that future all-sky surveys will reveal them in large numbers.

  9. Purification, identification and preliminary crystallographic studies of a 2S albumin seed protein from Lens culinaris

    Gupta, Pankaj; Gaur, Vineet; Salunke, Dinakar M.

    2008-01-01

    A 2S albumin from L. culinaris was purified and crystallized and preliminary crystallographic studies were carried out. Lens culinaris (lentil) is a widely consumed high-protein-content leguminous crop. A 2S albumin protein (26.5 kDa) has been identified using NH 2 -terminal sequencing from a 90% ammonium sulfate saturation fraction of total L. culinaris seed protein extract. The NH 2 -terminal sequence shows very high homology to PA2, an allergy-related protein from Pisum sativum. The 2S albumin protein was purified using a combination of size-exclusion and ion-exchange chromatography. Crystals of the 2S seed albumin obtained using the hanging-drop vapour-diffusion method diffracted to 2.5 Å resolution and were indexed in space group P4 1 (or P4 3 ), with unit-cell parameters a = b = 78.6, c = 135.2 Å

  10. Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without Addiction

    Yun-Fang Jia

    2017-07-01

    Full Text Available While downregulation of excitatory amino acid transporter 2 (EAAT2, the main transporter removing glutamate from the synapse, has been recognized in bipolar disorder (BD, the underlying mechanisms of downregulation have not been elucidated. BD is influenced by environmental factors, which may, via epigenetic modulation of gene expression, differentially affect illness presentation. This study thus focused on epigenetic DNA methylation regulation of SLC1A2, encoding for EAAT2, in BD with variable environmental influences of addiction. High resolution melting PCR (HRM-PCR and thymine–adenine (TA cloning with sequence analysis were conducted to examine methylation of the promoter region of the SLC1A2. DNA was isolated from blood samples drawn from BD patients (N = 150 with or without addiction to alcohol, nicotine, or food, defined as binge eating, and matched controls (N = 32. In comparison to controls, the SLC1A2 promoter region was hypermethylated in BD without addiction but was hypomethylated in BD with addiction. After adjusting for age and sex, the association of methylation levels with nicotine addiction (p = 0.0009 and binge eating (p = 0.0002 remained significant. Consistent with HRM-PCR, direct sequencing revealed increased methylation in CpG site 6 in BD, but decreased methylation in three CpG sites (6, 48, 156 in BD with alcohol and nicotine addictions. These results suggest that individual point methylation within the SLC1A2 promoter region may be modified by exogenous addiction and may have a potential for developing clinically valuable epigenetic biomarkers for BD diagnosis and monitoring.

  11. Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling

    Ježek, Jan; Jabůrek, Martin; Zelenka, Jaroslav; Ježek, Petr

    2010-01-01

    Roč. 59, č. 5 (2010), s. 737-747 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA303/07/0105; GA MŠk ME09018; GA AV ČR(CZ) KJB500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : Heart mitochondrial phospholipase A2 * Fatty Acids * Adenine nucleotide translocase Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  12. Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption.

    Cornelis, Marilyn C; El-Sohemy, Ahmed; Campos, Hannia

    2007-07-01

    Caffeine is the most widely consumed stimulant in the world, and individual differences in response to its stimulating effects may explain some of the variability in caffeine consumption within a population. We examined whether genetic variability in caffeine metabolism [cytochrome P450 1A2 (CYP1A2) -163A-->C] or the main target of caffeine action in the nervous system [adenosine A(2A) receptor (ADORA2A) 1083C-->T] is associated with habitual caffeine consumption. Subjects (n=2735) were participants from a study of gene-diet interactions and risk of myocardial infarction who did not have a history of hypertension. Genotype frequencies were examined among persons who were categorized according to their self-reported daily caffeine intake, as assessed with a validated food-frequency questionnaire. The ADORA2A, but not the CYP1A2, genotype was associated with different amounts of caffeine intake. Compared with persons consuming caffeine/d, the odds ratios for having the ADORA2A TT genotype were 0.74 (95% CI: 0.53, 1.03), 0.63 (95% CI: 0.48, 0.83), and 0.57 (95% CI: 0.42, 0.77) for those consuming 100-200, >200-400, and >400 mg caffeine/d, respectively. The association was more pronounced among current smokers than among nonsmokers (P for interaction = 0.07). Persons with the ADORA2A TT genotype also were significantly more likely to consume less caffeine (ie, caffeine consumption increases. This observation provides a biologic basis for caffeine consumption behavior and suggests that persons with this genotype may be less vulnerable to caffeine dependence.

  13. A partial gene deletion of SLC45A2 causes oculocutaneous albinism in Doberman pinscher dogs.

    Paige A Winkler

    Full Text Available The first white Doberman pinscher (WDP dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1 produce a detailed description of the ocular phenotype of WDPs, (2 objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3 determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs; cutaneous tumors were noted in 12/20 WDP (5 years of age: 8/8 and 1/20 SDPs (p<0.00001. Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968-77,067,051. This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model.

  14. With a 2k-ADC to 4k-spectrometry via two biased amplifiers

    Goerner, W; Kleeberg, H [Zentralinstitut fuer Kernforschung, Rossendorf bei Dresden (German Democratic Republic)

    1978-01-12

    In order to obtain the double digital spread in high resolution nuclear spectrometry, two biased amplifiers were linked in parallel mode to the 10 V-input of a 2k-ADC. The arrangement works like a hybrid (1 bit scale - 11 bits Wilkinson) converter. A careful adjustment of the two bias levels (approximately 0V and approximately 6V) and the post-amplification (approximately 2) delivered a good linearity of the 4k-spectrum.

  15. Operational characteristics of a 100-mA, 2-MeV radio-frequency quadrupole

    Johnson, K.F.; Cottingame, W.B.; Bolme, G.O.; Fortgang, C.M.; Ingalls, W.B.; Marquardt, J.; Rusthoi, D.P.; Sander, O.R.; Smith, M.; Worth, G.T.

    1993-01-01

    A 100-mA, 2.07-MeV Radio-Frequency Quadrupole (RFQ III) has been commissioned and operated routinely on the Accelerator Test Stand (ATS) [1] at Los Alamos National Laboratory. To characterize the RFQ output beam dynamics, measurements were made of the beam transmission and of the transverse and longitudinal phase-space distributions. Data were taken for different RFQ III operating conditions and compared to simulations

  16. A 2 MV heavy ion Van de Graaff implanter for research and development

    Hemment, P.L.F.; Sealy, B.J.; Stephens, K.G.; Mynard, J.E.; Jeynes, C.; Browton, M.D.; Wilson, R.J.; Ma, M.X.; Cansell, A.; Mous, D.J.W.; Koudijs, R.

    1993-01-01

    A high energy heavy ion implantation system is described which is based upon a 2 MV High Voltage Engineering Europa Van de Graaff accelerator, which incorporates an ion source rapid exchange mechanism. The design and performance are described with particular reference to the system mass resolution, beam transport and performance of a sputter ion source. The system is used to provide a wide ranging implantation service and also supports material science studies, some of which are described briefly. (orig.)

  17. Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa

    Zheng, Zhaojun; Tharmalingam, Nagendran; Liu, Qingzhong; Jayamani, Elamparithi; Kim, Wooseong; Fuchs, Beth Burgwyn; Zhang, Rijun; Vilcinskas, Andreas; Mylonakis, Eleftherios

    2017-01-01

    The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrug-resistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36-residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pat...

  18. Weak coupling theory of the ripplon limited mobility of a 2-D electron lattice

    Dahm, A.J.; Mehrotra, R.

    1981-01-01

    The one ripplon-n phonon scattering contribution to the mobility of a 2D electron lattice supported by a liquid helium substrate is calculated in first order perturbation theory to all orders of n in the weak coupling limit. The Debye Waller factor is shown to limit the momentum transfer at large ripplon wave-vectors and high temperatures causing a minimum in the mobility as a function of temperature. (orig.)

  19. Phase states of a 2D easy-plane ferromagnet with strong inclined anisotropy

    Fridman, Yu. A.; Klevets, F. N.; Gorelikov, G. A.; Meleshko, A. G.

    2012-01-01

    We investigate the spin states of a 2D film exhibiting easy-axis anisotropy and a strong single-ion inclined anisotropy whose axis forms a certain angle with the normal to the film surface. Such a system may have an angular ferromagnetic phase, a spatially inhomogeneous state, and a quadrupole phase, whose realization depends substantially on the inclined anisotropy and the orientation of the wavevector in the film plane.

  20. MULTIBAND OPTICAL OBSERVATION OF THE P/2010 A2 DUST TAIL

    Kim, Junhan [303-201, Mokdong Apartment, Mok-5-dong, Yangcheon-gu, Seoul 158-753 (Korea, Republic of); Ishiguro, Masateru [Department of Physics and Astronomy, Seoul National University, San 56-1, Silim-dong, Gwanak-gu, Seoul 151-742 (Korea, Republic of); Hanayama, Hidekazu [Ishigakijima Astronomical Observatory, National Astronomical Observatory of Japan, Ishigaki, Okinawa 907-0024 (Japan); Hasegawa, Sunao; Usui, Fumihiko; Sarugaku, Yuki [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 252-5210 (Japan); Yanagisawa, Kenshi [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Asaguchi, Okayama 719-0232 (Japan); Watanabe, Jun-ichi [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan); Yoshida, Michitoshi, E-mail: ishiguro@astro.snu.ac.kr [Hiroshima Astrophysical Science Center, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526 (Japan)

    2012-02-10

    An inner main-belt asteroid, P/2010 A2, was discovered on 2010 January 6. Based on its orbital elements, it is considered that the asteroid belongs to the Flora collisional family, where S-type asteroids are common, while showing a comet-like dust tail. Although analysis of images taken by the Hubble Space Telescope and Rosetta spacecraft suggested that the dust tail resulted from a recent head-on collision between asteroids, an alternative idea of ice sublimation was suggested based on the morphological fitting of ground-based images. Here, we report a multiband observation of P/2010 A2 made on 2010 January with a 105 cm telescope at the Ishigakijima Astronomical Observatory. Three broadband filters, g', R{sub c} , and I{sub c} , were employed for the observation. The unique multiband data reveal that the reflectance spectrum of the P/2010 A2 dust tail resembles that of an Sq-type asteroid or that of ordinary chondrites rather than that of an S-type asteroid. Due to the large error of the measurement, the reflectance spectrum also resembles the spectra of C-type asteroids, even though C-type asteroids are uncommon in the Flora family. The reflectances relative to the g' band (470 nm) are 1.096 {+-} 0.046 at the R{sub c} band (650 nm) and 1.131 {+-} 0.061 at the I{sub c} band (800 nm). We hypothesize that the parent body of P/2010 A2 was originally S-type but was then shattered upon collision into scattering fresh chondritic particles from the interior, thus forming the dust tail.

  1. Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy.

    Falik Zaccai, Tzipora C; Savitzki, David; Zivony-Elboum, Yifat; Vilboux, Thierry; Fitts, Eric C; Shoval, Yishay; Kalfon, Limor; Samra, Nadra; Keren, Zohar; Gross, Bella; Chasnyk, Natalia; Straussberg, Rachel; Mullikin, James C; Teer, Jamie K; Geiger, Dan; Kornitzer, Daniel; Bitterman-Deutsch, Ora; Samson, Abraham O; Wakamiya, Maki; Peterson, Johnny W; Kirtley, Michelle L; Pinchuk, Iryna V; Baze, Wallace B; Gahl, William A; Kleta, Robert; Anikster, Yair; Chopra, Ashok K

    2017-02-01

    Leukoencephalopathies are a group of white matter disorders related to abnormal formation, maintenance, and turnover of myelin in the central nervous system. These disorders of the brain are categorized according to neuroradiological and pathophysiological criteria. Herein, we have identified a unique form of leukoencephalopathy in seven patients presenting at ages 2 to 4 months with progressive microcephaly, spastic quadriparesis, and global developmental delay. Clinical, metabolic, and imaging characterization of seven patients followed by homozygosity mapping and linkage analysis were performed. Next generation sequencing, bioinformatics, and segregation analyses followed, to determine a loss of function sequence variation in the phospholipase A 2 -activating protein encoding gene (PLAA). Expression and functional studies of the encoded protein were performed and included measurement of prostaglandin E 2 and cytosolic phospholipase A 2 activity in membrane fractions of fibroblasts derived from patients and healthy controls. Plaa-null mice were generated and prostaglandin E 2 levels were measured in different tissues. The novel phenotype of our patients segregated with a homozygous loss-of-function sequence variant, causing the substitution of leucine at position 752 to phenylalanine, in PLAA, which causes disruption of the protein's ability to induce prostaglandin E 2 and cytosolic phospholipase A 2 synthesis in patients' fibroblasts. Plaa-null mice were perinatal lethal with reduced brain levels of prostaglandin E 2 The non-functional phospholipase A 2 -activating protein and the associated neurological phenotype, reported herein for the first time, join other complex phospholipid defects that cause leukoencephalopathies in humans, emphasizing the importance of this axis in white matter development and maintenance. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email

  2. Electron distributions of the first-row homonuclear diatomic molecules, A2

    Ramirez, B.I.; Bielefeld Univ.

    1982-08-01

    Electron momentum density contour maps of the first-row homonuclear diatomic molecules, A 2 , are obtained from near Hartree-Fock wave functions. Both the total momentum density and momentum density difference (molecule - isolated atoms) maps present trends that may be related to the binding in the molecules. These results are compared with the corresponding charge density maps in position space (Bader, Henneker and Cade 1967). (author)

  3. Quenching rates and fluorescence efficiency in the A 2Σ+ state of OH

    Selzer, P.M.; Wang, C.C.

    1979-01-01

    Using direct lifetime measurements at pressures up to 25 Torr, the quenching rates for the A 2 Σ + (v=0) state of OH due to N 2 , O 2 , H 2 O, and air have been determined. These values are in general agreement with other direct lifetime measurements obtained in the millitorr range and show that the quenching cross sections are pressure independent. The implications of these values on the previous ambient OH measurements are discussed

  4. A 2+1 non-isospectral discrete integrable system and its discrete integrable coupling system

    Yu Fajun; Zhang Hongqing

    2006-01-01

    In this Letter by considering a (2+1)-dimensional discrete non-isospectral linear problem, a new (2+1)-dimensional integrable lattice hierarchy is constructed. It shows that generalization of the Blaszak-Marciniak lattice hierarchy can be obtained as a reduction. Then an extended algebraic system X-bar of X is presented, from which the integrable coupling system of the (2+1)-dimensional discrete non-isospectral Blaszak-Marciniak lattice equations are obtained

  5. Condition Assessment of a 2,500-Year-Old Mummy Coffin

    Robert J. Ross; Turker Dundar

    2012-01-01

    This work was conducted to assess the condition of a 2,500-year-old mummy coffin. The coffin, part of a collection of funerary objects at the Nelson–Atkins Museum of Art in St. Louis, Missouri, is made of wood obtained from a sycamore fig tree, Ficus sycomorus. Visual and acoustic-based nondestructive testing techniques were used to inspect the...

  6. Antioxidant tempol suppresses heart cytosolic phospholipase A(2)alpha stimulated by chronic intermittent hypoxia

    Míčová, P.; Klevstig, Martina; Holzerová, Kristýna; Vecka, M.; Žurmanová, J.; Neckář, Jan; Kolář, František; Nováková, Olga; Novotný, J.; Hlaváčková, Markéta

    2017-01-01

    Roč. 95, č. 8 (2017), s. 920-927 ISSN 0008-4212 R&D Projects: GA ČR(CZ) GJ16-12420Y; GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : heart * chronic intermittent hypoxia * oxidative stress * phospholipases A(2) * tempol Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Biochemistry and molecular biology Impact factor: 1.822, year: 2016

  7. Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

    Zhang, Huan; Su, Yu-liang; Yu, Herbert; Qian, Bi-yun

    2012-01-01

    MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05–1.27; CC vs. TT, OR=1.23, 95%CI=1.08–1.39; Dominant model, OR=1.17, 95%CI=1.06–1.30; Additive model, OR=1.08, 95%CI=1.01–1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations

  8. A nutrient-regulated, dual localization phospholipase A2 in the symbiotic fungus Tuber borchii

    Soragni, Elisabetta; Bolchi, Angelo; Balestrini, Raffaella; Gambaretto, Claudio; Percudani, Riccardo; Bonfante, Paola; Ottonello, Simone

    2001-01-01

    Important morphogenetic transitions in fungi are triggered by starvation-induced changes in the expression of structural surface proteins. Here, we report that nutrient deprivation causes a strong and reversible up-regulation of TbSP1, a surface-associated, Ca2+-dependent phospholipase from the mycorrhizal fungus Tuber borchii. TbSP1 is the first phospholipase A2 to be described in fungi and identifies a novel class of phospholipid-hydrolyzing enzymes. The TbSP1 phospholipase, which is synthesized initially as a pre-protein, is processed efficiently and secreted during the mycelial phase. The mature protein, however, also localizes to the inner cell wall layer, close to the plasma membrane, in both free-living and symbiosis-engaged hyphae. It thus appears that a dual localization phospholipase A2 is involved in the adaptation of a symbiotic fungus to conditions of persistent nutritional limitation. Moreover, the fact that TbSP1-related sequences are present in Streptomyces and Neurospora, and not in wholly sequenced non-filamentous microorganisms, points to a general role for TbSP1 phospholipases A2 in the organization of multicellular filamentous structures in bacteria and fungi. PMID:11566873

  9. Effects of a phospholipase A2 inhibitor on uptake and toxicity of liposomes containing plant phosphatidylinositol

    Jett, M.; Alving, C.R.

    1986-01-01

    Plant phosphatidylinositol (PI) has been shown by us to have a direct cytotoxic effect on cultured tumor cells but not on normal cells. Synthetic PI containing 14 C-linoleic acid in the sn-2 position, also showed the same pattern of selective cytotoxicity. When the metabolic fate of synthetic PI was examined with tumor cells, the radioactivity which no longer occurred as PI, was found as either products of phospholipase A 2 (93%, free fatty acids and phosphatidylcholine) or phospholipase C (7%, diglycerides). Uptake of liposomal PI was directly correlated with cytotoxicity. They tested a variety of inhibitors to see the effect on uptake and/or cytotoxicity of plant PI. General metabolic inhibitors such as metrizamide or sodium azide did not alter cellular uptake of the plant PI liposomes. Inhibitors of lipoxygenase formation, such as indomethacin, also did not alter the uptake or cytotoxicity induced by plant PI. Quinacrine, an inhibitor of phospholipase A 2 , decreased the uptake of the PI containing liposomes to 50% of that seen in the presence or absence of any other inhibitor. Although quinacrine is itself toxic to cells, at low concentrations of quinacrine, plant PI did not show the same degree of cytotoxicity as in the absence of quinacrine. These data are compatible with the hypothesis that plant PI exerts cytotoxicity by serving as a substrate for phospholipase A 2

  10. Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells.

    Steffen Nyegaard

    Full Text Available Secretory phospholipase A2 (sPLA2 is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.

  11. Measurement of radiative widths of $a_2(1320)$ and $\\pi_2(1670)$

    Adolph, C; Alekseev, M G; Alexeev, G D; Amoroso, A; Andrieux, V; Anosov, V; Austregesilo, A; Badelek, B; Balestra, F; Barth, J; Baum, G; Beck, R; Bedfer, Y; Berlin, A; Bernhard, J; Bicker, K; Bieling, J; Birsa, R; Bisplinghoff, J; Bodlak, M; Boer, M; Bordalo, P; Bradamante, F; Braun, C; Bressan, A; Buchele, M; Burtin, E; Capozza, L; Chiosso, M; Chung, S U; Cicuttin, A; Crespo, M L; Curiel, Q; Dalla Torre, S; Dasgupta, S S; Dasgupta, S; Denisov, O Yu; Donskov, S V; Doshita, N; Duic, V; Dunnweber, W; Dziewiecki, M; Efremov, A; Elia, C; Eversheim, P D; Eyrich, W; Faessler, M; Ferrero, A; Filin, A; Finger, M; Finger jr, M; Fischer, H; Franco, C; du Fresne von Hohenesche, N; Friedrich, J.M; Frolov, V; Gautheron, F; Gavrichtchouk, O P; Gerassimov, S; Geyer, R; Gnesi, I; Gobbo, B; Goertz, S; Gorzellik, M; Grabmuller, S; Grasso, A; Grube, B; Guskov, A; Guthorl, T; Haas, F; von Harrach, D; Hahne, D; Hashimoto, R; Heinsius, F H; Herrmann, F; Hinterberger, F; Hoppner, Ch; Horikawa, N; d'Hose, N; Huber, S; Ishimoto, S; Ivanov, A; Ivanshin, Yu; Iwata, T; Jahn, R; Jary, V; Jasinski, P; Jorg, P; Joosten, R; Kabuss, E; Ketzer, B; Khaustov, G V; Khokhlov, Yu A; Kisselev, Yu; Klein, F; Klimaszewski, K; Koivuniemi, J H; Kolosov, V N; Kondo, K; Konigsmann, K; Konorov, I; Konstantinov, V F; Kotzinian, A M; Kouznetsov, O; Kral, Z; Kramer, M; Kroumchtein, Z V; Kuchinski, N; Kunne, F; Kurek, K; Kurjata, R P; Lednev, A.A; Lehmann, A; Levorato, S; Lichtenstadt, J; Maggiora, A; Magnon, A; Makke, N; Mallot, G K; Marchand, C; Martin, A; Marzec, J; Matousek, J; Matsuda, H; Matsuda, T; Meshcheryakov, G; Meyer, W; Michigami, T; Mikhailov, Yu V; Miyachi, Y; Nagaytsev, A; Nagel, T; Nerling, F; Neubert, S; Neyret, D; Nikolaenko, V I; Novy, J; Nowak, W D; Nunes, A S; Orlov, I; Olshevsky, A G; Ostrick, M; Panknin, R; Panzieri, D; Parsamyan, B; Paul, S; Pesek, M; Platchkov, S; Pochodzalla, J; Polyakov, V A; Pretz, J; Quaresma, M; Quintans, C; Ramos, S; Reicherz, G; Rocco, E; Rychter, A; Rossiyskaya, N S; Ryabchikov, D I; Samoylenko, V D; Sandacz, A; Sarkar, S; Savin, I A; Sbrizzai, G; Schiavon, P; Schill, C; Schluter, T; Schmidt, A; Schmidt, K; Schmieden, H; Schonning, K; Schopferer, S; Schott, M; Shevchenko, O Yu; Silva, L; Sinha, L; Sirtl, S; Slunecka, M; Sosio, S; Sozzi, F; Srnka, A; Steiger, L; Stolarski, M; Sulc, M; Sulej, R; Suzuki, H; Szabelski, A; Szameitat, T; Sznajder, P; Takekawa, S; ter Wolbeek, J; Tessaro, S; Tessarotto, F; Thibaud, F; Uhl, S; Uman, I; Vandenbroucke, M; Virius, M; Vondra, J; Wang, L; Weisrock, T; Wilfert, M; Windmolders, R; Wollny, H; Zaremba, K; Zavertyaev, M; Zemlyanichkina, E; Ziembicki, M

    2014-01-01

    The COMPASS Collaboration at CERN has investigated the reaction $\\pi^- \\gamma \\rightarrow \\pi^-\\pi^-\\pi^+$ embedded in the Primakoff reaction of $190~\\textrm{GeV}$ pions scattering in the Coulomb field of a lead target, $\\pi^- \\text{Pb} \\rightarrow \\pi^-\\pi^-\\pi^+ \\text{Pb}$. Exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at momentum transfer below $0.001~(\\text{GeV}/c)^2$. Using a partial-wave analysis the amplitudes and relative phases of the $a_2(1320)$ and $\\pi_2(1670)$ mesons have been extracted, and the Coulomb and the diffractive contributions have been disentangled. Measuring absolute production cross sections we have determined the radiative width of the $a_2(1320)$ to be $\\Gamma_0(a_2(1320) \\rightarrow \\pi\\gamma) = (358 \\pm 6_{\\textrm{stat}} \\pm 42_{\\textrm{syst}})~\\textrm{keV}$. As the first measurement, $\\Gamma_0(\\pi_2(1670) \\rightarrow \\pi\\gamma) = (181 \\pm 11_{\\textrm{stat}} \\pm 27_{\\textrm{syst}})~\\textrm{keV} \\cdot (\\textrm{BR}^{\\textrm{PDG}}_{f_2 \\pi}/...

  12. Measurement of radiative widths of a2(1320) and π2(1670)

    Adolph, C.; Braun, C.; Eyrich, W.; Lehmann, A.; Schmidt, A.; Akhunzyanov, R.; Alexeev, G.D.; Anosov, V.; Efremov, A.; Gavrichtchouk, O.P.; Guskov, A.; Ivanov, A.; Ivanshin, Yu.; Kisselev, Yu.; Kouznetsov, O.; Kroumchtein, Z.V.; Kuchinski, N.; Meshcheryakov, G.; Nagaytsev, A.; Orlov, I.; Olshevsky, A.G.; Rossiyskaya, N.S.; Savin, I.A.; Shevchenko, O.Yu.; Slunecka, M.; Zemlyanichkina, E.; Alexeev, M.G.; Birsa, R.; Dalla Torre, S.; Dasgupta, S.; Gobbo, B.; Levorato, S.; Sozzi, F.; Steiger, L.; Tessaro, S.; Tessarotto, F.; Amoroso, A.; Balestra, F.; Chiosso, M.; Gnesi, I.; Grasso, A.; Kotzinian, A.M.; Parsamyan, B.; Sosio, S.; Andrieux, V.; Bedfer, Y.; Boer, M.; Burtin, E.; Capozza, L.; Curiel, Q.; Ferrero, A.; Hose, N. d'; Kunne, F.; Magnon, A.; Marchand, C.; Neyret, D.; Platchkov, S.; Thibaud, F.; Vandenbroucke, M.; Wollny, H.; Austregesilo, A.; Bicker, K.; Badelek, B.; Barth, J.; Bieling, J.; Goertz, S.; Hahne, D.; Klein, F.; Panknin, R.; Pretz, J.; Schmieden, H.; Windmolders, R.; Baum, G.; Beck, R.; Bisplinghoff, J.; Eversheim, P.D.; Hinterberger, F.; Jahn, R.; Joosten, R.; Berlin, A.; Gautheron, F.; Koivuniemi, J.H.; Meyer, W.; Reicherz, G.; Wang, L.; Bernhard, J.; Harrach, D. von; Jasinski, P.; Kabuss, E.; Nerling, F.; Ostrick, M.; Pochodzalla, J.; Weisrock, T.; Wilfert, M.; Bodlak, M.; Finger, M.; Finger, M.; Matousek, J.; Pesek, M.; Bordalo, P.; Franco, C.; Nunes, A.S.; Quaresma, M.; Quintans, C.; Ramos, S.; Silva, L.; Stolarski, M.; Bradamante, F.; Bressan, A.; Elia, C.; Makke, N.; Martin, A.; Sbrizzai, G.; Schiavon, P.; Buechele, M.; Fischer, H.; Gorzellik, M.; Guthoerl, T.; Heinsius, F.H.; Herrmann, F.; Joerg, P.; Koenigsmann, K.; Nowak, W.D.; Schill, C.; Schmidt, K.; Schopferer, S.; Sirtl, S.; Szameitat, T.; Ter Wolbeek, J.; Chung, S.U.; Friedrich, J.M.; Grabmueller, S.; Grube, B.; Haas, F.; Hoeppner, C.; Huber, S.; Ketzer, B.; Kraemer, M.; Nagel, T.; Neubert, S.; Paul, S.; Uhl, S.; Cicuttin, A.; Crespo, M.L.; Dasgupta, S.S.; Sarkar, S.; Sinha, L.; Denisov, O.Yu.; Maggiora, A.; Takekawa, S.; Donskov, S.V.; Filin, A.; Khaustov, G.V.; Khokhlov, Yu.A.; Kolosov, V.N.; Konstantinov, V.F.; Lednev, A.A.; Mikhailov, Yu.V.; Nikolaenko, V.I.; Polyakov, V.A.; Ryabchikov, D.I.; Samoylenko, V.D.; Doshita, N.; Hashimoto, R.; Ishimoto, S.; Iwata, T.; Kondo, K.; Matsuda, H.; Michigami, T.; Miyachi, Y.; Suzuki, H.; Duic, V.; Duennweber, W.; Faessler, M.; Geyer, R.; Schlueter, T.; Uman, I.; Dziewiecki, M.; Kurjata, R.P.; Marzec, J.; Rychter, A.; Zaremba, K.; Ziembicki, M.; Fresne von Hohenesche, N. du; Frolov, V.; Mallot, G.K.; Rocco, E.; Schoenning, K.; Schott, M.; Gerassimov, S.; Konorov, I.; Horikawa, N.; Jary, V.; Kral, Z.; Novy, J.; Virius, M.; Vondra, J.; Klimaszewski, K.; Kurek, K.; Sandacz, A.; Sulej, R.; Szabelski, A.; Sznajder, P.; Panzieri, D.; Srnka, A.; Sulc, M.; Zavertyaev, M.; Matsuda, T.; Lichtenstadt, J.

    2014-01-01

    The COMPASS Collaboration at CERN has investigated the reaction π - γ → π - π - π + embedded in the Primakoff reaction of 190 GeV pions scattering in the Coulomb field of a lead target, π - Pb → π - π - π + Pb. Exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at momentum transfer below 0.001 (GeV/c) 2 . Using a partial-wave analysis the amplitudes and relative phases of the a 2 (1320) and π 2 (1670) mesons have been extracted, and the Coulomb and the diffractive contributions have been disentangled. Measuring absolute production cross sections we have determined the radiative width of the a 2 (1320) to be Γ 0 (a 2 (1320) → πγ) = (358 ± 6 stat ± 42 syst ) keV. As the first measurement, Γ 0 (π 2 (1670) → πγ) = (181 ± 11 stat ± 27 syst ) keV . (BR PDG f 2 π /BR f 2 π ) is obtained for the radiative width of the π 2 (1670), where in this analysis the branching ratio BR PDG f 2 π = 0.56 has been used. We compare these values to previous measurements and theoretical predictions. (orig.)

  13. Hydrolysis of short-chain phosphatidylcholines by bee venom phospholipase A2.

    Raykova, D; Blagoev, B

    1986-01-01

    In order to find out the aggregation state of the substrate, preferred by bee venom phospholipase A2 (EC 3.1.1.4), its action on short-chain phosphatidylcholines with two identical (C6-C10) fatty acids has been tested. The rate of hydrolysis as a function of acyl chain length showed a maximum at dioctanoylphosphatidylcholine. The effects of alcohols, NaCl and Triton X-100, which affect the aggregation state of phospholipids in water, were also studied. The addition of n-alcohol led to a significant inhibition of the hydrolysis of the substrates present in micellar form and activated the hydrolysis of substrates which form liposomes. The inhibitory effect increased with increasing length of the aliphatic carbon chain of the alcohol. Triton X-100 at low Triton/phospholipid molar ratios enhanced enzyme activity. These results do not agree with the accepted idea that bee venom phospholipase A2 hydrolyzes short-chain lecithins in their molecularly dispersed form and that micelles cannot act as substrates. The data indicate that short-chain lecithins in the aggregated state are hydrolyzed and that the requirements of bee venom phospholipase A2 for the aggregation state of the substrate are not strict.

  14. De novo giant A2 aneurysm following anterior communicating artery occlusion.

    Ibrahim, Tarik F; Hafez, Ahmad; Andrade-Barazarte, Hugo; Raj, Rahul; Niemela, Mika; Lehto, Hanna; Numminen, Jussi; Jarvelainen, Juha; Hernesniemi, Juha

    2015-01-01

    De novo intracranial aneurysms are reported to occur with varying incidence after intracranial aneurysm treatment. They are purported to be observed, however, with increased incidence after Hunterian ligation; particularly in cases of carotid artery occlusion for giant or complex aneurysms deemed unclippable. We report a case of right-sided de novo giant A2 aneurysm 6 years after an anterior communicating artery (ACoA) aneurysm clipping. We believe this de novo aneurysm developed in part due to patient-specific risk factors but also a significant change in cerebral hemodynamics. The ACoA became occluded after surgery that likely altered the cerebral hemodynamics and contributed to the de novo aneurysm. We believe this to be the first reported case of a giant de novo aneurysm in this location. Following parent vessel occlusion (mostly of the carotid artery), there are no reports of any de novo aneurysms in the pericallosal arteries let alone a giant one. The patient had a dominant right A1 and the sudden increase in A2 blood flow likely resulted in increased wall shear stress, particularly in the medial wall of the A2 where the aneurysm occurred 2 mm distal to the A1-2 junction. ACoA preservation is a key element of aneurysm surgery in this location. Suspected occlusion of this vessel may warrant closer radiographic follow-up in patients with other risk factors for aneurysm development.

  15. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Mesquita Sonia MF

    2009-11-01

    Full Text Available Abstract Background Signaling by the vitamin A-derived morphogen retinoic acid (RA is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2 is critical for cardiac development, we screened patients with congenital heart disease (CHDs for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430 at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that

  16. DMPD: Regulation of arachidonic acid release and cytosolic phospholipase A2activation. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 10080535 Regulation of arachidonic acid release and cytosolic phospholipase A2activ...on of arachidonic acid release and cytosolic phospholipase A2activation. PubmedID 10080535 Title Regulation ...of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gij

  17. 26 CFR 301.6104(a)-2 - Public inspection of material relating to pension and other plans.

    2010-04-01

    ... pension and other plans. 301.6104(a)-2 Section 301.6104(a)-2 Internal Revenue INTERNAL REVENUE SERVICE... and Returns Returns and Records § 301.6104(a)-2 Public inspection of material relating to pension and...— (i) A pension, profit-sharing, or stock bonus plan under section 401(a), (ii) An annuity plan under...

  18. 26 CFR 301.6231(a)(2)-1 - Persons whose tax liability is determined indirectly by partnership items.

    2010-04-01

    ... in a partnership. (b) Shareholder of C corporation. A shareholder of a C corporation (as defined in... indirectly by partnership items. 301.6231(a)(2)-1 Section 301.6231(a)(2)-1 Internal Revenue INTERNAL REVENUE... Assessment In General § 301.6231(a)(2)-1 Persons whose tax liability is determined indirectly by partnership...

  19. The V-ATPase a2-subunit as a putative endosomal pH-sensor.

    Marshansky, V

    2007-11-01

    V-ATPase (vesicular H(+)-ATPase)-driven intravesicular acidification is crucial for vesicular trafficking. Defects in vesicular acidification and trafficking have recently been recognized as essential determinants of various human diseases. An important role of endosomal acidification in receptor-ligand dissociation and in activation of lysosomal hydrolytic enzymes is well established. However, the molecular mechanisms by which luminal pH information is transmitted to the cytosolic small GTPases that control trafficking events such as budding, coat formation and fusion are unknown. Here, we discuss our recent discovery that endosomal V-ATPase is a pH-sensor regulating the degradative pathway. According to our model, V-ATPase is responsible for: (i) the generation of a pH gradient between vesicular membranes; (ii) sensing of intravesicular pH; and (iii) transmitting this information to the cytosolic side of the membrane. We also propose the hypothetical molecular mechanism involved in function of the V-ATPase a2-subunit as a putative pH-sensor. Based on extensive experimental evidence on the crucial role of histidine residues in the function of PSPs (pH-sensing proteins) in eukaryotic cells, we hypothesize that pH-sensitive histidine residues within the intra-endosomal loops and/or C-terminal luminal tail of the a2-subunit could also be involved in the pH-sensing function of V-ATPase. However, in order to identify putative pH-sensitive histidine residues and to test this hypothesis, it is absolutely essential that we increase our understanding of the folding and transmembrane topology of the a-subunit isoforms of V-ATPase. Thus the crucial role of intra-endosomal histidine residues in pH-dependent conformational changes of the V-ATPase a2-isoform, its interaction with cytosolic small GTPases and ultimately in its acidification-dependent regulation of the endosomal/lysosomal protein degradative pathway remain to be determined.

  20. Fabrication of titanium removable dental prosthesis frameworks with a 2-step investment coating method.

    Koike, Mari; Hummel, Susan K; Ball, John D; Okabe, Toru

    2012-06-01

    Although pure titanium is known to have good biocompatibility, a titanium alloy with better strength is needed for fabricating clinically acceptable, partial removable dental prosthesis (RDP) frameworks. The mechanical properties of an experimental Ti-5Al-5Cu alloy cast with a 2-step investment technique were examined for RDP framework applications. Patterns for tests for various properties and denture frameworks for a preliminary trial casting were invested with a 2-step coating method using 2 types of mold materials: a less reactive spinel compound (Al(2)O(3)·MgO) and a less expensive SiO(2)-based material. The yield and tensile strength (n=5), modulus of elasticity (n=5), elongation (n=5), and hardness (n=8) of the cast Ti-5Al-5Cu alloy were determined. The external appearance and internal porosities of the preliminary trial castings of denture frameworks (n=2) were examined with a conventional dental radiographic unit. Cast Ti-6Al-4V alloy and commercially pure titanium (CP Ti) were used as controls. The data for the mechanical properties were statistically analyzed with 1-way ANOVA (α=.05). The yield strength of the cast Ti-5Al-5Cu alloy was 851 MPa and the hardness was 356 HV. These properties were comparable to those of the cast Ti-6Al-4V and were higher than those of CP Ti (PAl-5Cu frameworks was found to have been incompletely cast. The cast biocompatible experimental Ti-5Al-5Cu alloy exhibited high strength when cast with a 2-step coating method. With a dedicated study to determine the effect of sprue design on the quality of castings, biocompatible Ti-5Al-5Cu RDP frameworks for a clinical trial can be produced. Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  1. Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A2-induced degranulation in mast cells

    Nishikawa, Hirofumi; Kitani, Seiichi

    2011-01-01

    Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of β-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G M1 ), di-sialoganglioside (G D1a ) and tri-sialoganglioside (G T1b ). In contrast, honeybee venom-derived phospholipase A 2 induced the net degranulation directly without cytotoxicity, which was not inhibited by G M1 , G D1a and G T1b . For analysis of distribution of Gα q and Gα i protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of Gα q and Gα i at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A 2 -induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A 2 -induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting.

  2. Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A(2)-induced degranulation in mast cells.

    Nishikawa, Hirofumi; Kitani, Seiichi

    2011-05-01

    Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of β-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G(M1)), di-sialoganglioside (G(D1a)) and tri-sialoganglioside (G(T1b)). In contrast, honeybee venom-derived phospholipase A(2) induced the net degranulation directly without cytotoxicity, which was not inhibited by G(M1), G(D1a) and G(T1b). For analysis of distribution of Gα(q) and Gα(i) protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of Gα(q) and Gα(i) at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A(2)-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A(2)-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Over-expression of DSCAM and COL6A2 cooperatively generates congenital heart defects.

    Tamar R Grossman

    2011-11-01

    Full Text Available A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS, which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD, and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders.

  4. Central giant cell lesion of the mandible in a 2-year old girl

    Oda, Takaaki; Sue, Mikiko; Okada, Yasuo; Kanri, Yoriaki; Ono, Junya; Ogura, Ichiro [The Nippon Dental University School of Life Dentistry at Niigata, Niigata (Japan)

    2017-09-15

    Central giant cell lesions are rare, benign, osteolytic, pseudocystic, solitary, localized lesions that are common in the skeletal structure, but less so in the maxillofacial region. Furthermore, to perform panoramic radiography and cone-beam computed tomography, it is necessary to prepare patients properly and to position their heads carefully. However, this can be difficult in pediatric patients, who may be anxious. In this report, we describe the case of a central giant cell lesion of the mandible in a 2-year-old girl that was evaluated with multidetector computed tomography.

  5. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation

    Kirkby, Nicholas S.; Reed, Daniel M.; Edin, Matthew L.; Rauzi, Francesca; Mataragka, Stefania; Vojnovic, Ivana; Bishop-Bailey, David; Milne, Ginger L.; Longhurst, Hilary; Zeldin, Darryl C.; Mitchell, Jane A.; Warner, Timothy D.

    2016-01-01

    Eicosanoids are important vascular regulators, but the phospholipase A2 (PLA2) isoforms supporting their production within the cardiovascular system are not fully understood. To address this, we have studied platelets, endothelial cells, and leukocytes from 2 siblings with a homozygous loss-of-function mutation in group IVA cytosolic phospholipase A2 (cPLA2α). Chromatography/mass spectrometry was used to determine levels of a broad range of eicosanoids produced by isolated vascular cells, and in plasma and urine. Eicosanoid release data were paired with studies of cellular function. Absence of cPLA2α almost abolished eicosanoid synthesis in platelets (e.g., thromboxane A2, control 20.5 ± 1.4 ng/ml vs. patient 0.1 ng/ml) and leukocytes [e.g., prostaglandin E2 (PGE2), control 21.9 ± 7.4 ng/ml vs. patient 1.9 ng/ml], and this was associated with impaired platelet activation and enhanced inflammatory responses. cPLA2α-deficient endothelial cells showed reduced, but not absent, formation of prostaglandin I2 (prostacyclin; control 956 ± 422 pg/ml vs. patient 196 pg/ml) and were primed for inflammation. In the urine, prostaglandin metabolites were selectively influenced by cPLA2α deficiency. For example, prostacyclin metabolites were strongly reduced (18.4% of control) in patients lacking cPLA2α, whereas PGE2 metabolites (77.8% of control) were similar to healthy volunteer levels. These studies constitute a definitive account, demonstrating the fundamental role of cPLA2α to eicosanoid formation and cellular responses within the human circulation.—Kirkby, N. S., Reed, D. M., Edin, M. L., Rauzi, F., Mataragka, S., Vojnovic, I., Bishop-Bailey, D., Milne, G. L., Longhurst, H., Zeldin, D. C., Mitchell, J. A., Warner, T. D. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation. PMID:26183771

  6. Characterization of blade throw from a 2.3MW horizontal axis wind turbine upon failure

    Sarlak, Hamid; Sørensen, Jens Nørkær

    2015-01-01

    The present work concerns aerodynamics of thrown objects from a 2.3 MW Horizontal Axis Wind Turbine (HAWT), as a consequence of blade failure. The governing set of ordinary differential equations for the flying objects are derived and numerically solved using a 4th order Runge-Kutta time advancing...... on their size. Thereafter, throw distance picks up exponentially with the tip speed. By comparing the throw distance calculations with and without dynamic stall model being active, it is concluded that dynamic stall does not play a major role in throw distances....

  7. Calibration of a silicon semiconductor detecter using a 2 MeV electron accelerator beam

    Fleurot, N.; Gouard, P.; Mazataud, E.; Nail, M.; Savy, C.; Bayer, C.; Cauchois, Y.; Kherouf, R.; Mathieu, D.

    1981-01-01

    This paper describes the current mode calibration, carried out on a 2 MeV electron accelerator, of PIN detectors involved in electron spectrum measurements for laser-matter interaction experiments. A theoretical analysis simulating the interaction between the incident electrons and the irradiated medium has been carried out using the FOTELEC code. It accounts well for the experimental results giving a reasonable value for the mean electron-hole pair formation energy when back-scattering corrections are included. This work provides the transfer function data required for a plasma diagnostic spectrometer. (orig.)

  8. Space-dependent perfusion coefficient estimation in a 2D bioheat transfer problem

    Bazán, Fermín S. V.; Bedin, Luciano; Borges, Leonardo S.

    2017-05-01

    In this work, a method for estimating the space-dependent perfusion coefficient parameter in a 2D bioheat transfer model is presented. In the method, the bioheat transfer model is transformed into a time-dependent semidiscrete system of ordinary differential equations involving perfusion coefficient values as parameters, and the estimation problem is solved through a nonlinear least squares technique. In particular, the bioheat problem is solved by the method of lines based on a highly accurate pseudospectral approach, and perfusion coefficient values are estimated by the regularized Gauss-Newton method coupled with a proper regularization parameter. The performance of the method on several test problems is illustrated numerically.

  9. A 2 MW, 170 GHz coaxial cavity gyrotron - experimental verification of the design of main components

    Piosczyk, B [Forschungszentrum Karlsruhe, Association EURATOM-FZK, Institut fuer Hochleistungsimpuls- und Mikrowellentechnik (IHM), Postfach 3640, D-76021 Karlsruhe (Germany); Dammertz, G [Forschungszentrum Karlsruhe, Association EURATOM-FZK, Institut fuer Hochleistungsimpuls- und Mikrowellentechnik (IHM), Postfach 3640, D-76021 Karlsruhe (Germany); Dumbrajs, O [Department of Engineering Physics and Mathematics, Helsinki University of Technology, Association EURATOM-TEKES, FIN-02150 Espoo (Finland)] (and others)

    2005-01-01

    A 2 MW, CW, 170 GHz coaxial cavity gyrotron is under development in cooperation between European Research Institutions (FZK Karlsruhe, CRPP Lausanne, HUT Helsinki) and the European tube industry (TED, Velizy, France). The design of critical components has recently been examined experimentally at FZK Karlsruhe with a short pulse ({approx} few ms) coaxial cavity gyrotron. This gyrotron uses the same cavity and the same quasioptical (q.o.) RF-output system as designed for the industrial prototype and a very similar electron gun.

  10. Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period.

    Lovering, E G; Matsui, F; Curran, N M; Robertson, D L; Sears, R W

    1983-08-01

    Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine have been measured over a 2-year period under ambient conditions and under temperature and humidity stress. Hydralazine tablets are stable under ambient conditions, but the hydrazine level in an injectable formulation increased from 4.5 to 10 micrograms/ml over a 23-month period. Isoniazid tablets are also stable, but hydrazine levels in an elixir and a pyridoxine combination product doubled to 44 micrograms/ml and 19 micrograms/tablet, respectively. Levels in phenelzine tablets appeared to remain constant at approximately 60 micrograms/tablet, with considerable tablet-to-tablet variation.

  11. 2-Cosemisimplicial objects in a 2-category, permutohedra and deformations of pseudofunctors

    Elgueta, Josep

    2004-01-01

    In this paper we take up again the deformation theory for $K$-linear pseudofunctors initiated in a previous work (Adv. Math. 182 (2004) 204-277). We start by introducing a notion of a 2-cosemisimplicial object in an arbitrary 2-category and analyzing the corresponding coherence question, where the permutohedra make their appearence. We then describe a general method to obtain cochain complexes of K-modules from (enhanced) 2-cosemisimplicial objects in the 2-category ${\\bf Cat}_K$ of small $K$...

  12. FENDL/A-2.0. Neutron activation cross section data library for fusion applications

    Pashchenko, A.B.; Wienke, H.; Kopecky, J.; Sublet, J.C. Sublet; Forrest, R.A.

    1997-01-01

    This document describes the contents of a comprehensive neutron cross section data library for 13,006 neutron activation reactions with 739 target nuclides from H (A=1,Z=1) to Cm (A=248,Z=96), in the incident energy range up to 20 MeV. FENDL/A-2 is a sublibrary of FENDL-2, the second revision of the evaluated nuclear data library for fusion applications. It is supplemented by a decay data library FENDL/D-2 in ENDF-6 format for 1867 nuclides. The data are available from the IAEA Nuclear Data Section online via INTERNET by FTP command, or on magnetic tape upon request. (author)

  13. Evolution of the EAF library following FENDL/A-2.0

    Forrest, R.A.; Sublet, J.C.

    1999-01-01

    The European Activation File (EAF) project has been an ongoing process performed through European and worldwide co-operation that has led to the creation of succeeding EAF versions. EAF-4.1 was used in the construction of the FENDL/A-2.0 activation library. Since then versions EAF-97, EAF-97.1 and EAF-99 have been released. The latest release, EAF-99, has benefited from the results of integral experiments that have been used to adjust data. Details of some of the corrections used in the construction of EAF-99, and the library itself are described. (author)

  14. Performance tests of a 2-meter grasshopper monochromator at photon factory

    Yanagihara, Mihiro; Maezawa, Hideki; Sasaki, Taizo; Suzuki, Yoshio; Iguchi, Yasuo.

    1984-12-01

    A 2-meter grasshopper monochromator was installed and adjusted at BL-11A in Photon Factory, and performance tests were carried out. The usable photon energy range for the monochromator is 90 to 1000 eV for a 2400 grooves/mm grating, and the flux is 10 8 - 10 9 photons/sec for entrance and exit slit widths of 15 μm. A resolving power of about 2000 is realized at 250 eV for this slit width. (author)

  15. [Dipylidium caninum infection in a 2 year old infant: case report and literature review].

    Neira O, Patricia; Jofré M, Leonor; Muñoz S, Nelson

    2008-12-01

    Dipylidiasis is a zoonotic parasitic infection caused by the dog tapeworm Dipylidium caninum; it affects both feline and canine species and accidentally, humans. In Chile, as well as in other countries, it is an uncommon infection. A case of a 2 year old child from Casablanca, (a city located in the Valparaíso Region), with an infection by D. caninum, is presented. Clinical manifestations are reviewed, as well as epidemiology in domestic and wild animals, cases among the published national literature and its treatment and prevention strategies.

  16. Recurrent parosteal osteosarcoma of the talus in a 2-year-old child

    Jee, W.H.; Choe Bo-Young; Choi, K.H.; Shinn Kyung-Sub; Ok In-Young; Kim Jung-Man; Choi Yeong-Jin

    1998-01-01

    Parosteal osteosarcoma is an uncommon, low-grade malignant bone tumor and is found in an older age group than conventional osteosarcoma. We present a talar parosteal osteosarcoma that recurred twice in a 2-year-old child. To our knowledge, this is the youngest patient reported with a parosteal osteosarcoma. The talus is an unusual site for parosteal osteosarcoma. Inadequate resection due to a diagnosis of juxtacortical chondroma resulted in recurrence of the tumor. The age of the patient, the thick cartilaginous cap, and well-differentiated trabecular bone all contributed to the critical erroneous diagnosis. (orig.)

  17. A Pole Pair Segment of a 2-MW High-Temperature Superconducting Wind Turbine Generator

    Song, Xiaowei (Andy); Mijatovic, Nenad; Kellers, Jürgen

    2017-01-01

    A 2-MW high-temperature superconducting (HTS) generator with 24 pole pairs has been designed for the wind turbine application. In order to identify potential challenges and obtain practical knowledge prior to production, a full-size stationary experimental setup, which is one pole pair segment...... and the setup in terms of the flux density, the operating condition of the HTS winding, and the force-generation capability. Finite element (FE) software MagNet is used to carry out numerical simulations. The findings show that the HTS winding in the setup is a good surrogate for these that would be used...

  18. A Pole Pair Segment of a 2 MW High Temperature Superconducting Wind Turbine Generator

    Song, Xiaowei (Andy); Mijatovic, Nenad; Kellers, Jürgen

    2016-01-01

    A 2 MW high temperature superconducting (HTS) generator with 24 pole pairs has been designed for the wind turbine application. In order to identify potential challenges and obtain practical knowledge prior to production, a fullsize stationary experimental set-up, which is one pole pair segment...... generator and the set-up in terms of the flux density, the operating condition of the HTS winding, and the force-generation capability. Finite element (FE) software MagNet is used to carry out numerical simulations. The findings show that the HTS winding in the set-up is a good surrogate...

  19. Design of a 2.5MW(e) biomass gasification power generation module

    McLellan, R.

    2000-07-01

    The purpose of this contract was to produce a detailed process and mechanical design of a gasification and gas clean up system for a 2.5MW(e) power generation module based on the generation of electrical power from a wood chip feed stock. The design is to enable the detailed economic evaluation of the process and to verify the technical performance data provided by the pilot plant programme. Detailed process and equipment design also assists in the speed at which the technology can be implemented into a demonstration project. (author)

  20. A 2 MJ drum-type homopolar motor-generator: developments and tests

    Bolognani, S.; Gnesotto, F.; Monelli, C.

    1981-01-01

    This paper presents the design work and the first results of a research program on kinetic energy storage and transfer in homopolar machines. A 2 MJ prototype with conventional excitation, two concentric counter-rotating aluminium alloy drum rotors, pneumostatic air bearings and solid brushes is under construction. The performances of several brush-ring materials under various operating conditions have been investigated with a suitable test apparatus and the main results are reported. A thyristor converter has been realized and tested for studying the power smoothing by the homopolar machine of a three-phase grid subject to repeated large power pulses. (author)

  1. [Deadly nightshade (Atropa belladonna) intoxication in a 2-year-old child].

    Laffargue, F; Oudot, C; Constanty, A; Bedu, A; Ketterer-Martinon, S

    2011-02-01

    Plant intoxications account for 5% of all intoxication cases according to French anti-poison centers. We report an uncommon case of intoxication with deadly nightshade (Atropa belladonna) in a 2-year-old child. The child presented at the ER with an atropinic syndrome, both central and peripheral, after ingestion of wild berries a few hours before. The fruit and leaves brought in by the mother allowed the anti-poison center to identify belladonna, in agreement with clinical findings. The child was kept in the intensive care unit for 48 h and progression was favorable with symptomatic treatment. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  2. A 2-Tesla active shield magnet for whole body imaging and spectroscopy

    Davies, F.J.; Elliott, R.T.; Hawksworth, D.G.

    1991-01-01

    This paper reports on the development and testing of a 2T superconducting Active Shield magnet, with a 0.99m diameter warm bore for whole-body Magnetic Resonance Imaging (MRI) and spectroscopy. The magnet and cryostat were designed to meet the same performance standards as existing MRI magnets, but with the volume of the stray field region reduced to less than 4% of that for an unshielded magnet. The 0.5 mT stray field contour is within 5m axially and 3m radially of the magnet center. The system weight is only 14 tonnes

  3. Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

    Gihyun Lee; Hyunsu Bae

    2016-01-01

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases inc...

  4. Membrane Restructuring by Phospholipase A2 Is Regulated by the Presence of Lipid Domains

    Leidy, Chad; Ocampo, Jackson; Duelund, Lars

    2011-01-01

    Secretory phospholipase A2 (sPLA2) catalyzes the hydrolysis of glycerophospholipids. This enzyme is sensitive to membrane structure, and its activity has been shown to increase in the presence of liquid-crystalline/gel (Lα/Lβ) lipid domains. In this work, we explore whether lipid domains can also...... without necessarily destroying the membrane. We confirm by high-performance liquid chromatography the preferential hydrolysis of DMPC within the phase coexistence region of the DMPC/DSPC phase diagram, showing that this preferential hydrolysis is accentuated close to the solidus phase boundary...

  5. Canonical vs. micro-canonical sampling methods in a 2D Ising model

    Kepner, J.

    1990-12-01

    Canonical and micro-canonical Monte Carlo algorithms were implemented on a 2D Ising model. Expressions for the internal energy, U, inverse temperature, Z, and specific heat, C, are given. These quantities were calculated over a range of temperature, lattice sizes, and time steps. Both algorithms accurately simulate the Ising model. To obtain greater than three decimal accuracy from the micro-canonical method requires that the more complicated expression for Z be used. The overall difference between the algorithms is small. The physics of the problem under study should be the deciding factor in determining which algorithm to use. 13 refs., 6 figs., 2 tabs

  6. Performance evaluation of a 2-mode PV grid connected system in Thailand -- Case study

    Jivacate, C.; Mongconvorawan, S.; Sinratanapukdee, E.; Limsawatt, W. [Electricity Generating Authority of Thailand, Nontha Buri (Thailand)

    1994-12-31

    A PV grid connected system with small battery bank has been set up in a rural district, North Thailand in order to demonstrate a 2-mode operation concept. The objective is to gain experience on the PV grid connected concept without battery storage. However, due to the evening peak demand and a rather weak distribution grid which is typical in rural areas, small battery bank is still required to enable the maximum energy transfer to grid for the time being before moving fully to the no battery mode. The analyzed data seems to indicate possible performance improvement by re-arranging the number of PV modules and battery in the string.

  7. The europium and praseodymium hydrolysis in a 2M NaCl environment

    Jimenez R, M.; Lopez G, H.; Solache R, M.; Rojas H, A.

    1998-01-01

    It was studied the europium and praseodymium hydrolysis in a 2M NaCl ion force environment at 303 K, through two methods: this one extraction with dissolvents (lanthanide-water-NaCl-dibenzoylmethane) in presence of a competitive ligand (diglycolic acid) and that one direct potentiometric titration, of soluble species, followed by a computer refining. The values of one or another techniques of the first hydrolysis constants obtained were similar, which demonstrates that the results are reliable. The set of data obtained on the stability constants of hydrolysis products allowed to draw up the distribution diagrams of chemical species, as europium as praseodymium in aqueous environment. (Author)

  8. Intelligent CAMAC crate controller with CC-A2 functionality and VICbus interface

    Erven, W.; Holzer, J.; Kopp, H.; Loevenich, H.W.; Meiling, W.; Zwoll, K.; Bovier, J.; Re, G.; Worm, F.

    1992-01-01

    This paper reports that for nuclear physics experiments at the Julich Cooler Synchrotron COSY a data acquisition system is under development. With this background, and in order to enhance existing CAMAC systems, an intelligent CAMAC crate controller with CC-A2 functionality was developed. The main enhancement is the replacement of the Branch Highway with a new standard of inter-crate connection: the VICbus. The other highlights are: optional use of a Motorola 68030 microprocessor as CAMAC list-processor and optimization of CAMAC blocktransfers, optional Ethernet or Cheapernet connection. This controller is commercially available from CES, Geneva and called VCC 2117

  9. Breakdown transient study of plasma distributions in a 2.45 GHz hydrogen discharge

    Cortázar, O.D., E-mail: daniel.cortazar@uclm.es [Universidad de Castilla-La Mancha, ETSII-INEI, Applied Mechanics and Projects Department, C.J. Cela s/n, 13170 Ciudad Real (Spain); Megía-Macías, A. [ESS Bilbao Consortium, Polígono Ugaldeguren-III Pol. A 7B, 48170-Zamudio, Vizcaya (Spain); Tarvainen, O.; Koivisto, H. [University of Jyväskylä, Department of Physics, PO Box 35 (YFL), 40500 Jyväskylä (Finland)

    2015-05-01

    Plasma distribution transients associated with the breakdown of a 2.45 GHz hydrogen discharge similar to high current microwave ion sources are studied by means of an ultra-fast frame image acquisition system in visible light range. Eight different plasma distributions have been studied by photographing the 2D projections of the discharge through a transparent plasma electrode. The temporal evolution of images in Balmer-alpha and Fulcher band wavelengths have been recorded associated to atomic and molecular excitation and ionization processes. Some unexpected plasma distributions transient behaviors during breakdown are reported.

  10. Atomically Phase-Matched Second-Harmonic Generation in a 2D Crystal

    2016-08-26

    OPEN ORIGINAL ARTICLE Atomically phase-matched second-harmonic generation in a 2D crystal Mervin Zhao1,2,*, Ziliang Ye1,2,*, Ryuji Suzuki3,4,*, Yu...photoluminescence mapping, Raman spectroscopy and atomic -force microscopy. (b) Image produced via scanning and gathering the SH light produced by the 3R-MoS2...arising from a single atomic layer, where the SH light elucidated important information such as the grain boundaries and electronic structure in these ultra

  11. The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation*

    Benilova, Iryna; Gallardo, Rodrigo; Ungureanu, Andreea-Alexandra; Castillo Cano, Virginia; Snellinx, An; Ramakers, Meine; Bartic, Carmen; Rousseau, Frederic; Schymkowitz, Joost; De Strooper, Bart

    2014-01-01

    Missense mutations in alanine 673 of the amyloid precursor protein (APP), which corresponds to the second alanine of the amyloid β (Aβ) sequence, have dramatic impact on the risk for Alzheimer disease; A2V is causative, and A2T is protective. Assuming a crucial role of amyloid-Aβ in neurodegeneration, we hypothesized that both A2V and A2T mutations cause distinct changes in Aβ properties that may at least partially explain these completely different phenotypes. Using human APP-overexpressing primary neurons, we observed significantly decreased Aβ production in the A2T mutant along with an enhanced Aβ generation in the A2V mutant confirming earlier data from non-neuronal cell lines. More importantly, thioflavin T fluorescence assays revealed that the mutations, while having little effect on Aβ42 peptide aggregation, dramatically change the properties of the Aβ40 pool with A2V accelerating and A2T delaying aggregation of the Aβ peptides. In line with the kinetic data, Aβ A2T demonstrated an increase in the solubility at equilibrium, an effect that was also observed in all mixtures of the A2T mutant with the wild type Aβ40. We propose that in addition to the reduced β-secretase cleavage of APP, the impaired propensity to aggregate may be part of the protective effect conferred by A2T substitution. The interpretation of the protective effect of this mutation is thus much more complicated than proposed previously. PMID:25253695

  12. Mapping and industrial IT project to a 2nd semester design-build project

    Nyborg, Mads; Høgh, Stig

    2010-01-01

    CDIO means bringing the engineer's daily life and working practice into the educational system. In our opinion this is best done by selecting an appropriate project from industry. In this paper we describe how we have mapped an industrial IT project to a 2nd semester design-build project in the D......CDIO means bringing the engineer's daily life and working practice into the educational system. In our opinion this is best done by selecting an appropriate project from industry. In this paper we describe how we have mapped an industrial IT project to a 2nd semester design-build project...... in the Diploma IT program at the Technical University of Denmark. The system in question is a weighing system operating in a LAN environment. The system is used in the medical industry for producing tablets. We present the design of a curriculum to support the development of major components of the weighing...... system. A simple teaching model for software engineering is presented which combines technical disciplines with disciplines from section 2-4 in the CDIO syllabus. The implementation of a joint project involving several courses supports the CDIO perspective. Already the traditional IT-diploma education...

  13. Impulse control disorder, lysosomal malfunction and ATP13A2 insufficiency in Parkinsonism.

    Liu, Jun-Ping; Li, Jianfeng; Lu, Yanhua; Wang, Lihui; Chen, Gang

    2017-02-01

    Lysosomal transport of cargos in neurons is essential for neuronal proteostasis, transmission and functional motors and behaviours. Lysosomal malfunction including storage disorders is involved in the pathogenesis of Parkinson's disease (PD). Given the unclear molecular mechanisms of diverse defects in PD phenotypes, especially behavioural deficits, this mini review explores the cellular contexts of PD impulse control disorders and the molecular aspects of lysosomal cross-membrane transports. Focuses are paid to trace metal involvements in α-synuclein assembly in Lewy bodies, the functions and molecular interactions of ATP13A2 as ATPase transporters in lysosomal membranes for cross-membrane trafficking and lysosomal homeostasis, and our current understandings of the neural circuits in ICD. Erroneously polarized distributions of cargos such as metals and lipids on each side of lysosomal membranes triggered by gene mutations and deregulated expression of ATP13A2 may thus instigate sensing protein structural changes such as aggregations, organelle degeneration, and specific neuronal ageing and death in Parkinsonism. © 2016 John Wiley & Sons Australia, Ltd.

  14. Performance assessment of diffuse optical spectroscopic imaging instruments in a 2-year multicenter breast cancer trial

    Leproux, Anaïs; O'Sullivan, Thomas D.; Cerussi, Albert; Durkin, Amanda; Hill, Brian; Hylton, Nola; Yodh, Arjun G.; Carp, Stefan A.; Boas, David; Jiang, Shudong; Paulsen, Keith D.; Pogue, Brian; Roblyer, Darren; Yang, Wei; Tromberg, Bruce J.

    2017-12-01

    We present a framework for characterizing the performance of an experimental imaging technology, diffuse optical spectroscopic imaging (DOSI), in a 2-year multicenter American College of Radiology Imaging Network (ACRIN) breast cancer study (ACRIN-6691). DOSI instruments combine broadband frequency-domain photon migration with time-independent near-infrared (650 to 1000 nm) spectroscopy to measure tissue absorption and reduced scattering spectra and tissue hemoglobin, water, and lipid composition. The goal of ACRIN-6691 was to test the effectiveness of optically derived imaging endpoints in predicting the final pathologic response of neoadjuvant chemotherapy (NAC). Sixty patients were enrolled over a 2-year period at participating sites and received multiple DOSI scans prior to and during 3- to 6-month NAC. The impact of three sources of error on accuracy and precision, including different operators, instruments, and calibration standards, was evaluated using a broadband reflectance standard and two different solid tissue-simulating optical phantoms. Instruments showed <0.0010 mm-1 (10.3%) and 0.06 mm-1 (4.7%) deviation in broadband absorption and reduced scattering, respectively, over the 2-year duration of ACRIN-6691. These variations establish a useful performance criterion for assessing instrument stability. The proposed procedures and tests are not limited to DOSI; rather, they are intended to provide methods to characterize performance of any instrument used in translational optical imaging.

  15. Objectif Express 1 le monde professionnel en français A1/A2

    Tauzin, Béatrice

    2013-01-01

    Avec un nouveau look et des contenus actualisés pour prendre en compte les évolutions du monde de l’entreprise française, la nouvelle édition d'Objectif Express 1 propose une parfaite association entre le français de tous les jours et le français de l'entreprise. 10 unités basées sur des thématiques de l'entreprise : Entrez en contact ; Organisez votre journée ; Trouvez un emploi ... Chaque unité propose : - 4 leçons d'apprentissage (1 leçon = 1 double page) basées sur des tâches concrètes et simples, ancrées dans le monde du travail francophone - 1 double page Outils linguistiques - 1 page Entrainez-vous - 1 page Testez-vous - 2 pages Repères dans chaque unité : des repères culturels et des repères professionnels Toutes les 3 unités, un scénario professionnel pour une mise en œuvre des acquis langagiers et une mobilisation des compétences professionnelles de l'apprenant. Une préparation aux diplômes DFP A2, DELF Pro A1 et A2 et au test BULATS En annexes : des tableaux d...

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

    Agarwal, Jessica; Jewitt, David; Weaver, Harold

    2013-01-01

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

  17. Summary report on the fuel performance modeling of the AFC-2A, 2B irradiation experiments

    Pavel G. Medvedev

    2013-09-01

    The primary objective of this work at the Idaho National Laboratory (INL) is to determine the fuel and cladding temperature history during irradiation of the AFC-2A, 2B transmutation metallic fuel alloy irradiation experiments containing transuranic and rare earth elements. Addition of the rare earth elements intends to simulate potential fission product carry-over from pyro-metallurgical reprocessing. Post irradiation examination of the AFC-2A, 2B rodlets revealed breaches in the rodlets and fuel melting which was attributed to the release of the fission gas into the helium gap between the rodlet cladding and the capsule which houses six individually encapsulated rodlets. This release is not anticipated during nominal operation of the AFC irradiation vehicle that features a double encapsulated design in which sodium bonded metallic fuel is separated from the ATR coolant by the cladding and the capsule walls. The modeling effort is focused on assessing effects of this unanticipated event on the fuel and cladding temperature with an objective to compare calculated results with the temperature limits of the fuel and the cladding.

  18. Textbook Evaluation: An Analysis of Listening Comprehension Parts in Top Notch 2A & 2B

    Afshin Soori

    2015-10-01

    Full Text Available Textbooks are the instruments that assist both teachers and learners in process of second language learning. With respect to the importance of textbooks in a language course, evaluation of course books is a significant issue for most researchers. The present study investigated and analyzed Listening Comprehension parts in Top Notch 2A & 2B 2nd edition. Top Notch 2A & 2B have 10 Units. The number of listening comprehension parts is in the range of 2 to 4 parts in each unit through the book. So the number of listening comprehension parts is not equally distributed. The participants of this study are 10 EFL teachers of two English language Institutes in Jahrom. Strong and weak aspects of Listening Comprehension parts have indicated in this research. The weaknesses involve the pictures and visuals are not clear enough to enhance students' motivation and interest, the audio is not completely suitable for students' English level, and Discussion parts are not stimulating students' talking. Furthermore this study revealed the crucial function of teachers in listening achievement of students. Keywords: textbook evaluation, listening comprehension, ELT

  19. Impact of a 2-Day Critical Care Ultrasound Course during Fellowship Training: A Pilot Study

    Vi Am Dinh

    2015-01-01

    Full Text Available Objectives. Despite the increasing utilization of point-of-care critical care ultrasonography (CCUS, standards establishing competency for its use are lacking. The purpose of this study was to evaluate the effectiveness of a 2-day CCUS course implementation on ultrasound-naïve critical care medicine (CCM fellows. Methods. Prospective evaluation of the impact of a two-day CCUS course on eight CCM fellows’ attitudes, proficiency, and use of CCUS. Ultrasound competency on multiple organ systems was assessed including abdominal, pulmonary, vascular, and cardiac systems. Subjects served as self-controls and were assessed just prior to, within 1 week after, and 3 months after the course. Results. There was a significant improvement in CCM fellows’ written test scores, image acquisition ability, and pathologic image interpretation 1 week after the course and it was retained 3 months after the course. Fellows also had self-reported increased confidence and usage of CCUS applications after the course. Conclusions. Implementation of a 2-day critical care ultrasound course covering general CCUS and basic critical care echocardiography using a combination of didactics, live models, and ultrasound simulators is effective in improving critical care fellows’ proficiency and confidence with ultrasound use in both the short- and long-term settings.

  20. Upgrade of the data acquisition system for the A2 experiment at MAMI

    Neiser, Andreas; Gradl, Wolfgang [Institut fuer Kernphysik, Johann-Joachim-Becher-Weg 45, Mainz (Germany)

    2015-07-01

    The A2 collaboration at the electron accelerator MAMI in Mainz uses energy-tagged photons to produce light mesons off the nucleon. Its current data acquisition system is the major performance bottleneck under typical trigger conditions. Furthermore, the availability of spare parts is limited, which renders the maintainability for the next decade difficult. Thus, an upgraded system is desirable for A2 to achieve the upcoming experimental goals. For this upgrade, an FPGA-based solution using the TRB3 is being considered. The TRB3 is a multi-purpose 4+1 FPGA board, where four peripheral FPGAs communicate with one add-on board each. The central FPGA provides data readout via standard gigabit Ethernet and interconnection to other TRB3s via optical links. The TRB3 collaboration currently provides flexible TDC-in-FPGA firmwares with various discrimination front-ends as well as a 48 channel ADC add-on board with 60 MHz sampling rate and 10 bit resolution. Additionally, an extensive software framework for slow control and readout is available. We present energy and timing measurements with the ADC add-on board at the Crystal Ball NaI(Tl) calorimeter and compare the performance to the currently used COMPASS data acquisition system. Furthermore, we give an outlook on possible feature extraction firmwares and estimate the costs for a complete upgrade of the system.

  1. Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings.

    Mozzillo, Enza; Melis, Daniela; Falco, Mariateresa; Fattorusso, Valentina; Taurisano, Roberta; Flanagan, Sarah E; Ellard, Sian; Franzese, Adriana

    2013-08-01

    Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disease caused by loss of function mutations in the SLC19A2 gene. TRMA is characterized by anemia, deafness, and diabetes. In some cases, optic atrophy or more rarely retinitis pigmentosa is noted. We now report two sisters, the eldest of which presented to a different hospital during childhood with sensorineural deafness, which was treated with a hearing prosthesis, insulin requiring diabetes, retinitis pigmentosa, optic atrophy, and macrocytic anemia. These features initially suggested a clinical diagnosis of Wolfram syndrome (WS). Therapy with thiamine was initiated which resulted in the resolution of the anemia. The younger sister, who was affected with sensorineural deafness, was referred to our hospital for non-autoimmune diabetes. She was found to have macrocytosis and ocular abnormalities. Because a diagnosis of TRMA was suspected, therapy with insulin and thiamine was started. Sequencing analysis of the SLC19A2 gene identified a compound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT) in both sisters. Non-autoimmune diabetes associated with deafness and macrocytosis, without anemia, suggests a diagnosis of TRMA. Patients clinically diagnosed with WS with anemia and/or macrocytosis should be reevaluated for TRMA. © 2012 John Wiley & Sons A/S.

  2. Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

    Lättig, Jens; Böhl, Markus; Fischer, Petra; Tischer, Sandra; Tietböhl, Claudia; Menschikowski, Mario; Gutzeit, Herwig O.; Metz, Peter; Pisabarro, M. Teresa

    2007-08-01

    The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.

  3. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  4. A2 Code - Internal Accident Report. Does it ring a bell?

    HSE Unit

    2015-01-01

    A2 Code* - It is under this designation (used by the CERN community) that the form for internal accident reports is hidden. More specifically it refers to the CERN Safety Code A2 “Reporting of Accidents and Near Misses” (EDMS: 335502 or here via the official Safety Rules website).   Which events should be declared? All accidental events, which cause or could have caused injuries or damage to property or the environment, must be reported especially if they involve: a) a member of the personnel, visitor, temporary labourer or contractor if it occurred on the CERN site or between sites. b) a member of the personnel if it occurred while commuting or during duty travel. Who can fill in the report? The reporting of occurred accidents or near misses should be made by the person involved or by any direct or indirect witness of the event as soon as possible after the event. Contribute to the improvement of Safety within the Organizatio...

  5. Assessment of the fate of silver nanoparticles in the A(2)O-MBR system.

    Yuan, Zhi-Hua; Yang, Xiaoyong; Hu, Anyi; Zheng, Yu-Ming; Yu, Chang-Ping

    2016-02-15

    In this study, we employed a bench scale A(2)O-MBR (anaerobic-anoxic-oxic membrane bioreactor) system to systematically investigate the behavior and distribution of silver nanoparticles (AgNPs) in the activated sludge. The results showed that AgNPs would aggregate and form Ag-sulfur complexes in the activated sludge, and the dissolved silver only reached 13.6 μg/L when AgNPs of 5mg/L was spiked into the A(2)O-MBR. The long-term mass balance analysis showed that most of the silver contents were accumulated in the bioreactor and wasted excess sludge. Only a small fraction (less than 0.5%) of silver could get across the hollow fiber membranes with 0.1 μm nominal pore size in the effluent. In addition, the comparison between total AgNP concentration in aerobic sludge supernatant and effluent suggested that the membrane modules played a role in controlling the discharge of AgNPs into the effluent, especially under a higher influent concentration of AgNPs. Our results also showed that the adsorbed AgNPs or silver complexes in activated sludge still could release dissolved silver at the ambient pH. Thus, since activated sludge could be a sink for AgNPs, the risks of AgNPs in wasted excess sludge during utilization and disposal should be further studied. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

    Grimaldi, Gabriel; Teva, Antonio; Porrozzi, Renato; Pinto, Marcelo A; Marchevsky, Renato S; Rocha, Maria Gabrielle L; Dutra, Miriam S; Bruña-Romero, Oscar; Fernandes, Ana-Paula; Gazzinelli, Ricardo T

    2014-06-01

    Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. The remarkable clinical protection induced by A2 in an animal model that is

  7. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

    Gabriel Grimaldi

    2014-06-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2 protein that protects against experimental L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12 adsorbed in alum (rA2/rhIL-12/alum; two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2 followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum; and plasmid DNA encoding A2 gene (DNA-A2 boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2. Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. CONCLUSIONS

  8. Characterization of Phytophthora infestans populations in Colombia: first report of the A2 mating type.

    Vargas, Angela M; Quesada Ocampo, Lina M; Céspedes, Maria Catalina; Carreño, Natalia; González, Adriana; Rojas, Alejandro; Zuluaga, A Paola; Myers, Kevin; Fry, William E; Jiménez, Pedro; Bernal, Adriana J; Restrepo, Silvia

    2009-01-01

    Phytophthora infestans, the causal agent of late blight in crops of the Solanaceae family, is one of the most important plant pathogens in Colombia. Not only are Solanum lycopersicum, and S. tuberosum at risk, but also several other solanaceous hosts (Physalis peruviana, S. betaceum, S. phureja, and S. quitoense) that have recently gained importance as new crops in Colombia may be at risk. Because little is known about the population structure of Phytophthora infestans in Colombia, we report here the phenotypic and molecular characterization of 97 isolates collected from these six different solanaceous plants in Colombia. All the isolates were analyzed for mating type, mitochondrial haplotypes, genotype for several microsatellites, and sequence of the internal transcribed spacer (ITS) region. This characterization identified a single individual of A2 mating type (from Physalis peruviana) for the first time in Colombia. All isolates had an ITS sequence that was at least 97% identical to the consensus sequence. Of the 97 isolates, 96 were mitochondrial haplotype IIa, with the single A2 isolate being Ia. All isolates were invariant for the microsatellites. Additionally, isolates collected from S. tuberosum and P. peruviana (64 isolates) were tested for: aggressiveness on both hosts, genotype for the isozymes (glucose-6-phosphate isomerase and peptidase), and restriction fragment length polymorphism fingerprint pattern as detected by RG57. Isolates from S. tuberosum were preferentially pathogenic on S. tuberosum, and isolates from P. peruviana were preferentially pathogenic on P. peruviana. The population from these two hosts was dominated by a single clonal lineage (59 of 64 individuals assayed), previously identified from Ecuador and Peru as EC-1. This lineage was mating type A1, IIa for mitochondrial DNA, invariant for two microsatellites, and invariant for both isozymes. The remaining four A1 isolates were in lineages very closely related to EC-1 (named EC-1.1, CO

  9. Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.

    Aase M Raddum

    Full Text Available Annexin A2 (AnxA2 is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motility. To address this question, we studied the effect of heterotetrameric and monomeric forms of AnxA2, as well as its two soluble domains on the formation and maintenance of capillary-like structures by using an in vitro co-culture system consisting of endothelial and smooth muscle cells. In particular, addition of purified domains I and IV of AnxA2 potently inhibited the vascular endothelial growth factor (VEGF-dependent formation of the capillary-like networks in a dose-dependent manner. In addition, these AnxA2 domains disrupted endothelial cell-cell contacts in preformed capillary-like networks, resulting in the internalisation of vascular endothelial (VE-cadherin and the formation of VE-cadherin-containing filopodia-like structures between the endothelial cells, suggesting increased cell motility. Addition of monoclonal AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly inhibited network formation in the co-culture system. These results suggest that extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal role in angiogenesis. The exogenously added AnxA2 domains most likely mediate their effects by competing with endogenous AnxA2 for extracellular factors necessary for the initiation and maintenance of angiogenesis, such as those involved in the formation/integrity of cell-cell contacts.

  10. The analysis of composite laminated beams using a 2D interpolating meshless technique

    Sadek, S. H. M.; Belinha, J.; Parente, M. P. L.; Natal Jorge, R. M.; de Sá, J. M. A. César; Ferreira, A. J. M.

    2018-02-01

    Laminated composite materials are widely implemented in several engineering constructions. For its relative light weight, these materials are suitable for aerospace, military, marine, and automotive structural applications. To obtain safe and economical structures, the modelling analysis accuracy is highly relevant. Since meshless methods in the recent years achieved a remarkable progress in computational mechanics, the present work uses one of the most flexible and stable interpolation meshless technique available in the literature—the Radial Point Interpolation Method (RPIM). Here, a 2D approach is considered to numerically analyse composite laminated beams. Both the meshless formulation and the equilibrium equations ruling the studied physical phenomenon are presented with detail. Several benchmark beam examples are studied and the results are compared with exact solutions available in the literature and the results obtained from a commercial finite element software. The results show the efficiency and accuracy of the proposed numeric technique.

  11. Solar Fuels: Photocatalytic Water Splitting Using a 2‐Photon Approach

    Seger, Brian; Mei, Bastian Timo; Bae, Dowon

    2014-01-01

    While the sun provides orders of magnitude more energy than we consume on earth, it is intermittent, and thus we must have storage reservoirs for when it is dark. Plants have realized early on that storing this energy in the form of molecular fuels is quite effective. In our work, we take...... a similarapproach and look to use solar cells to electrolyze water into hydrogen fuel and an oxygen byproduct. Modelling has shown that to optimize photoelectrolysis efficiency, a 2 photon tandem device (back toback solar cells) should be used. The underlying principle is that one solar cell should absorb high...... these issues and how to integrate them seamlessly together. In this talk I will discuss a) our optimizations of our solar cell, b) how we protect the solar cells from corrosion and c) our H2 and O2evolution catalysts. The talk will focus on what areas of the device we think are highly optimized and whatareas...

  12. Cholestasis caused by panhypopituitarism and acquired cytomegalovirus infection in a 2-month-old male infant

    Chan, U; Chan, Wai-Tao; Ting, Wei-Hsin; Ho, Che-Sheng; Liu, Hsi-Che; Lee, Hung-Chang

    2017-01-01

    Abstract Rationale: Septo-optic dysplasia (SOD) is a rare congenital disorder that may cause jaundice in infants. However, it is usually prone to neglect and misdiagnosis in infants with cholestasis because endocrine disorder such as panhypopituitarism is rare in the cause of infantile cholestasis. We report a case of SOD concurrent with acquired cytomegalovirus (CMV) infection, who presented with prolonged jaundice as the first clinical sign. Patient concerns: The patient was a 2-month-old male infant who presented with cholestasis, combined with fever and panhypopituitarism. Diagnoses: He was diagnosed with SOD and acquired CMV infection. Interventions: He was treated with hormone replacement therapy and ganciclovir. Outcomes: After correction of the pituitary hormone deficiency and ganciclovir treatment, significant improvements of cholestasis, retinal lesions, and growth rate were seen in our patient. Lessons: Although an endocrine disorder such as panhypopituitarism is rare in the cause of neonatal or infantile cholestasis, we must keep this reason in mind. PMID:28445302

  13. Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase

    Glukhova, Alisa; Hinkovska-Galcheva, Vania; Kelly, Robert; Abe, Akira; Shayman, James A.; Tesmer, John J. G.

    2015-03-01

    Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

  14. Enseñanza – aprendizaje de las Colocaciones en Nivel Inicial (A1-A2

    Fernández Lázaro, Gisele

    2014-09-01

    Full Text Available El aprendizaje de las colocaciones en una lengua extranjera conlleva diversos aspectos problemáticos que pueden dificultar la correcta expresión (oral o escrita del aprendiz. Uno de los problemas más recurrentes es la interferencia lingüística o transferencia negativa que los discentes aplican a ciertas colocaciones que se construyen de forma diferente en su lengua materna y en la lengua meta. En el presente trabajo, se analizarán las ventajas que puede implicar para el aprendiz de ELE el conocimiento explícito de las colocaciones desde los primeros niveles de su instrucción y de qué forma puede el docente abordar su enseñanza. Con este fin, se propondrán algunas herramientas y actividades del aula enfocadas a estudiantes de ELE de nivel inicial (A1-A2.

  15. Exercices de grammaire A2 du cadre européen

    Beaulieu, Christian

    2006-01-01

    Destiné à de grands adolescents ou des adultes ayant déjà acquis le niveau A1 en français, ce cahier propose des exercices de grammaire à faire en classe ou en autonomie. Tous les exercices répondent aux exigences du niveau A2 du Cadre européen commun de référence pour les langues. Une structure en 5 unités : Le groupe nominal, Le groupe verbal, Les mots invariables, La phrase, Exprimez. Des exercices variés, illustrés, au champ lexical homogène et classés selon un ordre de difficulté.

  16. Generalised tetanus in a 2-week-old foal: use of physiotherapy to aid recovery.

    Mykkänen, A K; Hyytiäinen, H K; McGowan, C M

    2011-11-01

    A 2-week-old Estonian Draft foal presented with signs of severe generalised tetanus, recumbency and inability to drink. The suspected source of infection was the umbilicus. Medical treatment was administered, including tetanus antitoxin, antimicrobial therapy and phenobarbital to control tetanic spasms. In addition, an intensive physiotherapy program was carried out during the recovery period. Techniques designed for syndromes involving upper motor neuron spasticity in humans were applied. Exercises aimed at weight-bearing and mobility were executed with the help of a walking-frame. The foal made a complete recovery. To our knowledge, this is the first report of the use of physiotherapy in the treatment of tetanus in horses. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

  17. Self-organization and oscillation of negatively charged dust particles in a 2-dimensional dusty plasma

    Song, Y.L. [College of Science, China Agricultural University, Beijing 100083 (China); Huang, F., E-mail: huangfeng@cau.edu.cn [College of Science, China Agricultural University, Beijing 100083 (China); Chen, Z.Y., E-mail: chenzy@mail.buct.edu.cn [Department of Physics, Beijing University of Chemical Technology, Beijing 100029 (China); State Key Laboratory of Laser Propulsion & Application, Beijing 101416 (China); Liu, Y.H. [School of Physics and Optoelectronic Engineering, Ludong University, Yantai 264025 (China); Yu, M.Y. [Institute for Fusion Theory and Simulation, Zhejiang University, Hangzhou 310027 (China); Institute for Theoretical Physics I, Ruhr University, D-44801 Bochum (Germany)

    2016-02-22

    Negatively charged dust particles immersed in 2-dimensional dusty plasma system are investigated by molecular dynamics simulations. The effects of the confinement potential and attraction interaction potential on dust particle self-organization are studied in detail and two typical dust particle distributions are obtained when the system reaches equilibrium. The average radial velocity (ARV), average radial force (ARF) and radial mean square displacement are employed to analyze the dust particles' dynamics. Both ARVs and ARFs exhibit oscillation behaviors when the simulation system reaches equilibrium state. The relationships between the oscillation and confinement potential and attraction potential are studied in this paper. The simulation results are qualitatively similar to experimental results. - Highlights: • Self-organization and oscillation of a 2-dimensional dusty plasma is investigated. • Effect of the confinement potential on dust self-organization and oscillation is given. • Effect of the attraction potential on dust self-organization and oscillation is studied.

  18. Antiphospholipase A2 Receptor Autoantibodies: A Step Forward in the Management of Primary Membranous Nephropathy

    Obrisca, Bogdan; Ismail, Gener; Jurubita, Roxana; Baston, Catalin; Andronesi, Andreea; Mircescu, Gabriel

    2015-01-01

    Since the identification of PLA2R (M-type phospholipase A2 receptor) as the first human antigenic target in primary membranous nephropathy (MN), perpetual progress has been made in understanding the pathogenesis of this disease. Accumulating clinical data support a pathogenic role for the anti-PLA2R antibodies (PLA2R ABs), but confirmation in an animal model is still lacking. However, PLA2R ABs were related to disease activity and outcome, as well as to response therapy. Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. Nevertheless, validation of a universal assay with high precision and definition of cut-off levels, followed by larger studies with a prolonged follow-up period, are needed to confirm these prospects. PMID:26576418

  19. Transition from static to kinetic friction: insights from a 2D model.

    Trømborg, J; Scheibert, J; Amundsen, D S; Thøgersen, K; Malthe-Sørenssen, A

    2011-08-12

    We describe a 2D spring-block model for the transition from static to kinetic friction at an elastic-slider-rigid-substrate interface obeying a minimalistic friction law (Amontons-Coulomb). By using realistic boundary conditions, a number of previously unexplained experimental results on precursory microslip fronts are successfully reproduced. From the analysis of the interfacial stresses, we derive a prediction for the evolution of the precursor length as a function of the applied loads, as well as an approximate relationship between microscopic and macroscopic friction coefficients. We show that the stress buildup due to both elastic loading and microslip-related relaxations depends only weakly on the underlying shear crack propagation dynamics. Conversely, crack speed depends strongly on both the instantaneous stresses and the friction coefficients, through a nontrivial scaling parameter.

  20. Transport Pathways for Light Duty Vehicles: Towards a 2° Scenario

    François Cuenot

    2013-04-01

    Full Text Available The transport sector is the second largest and one of the fastest growing energy end-use sectors, representing 24% of global energy-related greenhouse gas emissions. The International Energy Agency has developed scenarios for the transport sector within the overall concept of mitigation pathways that would be required to limit global warming to 2 °C. This paper builds on these scenarios and illustrates various passenger travel-related strategies for achieving a 2° transport scenario, in particular looking at how much technology improvement is needed in the light of different changes in travel and modal shares in OECD and non-OECD countries. It finds that an integrated approach using all feasible policy options is likely to deliver the required emission reductions at least cost, and that stronger travel-related measures result in significantly lower technological requirements.

  1. A (2 d,3 v) cylindrical, kinetic model of a time-independent, collisionless bounded plasma

    Pedit, H.; Kuhn, S.

    1994-01-01

    A (2 d,3 v) cylindrical, electrostatic, collisionless kinetic model for a wide class of negative-bias de states of the single-ended Q machine is developed. Based on the method presented recently by the authors for an analogous cartesian model, the self-consistent plasma state is found by means of an iterative scheme in which the charge-density and potential distributions are alternately advanced. The electron an ion velocity distribution functions are calculated via trajectory integration, which ensures high accuracy and resolution in both configuration and velocity space. The main differences between cartesian and cylindrical geometry are discussed, and typical macroscopic as well as microscopic quantities for an exemplary special case are presented. (author). 3 refs, 5 figs

  2. Phase Locking of a 2.7 THz Quantum Cascade Laser to a Microwave Reference

    Khosropanah, P.; Baryshev, A.; Zhang, W.; Jellema, W.; Hovenier, J. N.; Gao, J. R.; Klapwijk, T. M.; Paveliev, D. G.; Williams, B. S.; Hu, Q.; hide

    2009-01-01

    We demonstrate the phase locking of a 2.7 THz metal-metal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier chain (x 12) from a microwave synthesizer at approx. 15 GHz. Both laser and reference radiations are coupled into a bolometer mixer, resulting in a beat signal, which is fed into a phase-lock loop. The spectral analysis of the beat signal confirms that the QCL is phase locked. This result opens the possibility to extend heterodyne interferometers into the far-infrared range.

  3. A 2.5-mm diameter probe for photoacoustic and ultrasonic endoscopy.

    Yang, Joon-Mo; Chen, Ruimin; Favazza, Christopher; Yao, Junjie; Li, Chiye; Hu, Zhilin; Zhou, Qifa; Shung, K Kirk; Wang, Lihong V

    2012-10-08

    We have created a 2.5-mm outer diameter integrated photo-acoustic and ultrasonic mini-probe which can be inserted into a standard video endoscope's instrument channel. A small-diameter focused ultrasonic transducer made of PMN-PT provides adequate signal sensitivity, and enables miniaturization of the probe. Additionally, this new endoscopic probe utilizes the same scanning mirror and micromotor-based built-in actuator described in our previous reports; however, the length of the rigid distal section of the new probe has been further reduced to ~35 mm. This paper describes the technical details of the mini-probe and presents experimental results that both quantify the imaging performance and demonstrate its in vivo imaging capability, which suggests that it could work as a mini-probe for certain clinical applications.

  4. A 2-phase labeling and choice architecture intervention to improve healthy food and beverage choices.

    Thorndike, Anne N; Sonnenberg, Lillian; Riis, Jason; Barraclough, Susan; Levy, Douglas E

    2012-03-01

    We assessed whether a 2-phase labeling and choice architecture intervention would increase sales of healthy food and beverages in a large hospital cafeteria. Phase 1 was a 3-month color-coded labeling intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2 added a 3-month choice architecture intervention that increased the visibility and convenience of some green items. We compared relative changes in 3-month sales from baseline to phase 1 and from phase 1 to phase 2. At baseline (977,793 items, including 199,513 beverages), 24.9% of sales were red and 42.2% were green. Sales of red items decreased in both phases (P labeling intervention improved sales of healthy items and was enhanced by a choice architecture intervention.

  5. Ammodytoxin, a neurotoxic secreted phospholipase A2, can act in the cytosol of the nerve cell

    Petrovic, Uros; Sribar, Jernej; Paris, Alenka; Rupnik, Marjan; Krzan, Mojca; Vardjan, Nina; Gubensek, Franc; Zorec, Robert; Krizaj, Igor

    2004-01-01

    Recent identification of intracellular proteins that bind ammodytoxin (calmodulin, 14-3-3 proteins, and R25) suggests that this snake venom presynaptically active phospholipase A 2 acts intracellularly. As these ammodytoxin acceptors are cytosolic and mitochondrial proteins, the toxin should be able to enter the cytosol of a target cell and remain stable there to interact with them. Using laser scanning confocal microscopy we show here that Alexa-labelled ammodytoxin entered the cytoplasm of the rat hippocampal neuron and subsequently also its nucleus. The transport of proteins into the nucleus proceeds via the cytosol of a cell, therefore, ammodytoxin passed the cytosol of the neuron on its way to the nucleus. Although it is not yet clear how ammodytoxin is translocated into the cytosol of the neuron, our results demonstrate that its stability in the cytosol is not in question, providing the evidence that the toxin can act in this cellular compartment

  6. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  7. Determination of chemical concentration with a 2 dimensional CCD array in the Echelle grating spectrometer

    Lewis, D.K. [Lawrence Livermore National Lab., CA (United States); Stevens, C.G.

    1994-11-15

    The Echelle grating spectrometer (EGS) uses a stepped Echelle grating, prisms and a folded light path to miniaturize an infrared spectrometer. Light enters the system through a slit and is spread out along Y by a prism. This light then strikes the grating and is diffracted out along X. This spreading results in a superposition of spectral orders since the grating has a high spectral range. These orders are then separated by again passing through a prism. The end result of a measurement is a 2 dimensional image which contains the folded spectrum of the region under investigation. The data lies in bands from top to bottom, for example, with wavenumber increments as small as 0.1 lying from left to right such that the right end of band N is the same as the left end of band N+1. This is the image which must be analyzed.

  8. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

    Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde

    2009-01-01

    of alkylated compounds in liposomes, it was demonstrated that the MTX-analogue partitioned into the water phase and thereby became available for cell uptake. It was concluded that liposomes containing alkylated MTX-analogues show promise as a drug delivery system, although the MTX-analogue needs to be more......Two lipophilic methotrexate analogues have been synthesized and evaluated for cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues contained a C-16-alkyl chain attached to the gamma-carboxylic acid and one of the analogues had an additional benzyl group attached...... cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...

  9. Make a 2D RPG in a weekend with RPG maker VX Ace

    Perez, Darrin

    2015-01-01

    Make a 2D RPG in a Weekend shows you how to create your very own dungeon crawler game in RPG Maker VX Ace in a single weekend. The entire process, from start to finish, is covered within this book. You will see a variety of dungeon maps and events, all broken down for your convenience. One of the hardest parts of game development is actually finishing a game, but it is also one of the most important steps on the way to becoming a game developer. If you have yet to finish a game, this book will give you the confidence and resources you need to finally be able to create your very own RPG. Once

  10. Design and implementation of a 2-DOF PID compensation for magnetic levitation systems.

    Ghosh, Arun; Rakesh Krishnan, T; Tejaswy, Pailla; Mandal, Abhisek; Pradhan, Jatin K; Ranasingh, Subhakant

    2014-07-01

    This paper employs a 2-DOF (degree of freedom) PID controller for compensating a physical magnetic levitation system. It is shown that because of having a feedforward gain in the proposed 2-DOF PID control, the transient performance of the compensated system can be changed in a desired manner unlike the conventional 1-DOF PID control. It is also shown that for a choice of PID parameters, although the theoretical loop robustness is the same for both the compensated systems, in real-time, 2-DOF PID control may provide superior robustness if a suitable choice of the feedforward parameter is made. The results are verified through simulations and experiments. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Eruption of a boundary layer induced by a 2D vortex patch

    Kudela, H; Malecha, Z M

    2009-01-01

    The boundary-layer eruption phenomenon caused by a 2D patch of vorticity above a wall was investigated. It is shown that the eruption phenomenon depends on the viscosity (or Reynolds number, Re) of the fluid. There exists a threshold value of Re above which the eruption takes place. The initiation of the eruption goes through the creation of a small recirculation zone near the solid wall, the appearance of the saddle point on streamlines inside it and the tearing off process of the recirculation zone. Further increase of the Reynolds number causes a more complex flow. One can observe that eruption is regenerative and that the vortex patch can produce a cascade of secondary vortices. The vortex-in-cell method was employed to investigate the eruption phenomenon.

  12. A 2.5-mm diameter probe for photoacoustic and ultrasonic endoscopy

    Yang, Joon-Mo; Chen, Ruimin; Favazza, Christopher; Yao, Junjie; Li, Chiye; Hu, Zhilin; Zhou, Qifa; Shung, K. Kirk; Wang, Lihong V.

    2012-01-01

    We have created a 2.5-mm outer diameter integrated photo-acoustic and ultrasonic mini-probe which can be inserted into a standard video endoscope’s instrument channel. A small-diameter focused ultrasonic transducer made of PMN-PT provides adequate signal sensitivity, and enables miniaturization of the probe. Additionally, this new endoscopic probe utilizes the same scanning mirror and micromotor-based built-in actuator described in our previous reports; however, the length of the rigid distal section of the new probe has been further reduced to ~35 mm. This paper describes the technical details of the mini-probe and presents experimental results that both quantify the imaging performance and demonstrate its in vivo imaging capability, which suggests that it could work as a mini-probe for certain clinical applications. PMID:23188360

  13. A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium sp. 62-92.

    Witter, L; Anke, T; Sterner, O

    1998-01-01

    Penidiamide, a new tripetide containing dehydrotryptamine, glycine and anthranilic acid linked together by two amide bonds, and oxindole were isolated from submerged cultures of Penicillium sp. 62-92. Both compounds preferentially inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM and oxindole of 380 microM. With the exception of U 937 cells (leukemia, human), no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3- (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210-cells (leukemia, mouse). No antimicrobial activity was detected for oxindole, and only weak antibacterial activity for penidiamide. The structure of penidiamide was elucidated by spectroscopic methods.

  14. The ground testing of a 2 kWe solar dynamic space power system

    Calogeras, J.E.

    1992-01-01

    Over the past 25 years Space Solar Dynamic component development has advanced to the point where it is considered a leading candidate power source technology for the evolutionary phases of the Space Station Freedom (SSF) program. Selection of SD power was based on studies and analyses which indicated significant savings in life cycle costs, launch mass and EVA requirements were possible when the system is compared to more conventional photovoltaic/battery power systems. Issues associated with micro-gravity operation such as the behavior of the thermal energy storage materials are being addressed in other programs. This paper reports that a ground test of a 2 kWe solar dynamic system is being planned by the NASA Office of Aeronautics and Space Technology to address the integration issues. The test will be scalable up to 25 kWe, will be flight configured and will incorporate relevant features of the SSF Solar Dynamic Power Module design

  15. Self-organization and oscillation of negatively charged dust particles in a 2-dimensional dusty plasma

    Song, Y.L.; Huang, F.; Chen, Z.Y.; Liu, Y.H.; Yu, M.Y.

    2016-01-01

    Negatively charged dust particles immersed in 2-dimensional dusty plasma system are investigated by molecular dynamics simulations. The effects of the confinement potential and attraction interaction potential on dust particle self-organization are studied in detail and two typical dust particle distributions are obtained when the system reaches equilibrium. The average radial velocity (ARV), average radial force (ARF) and radial mean square displacement are employed to analyze the dust particles' dynamics. Both ARVs and ARFs exhibit oscillation behaviors when the simulation system reaches equilibrium state. The relationships between the oscillation and confinement potential and attraction potential are studied in this paper. The simulation results are qualitatively similar to experimental results. - Highlights: • Self-organization and oscillation of a 2-dimensional dusty plasma is investigated. • Effect of the confinement potential on dust self-organization and oscillation is given. • Effect of the attraction potential on dust self-organization and oscillation is studied.

  16. Antiphospholipase A2 Receptor Autoantibodies: A Step Forward in the Management of Primary Membranous Nephropathy.

    Obrisca, Bogdan; Ismail, Gener; Jurubita, Roxana; Baston, Catalin; Andronesi, Andreea; Mircescu, Gabriel

    2015-01-01

    Since the identification of PLA2R (M-type phospholipase A2 receptor) as the first human antigenic target in primary membranous nephropathy (MN), perpetual progress has been made in understanding the pathogenesis of this disease. Accumulating clinical data support a pathogenic role for the anti-PLA2R antibodies (PLA2R ABs), but confirmation in an animal model is still lacking. However, PLA2R ABs were related to disease activity and outcome, as well as to response therapy. Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. Nevertheless, validation of a universal assay with high precision and definition of cut-off levels, followed by larger studies with a prolonged follow-up period, are needed to confirm these prospects.

  17. Antiphospholipase A2 Receptor Autoantibodies: A Step Forward in the Management of Primary Membranous Nephropathy

    Bogdan Obrisca

    2015-01-01

    Full Text Available Since the identification of PLA2R (M-type phospholipase A2 receptor as the first human antigenic target in primary membranous nephropathy (MN, perpetual progress has been made in understanding the pathogenesis of this disease. Accumulating clinical data support a pathogenic role for the anti-PLA2R antibodies (PLA2R ABs, but confirmation in an animal model is still lacking. However, PLA2R ABs were related to disease activity and outcome, as well as to response therapy. Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. Nevertheless, validation of a universal assay with high precision and definition of cut-off levels, followed by larger studies with a prolonged follow-up period, are needed to confirm these prospects.

  18. CSR Interaction for a 2D Energy-Chirped Bunch on a General Orbit

    Li, Rui

    2009-01-01

    When an electron bunch with initial linear energy chirp traverses a bunch compression chicane, the bunch interacts with itself via coherent synchrotron radiation (CSR) and space charge force. The effective longitudinal CSR force for such kind of 2D bunch on a circular orbit has been analyzed earlier (1). In this paper, we present the analytical results of the effective longitudinal CSR force for a 2D energy-chirped bunch going through a general orbit, which includes the entrance and exit of a circular orbit. In particular, we will show the behavior of the force in the last bend of a chicane when the bunch is under extreme compression. This is the condition when bifurcation of bunch phase space occurs in many CSR measurements. (1) R. Li, Phys. Rev. ST Accel. Beams 11, 024401 (2008)

  19. PFAPA syndrome in a 2-year-old girl: a case report and literature review

    Jakub Haracz

    2018-03-01

    Full Text Available PFAPA syndrome is the most common periodic fever syndrome in our geographic zone. It usually develops in children under 5 years of age and is classified as an autoinflammatory disease. PFAPA syndrome is characterised by episodes of high fever (>39°C accompanied by aphthous stomatitis, pharyngitis, and cervical lymphadenopathy, which occur cyclically at 25–35-day intervals and last between 3 and 6 days. Patients experience no symptoms between these episodes. The disease resolves with age. The cause of PFAPA and the predisposing factors remain unknown. The paper presents a clinical case of a 2-year-old girl diagnosed in the Department of Paediatric Pulmonology and Rheumatology of the Medical University of Lublin due to recurrent fever episodes. After exclusion of other causes, PFAPA syndrome was diagnosed. Corticosteroid treatment was used and good therapeutic response was achieved. The paper also presents a literature review on the current diagnosis and treatment modalities in PFAPA.

  20. Charge storage in nanotubes: the case of a 2-1 electrolyte

    W. Schmickler

    2017-09-01

    Full Text Available We consider a 2-1 electrolyte in contact with a narrow nanotube, which only allows one-dimensional storage along the axis. The asymmetry does not allow an a priori definition of the potential of zero charge; instead, the natural reference is the electrode potential at which both ions have the same electrochemical potential; the value of the latter can serve as a measure of ionophilicity. Near this potential, ionophobic tubes are filled with a dilute gas, ionophilic tubes are filled with a one-dimensional solid containing about the same number of the divalent ions and the monovalent counterions, a structure that is stabilized by a strong screening of the Coulomb interaction by an induced counter charge on the walls of the tube. The filling of the tube by the application of an electrode potential exhibits a complicated pattern of interactions between the two kinds of ions.

  1. Elevated temperature creep and fatigue damage of a 2.25 Cr--1 Mo steel weldment

    Van Den Avyle, J.A.

    1978-01-01

    In weldments between dissimilar metals wide variations occur in metallurgical structure and mechanical properties, so that for good structural design it is necessary to understand the mechanical response of individual microstructural segments of the weld. This study investigates elevated temperature properties of a 2.25 Cr--1 Mo ferritic steel base metal welded with Chromenar 382V (Inconel 82) filler metal. Creep and low-cycle fatigue tests at 866 0 K (1100 0 F) show the filler metal and heat affected zone to be much stronger than the base metal. Optical microscopy does not show significant aging effects in the short-term fatigue tests or creep tests of 1180 hour duration

  2. Holographic method for site-resolved detection of a 2D array of ultracold atoms

    Hoffmann, Daniel Kai; Deissler, Benjamin; Limmer, Wolfgang; Hecker Denschlag, Johannes

    2016-08-01

    We propose a novel approach to site-resolved detection of a 2D gas of ultracold atoms in an optical lattice. A near-resonant laser beam is coherently scattered by the atomic array, and after passing a lens its interference pattern is holographically recorded by superimposing it with a reference laser beam on a CCD chip. Fourier transformation of the recorded intensity pattern reconstructs the atomic distribution in the lattice with single-site resolution. The holographic detection method requires only about two hundred scattered photons per atom in order to achieve a high reconstruction fidelity of 99.9 %. Therefore, additional cooling during detection might not be necessary even for light atomic elements such as lithium. Furthermore, first investigations suggest that small aberrations of the lens can be post-corrected in imaging processing.

  3. Aeroelastic Stability of a 2D Airfoil Section equipped with a Trailing Edge Flap

    Bergami, Leonardo

    Recent studies conclude that important reduction of the fatigue loads encountered by a wind turbine blade can be achieved using a deformable trailing edge control system. The focus of the current work is to determine the effect of this flap-like system on the aeroelastic stability of a 2D airfoil...... section. A simulation tool is implemented to predict the flow speed at which a flap equipped section may become unstable, either due to flutter or divergence. First, the stability limits of the airfoil without flap are determined, and, in the second part of the work, a deformable trailing edge flap...... is applied. Stability is investigated for the uncontrolled flap, and for three different control algorithms. The three controls are tuned for fatigue load alleviation and they are based on, respectively, measurement of the heave displacement and velocity, measurement of the local angle of attack, measurement...

  4. Radioiodsodestannylation. Convenient synthesis of a high affinity thromboxane A2/prostaglandin H2 receptor antagonist

    Mais, D.E.; Hamanaka, Nobuyuki

    1991-01-01

    Radioiodination of methyl-7-[(2R, 2S, 5R)-6,6-dimethyl-3-(4-trimethylstannylbenzenesulfononylamino3S) bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoate with [ 125 I] Na using a modification of the chloramine-T method in organic solvent is simple with high yields and site specific. The product, following hydrolysis of the ester, 7-[(2R, 2S, 3S, 5R)-6,6-dimethyl-3-(4[ 125 I]-iodobenzenesulfonylamino) bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid [( 125 I]-ISAP), was purified by HPLC. The high specific activity and specific binding will make the ligand a useful tool for the characterization of thromboxane A 2 /prostaglandin H 2 receptors. (author)

  5. Carvacrol attenuates serum levels of total protein, phospholipase A2 and histamine in asthmatic guinea pig

    Mohammad Hossein Boskabady

    2016-11-01

    Full Text Available Objective: Pharmacological effects of carvacrol such as its anti-inflammatory activities have been shows. In this study the effects of carvacrol on serum levels of total protein (TP, phospholipase A2 (PLA2 and histamine in sensitized guinea pigs was evaluated. Materials and Methods: Sensitized guinea pigs were given drinking water alone (group S, drinking water containing three concentrations of carvacrol (40, 80 and 160 µg/ml or dexamethasone. Serum levels of TP, PLA2 and histamine were examined I all sensitized groups as well as a non-sensitized control group (n=6 for each group. Results: In sensitized animals, serum levels of TP, PLA2 and histamine were significantly increased compared to control animals (p

  6. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

    Kolko, M; Bruhn, T; Christensen, Thomas

    1999-01-01

    The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

  7. Structure of the polysaccharides from the lipopolysaccharide of Azospirillum brasilense Jm125A2.

    Sigida, Elena N; Fedonenko, Yuliya P; Shashkov, Alexander S; Zdorovenko, Evelina L; Konnova, Svetlana A; Ignatov, Vladimir V; Knirel, Yuriy A

    2015-10-30

    Two polysaccharides were obtained by mild acid degradation of the lipopolysaccharide of associative nitrogen-fixing bacteria Azospirillum brasilense Jm125A2 isolated from the rhizosphere of a pearl millet. The following structures of the polysaccharides were established by sugar and methylation analyses, Smith degradation, and (1)H and (13)C NMR spectroscopy: [Formula: see text] Structure 1 has been reported earlier for a polysaccharide from A. brasilense S17 (Fedonenko YP, Konnova ON, Zdorovenko EL, Konnova SA, Zatonsky GV, Shaskov AS, Ignatov VV, Knirel YA. Carbohydr Res 2008;343:810-6), whereas to our knowledge structure 2 has not been hitherto found in bacterial polysaccharides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Evolution of a Rippled Membrane during Phospholipase A2 Hydrolysis Studied by Time-Resolved AFM

    Leidy, Chad; Mouritsen, Ole G.; Jørgensen, Kent

    2004-01-01

    The sensitivity of phospholipase A2 (PLA2) for lipid membrane curvature is explored by monitoring, through time-resolved atomic force microscopy, the hydrolysis of supported double bilayers in the ripple phase. The ripple phase presents a corrugated morphology. PLA2 is shown to have higher activity...... toward the ripple phase compared to the gel phase in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes, indicating its preference for this highly curved membrane morphology. Hydrolysis of the stable and metastable ripple structures is monitored for equimolar DMPC/1,2-distearoyl- sn-glycero-3....... This is reflected in an increase in ripple spacing, followed by a sudden flattening of the lipid membrane during hydrolysis. Hydrolysis of the ripple phase results in anisotropic holes running parallel to the ripples, suggesting that the ripple phase has strip regions of higher sensitivity to enzymatic attack. Bulk...

  9. Vlasov Fluid stability of a 2-D plasma with a linear magnetic field null

    Kim, J.S.

    1984-01-01

    Vlasov Fluid stability of a 2-dimensional plasma near an O type magnetic null is investigated. Specifically, an elongated Z-pinch is considered, and applied to Field Reversed Configurations at Los Alamos National Laboratory by making a cylindrical approximation of the compact torus. The orbits near an elliptical O type null are found to be very complicated; the orbits are large and some are stochastic. The kinetic corrections to magnetohydrodynamics (MHD) are investigated by evaluating the expectation values of the growth rates of a Vlasov Fluid dispersion functional by using a set of trial functions based on ideal MHD. The dispersion functional involves fluid parts and orbit dependent parts. The latter involves phase integral of two time correlations. The phase integral is replaced by the time integral both for the regular and for the stochastic orbits. Two trial functions are used; one has a large displacement near the null and the other away from the null

  10. Communication over the network of binary switches regulates the activation of A2A adenosine receptor.

    Yoonji Lee

    2015-02-01

    Full Text Available Dynamics and functions of G-protein coupled receptors (GPCRs are accurately regulated by the type of ligands that bind to the orthosteric or allosteric binding sites. To glean the structural and dynamical origin of ligand-dependent modulation of GPCR activity, we performed total ~ 5 μsec molecular dynamics simulations of A2A adenosine receptor (A2AAR in its apo, antagonist-bound, and agonist-bound forms in an explicit water and membrane environment, and examined the corresponding dynamics and correlation between the 10 key structural motifs that serve as the allosteric hotspots in intramolecular signaling network. We dubbed these 10 structural motifs "binary switches" as they display molecular interactions that switch between two distinct states. By projecting the receptor dynamics on these binary switches that yield 2(10 microstates, we show that (i the receptors in apo, antagonist-bound, and agonist-bound states explore vastly different conformational space; (ii among the three receptor states the apo state explores the broadest range of microstates; (iii in the presence of the agonist, the active conformation is maintained through coherent couplings among the binary switches; and (iv to be most specific, our analysis shows that W246, located deep inside the binding cleft, can serve as both an agonist sensor and actuator of ensuing intramolecular signaling for the receptor activation. Finally, our analysis of multiple trajectories generated by inserting an agonist to the apo state underscores that the transition of the receptor from inactive to active form requires the disruption of ionic-lock in the DRY motif.

  11. Anterior cruciate ligament injury profile in Italian Serie A1-A2 women's volleyball league.

    Devetag, Francesca; Mazzilli, Massimiliano; Benis, Roberto; LA Torre, Antonio; Bonato, Matteo

    2018-01-01

    The aim of this study was to assess how anterior cruciate ligament (ACL) ruptures with subsequent surgery reconstruction impact on the professional career of A1-A2 Italian women's volleyball league players. Using an observational study with a retrospective case-series design for ACL ruptures, 125 teams with 1488 players were monitored. Subjects had to report level, role, injury modality, lower limb injured, laterality, period of the season and age. A total of 34 ACL ruptures were reported. Thirty-three (97%) were non-contact and 1 (3%) with contact. Twenty-one (61.7%) occurred in landing from a jump attack, 3 (8.8%) in landing from wall jump, 1 (3%) with apparent contact and 9 (26.5%) in other landing conditions. The most injured knee was the left limb (22, 64.7%) respect to the right limb (12, 35.3%). Fourteen (41.2%) ruptures occurred in spikers, 10 (29.4%) in middle blockers, 6 (17.6%) in setters, 3 (8.8%) in liberos and 1 (3%) in opposite hitters. Nine (26.5%) occurred in pre-season period, 16 (47%) in the first round, 4 (11.8%) in the second round, and 5 (14.7%) during play-off. The average age of the first ACL rupture was 23±3 years. We observed that female volleyball players of A1-A2 Italian volleyball league occurred mostly in a left non-contact ACL rupture during a landing condition and the spikers were the players most at risk. Therefore, it is desirable that coaches teach players variations of landing in order to avoid possible chronic overloading of ACL.

  12. Virtual analysis of structurally diverse synthetic analogs as inhibitors of snake venom secretory phospholipase A2.

    Sivaramakrishnan, V; Ilamathi, M; Ghosh, K S; Sathish, S; Gowda, T V; Vishwanath, B S; Rangappa, K S; Dhananjaya, B L

    2016-01-01

    Due to the toxic pathophysiological role of snake venom phospholipase A2 (PLA2 ), its compelling limitations to anti-venom therapy in humans and the need for alternative therapy foster considerable pharmacological interest towards search of PLA2 specific inhibitors. In this study, an integrated approach involving homology modeling, molecular dynamics and molecular docking studies on VRV-PL-V (Vipera russellii venom phospholipase A2 fraction-V) belonging to Group II-B secretory PLA2 from Daboia russelli pulchella is carried out in order to study the structure-based inhibitor design. The accuracy of the model was validated using multiple computational approaches. The molecular docking study of this protein was undertaken using different classes of experimentally proven, structurally diverse synthetic inhibitors of secretory PLA2 whose selection is based on IC50 value that ranges from 25 μM to 100 μM. Estimation of protein-ligand contacts by docking analysis sheds light on the importance of His 47 and Asp 48 within the VRV-PL-V binding pocket as key residue for hydrogen bond interaction with ligands. Our virtual analysis revealed that compounds with different scaffold binds to the same active site region. ADME analysis was also further performed to filter and identify the best potential specific inhibitor against VRV-PL-V. Additionally, the e-pharmacophore was generated for the best potential specific inhibitor against VRV-PL-V and reported here. The present study should therefore play a guiding role in the experimental design of VRV-PL-V inhibitors that may provide better therapeutic molecular models for PLA2 recognition and anti-ophidian activity. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis

    Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Mmesi, Jonas; Bentham, Andrew; Tyreman, Matthew; Abraham, Sonya; Stevens, Molly M.

    2016-02-01

    Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08423g

  14. Some data of second sequence non standard austenitic ingot, A2

    Nurdin Effendi; Aziz K Jahja; Bandriana; Wisnu Ari Adi

    2012-01-01

    Synthesis of second sequence austenite stainless steel named A2 using extracted minerals from Indonesian mines has been carried out. The starting materials for austenite alloy consist of granular ferro scrap, nickel, ferro-chrome, ferro-manganese, and ferro-silicon. The second sequence composition differs from the former first sequence. This A2 sequence contained more nickel, meanwhile titanium element had not been added explicitly to it, and just been found from raw materials contents or impurities, as well as carbon content in the alloy. However before the actual alloying work started, the first important step was to carry out the determination of the fractional amount of each starting material necessary to form an austenite stainless steel alloy as specified. Once the component fraction of each base alloy-element was determined, the raw materials are weighed on the mini-balance. After the fractional quantities of each constituent have been computed, an appropriate amount of these base materials are weighed separately on the micro scale. The raw materials were then placed in the induction foundry furnace, which was operated by an electromagnetic inductive-thermal system. The foundry furnace system performs the stirring of the molten materials automatically. The homogenized molten metals were poured down into sand casting prepared in advance. Some of the austenite stainless steel were normalized at 600°C for 6 hours. The average density is 7.8 g cm -1 and the average hardness value of 'normalized' austenite stainless-steels is in the range of 460 on the Vickers scale. The microstructure observation concludes that an extensive portion of the sample's structure is dendritic and the surface turns out to be homogenous. X-ray diffraction analysis shows that the material belongs to the fcc crystallographic system, which fits in with the austenite class of the alloy. The experimental fractional elemental composition data acquired by OES method turn out to

  15. Identification and characterization of a putative human platelet thromboxane A2/prostaglandin H2 receptor

    Saussy, D.L. Jr.

    1986-01-01

    The thromboxane A 2 (TXA 2 ) analog, 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-omega-tetranor TXA 2 (I-PTA-OH) was characterized as a competitive antagonist of TXA 2 mimetic-induced platelet aggregation, with a K/sub d/ of 190 nM in platelet rich plasma. This antagonism was specific for the putative thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptor, since I-PTA-OH had no inhibitory effects on platelet aggregation stimulated by agonists which act independently of TXA 2 /PGH 2 , and did not inhibit platelet TXA 2 synthesis. [ 125 I]-PTA-OH binding to a particulate fraction from human platelets was saturable, displaceable, and linear with protein concentration. Scatchard analysis of equilibrium binding revealed a single class of high affinity binding sites, with a K/sub d/ of 30 +/- 4 nM and a B/sub max/ of 1.8 +/- 0.3 pmol/mg protein. Kinetic analysis yielded a k 1 of 1.35 x 10 6 M -1 x min -1 and a k√ 1 of 0.032 min -1 , K/sub d/ = k√ 1 /k 1 = 24 nM. The subcellular localization of the putative TXA 2 /PGH 2 receptor was determined using [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding, was coenriched with markers for plasma membranes and dense tubular system; but not with markers for cytoplasmic constituents, mitochondria, or granules

  16. Inverse agonism of SQ 29,548 and Ramatroban on Thromboxane A2 receptor.

    Raja Chakraborty

    Full Text Available G protein-coupled receptors (GPCRs show some level of basal activity even in the absence of an agonist, a phenomenon referred to as constitutive activity. Such constitutive activity in GPCRs is known to have important pathophysiological roles in human disease. The thromboxane A2 receptor (TP is a GPCR that promotes thrombosis in response to binding of the prostanoid, thromboxane A2. TP dysfunction is widely implicated in pathophysiological conditions such as bleeding disorders, hypertension and cardiovascular disease. Recently, we reported the characterization of a few constitutively active mutants (CAMs in TP, including a genetic variant A160T. Using these CAMs as reporters, we now test the inverse agonist properties of known antagonists of TP, SQ 29,548, Ramatroban, L-670596 and Diclofenac, in HEK293T cells. Interestingly, SQ 29,548 reduced the basal activity of both, WT-TP and the CAMs while Ramatroban was able to reduce the basal activity of only the CAMs. Diclofenac and L-670596 showed no statistically significant reduction in basal activity of WT-TP or CAMs. To investigate the role of these compounds on human platelet function, we tested their effects on human megakaryocyte based system for platelet activation. Both SQ 29,548 and Ramatroban reduced the platelet hyperactivity of the A160T genetic variant. Taken together, our results suggest that SQ 29,548 and Ramatroban are inverse agonists for TP, whereas, L-670596 and Diclofenac are neutral antagonists. Our findings have important therapeutic applications in the treatment of TP mediated pathophysiological conditions.

  17. Purification and biochemical characterization of pancreatic phospholipase A2 from the common stingray Dasyatis pastinaca

    Gargouri Youssef

    2011-02-01

    Full Text Available Abstract Background Mammalian sPLA2-IB are well characterized. In contrast, much less is known about aquatic ones. The aquatic world contains a wide variety of living species and, hence represents a great potential for discovering new lipolytic enzymes. Results A marine stingray phospholipase A2 (SPLA2 was purified from delipidated pancreas. Purified SPLA2, which is not glycosylated protein, was found to be monomeric protein with a molecular mass of 14 kDa. A specific activity of 750 U/mg for purified SPLA2 was measured at optimal conditions (pH 8.5 and 40 °C in the presence of 4 mM NaTDC and 8 mM CaCl2 using PC as substrate. The sequence of the first twenty first amino-acid residues at the N-terminal extremity of SPLA2 was determined and shows a close similarity with known mammal and bird pancreatic secreted phospholipases A2. SPLA2 stability in the presence of organic solvents, as well as in acidic and alkaline pH and at high temperature makes it a good candidate for its application in food industry. Conclusions SPLA2 has several advantageous features for industrial applications. Stability of SPLA2 in the presence of organic solvents, and its tolerance to high temperatures, basic and acidic pH, makes it a good candidate for application in food industry to treat phospholipid-rich industrial effluents, or to synthesize useful chemical compounds.

  18. Effectiveness of a 2-year menopause medicine curriculum for obstetrics and gynecology residents.

    Christianson, Mindy S; Washington, Chantel I; Stewart, Katherine I; Shen, Wen

    2016-03-01

    Previous work has shown American obstetrics and gynecology (OB/GYN) residents are lacking in menopause training. Our objective was to assess the effectiveness of a 2-year menopause medicine curriculum in improving OB/GYN residents' knowledge and self-assessed competency in menopause topics. We developed a menopause medicine-teaching curriculum for OB/GYN residents at our academic hospital-based residency program. The 2-year curriculum was composed of year 1: four 1-hour lectures and one 2-hour lab with cases presentations, and year 2: three 1-hour lectures and one 2-hour lab. Core topics included menopause physiology, hormone therapy, breast health, bone health, cardiovascular disease, and autoimmune disease. Pre- and posttests assessed resident knowledge and comfort in core topics, and a pre- and postcurriculum survey assessed utility and learning satisfaction. From July 2011 to June 2013, 34 OB/GYN residents completed the menopause curriculum annually with an average attendance at each module of 23 residents. Pre-/posttest scores improved from a mean pretest score of 57.3% to a mean posttest score of 78.7% (P menopause patients with 75.8% reporting feeling "barely comfortable" and 8.4% feeling "not at all comfortable." After the 2-year curriculum, 85.7% reported feeling "comfortable/very comfortable" taking care of menopause patients. The majority of residents (95.2%) reported the menopause curriculum was "extremely useful." A 2-year menopause medicine curriculum for OB/GYN residents utilizing lectures and a lab with case studies is an effective modality to improve resident knowledge required to manage menopause patients.

  19. Electrical characterization of the JET A2 antenna: Comparison of model with measurements

    Ryan, P.M.; Goulding, R.H.; Bhatnagar, V.; Kaye, A.; Wade, T.

    1993-01-01

    The JET experiment is replacing its previous (Al) antennas with upgraded designs (A2) for its upcoming ''pumped diverter'' operation. These antennas are more directional than the previous two-strap Al antennas when operated as a phased array. The frequency range is 23 to 57 MHz. A full-scale low power ''flat'' mockup was tested at JET; strap lengths were adjusted to give balanced operation with resonance at 42 MHz. A second mockup module, differing only slightly from the original, was subsequently fabricated and both modules were sent to ORNL for additional measurements and to test the operation of the power compensator circuit. There are benefits to using a transmission line model to characterize coupled antenna systems, primarily in the ease of incorporating the antennas into the overall analysis of the transmission, tuning, and matching system. The characteristics of the array under arbitrary phasing are also needed for the design, analysis, and control of the power compensator. There are aspects of the JET A2 antenna geometry that differ considerably from previously modeled cases. Each transmission line feeds two poloidally-stacked straps connected in parallel. The parallel straps present different electrical loads at the match point due to geometrical differences. Currents in one section of the strap influence other sections of the same strap as well as in neighboring straps due to internal inductive coupling. The lengths of the inner and outer straps differ; moreover, the inner straps are fed from ports located behind the outer straps, resulting in increased coupling between the inner and outer straps due to the long feed lines and in greater disparity between the electrical loads presented at the inner and outer feed ports. The present effort is to determine whether a more general coupled transmission line model can characterize the array response with sufficient accuracy for the purpose of design and analysis

  20. A 2D semi-analytical model for Faraday shield in ICP source

    Zhang, L.G.; Chen, D.Z.; Li, D.; Liu, K.F.; Li, X.F.; Pan, R.M.; Fan, M.W.

    2016-01-01

    Highlights: • In this paper, a 2D model of ICP with faraday shield is proposed considering the complex structure of the Faraday shield. • Analytical solution is found to evaluate the electromagnetic field in the ICP source with Faraday shield. • The collision-free motion of electrons in the source is investigated and the results show that the electrons will oscillate along the radial direction, which brings insight into how the RF power couple to the plasma. - Abstract: Faraday shield is a thin copper structure with a large number of slits which is usually used in inductive coupled plasma (ICP) sources. RF power is coupled into the plasma through these slits, therefore Faraday shield plays an important role in ICP discharge. However, due to the complex structure of the Faraday shield, the resulted electromagnetic field is quite hard to evaluate. In this paper, a 2D model is proposed on the assumption that the Faraday shield is sufficiently long and the RF coil is uniformly distributed, and the copper is considered as ideal conductor. Under these conditions, the magnetic field inside the source is uniform with only the axial component, while the electric field can be decomposed into a vortex field generated by changing magnetic field together with a gradient field generated by electric charge accumulated on the Faraday shield surface, which can be easily found by solving Laplace's equation. The motion of the electrons in the electromagnetic field is investigated and the results show that the electrons will oscillate along the radial direction when taking no account of collision. This interesting result brings insight into how the RF power couples into the plasma.

  1. IgE-Binding Epitope Mapping and Tissue Localization of the Major American Cockroach Allergen Per a 2.

    Lee, Mey Fann; Chang, Chia Wei; Song, Pei Pong; Hwang, Guang Yuh; Lin, Shyh Jye; Chen, Yi Hsing

    2015-07-01

    Cockroaches are the second leading allergen in Taiwan. Sensitization to Per a 2, the major American cockroach allergen, correlates with clinical severity among patients with airway allergy, but there is limited information on IgE epitopes and tissue localization of Per a 2. This study aimed to identify Per a 2 linear IgE-binding epitopes and its distribution in the body of a cockroach. The cDNA of Per a 2 was used as a template and combined with oligonucleotide primers specific to the target areas with appropriate restriction enzyme sites. Eleven overlapping fragments of Per a 2 covering the whole allergen molecule, except 20 residues of signal peptide, were generated by PCR. Mature Per a 2 and overlapping deletion mutants were affinity-purified and assayed for IgE reactivity by immunoblotting. Three synthetic peptides comprising the B cell epitopes were evaluated by direct binding ELISA. Rabbit anti-Per a 2 antibody was used for immunohistochemistry. Human linear IgE-binding epitopes of Per a 2 were located at the amino acid sequences 57-86, 200-211, and 299-309. There was positive IgE binding to 10 tested Per a 2-allergic sera in 3 synthetic peptides, but none in the controls. Immunostaining revealed that Per a 2 was localized partly in the mouth and midgut of the cockroach, with the most intense staining observed in the hindgut, suggesting that the Per a 2 allergen might be excreted through the feces. Information on the IgE-binding epitope of Per a 2 may be used for designing more specific diagnostic and therapeutic approaches to cockroach allergy.

  2. Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors.

    Xu, K; Di Luca, D G; Orrú, M; Xu, Y; Chen, J-F; Schwarzschild, M A

    2016-05-13

    Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined. Copyright © 2016 IBRO. All rights reserved.

  3. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

    Chen Leilei

    2011-05-01

    Full Text Available Abstract Background Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model. Methods An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF were isolated to further investigate molecular mechanism of eIF-5A2 in aging. Results Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p Conclusion These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability.

  4. Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis.

    Chen, Pengguo; Li, Jie; Huo, Yan; Lu, Jin; Wan, Lili; Li, Bin; Gan, Run; Guo, Cheng

    2015-01-01

    Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis, which is a pathological process characterized by extracellular matrix accumulation. NR4A2 is a nuclear receptor belonging to the NR4A subfamily and vital in regulating cell growth, metabolism, inflammation and other biological functions. However, its role in HSCs is unclear. We analyzed NR4A2 expression in fibrotic liver and stimulated HSCs compared with control group and studied the influence on cell proliferation, cell cycle, cell apoptosis and MAPK pathway after NR4A2 knockdown. NR4A2 expression was examined by real-time polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence analyses. NR4A2 expression was significantly lower in fibrotic liver tissues and PDGF BB or TGF-β stimulated HSCs compared with control group. After NR4A2 knockdown α-smooth muscle actin and Col1 expression increased. In addition, NR4A2 silencing led to the promotion of cell proliferation, increase of cell percentage in S phase and reduced phosphorylation of ERK1/2, P38 and JNK in HSCs. These results indicate that NR4A2 can inhibit HSC proliferation through MAPK pathway and decrease extracellular matrix in liver fibrogenesis. NR4A2 may be a promising therapeutic target for liver fibrosis.

  5. Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer.

    Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Cortés, Antoni; Volkow, Nora D; Schiffmann, Serge N; Ferré, Sergi; Casadó, Vicent

    2015-07-07

    Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

  6. [Modeling of a three-dimensional structure of cytochrome P-450 1A2 and search for its new ligands].

    Belkina, N V; Skvortsov, V S; Ivanov, A S; Archakov, A I

    1998-01-01

    The substances inhibiting cytochrome P450 1A2 (CYP1A2) represent a perspective class of new drugs, which application in clinical practice can become the important part in preventive maintenance in oncology. The present work is devoted to computer modelling of 3-D structure of CYP1A2 and searching of new inhibitors by database mining. The modelling of CYP1A2 was done based on homology with 4 bacterial cytochromes P450 with known 3-D structure. For optimization of CYP1A2 active site structure the models of its complexes with characteristic substrates (caffeine and 7-ethoxyresorufin) were designed. These complexes were optimized by molecular dynamics simulation in water. The models of 24 complexes of CYP1A2 with known ligands with known Kd were designed by means of DockSearch and LeapFrog programs. 3D-QSAR model with good predictive force was created based on these complexes. On a final stage the search of knew CYP1A2 ligands in testing database (more than 23.000 substances from database Maybridge and 112 known CYP1A2 ligands from database Metabolite, MDL) was executed. 680 potential ligands of CYP1A2 with Kd values, comparable with known ones were obtained. This number has included 73 compounds from 112 known ligands, introduced in tested database as the internal control.

  7. Design of a 2.4-GHz CMOS monolithic fractional-N frequency synthesizer

    Shu, Keliu

    The wireless communication technology and market have been growing rapidly since a decade ago. The high demand market is a driving need for higher integration in the wireless transceivers. The trend is to achieve low-cost, small form factor and low power consumption. With the ever-reducing feature size, it is becoming feasible to integrate the RF front-end together with the baseband in the low-cost CMOS technology. The frequency synthesizer is a key building block in the RF front-end of the transceivers. It is used as a local oscillator for frequency translation and channel selection. The design of a 2.4-GHz low-power frequency synthesizer in 0.35mum CMOS is a challenging task mainly due to the high-speed prescaler. In this dissertation, a brief review of conventional PLL and frequency synthesizers is provided. Design techniques of a 2.4-GHz monolithic SigmaDelta fractional-N frequency synthesizer are investigated. Novel techniques are proposed to tackle the speed and integration bottlenecks of high-frequency PLL. A low-power and inherently glitch-free phase-switching prescaler and an on-chip loop filter with capacitance multiplier are developed. Compared with the existing and popular dual-path topology, the proposed loop filter reduces circuit complexity and its power consumption and noise are negligible. Furthermore, a third-order three-level digital SigmaDelta modulator topology is employed to reduce the phase noise generated by the modulator. Suitable PFD and charge-pump designs are employed to reduce their nonlinearity effects and thus minimize the folding of the SigmaDelta modulator-shaped phase noise. A prototype of the fractional-N synthesizer together with some standalone building blocks is designed and fabricated in TSMC 0.35mum CMOS through MOSIS. The prototype frequency synthesizer and standalone prescaler and loop filter are characterized. The feasibility and practicality of the proposed prescaler and loop filter are experimentally verified.

  8. Preliminary forecasts of Pacific bigeye tuna population trends under the A2 IPCC scenario

    Lehodey, P.; Senina, I.; Sibert, J.; Bopp, L.; Calmettes, B.; Hampton, J.; Murtugudde, R.

    2010-07-01

    An improved version of the spatial ecosystem and population dynamics model SEAPODYM was used to investigate the potential impacts of global warming on tuna populations. The model included an enhanced definition of habitat indices, movements, and accessibility of tuna predators to different vertically migrant and non-migrant micronekton functional groups. The simulations covered the Pacific basin (model domain) at a 2° × 2° geographic resolution. The structure of the model allows an evaluation from multiple data sources, and parameterization can be optimized by adjoint techniques and maximum likelihood using fishing data. A first such optimized parameterization was obtained for bigeye tuna ( Thunnus obesus) in the Pacific Ocean using historical catch data for the last 50 years and a hindcast from a coupled physical-biogeochemical model driven by the NCEP atmospheric reanalysis. The parameterization provided very plausible biological parameter values and a good fit to fishing data from the different fisheries, both within and outside the time period used for optimization. We then employed this model to forecast the future of bigeye tuna populations in the Pacific Ocean. The simulation was driven by the physical-biogeochemical fields predicted from a global marine biogeochemistry - climate simulation. This global simulation was performed with the IPSL climate model version 4 (IPSL-CM4) coupled to the oceanic biogeochemical model PISCES and forced by atmospheric CO 2, from historical records over 1860-2000, and under the SRES A2 IPCC scenario for the 21st century (i.e. atmospheric CO 2 concentration reaching 850 ppm in the year 2100). Potential future changes in distribution and abundance under the IPCC scenario are presented but without taking into account any fishing effort. The simulation showed an improvement in bigeye tuna spawning habitat both in subtropical latitudes and in the eastern tropical Pacific (ETP) where the surface temperature becomes optimal for

  9. Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

    Aherne, Carol M

    2009-10-01

    Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

  10. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress.

    Kaster, Manuella P; Machado, Nuno J; Silva, Henrique B; Nunes, Ana; Ardais, Ana Paula; Santana, Magda; Baqi, Younis; Müller, Christa E; Rodrigues, Ana Lúcia S; Porciúncula, Lisiane O; Chen, Jiang Fan; Tomé, Ângelo R; Agostinho, Paula; Canas, Paula M; Cunha, Rodrigo A

    2015-06-23

    The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, p.o.); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons. Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function.

  11. Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia

    2013-01-01

    Background Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A2A receptors (A2ARs) control neuroinflammation, as well as the production and function of BDNF, we tested to see if A2AR controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation. Methods Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL) in the absence or in the presence of the A2AR antagonist, SCH58261 (50 nM), as well as other modulators of A2AR signaling. The BDNF cellular content and secretion were quantified by Western blotting and ELISA, A2AR density was probed by Western blotting and immunocytochemistry and cell proliferation was assessed by BrdU incorporation. Additionally, the A2AR modulation of LPS-driven cell proliferation was also tested in primary cultures of mouse microglia. Results LPS induced time-dependent changes of the intra- and extracellular levels of BDNF and increased microglial proliferation. The maximal LPS-induced BDNF release was time-coincident with an LPS-induced increase of the A2AR density. Notably, removing endogenous extracellular adenosine or blocking A2AR prevented the LPS-mediated increase of both BDNF secretion and proliferation, as well as exogenous BDNF-induced proliferation. Conclusions We conclude that A2AR activation plays a mandatory role controlling the release of BDNF from activated microglia, as well as the autocrine/paracrine proliferative role of BDNF. PMID:23363775

  12. Vite et bien 1 A1/A2 : méthode rapide pour adultes

    Miquel, Claire

    2009-01-01

    Vite et bien s'adresse à des adultes pressés et impatients de communiquer avec succès en français ! Le vocabulaire est simple et usuel et les thèmes, variés, pour faire face, efficacement, à toutes les situations de la vie quotidienne et professionnelle. Livre + CD audio et corrigés inclus. La méthode rapide Vite et bien 1 permet à la fois d'apprendre le français et de découvrir la réalité de la vie en France, les différences culturelles, le langage de la vie quotidienne, le tout en un temps record. En effet, le premier volume couvre, en vingt unités, les niveaux A1 et A2 du Cadre Européen de référence (CECR). Ainsi, en 100 à 120 heures de cours selon les publics, il sera possible d'acquérir une bonne base de grammaire et de vocabulaire, claire, simple, fonctionnelle, et de se sentir à l'aise dans la communication orale et écrite. L'ouvrage s'adresse aux vrais et et aux faux débutants, constituant donc un outil d'apprentissage et/ou de rafraîchissement des connaissances. Chacune des v...

  13. Exploring 4D quantum Hall physics with a 2D topological charge pump

    Lohse, Michael; Schweizer, Christian; Price, Hannah M.; Zilberberg, Oded; Bloch, Immanuel

    2018-01-01

    The discovery of topological states of matter has greatly improved our understanding of phase transitions in physical systems. Instead of being described by local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example is the two-dimensional (2D) integer quantum Hall effect: it is characterized by the first Chern number, which manifests in the quantized Hall response that is induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional (4D) systems leads to the appearance of an additional quantized Hall response, but one that is nonlinear and described by a 4D topological invariant—the second Chern number. Here we report the observation of a bulk response with intrinsic 4D topology and demonstrate its quantization by measuring the associated second Chern number. By implementing a 2D topological charge pump using ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small cloud of atoms as a local probe, we fully characterize the nonlinear response of the system via in situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probing higher-dimensional quantum Hall systems, in which additional strongly correlated topological phases, exotic collective excitations and boundary phenomena such as isolated Weyl fermions are predicted.

  14. Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict Biochemical Failure.

    Lamb, David S; Sondhauss, Sven; Dunne, Jonathan C; Woods, Lisa; Delahunt, Brett; Ferguson, Peter; Murray, Judith; Nacey, John N; Denham, James W; Jordan, T William

    2017-12-01

    We previously reported the use of mass spectrometry and western blotting to identify proteins from tumour regions of formalin-fixed paraffin-embedded biopsies from 16 men who presented with apparently localized prostate cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of subsequent biochemical failure than prostate-specific antigen (PSA). In this follow-up study, ANXA2 and PSA were measured using western blotting of proteins extracted from biopsies from 37 men from a subsequent prostate cancer trial. No significant differences in ANXA2 and PSA levels were observed between men with and without biochemical failure. The statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA. ANXA2 and PSA proteins measured from biopsy tumour regions are unlikely to be good biomarkers for prediction of the clinical outcome of prostate cancer presenting with apparently localized disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Validation of a 2-D semi-coupled numerical model for fluid-structure-seabed interaction

    Ye, Jianhong; Jeng, Dongsheng; Wang, Ren; Zhu, Changqi

    2013-10-01

    A 2-D semi-coupled model PORO-WSSI 2D (also be referred as FSSI-CAS 2D) for the Fluid-Structure-Seabed Interaction (FSSI) has been developed by employing RANS equations for wave motion in fluid domain, VARANS equations for porous flow in porous structures; and taking the dynamic Biot's equations (known as "u - p" approximation) for soil as the governing equations. The finite difference two-step projection method and the forward time difference method are adopted to solve the RANS, VARANS equations; and the finite element method is adopted to solve the "u - p" approximation. A data exchange port is developed to couple the RANS, VARANS equations and the dynamic Biot's equations together. The analytical solution proposed by Hsu and Jeng (1994) and some experiments conducted in wave flume or geotechnical centrifuge in which various waves involved are used to validate the developed semi-coupled numerical model. The sandy bed involved in these experiments is poro-elastic or poro-elastoplastic. The inclusion of the interaction between fluid, marine structures and poro-elastoplastic seabed foundation is a special point and highlight in this paper, which is essentially different with other previous coupled models The excellent agreement between the numerical results and the experiment data indicates that the developed coupled model is highly reliablefor the FSSI problem.

  16. Characterization of Serum Phospholipase A2 Activity in Three Diverse Species of West African Crocodiles

    Mark Merchant

    2011-01-01

    Full Text Available Secretory phospholipase A2, an enzyme that exhibits substantial immunological activity, was measured in the serum of three species of diverse West African crocodiles. Incubation of different volumes of crocodile serum with bacteria labeled with a fluorescent fatty acid in the sn-2 position of membrane lipids resulted in a volume-dependent liberation of fluorescent probe. Serum from the Nile crocodile (Crocodylus niloticus exhibited slightly higher activity than that of the slender-snouted crocodile (Mecistops cataphractus and the African dwarf crocodile (Osteolaemus tetraspis. Product formation was inhibited by BPB, a specific PLA2 inhibitor, confirming that the activity was a direct result of the presence of serum PLA2. Kinetic analysis showed that C. niloticus serum produced product more rapidly than M. cataphractus or O. tetraspis. Serum from all three species exhibited temperature-dependent PLA2 activities but with slightly different thermal profiles. All three crocodilian species showed high levels of activity against eight different species of bacteria.

  17. Thromboxane A2 increases endothelial permeability through upregulation of interleukin-8

    Kim, Su-Ryun; Bae, Soo-Kyung; Park, Hyun-Joo; Kim, Mi-Kyoung; Kim, Koanhoi; Park, Shi-Young; Jang, Hye-Ock; Yun, Il; Kim, Yung-Jin; Yoo, Mi-Ae; Bae, Moon-Kyoung

    2010-01-01

    Thromboxane A 2 (TXA 2 ), a major prostanoid formed from prostaglandin H 2 by thromboxane synthase, is involved in the pathogenesis of a variety of vascular diseases. In this study, we report that TXA 2 mimetic U46619 significantly increases the endothelial permeability both in vitro and in vivo. U46619 enhanced the expression and secretion of interleukin-8 (IL-8), a major inducer of vascular permeability, in endothelial cells. Promoter analysis showed that the U46619-induced expression of IL-8 was mainly regulated by nuclear factor-κB (NF-κB). U46619 induced the activation of NF-κB through IκB kinase (IKK) activation, IκB phosphorylation and NF-κB nuclear translocation. Furthermore, the inhibition of IL-8 or blockade of the IL-8 receptor attenuated the U46619-induced endothelial cell permeability by modulating the cell-cell junctions. Overall, these results suggest that U46619 promotes vascular permeability through the production of IL-8 via NF-κB activation in endothelial cells.

  18. Involuntary psychiatric hospitalisation, stigma stress and recovery: a 2-year study.

    Xu, Z; Lay, B; Oexle, N; Drack, T; Bleiker, M; Lengler, S; Blank, C; Müller, M; Mayer, B; Rössler, W; Rüsch, N

    2018-01-31

    Compulsory admission can be experienced as devaluing and stigmatising by people with mental illness. Emotional reactions to involuntary hospitalisation and stigma-related stress may affect recovery, but longitudinal data are lacking. We, therefore, examined the impact of stigma-related emotional reactions and stigma stress on recovery over a 2-year period. Shame and self-contempt as emotional reactions to involuntary hospitalisation, stigma stress, self-stigma and empowerment, as well as recovery were assessed among 186 individuals with serious mental illness and a history of recent involuntary hospitalisation. More shame, self-contempt and stigma stress at baseline were correlated with increased self-stigma and reduced empowerment after 1 year. More stigma stress at baseline was associated with poor recovery after 2 years. In a longitudinal path analysis more stigma stress at baseline predicted poorer recovery after 2 years, mediated by decreased empowerment after 1 year, controlling for age, gender, symptoms and recovery at baseline. Stigma stress may have a lasting detrimental effect on recovery among people with mental illness and a history of involuntary hospitalisation. Anti-stigma interventions that reduce stigma stress and programs that enhance empowerment could improve recovery. Future research should test the effect of such interventions on recovery.

  19. Development of a 2-site radioimmunoassay for antithyroglobulin antibodies using 125I-thyroglobulin

    Leonard, J.P.; Taymans, F.; Beckers, C.

    1977-01-01

    A 2-site radioassay for human antithyroglobulin auto-antibodies has been developed using human thyroglobulin (Tg) labelled with 125 I. The technique is based on (1) the use of polystyrene tubes coated with Tg, (2) the binding of the antibodies to the solid phase Tg, (3) the reaction of the labelled Tg with the insolubilized antibodies. Factors affecting the assay were evaluated including (a) the effect of the temperature, Tg concentration and coating time on the adsorption of Tg, (b) the stability and storage of the solid phase Tg, (c) the variations in temperature, reaction times and incubation volumes, (d) the effect of the serum proteins, (e) the influence of the variations in concentration and specific activity of the labelled Tg. Increasing sensitivity resulted from a prolonged incubation at low temperature, the addition of serum proteins and the use of an appropriate specific activity of 125 I-Tg. Nonspecific radioactive uptake normally averaged 1% or less of the total radioactivity added. The use of Tg coated tubes makes the technique rapid and simple to be operated. The ability of the coated tubes to be stored and the relative insensitivity of the test to fluctuations in the quality of the tracer represent additional advantages in the routine application of the method. (orig.) [de

  20. Toroidal magnetic field system for a 2-MA reversed-field pinch experiment

    Melton, J.G.; Linton, T.W.

    1983-01-01

    The engineering design of the toroidal magnetic field (TF) system for a 2-MA Reversed-Field Pinch experiment (ZT-H) is described. ZT-H is designed with major radius 2.15 meters, minor radius 0.40 meters, and a peak toroidal magnetic field of 0.85 Tesla. The requirement for highly uniform fields, with spatial ripple <0.2% leads to a design with 72 equally spaced circular TF coils, located at minor radius 0.6 meters, carrying a maximum current of 9.0 MA. The coils are driven by a 12-MJ capacitor bank which is allowed to ring in order to aid the reversal of magnetic field. A stress analysis is presented, based upon calculated hoop tension, centering force, and overturning moment, treating these as a combination of static loads and considering that the periodic nature of the loading causes little amplification. The load transfer of forces and moments is considered as a stress distribution resisted by the coils, support structures, wedges, and the structural shell

  1. Temperature dependence of the partially localized state in a 2D molecular nanoporous network

    Piquero-Zulaica, Ignacio, E-mail: ipiquerozulaica@gmail.com [Centro de Física de Materiales (CSIC/UPV-EHU)—Materials Physics Center, Manuel Lardizabal 5, 20018 San Sebastián (Spain); Nowakowska, Sylwia [Department of Physics, University of Basel, Klingelbergstrasse 82, 4056 Basel (Switzerland); Ortega, J. Enrique [Centro de Física de Materiales (CSIC/UPV-EHU)—Materials Physics Center, Manuel Lardizabal 5, 20018 San Sebastián (Spain); Donostia International Physics Center (DIPC), Manuel Lardizabal 4, 20018 San Sebastián (Spain); Departamento Física Aplicada I, Universidad del País Vasco, 20018 San Sebastián (Spain); Stöhr, Meike [Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen (Netherlands); Gade, Lutz H. [Anorganisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg (Germany); Jung, Thomas A. [Laboratory for Micro- and Nanotechnology, Paul Scherrer Institute, 5232 Villigen (Switzerland); Lobo-Checa, Jorge, E-mail: jorge.lobo@csic.es [Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC-Universidad de Zaragoza, E-50009 Zaragoza (Spain); Departamento de Física de la Materia Condensada, Universidad de Zaragoza, E-50009 Zaragoza (Spain)

    2017-01-01

    Highlights: • A state of a 2D porous network is demonstrated to originate from the Shockley state. • The temperature evolution of both states is followed by means of ARPES. • Identical energy shifts are observed for both states, proving their common origin. - Abstract: Two-dimensional organic and metal-organic nanoporous networks can scatter surface electrons, leading to their partial localization. Such quantum states are related to intrinsic surface states of the substrate material. We further corroborate this relation by studying the thermally induced energy shifts of the electronic band stemming from coupled quantum states hosted in a metal-organic array formed by a perylene derivative on Cu(111). We observe by angle-resolved photoemission spectroscopy (ARPES), that both, the Shockley and the partially localized states, shift by the same amount to higher binding energies upon decreasing the sample temperature, providing evidence of their common origin. Our experimental approach and results further support the use of surface states for modelling these systems, which are expected to provide new insight into the physics concerning partially confined electronic states: scattering processes, potential barrier strengths, excited state lifetimes or the influence of guest molecules.

  2. A radiographic imaging system based upon a 2-D silicon microstrip sensor

    Papanestis, A; Corrin, E; Raymond, M; Hall, G; Triantis, F A; Manthos, N; Evagelou, I; Van den Stelt, P; Tarrant, T; Speller, R D; Royle, G F

    2000-01-01

    A high resolution, direct-digital detector system based upon a 2-D silicon microstrip sensor has been designed, built and is undergoing evaluation for applications in dentistry and mammography. The sensor parameters and image requirements were selected using Monte Carlo simulations. Sensors selected for evaluation have a strip pitch of 50mum on the p-side and 80mum on the n-side. Front-end electronics and data acquisition are based on the APV6 chip and were adapted from systems used at CERN for high-energy physics experiments. The APV6 chip is not self-triggering so data acquisition is done at a fixed trigger rate. This paper describes the mammographic evaluation of the double sided microstrip sensor. Raw data correction procedures were implemented to remove the effects of dead strips and non-uniform response. Standard test objects (TORMAX) were used to determine limiting spatial resolution and detectability. MTFs were determined using the edge response. The results indicate that the spatial resolution of the...

  3. Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

    Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

    2015-12-01

    Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

  4. 3D Vector Velocity Estimation using a 2D Phased Array

    Pihl, Michael Johannes; Jensen, Jørgen Arendt

    2011-01-01

    of using the TO method for estimation 3D velocity vectors, and the proposed decoupling is demonstrated. A 64x64 and a 32x32 elements transducer are emulated using Field II. Plug flow with a speed of 1 m/s in a small region is rotated in the XY -plane. A binary flow example with [vx,vy]=[1,0] and [0,1] m......A method to estimate the three dimensional (3D) velocity vector is presented is this paper. 3D velocity vector techniques are needed to measure the full velocity and characterize the complicated flow patterns in the human body. The Transverse Oscillation (TO) method introduces oscillations...... matrix transducer. For the 32x32 transducer, the mean and standard deviation for the speed are 0.94 0.11 m/s and for the angle bias -0.487.7. The simulation study clearly demonstrates, that the new method can be used to estimate the 3D velocity vector using a 2D phased matrix array, and that the velocity...

  5. Structural and energetic effects of A2A adenosine receptor mutations on agonist and antagonist binding.

    Henrik Keränen

    Full Text Available To predict structural and energetic effects of point mutations on ligand binding is of considerable interest in biochemistry and pharmacology. This is not only useful in connection with site-directed mutagenesis experiments, but could also allow interpretation and prediction of individual responses to drug treatment. For G-protein coupled receptors systematic mutagenesis has provided the major part of functional data as structural information until recently has been very limited. For the pharmacologically important A(2A adenosine receptor, extensive site-directed mutagenesis data on agonist and antagonist binding is available and crystal structures of both types of complexes have been determined. Here, we employ a computational strategy, based on molecular dynamics free energy simulations, to rationalize and interpret available alanine-scanning experiments for both agonist and antagonist binding to this receptor. These computer simulations show excellent agreement with the experimental data and, most importantly, reveal the molecular details behind the observed effects which are often not immediately evident from the crystal structures. The work further provides a distinct validation of the computational strategy used to assess effects of point-mutations on ligand binding. It also highlights the importance of considering not only protein-ligand interactions but also those mediated by solvent water molecules, in ligand design projects.

  6. Results from recent hydrogen pellet acceleration studies with a 2-m railgun

    Kim, K.; Zhang, D.J.; King, T.; Haywood, R.; Manns, W.; Venneri, F.

    1989-12-01

    A new 3.2-mm-diameter, two-stage, fuseless, plasma-arc-driven electromagnetic railgun has been designed, constructed, and successfully operated to achieve a record velocity of 2.67 km/s( b ) for 3.2 mmD x 4 mmL solid hydrogen pellet. The first stage of this hydrogen pellet injector is a combination of a hydrogen pellet generator and a gas fun. The second stage is a 2-m-long railgun which serves as a booster accelerator. The gas fun accelerates a frozen hydrogen pellet to a medium velocity and injects it into the railgun through a perforated coupling piece, which also serves a pressure-relieving mechanism. An electrical breakdown of the propellant gas, which has followed the pellet from the gas fun into the railgun, forms a conducting plasma-arc armature immediately behind the pellet allowing for fuseless operation of the railgun. Study of the pressure profile and the behavior of the plasma-arc armature inside the railgun bore led to elimination of spurious arcing, which prevents operation of the railgun at high voltages (and, therefore, at high currents). A timing circuit that can automatically measure the pellet input velocity and allows for accurate control of arc initiation behind the pellet helps prevent pellet disintegration and mistriggering of the arc initiation circuit. Results from the recent cryogenic operation of the two-stage pellet acceleration system are reported. 11 refs., 2 figs., 1 tab

  7. Assay of phospholipases A2 and their inhibitors by kinetic analysis in the scooting mode

    Mahendra Kumar Jain

    1992-01-01

    Full Text Available Several cellular processes are regulated by interfacial catalysis on biomembrane surfaces. Phospholipases A2 (PLA2 are interesting not only as prototypes for interfacial catalysis, but also because they mobilize precursors for the biosynthesis of eicosanoids and platelet activating factor, and these agents ultimately control a wide range of secretory and inflammatory processes. Since PLA2 carry out their catalytic function at membrane surfaces, the kinetics of these enzymes depends on what the enzyme ‘sees’ at the interface, and thus the observed rate is profoundly influenced by the organization and dynamics of the lipidwater interface (‘quality of the interface’. In this review we elaborate the advantages of monitoring interfacial catalysis in the scooting mode, that is, under the conditions where the enzyme remains bound to vesicles for several thousand catalytic turnover cycles. Such a highly processive catalytic turnover in the scooting mode is useful for a rigorous and quantitative characterization of the kinetics of interfacial catalysis. This analysis is now extended to provide insights into designing strategy for PLA2 assays and screens for their inhibitors.

  8. Feasibility of a 2{sup nd} generation MR-compatible manipulator for transrectal prostate biopsy guidance

    Bomers, J.G.R.; Yakar, D. [Radboud University Nijmegen Medical Center, Department of Radiology, route 766, P.O Box 9101, Nijmegen (Netherlands); Bosboom, D.G.H. [Radboud University Nijmegen Medical Center, Department of Radiology, route 766, P.O Box 9101, Nijmegen (Netherlands); Soteria Medical, Arnhem (Netherlands); Tigelaar, G.H.; Sabisch, J. [Soteria Medical, Arnhem (Netherlands); Fuetterer, J.J. [Radboud University Nijmegen Medical Center, Department of Radiology, route 766, P.O Box 9101, Nijmegen (Netherlands); University of Twente, MIRA Institute for Biomedical Technology and Technical Medicine, Enschede (Netherlands)

    2017-04-15

    To assess the feasibility of a 2{sup nd} generation MR-compatible, remote-controlled manipulator (RCM) as an aid to perform MR-guided transrectal prostate biopsy in males with suspicion of prostate cancer (PCa). This prospective phase I study was approved by the local ethical committee and written informed consent was obtained from each patient. Twenty patients with ≥1 cancer suspicious region (CSR) with a PI-RADS score of ≥3 detected on the diagnostic multi-parametric MRI and no prior prostate treatment underwent MR-guided biopsy with the aid of the RCM. Complications were classified according to the modified Clavien system for reporting surgical complications. For evaluation of the workflow, procedure- and manipulation times were recorded. All CSR's (n=20) were reachable with the MR-compatible RCM and the cancer detection rate was 70 %. The median procedure time was 36:44 minutes (range, 23 - 61 minutes) and the median manipulation time for needle guide movement was 5:48 minutes (range, 1:15 - 18:35 minutes). Two Clavien grade 1 complications were reported. It is feasible and safe to perform transrectal MR-guided prostate biopsy using a MR-compatible RCM as an aid. It is a fast and efficient way to biopsy suspicious prostate lesions with a minimum number of biopsies per patient. (orig.)

  9. Nutritional status and oral status of the elderly with dementia: a 2-year study.

    Sadamori, Shinsuke; Hayashi, Syouji; Fujihara, Isao; Abekura, Hitoshi; Hamada, Taizo; Akagawa, Yasumasa

    2012-06-01

    To determine the relationship between denture wearing and nutritional status in the elderly with dementia. There could be a correlation between nutrition, oral health, dietary habits, patients' satisfaction, and their socio-economic status in the elderly, and the relationship between compromised oral status and nutritional status in the elderly with dementia. A 2-year follow-up study of 63 elderly Japanese women with and without dentures from a nursing home was undertaken to investigate their oral, physical and mental, and nutritional status. Each item for 2006 and 2008 in this study showed no significant difference between 2006 and 2008, except the calories/day. The elderly with dementia without complete dentures during the 2 years of the study only significantly decreased the mean of the calories/day. The calories/day of the elderly with dementia without dentures decreased after 2 years. Denture wearing for the elderly with dementia could be necessary to maintain a satisfactory intake of calories. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

  10. Exploring 4D quantum Hall physics with a 2D topological charge pump.

    Lohse, Michael; Schweizer, Christian; Price, Hannah M; Zilberberg, Oded; Bloch, Immanuel

    2018-01-03

    The discovery of topological states of matter has greatly improved our understanding of phase transitions in physical systems. Instead of being described by local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example is the two-dimensional (2D) integer quantum Hall effect: it is characterized by the first Chern number, which manifests in the quantized Hall response that is induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional (4D) systems leads to the appearance of an additional quantized Hall response, but one that is nonlinear and described by a 4D topological invariant-the second Chern number. Here we report the observation of a bulk response with intrinsic 4D topology and demonstrate its quantization by measuring the associated second Chern number. By implementing a 2D topological charge pump using ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small cloud of atoms as a local probe, we fully characterize the nonlinear response of the system via in situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probing higher-dimensional quantum Hall systems, in which additional strongly correlated topological phases, exotic collective excitations and boundary phenomena such as isolated Weyl fermions are predicted.

  11. Tubular immunostimulating complex based on cucumarioside A2-2 and monogalactosyldiacylglycerol from marine macrophytes

    Vorobyeva Natalia S

    2011-09-01

    Full Text Available Abstract Background There is an urgent need to develop safe and effective adjuvants for the new generation of subunit vaccines. We developed the tubular immunostimulating complex (TI-complex as a new nanoparticulate antigen delivery system. The morphology and composition of TI-complexes principally differ from the known vesicular immunostimulating complexes (ISCOMs. However, methodology for the preparation of TI-complexes has suffered a number of shortcomings. The aim of the present work was to obtain an antigen carrier consisting of triterpene glycosides from Cucumaria japonica, cholesterol, and monogalactosyldiacylglycerol from marine macrophytes with reproducible properties and high adjuvant activity. Results The cucumarioside A2-2 - cholesterol - MGalDG ratio of 6:2:4 (by weight was found to provide the most effective formation of TI-complexes and the minimum hemolytic activity in vitro. Tubules of TI-complexes have an outer diameter of about 16 nm, an inner diameter of 6 nm, and a length of 500 nm. A significant dilution by the buffer gradually destroyed the tubular nanoparticles. The TI-complex was able to increase the immunogenicity of the protein antigens from Yersinia pseudotuberculosis by three to four times. Conclusions We propose an optimized methodology for the preparation of homogeneous TI-complexes containing only tubular particles, which would achieve reproducible immunization results. We suggest that the elaborated TI-complexes apply as a universal delivery system for different subunit antigens within anti-infectious vaccines and enhance their economic efficacy and safety.

  12. A 2-Phase Labeling and Choice Architecture Intervention to Improve Healthy Food and Beverage Choices

    Sonnenberg, Lillian; Riis, Jason; Barraclough, Susan; Levy, Douglas E.

    2012-01-01

    Objectives. We assessed whether a 2-phase labeling and choice architecture intervention would increase sales of healthy food and beverages in a large hospital cafeteria. Methods. Phase 1 was a 3-month color-coded labeling intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2 added a 3-month choice architecture intervention that increased the visibility and convenience of some green items. We compared relative changes in 3-month sales from baseline to phase 1 and from phase 1 to phase 2. Results. At baseline (977 793 items, including 199 513 beverages), 24.9% of sales were red and 42.2% were green. Sales of red items decreased in both phases (P beverages. Red beverages decreased 16.5% during phase 1 (P beverages increased 9.6% in phase 1 (P < .001) and further increased 4.0% in phase 2 (P < .001). Bottled water increased 25.8% during phase 2 (P < .001) but did not increase at 2 on-site comparison cafeterias (P < .001). Conclusions. A color-coded labeling intervention improved sales of healthy items and was enhanced by a choice architecture intervention. PMID:22390518

  13. Surveillance of a 2D Plane Area with 3D Deployed Cameras

    Yi-Ge Fu

    2014-01-01

    Full Text Available As the use of camera networks has expanded, camera placement to satisfy some quality assurance parameters (such as a good coverage ratio, an acceptable resolution constraints, an acceptable cost as low as possible, etc. has become an important problem. The discrete camera deployment problem is NP-hard and many heuristic methods have been proposed to solve it, most of which make very simple assumptions. In this paper, we propose a probability inspired binary Particle Swarm Optimization (PI-BPSO algorithm to solve a homogeneous camera network placement problem. We model the problem under some more realistic assumptions: (1 deploy the cameras in the 3D space while the surveillance area is restricted to a 2D ground plane; (2 deploy the minimal number of cameras to get a maximum visual coverage under more constraints, such as field of view (FOV of the cameras and the minimum resolution constraints. We can simultaneously optimize the number and the configuration of the cameras through the introduction of a regulation item in the cost function. The simulation results showed the effectiveness of the proposed PI-BPSO algorithm.

  14. In vitro inactivation of hepatic microsomal phospholipase A2 by the marine natural product manoalide

    Master, M.M.; Jacobs, R.S.

    1986-01-01

    The effects of manoalide (MLD) and several analogs (isolated from the sponge Luffariella variabilis) on mouse hepatic microsomal phospholipase A 2 (PLA 2 ) activity was investigated. Microsomal PLA 2 , a membrane bound, Ca ++ dependent enzyme with an alkaline pH optimum, functions in intracellular phospholipid turnover. In vitro PLA 2 activity was assayed by preincubating MLD or analogs (2.5-100μM) with microsomes for 60 min. at 37 0 C, combining this mixture with 14 C-phosphatidylcholine and CaCl 2 , and incubating at 37 0 C for 40 minutes. Enzyme activity was quantitated by measurement of the extracted 14 C-arachidonic acid product. MLD inhibited PLA 2 in a dose-dependent manner, with an IC 50 = 94μM. Lineweaver-Burk analysis suggests that MLD inhibits PLA 2 noncompetitively. One of the analogs, producing a comparable dose-response curve to MLD, was found to be more potent (IC 50 = 33μM). Another analog facilitated PLA 2 activity (15%) at 25μM, followed by inactivation at higher doses (IC 50 > 100 μM). Facilitation of PLA 2 activity was seen with concentrations as low as 2.5μM of a third analog, and significant inactivation of PLA 2 was evident. These results indicate that MLD is not as potent against microsomal PLA 2 as has been shown with purified bee venom and cobra venom PLA 2 's

  15. The electronic quenching rates of NO(A2Σ+, v'=0-2)

    Nee, J.B.; Juan, C.Y.; Hsu, J.Y.; Yang, J.C.; Chen, W.J.

    2004-01-01

    The electronic quenching rates of NO(A 2 Σ + , v ' =0-2) are measured for the gases He, Ar, Xe, N 2 , O 2 , CO 2 , N 2 O, and SF 6 . The variations of the fluorescence intensity were measured for the (0,0), (1,0), and (2,0) bands of the γ band system when the quencher gases were added. The quenching rates were determined by using the Stern-Volmer plots with the known radiative lifetimes of the excited states. The electronic quenching rate constants are fast for the group of gases of O 2 , CO 2 , N 2 O, and SF 6 , whose quenching rate constants are in the order of 10 -10 cm 3 /s. The quenching rate constants are slow for the group of gases including He, Ar, Xe, and N 2 whose rate constants are in the order of 10 -14 cm 3 /s. For the slow group, the quenching rate constants increase rapidly for v ' =2 compared with those of v ' =0 and 1. The charge transfer model and collision complex model are used to understand the quenching mechanism. For the fast group which mainly consists of gases with positive electron affinities, the charge transfer model adequately describes the mechanism. For the slow quenching group, a theoretical background is provided by consider the coupling of initial and final states in the complex potential surfaces

  16. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

    Draughn GL

    2017-01-01

    Full Text Available G Logan Draughn,1 C Leigh Allen,1 Patricia A Routh,2 Maria R Stone,2 Kelly R Kirker,3 Laura Boegli,3 Ryan M Schuchman,1 Keith E Linder,2 Ronald E Baynes,2 Garth James,3 Christian Melander,4 Angela Pollard,5 John Cavanagh1 1Department of Molecular and Structural Biochemistry, 2Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 3Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA; 4Department of Chemistry, North Carolina State University, Raleigh, NC, USA; 5Agile Sciences Inc., Raleigh, NC, USA Abstract: 2-Aminoimidazole (2-AI-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound. Keywords: transdermal absorption, antimicrobial activity, skin irritation, synergism, oroidin derivative, drip-flow reactor, ESKAPE pathogens

  17. Predicting expressive vocabulary acquisition in children with intellectual disabilities: a 2-year longitudinal study.

    Vandereet, Joke; Maes, Bea; Lembrechts, Dirk; Zink, Inge

    2010-12-01

    This study's objectives were to describe expressive vocabulary acquisition in children with intellectual disabilities (ID) and to examine specific pre- and early linguistic behaviors used to request and comment, chronological age, cognitive skills, and vocabulary comprehension as predictors of expressive vocabulary. This study included 36 children with ID, age 3;00 (years;months) to 6;05, with an average initial expressive vocabulary of 67 words. Expressive vocabulary acquisition was longitudinally followed over a 2-year period based on 4-monthly administrations of the Dutch version of the MacArthur Communicative Development Inventory/Words and Gestures (I. Zink & M. Lejaegere, 2002). Specific pre- and early linguistic behaviors used to request and comment as well as cognitive skills and vocabulary comprehension were measured at baseline. Individual growth modeling indicated that vocabulary comprehension was the only unique predictor of initial expressive vocabulary. Subsequent vocabulary growth was uniquely predicted by proportion of bimodal gesture + vocalization comments, chronological age, and cognitive skills. The results of this study underscore the great heterogeneity in expressive vocabulary skills in children with ID. The importance of prelinguistic communication, chronological age, cognitive skills, and vocabulary comprehension for explaining differences in expressive vocabulary skills is discussed.

  18. Deliveries in maternity homes in Norway: results from a 2-year prospective study.

    Schmidt, Nina; Abelsen, Birgit; Øian, Pål

    2002-08-01

    The study aims to report the short-term outcome for the mothers and newborns for all pregnancies accepted for birth at maternity homes in Norway. A 2-year prospective study of all mothers in labor in maternity homes, i.e. all births including women and newborns transferred to hospital intra partum or the first week post partum. The study included 1275 women who started labor in the maternity homes in Norway; 1% of all births in Norway during this period. Of those who started labor in a maternity home, 1217 (95.5%) also delivered there while 58 (4.5%) women were transferred to hospital during labor. In the post partum period there were 57 (4.7%) transferrals of mother and baby. Nine women had a vacuum extraction, one had a forceps and three had a vaginal breech (1.1% operative vaginal births in the maternity homes). Five babies (0.4%) had an Apgar score below 7 at 5 min. There were two (0.2%) neonatal deaths; both babies were born with a serious group B streptococcal infection. Midwives and general practitioners working in the districts can identify a low-risk population (estimated at 35%) of all pregnant women in the catchment areas who can deliver safely at the maternity homes in Norway. Only 4.5% of those who started labor in the maternity homes had to be transferred to hospital during labor.

  19. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

    Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

    2015-01-01

    Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa -/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa -/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa -/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. PMID:26637123

  20. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme.

    Daishi Yui

    Full Text Available Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD model mice showed decreased insulin-degrading enzyme (IDE levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/- mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3; Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD.