276 research outputs found

    Митна політика Запорозької Січі: деякі аспекти дослідження проблеми.

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    Про те, що Запорозька Січ мала свою, хоча і слабо структуровану, митну систему, і що вона була важливою складовою економічного існування Січі, історики побіжно згадують, відносячи цей факт до сер. 50-х рр. XVIII ст., пояснюючи її складання прискоренням внутрішнього економічного розвитку Запорожжя, не забуваючи, однак, що стратегічне положення Січі давало їй величезні переваги від транзитної торгівлі та її забезпечення. Можливо, справедливим є припущення українського історика Я. Дашкевича про те, що “зони впливу (народів) з середини XVII ст. почали оформлюватися у вигляді юридичних кордонів, щоб остаточно стабілізуватися наприкінці XVIII ст.” [1]. Імовірно, що оформлення структури митної мережі, як і прикордонної, чітке оформлення географічних і політичних кордонів для захисту економічних інтересів відбувається на території Запорозьких Вольностей в період Нової Запорозької Січі. Питання функціонування і остаточного визначення структури митної мережі в період Нової Запорозької Січі (1734–1775 рр.) набуває актуальності і окреслених рис під тиском не лише внутрішніх, але і зовнішніх обставин. Ініціатива у цій справі з початку XVIII ст. поступово перехоплювалася царським урядом. Йшлося не про захист інтересів російської держави, а про наміри контролювати важливі торгівельні потоки і спрямовувати їх у загальноімперських інтересах. У введенні митної мережі на південних рубежах Вольностей Запорозьких найбільш показовим було ігнорування інтересів Війська Запорозького. На поверхні чітко відстежувалася загальна політика на завоювання Чорноморського узбережжя, вільну, без будь-яких політичних обмежень і перешкод східну торгівлю, виключно в інтересах Росії

    Untersuchungen zu Möglichkeiten und Grenzen der Zitratmethode zur Geschlechterbestimmung alter bodengelagerter menschlicher Knochen

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    Die anthropologische Geschlechtsbestimmung Erwachsener beruht in erster Linie auf dem Ausprägungsgrad bestimmter Form- und Größenmerkmale des Skelettes. Eine Bestimmung ist dann nur eingeschränkt oder gar nicht möglich, wenn das zu untersuchende Skelettindividuum nur fragmentarisch vorhanden ist und entsprechende Geschlechtsmarker fehlen. Mitte des 20.Jh. fand man bei Sektionsmaterial heraus, daß der Gehalt an Zitrat (Kalziumsalz der Zitronensäure) in den Wirbelkörpern der Frauen im Alter zwischen dem Beginn der geschlechtlichen Reife und dem Klimakterium signifikant höher ist als bei Männern des gleichen Alters. Für die quantitative Bestimmung der Zitratkonzentration werden mehrere Methoden beschrieben, die alle als mehr oder weniger kosten- und zeitintensiv beschrieben werden. In den letzten 50 Jahren wurde hauptsächlich die Methode nach HESS (1956) angewendet, bei der es allerdings zu vielen Fehlern kommen kann. Aus diesem Grunde ist in dieser Arbeit zum ersten Mal auch die enzymatische Methode nach BOEHRINGER MANNHEIM (1994) auf ihre Anwendbarkeit auf Knochenmaterial getestet worden. Diese Methode diente bisher nur zur Bestimmung des Zitratgehaltes von Lebensmitteln und besticht im allgemeinen durch ihre Einfachheit und Genauigkeit. Es wurden insgesamt 225 verschiedene Knochenproben aus 6 verschiedenen Untersuchungsgruppen auf ihren Zitratgehalt getestet. Sie wurden alle geschlechtsbestimmt und das Ergebnis mit dem wirklichen Geschlecht, bzw. der anthropologischen (morphometrischen) Geschlechtsbestimmung verglichen. Dabei konnten folgende Ergebnisse erzielt werden: Die mit der enzymatischen Methode nach BOEHRINGER MANNHEIM (1994) errechneten Zitratkonzentrationen liegen bei beiden Geschlechtern und in allen Altersgruppen (insgesamt 54 Knochenproben der Lendenwirbelsäule) bei frischem Knochenmaterial aus Obduktionen und Operationen über denen, die mit Hilfe der Methode nach HESS (1956) am gleichen Material gewonnen wurden. Die Bestimmungssicherheit der Methode nach BOEHRINGER MANNHEIM (1994) liegt geringfügig, aber nicht signifikant, über der der Methode nach HESS (1956) und bei beiden Methoden bei über 90%. Darüber hinaus ist die Bearbeitung einer Untersuchungsserie mit der Zitratmethode nach BOEHRINGER MANNHEIM (1994) billiger, wesentlich einfacher und weniger zeitaufwendig. Die Zitratkonzentrationen zeigen an historischem Material (hier 68 Proben von je 5 verschiedenen Skelettregionen) keine signifikanten Unterschiede zwischen verschiedenen Skelettregionen oder zwischen den Knochenzonen Kompakta und Spongiosa. Da der Zitratgehalt des Knochens aber nicht nur durch die Einlagerung während des Lebens, sondern auch durch den Abbau während der Bodenlagerung bestimmt wird, läßt sich keine Aussage über unterschiedliche Einlagerungen in die verschiedenen Knochenzonen Kompakta und Spongiosa treffen. Die Bestimmungssicherheit mit der Zitratmethode liegt bei der Verwendung von Lendenwirbelkörperspongiosa (hier 100%) etwas über der von Extremitätenkompakta (hier 94,4%). Die Methode der Zitratbestimmung zur Geschlechtsbestimmung läßt sich offenbar nur dann auf Kinder der Altersgruppen Infans I und Infans II (0-12 Jahre) anwenden, wenn wenigstens eines der Kinder mit anthropologischen oder archäologischen Methoden als männlich oder weiblich bestimmt wurde. Mit diesem \u27Marker\u27 können dann die anderen Kinder ebenfalls einem Geschlecht zugeordnet werden. Die Bestimmungssicherheit liegt dabei bei 87,5% und damit deutlich unter der Bestimmungssicherheit bei Erwachsenen (hier 100%). Der Nachweis, daß auch Skelettindividuen im Alter von über 60 Jahren mit dieser Methode nicht mehr als männlich oder weiblich zu bestimmen sind, konnte nicht erbracht werden. Anscheinend sinkt die Bestimmungssicherheit aber ab (hier 80% bei 61-82jährigen gegenüber 100% bei 18-60jährigen). Die Bestimmungssicherheit der Zitratmethode nach BOEHRINGER MANNHEIM (1994) liegt bei allen Untersuchungsgruppen bei über 90% (zwischen 94% und 100%), im Durchschnitt aller untersuchten Knochenproben bei 96%. Skelettserien von verschiedener geographischer Herkunft oder aus unterschiedlichen zeitlichen Epochen lassen sich prinzipiell nicht miteinander vergleichen. Ein einzelnes gefundenes Skelett kann demnach nicht als männlich oder weiblich bestimmt werden, da keine Vergleichsdaten zur Verfügung stehen. Ein Vergleich der Zitratkonzentration dieses Skelettes mit einer zeitlich und räumlich benachbarten Serie kann, muß aber nicht, ein richtiges Ergebnis bei der Geschlechtsbestimmung ergeben. Weiterhin ist es wichtig, das ungefähre Alter des Skelettindividuums zum Zeitpunkt des Todes, bzw. der Knochenentnahme zu kennen, da die Zitratkonzentration des Knochens altersabhängig ist. Die Anwendbarkeit der Zitratmethode auf Leichenbrände (hier 25 Individuen) bietet eine neue Möglichkeit der Geschlechtsbestimmung an nur fragmentarisch vorhandenen Skelettindividuen. Insgesamt kann aus den in dieser Arbeit durchgeführten Untersuchungen zu Möglichkeiten und Grenzen der Zitratmethode zur Geschlechtsbestimmung alter bodengelagerter menschlicher Knochen geschlossen werden, daß es nicht möglich ist, ein einzelnes Skelett oder Skelettfragment durch die Erfassung der Zitratkonzentration als männlich oder weiblich zu bestimmen. Eine Geschlechtsbestimmung ist durchführbar, wenn eine möglichst große Anzahl von Skelettindividuen der gleichen Serie untersucht wird, die also den gleichen geologischen und klimatischen Bedingungen unterworfen war. Auf diese Weise erhält man einen Überblick über die Variabilität der Zitratkonzentration innerhalb dieser Serie und kann mit Hilfe eines statistisch ermittelten Trennwertes zwischen Männern und Frauen einer Altersgruppe hohe Werte den Frauen und niedrige Werte den Männern zuweisen. Ebenso kann eine Probe eines als Mann oder Frau bekannten Skelettes als \u27Geschlechtsmarker\u27 zur Wiederfindung der Geschlechter der gleichen Altersklasse und der gleichen Serie dienen. Eine relativ große Konzentrationsdifferenz zwischen den Geschlechtern (hier zwischen 4,2% in der Altersstufe Senil bis 46,4% bei 21-30jährigen) erlaubt eine Einordnung der Individuen. Die Geschlechtsbestimmung mit der Zitratmethode nach BOEHRINGER MANNHEIM (1994) ist einfach, sicher und günstig. Sie bietet damit die Möglichkeit die anhand morphometrischer Merkmale erstellten Geschlechtsbestimmungen abzusichern, bzw. nicht bestimmbare Individuen einer Serie einem Geschlecht zuzuordnen

    Charge Imbalance Effects on Interlayer Hopping and Fermi Surfaces in Multilayered High-T_c Cuprates

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    We study doping dependence of interlayer hoppings, t_\perp, in multilayered cuprates with four or more CuO_2 planes in a unit cell. When the double occupancy is forbidden in the plane, an effective amplitude of t_\perp in the Gutzwiller approximation is shown to be proportional to the square root of the product of doping rates in adjacent two planes, i.e., t^eff_\perp \propto t_\perp \sqrt{\delta_1\delta_2}, where \delta_1 and \delta_2 represent the doping rates of the two planes. More than three-layered cuprates have two kinds of \cuo planes, i.e., inner- and outer planes (IP and OP), resulting in two different values of t^eff_{\perp}, i.e., t^eff_\perp 1 \propto t_\perp \sqrt{\delta_IP \delta_IP} between IP's, and t^eff_\perp 2 \propto t_\perp \sqrt{\delta_IP \delta_OP} between IP and OP. Fermi surfaces are calculated in the four-layered t-t'-t''-J model by the mean-field theory. The order parameters, the renormalization factor of t_\perp, and the site-potential making the charge imbalance between IP and OP are self-consistently determined for several doping rates. We show the interlayer splitting of the Fermi surfaces, which may be observed in the angle resolved photoemission spectroscopy measurement.Comment: Some typographical errors are revised. Journal of Physical Society of Japan, Vol.75, No.3, in pres

    Thermally-activated cation ordering in ZnGa2Se4 single crystals studied by Raman scattering, optical absorption, and ab initio calculations

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    Order-disorder phase transitions induced by thermal annealing have been studied in the ordered-vacancy compound ZnGa2Se4 by means of Raman scattering and optical absorption measurements. The partially disordered as-grown sample with tetragonal defect stannite (DS) structure and I (4) over bar 2m space group has been subjected to controlled heating and cooling cycles. In situ Raman scattering measurements carried out during the whole annealing cycle show that annealing the sample to 400 degrees C results in a cation ordering in the sample, leading to the crystallization of the ordered tetragonal defect chalcopyrite (DC) structure with I (4) over bar space group. On decreasing temperature the ordered cation scheme of the DC phase can be retained at ambient conditions. The symmetry of the Raman-active modes in both DS and DC phases is discussed and the similarities and differences between the Raman spectra of the two phases emphasized. The ordered structure of annealed samples is confirmed by optical absorption measurements and ab initio calculations, that show that the direct bandgap of DC-ZnGa2Se4 is larger than that of DS-ZnGa2Se4.This study was supported by the Spanish government MEC under grants MAT2010-21270-C04-01/03/04 and MAT2010-19837-C06-06, by MALTA Consolider Ingenio 2010 project (CSD2007-00045), and by the Vicerrectorado de Investigacion y Desarrollo of the Universitat Politecnica de Valencia (UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11). EP-G, AM, and PR-H acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster. Finally, the authors would also like to acknowledge M C Moron for stimulating discussions and revision of the present manuscript.Vilaplana Cerda, RI.; Gomis Hilario, O.; Pérez-González, E.; Ortiz, HM.; Manjón Herrera, FJ.; Rodríguez-Hernández, P.; Muñoz, A.... (2013). Thermally-activated cation ordering in ZnGa2Se4 single crystals studied by Raman scattering, optical absorption, and ab initio calculations. Journal of Physics: Condensed Matter. 25(16):165802-1-165802-11. https://doi.org/10.1088/0953-8984/25/16/165802S165802-1165802-112516Bernard, J. E., & Zunger, A. (1988). Ordered-vacancy-compound semiconductors: PseudocubicCdIn2Se4. Physical Review B, 37(12), 6835-6856. doi:10.1103/physrevb.37.6835Jiang, X., & Lambrecht, W. R. L. (2004). Electronic band structure of ordered vacancy defect chalcopyrite compounds with formulaII−III2−VI4. Physical Review B, 69(3). doi:10.1103/physrevb.69.035201Yahia, I. S., Fadel, M., Sakr, G. B., & Shenouda, S. S. (2010). Memory switching of ZnGa2Se4 thin films as a new material for phase change memories (PCMs). Journal of Alloys and Compounds, 507(2), 551-556. doi:10.1016/j.jallcom.2010.08.021Yahia, I. S., Fadel, M., Sakr, G. B., Yakuphanoglu, F., Shenouda, S. S., & Farooq, W. A. (2011). Analysis of current–voltage characteristics of Al/p-ZnGa2Se4/n-Si nanocrystalline heterojunction diode. Journal of Alloys and Compounds, 509(12), 4414-4419. doi:10.1016/j.jallcom.2011.01.068Hahn, H., Frank, G., Klingler, W., St�rger, A. D., & St�rger, G. (1955). Untersuchungen �ber tern�re Chalkogenide. VI. �ber Tern�re Chalkogenide des Aluminiums, Galliums und Indiums mit Zink, Cadmium und Quecksilber. Zeitschrift f�r anorganische und allgemeine Chemie, 279(5-6), 241-270. doi:10.1002/zaac.19552790502Errandonea, D., Kumar, R. S., Manjón, F. J., Ursaki, V. V., & Tiginyanu, I. M. (2008). High-pressure x-ray diffraction study on the structure and phase transitions of the defect-stannite ZnGa2Se4 and defect-chalcopyrite CdGa2S4. Journal of Applied Physics, 104(6), 063524. doi:10.1063/1.2981089Morón, M. C., & Hull, S. (2003). Order-disorder phase transition inZn1−xMnxGa2Se4: Long-range order parameter versusx. Physical Review B, 67(12). doi:10.1103/physrevb.67.125208Morón, M. C., & Hull, S. (2005). Effect of magnetic dilution in Zn1−xMnxGa2Se4 (0<x<0.5). Journal of Applied Physics, 98(1), 013904. doi:10.1063/1.1944220Morón, M. C., & Hull, S. (2007). The influence of magnetic dilution in the Zn1−xMnxGa2Se4 series with 0.5<x⩽1. Journal of Applied Physics, 102(3), 033919. doi:10.1063/1.2767273Antonioli, G., Lottici, P. P., & Razzetti, C. (1989). The structure of the defect chalcopyrite ZnGa2Se4 studied by EXAFS. physica status solidi (b), 152(1), 39-49. doi:10.1002/pssb.2221520104Haeuseler, H. (1978). FIR- und Ramanspektren von ternären Chalkogeniden des Galliums und Indiums mit Zink, Cadmium und Quecksilber. Journal of Solid State Chemistry, 26(4), 367-376. doi:10.1016/0022-4596(78)90171-8Eifler, A., Krauss, G., Riede, V., Krämer, V., & Grill, W. (2005). Optical phonon modes and structure of ZnGa2Se4 and ZnGa2S4. Journal of Physics and Chemistry of Solids, 66(11), 2052-2057. doi:10.1016/j.jpcs.2005.09.049Lottici, P. P., & Razzetti, C. (1983). A comparison of the raman spectra of ZnGa2Se4 and other gallium defect chalcopyrites. Solid State Communications, 46(9), 681-684. doi:10.1016/0038-1098(83)90506-9Razzetti, C., Lottici, P. P., & Antonioli, G. (1987). Structure and lattice dynamics of nonmagnetic defective AIIBIII2XIV4 compounds and alloys. Progress in Crystal Growth and Characterization, 15(1), 43-73. doi:10.1016/0146-3535(87)90009-8Attolini, G., Bini, S., Lottici, P. P., & Razzetti, C. (1992). Effects of Group III Cation Substitution in the Raman Spectra of Some Defective Chalcopyrites. Crystal Research and Technology, 27(5), 685-690. doi:10.1002/crat.2170270519Takahashi, Y., Namatsu, H., Machida, K., & Minegishi, K. (1993). Measurements of Diffusion Coefficiens of Water in Electron Cryclotron Resonance Plasma SiO2. Japanese Journal of Applied Physics, 32(Part 2, No. 3B), L431-L433. doi:10.1143/jjap.32.l431Ursaki, V. V., Burlakov, I. I., Tiginyanu, I. M., Raptis, Y. S., Anastassakis, E., & Anedda, A. (1999). Phase transitions in defect chalcopyrite compounds under hydrostatic pressure. Physical Review B, 59(1), 257-268. doi:10.1103/physrevb.59.257Allakhverdiev, K., Gashimzade, F., Kerimova, T., Mitani, T., Naitou, T., Matsuishi, K., & Onari, S. (2003). Raman scattering under pressure in ZnGa2Se4. Journal of Physics and Chemistry of Solids, 64(9-10), 1597-1601. doi:10.1016/s0022-3697(03)00077-5Alonso-Gutiérrez, P., Sanjuán, M. L., & Morón, M. C. (2009). Thermally activated cation ordering in Zn0.5Mn0.5Ga2Se4single crystals studied by Raman scattering. physica status solidi (c), 6(5), 1182-1186. doi:10.1002/pssc.200881218Caldera, D., Morocoima, M., Quintero, M., Rincon, C., Casanova, R., & Grima, P. (2011). On the crystal structure of the defective ternary compound. Solid State Communications, 151(3), 212-215. doi:10.1016/j.ssc.2010.11.031Gomis, O., Vilaplana, R., Manjón, F. J., Pérez-González, E., López-Solano, J., Rodríguez-Hernández, P., … Ursaki, V. V. (2012). High-pressure optical and vibrational properties of CdGa2Se4: Order-disorder processes in adamantine compounds. Journal of Applied Physics, 111(1), 013518. doi:10.1063/1.3675162Eifler, A., Hecht, J.-D., Lippold, G., Riede, V., Grill, W., Krauß, G., & Krämer, V. (1999). Combined infrared and Raman study of the optical phonons of defect chalcopyrite single crystals. Physica B: Condensed Matter, 263-264, 806-808. doi:10.1016/s0921-4526(98)01292-7Sanjuán, M. L., & Morón, M. C. (2002). Raman study of Zn1−xMnxGa2Se4 diluted magnetic semiconductors: disorder and resonance effects. Physica B: Condensed Matter, 316-317, 565-567. doi:10.1016/s0921-4526(02)00574-4Letoullec, R., Pinceaux, J. P., & Loubeyre, P. (1988). The membrane diamond anvil cell: A new device for generating continuous pressure and temperature variations. High Pressure Research, 1(1), 77-90. doi:10.1080/08957958808202482Perdew, J. P., Burke, K., & Ernzerhof, M. (1997). Generalized Gradient Approximation Made Simple [Phys. Rev. Lett. 77, 3865 (1996)]. Physical Review Letters, 78(7), 1396-1396. doi:10.1103/physrevlett.78.1396Manjón, F. J., Gomis, O., Rodríguez-Hernández, P., Pérez-González, E., Muñoz, A., Errandonea, D., … Ursaki, V. V. (2010). Nonlinear pressure dependence of the direct band gap in adamantine ordered-vacancy compounds. Physical Review B, 81(19). doi:10.1103/physrevb.81.195201Santamaría-Pérez, D., Amboage, M., Manjón, F. J., Errandonea, D., Muñoz, A., Rodríguez-Hernández, P., … Tiginyanu, I. M. (2012). Crystal Chemistry of CdIn2S4, MgIn2S4, and MnIn2S4 Thiospinels under High Pressure. The Journal of Physical Chemistry C, 116(26), 14078-14087. doi:10.1021/jp303164kBaroni, S., de Gironcoli, S., Dal Corso, A., & Giannozzi, P. (2001). Phonons and related crystal properties from density-functional perturbation theory. Reviews of Modern Physics, 73(2), 515-562. doi:10.1103/revmodphys.73.515Giannozzi, P., Baroni, S., Bonini, N., Calandra, M., Car, R., Cavazzoni, C., … Wentzcovitch, R. M. (2009). QUANTUM ESPRESSO: a modular and open-source software project for quantum simulations of materials. Journal of Physics: Condensed Matter, 21(39), 395502. doi:10.1088/0953-8984/21/39/395502Kroumova, E., Aroyo, M. I., Perez-Mato, J. M., Kirov, A., Capillas, C., Ivantchev, S., & Wondratschek, H. (2003). Bilbao Crystallographic Server : Useful Databases and Tools for Phase-Transition Studies. Phase Transitions, 76(1-2), 155-170. doi:10.1080/0141159031000076110Loudon, R. (1964). The Raman effect in crystals. Advances in Physics, 13(52), 423-482. doi:10.1080/00018736400101051Alonso-Gutiérrez, P., & Sanjuán, M. L. (2008). Ordinary and extraordinary phonons and photons: Raman study of anisotropy effects in the polar modes ofMnGa2Se4. Physical Review B, 78(4). doi:10.1103/physrevb.78.045212Manjón, F. J., Marí, B., Serrano, J., & Romero, A. H. (2005). Silent Raman modes in zinc oxide and related nitrides. Journal of Applied Physics, 97(5), 053516. doi:10.1063/1.1856222Garbato, L., Ledda, F., & Rucci, A. (1987). Structural distortions and polymorphic behaviour in ABC2 and AB2C4 tetrahedral compounds. Progress in Crystal Growth and Characterization, 15(1), 1-41. doi:10.1016/0146-3535(87)90008-6Grzechnik, A., Ursaki, V. V., Syassen, K., Loa, I., Tiginyanu, I. M., & Hanfland, M. (2001). Pressure-Induced Phase Transitions in Cadmium Thiogallate CdGa2Se4. Journal of Solid State Chemistry, 160(1), 205-211. doi:10.1006/jssc.2001.9224Marquina, J., Power, C., Grima, P., Morocoima, M., Quintero, M., Couzinet, B., … González, J. (2006). Crystallographic properties of the MnGa2Se4 compound under high pressure. Journal of Applied Physics, 100(9), 093513. doi:10.1063/1.2358826Meenakshi, S., Vijayakumar, V., Eifler, A., & Hochheimer, H. D. (2010). Pressure-induced phase transition in defect Chalcopyrites HgAl2Se4 and CdAl2S4. Journal of Physics and Chemistry of Solids, 71(5), 832-835. doi:10.1016/j.jpcs.2010.02.007Gomis, O., Vilaplana, R., Manjón, F. J., Santamaría-Pérez, D., Errandonea, D., Pérez-González, E., … Ursaki, V. V. (2013). High-pressure study of the structural and elastic properties of defect-chalcopyrite HgGa2Se4. Journal of Applied Physics, 113(7), 073510. doi:10.1063/1.4792495Lowe-Ma, C. K., & Vanderah, T. A. (1991). Structure of ZnGa2S4, a defect sphalerite derivative. Acta Crystallographica Section C Crystal Structure Communications, 47(5), 919-924. doi:10.1107/s0108270190011192Roa, L., Chervin, J. C., Chevy, A., Davila, M., Grima, P., & Gonzáez, J. (1996). Optical Absorption and Raman Scattering Measurements in CuAlSe2 at High Pressure. physica status solidi (b), 198(1), 99-104. doi:10.1002/pssb.222198011

    Genetic Analyses of Heme Oxygenase 1 (HMOX1) in Different Forms of Pancreatitis

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    Contains fulltext : 107993.pdf (publisher's version ) (Open Access)BACKGROUND: Heme oxygenase 1 (HMOX1) is the rate limiting enzyme in heme degradation and a key regulator of inflammatory processes. In animal models the course of pancreatitis was ameliorated by up-regulation of HMOX1 expression. Additionally, carbon monoxide released during heme breakdown inhibited proliferation of pancreatic stellate cells and might thereby prevent the development of chronic pancreatitis (CP). Transcription of HMOX1 in humans is influenced by a GT-repeat located in the promoter. As such, HMOX1 variants might be of importance in the pathogenesis of pancreatitis. METHODS: The GT-repeat and SNP rs2071746 were investigated with fluorescence labelled primers and by melting curve analysis in 285 patients with acute pancreatitis, 208 patients with alcoholic CP, 207 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and in 289 controls, respectively. GT-repeat analysis was extended to a total of 446 alcoholic CP patients. In addition, we performed DNA sequencing in 145 patients with alcoholic CP, 138 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and 151 controls. Exon 3 screening was extended to additional patients and controls. RESULTS: S- and L-alleles of the GT-repeat, genotypes and alleles of SNP rs2071746 and non-synonymous variants detected by sequencing were found with similar frequencies in all groups. CONCLUSIONS: Although functional data implicate a potential influence of HMOX1 variants on the pathogenesis of pancreatitis, we did not find any association. As rare non-synonymous HMOX1 variants were found in patients and controls, it is rather unlikely that they will have functional consequences essential for pancreatitis development

    The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

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    TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain. RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to individualize decision-making: First, the majority of the data are limited to non small cell lung (NSCLC) and breast cancer; therefore, in other tumor histologies, the possibility of clinical benefit cannot be absolutely ruled out. Second, the addition of chemotherapy to WBRT improved response rates in some, but not all trials; response rate was not the primary endpoint in most of these trials and end-point assessment was non-centralized, non-blinded, and post-hoc. Enrollment in chemotherapy-related clinical trials is encouraged

    USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

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    Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy

    Structural and vibrational properties of CdAl2S4 under high pressure: Experimental and theoretical approach

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    "This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp5037926.”The behavior of defect chalcopyrite CdAl2S4 at high pressures and ambient temperature has been investigated in a joint experimental and theoretical study. High-pressure X-ray diffraction and Raman scattering measurements were complemented with theoretical ab initio calculations. The equation of state and pressure dependences of the structural parameters of CdAl2S4 were determined and compared to those of other AB(2)X(4) ordered-vacancy compounds. The pressure dependence of the Raman-active mode frequencies is reported, as well as the theoretical phonon dispersion curves and phonon density of states at 1 atm. Our measurements suggest that defect chalcopyrite CdAl2S4 undergoes a phase transition above 15 GPa to a disordered-rocksalt structure, whose equation of state was also obtained up to 25 GPa. In a downstroke from 25 GPa to 1 atm, our measurements indicate that CdAl2S4 does not return to the defect chalcopyrite phase; it partially retains the disordered-rocksalt phase and partially transforms into the spinel structure. The nature of the spinel structure was confirmed by the good agreement of our experimental results with our theoretical calculations. All in all, our experimental and theoretical results provide evidence that the spinel and defect chalcopyrite phases of CdAl2S4 are competitive at 1 atm. This result opens the way to the synthesis of spinel-type CdAl2S4 at near-ambient conditions.Financial support from the Spanish Consolider Ingenio 2010 Program (Project CSD2007-00045) is acknowledged. This work was also supported by Spanish MICCIN under Project MAT2010-21270-C04-03/04 and by Vicerrectorado de Investigacion de la Universitat Politecnica de Valencia under Projects UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11. Supercomputer time was provided by the Red Espanola de Supercomputacion (RES) and the MALTA cluster. J.A.S. acknowledges the Juan de la Cierva fellowship program for financial support. AM. and P.R.-H. acknowledge S. Munoz Rodriguez for providing a data-parsing application.Sans Tresserras, JÁ.; Santamaría Pérez, D.; Popescu, C.; Gomis, O.; Manjón Herrera, FJ.; Vilaplana Cerda, RI.; Muñoz, A.... (2014). Structural and vibrational properties of CdAl2S4 under high pressure: Experimental and theoretical approach. Journal of Physical Chemistry C. 118(28):15363-15374. https://doi.org/10.1021/jp5037926S15363153741182

    Neuronal Sirt3 Protects against Excitotoxic Injury in Mouse Cortical Neuron Culture

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    BACKGROUND: Sirtuins (Sirt), a family of nicotinamide adenine nucleotide (NAD) dependent deacetylases, are implicated in energy metabolism and life span. Among the known Sirt isoforms (Sirt1-7), Sirt3 was identified as a stress responsive deacetylase recently shown to play a role in protecting cells under stress conditions. Here, we demonstrated the presence of Sirt3 in neurons, and characterized the role of Sirt3 in neuron survival under NMDA-induced excitotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: To induce excitotoxic injury, we exposed primary cultured mouse cortical neurons to NMDA (30 µM). NMDA induced a rapid decrease of cytoplasmic NAD (but not mitochondrial NAD) in neurons through poly (ADP-ribose) polymerase-1 (PARP-1) activation. Mitochondrial Sirt3 was increased following PARP-1 mediated NAD depletion, which was reversed by either inhibition of PARP-1 or exogenous NAD. We found that massive reactive oxygen species (ROS) produced under this NAD depleted condition mediated the increase in mitochondrial Sirt3. By transfecting primary neurons with a Sirt3 overexpressing plasmid or Sirt3 siRNA, we showed that Sirt3 is required for neuroprotection against excitotoxicity. CONCLUSIONS: This study demonstrated for the first time that mitochondrial Sirt3 acts as a prosurvival factor playing an essential role to protect neurons under excitotoxic injury

    Treatment strategies for oesophageal cancer - time-trends and long term outcome data from a large tertiary referral centre

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    <p>Abstract</p> <p>Background and objectives</p> <p>Treatment options for oesophageal cancer have changed considerably over the last decades with the introduction of multimodal treatment concepts dominating the progress in the field. However, it remains unclear in how far the documented scientific progress influenced and changed the daily routine practice. Since most patients with oesophageal cancer generally suffer from reduced overall health conditions it is uncertain how high the proportion of aggressive treatments is and whether outcomes are improved substantially. In order to gain insight into this we performed a retrospective analysis of patients treated at a larger tertiary referral centre over time course of 25 years.</p> <p>Patients and methods</p> <p>Data of all patients diagnosed with squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus, treated between 1983 and 2007 in the department of radiation oncology of the LMU, were obtained. The primary endpoint of the data collection was overall survival (calculated from the date of diagnosis until death or last follow up). Changes in basic clinical characteristics, treatment approach and the effect on survival were analysed after dividing the cohort into five subsequent time periods (I-V) with 5 years each. In a second analysis any pattern of change regarding the use of radio(chemo)therapy (R(C)T) with and without surgery was determined.</p> <p>Results</p> <p>In total, 503 patients with SCC (78.5%) and AC (18.9%) of the oesophagus were identified. The average age was 60 years (range 35-91 years). 56.5% of the patients were diagnose with advanced UICC stages III-IV. R(C)T was applied to 353 (70.2%) patients; R(C)T+ surgery was performed in 134 (26.6%) patients, 63.8% of all received chemotherapy (platinum-based 5.8%, 5-fluorouracil (5-FU)12.1%, 42.3% 5-FU and mitomycin C (MMC)). The median follow-up period was 4.3 years. The median overall survival was 21.4 months. Over the time, patients were older, the formal tumour stage was more advanced, the incidence of AC was higher and the intensified treatment had a higher prevalence. However there was only a trend for an improved OS over the years with no difference between RCT with or without surgery (p = 0.09). The use of radiation doses over 54 Gy and the addition of chemotherapy (p = 0.002) were associated with improved OS.</p> <p>Conclusion</p> <p>Although more complex treatment protocols were introduced into clinical routine, only a minor progress in OS rates was detectable. Main predictors of outcome in this cohort was the addition of chemotherapy. The addition of surgery to radio-chemotherapy may only be of value for very limited patient groups.</p
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