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Sample records for francais g1 el2

  1. Recent progress in the detection of bursts in the canning in French reactors; Progres recents de la detection des ruptures de gaines dans les reacteurs francais G1, EL2, G3, EL3

    Energy Technology Data Exchange (ETDEWEB)

    Goupil, J.; Grenon, M.; Raffailhac, J.; Roguin, A. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1959-07-01

    In piles cooled by pressurized carbon dioxide, type G{sub 3}, the chief radioactivity of the gas is that of nitrogen - 16 created by {sup 16}O (n, p) {sup 16}N reaction of the fact neutrons on the oxygen. This activity short-lived and with a high {beta} energy, masks the activity of fission gases escaping through a crack in the canning into the carbon dioxide, and makes it necessary to use a material method to separate the solid fission products before the detection proper. This detection is carried out by means of a special electronic system whose input is a scintillator associated with a photomultiplier. A system for measuring the evolution of a crack with compensation for power variations allows the speed of development of a crack to be followed. This instrument, baptised 'evolution-meter', is designed to make the measurement of the activity of the cooling gas in the canals by a zero method, and thus to be independent of: 1) the activity of the gas itself, left after discrimination of the fission products; 2) uranium pollution of the canning and eventual pollution of the canals after rapid splits in the canning. The 'evolution-meter' consists of a memory which stores canal activity values taken at a given moment considered as a reference. The values of canal activity during the course of prospection are compared to this memory. A difference between the values indicates the appearance or the evolution of a crack in the canning. To account for the variations of thermodynamic running conditions in the canals, the values taken from the memory are corrected by a signal from an activity detector placed in the general circuit of gas leaving the pile. In the case of the pile EL{sub 2}, also cooled by pressurized CO{sub 2}, a method similar to that of G{sub 3}, has been used. Samples of cooling gas are taken successively in each of the 133 pile cells by the opening of electro-valves. The gas is filtered and the fission products extracted by an electrostatic collecting method. A scintillator and an electronic system provide a specific signal of the fission products which is then marked on a recorder. In a case where the activity threshold is exceeded, the cell involved is isolated from the prospection system and taker, over by a 'follow-up' detector which follows the evolution of the crack. A year of working on the pile G{sub 1}, which is cooled by air at atmospheric pressure, has made it possible to obtain results on the operation of the canning-burst detection appliance, which has led us to perfect the original device by installing an 'evolution-meter' of the type described above for G{sub 3}. The reactor EL{sub 3}, cooled by heavy water, uses a detection system based on the measurement by GM counters of the activity of the fission gases carried by diluted helium into the heavy water, then extracted by hydro-cyclones. The selectivity of the system gives it a low sensitivity to parasite activities, and an excellent performance. (author) [French] Dans les piles refroidies par gaz carbonique sous pression, du type G{sub 3}, la radioactivite principale du gaz est celle de l'azote 16 creee par reaction {sup 16}O(n, p) {sup 16}N des neutrons rapides sur l'oxygene. Cette activite, de vie courte et de forte energie {beta}, masque l'activite des gaz de fission s'echappant par une fissure de gaine dans le gaz carbonique et oblige a utiliser une methode de separation materielle des produits de fission solides avant la detection proprement dite. Cette detection est faite par une chaine electronique speciale dont l'entree est un scintillateur associe a un photomultiplicateur. Un systeme de mesure d'evolution de fissure avec compensation des variations de puissance permet de suivre la vitesse d'evolution d'une fissure. Cet appareil, baptise evolumetre, est destine a ramener a une methode de zero la mesure de l'activite du gaz de refroidissement des canaux, il permet de s'affranchir: 1) de l'activite propre du gaz restant apres la discrimination d

  2. Le Francais Courant: Part V, French.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    Instructional objectives of the Dade County Public Schools Quinmester Program in French for use with "Le Francais Courant: Part 5" focus on the development of mastery of the basic numbering system and other grammatical structures. Structures include the formation of the present tense of the irregular verbs…

  3. Neues "Francais fondamental?" Das Europa-Projekt "Un niveau seuil." (A New "Francais fondamental?" The European Project "A Threshold Level").

    Science.gov (United States)

    Raasch, Albert

    1978-01-01

    The project "Threshold Level," initiated by the Council of Europe in 1976, is compared with "Francais fondamental," comparing their aims and their differences. Offered as an interim statement, the article leaves open the question of whether Francais fondamental should be replaced by the the Threshold Level. (IFS/WGA)

  4. The Language Laboratory of the Ecole de Francais Moderne of the University of Lausanne

    Science.gov (United States)

    Guex, Andre

    1974-01-01

    This is a description of the materials developed for the language laboratory of the Ecole de Francais Moderne at the University of Lausanne. The tapes are designed to deal specifically with French phonetics, grammar, and lexicon. (AM)

  5. Youth Delegation of Secours Populaire Francais Visits China

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>At the invitation of the CPAFFC, a 30-member youth delegation of the Secours Populaire Francais (SPF) visited China from August 10 to 18, 2008. Through organizing the Chinese and French young people to watch the Olympic Games together, the visit aimed to enhance understanding and friendship and promote the Olympic spirit. During their visit, the delegation went to Gansu Province to attend the inauguration of the Friendship Water Cellars built with the SPF’s fund, watched Olympic games together with the students coming from the Dongqi Middle School of Hanwang County, Mianzhu City which suffered severe damage in the Sichuan earthquake and the Beijing No. 22 Middle School, and participated in the Chinese and French youth social activities.

  6. G8: trois Francais, auteurs presumes de violences à Genève, arretes mercredi

    CERN Multimedia

    2003-01-01

    "Trois Francais, soupconnes d'avoir participe a des violences survenues a Geneve en marge du sommet du G8 en juin dernier, ont ete arretes mercredi a Geneve, apres avoir reconnu les faits qui leur sont reproches, a annonce la police locale" (1/2 page).

  7. "Le Francais Des Affaires": At the Crossroads of US/EU Trade and Language Policies.

    Science.gov (United States)

    Finel-Honigman, Irene

    1997-01-01

    Discusses the need to enhance United States/European Union (EU) commercial and educational cooperation. Differences between US and EU language and trade policies are explored and the importance of plurilingualism in the global economy is examined. The role of the French Language, especially "Le francais des affaires," in facilitating access to the…

  8. The Lycee Francais in New York: A Showcase for the French-Speaking Community

    Science.gov (United States)

    Michel, Florence

    2004-01-01

    In New York they say that the architecture of the new "Lycee francais" (serving French students from kindergarten through upper secondary education) was inspired by the rationalism of Descartes. What is beyond doubt, however, is that the design and materials chosen by the American firm of architects, "Polshek Partnership Architects," which…

  9. Le francais parle dans la ville de Quebec: une etude sociolinguistique (The Spoken French in the City of Quebec: A Sociolinguistic Study). Publication G-1.

    Science.gov (United States)

    Deshaies, Denise

    This study is divided into two major sections. The first, the study of language in a sociolinguistic perspective, includes: (1) an analysis of the attitudes associated with linguistic variation, and a review of (2) studies conducted in French Quebec, (3) the linguistic and cultural deficit theories, (4) the theory of cross-linguistic and…

  10. RELIEF: Revue de linguistique et d'enseignement du francais (Review of Linguistics and French Language Instruction), 1994.

    Science.gov (United States)

    Mahler, M., Ed.; Haillet, P., Ed.

    1994-01-01

    Contains five articles, all in French, reporting research on French second language instruction. "Francophonie et francais langue seconde a l'oral: quel(s) culture(s), quelles methodes?" (Francophony and Spoken French as a Second Language: What Cultures(s), What Method(s) (D. Issa-Sayegh) discusses the content and structure of a university course…

  11. RELIEF: Revue de linguistique et d'enseignement du francais (Review of Linguistics and French Language Instruction), 1991-1993.

    Science.gov (United States)

    Haillet, P., Ed.; And Others

    1993-01-01

    This document consists of the first two issues of the journal RELIEF. Each issue contains four articles. All articles deal with French second language instruction: (1) "Utiliser la presse ecrite en classe de francais-langue seconde (Using the Print Media in French Second Language Class)" (H. Canto); (2) "Une lecon de grammaire…

  12. 26 CFR 1.149(g)-1 - Hedge bonds.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Hedge bonds. 1.149(g)-1 Section 1.149(g)-1...) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(g)-1 Hedge bonds... of replacement proceeds (other than amounts in a bona fide debt service fund or a reasonably...

  13. 26 CFR 1.475(g)-1 - Effective dates.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Effective dates. 1.475(g)-1 Section 1.475(g)-1...) INCOME TAXES Inventories § 1.475(g)-1 Effective dates. (a)-(b) (c) Section 1.475(a)-3 (concerning... to apply to the security solely because of the effective dates in this paragraph (d) (rather...

  14. G1 Continuity Conditions of B-spline Surfaces

    Institute of Scientific and Technical Information of China (English)

    车翔玖; 梁学章

    2002-01-01

    According to the B-spline theory and Boehm algorithm,this paper presents several necessary and sufficient G1 continuity conditions betwwen two adjacent B-spline surfaces,In Order to meet the need of application,a kind of sufficient conditions of G1 continuity are developed,and a kind of sufficient conditions of G1 continuity among N(N>2) patch B-shline surfaces meeting at a common corner are given at the end.

  15. Reduced hepatic tumor incidence in cyclin G1-deficient mice

    DEFF Research Database (Denmark)

    Jensen, Michael Rugaard; Factor, Valentina M; Fantozzi, Anna

    2003-01-01

    Cyclin G1 is a transcriptional target of the tumor suppressor p53, and its expression is increased after DNA damage. Recent data show that cyclin G1 can regulate the levels of p53 by a mechanism that involves dephosphorylation of Mdm2 by protein phosphatase 2A. To understand the biologic role of ...

  16. Functional overlap among distinct G1/S inhibitory pathways allows robust G1 arrest by yeast mating pheromones.

    Science.gov (United States)

    Pope, Patricia A; Pryciak, Peter M

    2013-12-01

    In budding yeast, mating pheromones arrest the cell cycle in G1 phase via a pheromone-activated Cdk-inhibitor (CKI) protein, Far1. Alternate pathways must also exist, however, because deleting the cyclin CLN2 restores pheromone arrest to far1 cells. Here we probe whether these alternate pathways require the G1/S transcriptional repressors Whi5 and Stb1 or the CKI protein Sic1, whose metazoan analogues (Rb or p27) antagonize cell cycle entry. Removing Whi5 and Stb1 allows partial escape from G1 arrest in far1 cln2 cells, along with partial derepression of G1/S genes, which implies a repressor-independent route for inhibiting G1/S transcription. This route likely involves pheromone-induced degradation of Tec1, a transcriptional activator of the cyclin CLN1, because Tec1 stabilization also causes partial G1 escape in far1 cln2 cells, and this is additive with Whi5/Stb1 removal. Deleting SIC1 alone strongly disrupts Far1-independent G1 arrest, revealing that inhibition of B-type cyclin-Cdk activity can empower weak arrest pathways. Of interest, although far1 cln2 sic1 cells escaped G1 arrest, they lost viability during pheromone exposure, indicating that G1 exit is deleterious if the arrest signal remains active. Overall our findings illustrate how multiple distinct G1/S-braking mechanisms help to prevent premature cell cycle commitment and ensure a robust signal-induced G1 arrest.

  17. Rapid biodegradation of organophosphorus pesticides by Stenotrophomonas sp. G1

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Shuyan; Chen, Yao [Key Laboratory of Agri-food Safety of Anhui Province, Lab of Quality & Safety and Risk Assessment for Agro-products on Storage and Preservation (Hefei), Ministry of Agriculture, School of Resource and Environment, Anhui Agricultural University, Hefei 230036 (China); Wang, Daosheng [School of Life Science, Anhui Agricultural University, Hefei 230036 (China); Shi, Taozhong; Wu, Xiangwei; Ma, Xin; Li, Xiangqiong [Key Laboratory of Agri-food Safety of Anhui Province, Lab of Quality & Safety and Risk Assessment for Agro-products on Storage and Preservation (Hefei), Ministry of Agriculture, School of Resource and Environment, Anhui Agricultural University, Hefei 230036 (China); Hua, Rimao, E-mail: rimaohua@ahau.edu.cn [Key Laboratory of Agri-food Safety of Anhui Province, Lab of Quality & Safety and Risk Assessment for Agro-products on Storage and Preservation (Hefei), Ministry of Agriculture, School of Resource and Environment, Anhui Agricultural University, Hefei 230036 (China); Tang, Xinyun [School of Life Science, Anhui Agricultural University, Hefei 230036 (China); Li, Qing X. [Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 1955 East–West Road, Honolulu, HI 957822 (United States)

    2015-10-30

    Highlights: • Stenotrophomonas sp. G1 was isolated from chlorpyrifos contaminated sludge. • Strain G1 is closest to Stenotrophomonas acidaminiphila. • Strain G1 can efficiently degrade 8 organophosphorus pesticides (OPs). • Intracellular methyl parathion hydrolase is responsible for the OP degradation. • Three factors were orthogonally optimized for degradation of methyl parathion. - Abstract: Organophosphorus insecticides have been widely used, which are highly poisonous and cause serious concerns over food safety and environmental pollution. A bacterial strain being capable of degrading O,O-dialkyl phosphorothioate and O,O-dialkyl phosphate insecticides, designated as G1, was isolated from sludge collected at the drain outlet of a chlorpyrifos manufacture plant. Physiological and biochemical characteristics and 16S rDNA gene sequence analysis suggested that strain G1 belongs to the genus Stenotrophomonas. At an initial concentration of 50 mg/L, strain G1 degraded 100% of methyl parathion, methyl paraoxon, diazinon, and phoxim, 95% of parathion, 63% of chlorpyrifos, 38% of profenofos, and 34% of triazophos in 24 h. Orthogonal experiments showed that the optimum conditions were an inoculum volume of 20% (v/v), a substrate concentration of 50 mg/L, and an incubation temperature in 40 °C. p-Nitrophenol was detected as the metabolite of methyl parathion, for which intracellular methyl parathion hydrolase was responsible. Strain G1 can efficiently degrade eight organophosphorus pesticides (OPs) and is a very excellent candidate for applications in OP pollution remediation.

  18. Sur le programme de licence à double orientation fran(c)ais- économie%中法经济双学位班培养方案探析

    Institute of Scientific and Technical Information of China (English)

    张彬

    2004-01-01

    Mis en place en 1992 dans le cadre de l'accord ofliciel sino-francais des echanges economiques et culturels par la Faculte de Commerce de 1' Universite de Wuhan et en collaboration avec le Departement de Francais, le programme de licence a double orientation (LDO francais/economie, Bac + 4) se developpe jusqu' alors depuis plus de dix ans. Grace aux efforts communs de la partie francaise et chinoise, ce programme bilingue jouit d' une tres bonne reputation rant sur le campus qu'a l'exterieur de l'universite.

  19. HERMES Precision Results on g1p, g1d and g1n and the First Measurement of the Tensor Structure Function b1d

    CERN Document Server

    Riedl, C; Akopov, Z; Amarian, M; Ammosov, V V; Andrus, A; Aschenauer, E C; Augustyniak, W; Avakian, R; Avetisian, A; Avetissian, E; Bailey, P; Baturin, V; Baumgarten, C; Beckmann, M; Belostotskii, S; Bernreuther, S; Bianchi, N; Blok, H P; Böttcher, Helmut B; Borisov, A; Bouwhuis, M; Brack, J; Brüll, A; Bryzgalov, V V; Capitani, G P; Chiang, H C; Ciullo, G; Contalbrigo, M; Dalpiaz, P F; De Leo, R; De Nardo, L; De Sanctis, E; Devitsin, E G; Di Nezza, P; Düren, M; Ehrenfried, M; Elalaoui-Moulay, A; Elbakian, G M; Ellinghaus, F; Elschenbroich, U; Ely, J; Fabbri, R; Fantoni, A; Feshchenko, A; Felawka, L; Fox, B; Franz, J; Frullani, S; Gärber, Y; Gapienko, G; Gapienko, V; Garibaldi, F; Garrow, K; Garutti, E; Gaskell, D; Gavrilov, G E; Karibian, V; Graw, G; Grebenyuk, O; Greeniaus, L G; Hafidi, K; Hartig, M; Hasch, D; Heesbeen, D; Henoch, M; Hertenberger, R; Hesselink, W H A; Hillenbrand, A; Hoek, M; Holler, Y; Hommez, B; Iarygin, G; Ivanilov, A; Izotov, A; Jackson, H E; Jgoun, A; Kaiser, R; Kinney, E; Kiselev, A; Königsmann, K C; Kopytin, M; Korotkov, V A; Kozlov, V; Krauss, B; Krivokhizhin, V G; Lagamba, L; Lapikas, L; Laziev, A; Lenisa, P; Liebing, P; Lindemann, T; Lipka, K; Lorenzon, W; Lü, J; Maiheu, B; Makins, N C R; Marianski, B; Marukyan, H O; Masoli, F; Mexner, V; Meyners, N; Miklukho, O; Miller, C A; Miyachi, Y; Muccifora, V; Nagaitsev, A; Nappi, E; Naryshkin, Yu; Nass, A; Negodaev, M A; Nowak, Wolf-Dieter; Oganessyan, K; Ohsuga, H; Orlandi, G; Pickert, N; Potashov, S Yu; Potterveld, D H; Raithel, M; Reggiani, D; Reimer, P E; Reischl, A; Reolon, A R; Rith, K; Airapetian, A; Rosner, G; Rostomyan, A; Rubacek, L; Ryckbosch, D; Salomatin, Yu I; Sanjiev, I; Savin, I; Scarlett, C; Schäfer, A; Schill, C; Schnell, G; Schüler, K P; Schwind, A; Seele, J; Seidl, R; Seitz, B; Shanidze, R G; Shearer, C; Shibata, T A; Shutov, V B; Simani, M C; Sinram, K; Stancari, M D; Statera, M; Steffens, E; Steijger, J J M; Stewart, J; Stösslein, U; Tait, P; Tanaka, H; Taroian, S P; Tchuiko, B; Terkulov, A R; Tkabladze, A V; Trzcinski, A; Tytgat, M; Vandenbroucke, A; Van der Nat, P B; van der Steenhoven, G; Vetterli, Martin C; Vikhrov, V; Vincter, M G; Visser, J; Vogel, C; Vogt, M; Volmer, J; Weiskopf, C; Wendland, J; Wilbert, J; Ybeles-Smit, G V; Yen, S; Zihlmann, B; Zohrabyan, H G; Zupranski, P; Riedl, Caroline

    2005-01-01

    Final HERMES results on the proton, deuteron and neutron structure function g1 are presented in the kinematic range 0.0021

  20. Tolerance of Deregulated G1/S Transcription Depends on Critical G1/S Regulon Genes to Prevent Catastrophic Genome Instability

    Directory of Open Access Journals (Sweden)

    Catia Caetano

    2014-12-01

    Full Text Available Expression of a G1/S regulon of genes that are required for DNA replication is a ubiquitous mechanism for controlling cell proliferation; moreover, the pathological deregulated expression of E2F-regulated G1/S genes is found in every type of cancer. Cellular tolerance of deregulated G1/S transcription is surprising because this regulon includes many dosage-sensitive proteins. Here, we used the fission yeast Schizosaccharomyces pombe to investigate this issue. We report that deregulating the MBF G1/S regulon by eliminating the Nrm1 corepressor increases replication errors. Homology-directed repair proteins, including MBF-regulated Ctp1CtIP, are essential to prevent catastrophic genome instability. Surprisingly, the normally inconsequential MBF-regulated S-phase cyclin Cig2 also becomes essential in the absence of Nrm1. This requirement was traced to cyclin-dependent kinase inhibition of the MBF-regulated Cdc18Cdc6 replication origin-licensing factor. Collectively, these results establish that, although deregulation of G1/S transcription is well tolerated by cells, nonessential G1/S target genes become crucial for preventing catastrophic genome instability.

  1. Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.

    Directory of Open Access Journals (Sweden)

    Benjamin Pfeuty

    Full Text Available Transitions between consecutive phases of the eukaryotic cell cycle are driven by the catalytic activity of selected sets of cyclin-dependent kinases (Cdks. Yet, their occurrence and precise timing is tightly scheduled by a variety of means including Cdk association with inhibitory/adaptor proteins (CKIs. Here we focus on the regulation of G1-phase duration by the end of which cells of multicelled organisms must decide whether to enter S phase or halt, and eventually then, differentiate, senesce or die to obey the homeostatic rules of their host. In mammalian cells, entry in and progression through G1 phase involve sequential phosphorylation and inactivation of the retinoblastoma Rb proteins, first, by cyclin D-Cdk4,6 with the help of CKIs of the Cip/Kip family and, next, by the cyclin E-Cdk2 complexes that are negatively regulated by Cip/Kip proteins. Using a dynamical modeling approach, we show that the very way how the Rb and Cip/Kip regulatory modules interact differentially with cyclin D-Cdk4,6 and cyclin E-Cdk2 provides to mammalian cells a powerful means to achieve an exquisitely-sensitive control of G1-phase duration and fully reversible G1 arrests. Consistently, corruption of either one of these two modules precludes G1 phase elongation and is able to convert G1 arrests from reversible to irreversible. This study unveils fundamental design principles of mammalian G1-phase regulation that are likely to confer to mammalian cells the ability to faithfully control the occurrence and timing of their division process in various conditions.

  2. Spin-Dependent Structure Function $g_1$ at Small x

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2004-01-01

    Accounting for double-logarithms of x and running QCD coupling leads to expressions for both the non-singlet and singlet components of $g_1$. These expressions manifest the Regge asymptotics when x ->0 and differ considerably from the DGLAP expressions at small values of x.

  3. 26 CFR 1.514(g)-1 - Business lease indebtedness.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Business lease indebtedness. 1.514(g)-1 Section 1... Business lease indebtedness. (a) Definition. The term business lease indebtedness means, with respect to... subsidiary corporations. (b) Examples. The rules of section 514(g) respecting business leases also...

  4. SNAILs promote G1 phase in selected cancer cells.

    Science.gov (United States)

    Wu, Ya-Lan; Xue, Jian-Xin; Zhou, Lin; Deng, Lei; Shang, Yan-Na; Liu, Fang; Mo, Xian-Ming; Lu, You

    2015-11-01

    Cells can acquire a stem-like cell phenotype through epithelial-mesenchymal transition (EMT). However, it is not known which of the stem-like cancer cells are generated by these phenotype transitions. We studied the EMT-inducing roles of SNAILs (the key inducers for the onset of EMT) in selected cancer cells (lung cancer cell line with relatively stable genome), in order to provide more implications for the investigation of EMT-related phenotype transitions in cancer. However, SNAILs fail to induce completed EMT. In addition, we proved that Snail accelerates the early G1 phase whereas Slug accelerates the late G1 phase. Blocking G1 phase is one of the basic conditions for the onset of EMT-related phenotype transitions (e.g., metastasis, acquiring stemness). The discovery of this unexpected phenomenon (promoting G1 phase) typically reveals the heterogeneity of cancer cells. The onset of EMT-related phenotype transitions in cancer needs not only the induction and activation of SNAILs, but also some particular heredity alterations (genetic or epigenetic alterations, which cause heterogeneity). The new connection between heredity alteration (heterogeneity) and phenotype transition suggests a novel treatment strategy, the heredity alteration-directed specific target therapy. Further investigations need to be conducted to study the relevant heredity alterations.

  5. Nonparametric inference from the M/G/1 workload

    DEFF Research Database (Denmark)

    Hansen, Martin Bøgsted; Pitts, Susan M.

    2006-01-01

    Consider an M/G/1 queue with unknown service-time distribution and unknown traffic intensity ρ. Given systematically sampled observations of the workload, we construct estimators of ρ and of the service-time distribution function, and we study asymptotoic properties of these estimators....

  6. Rapid biodegradation of organophosphorus pesticides by Stenotrophomonas sp. G1.

    Science.gov (United States)

    Deng, Shuyan; Chen, Yao; Wang, Daosheng; Shi, Taozhong; Wu, Xiangwei; Ma, Xin; Li, Xiangqiong; Hua, Rimao; Tang, Xinyun; Li, Qing X

    2015-10-30

    Organophosphorus insecticides have been widely used, which are highly poisonous and cause serious concerns over food safety and environmental pollution. A bacterial strain being capable of degrading O,O-dialkyl phosphorothioate and O,O-dialkyl phosphate insecticides, designated as G1, was isolated from sludge collected at the drain outlet of a chlorpyrifos manufacture plant. Physiological and biochemical characteristics and 16S rDNA gene sequence analysis suggested that strain G1 belongs to the genus Stenotrophomonas. At an initial concentration of 50 mg/L, strain G1 degraded 100% of methyl parathion, methyl paraoxon, diazinon, and phoxim, 95% of parathion, 63% of chlorpyrifos, 38% of profenofos, and 34% of triazophos in 24 h. Orthogonal experiments showed that the optimum conditions were an inoculum volume of 20% (v/v), a substrate concentration of 50 mg/L, and an incubation temperature in 40 °C. p-Nitrophenol was detected as the metabolite of methyl parathion, for which intracellular methyl parathion hydrolase was responsible. Strain G1 can efficiently degrade eight organophosphorus pesticides (OPs) and is a very excellent candidate for applications in OP pollution remediation.

  7. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167... for depreciation. The basis upon which the allowance for depreciation is to be computed with respect... property at that time, is the basis for computing depreciation....

  8. Identification of waiting time distribution of M/G/1, Mx/G/1, GIr/M/1 queueing systems

    Directory of Open Access Journals (Sweden)

    A. Ghosal

    1988-01-01

    Full Text Available This paper brings out relations among the moments of various orders of the waiting time of the 1st customer and a randomly selected customer of an arrival group for bulk arrivals queueing models, and as well as moments of the waiting time (in queue for M/G/1 queueing system. A numerical study of these relations has been developed in order to find the (β1,β2 measures of waiting time distribution in a comutable form. On the basis of these measures one can look into the nature of waiting time distribution of bulk arrival queues and the single server M/G/1 queue.

  9. La diffusion du fran(c)ais en Chine du milieu du 19e siècle à nos jours (1)%La diffusion du fran(c)ais en Chine du milieu du19e siècle à nos jours (1)

    Institute of Scientific and Technical Information of China (English)

    戴冬梅

    2011-01-01

    @@ Ce travail tente le pari d'esquisser I'évolution historique de la diffusion du francais en Chine du milieu du 19e siècle jusqu'à nos jours.La Chine désigne ici essentiellement le continent chinois.Hongkong, Taiwan et Macao ne sont pas pour autant totalement exclus.La question posée est toute simple : qui parle le francais en Chine ? Pour retrouver ces personnes, les établissements d'enseignement nous servent de fil rouge.

  10. Design principles of the yeast G1/S switch.

    Directory of Open Access Journals (Sweden)

    Xiaojing Yang

    2013-10-01

    Full Text Available A hallmark of the G1/S transition in budding yeast cell cycle is the proteolytic degradation of the B-type cyclin-Cdk stoichiometric inhibitor Sic1. Deleting SIC1 or altering Sic1 degradation dynamics increases genomic instability. Certain key facts about the parts of the G1/S circuitry are established: phosphorylation of Sic1 on multiple sites is necessary for its destruction, and both the upstream kinase Cln1/2-Cdk1 and the downstream kinase Clb5/6-Cdk1 can phosphorylate Sic1 in vitro with varied specificity, cooperativity, and processivity. However, how the system works as a whole is still controversial due to discrepancies between in vitro, in vivo, and theoretical studies. Here, by monitoring Sic1 destruction in real time in individual cells under various perturbations to the system, we provide a clear picture of how the circuitry functions as a switch in vivo. We show that Cln1/2-Cdk1 sets the proper timing of Sic1 destruction, but does not contribute to its destruction speed; thus, it acts only as a trigger. Sic1's inhibition target Clb5/6-Cdk1 controls the speed of Sic1 destruction through a double-negative feedback loop, ensuring a robust all-or-none transition for Clb5/6-Cdk1 activity. Furthermore, we demonstrate that the degradation of a single-phosphosite mutant of Sic1 is rapid and switch-like, just as the wild-type form. Our mathematical model confirms our understanding of the circuit and demonstrates that the substrate sharing between the two kinases is not a redundancy but a part of the design to overcome the trade-off between the timing and sharpness of Sic1 degradation. Our study provides direct mechanistic insight into the design features underlying the yeast G1/S switch.

  11. D'une ouverture de la voyelle /epsilon/ en finale absolue en francais quebecois : analyse acoustique et perceptive

    Science.gov (United States)

    Riverin-Coutlee, Josiane

    Cette contribution est consacree a l'ouverture du /epsilon/ en finale absolue, un phenomene phonetique repute etre en declin en francais quebecois et caracteristique de locuteurs âges, peu scolarises, issus de milieux populaires et s'exprimant en situation de communication informelle. Une analyse acoustique de 480 voyelles /epsilon/ issues de la parole formelle de 40 jeunes etudiants universitaires originaires des centres urbains de Saguenay et de Quebec revele toutefois que le phenomene est encore bien vivant en francais quebecois et qu'il est plus frequent chez les locuteurs de Saguenay, une tendance validee auditivement par accord inter-juges. Les resultats d'un test de discrimination et d'identification mene aupres de 26 etudiants universitaires originaires de ces deux memes villes indiquent que les auditeurs naifs de Saguenay semblent moins sensibles a la variation et moins enclins a juger de l'origine geographique d'un locuteur a partir de sa prononciation de la voyelle /epsilon/ en fin de mot.

  12. EL-2 reactor: Thermal neutron flux distribution; EL-2: Repartition du flux de neutrons thermiques

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, A.; Genthon, J.P. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1958-07-01

    The flux distribution of thermal neutrons in EL-2 reactor is studied. The reactor core and lattices are described as well as the experimental reactor facilities, in particular, the experimental channels and special facilities. The measurement shows that the thermal neutron flux increases in the central channel when enriched uranium is used in place of natural uranium. However the thermal neutron flux is not perturbed in the other reactor channels by the fuel modification. The macroscopic flux distribution is measured according the radial positioning of fuel rods. The longitudinal neutron flux distribution in a fuel rod is also measured and shows no difference between enriched and natural uranium fuel rods. In addition, measurements of the flux distribution have been effectuated for rods containing other material as steel or aluminium. The neutron flux distribution is also studied in all the experimental channels as well as in the thermal column. The determination of the distribution of the thermal neutron flux in all experimental facilities, the thermal column and the fuel channels has been made with a heavy water level of 1825 mm and is given for an operating power of 1000 kW. (M.P.)

  13. L'enseignement modulaire et le laboratoire de langues: conception et experimentation d'un nouveau cours de francais oral au Centre d'anglais et de francais, Universite McGill (Modular Instruction and the Language Laboratory: Conception and Experimentation with a New Course in Oral French at the English and French Center, McGill University).

    Science.gov (United States)

    Legoux, Marie-Noelle

    1980-01-01

    A modular-type course in French was developed at the "Centre d'anglais et de francais" at McGill University (Montreal) to meet the needs of incoming students who were lacking skills in listening and oral expression. The course is composed of eight modules a semester, each module corresponding to 15 to 20 hours work on the student's part. The…

  14. L'enseignement du francais en Republique Federale d'Allemagne (The Teaching of French in the Federal Republic of Germany). L'enseignement du francais dans les classes terminales des lycees allemands (The Teaching of French in the Final Year in German Schools).

    Science.gov (United States)

    Abel, Fritz; Lang, Jurgen

    Two papers describe two aspects of French foreign language instruction in West Germany. The first, "L'enseignement du francais en Republique Federale d'Allemagne" by Abel, deals with the institutional framework for French instruction in West Germany. A discussion of the instructional situation looks first at the history of French instruction since…

  15. ATP6V1G1 — EDRN Public Portal

    Science.gov (United States)

    ATP6V1G1 is a subunit of vacuolar ATPase (V-ATPase), a multisubunit enzyme. V-ATPase is an enzyme transporter that functions to acidify intracellular compartments in eukaryotic cells. This acidification process is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is ubiquitously expressed and is present in endomembrane organelles such as vacuoles, lysosomes, endosomes, the Golgi apparatus, chromaffin granules and coated vesicles, as well as in the plasma membrane. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site.

  16. Early evolution of disrupted asteroid P/2016 G1 (PANSTARRS)

    CERN Document Server

    Moreno, Fernando; Cabrera-Lavers, Antonio; Pozuelos, Francisco J

    2016-01-01

    We present deep imaging observations of activated asteroid P/2016 G1 (PANSTARRS) using the 10.4m Gran Telescopio Canarias (GTC) from late April to early June 2016. The images are best interpreted as the result of a relatively short-duration event with onset about $\\mathop{350}_{-30}^{+10}$ days before perihelion (i.e., around 10th February, 2016), starting sharply and decreasing with a $\\mathop{24}_{-7}^{+10}$ days (Half-width at half-maximum, HWHM). The results of the modeling imply the emission of $\\sim$1.7$\\times$10$^7$ kg of dust, if composed of particles of 1 micrometer to 1 cm in radius, distributed following a power-law of index --3, and having a geometric albedo of 0.15. A detailed fitting of a conspicuous westward feature in the head of the comet-like object indicates that a significant fraction of the dust was ejected along a privileged direction right at the beginning of the event, which suggests that the parent body has possibly suffered an impact followed by a partial or total disruption. From th...

  17. Reactor G1: high power experiments; Experiences a forte puissance

    Energy Technology Data Exchange (ETDEWEB)

    Laage, F. de; Teste du Baillet, A.; Veyssiere, A.; Wanner, G. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Retel, H. [Societe Rateau, D.E.A. (France)

    1957-07-01

    The experiments carried out in the starting-up programme of the reactor G1 comprised a series of tests at high power, which allowed the following points to be studied: 1- Effect of poisoning by Xenon (absolute value, evolution). 2- Temperature coefficients of the uranium and graphite for a temperature distribution corresponding to heating by fission. 3- Effect of the pressure (due to the coiling system) on the reactivity. 4- Calibration of the security rods as a function of their position in the pile (1). 5- Temperature distribution of the graphite, the sheathing, the uranium and the air leaving the canals, in a pile running normally at high power. 6- Neutron flux distribution in a pile running normally at high power. 7- Determination of the power by nuclear and thermodynamic methods. These experiments have been carried out under two very different pile conditions. From the 1. to the 15. of August 1956, a series of power increases, followed by periods of stabilisation, were induced in a pile containing uranium only, in 457 canals, amounting to about 34 tons of fuel. A knowledge of the efficiency of the control rods in such a pile has made it possible to measure with good accuracy the principal effects at high temperatures, that is, to deal with points 1, 2, 3, 5. Flux charts giving information on the variations of the material Laplacian and extrapolation lengths in the reflector have been drawn up. Finally the thermodynamic power has been measured under good conditions, in spite of some installation difficulties. On September 16, the pile had its final charge of 100 tons. All the canals were loaded, 1,234 with uranium and 53 (i.e. exactly 4 per cent of the total number) with thorium uniformly distributed in a square lattice of 100 cm side. Since technical difficulties prevented the calibration of the control rods, the measurements were limited to the determination of the thermodynamic power and the temperature distributions (points 5 and 7). This report will

  18. 26 CFR 1.904(g)-1 - Overall domestic loss and the overall domestic loss account.

    Science.gov (United States)

    2010-04-01

    ... loss account. 1.904(g)-1 Section 1.904(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... States § 1.904(g)-1 Overall domestic loss and the overall domestic loss account. For further guidance, see § 1.904(g)-1T....

  19. G1 Continuity Conditions of B-spline Surfaces%B样条曲面间的G1连续条件

    Institute of Scientific and Technical Information of China (English)

    车翔玖; 梁学章

    2002-01-01

    According to the B-spline theory and Boehm algorithm, this paper presents severalnecessary and sufficient G1 continuity conditions between two adjacent B-spline surfaces. In orderto meet the need of application, a kind of sufficient conditions of G1 continuity are developed, anda kind of sufficient conditions of G1 continuity among N(N > 2) patch B-spline surfaces meetingat a common corner are given at the end.

  20. Running coupling effects for the singlet structure function g_1 at small x

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2004-01-01

    The running of the QCD coupling is incorporated into the infrared evolution equations for the flavour singlet component, g_1^S of g_1. The explicit expressions for g_1^S including the total resummation of the double-logarithmic contributions and accounting for the running coupling are obtained. We predict that asymptotically g_1^S ~ x^{- \\Delta_S}, with the intercept \\Delta_S = 0.8, which is a factor of 2 larger than the non-singlet intercept.

  1. Recruitment of Cdc28 by Whi3 restricts nuclear accumulation of the G1 cyclin-Cdk complex to late G1.

    Science.gov (United States)

    Wang, Hongyin; Garí, Eloi; Vergés, Emili; Gallego, Carme; Aldea, Martí

    2004-01-14

    The G1 cyclin Cln3 is a key activator of cell-cycle entry in budding yeast. Here we show that Whi3, a negative G1 regulator of Cln3, interacts in vivo with the cyclin-dependent kinase Cdc28 and regulates its localization in the cell. Efficient interaction with Cdc28 depends on an N-terminal domain of Whi3 that is also required for cytoplasmic localization of Cdc28, and for proper regulation of G1 length and filamentous growth. On the other hand, nuclear accumulation of Cdc28 requires the nuclear localization signal of Cln3, which is also found in Whi3 complexes. Both Cln3 and Cdc28 are mainly cytoplasmic during early G1, and become nuclear in late G1. However, Whi3-deficient cells show a distinct nuclear accumulation of Cln3 and Cdc28 already in early G1. We propose that Whi3 constitutes a cytoplasmic retention device for Cln3-Cdc28 complexes, thus defining a key G1 event in yeast cells.

  2. Measurements of the $Q^{2}$-Dependence of the Proton and Neutron Spin Structure Functions g1p and g1n

    CERN Document Server

    Anthony, P L; Averett, T; Band, H R; Berisso, M C; Borel, H; Bosted, P E; Bültmann, S; Buénerd, M; Chupp, T E; Churchwell, S; Court, G R; Crabb, D; Day, D; Decowski, P; De Pietro, P; Erbacher, R D; Erickson, R; Feltham, A; Fonvieille, H; Frlez, E; Gearhart, R A; Ghazikhanian, V; Gómez, J; Griffioen, K A; Harris, C; Houlden, M A; Hughes, E W; Hyde-Wright, C E; Igo, G; Incerti, S; Jensen, J; Johnson, J R; King, P M; Kolomensky, Yu G; Kuhn, S E; Lindgren, R; Lombard-Nelsen, R M; Marroncle, J; McCarthy, J; McKee, P M; Meyer, Werner T; Mitchell, G S; Mitchell, J; Olson, M N; Penttilä, S; Peterson, G A; Petratos, G G; Pitthan, R; Pocanic, D; Prepost, R; Prescott, C; Qin, L M; Raue, B A; Reyna, D; Rochester, L S; Rock, S E; Rondon-Aramayo, O A; Sabatié, F; Sick, I; Smith, T; Sorrell, L; Staley, F; Saint-Lorant, S; Stuart, L M; Szalata, Z M; Terrien, Y; Tobias, A; Todor, L; Toole, T; Trentalange, S; Walz, D; Welsh, R C; Wesselmann, F R; Wright, T R; Young, C C; Zeier, M; Zhu, H; Zihlmann, B

    2000-01-01

    The structure functions g1p and g1n have been measured over the range 0.014 < x < 0.9 and 1 < Q2 < 40 GeV2 using deep-inelastic scattering of 48 GeV longitudinally polarized electrons from polarized protons and deuterons. We find that the Q2 dependence of g1p (g1n) at fixed x is very similar to that of the spin-averaged structure function F1p (F1n). From a NLO QCD fit to all available data we find $\\Gamma_1^p - \\Gamma_1^n =0.176 \\pm 0.003 \\pm 0.007$ at Q2=5 GeV2, in agreement with the Bjorken sum rule prediction of 0.182 \\pm 0.005.

  3. Effect of PKC pathway on G1/S progression control in HeLa cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The effect of PKC activity on G1/S progression in HeLa cells has been studied.The result shows that (ⅰ) PKC activity alteration in G1 phase affects G1/S progression in HeLa cells.It has been observed that G1/S progression is stimulated by PKC agonist TPA and inhibited by PKC inhibitor GF-109203X.(ⅱ) The expression of c-myc and c-jun is stimulated by TPA and inhibited by GF-109203X treatment in early G1 phase.(ⅲ) During G1/S progression,the expression of CyclinD1 is stimulated by TPA treatment and inhibited by GF-109203X treatment.There is no effect on the expression of CDK4.It is likely that PKC pathway regulates G1/S progression through regulating the expression of some early response genes and engine molecules in HeLa cells.

  4. Cytometry of chromatin bound Mcm6 and PCNA identifies two states in G1 that are separated functionally by the G1 restriction point1

    Directory of Open Access Journals (Sweden)

    Jacobberger James W

    2010-04-01

    Full Text Available Abstract Background Cytometric measurements of DNA content and chromatin-bound Mcm2 have demonstrated bimodal patterns of expression in G1. These patterns, the replication licensing function of Mcm proteins, and a correlation between Mcm loading and cell cycle commitment for cells re-entering the cell cycle, led us to test the idea that cells expressing a defined high level of chromatin-bound Mcm6 in G1 are committed - i.e., past the G1 restriction point. We developed a cell-based assay for tightly-bound PCNA (PCNA* and Mcm6 (Mcm6*, DNA content, and a mitotic marker to clearly define G1, S, G2, and M phases of the cell cycle. hTERT-BJ1, hTERT-RPE-1, and Molt4 cells were extracted with Triton X-100 followed by methanol fixation, stained with antibodies and DAPI, then measured by cytometry. Results Bivariate analysis of cytometric data demonstrated complex patterns with distinct clustering for all combinations of the 4 variables. In G1, cells clustered in two groups characterized by low and high Mcm6* expression. Serum starvation and release experiments showed that residence in the high group was in late G1, just prior to S phase. Kinetic experiments, employing serum withdrawal, and stathmokinetic analysis with aphidicolin, mimosine or nocodazole demonstrated that cells with high levels of Mcm6* cycled with the committed phases of the cell cycle (S, G2, and M. Conclusions A multivariate assay for Mcm6*, PCNA*, DNA content, and a mitotic marker provides analysis capable of estimating the fraction of pre and post-restriction point G1 cells and supports the idea that there are at least two states in G1 defined by levels of chromatin bound Mcm proteins.

  5. Diversity of VP7 genes of G1 rotaviruses isolated in Iran, 2009-2013.

    Science.gov (United States)

    Jalilvand, Somayeh; Afchangi, Atefeh; Mohajel, Nasir; Roohvand, Farzin; Shoja, Zabihollah

    2016-01-01

    Genotype G1 of rotaviruses (RVs) is the most prevalent strain in human RV infections around the world. The present study evaluated genetic variations in the VP7 gene of RV G1 genotype isolates from Iran. Genetic and phylogenetic analyses indicated that RV strains from Iran clustered with G1 lineages IA, IC, and IIC, showing highest average of similarity versus reference sequences of the G1 lineages I and II. This study highlights the genetic pattern of G1 RV on the basis of distinct lineages and sublineages and indicates the importance of continuous monitoring on genetic variation and evolution pattern of G1 RV strains across the Iranian population for the final aim of RV vaccine introduction.

  6. Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

    DEFF Research Database (Denmark)

    Aszodi, Attila; Hunziker, Ernst B; Brakebusch, Cord;

    2003-01-01

    -actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21...

  7. 16 CFR Appendix G1 to Part 305 - Furnaces-Gas

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Furnaces-Gas G1 Appendix G1 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE CONCERNING... Part 305—Furnaces—Gas Manufacturer's rated heating capacities (Btu's/hr.) Range of annual fuel...

  8. A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition.

    Science.gov (United States)

    Hsiung, Chris C-S; Bartman, Caroline R; Huang, Peng; Ginart, Paul; Stonestrom, Aaron J; Keller, Cheryl A; Face, Carolyne; Jahn, Kristen S; Evans, Perry; Sankaranarayanan, Laavanya; Giardine, Belinda; Hardison, Ross C; Raj, Arjun; Blobel, Gerd A

    2016-06-15

    During mitosis, RNA polymerase II (Pol II) and many transcription factors dissociate from chromatin, and transcription ceases globally. Transcription is known to restart in bulk by telophase, but whether de novo transcription at the mitosis-G1 transition is in any way distinct from later in interphase remains unknown. We tracked Pol II occupancy genome-wide in mammalian cells progressing from mitosis through late G1. Unexpectedly, during the earliest rounds of transcription at the mitosis-G1 transition, ∼50% of active genes and distal enhancers exhibit a spike in transcription, exceeding levels observed later in G1 phase. Enhancer-promoter chromatin contacts are depleted during mitosis and restored rapidly upon G1 entry but do not spike. Of the chromatin-associated features examined, histone H3 Lys27 acetylation levels at individual loci in mitosis best predict the mitosis-G1 transcriptional spike. Single-molecule RNA imaging supports that the mitosis-G1 transcriptional spike can constitute the maximum transcriptional activity per DNA copy throughout the cell division cycle. The transcriptional spike occurs heterogeneously and propagates to cell-to-cell differences in mature mRNA expression. Our results raise the possibility that passage through the mitosis-G1 transition might predispose cells to diverge in gene expression states.

  9. Asymptotical small-x behaviour of the spin structure functions $g_1$ and $g_2$

    CERN Document Server

    Ermolaev, B I

    1997-01-01

    We show that for small x and in the double logarithmic approximation (DLA) g_2 can be expressed through derivative of g_1 with respect to logarithm of the QCD coupling. Therefore the small-x behavior of the both structure functions is similar. The analytical expression for flavor nonsinglet structure function g_1 is presented and its asymptotical behaviour is calculated.

  10. 26 CFR 1.45G-1 - Railroad track maintenance credit.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Railroad track maintenance credit. 1.45G-1... TAXES Rules for Computing Credit for Investment in Certain Depreciable Property § 1.45G-1 Railroad track maintenance credit. (a) In general. For purposes of section 38, the railroad track maintenance credit (RTMC...

  11. Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Meyuhas, Ronit; Noy, Hava; Fishman, Sigal [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Margalit, Alon [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel); Montefiori, David C. [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Gross, Gideon, E-mail: gidi@migal.org.il [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel)

    2009-08-21

    HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immunoligands harboring VH3. Unlike VH3-IgG1 or VH3-CD4-IgG1, CD4-VH3-IgG1 bound gp120 considerably stronger than CD4-IgG1. CD4-VH3-IgG1 exhibited {approx}1.5-2.5-fold increase in neutralization of two T-cell laboratory-adapted strains when compared to CD4-IgG1. CD4-VH3-IgG1 improved neutralization of 7/10 clade B primary isolates or pseudoviruses, exceeding 20-fold for JR-FL and 13-fold for Ba-L. It enhanced neutralization of 4/8 clade C viruses, and had negligible effect on 1/4 clade A pseudoviruses. We attribute this improvement to possible pairing of VH3 with CD4 D1 and stabilization of an Ig Fv-like structure, rather than to superantigen interactions. These novel findings support the current notion that CD4 fusion proteins can act as better HIV-1 entry inhibitors with potential clinical implications.

  12. Acrocentric Chromosomes in Cultured Leukocytes from Mothers of Children Affected With the G1- Trisomy Syndrome

    Science.gov (United States)

    And Others; Cotton, James E.

    1973-01-01

    Analysis of venous blood samples from 24 mothers of G1-trisomy-affected (Down's Syndrome) children and 23 mothers of chromosomally normal children indicated that mothers of G1-trisomy-affected children had a greater than expected involvement of the G-chromosomes in associations of acrocentric satellited (chromosome configuration) chromosomes.…

  13. 26 CFR 1.665(g)-1A - Capital gain distribution.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Capital gain distribution. 1.665(g)-1A Section 1... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(g)-1A Capital gain distribution. For any taxable year of a...

  14. Nucleon spin structure II: Spin structure function $g_1^p$ at small $x$

    CERN Document Server

    Zhu, Wei

    2015-01-01

    The spin structure function $g_1^p$ of the proton is studied in a two component framework, where the perturbative evolution of parton distributions and nonperturbative vector meson dominance model are used. We predict the $g_1^p$ asymmetric behavior at small $x$ from lower $Q^2$ to higher $Q^2$. We find that the contribution of the large gluon helicity dominates $g_1^p$ at $x>10^{-3}$ but mixed with nonperturbative component which complicates the asymptomatic behavior of $g_1^p$ at $x<10^{-3}$. The results are compatible with the data including the HERA early estimations and COMPASS new results. The predicted strong $Q^2$- and $x$-dependence of $g_1^p$ at $0.01

  15. Msa1 and Msa2 Modulate G1-Specific Transcription to Promote G1 Arrest and the Transition to Quiescence in Budding Yeast.

    Directory of Open Access Journals (Sweden)

    Shawna Miles

    2016-06-01

    Full Text Available Yeast that naturally exhaust their glucose source can enter a quiescent state that is characterized by reduced cell size, and high cell density, stress tolerance and longevity. The transition to quiescence involves highly asymmetric cell divisions, dramatic reprogramming of transcription and global changes in chromatin structure and chromosome topology. Cells enter quiescence from G1 and we find that there is a positive correlation between the length of G1 and the yield of quiescent cells. The Swi4 and Swi6 transcription factors, which form the SBF transcription complex and promote the G1 to S transition in cycling cells, are also critical for the transition to quiescence. Swi6 forms a second complex with Mbp1 (MBF, which is not required for quiescence. These are the functional analogues of the E2F complexes of higher eukaryotes. Loss of the RB analogue, Whi5, and the related protein Srl3/Whi7, delays G1 arrest, but it also delays recovery from quiescence. Two MBF- and SBF-Associated proteins have been identified that have little effect on SBF or MBF activity in cycling cells. We show that these two related proteins, Msa1 and Msa2, are specifically required for the transition to quiescence. Like the E2F complexes that are quiescence-specific, Msa1 and Msa2 are required to repress the transcription of many SBF target genes, including SWI4, the CLN2 cyclin and histones, specifically after glucose is exhausted from the media. They also activate transcription of many MBF target genes. msa1msa2 cells fail to G1 arrest and rapidly lose viability upon glucose exhaustion. msa1msa2 mutants that survive this transition are very large, but they attain the same thermo-tolerance and longevity of wild type quiescent cells. This indicates that Msa1 and Msa2 are required for successful transition to quiescence, but not for the maintenance of that state.

  16. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Feng, E-mail: jiangfeng1161@163.com [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Zhao, Hongxi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Wang, Li [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Guo, Xinyu [Assisted Reproductive Center, General Hospital of Guangzhou Military Command, Guangzhou 510010 (China); Wang, Xiaohong; Yin, Guowu [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Hu, Yunsheng [Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Li, Yi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Yao, Yuanqing, E-mail: yuanqingyaoxa@163.com [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China)

    2015-02-27

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions.

  17. Quarter variation and correlations of colostrum albumin, immunoglobulin G1 and G2 in dairy cows.

    Science.gov (United States)

    Samarütel, Jaak; Baumrucker, Craig R; Gross, Josef J; Dechow, Chad D; Bruckmaier, Rupert M

    2016-05-01

    A high variation in immunoglobulin G1 (IgG1) concentration in first milked quarter colostrum has been reported, but BSA quarter colostrum variation is not known. The occurrence of serum albumin in milk has been attributed to increased blood-milk barrier penetration. Reports of serum albumin binding to the Fc Receptor of the neonate, the receptor thought to be responsible for IgG1 transcytosis, suggested that a correlation with the appearance of IgG1 in colostrum of dairy cows was likely. The objective of the study was to establish the quarter colostrum concentration and mass of immunoglobulins and serum albumin. First colostrum was quarter collected within 4 h of parturition from healthy udders of 31 multiparous dairy cows. Individual quarter colostrum weight was determined and a sample of each was frozen for subsequent analysis. Concentrations of immunoglobulin G1, G2, and BSA were measured by ELISA and total mass of components was calculated. In addition, colostrum was also analysed for L-lactate dehydrogenase activity. Analysis of concentration and mass of BSA, immunoglobulin G1, G2 established that the quarter variations were different by cow, quarter and quarter within cow. Partial correlations corrected for colostrum weight indicated that BSA and IgG2 concentration and mass are closely correlated while that of BSA and IgG1 concentration and mass exhibited no correlation suggesting that BSA and IgG1 may have different transport mechanisms. Interestingly, immunoglobulin G1 and G2 concentration and mass exhibited strong correlations suggesting that also some unknown mechanism of immunoglobulin G2 appearance in colostrum is occurring. Finally, no measured protein exhibited any correlation with the activity of lactate dehydrogenase in colostrum.

  18. Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1

    DEFF Research Database (Denmark)

    Kjaerulff, Søren; Andersen, Nicoline Resen; Borup, Mia Trolle;

    2007-01-01

    Eukaryotic cells normally differentiate from G(1); here we investigate the mechanism preventing expression of differentiation-specific genes outside G(1). In fission yeast, induction of the transcription factor Ste11 triggers sexual differentiation. We find that Ste11 is only active in G(1) when...... S phase. When we mutated T82 to aspartic acid, mimicking constant phosphorylation, cells no longer underwent differentiation. Conversely, changing T82 to alanine rendered Ste11-controlled transcription constitutive through the cell cycle, and allowed mating from S phase with increased frequency...

  19. Description of the spin structure function g_1 at arbitrary $x$ and arbitrary Q^2

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2007-01-01

    The explicit expressions describing the structure function g_1 at arbitrary x and Q^2 are obtained. In the first place, they combine the well-known DGLAP expressions for g_1 with the total resummation of leading logarithms of x, which makes possible to cover the kinematic region of arbitrary x and large Q^2. In order to cover the small-Q^2 region the shift Q^2 -> Q^2 + mu^2 in the large-Q^2 expressions for g_1 is suggested and values of mu are estimated. The expressions obtained do not require singular factors x^{-a} in the fits for initial parton densities.

  20. Singlet structure function g_1 at small x and small Q^2

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2006-01-01

    Explicit expressions for the singlet g_1 at small x and small Q^2 are obtained with the total resummation of the leading logarithmic contributions. It is shown that g_1 practically does not depend on Q^2 in this kinematic region. In contrast, it would be interesting to investigate its dependence on the invariant energy 2pq because, being g_1 positive at small 2pq, it can turn negative at greater values of this variable. The position of the turning point is sensitive to the ratio between the initial quark and gluon densities, so its experimental detection would enable to estimate this ratio

  1. Small -x behavior of the non-singlet and singlet structure functions g_1

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2003-01-01

    Explicit expressions for the non-singlet and singlet structure functions g_1 at the small $x$-region are obtained. They include the total resummation of double-logarithmic contributions and accounting for the running QCD coupling effects. We predict that both the non-singlet and singlet g_1 asymptotically ~ x^{- \\Delta}, with the singlet intercept = 0.86 and being more than twice larger than the non-singlet intercept = 0.4. The impact of the initial quark and gluon densities on the sign of g_1 at x << 1 is discussed.

  2. M/G/1 Subject to an Initial Quorum of Customers.

    Science.gov (United States)

    1986-11-01

    is the maximal queue size (and system size) while the server idles or vacations. The modified model is designated as M/G/I1(m). When m=O we have the... designate this model as M/G/1/(m). Thus, when m = 0 we have the regular M/G/1. In a prior report (Krakowski, 1986) we dealt with the process "queue...size" for : i M/G/1(m). (Note: In that prior report m stands for the current m+1. The change simplifies somewhat the typography of many formulas.) We

  3. Synthesis and characterization of supramolecule self-assembly polyami-doamine (PAMAM G1-G1 NH2, CO2H end group Megamer

    Directory of Open Access Journals (Sweden)

    Omid Louie

    2014-10-01

    Full Text Available Supramolecule self-assembly polyamidoamine (PAMAM dendrimer refers to the chemical sys-tems made up of a discrete number of assembled molecular subunits or components. These strat-egies involve the covalent assembly of hierarchical components reactive monomers, branch cells or dendrons around atomic or molecular cores according to divergent/convergent dendritic branching principles, systematic filling of space around a core with shells (layers of branch cells. The polydispersity index (PDI for the supramolecule megamer are pretty closed to one, are in agreement with the Poisson probability distribution. Polyamidoamine (PAMAM den-drimer G1-G1 that it was PAMAM Megamer NH2, COOH end groupsynthesized and character-ized by FT-IR, 1H NMR, 13C NMRspectra and GelPermeation Chromatography (GPC.

  4. Moments of the Spin Structure Functions g_1^p and g_1^d for 0.05 < Q^2 < 3.0 GeV^2

    CERN Document Server

    Prok, Y; Burkert, V D; Deur, A; Dharmawardane, K V; Dodge, G E; Griffioen, K A; Kuhn, S E; Minehart, R; Adams, G; Amaryan, M J; Anghinolfi, M; Asryan, G; Audit, G; Avakian, H; Bagdasaryan, H; Baillie, N; Ball, J P; Baltzell, N A; Barrow, S; Battaglieri, M; Beard, K; Bedlinskiy, I; Bektasoglu, M; Bellis, M; Benmouna, N; Berman, B L; Biselli, A S; Blaszczyk, L; Boiarinov, S; Bonner, B E; Bouchigny, S; Bradford, R; Branford, D; Briscoe, W J; Brooks, W K; Bültmann, S; Butuceanu, C; Calarco, J R; Careccia, S L; Carman, D S; Casey, L; Cazes, A; Chen, S; Cheng, L; Cole, P L; Collins, P; Coltharp, P; Cords, D; Corvisiero, P; Crabb, D; Credé, V; Cummings, J P; Dale, D; Dashyan, N; De Masi, R; De Vita, R; De Sanctis, E; Degtyarenko, P V; Denizli, H; Dennis, L; Dhuga, K S; Dickson, R; Djalali, C; Doughty, D; Dugger, M; Dytman, S; Dzyubak, O P; Egiyan, H; Egiyan, K S; El Fassi, L; Elouadrhiri, L; Eugenio, P; Fatemi, R; Fedotov, G; Feldman, G; Fersh, R G; Feuerbach, R J; Forest, T A; Fradi, A; Funsten, H; Garçon, M; Gavalian, G; Gevorgyan, N; Gilfoyle, G P; Giovanetti, K L; Girod, F X; Goetz, J T; Golovatch, E; Gothe, R W; Guidal, M; Guillo, M; Guler, N; Guo, L; Gyurjyan, V; Hadjidakis, C; Hafidi, K; Hakobyan, H; Hanretty, C; Hardie, J; Hassall, N; Heddle, D; Hersman, F W; Hicks, K; Hleiqawi, I; Holtrop, M; Huertas, M; Hyde-Wright, C E; Ilieva, Y; Ireland, D G; Ishkhanov, B S; Isupov, E L; Ito, M M; Jenkins, D; Jo, H S; Johnstone, J R; Joo, K; Jüngst, H G; Kalantarians, N; Keith, C D; Kellie, J D; Khandaker, M; Kim, K Y; Kim, K; Kim, W; Klein, A; Klein, F J; Klusman, M; Kossov, M; Krahn, Z; Kramer, L H; Kubarovski, V; Kühn, J; Kuleshov, S V; Kuznetsov, V; Lachniet, J; Laget, J M; Langheinrich, J; Lawrence, D; Ji Li; Lima, A C S; Livingston, K; Lu, H Y; Lukashin, K; MacCormick, M; Marchand, C; Markov, N; Mattione, P; McAleer, S; McKinnon, B; McNabb, J W C; Mecking, B A; Mestayer, M D; Meyer, C A; Mibe, T; Mikhailov, K; Mirazita, M; Miskimen, R; Mokeev, V; Morand, L; Moreno, B; Moriya, K; Morrow, S A; Moteabbed, M; Müller, J; Munevar, E; Mutchler, G S; Nadel-Turonski, P; Nasseripour, R; Niccolai, S; Niculescu, G; Niculescu, I; Niczyporuk, B B; Niroula, M R; Niyazov, R A; Nozar, M; O'Rielly, G V; Osipenko, M; Ostrovidov, A I; Park, K; Pasyuk, E; Paterson, C; Anefalos Pereira, S; Philips, S A; Pierce, J; Pivnyuk, N; Pocanic, D; Pogorelko, O; Popa, I; Pozdniakov, S; Preedom, B M; Price, J W; Procureur, S; Protopopescu, D; Qin, L M; Raue, B A; Riccardi, G; Ricco, G; Ripani, M; Ritchie, B G; Rosner, G; Rossi, P; Rowntree, D; Rubin, P D; Sabati, F; Salamanca, J; Salgado, C; Santoro, e J P; Sapunenko, V; Schumacher, R A; Seely, M L; Serov, V S; Sharabyan, Yu G; Sharov, D; Shaw, J; Shvedunov, N V; Skabelin, A V; Smith, E S; Smith, L C; Sober, D I; Sokhan, D; Stavinsky, A; Stepanyan, S S; Stepanyan, S; Stokes, B E; Stoler, P; Strakovsky, I I; Strauch, S; Suleiman, R; Taiuti, M; Tedeschi, D J; Tkabladze, A; Tkachenko, S; Todor, L; Ungaro, M; Vineyard, M F; Vlassov, A V; Watts, D P; Weinstein, L B; Weygand, D P; Williams, M; Wolin, E; Wood, M H; Yegneswaran, A; Yun, J; Zana, L; Zhang, J; Zhao, B; Zhao, Z W

    2008-01-01

    The spin structure functions g_1 for the proton and the deuteron have been measured over a wide kinematic range in x and Q2 using 1.6 and 5.7 GeV longitudinally polarized electrons incident upon polarized NH_3 and ND_3 targets at Jefferson Lab. Scattered electrons were detected in the CEBAF Large Acceptance Spectrometer, for 0.05 < Q^2 < 5 GeV^2 and W < 3 GeV. The first moments of g_1 for the proton and deuteron are presented -- both have a negative slope at low Q2, as predicted by the extended Gerasimov-Drell-Hearn sum rule. The first result for the generalized forward spin polarizability of the proton gamma_0^p is also reported, and shows evidence of scaling above Q^2 = 1.5 GeV^2. Although the first moments of g_1 are consistent with Chiral Perturbation Theory (ChPT) calculations up to approximately Q^2 = 0.06 GeV^2, a significant discrepancy is observed between the \\gamma_0^p data and ChPT for gamma_0^p,even at the lowest Q2.

  5. Moments of the Spin Structure Functions g1p and g1d for 0.05 < Q2 < 3.0 GeV2

    Energy Technology Data Exchange (ETDEWEB)

    Prok, Yelena; Bosted, Peter; Burkert, Volker; Deur, Alexandre; Dharmawardane, Kahanawita; Dodge, Gail; Griffioen, Keith; Kuhn, Sebastian; Minehart, Ralph; Adams, Gary; Amaryan, Moscov; Amaryan, Moskov; Anghinolfi, Marco; Asryan, G.; Audit, Gerard; Avagyan, Harutyun; Baghdasaryan, Hovhannes; Baillie, Nathan; Ball, J.P.; Ball, Jacques; Baltzell, Nathan; Barrow, Steve; Battaglieri, Marco; Beard, Kevin; Bedlinskiy, Ivan; Bektasoglu, Mehmet; Bellis, Matthew; Benmouna, Nawal; Berman, Barry; Biselli, Angela; Blaszczyk, Lukasz; Boyarinov, Sergey; Bonner, Billy; Bouchigny, Sylvain; Bradford, Robert; Branford, Derek; Briscoe, William; Brooks, William; Bultmann, S.; Bueltmann, Stephen; Butuceanu, Cornel; Calarco, John; Careccia, Sharon; Carman, Daniel; Casey, Liam; Cazes, Antoine; Chen, Shifeng; Cheng, Lu; Cole, Philip; Collins, Patrick; Coltharp, Philip; Cords, Dieter; Corvisiero, Pietro; Crabb, Donald; Crede, Volker; Cummings, John; Dale, Daniel; Dashyan, Natalya; De Masi, Rita; De Vita, Raffaella; De Sanctis, Enzo; Degtiarenko, Pavel; Denizli, Haluk; Dennis, Lawrence; Dhuga, Kalvir; Dickson, Richard; Djalali, Chaden; Doughty, David; Dugger, Michael; Dytman, Steven; Dzyubak, Oleksandr; Egiyan, Hovanes; Egiyan, Kim; Elfassi, Lamiaa; Elouadrhiri, Latifa; Eugenio, Paul; Fatemi, Renee; Fedotov, Gleb; Feldman, Gerald; Fersch, Robert; Feuerbach, Robert; Forest, Tony; Fradi, Ahmed; Funsten, Herbert; Garcon, Michel; Gavalian, Gagik; Gevorgyan, Nerses; Gilfoyle, Gerard; Giovanetti, Kevin; Girod, Francois-Xavier; Goetz, John; Golovach, Evgeny; Gothe, Ralf; Guidal, Michel; Guillo, Matthieu; Guler, Nevzat; Guo, Lei; Gyurjyan, Vardan; Hadjidakis, Cynthia; Hafidi, Kawtar; Hakobyan, Hayk; Hanretty, Charles; Hardie, John; Hassall, Neil; Heddle, David; Hersman, F.; Hicks, Kenneth; Hleiqawi, Ishaq; Holtrop, Maurik; Huertas, Marco; Hyde, Charles; Ilieva, Yordanka; Ireland, David; Ishkhanov, Boris; Isupov, Evgeny; Ito, Mark; Jenkins, David; Jo, Hyon-Suk; Johnstone, John; Joo, Kyungseon; Juengst, Henry; Kalantarians, Narbe; Keith, Christopher; Kellie, James; Khandaker, Mahbubul; Kim, Kui; Kim, Kyungmo; Kim, Wooyoung; Klein, Andreas; Klein, Franz; Klusman, Mike; Kossov, Mikhail; Krahn, Zebulun; Kramer, Laird; Kubarovsky, Valery; Kuhn, Joachim; Kuleshov, Sergey; Kuznetsov, Viacheslav; Lachniet, Jeff; Laget, Jean; Langheinrich, Jorn; Lawrence, Dave; Lima, Ana; Livingston, Kenneth; Lu, Haiyun; Lukashin, K.; MacCormick, Marion; Marchand, Claude; Markov, Nikolai; Mattione, Paul; McAleer, Simeon; McKinnon, Bryan; McNabb, John; Mecking, Bernhard; Mestayer, Mac; Meyer, Curtis; Mibe, Tsutomu; Mikhaylov, Konstantin; Mirazita, Marco; Miskimen, Rory; Mokeev, Viktor; Morand, Ludyvine; Moreno, Brahim; Moriya, Kei; Morrow, Steven; Moteabbed, Maryam; Mueller, James; Munevar Espitia, Edwin; Mutchler, Gordon; Nadel-Turonski, Pawel; Nasseripour, Rakhsha; Niccolai, Silvia; Niculescu, Gabriel; Niculescu, Maria-Ioana; Niczyporuk, Bogdan; Niroula, Megh; Niyazov, Rustam; Nozar, Mina; O' Rielly, Grant; Osipenko, Mikhail; Ostrovidov, Alexander; Park, Kijun; Pasyuk, Evgueni; Paterson, Craig; Anefalos Pereira, S.; Philips, Sasha; Pierce, J.; Pivnyuk, Nikolay; Pocanic, Dinko; Pogorelko, Oleg; Popa, Iulian; Pozdnyakov, Sergey; Preedom, Barry; Price, John; Procureur, Sebastien; Protopopescu, Dan; Qin, Liming; Raue, Brian; Riccardi, Gregory; Ricco, Giovanni; Ripani, Marco; Ritchie, Barry; Rosner, Guenther; Rossi, Patrizia; Rowntree, David; Rubin, Philip; Sabatie, Franck; Salamanca, Julian; Salgado, Carlos; Santoro, Joseph; Sapunenko, Vladimir; Schumacher, Reinhard; Seely, Mikell; Serov, Vladimir; Sharabian, Youri; Sharov, Dmitri; Shaw, Jeffrey; Shvedunov, Nikolay; Skabelin, Alexander; Smith, Elton; Smith, Lee; Sober, Daniel; Sokhan, Daria; Stavinskiy, Aleksey; Stepanyan, Samuel; Stepanyan, Stepan; Stokes, Burnham; Stoler, Paul; Strakovski, Igor; Strauch, Steffen; Suleiman, Riad; Taiuti, Mauro; Tedeschi, David; Tkabladze, Avtandil; Tkachenko, Svyatoslav; Todor, Luminita; Ungaro, Maurizio; V

    2009-02-01

    The spin structure functions $g_1$ for the proton and the deuteron have been measured over a wide kinematic range in $x$ and \\Q2 using 1.6 and 5.7 GeV longitudinally polarized electrons incident upon polarized NH$_3$ and ND$_3$ targets at Jefferson Lab. Scattered electrons were detected in the CEBAF Large Acceptance Spectrometer, for $0.05 < Q^2 < 5 $\\ GeV$^2$ and $W < 3$ GeV. The first moments of $g_1$ for the proton and deuteron are presented -- both have a negative slope at low \\Q2, as predicted by the extended Gerasimov-Drell-Hearn sum rule. The first result for the generalized forward spin polarizability of the proton $\\gamma_0^p$ is also reported, and shows evidence of scaling above $Q^2$ = 1.5 GeV$^2$. Although the first moments of $g_1$ are consistent with Chiral Perturbation Theory (\\ChPT) calculations up to approximately $Q^2 = 0.06$ GeV$^2$, a significant discrepancy is observed between the $\\gamma_0^p$ data and \\ChPT\\ for $\\gamma_0^p$,even at the lowest \\Q2.

  6. Redox-mediated bypass of restriction point via skipping of G1pm

    Directory of Open Access Journals (Sweden)

    Greene James J

    2006-07-01

    Full Text Available Abstract Background It is well known that cancer cells bypass the restriction point, R, and undergo uncontrolled cell proliferation. Hypothesis and evidence We suggest here that fibrosarcoma cells enter G1ps directly from M, skipping G1pm, hence bypassing R, in response to redox modulation. Evidence is presented from the published literature that demonstrate a shortening of the cycle period of transformed fibroblasts (SV-3T3 compared to the nontransformed 3T3 fibroblasts, corresponding to the duration of G1pm in the 3T3 fibroblasts. Evidence is also presented that demonstrate that redox modulation can induce the CUA-4 fibroblasts to bypass R, resulting in a cycle period closely corresponding to the cycle period of fibrosarcoma cells (HT1080. Conclusion The evidence supports our hypothesis that a low internal redox potential can cause fibrosarcoma cells to skip the G1pm phase of the cell cycle.

  7. 法国海湾战争后的伊拉克政策分析%Politique irakienne du gouvernement fran(c)ais depuis la fin de la guerre du Golf

    Institute of Scientific and Technical Information of China (English)

    汪波

    2004-01-01

    Depuis la fin de la guerre du Golf du debut des annees 1990, le gouvernement francais pratique une politique specifique des affaires etrangeres dans les affaires en lrak. En montrant sa position et son influence intemationale., cette politique consists, d'une part, a s'opposer a la politique unilaterale des Etats-Unis au Moyen-Orient,de 1'autre, a y maintenir ses propres interets economiques et politiques.

  8. IgG1 variations in the colostrum of Holstein dairy cows.

    Science.gov (United States)

    Le Cozler, Y; Guatteo, R; Le Dréan, E; Turban, H; Leboeuf, F; Pecceu, K; Guinard-Flament, J

    2016-02-01

    High-immune quality colostrum (IgG1 concentration ⩾50 g/l) is crucial for the health and development of the young calf. Studies on colostrum quality tend to focus on external factors such as breed, parity or dry period length, but few have focused on within-cow variations. Here we ran experiments to gain a deeper insight into within-cow variation in IgG1 concentrations in dairy cow colostrum. Trials were performed in an experimental farm, located in the Western part of France. Colostrum from each quarter and a composite sample (mix of four quarters) were concomitantly collected on 77 Holstein dairy cows just after calving to assess the influence of sample type on IgG1 concentrations. Variation in IgG1 concentrations during the first milking was studied on samples from nine cows collected every minute from the start of milking. Repeatability of colostral IgG1 concentration was estimated from 2009 and 2010 data on 16 healthy cows. IgG1 concentrations were tested using a radial immunodiffusion method. Sensitivity and specificity were similar regardless of sample type tested (individual quarter or composite milk). Mean average IgG1 concentration was 54.1 g/l in composite colostrum, and was significantly higher in hind quarter teats (56.2 g/l) than front quarter teats (53.1 g/l). Average IgG1 concentration did not change significantly during colostrum milking, and the variations observed (15% or less) were likely due to the laboratory method (CV 15%). IgG1 concentrations in dam colostrum increased slightly from 2009 to 2010 due to BW and parity effects. In 56% of cases, colostrum quality could have been assessed on either individual or composite colostrum samples collected at any time during the first milking without affecting the reliability of the measurement. However, in other cases, differences were significant enough to mean that estimates of average IgG1 concentration in colostrum from any one quarter would not be reliable. It is concluded that colostrum quality

  9. Molecular basis for the dissociation dynamics of protein A-immunoglobulin G1 complex.

    Directory of Open Access Journals (Sweden)

    Fu-Feng Liu

    Full Text Available Staphylococcus aureus protein A (SpA is the most popular affinity ligand for immunoglobulin G1 (IgG1. However, the molecular basis for the dissociation dynamics of SpA-IgG1 complex is unclear. Herein, coarse-grained (CG molecular dynamics (MD simulations with the Martini force field were used to study the dissociation dynamics of the complex. The CG-MD simulations were first verified by the agreement in the structural and interactional properties of SpA and human IgG1 (hIgG1 in the association process between the CG-MD and all-atom MD at different NaCl concentrations. Then, the CG-MD simulation studies focused on the molecular insight into the dissociation dynamics of SpA-hIgG1 complex at pH 3.0. It is found that there are four steps in the dissociation process of the complex. First, there is a slight conformational adjustment of helix II in SpA. This is followed by the phenomena that the electrostatic interactions provided by the three hot spots (Glu143, Arg146 and Lys154 of helix II of SpA break up, leading to the dissociation of helix II from the binding site of hIgG1. Subsequently, breakup of the hydrophobic interactions between helix I (Phe132, Tyr133 and His137 in SpA and hIgG1 occurs, resulting in the disengagement of helix I from its binding site of hIgG1. Finally, the non-specific interactions between SpA and hIgG1 decrease slowly till disappearance, leading to the complete dissociation of the SpA-hIgG1 complex. This work has revealed that CG-MD coupled with the Martini force field is an effective method for studying the dissociation dynamics of protein-protein complex.

  10. Dillapiol and Apiol as specific inhibitors of the biosynthesis of aflatoxin G1 in Aspergillus parasiticus.

    Science.gov (United States)

    Razzaghi-Abyaneh, Mehdi; Yoshinari, Tomoya; Shams-Ghahfarokhi, Masoomeh; Rezaee, Mohammad-Bagher; Nagasawa, Hiromichi; Sakuda, Shohei

    2007-09-01

    Dillapiol was isolated from the essential oil of dill as a specific inhibitor of aflatoxin G1 production. It inhibited aflatoxin G1 production by Aspergillus parasiticus with an IC50 value of 0.15 microM without inhibiting aflatoxin B1 production or fungal growth. Apiol and myristicin, congeners of dillapiol, showed similar activity with IC50 values of 0.24 and 3.5 microM, respectively.

  11. Matrix metalloproteinase-2 (MMP-2) generates soluble HLA-G1 by cell surface proteolytic shedding.

    Science.gov (United States)

    Rizzo, Roberta; Trentini, Alessandro; Bortolotti, Daria; Manfrinato, Maria C; Rotola, Antonella; Castellazzi, Massimiliano; Melchiorri, Loredana; Di Luca, Dario; Dallocchio, Franco; Fainardi, Enrico; Bellini, Tiziana

    2013-09-01

    Human leukocyte antigen-G (HLA-G) molecules are non-classical HLA class I antigens with an important role in pregnancy immune regulation and inflammation control. Soluble HLA-G proteins can be generated through two mechanisms: alternative splicing and proteolytic release, which is known to be metalloprotease mediated. Among this class of enzymes, matrix metalloproteinases (MMPs) might be involved in the HLA-G1 membrane cleavage. Of particular interest are MMP-2 and MMP-9, which regulate the inflammatory process by cytokine and chemokine modulation. We evaluated the effect of MMP-9 and MMP-2 on HLA-G1 membrane shedding. In particular, we analyzed the in vitro effect of these two gelatinases on the secretion of HLA-G1 via proteolytic cleavage in 221-G1-transfected cell line, in JEG3 cell line, and in peripheral blood mononuclear cells. The results obtained by both cell lines showed the role of MMP-2 in HLA-G1 shedding. On the contrary, MMP-9 was not involved in this process. In addition, we identified three possible highly specific cleavage sites for MMP-2, whereas none were detected for MMP-9. This study suggests an effective link between MMP-2 and HLA-G1 shedding, increasing our knowledge on the regulatory machinery beyond HLA-G regulation in physiological and pathological conditions.

  12. The amrG1 gene is involved in the activation of acetate in Corynebacterium glutamicum

    Institute of Scientific and Technical Information of China (English)

    RUAN; Hong; R.; Gerstmeir; S.; Schnicke; B.J.; Eikmanns

    2005-01-01

    During growth of Corynebacterium glutamicum on acetate as its carbon and energy source, the expression of the pta-ack operon is induced, coding for the acetate-activating enzymes, which are phosphotransacetylase (PTA) and acetate kinase (AK). By transposon rescue, we identified the two genes amrG1 and amrG2 found in the deregulated transposon mutant C. glutamicum G25. The amrG1 gene (NCBI-accession: AF532964) has a size of 732 bp, encoding a polypeptide of 243 amino acids and apparently is partially responsible for the regulation of acetate metabolism in C. glutamicum. We constructed an in-frame deletion mutant and an overexpressing strain of amrG1 in the C. glutamicum ATCC13032 wildtype. The strains were then analyzed with respect to their enzyme activities of PTA and AK during growth on glucose, acetate and glucose or acetate alone as carbon sources. Compared to the parental strain, the amrG1 deletion mutant showed higher specific AK and PTA activities during growth on glucose but showed the same high specific activities of AK and PTA on medium containing acetate plus glucose and on medium containing acetate. In contrast to the gene deletion, overexpression of the amrG1 gene in C. glutamicum 13032 had the adverse regulatory effect. These results indicate that the amrG1 gene encodes a repressor or co-repressor of the pta-ack operon.

  13. Observation of an additional electronic level of the EL2 defect

    Science.gov (United States)

    Stiévenard, D.; Delerue, C.; von Bardeleben, H. J.; Bourgoin, J. C.; Guillot, G.; Brémond, G.; Azoulay, R.

    1991-07-01

    Using deep-level transient spectroscopy (DLTS), we have studied the properties of the EL2 defect in the alloy system Ga1-xAlxAs grown by metal-organic chemical-vapor deposition, with x=0.145. We have observed the stable state of the defect, i.e., its quench under a 1.18-eV illumination and a different DLTS peak, associated with EL2. The study of the behavior of this peak versus the illumination and thermal treatment allows us to associate this peak with a different electronic level of EL2: the (-/0) level if EL2 is an isolated antisite AsGa or the (0/+) level if EL2 is associated with the (AsGa-As+i) pair.

  14. SENSITIVITY ANALYSIS OF PERFORMANCEFOR M/G/1 QUEUEING SYSTEMS%M/G/1排队系统的性能灵敏度分析

    Institute of Scientific and Technical Information of China (English)

    殷保群; 奚宏生; 周亚平

    2001-01-01

    The queueing system which is not Markov-type is often used as amodel to study some practical engineering problems,for example,communication networks.In this paper,the problems of sensitivity analysis of the steady-state performance for an M/G/1 queueing system are discussed by studying its embedded Markov chain.The sensitivity formulas of the steady-state performance are given by the potentials of the embedded Markov chain.Since the embedded Markov chain is much simpler than the semi-Markov process that is used to describe the system states,the results in this paper will be very convenient for simulating computation of performance sensitivity and optimization of the system.%非Markov型排队系统经常被用来作为某些实际工程问题(如通讯网络)的研究模型.对于一般的M/G/1排队系统,本文通过研究其嵌入Markov链,讨论了系统的稳态性能灵敏度分析问题,并给出用嵌入Markov链的势能表示的稳态性能灵敏度公式.由于嵌入Markov链要比描述其系统状态的半Markov过程简单得多,故本文的结果对M/G/1排队系统的性能灵敏度仿真计算及系统的优化,都将带来极大的方便.

  15. 双三次B样条曲面的G1连续条件%G1 Continuity Conditions of Bicubic B-Spline Surfaces

    Institute of Scientific and Technical Information of China (English)

    施锡泉; 赵岩

    2002-01-01

    讨论并得到关于两个双三次非均匀内部单节点B样条曲面片G1连续的充分必要条件,以及在公共边界线上控制向量的本征条件.这些条件直接由两个非均匀B样条曲面的控制向量表示.并证明了用单节点双三次非均匀B样条不能构造出具有局部性质的曲面模型.

  16. 26 CFR 6a.6652(g)-1 - Failure to make return or furnish statement required under section 6039C.

    Science.gov (United States)

    2010-04-01

    ... required under section 6039C. 6a.6652(g)-1 Section 6a.6652(g)-1 Internal Revenue INTERNAL REVENUE SERVICE... OMNIBUS RECONCILIATION ACT OF 1980 § 6a.6652(g)-1 Failure to make return or furnish statement required... limitation under § 6a.6652(g)-1(b)(3) with respect to failure to meet the requirements of section 6039C(c),...

  17. Human pancreatic β-cell G1/S molecule cell cycle atlas.

    Science.gov (United States)

    Fiaschi-Taesch, Nathalie M; Kleinberger, Jeffrey W; Salim, Fatimah G; Troxell, Ronnie; Wills, Rachel; Tanwir, Mansoor; Casinelli, Gabriella; Cox, Amy E; Takane, Karen K; Scott, Donald K; Stewart, Andrew F

    2013-07-01

    Expansion of pancreatic β-cells is a key goal of diabetes research, yet induction of adult human β-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human β-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control molecules in the human β-cell. This atlas reveals that the majority of these molecules, previously known to be present in islets, are actually present in the β-cell. More importantly, and in contrast to anticipated results, the human β-cell G1/S atlas reveals that almost all of the critical G1/S cell cycle control molecules are located in the cytoplasm of the quiescent human β-cell. Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human β-cell proliferation are present in the nuclear compartment. This observation may provide an explanation for the refractoriness of human β-cells to proliferation. Thus, in addition to known obstacles to human β-cell proliferation, restriction of G1/S molecules to the cytoplasm of the human β-cell represents an unanticipated obstacle to therapeutic human β-cell expansion.

  18. A comparative genomic analysis of the alkalitolerant soil bacterium Bacillus lehensis G1.

    Science.gov (United States)

    Noor, Yusuf Muhammad; Samsulrizal, Nurul Hidayah; Jema'on, Noor Azah; Low, Kheng Oon; Ramli, Aizi Nor Mazila; Alias, Noor Izawati; Damis, Siti Intan Rosdianah; Fuzi, Siti Fatimah Zaharah Mohd; Isa, Mohd Noor Mat; Murad, Abdul Munir Abdul; Raih, Mohd Firdaus Mohd; Bakar, Farah Diba Abu; Najimudin, Nazalan; Mahadi, Nor Muhammad; Illias, Rosli Md

    2014-07-25

    Bacillus lehensis G1 is a Gram-positive, moderately alkalitolerant bacterium isolated from soil samples. B. lehensis produces cyclodextrin glucanotransferase (CGTase), an enzyme that has enabled the extensive use of cyclodextrin in foodstuffs, chemicals, and pharmaceuticals. The genome sequence of B. lehensis G1 consists of a single circular 3.99 Mb chromosome containing 4017 protein-coding sequences (CDSs), of which 2818 (70.15%) have assigned biological roles, 936 (23.30%) have conserved domains with unknown functions, and 263 (6.55%) have no match with any protein database. Bacillus clausii KSM-K16 was established as the closest relative to B. lehensis G1 based on gene content similarity and 16S rRNA phylogenetic analysis. A total of 2820 proteins from B. lehensis G1 were found to have orthologues in B. clausii, including sodium-proton antiporters, transport proteins, and proteins involved in ATP synthesis. A comparative analysis of these proteins and those in B. clausii and other alkaliphilic Bacillus species was carried out to investigate their contributions towards the alkalitolerance of the microorganism. The similarities and differences in alkalitolerance-related genes among alkalitolerant/alkaliphilic Bacillus species highlight the complex mechanism of pH homeostasis. The B. lehensis G1 genome was also mined for proteins and enzymes with potential viability for industrial and commercial purposes.

  19. Overview of the spin structure function g_1 at arbitrary x and Q^2

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2009-01-01

    In the present paper we summarize our results on the structure function g_1 and present explicit expressions for the non-singlet and singlet components of g_1 which can be used at arbitrary x and Q^2. These expressions combine the well-known DGLAP-results for the anomalous dimensions and coefficient functions with the total resummation of the leading logarithmic contributions and the shift of Q^2 -> Q^2 + \\mu^2, with \\mu/\\Lambda_{QCD} approx 10 (approx 55) for the non-singlet (singlet) components of g_1 respectively. In contrast to DGLAP, these expressions do not require the introduction of singular parameterizations for the initial parton densities. We also apply our results to describe the experimental data in the kinematic regions beyond the reach of DGLAP.

  20. Nonuniform expansion and brightening of the youngest Galactic SNR G1.9+0.3

    Science.gov (United States)

    Borkowski, Kazimierz

    2014-09-01

    We propose a 400-ks observation of the youngest Galactic supernova remnant (SNR) G1.9+0.3, to study its nonuniform expansion and monitor increase in brightness. Expansion along the major axis of G1.9+0.3 has been found to decrease with radius. The longer time baseline should help in understanding these surprising variations in expansion. No other Galactic SNR is brightening. The X-rays are mainly produced as synchrotron radiation from 10 -- 100 TeV electrons, so the magnitude and spatial dependence of the brightening rate have important implications for the physics of particle acceleration and magnetic-field amplification in fast shock waves. G1.9+0.3 is a unique SNR whose continued monitoring should greatly advance our understanding of Type Ia supernovae and nonthermal shock physics.

  1. Asymmetric High-Velocity Ejecta in the Youngest Galactic SNR G1.9+0.3

    Science.gov (United States)

    Borkowski, Kazimierz

    2014-11-01

    Chandra has revealed highly asymmetric supernova ejecta in G1.9+0.3. Iron dominates thermal emission in the radio-bright northern rim, while only intermediate-mass elements are found along the SE-NW axis. The measured X-ray expansion rates decrease radially by about 60% along this axis from 0.84% yr^{-1) to 0.52% yr^{-1}. This corresponds to undecelerated ages of 120 - 190 yr, confirming the young age of G1.9+0.3, and implying that the blast wave is much more decelerated than the reverse shock. Only the outermost ejecta with very high (>18,000 km s^{-1}) free-expansion velocities have been shocked so far. We discuss G1.9+0.3 in the framework of recent asymmetric 3D delayed-detonation Type Ia explosions from Seitenzahl et al. (2013). Their N3 model provides the best match.

  2. Extraction of monoclonal antibodies (IgG1) using anionic and anionic/nonionic reverse micelles.

    Science.gov (United States)

    George, Daliya A; Stuckey, David C

    2010-01-01

    Purification schemes for antibody production based on affinity chromatography are trying to keep pace with increases in cell culture expression levels and many current research initiatives are focused on finding alternatives to chromatography for the purification of Monoclonal antibodies (MAbs). In this article, we have investigated an alternative separation technique based on liquid-liquid extraction called the reverse micellar extraction. We extracted MAb (IgG1) using reverse micelles of an anionic surfactant, sodium bis 2-ethyl-hexyl sulfosuccinate (AOT) and a combination of anionic (AOT) and nonionic surfactants (Brij-30, Tween-85, Span-85) using isooctane as the solvent system. The extraction efficiency of IgG1 was studied by varying parameters, such as pH of the aqueous phase, cation concentration, and type and surfactant concentration. Using the AOT/Isooctane reverse micellar system, we could achieve good overall extraction of IgG1 (between 80 and 90%), but only 30% of the bioactivity of IgG1 could be recovered at the end of the extraction by using its binding to affinity chromatography columns as a surrogate measure of activity. As anionic surfactants were suspected as being one of the reasons for the reduced activity, we decided to combine a nonionic surfactant with an anionic surfactant and then study its effect on the extraction efficiency and bioactivity. The best results were obtained using an AOT/Brij-30/Isooctane reverse micellar system, which gave an overall extraction above 90 and 59% overall activity recovery. An AOT/Tween-85/Isooctane reverse micellar system gave an overall extraction of between 75 and 80% and overall activity recovery of around 40-45%. The results showed that the activity recovery of IgG1 can be significantly enhanced using different surfactant combination systems, and if the recovery of IgG1 can be further enhanced, the technique shows considerable promise for the downstream purification of MAbs.

  3. On the first $G_1$ stiff fluid spike solution in General Relativity

    CERN Document Server

    Coley, Alan; Lim, Woei Chet

    2016-01-01

    Using the Geroch transformation we obtain the first example of a stiff fluid solution to the Einstein field equations in a closed form exhibiting a spacelike $G_1$ group of symmetries (i.e., with a single isometry). This new solution can be interpreted as an exact example of a close-to-Friedmann-Lemaitre (perturbative) solution. The exact solution is the first (non-null) $G_1$ solution found, and exhibits a spike crossing which persists to the past, which allows us to better understand spike crossings in the context of structure formation.

  4. Amino acids and mTOR mediate distinct metabolic checkpoints in mammalian G1 cell cycle.

    Directory of Open Access Journals (Sweden)

    Mahesh Saqcena

    Full Text Available OBJECTIVE: In multicellular organisms, cell division is regulated by growth factors (GFs. In the absence of GFs, cells exit the cell cycle at a site in G1 referred to as the restriction point (R and enter a state of quiescence known as G0. Additionally, nutrient availability impacts on G1 cell cycle progression. While there is a vast literature on G1 cell cycle progression, confusion remains - especially with regard to the temporal location of R relative to nutrient-mediated checkpoints. In this report, we have investigated the relationship between R and a series of metabolic cell cycle checkpoints that regulate passage into S-phase. METHODS: We used double-block experiments to order G1 checkpoints that monitor the presence of GFs, essential amino acids (EEAs, the conditionally essential amino acid glutamine, and inhibition of mTOR. Cell cycle progression was monitored by uptake of [(3H]-thymidine and flow cytometry, and analysis of cell cycle regulatory proteins was by Western-blot. RESULTS: We report here that the GF-mediated R can be temporally distinguished from a series of late G1 metabolic checkpoints mediated by EAAs, glutamine, and mTOR - the mammalian/mechanistic target of rapamycin. R is clearly upstream from an EAA checkpoint, which is upstream from a glutamine checkpoint. mTOR is downstream from both the amino acid checkpoints, close to S-phase. Significantly, in addition to GF autonomy, we find human cancer cells also have dysregulated metabolic checkpoints. CONCLUSION: The data provided here are consistent with a GF-dependent mid-G1 R where cells determine whether it is appropriate to divide, followed by a series of late-G1 metabolic checkpoints mediated by amino acids and mTOR where cells determine whether they have sufficient nutrients to accomplish the task. Since mTOR inhibition arrests cells the latest in G1, it is likely the final arbiter for nutrient sufficiency prior to committing to replicating the genome.

  5. Brill-Noether locus of rank 1 and degree g-1 on a nodal curve

    CERN Document Server

    Coelho, Juliana

    2011-01-01

    In this paper we consider the Brill-Noether locus $W_{\\underline d}(C)$ of line bundles of multidegree $\\underline d$ of total degree $g-1$ having a nonzero section on a nodal reducible curve $C$ of genus $g\\geq2$. We give an explicit description of the irreducible components of $W_{\\underline d}(C)$ for a semistable multidegre $\\underline d$. As a consequence we show that, if two semistable multidegrees of total degre $g-1$ on a curve with no rational components differ by a twister, then the respective Brill-Noether loci have isomorphic components.

  6. Data of evolutionary structure change: 1N32G-1IQVA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available ain>G 1N32G INKIM---RDGKK e>HHHH --- H...Chain> 1IQVA INKVMRSGGSSKK ...>HHHHH H> ATOM 293 CA ILE A 71 40.019 9.985 12....in> 1N32G QRPER---RAAVR > --- HHHH... 1IQVA AKCYRTKMSFAEA >HHHHH HHHH

  7. Nonparametric estimation of the stationary M/G/1 workload distribution function

    DEFF Research Database (Denmark)

    Hansen, Martin Bøgsted

    2005-01-01

    In this paper it is demonstrated how a nonparametric estimator of the stationary workload distribution function of the M/G/1-queue can be obtained by systematic sampling the workload process. Weak convergence results and bootstrap methods for empirical distribution functions for stationary associ...

  8. Differential regulation of the cellular response to DNA double-strand breaks in G1

    DEFF Research Database (Denmark)

    Barlow, Jacqueline H; Lisby, Michael; Rothstein, Rodney

    2008-01-01

    Double-strand breaks (DSBs) are potentially lethal DNA lesions that can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). We show that DSBs induced by ionizing radiation (IR) are efficiently processed for HR and bound by Rfa1 during G1, while endonuclease-in...

  9. Learning Progression of Ecological System Reasoning for Lower Elementary (G1-4) Students

    Science.gov (United States)

    Hokayem, Hayat Al

    2012-01-01

    In this study, I utilized a learning progression framework to investigate lower elementary students (G1-4) systemic reasoning in ecology and I related students reasoning to their sources of knowledge. I used semi-structured interviews with 44 students from first through fourth grade, four teachers, and eight parents. The results revealed that a…

  10. Generalization of the DGLAP for the structure function g_1 to the region of small x

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2005-01-01

    The explicit expressions for the non-singlet and singlet components of the DIS structure function g_1 comprising the DGLAP -expressions for the coefficient functions and the anomalous dimensions, and accounting for the total resummation of the most singular contributions to those are obtained.

  11. Comment on the recent COMPASS data on the spin structure function g_1

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2008-01-01

    We examine the recent COMPASS data on the spin structure function g_1 singlet. We show that it is rather difficult to use the data in the present form in order to draw conclusions on the initial parton densities. However, our tentative estimate is that the data better agree with positive rather than negative initial gluon densities.

  12. ON THE TRANSIENT DEPARTURE PROCESS OF Mx/G/1 QUEUEING SYSTEM WITH SINGLE SERVER VACATION

    Institute of Scientific and Technical Information of China (English)

    Yinghui TANG

    2007-01-01

    This paper studies the transient departure process of Mx/G/1 queueing system with single server vacation. We present a simple probability decomposition method to derive the expected number of departures occurring in finite time interval from any initial state and the asymptotic expansion of the expected number. Especially, we derive some more practical results for some special cases.

  13. Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome

    DEFF Research Database (Denmark)

    Borg, Isabella; Freude, Kristine; Kübart, Sabine;

    2005-01-01

    hybridisations, utilizing probes derived from breakpoint spanning BACs, detected several aberrant fragments specific for the patient. Sequence analysis of the cloned junction fragment indicated that on chromosome 1 the predominantly brain-expressed Netrin G1 (NTNG1) gene is disrupted, whereas on chromosome 7...

  14. 17 CFR 240.12g-1 - Exemption from section 12(g).

    Science.gov (United States)

    2010-04-01

    ... pursuant to section 12(g)(1) if on the last day of its most recent fiscal year the issuer had total assets... quoted in an automated inter-dealer quotation system. (Secs. 6, 7, 8, 10, 19(a), 48 Stat. 78, 79, 81,...

  15. Solid-phase synthesis and biological activity of a thioether analogue of conotoxin G1

    DEFF Research Database (Denmark)

    Bondebjerg, Jon; Grunnet, Morten; Jespersen, Thomas;

    2003-01-01

    of two isomers, which were evaluated for their ability to inhibit the muscular nicotinic acetylcholine receptor expressed in Xenopus oocytes. The two isomers were found to have IC(50) values (inhibitory activities) of 144 microM and 48 microM, compared to 0.18 microM for native conotoxin G1....

  16. Bayesian Inference and Prediction in an M/G/1 with Optional Second Service

    NARCIS (Netherlands)

    Mohammadi, A.; Salehi-Rad, M. R.

    2012-01-01

    In this article, we exploit the Bayesian inference and prediction for an M/G/1 queuing model with optional second re-service. In this model, a service unit attends customers arriving following a Poisson process and demanding service according to a general distribution and some of customers need to r

  17. Phosphate-Activated Cyclin-Dependent Kinase Stabilizes G1 Cyclin To Trigger Cell Cycle Entry

    Science.gov (United States)

    Menoyo, S.; Ricco, N.; Bru, S.; Hernández-Ortega, S.; Escoté, X.; Aldea, M.

    2013-01-01

    G1 cyclins, in association with a cyclin-dependent kinase (CDK), are universal activators of the transcriptional G1-S machinery during entry into the cell cycle. Regulation of cyclin degradation is crucial for coordinating progression through the cell cycle, but the mechanisms that modulate cyclin stability to control cell cycle entry are still unknown. Here, we show that a lack of phosphate downregulates Cln3 cyclin and leads to G1 arrest in Saccharomyces cerevisiae. The stability of Cln3 protein is diminished in strains with low activity of Pho85, a phosphate-sensing CDK. Cln3 is an in vitro substrate of Pho85, and both proteins interact in vivo. More interestingly, cells that carry a CLN3 allele encoding aspartic acid substitutions at the sites of Pho85 phosphorylation maintain high levels of Cln3 independently of Pho85 activity. Moreover, these cells do not properly arrest in G1 in the absence of phosphate and they die prematurely. Finally, the activity of Pho85 is essential for accumulating Cln3 and for reentering the cell cycle after phosphate refeeding. Taken together, our data indicate that Cln3 is a molecular target of the Pho85 kinase that is required to modulate cell cycle entry in response to environmental changes in nutrient availability. PMID:23339867

  18. Old stellar population synthesis: new age and mass estimates for Mayall Ⅱ = G1

    Institute of Scientific and Technical Information of China (English)

    Jun Ma; Richard de Grijs; Zhou Fan; Soo-Chang Rey; Zhen-Yu Wu; Xu Zhou; Jiang-Hua Wu; Zhao-Ji Jiang; Jian-Sheng Chen; Kyungsook Lee; Sangmo Tony Sohn

    2009-01-01

    Mayall Ⅱ = G1 is one of the most luminous globular clusters (GCs) in M31. Here, we determine its age and mass by comparing multicolor photometry with theo-retical stellar population synthesis models. Based on far- and near-ultraviolet GALEX photometry, broad-band UBV RI, and infrared JHK8 2MASS data, we construct the most extensive spectral energy distribution of G1 to date, spanning the wavelength range from 1538 to 20000A. A quantitative comparison with a variety of simple stellar pop-ulation (SSP) models yields a mean age which is consistent with G1 being among the oldest building blocks of M31 and having formed within ~1.7Gyr after the Big Bang. Irrespective of the SSP model or stellar initial mass function adopted, the resulting mass estimates (of order 107M⊙) indicate that G1 is one of the most massive GCs in the Local Group. However, we speculate that the cluster's exceptionally high mass suggests that it may not be a genuine GC. Our results also suggest that G1 may contain, on average, (1.65±0.63) × 102L⊙ far-ultraviolet-bright, hot, extreme horizontal-branch stars, depend-ing on the adopted SSP model. In addition, we demonstrate that extensive multi-passband photometry coupled with SSP analysis enables one to obtain age estimates for old SSPs that have similar accuracies as those from integrated spectroscopy or resolved stellar pho-tometry, provided that some of the free parameters can be constrained independently.

  19. Identification of G1-regulated genes in normally cycling human cells.

    Directory of Open Access Journals (Sweden)

    Maroun J Beyrouthy

    Full Text Available BACKGROUND: Obtaining synchronous cell populations is essential for cell-cycle studies. Methods such as serum withdrawal or use of drugs which block cells at specific points in the cell cycle alter cellular events upon re-entry into the cell cycle. Regulatory events occurring in early G1 phase of a new cell cycle could have been overlooked. METHODOLOGY AND FINDINGS: We used a robotic mitotic shake-off apparatus to select cells in late mitosis for genome-wide gene expression studies. Two separate microarray experiments were conducted, one which involved isolation of RNA hourly for several hours from synchronous cell populations, and one experiment which examined gene activity every 15 minutes from late telophase of mitosis into G1 phase. To verify synchrony of the cell populations under study, we utilized methods including BrdU uptake, FACS, and microarray analyses of histone gene activity. We also examined stress response gene activity. Our analysis enabled identification of 200 early G1-regulated genes, many of which currently have unknown functions. We also confirmed the expression of a set of genes candidates (fos, atf3 and tceb by qPCR to further validate the newly identified genes. CONCLUSION AND SIGNIFICANCE: Genome-scale expression analyses of the first two hours of G1 in naturally cycling cells enabled the discovery of a unique set of G1-regulated genes, many of which currently have unknown functions, in cells progressing normally through the cell division cycle. This group of genes may contain future targets for drug development and treatment of human disease.

  20. The existence of inflection points for generalized log-aesthetic curves satisfying G1 data

    Science.gov (United States)

    Karpagavalli, R.; Gobithaasan, R. U.; Miura, K. T.; Shanmugavel, Madhavan

    2015-12-01

    Log-Aesthetic (LA) curves have been implemented in a CAD/CAM system for various design feats. LA curves possess linear Logarithmic Curvature Graph (LCG) with gradient (shape parameter) denoted as α. In 2009, a generalized form of LA curves called Generalized Log-Aesthetic Curves (GLAC) has been proposed which has an extra shape parameter as ν compared to LA curves. Recently, G1 continuous GLAC algorithm has been proposed which utilizes the extra shape parameter using four control points. This paper discusses on the existence of inflection points in a GLAC segment satisfying G1 Hermite data and the effect of inflection point on convex hull property. It is found that the existence of inflection point can be avoided by manipulating the value of α. Numerical experiments show that the increase of α may remove the inflection point (if any) in a GLAC segment.

  1. Rare Coumarins Induce Apoptosis, G1 Cell Block and Reduce RNA Content in HL60 Cells

    Directory of Open Access Journals (Sweden)

    Widelski Jarosław

    2017-02-01

    Full Text Available The rare coumarins stenocarpin, stenocarpin isobutyrate, oficinalin, oficinalin isobutyrate, 8-methoxypeucedanin and the known xanthotoxin, isoimperatorin, bergapten, peucedanin and 8–methoxyisoimperatorin were isolated from Peucedanum luxurians Tamamsch. (Apiaceae and identified by means of spectral data (1D and 2D NMR. Their immunomodulating activity was evaluated by flow cytometry and their influence on HL60 cells as well as on PHA-stimulated PBLs was tested. All tested coumarins induce apoptosis (maximal in the 48 h culture and decrease cell proliferation in a time- and dose-dependent manner, especially in HL60 cells. They also induce partial G1 block, but only in HL60 cells (at 100 µM concentrations. Dose-dependent reduction of RNA content was also found in G1 cells treated by the coumarins. All of the tested coumarins also possessed immunomodulatory activities. Bergapten and xanthotoxin were found to be the best candidates for further evaluation as anti-cancer drugs.

  2. The MAP, M/G1,G2/1 queue with preemptive priority

    Directory of Open Access Journals (Sweden)

    Bong Dae Choi

    1997-01-01

    Full Text Available We consider the MAP, M/G1,G2/1 queue with preemptive resume priority, where low priority customers arrive to the system according to a Markovian arrival process (MAP and high priority customers according to a Poisson process. The service time density function of low (respectively: high priority customers is g1(x (respectively: g2(x. We use the supplementary variable method with Extended Laplace Transforms to obtain the joint transform of the number of customers in each priority queue, as well as the remaining service time for the customer in service in the steady state. We also derive the probability generating function for the number of customers of low (respectively, high priority in the system just after the service completion epochs for customers of low (respectively, high priority.

  3. OPTIMAL CONTROL OF AN M/G/1 RETRIAL QUEUE WITH VACATIONS

    Institute of Scientific and Technical Information of China (English)

    Arnar AISSANI

    2008-01-01

    In this note, we consider an M/G/1 retrial queue with server vacations, when retrial times, servicetimes and vacation times are arbitrary distributed. The distribution of the number of customers in the system in stationary regime is obtained in terms of generating function. Next, we give heavy traffic approximation of such distribution. We show that the system size can be decomposed into two random variables, one of which corresponds to the system size of the ordinary M/G/1 FIFO queue without vacation. Such a stochastic decomposition property is useful for the computation of performance measures of interest. Finally, we solve simple problems of optimal control of vacation and retrial policies.

  4. Regulation of the G1 phase of the mammalian cell cycle

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In any multi-cellular organism, the balance between cell division and cell death maintains a constant cell num ber. Both cell division cycle and cell death are highly regulated events. Whether the cell will proceed through the cycle or not, depends upon whether the conditions re quired at the checkpoints during the cycle are filfilled. In higher eucaryotic cells, such as mammalian cells, signals that arrest the cycle usually act at a G1 checkpoint. Cells that pass this restriction point are committed to complete the cycle. Regulation of the G1 phase of the cell cycle is extremely complex and involves many different families of proteins such as retinoblastoma family, cyclin dependent kinases, cyclins, and cyclin kinase inhibitors.

  5. Replicatively senescent cells are arrested in G1 and G2 phases

    Science.gov (United States)

    Mao, Zhiyong; Ke, Zhonghe; Gorbunova, Vera; Seluanov, Andrei

    2012-01-01

    Most human somatic cells do not divide indefinitely but enter a terminal growth arrest termed replicative senescence. Replicatively senescent cells are generally believed to arrest in G1 or G0 stage of the cell cycle. While doing cell cycle analysis on three different lines of normal human fibroblasts we observed that 36-60% of the replicatively senescent cells had 4N DNA content. Only up to 5% of senescent cells had more than one nucleus ruling out the possibility that the 4N cell population were G1-arrested bi-nucleated cells. Furthermore, it is unlikely that the 4N cells are tetraploids, because actively dividing pre-senescent cultures lacked the 8N tetraploid G2 population. Collectively these results suggest that the 4N population consists of G2 arrested cells. The notion that a large fraction of senescent cell population is arrested in G2 is important for understanding the biology of replicative senescence. PMID:22745179

  6. Expansion of the Youngest Galactic Supernova Remnant G1.9+0.3

    CERN Document Server

    Carlton, A K; Reynolds, S P; Hwang, U; Petre, R; Green, D A; Krishnamurthy, K; Willett, R

    2011-01-01

    We present a measurement of the expansion and brightening of G1.9+0.3, the youngest Galactic supernova remnant, comparing Chandra X-ray images obtained in 2007 and 2009. A simple uniform expansion model describes the data well, giving an expansion rate of 0.642 +/- 0.049 % yr^-1, and a flux increase of 1.7 +/- 1.0 % yr^-1. Without deceleration, the remnant age would then be 156 +/- 11 yr, consistent with earlier results. Since deceleration must have occurred, this age is an upper limit; we estimate an age of about 110 yr, or an explosion date of about 1900. The flux increase is comparable to reported increases at radio wavelengths. G1.9+0.3 is the only Galactic supernova remnant increasing in flux, with implications for the physics of electron acceleration in shock waves

  7. An ATCA Observation of the Youngest Known Galactic SNR G1.9+0.3

    CERN Document Server

    De Horta, A Y; Crawford, E J; Stootman, F H; Pannuti, T G

    2008-01-01

    We present an analysis of a previously unpublished radio-continuum observation of SNR G1.9+0.3 which at an age of <=150 years is the youngest known in the Galaxy. The observations were made in 1993 using the Australia Telescope Compact Array (ATCA) at two 6-cm frequencies. We note two previously unseen blow-out structures in the north and south direcions. We estimate a flux density of 1.545Jy, an outer diameter of ~80" and confirm an expansion rate of ~0.65% per year between 1985 and 2008. No polarisation was detected in the radio emission from SNR G1.9+0.3 above the 1% level. We also present these previously unpublished results as a high resolution reference point from which to study the evolution of SNRs at times for which there is a gap in our knowledge.

  8. 26 CFR 1.904(g)-1T - Overall domestic loss and the overall domestic loss account (temporary).

    Science.gov (United States)

    2010-04-01

    ... loss account (temporary). 1.904(g)-1T Section 1.904(g)-1T Internal Revenue INTERNAL REVENUE SERVICE... United States § 1.904(g)-1T Overall domestic loss and the overall domestic loss account (temporary). (a... accounts for purposes of section 904(g). Section 1.904(g)-2T provides rules for recapturing the balance...

  9. 26 CFR 1.1402(g)-1 - Treatment of certain remuneration erroneously reported as net earnings from self-employment.

    Science.gov (United States)

    2010-04-01

    ... reported as net earnings from self-employment. 1.1402(g)-1 Section 1.1402(g)-1 Internal Revenue INTERNAL...-Employment Income § 1.1402(g)-1 Treatment of certain remuneration erroneously reported as net earnings from... request, and should indicate clearly that it is a request that, pursuant to section 1402(g) of the...

  10. Cell size at S phase initiation: an emergent property of the G1/S network.

    Directory of Open Access Journals (Sweden)

    Matteo Barberis

    2007-04-01

    Full Text Available The eukaryotic cell cycle is the repeated sequence of events that enable the division of a cell into two daughter cells. It is divided into four phases: G1, S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular interaction network, which involves the periodic synthesis and destruction of cyclins that bind and activate cyclin-dependent kinases that are present in nonlimiting amounts. Cyclin-dependent kinase inhibitors contribute to cell cycle control. Budding yeast is an established model organism for cell cycle studies, and several mathematical models have been proposed for its cell cycle. An area of major relevance in cell cycle control is the G1 to S transition. In any given growth condition, it is characterized by the requirement of a specific, critical cell size, PS, to enter S phase. The molecular basis of this control is still under discussion. The authors report a mathematical model of the G1 to S network that newly takes into account nucleo/cytoplasmic localization, the role of the cyclin-dependent kinase Sic1 in facilitating nuclear import of its cognate Cdk1-Clb5, Whi5 control, and carbon source regulation of Sic1 and Sic1-containing complexes. The model was implemented by a set of ordinary differential equations that describe the temporal change of the concentration of the involved proteins and protein complexes. The model was tested by simulation in several genetic and nutritional setups and was found to be neatly consistent with experimental data. To estimate PS, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins. Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S network that strongly depends on growth rate.

  11. Perturbative power Q^2-corrections to the structure function g(1)

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2006-01-01

    We show that regulating infrared divergencies generates power (\\sim 1/(Q^2)^k) corrections to the spin structure function g_1 at small x. We present the explicit series of such terms as well as the formulae for their resummation. These contributions are not included in the standard analysis of the experimental data. We argue that accounting for such terms can sizably change the impact of the other power corrections conventionally attributed to the higher twists.

  12. Kinematical analysis of 5-axis corner smoothing for transitions between linear (G1) blocks

    OpenAIRE

    Beudaert, Xavier; Lavernhe, Sylvain; Tournier, Christophe

    2012-01-01

    5-axis high speed machine tools are widely used in industry. The axis movements are generated by the Computer Numerical Controller (CNC) which has to transform the part program into a sequence of axis setpoints. Most of the time, the tool path is described with linear segments (G1) which lead to tangency discontinuities between blocks. With acceleration and jerk limitations, these discontinuities will induce a zero feedrate and thus surface marks and an increase in machining time. The aim of ...

  13. On the first G 1 stiff fluid spike solution in General Relativity

    Science.gov (United States)

    Coley, A. A.; Gregoris, D.; Lim, W. C.

    2016-11-01

    Using the Geroch transformation we obtain the first example of an exact stiff fluid spike solution to the Einstein field equations in a closed form exhibiting a spacelike G 1 group of symmetries (i.e., with a single isometry). This new solution is of Petrov type I and exhibits a spike crossing which persists to the past, which allows us to better understand spike crossings in the context of structure formation.

  14. NONUNIFORM EXPANSION OF THE YOUNGEST GALACTIC SUPERNOVA REMNANT G1.9+0.3

    Energy Technology Data Exchange (ETDEWEB)

    Borkowski, Kazimierz J.; Reynolds, Stephen P. [Department of Physics, North Carolina State University, Raleigh, NC 27695-8202 (United States); Green, David A. [Cavendish Laboratory, 19 J.J. Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Hwang, Una [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Petre, Robert [NASA/GSFC, Code 660, Greenbelt, MD 20771 (United States); Krishnamurthy, Kalyani [Department of Electrical and Computer Engineering, Duke University, Durham, NC 27708 (United States); Willett, Rebecca, E-mail: kborkow@unity.ncsu.edu [Department of Electrical and Computing Engineering, University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2014-08-01

    We report measurements of the X-ray expansion of the youngest Galactic supernova remnant, G1.9+0.3, using Chandra observations in 2007, 2009, and 2011. The measured rates strongly deviate from uniform expansion, decreasing radially by about 60% along the X-ray bright SE-NW axis from 0.84% ± 0.06% yr{sup –1} to 0.52% ± 0.03% yr{sup –1}. This corresponds to undecelerated ages of 120-190 yr, confirming the young age of G1.9+0.3 and implying a significant deceleration of the blast wave. The synchrotron-dominated X-ray emission brightens at a rate of 1.9% ± 0.4% yr{sup –1}. We identify bright outer and inner rims with the blast wave and reverse shock, respectively. Sharp density gradients in either the ejecta or ambient medium are required to produce the sudden deceleration of the reverse shock or the blast wave implied by the large spread in expansion ages. The blast wave could have been decelerated recently by an encounter with a modest density discontinuity in the ambient medium, such as may be found at a wind termination shock, requiring strong mass loss in the progenitor. Alternatively, the reverse shock might have encountered an order-of-magnitude density discontinuity within the ejecta, such as may be found in pulsating delayed-detonation Type Ia models. We demonstrate that the blast wave is much more decelerated than the reverse shock in these models for remnants at ages similar to G1.9+0.3. Similar effects may also be produced by dense shells possibly associated with high-velocity features in Type Ia spectra. Accounting for the asymmetry of G1.9+0.3 will require more realistic three-dimensional Type Ia models.

  15. Aircraft measurements of aerosol properties during GoAmazon - G1 and HALO inter-comparison

    Science.gov (United States)

    Mei, F.; Cecchini, M. A.; Wang, J.; Tomlinson, J. M.; Comstock, J. M.; Hubbe, J. M.; Pekour, M. S.; Machado, L.; Wendisch, M.; Longo, K.; Martin, S. T.; Schmid, B.; Weinzierl, B.; Krüger, M. L.; Zöger, M.

    2015-12-01

    Currently, the indirect effects of atmospheric aerosols remain the most uncertain components in forcing of climate change over the industrial period (IPCC, 2013). This large uncertainty is partially a result of our incomplete understanding of the ability of particles to form cloud droplets under atmospherically relevant supersaturations. One objective of the US Department of Energy (DOE) Green Ocean Amazon Project (GoAmazon2014/5) is to understand the influence of the emission from Manaus, a tropical megacity, on aerosol size, concentration, and chemical composition, and their impact on cloud condensation nuclei (CCN) spectrum. The GoAmazon2014/5 study was an international campaign with the collaboration efforts from US, Brazil and Germany. During the intensive operation period, in the dry season (Sep. 1st - Oct. 10th, 2014), aerosol concentration, size distributions, and CCN spectra, both under pristine conditions and inside the Manaus plume, were characterized in-situ from the DOE Gulfstream-1 (G-1) research aircraft and German HALO aircraft during 4 coordinated flights on Sep. 9th, Sep. 16th, Sep 21st and Oct. 1st, 2014. During those four flights, aerosol number concentrations and CCN concentrations at two supersaturations (0.25% and 0.5%) were measured by condensation particle counters (CPCs) and a DMT dual column CCN counter onboard both G-1 and HALO. Aerosol size distribution was also measured by a Fast Integrated Mobility Spectrometer (FIMS) aboard the G-1 and is compared with the size distribution from Ultra High Sensitivity Aerosol Spectrometer - Airborne (UHSAS-A, DMT), which were deployed both on the G-1 and the HALO. Good agreement between the aerosol properties measured from the two aircraft has been achieved. The vertical profiles of aerosol size distribution and CCN spectrum will be discussed.

  16. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Zheng, Lemin [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing 100191 (China); Zhou, Boda [The Department of Cardiology, Peking University Third Hospital, Beijing 100191 (China); Zhang, Wei; Lv, He [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Yuan, Yun, E-mail: yuanyun2002@sohu.com [Department of Neurology, Peking University First Hospital, Beijing 100034 (China)

    2014-03-28

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21.

  17. Optimized culture condition for enhancing lytic performance of waste activated sludge by Geobacillus sp. G1.

    Science.gov (United States)

    Yang, Chunxue; Zhou, Aijuan; Hou, Yanan; Zhang, Xu; Guo, Zechong; Wang, Aijie; Liu, Wenzong

    2014-01-01

    Hydrolysis is known as the rate-limiting step during waste activated sludge (WAS) digestion. The optimization of the culture conditions of Geobacillus sp. G1 for enhancing WAS hydrolysis was conducted in this study with uniform design and response surface methodology. Taking the lysis rate of Escherichia coli as the response, the Plackett-Burman design was used to screen the most important variables. Experimental results showed that the maximum predicted lysis rate of E. coli was 50.9% for 4 h treatment time with concentrations of skim milk, NaCl and NH4SO4 at 10.78, 4.36 and 11.28 g/L, respectively. The optimized dosage ratio of Geobacillus sp. G1 to WAS was 35%:65% (VG1:VWAS). Under this condition, soluble protein was increased to 695 mg chemical oxygen demand (COD)/L, which was 5.0 times higher than that obtained in the control (140 mg COD/L). The corresponding protease activity reached 1.1 Eu/mL. Scanning electron microscopy showed that abundant cells were apparently lysed with treatment of Geobacillus sp. G1.

  18. Modeling SNR G1.9+0.3 as a Supernova Inside a Planetary Nebula

    CERN Document Server

    Tsebrenko, Danny

    2014-01-01

    Using 3D numerical hydrodynamical simulations we show that a type Ia supernova (SN Ia) explosion inside a planetary nebula (PN) can explain the observed shape of the G1.9+0.3 supernova remnant (SNR), and its X-ray morphology. The SNR G1.9+0.3 morphology can be generally described as a sphere with two small and incomplete lobes protruding on opposite sides of the SNR, termed "ears", a structure resembling many elliptical PNe. Observations show the synchrotron X-ray emission to be much stronger inside the two ears than in the rest of the SNR. We numerically show that a spherical SN Ia explosion into a circumstellar matter (CSM) with the structure of an elliptical PN with ears can explain the X-ray properties of SNR G1.9+0.3. While the ejecta has already collided with the PN shell in most of the SNR and its forward shock has been slowed down, the ejecta is still advancing inside the ears. The fast forward shock inside the ears explains the stronger X-ray emission there. SN Ia inside PNe (SNIPs) seem to comprise ...

  19. The Youngest Galactic Supernova Remnant: G1.9+0.3

    CERN Document Server

    Reynolds, S P; Green, D A; Hwang, U; Harrus, I; Petre, R

    2008-01-01

    Our 50 ks Chandra observation of the small radio supernova remnant (SNR) G1.9+0.3 shows a complete shell structure with strong bilateral symmetry, about $100''$ in diameter. The radio morphology is also shell-like, but about 17% smaller, based on observations made in 1985. We attribute the size difference to expansion between 1985 and our Chandra observations of 2007. Expansion is confirmed in comparing radio images from 1985 and 1989. We deduce that G1.9+0.3 is of order 100 years old -- the youngest supernova remnant in the Galaxy. Based on a very high absorbing column density of $5.5 \\times 10^{22}$ cm$^{-2}$, we place G1.9+0.3 at the Galactic Center, at a distance of about 8.5 kpc, at which the mean remnant radius is about 2 pc, and the required expansion speed about $15,000$ km s$^{-1}$. The X-ray spectrum is featureless and well-described by the exponentially cut off synchrotron model {\\tt srcut}. With the radio flux at 1 GHz fixed at 0.9 Jy, we find a spectral index of 0.65 and a rolloff frequency of $1...

  20. Hpz1 modulates the G1-S transition in fission yeast.

    Directory of Open Access Journals (Sweden)

    Cathrine A Bøe

    Full Text Available Here we characterize a novel protein in S. pombe. It has a high degree of homology with the Zn-finger domain of the human Poly(ADP-ribose polymerase (PARP. Surprisingly, the gene for this protein is, in many fungi, fused with and in the same reading frame as that encoding Rad3, the homologue of the human ATR checkpoint protein. We name the protein Hpz1 (Homologue of PARP-type Zn-finger. Hpz1 does not possess PARP activity, but is important for resistance to ultraviolet light in the G1 phase and to treatment with hydroxyurea, a drug that arrests DNA replication forks in the S phase. However, we find no evidence of a checkpoint function of Hpz1. Furthermore, absence of Hpz1 results in an advancement of S-phase entry after a G1 arrest as well as earlier recovery from a hydroxyurea block. The hpz1 gene is expressed mainly in the G1 phase and Hpz1 is localized to the nucleus. We conclude that Hpz1 regulates the initiation of the S phase and may cooperate with Rad3 in this function.

  1. A Whi7-anchored loop controls the G1 Cdk-cyclin complex at start.

    Science.gov (United States)

    Yahya, Galal; Parisi, Eva; Flores, Alba; Gallego, Carme; Aldea, Martí

    2014-01-09

    Cells commit to a new cell cycle at Start by activation of the G1 Cdk-cyclin complex which, in turn, triggers a genome-wide transcriptional wave that executes the G1/S transition. In budding yeast, the Cdc28-Cln3 complex is regulated by an ER-retention mechanism that is important for proper cell size control. We have isolated small-cell-size CDC28 mutants showing impaired retention at the ER and premature accumulation of the Cln3 cyclin in the nucleus. The differential interactome of a quintuple Cdc28(wee) mutant pinpointed Whi7, a Whi5 paralog targeted by Cdc28 that associates to the ER in a phosphorylation-dependent manner. Our results demonstrate that the Cln3 cyclin and Whi7 act in a positive feedback loop to release the G1 Cdk-cyclin complex and trigger Start once a critical size has been reached, thus uncovering a key nonlinear mechanism at the earliest known events of cell-cycle entry.

  2. Les emissions de radio et de television en langue francaise pour l'enseignement du francais et pour la diffusion de la culture francaise (French Language Radio and Television Broadcasts for French Language Instruction and for the Diffusion of the French Culture).

    Science.gov (United States)

    Thureau, Josiane; Koesten, Leo

    1980-01-01

    Provides a listing of radio and television programs that teach French language and civilization, the result of two worldwide surveys, one conducted by "Le Francais dans le Monde," the other by the French Foreign Affairs Ministry. The programs are listed alphabetically by country and accompanied by a brief description. (MES)

  3. The origin of EL2 family evidenced by STM direct observations of individual photoquenching behaviors

    Science.gov (United States)

    Hida, Akira; Mera, Yutaka; Maeda, Koji

    2003-12-01

    Abundant point defects in low-temperature grown (LT-) GaAs, presumably As antisite defects, exhibit a photo-induced transformation at low temperatures with an excitation spectrum very close to that obtained for the macroscopic photoquenching effect of EL2 centers. Some of the defects do not exhibit the photo-induced transformation, disfavoring the hypothesis of variants of EL2-like centers differing in the atomic structures. The unquenchable EL2 centers are commonly located near the interface between the LT-GaAs epi-layer and the n-GaAs substrate. Separate macroscopic photoluminescence experiments showed that the photoquenching efficiency is strongly decreased by external compressive stress, which suggests that the absence of the phototransformation behavior in some centers was due to a local stress field induced by the lattice mismatch between the epi-layer and the substrate. This is shown by STM-electric field modulation spectroscopy that the epi-layer was locally strained to a different degree depending on the position from the interface. Therefore, we conclude that the EL2 variants are the result of the spatial variation of the internal stress environment that is felt by the EL2 centers in an identical atomic structure.

  4. The origin of EL2 family evidenced by STM direct observations of individual photoquenching behaviors

    Energy Technology Data Exchange (ETDEWEB)

    Hida, Akira; Mera, Yutaka; Maeda, Koji

    2003-12-31

    Abundant point defects in low-temperature grown (LT-) GaAs, presumably As antisite defects, exhibit a photo-induced transformation at low temperatures with an excitation spectrum very close to that obtained for the macroscopic photoquenching effect of EL2 centers. Some of the defects do not exhibit the photo-induced transformation, disfavoring the hypothesis of variants of EL2-like centers differing in the atomic structures. The unquenchable EL2 centers are commonly located near the interface between the LT-GaAs epi-layer and the n-GaAs substrate. Separate macroscopic photoluminescence experiments showed that the photoquenching efficiency is strongly decreased by external compressive stress, which suggests that the absence of the phototransformation behavior in some centers was due to a local stress field induced by the lattice mismatch between the epi-layer and the substrate. This is shown by STM-electric field modulation spectroscopy that the epi-layer was locally strained to a different degree depending on the position from the interface. Therefore, we conclude that the EL2 variants are the result of the spatial variation of the internal stress environment that is felt by the EL2 centers in an identical atomic structure.

  5. Monoclonal IgG1κ anti-glomerular basement membrane disease: a case report.

    Science.gov (United States)

    Coley, Shana M; Shirazian, Shayan; Radhakrishnan, Jai; D'Agati, Vivette D

    2015-02-01

    We report a case of anti-glomerular basement membrane (anti-GBM) nephritis with indolent course, monoclonal IgG1κ (immunoglobulin G, subclass 1, κ light chain) linear staining of the GBM, and multifocal GBM breaks but without crescents or detectable serum anti-GBM antibody in a patient followed over 9 years. Atypically, anti-GBM nephritis follows an indolent course. A very small fraction of patients with anti-GBM nephritis lack detectable circulating anti-GBM antibodies, and rare reports of monoclonal anti-GBM nephritis exist. We report what is to our knowledge the first case manifesting all 3 of these rare variations. Our patient initially presented with asymptomatic decreased kidney function following an upper respiratory tract infection. He was found to have microhematuria and subnephrotic proteinuria with mild diffuse endocapillary proliferative and exudative glomerulonephritis with linear IgG1κ staining of the GBM. He was treated with an induction regimen of intravenous cyclophosphamide and corticosteroids followed by maintenance monotherapy with mycophenolic acid. Nine years later, repeat kidney biopsy for worsening kidney function after an upper respiratory tract infection showed persistent monoclonal staining of the GBM and acute glomerulonephritis with increased chronicity, including a single fibrocellular crescent. Despite extensive clinical investigations spanning nearly a decade, no circulating anti-GBM antibody or monoclonal protein has been detected. In this case report, we explore the unique features of this monoclonal IgG1κ-associated anti-GBM nephritis. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. The G1 restriction point as critical regulator of neocortical neuronogenesis

    Science.gov (United States)

    Caviness, V. S. Jr; Takahashi, T.; Nowakowski, R. S.

    1999-01-01

    Neuronogenesis in the pseudostratified ventricular epithelium is the initial process in a succession of histogenetic events which give rise to the laminate neocortex. Here we review experimental findings in mouse which support the thesis that the restriction point of the G1 phase of the cell cycle is the critical point of regulation of the overall neuronogenetic process. The neuronogenetic interval in mouse spans 6 days. In the course of these 6 days the founder population and its progeny execute 11 cell cycles. With each successive cycle there is an increase in the fraction of postmitotic cells which leaves the cycle (the Q fraction) and also an increase in the length of the cell cycle due to an increase in the length of the G1 phase of the cycle. Q corresponds to the probability that postmitotic cells will exit the cycle at the restriction point of the G1 phase of the cell cycle. Q increases non-linearly, but the rate of change of Q with cycle (i.e., the first derivative) over the course of the neuronogenetic interval is a constant, k, which appears to be set principally by cell internal mechanisms which are species specific. Q also seems to be modulated, but at low amplitude, by a balance of mitogenic and antimitogenic influences acting from without the cell. We suggest that intracellular signal transduction systems control a general advance of Q during development and thereby determine the general developmental plan (i.e., cell number and laminar composition) of the neocortex and that external mitogens and anti-mitogens modulate this advance regionally and temporally and thereby produce regional modifications of the general plan.

  7. Modelling M/G/1 queueing systems with server vacations using stochastic Petri nets

    Directory of Open Access Journals (Sweden)

    K Ramanath

    2006-12-01

    Full Text Available The theory of non-Markovian stochastic Petri nets is employed in this paper to derive an alternative method for studying the steady state behaviour of the M/G/1 vacation queueing system with a limited service discipline. Three types of vacation schemes are considered, and sytems with both a finite population and those with an infinite population (but finite capacity are considered. Simple numerical examples are also provided to illustrate the functionality of the methods and some useful performance measures for the system are obtained.

  8. Asymmetric expansion of the youngest Galactic supernova remnant G1.9+0.3

    Science.gov (United States)

    Reynolds, Stephen P.

    2016-06-01

    The youngest Galactic supernova remnant (SNR) G1.9+0.3, produced by a (probable) Type Ia SN that exploded around CE 1900, is strongly asymmetric at radio wavelengths, with a single bright maximum in its shell, but exhibits a bilaterally symmetric morphology in X-rays. It has been difficult to understand the origin of these contrasting morphologies. We present the results of expansion measurements of G1.9+0.3 that illuminate the origin of the radio asymmetry. These measurements are based on a comparison of our 2015 400-ks Chandra observation with earlier Chandra observations, including a 1-Ms observation in 2011. The mean expansion rate from 2011 to 2015 is 0.58% per yr, in agreement with previous measurements. We also confirm that the expansion decreases radially away from the remnant's center along the major E-W axis, from 0.77% per yr to 0.53% per yr. Large variations in expansion are also present along the minor N-S axis, but expansion there is strongly asymmetric and varies on small spatial scales. We use the “Demons” method to study the complex motions within G1.9+0.3. This method provides a nonparametric way for measuring these motions globally. We find motions varying by a factor of 5, from 0.09" to 0.44" per year. The slowest shocks are in the north, at the outer boundary of the bright radio emission, with speeds there as low as 3,600 km/s (for an assumed distance of 8.5 kpc), much less than the average shock speed of 12,000 km/s. Such strong deceleration of the northern blast wave most likely arises from the collision of SN ejecta with a much denser than average ambient medium there. The presence of this asymmetric ambient medium naturally explains the radio asymmetry. The SN ejecta have also been strongly decelerated in the N, but they expand faster than the blast wave. In several locations, significant morphological changes and strongly nonradial motions are apparent. The spatially-integrated X-ray flux continues to increase with time. As with Kepler

  9. Properties of Multi-Stage M/G/1/K Queues with Series Arrangement

    Directory of Open Access Journals (Sweden)

    Hernández-González Salvador

    2015-07-01

    Full Text Available We propose a modification to the Buzacott & Shantikumar (1993 method to evaluate the properties of M/G/1/K queues with series arrangement. We made several tests and compared with simulation to validate the results. We observed that, with the proposed modification, the method has an acceptable level of exactitude. It can be considered an alternative calculation to other methods in the literature. The fact that this method requires less computational effort, can be useful to practitioners and managers that require tools to analyze the performance of systems in production and services areas.

  10. SOME NEW RESULTS ON WAITING TIME AND BUSY TIME IN M/G/1 QUEUE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper considers an M/G/1 queue with Poisson rate λ > 0 and servicetime distribution G(t) which is supposed to have finite mean 1/μ. The following questions are first studied: (a) The closed bounds of the probability that waiting time is more than a fixed value; (b)The total busy time of the server, which including the distribution,probability that are more than a fixed value during a given time interval (0, t], and the expected value. Some new and important results are obtained by theories of the classes of life distributions and renewal process.

  11. Analysis of Repairable Geo/G/1 Queues with Negative Customers

    Directory of Open Access Journals (Sweden)

    Doo Ho Lee

    2014-01-01

    Full Text Available We consider discrete-time Geo/G/1 queues with negative customers and a repairable server. The server is subject to failure due to a negative customer arrival. As soon as a negative customer arrives at a system, the server fails and one positive (ordinary customer is forced to leave. At a failure instant, the server is turned off and the repair process immediately begins. We construct the mathematical model and present the probability generating functions of the system size distribution and the FCFS sojourn time distribution. Finally, some numerical examples are given to show the influence of negative customer arrival on the performance measures of the system.

  12. On the M/G/1 queueing system with multiclass customers and fixed feedback

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qi-zhi

    2008-01-01

    The M/G/1 queueing system with multiclass customer arrivals, fixed feedback, and first come first served policy is considered, where different classes of customers have different arrival rates, service-time distributions, and feedback numbers. The joint probability generation function of queue size of each class and the Laplace-Stieltjes transform of the total sojourn time of a customer in each class are presented, which extended the results obtained by Choi B D. The mean queue size of each class and mean total sojourn time of a customer in each class are obtained with this result. The results can be used in computer and communication networks for their performance analysis.

  13. Reservicing some customers in M/G/1 queues under three disciplines

    Directory of Open Access Journals (Sweden)

    M. R. Salehi-Rad

    2004-01-01

    Full Text Available Consider an M/G/1 production line in which a production item is failed with some probability and is then repaired. We consider three repair disciplines depending on whether the failed item is repaired immediately or first stockpiled and repaired after all customers in the main queue are served or the stockpile reaches a specified threshold. For each discipline, we find the probability generating function (p.g.f. of the steady-state size of the system at the moment of departure of the customer in the main queue, the mean busy period, and the probability of the idle period.

  14. Nonuniform Expansion of the Youngest Galactic Supernova Remnant G1.9+0.3

    Science.gov (United States)

    Reynolds, Stephen P.; Borkowski, Kazimierz J.; Green, David; Hwang, Una; Petre, Robert

    2014-08-01

    G1.9+0.3 is the youngest known Galactic supernova remnant (SNR), about 100 yr old from global expansion measurements, and most likely the result of an asymmetric Type Ia supernova explosion. We smoothed a Chandra image from a 1 Ms observation in 2011 and fit the resulting model to unsmoothed images from 2007 and 2009, allowing for expansion and image shifts. The measured expansion rates strongly deviate from uniform expansion, increasing inward by about 60% along the X-ray bright SE-NW axis, from 0.52% +- 0.03% per yr to 0.84% +- 0.06% per yr. This corresponds to undecelerated ages of 120 - 190 yr, confirming the young age of G1.9 +0.3, and implying a significant (deceleration parameter m < 0.6) deceleration of the blast wave. The spatially-integrated X-ray flux, strongly dominated by synchrotron emission, increases at a rate of 1.9% +- 0.7% per year, in agreement with previous measurements. G1.9+0.3 is the only Galactic SNR brightening at X-ray and radio wavelengths. We identify the inner rims with the reverse shock and more slowly-expanding rims farther out with the blast wave. The large spread in expansion ages between the reverse shock and the blast wave requires abrupt density gradients in either the ejecta or the ambient medium, to suddenly decelerate the reverse shock or the blast wave. The blast wave could have been decelerated recently by an encounter with a modest (factor of several) density discontinuity in the ambient medium, such as found at a wind termination shock, implying a strong presupernova wind from the progenitor system. Alternatively, the reverse shock might have encountered a larger (factor of 10 or more) density discontinuity within the SN ejecta, such as found in pulsating delayed-detonation Type Ia SN models. Through 1D hydrodynamical simulations, we demonstrate that the blast wave is much more decelerated than the reverse shock in these models for remnants at ages similar to G1.9+0.3. The presence of strong density gradients in the outer

  15. Modeling and Optimization of M/G/1-Type Queueing Networks: An Efficient Sensitivity Analysis Approach

    Directory of Open Access Journals (Sweden)

    Liang Tang

    2010-01-01

    Full Text Available A mathematical model for M/G/1-type queueing networks with multiple user applications and limited resources is established. The goal is to develop a dynamic distributed algorithm for this model, which supports all data traffic as efficiently as possible and makes optimally fair decisions about how to minimize the network performance cost. An online policy gradient optimization algorithm based on a single sample path is provided to avoid suffering from a “curse of dimensionality”. The asymptotic convergence properties of this algorithm are proved. Numerical examples provide valuable insights for bridging mathematical theory with engineering practice.

  16. Post-translational Regulation of Cas9 during G1 Enhances Homology-Directed Repair

    Directory of Open Access Journals (Sweden)

    Tony Gutschner

    2016-02-01

    Full Text Available CRISPR/Cas9 induces DNA double-strand breaks that are repaired by cell-autonomous repair pathways, namely, non-homologous end-joining (NHEJ, or homology-directed repair (HDR. While HDR is absent in G1, NHEJ is active throughout the cell cycle and, thus, is largely favored over HDR. We devised a strategy to increase HDR by directly synchronizing the expression of Cas9 with cell-cycle progression. Fusion of Cas9 to the N-terminal region of human Geminin converted this gene-editing protein into a substrate for the E3 ubiquitin ligase complex APC/Cdh1, resulting in a cell-cycle-tailored expression with low levels in G1 but high expression in S/G2/M. Importantly, Cas9-hGem(1/110 increased the rate of HDR by up to 87% compared to wild-type Cas9. Future developments may enable high-resolution expression of genome engineering proteins, which might increase HDR rates further, and may contribute to a better understanding of DNA repair pathways due to spatiotemporal control of DNA damage induction.

  17. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

    Directory of Open Access Journals (Sweden)

    Wei-chuan Mo

    Full Text Available Organisms have been exposed to the geomagnetic field (GMF throughout evolutionary history. Exposure to the hypomagnetic field (HMF by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF.

  18. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

    Science.gov (United States)

    Mo, Wei-chuan; Zhang, Zi-jian; Liu, Ying; Bartlett, Perry F; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF.

  19. Involvement of ATM/ATR-p38 MAPK cascade in MNNG induced G1-S arrest

    Institute of Scientific and Technical Information of China (English)

    Ke-Qing Zhu; Suo-Jiang Zhang

    2003-01-01

    AIM: To understand the effect of low concentration of Nmethyl-N′-nitro-nitrosoguanidine (MNNG), which is a widely distributed environmental mutagen and carcinogen especially for human gastric cancer, on DNA damage and to study its possible pathway in regulating cell cycle arrest.METHODS: The DNA damage effect was measured by Comet assay. A specific phospho-(Ser/Thr) ATM/ATR substrate antibody was used to detect the damage sensor by Western blot. p38 kinase activity was measured by direct kinase assay,and immunoprecipitation for the possible connection between ATM/ATR and p38 MAPK. Flow cytometry analysis and p38MAPK specific inhibitor SB203580 were combined to detect the possible cell cycle arrest by p38 MAPK.RESULTS: With the same low concentration MNNG exposure (0.2μM 2.5 h), Comet assays indicated that strand breaks accumulated, Western blot and kinase assay showed ATM/ATR and p38 kinase activated, immunoprecipitation showed phospho-ATM/ATR substrate antibody combined with both p38 MAPK antibody and phospho-p38 MAPK antibody, p38MAPK pathway was involved in the G1-S arrest.CONCLUSION: Activation of ATM/ATR by MNNG induced DNA damage leads to activation of p38 MAPK, which involves in the G1 checkpoint in mammalian cells.

  20. Engineering upper hinge improves stability and effector function of a human IgG1.

    Science.gov (United States)

    Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf

    2012-02-17

    Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys(231) directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His(229)-mediated hinge cleavage. On the other hand, the substitution of His(229) with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2-3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed.

  1. Nonuniform Expansion of the Youngest Galactic Supernova Remnant G1.9+0.3

    CERN Document Server

    Borkowski, K J; Green, D A; Hwang, U; Petre, R; Krishnamurthy, K; Willett, R

    2014-01-01

    We report measurements of X-ray expansion of the youngest Galactic supernova remnant (SNR), G1.9+0.3, using Chandra observations in 2007, 2009, and 2011. The measured rates strongly deviate from uniform expansion, decreasing radially by about 60% along the X-ray bright SE-NW axis from 0."84% +/- 0."06% per yr to 0."52% +/- 0."03% per yr. This corresponds to undecelerated ages of 120-190 yr, confirming the young age of G1.9+0.3, and implying a significant deceleration of the blast wave. The spatially-integrated dominantly synchrotron X-ray flux increases at 1.9% +/- 0.4% per yr. We identify the outer and inner rims with the blast wave and reverse shock, respectively. Sudden large density gradients in either ejecta or ambient medium are required to produce the sudden deceleration of the reverse shock or the blast wave implied by the large spread in expansion ages. The blast wave could have been decelerated recently by an encounter with a modest density discontinuity in the ambient medium, such as found at a win...

  2. Permanent draft genome sequence of the gliding predator Saprospira grandis strain Sa g1 (= HR1)

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Chertkov, Olga [Los Alamos National Laboratory (LANL); Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Glavina Del Rio, Tijana [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Tapia, Roxanne [Los Alamos National Laboratory (LANL); Bruce, David [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Huntemann, Marcel [U.S. Department of Energy, Joint Genome Institute; Liolios, Konstantinos [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Palaniappan, Krishna [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Brambilla, Evelyne-Marie [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Rohde, Manfred [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Spring, Stefan [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Goker, Markus [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Bristow, James [U.S. Department of Energy, Joint Genome Institute; Eisen, Jonathan [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Hugenholtz, Philip [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute

    2012-01-01

    Saprospira grandis Gross et al. 1911 is a member of the Saprospiraceae, a family in the class 'Sphingobacteria' that remains poorly characterized at the genomic level. The species is known for preying on other marine bacteria via 'ixotrophy'. S. grandis strain Sa g1 was isolated from decaying crab carapace in France and was selected for genome sequencing because of its isolated location in the tree of life. Only one type strain genome has been published so far from the Saprospiraceae, while the sequence of strain Sa g1 represents the second genome to be published from a non-type strain of S. grandis. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 4,495,250 bp long Improved-High-Quality draft of the genome with its 3,536 protein-coding and 62 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

  3. Berberine inhibits growth and induces G1 arrest and apoptosis in human cholangiocarcinoma QBC939 cells.

    Science.gov (United States)

    He, Wei; Wang, Bin; Zhuang, Yun; Shao, Dong; Sun, Kewen; Chen, Jianping

    2012-01-01

    The chemotherapeutic approach using non-toxic natural products may be one of the strategies for the management of the cholangiocarcinoma. Here we report that in vitro treatment of human cholangiocarcinoma QBC939 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability and induced cell death in a dose-dependent manner, which was associated with an increase in G1 arrest. Our western blot analysis showed that berberine-induced G1 cell cycle arrest was mediated through the increased expression of cyclin-dependent kinase inhibitors (Cdki) proteins (Cip1/p21 and Kip1/p27); a simultaneous decrease in Cdk2 and Cdk4 and cyclins D1, and reduced activity of the Cyclins-Cdk complex. In additional studies, treatment of QBC939 cells with different concentrations (10, 40, 80 μM) of berberine for 48 h resulted in a significant dose-dependent increase in apoptosis compared to the non-berberine-treated control, which was associated with an increased expression of pro-apoptotic protein Bax and decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Together, this study for the first time identified berberine as a chemotherapeutic agent against human cholangiocarcinoma cells QBC939 cells in vitro. Further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of cholangiocarcinoma.

  4. Mutational epitope analysis and cross-reactivity of two isoforms of Api g 1, the major celery allergen.

    Science.gov (United States)

    Wangorsch, Andrea; Ballmer-Weber, Barbara K; Rösch, Paul; Holzhauser, Thomas; Vieths, Stefan

    2007-04-01

    For better understanding the cross-reactivity between the major birch pollen and celery allergens, Bet v 1 and Api g 1, respectively, putative epitope areas and structurally important positions for IgE-binding of the isoforms Api g 1.01 and Api g 1.02 were point mutated. The IgE binding capacities were measured in ELISA, the IgE cross-reactivity between the isoforms, mutants and Bet v 1 investigated by ELISA-inhibition experiments with serum pools from patients with confirmed celery allergy (DBPCFC). Api g 1.01 displayed a clearly higher frequency and capacity of IgE binding than Api g 1.02. In Api g 1.01, substitution of lysine against glutamic acid at amino acid position 44, a key residue of the Bet v 1 "P-loop", increased the IgE-binding properties. Structural instability due to proline insertion at position 111/112 resulted in loss of IgE binding of Api g 1.01, but not of Api g 1.02. Between Api g 1.01 and Api g 1.02 only partial cross-reactivity was seen. The data suggest that the IgE epitopes of the two isoforms are distinct and that in contrast to Api g 1.01, the "P-loop" region plays an important role for IgE binding of celery allergic subjects to Api g 1.02. Understanding and investigation of the molecular mechanisms in celery allergy is an important step to generate hypoallergenic proteins for safe and efficacious immunotherapy of food allergy.

  5. Dectin-1 agonist selectively induces IgG1 class switching by LPS-activated mouse B cells.

    Science.gov (United States)

    Seo, Beom-Seok; Park, Ha-Yan; Yoon, Hee-Kyung; Yoo, Yung-Choon; Lee, Junglim; Park, Seok-Rae

    2016-10-01

    Heat-killed Saccharomyces cerevisiae (HKSC) is an agonist for Dectin-1, a major fungal cell wall β-glucan receptor. We previously reported that HKSC selectively enhances IgG1 production by LPS-activated mouse B cells. To determine if this IgG1 selectivity is caused by selective IgG1 class switching, we performed RT-PCRs for measuring germline transcripts (GLTs), flow cytometric analyses for detecting Ig-expressing cells, and ELISPOT assays for measuring the number of Ig-secreting cells in HKSC/LPS-stimulated mouse B cell cultures. HKSC selectively enhanced expression of GLTγ1, the number of IgG1-expressing cells, and the number of IgG1-secreting B cells in the presence of LPS stimulation. In addition, HKSC induced the expression of CD69, an activation marker for B lymphocytes, and the expression of surface Dectin-1. Two Dectin-1 antagonists, laminarin and a neutralizing Dectin-1 antibody, selectively diminished HKSC-reinforced IgG1 production by LPS-stimulated B cells. Furthermore, depleted zymosan (dzn), a Dectin-1 agonist with increased selectivity, also selectively enhanced GLTγ1 transcription. The Dectin-1 antagonists blocked dzn-induced IgG1 production by LPS-activated B cells. Collectively, these results suggest that Dectin-1 agonists selectively induce IgG1 class switching by direct stimulation of Dectin-1 on LPS-activated B cells resulting in selective production of IgG1.

  6. Human anti-rhesus D IgG1 antibody produced in transgenic plants

    DEFF Research Database (Denmark)

    Bouquin, Thomas; Thomsen, Mads; Nielsen, Leif Kofoed

    2002-01-01

    antigen, which is responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD extracted from plants specifically reacted with RhD+ cells in antiglobulin technique, and elicited a respiratory burst in human peripheral blood mononuclear cells. Plant-derived antibody had equivalent......Transgenic plants represent an alternative to cell culture systems for producing cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the functional properties of a 'plantibody', we generated transgenic Arabidopsis plants expressing full-length human IgG1 against the Rhesus D...... properties to CHO cell-produced anti-RhD antibody, indicating its potential usefulness in diagnostic and therapeutic programs....

  7. Fluid Approximation and Its Convergence Rate for GI/G/1 Queue with Vacations

    Institute of Scientific and Technical Information of China (English)

    Yong-jiang Guo

    2011-01-01

    A GI/G/1 queue with vacations is considered in this paper. We develop an approximating technique on max function of independent and identically distributed (i.i.d.) random variables, that is max{ηi, 1 ≤ i ≤ n}.The approximating technique is used to obtain the fluid approximation for the queue length, workload and busy time processes. Furthermore, under uniform topology, if the scaled arrival process and the scaled service process converge to the corresponding fluid processes with an exponential rate, we prove by the approximating technique that the scaled processes characterizing the queue converge to the corresponding fluid limits with the exponential rate only for large N. Here the scaled processes include the queue length process, workload process and busy time process.

  8. The Performance Analysis of Web Services Composition Based on Queueing Network with G/G/1-FCFS、M/G/1-PS and M/G/∞ Nodes%基于G/G/1-FCFS、M/G/1-PS和M/G/∞排队网络的Web服务组合性能分析

    Institute of Scientific and Technical Information of China (English)

    汪浩; 黄明和; 龙浩

    2013-01-01

    影响Web服务组合性能的因素分为“内因”和“外因”,内因具体表现为:BPEL流程的结构、BPEL流程中变量取值的概率分布;外因具体表现为:Web服务器的软硬件处理能力、Web服务器的负载(包括“正对其进行性能分析的Web服务组合”对Web服务器形成的负载和“其它Web服务组合”对Web服务器形成的负载)以及Web服务器的调度策略.目前广泛采用的广义Petri网、排队Petri网、Markov过程和随机进程代数等模型不能同时综合建模上述各种“内因”和“外因”对Web服务组合性能的影响,导致不能全面分析Web服务组合在互联网环境下的性能.文中建立了一组把影响Web服务组合性能的各种“内因”和“外因”映射到具有G/G/1-FCFS、M/G/1-PS和M/G/∞排队节点类型的排队网络的映射规则,给出了一组建立在排队网络基础上的Web服务组合性能分析指标体系及其计算公式,并以这些性能分析指标体系为基础,分析了Web服务组合的性能及其变化规律,以便在Web服务组合部署前,分析预测Web服务组合在互联网环境下的性能.%Elements affecting the performance of Web services composition consist of internal and external factors. The internal factors include the structure of the BPEL process, the probability distribution of the variables of BPEL process. The external factors include the processing capabilities of hardware and software of Web servers, the load of Web servers, and the scheduling policy of Web servers. The generalized Petri nets, queuing Petri nets, Markov processes and stochastic process algebra model can not comprehensively establish the performance model of Web services composition employing these various internal and external factors at the same time, resulted in lack of obtaining the actual performance of Web services composition in the Internet environment. In this paper, a set of mapping rules is established to transform the

  9. Echinococcus canadensis (G7) and Echinococcus granulosus sensu stricto (G1) in swine of southern Brazil.

    Science.gov (United States)

    Monteiro, D U; Botton, S A; Tonin, A A; Azevedo, M I; Graichen, D A S; Noal, C B; de la Rue, M L

    2014-05-28

    The cystic echinococcosis (CE) is an important zoonotic disease caused by the parasite Echinococcus spp. In Brazil, this parasite is present in Rio Grande do Sul (RS) state, border with Argentina and Uruguay, causing several damages to human and animal health. This study aimed to identify Echinococcus spp. in hydatid cysts of swine and evaluate the similarity of the genotypes through the phylogenetic analysis. A total of 3,101,992 swine were slaughtered in the central/northern region of RS/Brazil, during 2008-2012. Five isolates were characterized as hydatid cyst by molecular analysis, based on the mitochondrial gene cytochrome c oxidase subunit I (cox-I). The genotypes E. granulosus sensu stricto (G1) (n=2) and E. canadensis (G7) (n=3) were identified in the hydatid cysts. The swine represents a potential intermediate host for different genotypes of Echinococcus spp., besides it can contribute to the perpetuation of the parasite's life cycle in rural areas.

  10. Optimization on bicriterion policies for M/G/1 system with second optional service

    Institute of Scientific and Technical Information of China (English)

    Jau-chuan KE; Yunn-kuang CHU

    2008-01-01

    We compare the optimal operating cost of the two bicriterion policies, p,T and p,N, for an M/G/1 queueing system with second optional service, in which the length of the vacation period is randomly controlled either by the number of arrivals during the idle period or by a timer. After all the customers are served in the queue exhaustively, the server immediately takes a vacation and may operate p, T policy or p,N policy. For the two bicriterion policies, the total average cost function per unit time is developed to search the optimal stationary operating policies at a minimum cost. Based upon the optimal cost the explicit forms for joint optimum threshold values of (p,T) and (p,N) are obtained.

  11. 惊艳逆袭索尼PRS-T1/PRS—G1

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    索尼于近日正式发售最新的电子书阅读器PRS-T1和PRS—G1。最大的亮点便是其独有的Cleat Touch Infrared红外触屏技术,可以在T1的电子墨水珍珠屏上实现多点触摸功能。随机还附赠一支触控笔。方便用户在阅读时进行批注。得益于索尼优秀的工业设计能力,T1的厚度保持在89mm,重量也仅为168g,是目前市面上最轻薄的6英寸电子阅读器。

  12. On a BMAP/G/1 G-queue with Setup Times andMultiple Vacations

    Institute of Scientific and Technical Information of China (English)

    Yi PENG; Xiang-qun YANG

    2011-01-01

    In this paper,we consider a BMAP/G/1 G-queue with setup times and multiple vacations.Arrivals of positive customers and negative customers follow a batch Markovian arrival process (BMAP) and Markovian arrival process (MAP) respectively.The arrival of a negative customer removes all the customers in the system when the server is working.The server leaves for a vacation as soon as the system empties and is allowed to take repeated (multiple) vacations.By using the supplementary variables method and the censoring technique,we obtain the queue length distributions.We also obtain the mean of the busy period based on the renewal theory.

  13. Reliability analysis of M/G/1 queues with general retrial times and server breakdowns

    Institute of Scientific and Technical Information of China (English)

    WANG Jinting

    2006-01-01

    This paper concerns the reliability issues as well as queueing analysis of M/G/1 retrial queues with general retrial times and server subject to breakdowns and repairs. We assume that the server is unreliable and customers who find the server busy or down are queued in the retrial orbit in accordance with a first-come-first-served discipline. Only the customer at the head of the orbit queue is allowed for access to the server. The necessary and sufficient condition for the system to be stable is given. Using a supplementary variable method, we obtain the Laplace-Stieltjes transform of the reliability function of the server and a steady state solution for both queueing and reliability measures of interest. Some main reliability indexes, such as the availability, failure frequency, and the reliability function of the server, are obtained.

  14. SUBGEOMETRIC RATES OF CONVERGENCE OF THE GI/G/1 QUEUEING SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Li Xiaohua; Hou Zhenting

    2012-01-01

    The article deals with the waiting time process of the GI/G/1 queueing system.We shall give that the rate of convergence to the stationary distribution and the decay of the stationary tail only depend on the tail of the service distribution,but not on the interarrival distribution.We shall also give explicit criteria for the rate of convergence and decay of stationary tail for three specific types of subgeometric cases (Case 1:the rate function r(n) =exp(sn1/1+α),α > 0,s > 0; Case 2:polynomial rate function r(n) =nα,α > 0; Case 3:logarithmic rate function r(n) =logα n,α > 0).

  15. TRANSIENT SOLUTION FOR QUEUE-LENGTH DISTRIBUTION OF Geometry/G/1 QUEUEING MODEL

    Institute of Scientific and Technical Information of China (English)

    Luo Chuanyi; Tang Yinghui; Liu Renbin

    2007-01-01

    In this paper, the Geometry/G/1 queueing model with inter-arrival times generated by a geometric(parameter p) distribution according to a late arrival system with delayed access and service times independently distributed with distribution {gj}, j ≥ 1 is studied. By a simple method (techniques of probability decomposition, renewal process theory) that is different from the techniques used by Hunter(1983), the transient property of the queue with initial state i(i ≥ 0) is discussed. The recursion expression for u -transform of transient queue-length distribution at any time point n+ is obtained, and the recursion expression of the limiting queue length distribution is also obtained.

  16. Explicit Convergence Rates of the Embedded M/G/1 Queue

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan LIU; Zhen Ting HOU

    2007-01-01

    This paper investigates the explicit convergence rates to the stationary distribution π of the embedded M/G/1 queue; specifically, for suitable rate functions r(n) which may be polynomial with r(n)=nl,l>0 or geometric with r(n) =αn,α> 1 and "moments" f≥1, we find the conditions under which ∑∞n=0r(n)||Pn(i,·)-π(·)||f≤M(i) for all i∈E. For the polynomial case, the explicit bounds on M(i) are given in terms of both "drift functions" and behavior of the first hitting time on the state 0; and for the geometric case, the largest geometric convergence rate α* is obtained.

  17. Birth of Archaeal Cells: Molecular Phylogenetic Analyses of G1P Dehydrogenase, G3P Dehydrogenases, and Glycerol Kinase Suggest Derived Features of Archaeal Membranes Having G1P Polar Lipids

    Science.gov (United States)

    2016-01-01

    Bacteria and Eukarya have cell membranes with sn-glycerol-3-phosphate (G3P), whereas archaeal membranes contain sn-glycerol-1-phosphate (G1P). Determining the time at which cells with either G3P-lipid membranes or G1P-lipid membranes appeared is important for understanding the early evolution of terrestrial life. To clarify this issue, we reconstructed molecular phylogenetic trees of G1PDH (G1P dehydrogenase; EgsA/AraM) which is responsible for G1P synthesis and G3PDHs (G3P dehydrogenase; GpsA and GlpA/GlpD) and glycerol kinase (GlpK) which is responsible for G3P synthesis. Together with the distribution of these protein-encoding genes among archaeal and bacterial groups, our phylogenetic analyses suggested that GlpA/GlpD in the Commonote (the last universal common ancestor of all extant life with a cellular form, Commonote commonote) acquired EgsA (G1PDH) from the archaeal common ancestor (Commonote archaea) and acquired GpsA and GlpK from a bacterial common ancestor (Commonote bacteria). In our scenario based on this study, the Commonote probably possessed a G3P-lipid membrane synthesized enzymatically, after which the archaeal lineage acquired G1PDH followed by the replacement of a G3P-lipid membrane with a G1P-lipid membrane.

  18. Preliminary stratigraphic and petrologic characterization of core samples from USW-G1, Yucca Mountain, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Waters, A.C.; Carroll, P.R. (eds.)

    1981-11-01

    Tuffs of the Nevada Test Site are currently under investigation to determine their potential for long-term storage of radioactive waste. As part of this program, hole USW-G1 was drilled to a depth of 6000 ft below the surface, in the central part of the Yucca Mountain area, Nevada Test Site, Nevada. Petrographic study of the USW-G1 core is presented in this report and shows the tuffs (which generally were variably welded ash flows) are partly recrystallized to a variety of secondary minerals. The important alteration products are zeolites (heulandite, clinoptilolite, mordenite and analcime), smectite clays with minor interstratified illite, albite, micas, potassium feldspar, and various forms of silica. Iijima`s zeolite zones I through IV of burial metamorphism can be recognized in the core. Zeolites are first observed at about the 1300-ft depth, and the high-temperature boundary of zeolite stability in this core occurs at about 4350 ft. Analcime persists, either metastably or as a retrograde mineral, deeper in the core. The oxidation state of Fe-Ti oxide minerals, through most of the core, increases as the degree of welding decreases, but towards the bottom of the hole, reducing conditions generally prevail. Four stratigraphic units transected by the core may be potentially favorable sites for a waste repository. These four units, in order of increasing depth in the core, are (1) the lower cooling unit of the Topopah Spring Member, (2) cooling unit II of the Bullfrog Member, (3) the upper part of the Tram tuff, and (4) the Lithic-rich tuff.

  19. Cost-effectiveness of antiviral therapy in chronic hepatitis C (G1

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2015-01-01

    Full Text Available Updated HCV clinical guidelines placed direct acting agents (DAAs as the preferable the first line regimens.The objective of the study was PE assessment of HCV therapy among G1 naïve patientsMethods: Analysis is based on data of randomized clinical trials and average price of HCV medicines from state auctions placed in state procurement system in 2015.Results: PTV/OBV/DSV/r cost is 30,5% lower vs PegIFN/RBV/SMV. In comparison with PegIFN/RBV/BCV combination PTV/OBV/DSV/r is cost saving by 10,6% at patients without cirrhosis and 36,2% at patients with cirrhosis. DCV/ASV combination is chipper PTV/OBV/DSV/r and it would be used for G1 naïve patient (cost saving is 9,4-10,4%. DCV/ASV and PTV/OBV/DSV/r SVR12 costs are comparable and significantly lower than PegIFN-based regimen: PegIFN/RBV/SMV and PegIFN/RBV/BCV. 4 weeks stop rules due to therapy inefficiency for PegIFN/RBV/SMV regimen could cut cost by 12,6% и 28,0% among patients without and cirrhosis accordingly. By way PTV/OBV/DSV/r is the most cost effective versus PegIFN/RBV/SMV. PTV/OBV/DSV/r as the first line therapy for PegIFN experienced patients provides budget saving 118,2 thousand RUB or 12,2% of budget.Conclusion: Right now PTV/OBV/DSV/r regimen is the most cost effective the first line therapy for naïve patients.

  20. Supernova Ejecta in the Youngest Galactic Supernova Remnant G1.9+0.3

    Science.gov (United States)

    Borkowski, Kazimierz J.; Reynolds, Stephen P.; Hwang, Una; Green, David A.; Petre, Robert; Krishnamurthy, Kalyani; Willett, Rebecca

    2013-01-01

    G1.9+0.3 is the youngest known Galactic supernova remnant (SNR), with an estimated supernova (SN) explosion date of approximately 1900, and most likely located near the Galactic Center. Only the outermost ejecta layers with free-expansion velocities (is) approximately greater than 18,000 km s-1 have been shocked so far in this dynamically young, likely Type Ia SNR. A long (980 ks) Chandra observation in 2011 allowed spatially-resolved spectroscopy of heavy-element ejecta. We denoised Chandra data with the spatio-spectral method of Krishnamurthy et al., and used a wavelet based technique to spatially localize thermal emission produced by intermediate-mass elements (IMEs: Si and S) and iron. The spatial distribution of both IMEs and Fe is extremely asymmetric, with the strongest ejecta emission in the northern rim. Fe K alpha emission is particularly prominent there, and fits with thermal models indicate strongly oversolar Fe abundances. In a localized, outlying region in the northern rim, IMEs are less abundant than Fe, indicating that undiluted Fe-group elements (including 56Ni) with velocities greater than 18,000 km s-1 were ejected by this SN. But in the inner west rim, we find Si- and S-rich ejecta without any traces of Fe, so high-velocity products of O-burning were also ejected. G1.9+0.3 appears similar to energetic Type Ia SNe such as SN 2010jn where iron-group elements at such high free-expansion velocities have been recently detected. The pronounced asymmetry in the ejecta distribution and abundance inhomogeneities are best explained by a strongly asymmetric SN explosion, similar to those produced in some recent 3D delayed-detonation Type Ia models.

  1. Retinoic acid receptor agonists regulate expression of ATP-binding cassette transporter G1 in macrophages.

    Science.gov (United States)

    Ayaori, Makoto; Yakushiji, Emi; Ogura, Masatsune; Nakaya, Kazuhiro; Hisada, Tetsuya; Uto-Kondo, Harumi; Takiguchi, Shunichi; Terao, Yoshio; Sasaki, Makoto; Komatsu, Tomohiro; Iizuka, Maki; Yogo, Makiko; Uehara, Yoshinari; Kagechika, Hiroyuki; Nakanishi, Tsuyoshi; Ikewaki, Katsunori

    2012-04-01

    ABC transporter G1 (ABCG1) plays a pivotal role in HDL-mediated cholesterol efflux and atherogenesis. We investigated whether, and how, retinoic acid receptors (RARs) regulate ABCG1 expression in macrophages. All-trans retinoic acid (ATRA), an RAR ligand, increased ABCG1 protein levels and apoA-I/HDL-mediated cholesterol efflux from the macrophages. Both ATRA and other RAR agonists, TTNPB and Am580, increased major transcripts driven by promoter B upstream of exon 5, though minor transcripts driven by promoter A upstream of exon 1 were only increased by ATRA. The stimulatory effects of ATRA on ABCG1 expression were completely abolished in the presence of RAR/RXR antagonists but were only partially canceled in the presence of an LXR antagonist. Adenovirus with overexpressed oxysterol sulfotransferase abolished the LXR pathway, as previously reported, and ATRA-responsiveness in ABCA1/ABCG1 expressions were respectively attenuated by 38 and 22% compared to the control virus. Promoter assays revealed that ABCG1 levels were regulated more by promoter B than promoter A, and ATRA activated promoter B in a liver X receptor-responsive element (LXRE)-dependent manner. Further, LXRE-B in intron 7, but not LXRE-A in intron 5, enhanced ATRA responsiveness under overexpression of all RAR isoforms-RARα/β/γ. In contrast, the activation of promoter B by TTNPB depended on LXRE-B and RARα, but not on RARβ/γ. Finally, chromatin immunoprecipitation and gel-shift assays revealed a specific and direct repeat 4-dependent binding of RARα to LXRE-B. In conclusion, RAR ligands increase ABCA1/G1 expression and apoA-I/HDL-mediated cholesterol efflux from macrophages, and modulate ABCG1 promoter activity via LXRE-dependent mechanisms.

  2. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

    Science.gov (United States)

    Kapur, Rick; Kustiawan, Iwan; Vestrheim, Anne; Koeleman, Carolien A M; Visser, Remco; Einarsdottir, Helga K; Porcelijn, Leendert; Jackson, Dave; Kumpel, Belinda; Deelder, André M; Blank, Dennis; Skogen, Björn; Killie, Mette Kjaer; Michaelsen, Terje E; de Haas, Masja; Rispens, Theo; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2014-01-23

    Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.

  3. The impact of geoengineering on vegetation in experiment G1 of the GeoMIP

    Science.gov (United States)

    Glienke, Susanne; Irvine, Peter J.; Lawrence, Mark G.

    2015-10-01

    Solar Radiation Management (SRM) has been proposed as a mean to partly counteract global warming. The Geoengineering Model Intercomparison Project (GeoMIP) has simulated the climate consequences of a number of SRM techniques. Thus far, the effects on vegetation have not yet been thoroughly analyzed. Here the vegetation response to the idealized GeoMIP G1 experiment from eight fully coupled Earth system models (ESMs) is analyzed, in which a reduction of the solar constant counterbalances the radiative effects of quadrupled atmospheric CO2 concentrations (abrupt4 × CO2). For most models and regions, changes in net primary productivity (NPP) are dominated by the increase in CO2, via the CO2 fertilization effect. As SRM will reduce temperatures relative to abrupt4 × CO2, in high latitudes this will offset increases in NPP. In low latitudes, this cooling relative to the abrupt4 × CO2 simulation decreases plant respiration while having little effect on gross primary productivity, thus increasing NPP. In Central America and the Mediterranean, generally dry regions which are expected to experience increased water stress with global warming, NPP is highest in the G1 experiment for all models due to the easing of water limitations from increased water use efficiency at high-CO2 concentrations and the reduced evaporative demand in a geoengineered climate. The largest differences in the vegetation response are between models with and without a nitrogen cycle, with a much smaller CO2 fertilization effect for the former. These results suggest that until key vegetation processes are integrated into ESM predictions, the vegetation response to SRM will remain highly uncertain.

  4. Nuclear vasohibin-2 promotes cell proliferation by inducing G0/G1 to S phase progression.

    Science.gov (United States)

    Ge, Qianqian; Zhou, Jia; Tu, Min; Xue, Xiaofeng; Li, Zhanjun; Lu, Zipeng; Wei, Jishu; Song, Guoxin; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Miao, Yi; Gao, Wentao

    2015-09-01

    As a member of the vasohibin (VASH2) family, VASH2 is localized intracellularly as a nuclear and cytoplasmic type. Cytoplasmic VASH2 is associated with carcinoma angiogenesis and malignant transformation and promotes cancer growth. However, the function of nuclear VASH2 has yet to be investigated. The aim of the present study was to detect the nuclear VASH2 expression profile in human organs and tissues by protein microarray technique. To examine the function of nuclear VASH2, we analyzed the relationship between nuclear VASH2 and Ki-67, and stably constructed VASH2 overexpression and knockdown in LO2 and HepG2 cell lines, based on a previous study in hepatic cells. The study was conducted using bromodeoxyuridine, immunofluorescent staining, western blot analysis and flow cytometry. Nuclear VASH2 was highly expressed in actively dividing cells in normal and cancer tissues. There was a significant positive correlation between nuclear VASH2 and Ki-67, indicating that nuclear VASH2 positively correlated with cell proliferation in normal and cancer tissues. The bromodeoxyuridine (BrdU) proliferation test showed that nuclear VASH2 increased the S-phase population and promoted cell proliferation, while VASH2 knockdown reduced BrdU absorbance. Cell cycle analysis revealed that nuclear VASH2 overexpression increased the S-phase population in LO2 and HepG2 cells, while nuclear VASH2 knockdown reduced the S-phase population and increased the G0/G1 population. The findings of this study challenge the classic view of VASH2, which was previously reported as an angiogenesis factor. Furthermore, to the best of our knowledge, these results are the first clinical data indicating that nuclear VASH2, but not cytoplasmic VASH2, promotes cell proliferation by driving the cell cycle from the G0/G1 to S phase.

  5. SUPERNOVA EJECTA IN THE YOUNGEST GALACTIC SUPERNOVA REMNANT G1.9+0.3

    Energy Technology Data Exchange (ETDEWEB)

    Borkowski, Kazimierz J.; Reynolds, Stephen P. [Department of Physics, North Carolina State University, Raleigh, NC 27695-8202 (United States); Hwang, Una [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Green, David A. [Cavendish Laboratory, 19 J.J. Thomson Ave., Cambridge CB3 0HE (United Kingdom); Petre, Robert [NASA/GSFC, Code 660, Greenbelt, MD 20771 (United States); Krishnamurthy, Kalyani; Willett, Rebecca, E-mail: kborkow@unity.ncsu.edu [Department of Electrical and Computer Engineering, Duke University, Durham, NC 27708 (United States)

    2013-07-01

    G1.9+0.3 is the youngest known Galactic supernova remnant (SNR), with an estimated supernova (SN) explosion date of {approx}1900, and most likely located near the Galactic center. Only the outermost ejecta layers with free-expansion velocities {approx}>18,000 km s{sup -1} have been shocked so far in this dynamically young, likely Type Ia SNR. A long (980 ks) Chandra observation in 2011 allowed spatially resolved spectroscopy of heavy-element ejecta. We denoised Chandra data with the spatio-spectral method of Krishnamurthy et al., and used a wavelet-based technique to spatially localize thermal emission produced by intermediate-mass elements (IMEs; Si and S) and iron. The spatial distribution of both IMEs and Fe is extremely asymmetric, with the strongest ejecta emission in the northern rim. Fe K{alpha} emission is particularly prominent there, and fits with thermal models indicate strongly oversolar Fe abundances. In a localized, outlying region in the northern rim, IMEs are less abundant than Fe, indicating that undiluted Fe-group elements (including {sup 56}Ni) with velocities >18,000 km s{sup -1} were ejected by this SN. However, in the inner west rim, we find Si- and S-rich ejecta without any traces of Fe, so high-velocity products of O-burning were also ejected. G1.9+0.3 appears similar to energetic Type Ia SNe such as SN 2010jn where iron-group elements at such high free-expansion velocities have been recently detected. The pronounced asymmetry in the ejecta distribution and abundance inhomogeneities are best explained by a strongly asymmetric SN explosion, similar to those produced in some recent three-dimensional delayed-detonation Type Ia models.

  6. The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling

    Science.gov (United States)

    Trivigno, Catherine; Haerry, Theodor E.

    2011-01-01

    Mutations in the human mitochondrial elongation factor G1 (EF-G1) are recessive lethal and cause death shortly after birth. We have isolated mutations in iconoclast (ico), which encodes the highly conserved Drosophila orthologue of EF-G1. We find that EF-G1 is essential during fly development, but its function is not required in every tissue. In contrast to null mutations, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to premature death during embryogenesis. Our experiments show that EF-G1 contains a secondary C-terminal nuclear localization signal. Expression of missense mutant forms of EF-G1 can accumulate in the nucleus and cause growth and patterning defects and animal lethality. We find that transgenes that encode mutant human EF-G1 proteins can rescue ico mutants, indicating that the underlying problem of the human disease is not just the loss of enzymatic activity. Our results are consistent with a model where EF-G1 acts as a retrograde signal from mitochondria to the nucleus to slow down cell proliferation if mitochondrial energy output is low. PMID:21364917

  7. Synthesis of DGLAP and total resummation of leading logarithms for the non-singlet spin structure function $g_{1}$

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2005-01-01

    The explicit expressions for the non-singlet DIS structure function g_1 at small $x$ are obtained by resumming the leading logarithmic contributions. The role played by the fits for the initial parton densities currently used in the DGLAP on the small-x behavior of the non-singlet g_1 is discussed. Explicit expressions combining DGLAP with our results are presented.

  8. Phosphorylation-triggered CUEDC2 degradation promotes UV-induced G1 arrest through APC/C(Cdh1) regulation.

    Science.gov (United States)

    Zhang, Wei-Na; Zhou, Jie; Zhou, Tao; Li, Ai-Ling; Wang, Na; Xu, Jin-Jing; Chang, Yan; Man, Jiang-Hong; Pan, Xin; Li, Tao; Li, Wei-Hua; Mu, Rui; Liang, Bing; Chen, Liang; Jin, Bao-Feng; Xia, Qing; Gong, Wei-Li; Zhang, Xue-Min; Wang, Li; Li, Hui-Yan

    2013-07-02

    DNA damage triggers cell cycle arrest to provide a time window for DNA repair. Failure of arrest could lead to genomic instability and tumorigenesis. DNA damage-induced G1 arrest is generally achieved by the accumulation of Cyclin-dependent kinase inhibitor 1 (p21). However, p21 is degraded and does not play a role in UV-induced G1 arrest. The mechanism of UV-induced G1 arrest thus remains elusive. Here, we have identified a critical role for CUE domain-containing protein 2 (CUEDC2) in this process. CUEDC2 binds to and inhibits anaphase-promoting complex/cyclosome-Cdh1 (APC/C(Cdh1)), a critical ubiquitin ligase in G1 phase, thereby stabilizing Cyclin A and promoting G1-S transition. In response to UV irradiation, CUEDC2 undergoes ERK1/2-dependent phosphorylation and ubiquitin-dependent degradation, leading to APC/C(Cdh1)-mediated Cyclin A destruction, Cyclin-dependent kinase 2 inactivation, and G1 arrest. A nonphosphorylatable CUEDC2 mutant is resistant to UV-induced degradation. Expression of this stable mutant effectively overrides UV-induced G1-S block. These results establish CUEDC2 as an APC/C(Cdh1) inhibitor and indicate that regulated CUEDC2 degradation is critical for UV-induced G1 arrest.

  9. RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus (HPV) infection.Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ (HC-Ⅱ) in normal group (25 cases), CIN Ⅰ (48 cases), CIN Ⅱ (56 cases), CIN Ⅲ (54 cases), and invasive cervical squamous-cell carcinoma (SCC, 31 cases).Results The positive rates of cyclin G1 expression in CIN (77. 85%) and SCC cervical tissues (87.10%) were significantly higher than normal (8.00%,P<0.01), and the intensities of cyclin G1 expression in CIN (40.60%)and SCC cervical tissues (61.51%) were significantly higher than normal (2.72%,P<0.05). The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups (P<0.05). There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ (Kendall's tau-b =0.316, 0.269, 0.352, and 0. 474 in CIN Ⅰ, CINⅡ, CIN Ⅲ, and SCC, respectively, P<0.05).Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.

  10. PAI-1 transcriptional regulation during the G0 --> G1 transition in human epidermal keratinocytes.

    Science.gov (United States)

    Qi, Li; Allen, Rosalie R; Lu, Qi; Higgins, Craig E; Garone, Rosemarie; Staiano-Coico, Lisa; Higgins, Paul J

    2006-10-01

    Plasminogen activator inhibitor type-1 (PAI-1) is the major negative regulator of the plasmin-dependent pericellular proteolytic cascade. PAI-1 gene expression is normally growth state regulated but frequently elevated in chronic fibroproliferative and neoplastic diseases affecting both stromal restructuring and cellular migratory activities. Kinetic modeling of cell cycle transit in synchronized human keratinocytes (HaCaT cells) indicated that PAI-1 transcription occurred early after serum stimulation of quiescent (G0) cells and prior to entry into a cycling G1 condition. PAI-1 repression (in G0) was associated with upstream stimulatory factor-1 (USF-1) occupancy of two consensus E box motifs (5'-CACGTG-3') at the PE1 and PE2 domains in the PF1 region (nucleotides -794 to -532) of the PAI-1 promoter. Chromatin immunoprecipitation (ChIP) analysis established that the PE1 and PE2 site E boxes were occupied by USF-1 in quiescent cells and by USF-2 in serum-activated, PAI-1-expressing keratinocytes. This reciprocal and growth state-dependent residence of USF family members (USF-1 vs. USF-2) at PE1/PE2 region chromatin characterized the G0 --> G1 transition period and the transcriptional status of the PAI-1 gene. A consensus E box motif was required for USF/E box interactions, as a CG --> AT substitution at the two central nucleotides inhibited formation of USF/probe complexes. The 5' flanking sites (AAT or AGAC) in the PE2 segment were not necessary for USF binding. USF recognition of the PE1/PE2 region E box sites required phosphorylation with several potential involved residues, including T153, maping to the USF-specific region (USR). A T153A substitution in USF-1 did not repress serum-induced PAI-1 expression whereas the T153D mutant was an effective suppressor. As anticipated from the ChIP results, transfection of wild-type USF-2 failed to inhibit PAI-1 induction. Collectively, these data suggest that USF family members are important regulators of PAI-1 gene

  11. Screening of recombinant glycosyltransferases reveals the broad acceptor specificity of stevia UGT-76G1.

    Science.gov (United States)

    Dewitte, Griet; Walmagh, Maarten; Diricks, Margo; Lepak, Alexander; Gutmann, Alexander; Nidetzky, Bernd; Desmet, Tom

    2016-09-10

    UDP-glycosyltransferases (UGTs) are a promising class of biocatalysts that offer a sustainable alternative for chemical glycosylation of natural products. In this study, we aimed to characterize plant-derived UGTs from the GT-1 family with an emphasis on their acceptor promiscuity and their potential application in glycosylation processes. Recombinant expression in E. coli provided sufficient amounts of enzyme for the in-depth characterization of the salicylic acid UGT from Capsella rubella (UGT-SACr) and the stevia UGT from Stevia rebaudiana (UGT-76G1Sr). The latter was found to have a remarkably broad specificity with activities on a wide diversity of structures, from aliphatic and branched alcohols, over small phenolics to larger flavonoids, terpenoids and even higher glycoside compounds. As an example for its industrial potential, the glycosylation of curcumin was thoroughly evaluated. Under optimized conditions, 96% of curcumin was converted within 24h into the corresponding curcumin β-glycosides. In addition, the reaction was performed in a coupled system with sucrose synthase from Glycine max, to enable the cost-efficient (re)generation of UDP-Glc from sucrose as abundant and renewable resource.

  12. Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Naoya Matsunaga

    2016-11-01

    Full Text Available Chronic kidney disease (CKD is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2 ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif ligand 2 (Ccl2 was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK, did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

  13. Biosimilarity Assessments of Model IgG1-Fc Glycoforms Using a Machine Learning Approach.

    Science.gov (United States)

    Kim, Jae Hyun; Joshi, Sangeeta B; Tolbert, Thomas J; Middaugh, C Russell; Volkin, David B; Smalter Hall, Aaron

    2016-02-01

    Biosimilarity assessments are performed to decide whether 2 preparations of complex biomolecules can be considered "highly similar." In this work, a machine learning approach is demonstrated as a mathematical tool for such assessments using a variety of analytical data sets. As proof-of-principle, physical stability data sets from 8 samples, 4 well-defined immunoglobulin G1-Fragment crystallizable glycoforms in 2 different formulations, were examined (see More et al., companion article in this issue). The data sets included triplicate measurements from 3 analytical methods across different pH and temperature conditions (2066 data features). Established machine learning techniques were used to determine whether the data sets contain sufficient discriminative power in this application. The support vector machine classifier identified the 8 distinct samples with high accuracy. For these data sets, there exists a minimum threshold in terms of information quality and volume to grant enough discriminative power. Generally, data from multiple analytical techniques, multiple pH conditions, and at least 200 representative features were required to achieve the highest discriminative accuracy. In addition to classification accuracy tests, various methods such as sample space visualization, similarity analysis based on Euclidean distance, and feature ranking by mutual information scores are demonstrated to display their effectiveness as modeling tools for biosimilarity assessments.

  14. G1/S Cell Cycle Checkpoint Dysfunction in Lymphoblasts from Sporadic Parkinson's Disease Patients.

    Science.gov (United States)

    Esteras, Noemí; Alquézar, Carolina; Bartolomé, Fernando; de la Encarnación, Ana; Bermejo-Pareja, Félix; Molina, José Antonio; Martín-Requero, Ángeles

    2015-08-01

    Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among aging individuals, affecting greatly the quality of their life. However, the pathogenesis of Parkinson's disease is still incompletely understood to date. Increasing experimental evidence suggests that cell cycle reentry of postmitotic neurons precedes many instances of neuronal death. Since cell cycle dysfunction is not restricted to neurons, we investigated this issue in peripheral cells from patients suffering from sporadic PD and age-matched control individuals. Here, we describe increased cell cycle activity in immortalized lymphocytes from PD patients that is associated to enhanced activity of the cyclin D3/CDK6 complex, resulting in higher phosphorylation of the pRb family protein and thus, in a G1/S regulatory failure. Decreased degradation of cyclin D3, together with increased p21 degradation, as well as elevated levels of CDK6 mRNA and protein were found in PD lymphoblasts. Inhibitors of cyclin D3/CDK6 activity like sodium butyrate, PD-332991, and rapamycin were able to restore the response of PD cells to serum stimulation. We conclude that lymphoblasts from PD patients are a suitable model to investigate cell biochemical aspects of this disease. It is suggested that cyclin D3/CDK6-associated kinase activity could be potentially a novel therapeutic target for the treatment of PD.

  15. First passage times in M2[X ]|G |1 |R queue with hysteretic overload control policy

    Science.gov (United States)

    Pechinkin, Alexander V.; Razumchik, Rostislav R.; Zaryadov, Ivan S.

    2016-06-01

    One of the reported approaches towards the solution of overload problem in networks of SIP servers is the implementation of multi-level hysteretic control of arrivals in SIP servers. Each level, being the parameter of the policy, specifies operation mode of SIP server i.e. it implicitly indicates what SIP server must do with the arriving packets. The choice of parameters' values is not guided by standards and is usually left for the network owner. In general, all operation modes of the considered policy can be grouped into two groups: normal mode (when all arriving packets are accepted) and congested mode (when part or all arriving packets are being dropped). Such grouping may serve as the criteria for choosing parameters' values of the policy: pick those values which minimize SIP server sojourn time in congested mode. In this short note we propose some analytical results which facilitate the solution of stated minimization problem. The considered mathematical model of SIP server is the queueing system M2[X ]|G |1 |R with batch arrivals and bi-level hysteretic control policy, which specifies three operation modes: normal (customers both flows are accepted), overload (only customers from one flow are accepted), discard (customers from both flows are blocked/lost)). The switching between modes can occur only on service completions. Analytical method allowing computation of stationary sojourn times in different operation modes (as well as first passage times between modes) is presented in brief. Numerical example is given.

  16. A case of neuroendocrine tumor G1 with unique histopathological growth progress

    Institute of Scientific and Technical Information of China (English)

    Misuzu; Hirai; Kenshi; Matsumoto; Hiroya; Ueyama; Hirohumi; Fukushima; Takashi; Murakami; Hitoshi; Sasaki; Akihito; Nagahara; Takashi; Yao; Sumio; Watanabe

    2013-01-01

    A gastric neuroendocrine tumor(NET)is generated from deep within the tissue mucosal layers.In many cases,NETs are discovered as submucosal tumor(SMT)-like structures by forming a tumor mass.This case has a clear mucosal demarcation line and developed like a polyp.A dilated blood vessel was found on the surface.The mass lacked the yellow color characteristic of NETs,and a SMT-like form was evident.Therefore,a nonspecific epithelial lesion was suspected and we performed endoscopy with magnifying narrowband imaging(M-NBI).However,this approach did not lead to the diagnosis,as we diagnosed the lesion as a NET by biopsy examination.The lesion was excised by endoscopic submucosal dissection.The histopathological examination proved that the lesion was a polypoid lesion although it was also a NET because the tumorcells extended upward through the normal gland ducts scatteredly.To our knowledge,there is no previous report of NET G1 with such unique histopathological growth progress and macroscopic appearance shown by detailed examination using endoscopy with M-NBI.

  17. TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

    Science.gov (United States)

    Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

    2014-12-01

    Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells.

  18. Liquid high concentration IgG1 antibody formulations by precipitation.

    Science.gov (United States)

    Matheus, Susanne; Friess, Wolfgang; Schwartz, Daniel; Mahler, Hanns-Christian

    2009-09-01

    A manufacturing approach for liquid high concentration antibody formulations based on precipitation and subsequent re-dissolution was investigated. IgG1 antibody solutions were concentrated from 20 to 100 mg/mL by intermediate precipitation, with a recovery exceeding 95%, retention of the native secondary structure and binding activity as well as adequate stability. Quantitative, reproducible precipitation was performed using 1.45 M ammonium sulphate (pH 5.5 and 8.0), 0.67 M sodium citrate (pH 8.0) and 9% (w/v) PEG 4000 (pH 5.5 and 8.0). Scalability was confirmed from 1 to 100 mL. The concentrations achievable in the re-dissolution step were less affected by the re-dissolution medium, but limited by the residual precipitant. Both, improved removal of remaining precipitant liquid and larger precipitation scales were successful in increasing the final protein concentration. SEC and turbidity analysis directly after re-dissolution indicated that similar protein qualities were obtained, independent from the precipitant used. However, increased aggregate formation was observed after short term storage of the precipitated protein particles at either 2-8 degrees C or ambient temperature. An accelerated mechanical and thermal stability program verified comparable stability of the re-dissolved liquid 100 mg/mL formulations produced by intermediate precipitation to a control formulation obtained by standard ultrafiltration.

  19. Supernova Ejecta in the Youngest Galactic Supernova Remnant G1.9+0.3

    CERN Document Server

    Borkowski, K J; Hwang, U; Green, D A; Petre, R; Krishnamurthy, K; Willett, R

    2013-01-01

    G1.9+0.3 is the youngest known Galactic supernova remnant (SNR), with an estimated supernova (SN) explosion date of about 1900, and most likely located near the Galactic Center. Only the outermost ejecta layers with free-expansion velocities larger than about 18,000 km/s have been shocked so far in this dynamically young, likely Type Ia SNR. A long (980 ks) Chandra observation in 2011 allowed spatially-resolved spectroscopy of heavy-element ejecta. We denoised Chandra data with the spatio-spectral method of Krishnamurthy et al., and used a wavelet-based technique to spatially localize thermal emission produced by intermediate-mass elements (IMEs: Si and S) and iron. The spatial distribution of both IMEs and Fe is extremely asymmetric, with the strongest ejecta emission in the northern rim. Fe Kalpha emission is particularly prominent there, and fits with thermal models indicate strongly oversolar Fe abundances. In a localized, outlying region in the northern rim, IMEs are less abundant than Fe, indicating tha...

  20. Radioactive Scandium in the Youngest Galactic Supernova Remnant G1.9+0.3

    CERN Document Server

    Borkowski, Kazimierz J; Green, David A; Hwang, Una; Petre, Robert; Krishnamurthy, Kalyani; Willett, Rebecca

    2010-01-01

    We report the discovery of thermal X-ray emission from the youngest Galactic supernova remnant (SNR) G1.9+0.3, from a 237-ks Chandra observation. We detect strong K-shell lines of Si, S, Ar, Ca, and Fe. In addition, we detect a 4.1 keV line with 99.971% confidence which we attribute to 44Sc, produced by electron capture from 44Ti. Combining the data with our earlier Chandra observation allows us to detect the line in two regions independently. For a remnant age of 100 yr, our measured total line strength indicates synthesis of $(1 - 7) \\times 10^{-5}$ solar masses of 44Ti, in the range predicted for both Type Ia and core-collapse (CC) supernovae, but somewhat smaller than the $2 \\times 10^{-4}$ solar masses reported for Cas A. The line spectrum indicates supersolar abundances. The Fe emission has a width of about 26,000 km/s, consistent with an age of about 100 yr and with the inferred mean shock velocity of 14,000 km/s deduced assuming a distance of 8.5 kpc. Most thermal emission comes from regions of lower ...

  1. Antiviral therapy in chronic hepatitis C (G1 in Russia: cost and effectiveness

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2015-01-01

    Full Text Available Genotype 1 HCV treatment in Russia assume as bitherapy (pegylated interferon – PG plus ribavirin – RBV as three therapy based on HCV protease inhibitor such as telaprevir (TLV, boceprevir (BCV or simeprevir (SMV plus PG/RBV. Medical technologies characterize neither clinical effectiveness, safety profile nor cost-effectiveness so it’s crucial to assess different costs related antiviral regimens. Three therapy costs for naïve patients including TLV, BCV, SMV are higher bitherapy 2,6; 2,5; 3,1 times accordingly. Similar TLV and BCV effectiveness for naïve patients defines TLV or BCV as the preferable 1-st line regimen, depending on regional features of pricing. SMV and TLV efficacy is similar among naïve patients and ralapsers but SMV is affordable for partially responders and non-responders after previous bitherapy. SMV cost is 1,4 times higher vs TLV but SMV has improved tolerability, less drug-drug interactions and shorter course. Insufficient bitherapy effectiveness for G1 HCV (SVR 24 – 39%-55% is required repeated course of three therapy for half of patient population. The first line regimen based on innovation will improve clinical outcomes for more patients and provide cost saving vs previous bitherapy based on PG/RBV. 

  2. Site-specific conjugation of bifunctional chelator BAT to mouse IgG1 Fab' fragment

    Institute of Scientific and Technical Information of China (English)

    Jun LI; Xue-hao WANG; Xiao-ming WANG; Zhao-lai CHEN

    2006-01-01

    Aim: To perform a site-specific conjugation of Fab' fragments of a mouse monoclonal antibody(MoAb) B43(of IgG1 subtype) to a bifunctional chelator 6-[p-(bromoacetamido) benzyl]-l,4,8,11-tetraazacyclotetradecane-N,N',N",N'"-tetraacetic acid (BAT) via the thiol groups in the hinge distal to the antigenbinding site of the Fab'. Methods: B43 was cleaved using a simple 2-step method.First, stable F(ab')2 was produced by pepsin treatment. Fab' with free thiol in the hinge region was then obtained by cysteine reduction of F(ab')2. Second, a sitespecific conjugation of Fab' to thiol-specific BAT was performed in a one-step reaction. Results: The Fab' fragment had approximately 1.8 free thiol groups per molecule after cysteine reduction. The conjugation efficiency and the chemical yield were approximately 1.28 moles chelator/Fab' and 74% of the initial concentration of Fab', respectively. The F(ab')2, Fab' and Fab'-BAT all maintained reasonable antigen-binding properties. 67Cu labeling of the conjugate under standard conditions did not impair the immunoreactivity of Fab'-BAT. Conclusion: This is a simple and efficient method for producing immunoreactive conjugates of Fab'-BAT, which can be used to make radiometal-labeled conjugates for further diagnostic and therapeutic applications.

  3. Optimal Control of the D-Policy M/G/1 Queueing System with Server Breakdowns

    Directory of Open Access Journals (Sweden)

    Kuo-Hsiung Wang

    2008-01-01

    Full Text Available This study deals with a single server in the D-policy M/G/1 queueing system in which the server is turned off at the end of each complete period and is activated again only when the cumulative completion times of the customers in the system exceeds a given level D. While the server is working, he is subject to breakdowns according to a Poisson process. When the server breaks down, he requires repair at a repair facility, where the repair time obeys a general distribution. We have demonstrated that the probability that the server is busy in the steady-state is equal to the traffic intensity. The total expected cost function per customer per unit time is constructed to determine the optimal operating D-policy at a minimum cost. We use the steady-state analytic results and apply an efficient Matlab computer program to calculate the optimal value of D. Based on three different service distributions: exponential, 3-stage Erlang and deterministic, we provide extensive numerical computation for illustration purpose. Sensitivity analysis is also investigated.

  4. The phytohormone auxin induces G1 cell-cycle arrest of human tumor cells.

    Science.gov (United States)

    Ester, Katja; Curković-Perica, Mirna; Kralj, Marijeta

    2009-10-01

    The plant hormone auxin is the key regulator of plant growth and development. Auxin regulates transcription of plant genes by targeting degradation of transcriptional repressor proteins Aux/IAA. While there are many reports describing its potential to modulate human cell functions, the majority are based on auxin action following enzymatic activation. A study focused on auxin alone and its antiproliferative potential, with emphasis on modulation of the cell cycle, has not been performed. Therefore, we analyzed tumor growth inhibitory effects and the cell-cycle perturbations of natural (IAA, IBA) and synthetic (NAA, 2,4-D) auxins. All derivatives showed cytostatic effects on selected human tumor cell lines. The cell-cycle analysis revealed that IAA and 2,4-D induce strong G1 arrest, along with a drastic decrease in the percentage of S-phase cells in MCF-7 cell line. This phenomenon demonstrates that auxins may have novel, unexploited antitumor potential and should be further investigated. Georg Thieme Verlag KG Stuttgart-New York.

  5. Asymmetric Expansion of the Youngest Galactic Supernova Remnant G1.9+0.3

    Science.gov (United States)

    Borkowski, Kazimerz J.; Gwynne, Peter; Reynolds, Stephen P.; Green, David A.; Hwang, Una; Petre, Robert; Willett, Rebecca

    2017-01-01

    The youngest Galactic supernova remnant (SNR) G1.9+0.3, produced by a (probable) SN Ia that exploded approximately 1900 CE, is strongly asymmetric at radio wavelengths, much brighter in the north, but bilaterally symmetric in X-rays. We present the results of X-ray expansion measurements that illuminate the origin of the radio asymmetry. We confirm the mean expansion rate (2011-2015) of 0.58% per yr, but large spatial variations are present. Using the nonparametric 'Demons' method, we measure the velocity field throughout the entire SNR, finding that motions vary by a factor of 5, from 0.''09 to 0.''44 per yr. The slowest shocks are at the outer boundary of the bright northern radio rim, with velocities v(sub s) as low as 3600 km per sec (for an assumed distance of 8.5 kpc), much less than v(sub s) = 12,000-13,000 km per sec along the X-ray-bright major axis. Such strong deceleration of the northern blast wave most likely arises from the collision of SN ejecta with a much denser than average ambient medium there. This asymmetric ambient medium naturally explains the radio asymmetry. In several locations, significant morphological changes and strongly nonradial motions are apparent. The spatially integrated X-ray flux continues to increase with time. Based on Chandra observations spanning 8.3 yr, we measure its increase at 1.3% +/- 0.8% per yr. The SN ejecta are likely colliding with the asymmetric circumstellar medium ejected by the SN progenitor prior to its explosion.

  6. The impact of geoengineering on vegetation in experiment G1 of the Geoengineering Model Intercomparison Project

    Science.gov (United States)

    Irvine, Peter; Glienke, Susanne; Lawrence, Mark

    2015-04-01

    Solar Radiation Management (SRM) has been proposed as a means to partly counteract global warming. The Geoengineering Model Intercomparison Project (GeoMIP) simulated the climate consequences of a number of SRM techniques, but the effects on vegetation have not yet been thoroughly studied. Here, the vegetation response to the idealized GeoMIP G1 experiment is analyzed, in which a reduction of the solar constant counterbalances the radiative effects of quadrupled atmospheric CO2 concentrations; the results from eight fully coupled earth system models (ESMs) are included. For most models and regions, changes in net primary productivity (NPP) are dominated by the increase in CO2, via the CO2 fertilization effect. As SRM will lower temperatures, in high latitudes this will reverse gains in NPP from the lifting of temperature limitations. In low latitudes this cooling relative to the 4xCO2 simulation decreases plant respiration whilst having little effect on gross primary productivity, increasing NPP. Despite reductions in precipitation in most regions in response to SRM, runoff and NPP increase in many regions including those previously highlighted as potentially being at risk of drought under SRM. This is due to simultaneous reductions in evaporation and increases in water use efficiency by plants due to higher CO2 concentrations. The relative differences between models in the vegetation response are substantially larger than the differences in their climate responses. The largest differences between models are for those with and without a nitrogen-cycle, with a much smaller CO2 fertilization effect for the former. These results suggest that until key vegetation processes are integrated into ESM predictions, the vegetation response to SRM will remain highly uncertain.

  7. Nicotine overrides DNA damage-induced G1/S restriction in lung cells.

    Directory of Open Access Journals (Sweden)

    Takashi Nishioka

    Full Text Available As an addictive substance, nicotine has been suggested to facilitate pro-survival activities (such as anchorage-independent growth or angiogenesis and the establishment of drug resistance to anticancer therapy. Tobacco smoking consists of a variety of carcinogens [such as benzopyrene (BP and nitrosamine derivatives] that are able to cause DNA double strand breaks. However, the effect of nicotine on DNA damage-induced checkpoint response induced by genotoxins remains unknown. In this study, we investigated the events occurred during G(1 arrest induced by γ-radiation or BP in nicotine-treated murine or human lung epithelial cells. DNA synthesis was rapidly inhibited after exposure to γ-radiation or BP treatment, accompanied with the activation of DNA damage checkpoint. When these cells were co-treated with nicotine, the growth restriction was compromised, manifested by upregulation of cyclin D and A, and attenuation of Chk2 phosphorylation. Knockdown of cyclin D or Chk2 by the siRNAs blocked nicotine-mediated effect on DNA damage checkpoint activation. However, nicotine treatment appeared to play no role in nocodazole-induced mitotic checkpoint activation. Overall, our study presented a novel observation, in which nicotine is able to override DNA damage checkpoint activated by tobacco-related carcinogen BP or γ-irradiation. The results not only indicates the potentially important role of nicotine in facilitating the establishment of genetic instability to promote lung tumorigenesis, but also warrants a dismal prognosis for cancer patients who are smokers, heavily exposed second-hand smokers or nicotine users.

  8. The g0/g1 switch gene 2 is an important regulator of hepatic triglyceride metabolism.

    Directory of Open Access Journals (Sweden)

    Yinfang Wang

    Full Text Available Nonalcoholic fatty liver disease is associated with obesity and insulin resistance. Factors that regulate the disposal of hepatic triglycerides contribute to the development of hepatic steatosis. G0/G1 switch gene 2 (G0S2 is a target of peroxisome proliferator-activated receptors and plays an important role in regulating lipolysis in adipocytes. Therefore, we investigated whether G0S2 plays a role in hepatic lipid metabolism. Adenovirus-mediated expression of G0S2 (Ad-G0S2 potently induced fatty liver in mice. The liver mass of Ad-G0S2-infected mice was markedly increased with excess triglyceride content compared to the control mice. G0S2 did not change cellular cholesterol levels in hepatocytes. G0S2 was found to be co-localized with adipose triglyceride lipase at the surface of lipid droplets. Hepatic G0S2 overexpression resulted in an increase in plasma Low-density lipoprotein (LDL/Very-Low-density (VLDL lipoprotein cholesterol level. Plasma High-density lipoprotein (HDL cholesterol and ketone body levels were slightly decreased in Ad-G0S2 injected mice. G0S2 also increased the accumulation of neutral lipids in cultured HepG2 and L02 cells. However, G0S2 overexpression in the liver significantly improved glucose tolerance in mice. Livers expressing G0S2 exhibited increased 6-(N-(7-nitrobenz-2-oxa-1-3-diazol-4-yl amino-6-deoxyglucose uptake compared with livers transfected with control adenovirus. Taken together, our results provide evidence supporting an important role for G0S2 as a regulator of triglyceride content in the liver and suggest that G0S2 may be a molecular target for the treatment of insulin resistance and other obesity-related metabolic disorders.

  9. Modelling of aflatoxin G1 reduction by kefir grain using response surface methodology.

    Science.gov (United States)

    Ansari, Farzaneh; Khodaiyan, Faramarz; Rezaei, Karamatollah; Rahmani, Anosheh

    2015-01-01

    Aflatoxin G1 (AFG1) is one of the main toxic contaminants in pistachio nuts and causes potential health hazards. Hence, AFG1 reduction is one of the main concerns in food safety. Kefir-grains contain symbiotic association of microorganisms well known for their aflatoxin decontamination effects. In this study, a central composite design (CCD) using response surface methodology (RSM) was applied to develop a model in order to predict AFG1 reduction in pistachio nuts by kefir-grain (already heated at 70 and 110°C). The independent variables were: toxin concentration (X1: 5, 10, 15, 20 and 25 ng/g), kefir-grain level (X2: 5, 10, 20, 10 and 25%), contact time (X3: 0, 2, 4, 6 and 8 h), and incubation temperature (X4: 20, 30, 40, 50 and 60°C). There was a significant reduction in AFG1 (p kefir-grain used. The variables including X1, X3 and the interactions between X2-X4 as well as X3-X4 have significant effects on AFG1 reduction. The model provided a good prediction of AFG1 reduction under the assay conditions. Optimization was used to enhance the efficiency of kefir-grain on AFG1 reduction. The optimum conditions for the highest AFG1 reduction (96.8%) were predicted by the model as follows: toxin concentration = 20 ng/g, kefir-grain level = 10%, contact time = 6 h, and incubation temperature = 30°C which validated practically in six replications.

  10. Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells.

    Science.gov (United States)

    Yan, Keqiang; Zhang, Cheng; Feng, Jinbo; Hou, Lifang; Yan, Lei; Zhou, Zunlin; Liu, Zhaoxu; Liu, Cheng; Fan, Yidon; Zheng, Baozhong; Xu, Zhonghua

    2011-07-01

    Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. 草鱼cyclin G1基因的克隆、鉴定及适应性进化分析%Cloning,Identification and Adaptive Evolution Analysis of cyclin G1 Gene for Grass Crap(Ctenopharyngodon idellus)

    Institute of Scientific and Technical Information of China (English)

    王海舟; 胡成钰

    2011-01-01

    本研究从草鱼(Ctenopharyngodon idellus)肝肾cDNA文库中克隆到草鱼cyclin G1基因。测序结果表明,草鱼cyclin G1全长cDNA为2118bp,使用ORF finder推译其开放阅读框为第256bp~第1155bp,编码299个aa,SMART在线软件预测其中N端第57个aa~第143个aa为细胞周期蛋白盒。同源性比对分析显示cyclin G1在鱼类中同源性极高,其中草鱼cyclin G1与斑马鱼的同源性为90%。通过PAML软件的密码子替换模型进行适应性进化分析,结果%In this research,we cloned cyclin G1 gene from the liver and kideny cDNA library in grass crap.The result of sequencing showed that the full length of cDNA of grass crap cyclin G1 was 2 118 bp,and the open reading frame was 256th~1 155th bp predicted by O

  12. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

    Science.gov (United States)

    Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

    2016-01-01

    Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus.

  13. Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus

    National Research Council Canada - National Science Library

    Schmidt, Joshua M; Good, Robert T; Appleton, Belinda; Sherrard, Jayne; Raymant, Greta C; Bogwitz, Michael R; Martin, Jon; Daborn, Phillip J; Goddard, Mike E; Batterham, Philip; Robin, Charles

    2010-01-01

    The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change...

  14. Galactosylation of IgG1 modulates FcγRIIB-mediated inhibition of murine autoimmune hemolytic anemia.

    Science.gov (United States)

    Yamada, Kazunori; Ito, Kiyoaki; Furukawa, Jun-Ichi; Nakata, Junichiro; Alvarez, Montserrat; Verbeek, J Sjef; Shinohara, Yasuro; Izui, Shozo

    2013-12-01

    Murine immune effector cells express three different stimulatory FcγRs (FcγRI, FcγRIII and FcγRIV) and one inhibitory receptor, FcγRIIB. Competitive engagement of stimulatory and inhibitory FcγRs has been shown to be critical for the development of immune complex-mediated inflammatory disorders. Because of the previous demonstration that FcγRIIB was unable to inhibit FcγRIII-mediated autoimmune hemolytic anemia induced by 105-2H IgG1 anti-RBC mAb, we reevaluated the regulatory role of FcγRIIB on the development of anemia using two additional IgG1 anti-RBC mAbs (34-3C and 3H5G1) and different 34-3C IgG subclass-switch variants. We were able to induce a more severe anemia in FcγRIIB-deficient mice than in FcγRIIB-sufficient mice after injection of 34-3C and 3H5G1 IgG1, but not 105-2H IgG1. Structural analysis of N-linked oligosaccharides attached to the CH2 domain revealed that 105-2H was poorly galactosylated as compared with the other mAbs, while the extent of sialylation was comparable between all mAbs. In addition, we observed that a more galactosylated 105-2H variant provoked more severe anemia in FcγRIIB-deficient mice than FcγRIIB-sufficient mice. In contrast, the development of anemia induced by three non-IgG1 subclass variants of the 34-3C mAb was not down-regulated by FcγRIIB, although they were more galactosylated than its IgG1 variant. These data indicate that FcγRIIB-mediated inhibition of autoimmune hemolytic anemia is restricted to the IgG1 subclass and that galactosylation, but not sialylation, of IgG1 (but not other IgG subclasses) is critical for the interaction with FcγR, thereby determining the pathogenic potential of IgG1 autoantibodies.

  15. Final COMPASS results on the deuteron spin-dependent structure function g1d and the Bjorken sum rule

    Directory of Open Access Journals (Sweden)

    C. Adolph

    2017-06-01

    Full Text Available Final results are presented from the inclusive measurement of deep-inelastic polarised-muon scattering on longitudinally polarised deuterons using a 6LiD target. The data were taken at 160 GeV beam energy and the results are shown for the kinematic range 1(GeV/c24GeV/c2 in the mass of the hadronic final state. The deuteron double-spin asymmetry A1d and the deuteron longitudinal-spin structure function g1d are presented in bins of x and Q2. Towards lowest accessible values of x, g1d decreases and becomes consistent with zero within uncertainties. The presented final g1d values together with the recently published final g1p values of COMPASS are used to again evaluate the Bjorken sum rule and perform the QCD fit to the g1 world data at next-to-leading order of the strong coupling constant. In both cases, changes in central values of the resulting numbers are well within statistical uncertainties. The flavour-singlet axial charge a0, which is identified in the MS‾ renormalisation scheme with the total contribution of quark helicities to the nucleon spin, is extracted at next-to-leading order accuracy from only the COMPASS deuteron data: a0(Q2=3(GeV/c2=0.32±0.02stat±0.04syst±0.05evol. Together with the recent results on the proton spin structure function g1p, the results on g1d constitute the COMPASS legacy on the measurements of g1 through inclusive spin-dependent deep inelastic scattering.

  16. Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Shanshan [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 (China); Wang, Jiaxing [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Zhang, Xu; Shi, Ying; Li, Bochuan; Bao, Qiankun [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Pang, Wei [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Ai, Ding [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Zhu, Yi [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); He, Jinlong, E-mail: hejinlong@tmu.edu.cn [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)

    2016-08-19

    Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.

  17. FACT prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in G1.

    Directory of Open Access Journals (Sweden)

    Macarena Morillo-Huesca

    2010-05-01

    Full Text Available The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3 in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA-damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication.

  18. Characterization of a G1 inhibitor from old JB-1 ascites tumor fluid. Interaction with polyions and ion exchangers.

    Science.gov (United States)

    Barfod, N M; Bichel, P

    1976-09-17

    In most experimental ascites tumors the growth rate decreases with increasing age and cell number. This decrease is caused by a prolongation of the cell cycle and an increasing accumulation of noncycling cells in resting (or quiescent) G1 and G2 compartments. In cell-free ascitic fluid from the JB-1 ascites tumor in the plateau phase of growth, low molecular weight substances have been found which reversibly and specifically arrest JB-1 cells in G1 and G2. In order to characterize the JB-1 G1 inhibitor we have investigated the effect of ion exchangers and polyions on the activity of this inhibitor assayed in vitro by means of a partially synchronized JB-1 cell population analyzed by flow microfluorometry. The results indicate that polyanions and cation exchangers (immobilized polyanions) bind and abolish the G1-inhibitory activity. From this it is suggested that the G1 inhibitor is of a basic or polycationic nature. Since anion exchangers (immobilized polycations) are without effect on this activity it was surprising to find that polycations also neutralize the activity. The results indicate that this occurs by blocking an anionic G2-inhibitor receptor on the cell, thus preventing the polycationic G1 inhibitor from being bound to this receptor.

  19. FACT prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in G1.

    Directory of Open Access Journals (Sweden)

    Macarena Morillo-Huesca

    2010-05-01

    Full Text Available The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3 in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA-damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication.

  20. A组轮状病毒G1和G9亚型的二重qPCR检测%The duplex qPCR assay for G1 and G9 subtypes of group A Rotavirius

    Institute of Scientific and Technical Information of China (English)

    徐垚; 曹以诚; 李晖; 方苓; 祖冬梅

    2013-01-01

    目的 建立快速检测A组轮状病毒G1和G9亚型的二重实时荧光定量PCR(qPCR)检测法.方法 针对A组轮状病毒G1和G9亚型VP7基因的保守区域与高变区域,设计特异的引物、探针.构建含A组轮状病毒G1和G9亚型VP7基因的质粒,将其作为该检测系统的阳性标准品,优化A组轮状病毒G1和G9亚型的qPCR检测系统.结果 该方法检测A组轮状病毒G1和G9亚型阳性样本的灵敏度为103 copies/μL,对其他亚型的标准质粒检测呈阴性.结论 本实验建立的A组轮状病毒G1和G9亚型的二重qPCR检测方法具有良好的特异度、敏感度和重复性,该方法的应用有助于A组轮状病毒G1与G9亚型感染的早期快速诊断.

  1. Binding of fusion protein FLSC IgG1 to CCR5 is enhanced by CCR5 antagonist Maraviroc.

    Science.gov (United States)

    Latinovic, Olga; Schneider, Kate; Szmacinski, Henryk; Lakowicz, Joseph R; Heredia, Alonso; Redfield, Robert R

    2014-12-01

    The CCR5 chemokine receptor is crucial for human immunodeficiency virus type 1 (HIV-1) infection, acting as the principal coreceptor for HIV-1 entry and transmission and is thus an attractive target for antiviral therapy. Studies have suggested that CCR5 surface density and its conformational changes subsequent to virion engagement are rate limiting for entry, and consequently, infection. Not all CCR5 antibodies inhibit HIV-1 infection, suggesting a need for more potent reagents. Here we evaluated full length single chain (FLSC) IgG1, a novel IgG-CD4-gp120(BAL) fusion protein with several characteristics that make it an attractive candidate for treatment of HIV-1 infections, including bivalency and a potentially increased serum half-life over FLSC, the parental molecule. FLSC IgG1 binds two domains on CCR5, the N-terminus and the second extracellular loop, lowering the levels of available CCR5 viral attachment sites. Furthermore, FLSC IgG1 synergizes with Maraviroc (MVC), the only licensed CCR5 antagonist. In this study, we used both microscopy and functional assays to address the mechanistic aspects of the interactions of FLSC IgG1 and MVC in the context of CCR5 conformational changes and viral infection. We used a novel stochastic optical reconstruction microscopy (STORM), based on high resolution localization of photoswitchable dyes to visualize direct contacts between FLSC IgG1 and CCR5. We compared viral entry inhibition by FLSC IgG1 with that of other CCR5 blockers and showed FLSC IgG1 to be the most potent. We also showed that lower CCR5 surface densities in HIV-1 infected primary cells result in lower FLSC IgG1 EC50 values. In addition, CCR5 binding by FLSC IgG1, but not CCR5 Ab 2D7, was significantly increased when cells were treated with MVC, suggesting MVC allosterically increases exposure of the FLSC IgG1 binding site. These data have implications for future antiviral therapy development.

  2. Staurosporine is chemoprotective by inducing G1 arrest in a Chk1- and pRb-dependent manner.

    Science.gov (United States)

    Murray, Mollianne McGahren; Bui, Tuyen; Smith, Michelle; Bagheri-Yarmand, Rozita; Wingate, Hannah; Hunt, Kelly K; Keyomarsi, Khandan

    2013-10-01

    Chemotherapeutic agents have been the mainstay of cancer therapy for years. However, their effectiveness has been limited by toxicities they impart on normal cells. Staurosporine (ST) has been shown to arrest normal, but not breast cancer, cells in G1. Therefore, ST may become a chemoprotective agent, arresting normal cells while allowing tumor cells to enter cell cycle phases where they are sensitive to chemotherapeutic agents. Understanding the mechanism of ST-mediated G1 arrest may allow for a beneficial chemoprotective treatment strategy for patients. We utilized 76NE6 (pRb+/p53-), 76NF2V (pRb+/p53+) and 76NE7 (pRb-/P53+) non-tumorigenic human mammary epithelial cell lines to understand the role of the Rb and p53 pathways in ST-directed G1 arrest. CDK4 was downregulated by ST in Rb+ cells, but its presence could not reverse the arrest, neither did its stable downregulation alter ST-mediated cellular response. ST-mediated G1 arrest required pRb, which in turn initiated a cascade of events leading to inhibition of CDK4. Further assessment of this pathway revealed that Chk1 expression and activity were required for the Rb-dependent arrest. For example, pRb+ cells with small interfering RNA to Chk1 had approximately 60% less cells in G1 phase compared with controls and pRb- cells do not arrest upon ST. Furthermore, Chk1 expression facilitates the release of the Rb+ cells from G1 arrest. Collectively, our data suggest that pRb cooperates with Chk1 to mediate a G1 arrest only in pRb+ cells. The elucidation of this pathway can help identify novel agents to protect cancer patients against the debilitating effects of chemotherapy.

  3. Isolation and characteristics of autoreactive T cells spe cific to aggrecan G1 domain from rheumatoid arthritis patients

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Our previous work showed that the cartilage proteo glycan aggrecan could induce an erosive polyarthritis and spondylitis in BALB/c mice and the G1 globular domain of the aggrecan (G1) contained the arthritogenic region. To elucidate whether autoreactive T cells to G1 are ex pressed in rheumatoid arthritis patients, we analyzed the frequency of human G1-specific T cells in the peripheral blood of five rheumatoid arthritis patients and tried to establish G1-reactive T cell lines from these rheumatoid arthritis patients. The results showed that the Gl-specific T cells in PBL were detectable at the range of 4.97 + 0.5 × 10-6 in peripheral blood lymphocytes. We have also generated 15 G1-specific T lymphocyte lines from these pateints with a standard split-well method. All these cells expressed fine specificity to human recombinant G1, but not to unrelated antigen. All the 15 lines expressed a pan T cell marker and 13 of them selectively used the αβ T cell receptor. Two of them used γδ T cell receptor. The 13 of these T cell lines was CD4 positive. One line expressed CD8. One line expressed both CD4 and CD8. More over, 14 out of 15 lines expressed the Th-1 cytokine profile, characterized by interferon-γ positivity and IL-4 negativ ity. No Th-2 type cell line was generated. These data provide strong evidence in favor of the presence of autore active T cells in the rheumatoid arthritis pateints. What is the mechanism(s) that these autoreactive T cells attack self-target and whether these Gl-specific, Th-1 type T cell lines can induce arthritis in immune deficiency mice are currently under investigation.

  4. Research on G1 Continuity Conditions between B-Spline Surfaces and Construction of Local Scheme%B样条曲面间G1连续条件及局部格式构造问题

    Institute of Scientific and Technical Information of China (English)

    高占恒; 梁学章; 高福顺; 马婷

    2007-01-01

    研究了内部单节点张量积B样条曲面间G1连续的条件.通过选择特殊类型的拼接函数,打破了公共边界必须是整体多项式曲线的限制,给出了以内部单节点双四次B样条曲面为工具、使用局部格式构造G1连续曲面的算法.最后给出了计算实例.

  5. Construction and Expression of the Echinococcus granulosus Recombinant BCG-EgG1Y162%细粒棘球绦虫重组BCG-EgG1Y162菌株的构建和表达

    Institute of Scientific and Technical Information of China (English)

    祖力皮也·吐尔逊; 德力夏提·依米提; 曹春宝; 马海梅; 李玉娇; 周晓涛; 朱明; 马秀敏; 温浩

    2013-01-01

    Objective To construct and express Echinococcus granulosus recombinant bacille Calmette-Guerin (BCG) strain rBCG-EgG1Y162. Methods The encoding gene of the antigen EgG1Y162 of E. granulosus was recombined with E. coli-Mycobacterium shuttle expression plasmid vector pMV361 by genetic engineering technique, and transformed into E. coll for amplification. The recombinant plasmid rpMV-EgG1Y162 was identified by PCR, double digestion with restriction enzymes, and sequence analysis. The confirmed rpMV-EgG1Y162 was transformed into BCG strain via electroporation technique to construct the recombinant rBCG-EgG1Y162. After identification by PCR and double digestion with restriction enzymes, the recombinant strain was cultured for about 2 weeks. In order to induce the expression of target protein, the rBCG was placed in 45℃ for 30 min. SDS-PAGE and Western blotting were used to analyze the expressive protein. Results The product of recombinant plasmid rpMV-EgG1Y162 was approximately 360 bp by PCR amplification and double digestion with restriction enzymes, consistent with the expected fragment length. Sequencing results showed that the inserted sequence was correct. The rBCG-EgG1Y162 grew well and the identification of PCR and enzyme digestion revealed accuracy. The results of SDS-PAGE and Western blotting showed that the relative molecular weight (Mr) of the protein was about 71 000. Conclusion The E. granulosus rBCG-EgG1Y162 strain is constructed and expressed.%目的 构建和表达细粒棘球绦虫重组卡介苗(BCG)菌株rBCG-EgG1Y162.方法 通过基因工程技术将细粒棘球绦虫抗原EgG1Y162的编码基因与大肠埃希菌(E.coli)-分枝杆菌穿梭表达质粒载体pMV361重组,并转化E.coli后进行扩增.重组质粒pMV-EgG1Y162经PCR和双酶切鉴定后,进行测序.将鉴定正确的rpMV-EgG1Y162通过电穿孔技术转化至感受态BCG菌株中,构建rBCG-EgG1Y162.经PCR和双酶切鉴定正确后,扩增培养2周,并于45℃放置30 min,诱导

  6. 免疫初乳中IgG1和IgG2的分离纯化%Isolation and purification of IgG1 and IgG2 from immune colostrum

    Institute of Scientific and Technical Information of China (English)

    张和平; 李立民; 孙天松; 郭军

    2001-01-01

    采用硫酸胺盐析、DE-52离子交换色谱、Sephacryl S-100凝胶过滤色谱从免疫初乳分离纯化出了IgG1和IgG2,经SDS-PAGE电泳及免疫电泳证实为纯品;并对IgG1和IgG2的抗体凝集价进行了测定.

  7. 尿G1红细胞对肾小球性血尿的诊断价值%The Value of G1 Red Blood Cell to Diagnose Glomerular Hematuria

    Institute of Scientific and Technical Information of China (English)

    黄芸; 高兵

    2011-01-01

    Objective To explore the accuracy and clinical value of examining morphology of a special shaped red blood cell - G1 red blood cell in urine by common microscopy in localization of hematuria. The diagnostic standard of glomerular hematuria was G1 red blood cell≥5%. Methods Research 101 patients with hematuria patients, 73 cases of glomerular disease, 28 cases with non - glomerular diseases. Contact microscope examination and the patient's clinical diagnosis to calculate the sensitivity and specificity. Results The sensitivity of the diagnostic standard of G1 red blood ce11≥5% was 32.88% and the specificity was 96.43% ;the sensitivity of the diagnostic standard of G1 red blood cell ≥2% was 53.43% and the specificity was 96.43%. Conclusion The diagnostic standard of Gl red blood cell ≥2% is high specificity, sensitivity is acceptable to promote in the clinical.%目的:探讨尿液中一种特殊形态的红细胞--C1红细胞对血尿原因鉴别诊断的临床意义.以镜检G1红细胞≥2%,作为肾小球性血尿的诊断标准,评估其准确性及临床应用价值.方法:研究101例血尿患者,其中73例为肾小球疾病,28例为非肾小球性疾病.联系镜检结果与病人临床诊断,计算其灵敏度和特异度.结果:以G1细胞≥5%为诊断标准的敏感度为32.88%,特异度为96.43%;以G1细胞≥2%为诊断标准的敏感度为53.43%,特异度为96.43%.结论:以G1红细胞≥2%为诊断标准的特异度很高,敏感度尚可,可以在临床上进行推广.

  8. The spin structure function g1p of the proton and a test of the Bjorken sum rule

    Directory of Open Access Journals (Sweden)

    C. Adolph

    2016-02-01

    Full Text Available New results for the double spin asymmetry A1p and the proton longitudinal spin structure function g1p are presented. They were obtained by the COMPASS Collaboration using polarised 200 GeV muons scattered off a longitudinally polarised NH3 target. The data were collected in 2011 and complement those recorded in 2007 at 160 GeV, in particular at lower values of x. They improve the statistical precision of g1p(x by about a factor of two in the region x≲0.02. A next-to-leading order QCD fit to the g1 world data is performed. It leads to a new determination of the quark spin contribution to the nucleon spin, ΔΣ, ranging from 0.26 to 0.36, and to a re-evaluation of the first moment of g1p. The uncertainty of ΔΣ is mostly due to the large uncertainty in the present determinations of the gluon helicity distribution. A new evaluation of the Bjorken sum rule based on the COMPASS results for the non-singlet structure function g1NS(x,Q2 yields as ratio of the axial and vector coupling constants |gA/gV|=1.22±0.05 (stat.±0.10 (syst., which validates the sum rule to an accuracy of about 9%.

  9. Impacts, Effectiveness and Regional Inequalities of the GeoMIP G1 to G4 Solar Radiation Management Scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiaoyong; Moore, John; Cui, Xuefeng; Rinke, Annette; Ji, Duoying; Kravitz, Benjamin S.; Yoon, Jin-Ho

    2015-06-01

    We evaluate the regional effectiveness of solar radiation management (SRM) to compensate for simultaneous changes in temperature and precipitation induced by increased greenhouse gas concentrations. We analyze results from multiple earth system models under four Geoengineering Model Intercomparison Project(GeoMIP) experiments with a modified form of the Residual Climate Response approach. Under the solar dimming geoengineering experiments G1(4xCO2) and G2(increasing CO2 by 1% per year), global average temperature is successfully restored to pre-industrial level over 50 years simulations. However, these two SRM experiments also produce a robust global precipitation decrease. The stratospheric aerosol GeoMIP geoengineering experiment, G4 has significantly greater regional inequality and lower effectiveness for compensating temperature change than G1 and G2. G4 also has significantly larger regional inequality for compensating precipitation change than G1and G2. However, there is no significant difference between precipitation change compensation effectiveness of G4 and G2, though there is much larger across model variability in G4 results. G3 has significant greater regional inequality for compensating temperature change than G1 and G2, and has significant lower effectiveness than G1. The effectiveness of four SRMs to compensate for temperature change is much higher than for precipitation. The large cross-model variation in adjustment percentage of compensated SAT and precipitation change by SRM to achieve optimal compensation effectiveness shed a light on the uncertainty accumulation effect in optimizing compensation effectiveness of SRM.

  10. The Spin Structure Function $g_1^{\\rm p}$ of the Proton and a Test of the Bjorken Sum Rule

    CERN Document Server

    Adolph, C.; Alexeev, M.G.; Alexeev, G.D.; Amoroso, A.; Andrieux, V.; Anosov, V.; Austregesilo, A.; Azevedo, C.; Badelek, B.; Balestra, F.; Barth, J.; Baum, G.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E.R.; Birsa, R.; Bisplinghoff, J.; Bodlak, M.; Boer, M.; Bordalo, P.; Bradamante, F.; Braun, C.; Bressan, A.; Buchele, M.; Burtin, E.; Capozza, L.; Chang, W.C.; Chiosso, M.; Choi, I.; Chung, S.U.; Cicuttin, A.; Crespo, M.L.; Curiel, Q.; Dalla Torre, S.; Dasgupta, S.S.; Dasgupta, S.; Denisov, O.Yu.; Dhara, L.; Donskov, S.V.; Doshita, N.; Duic, V.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Eyrich, W.; Ferrero, A.; Finger, M.; M. Finger jr; Fischer, H.; Franco, C.; von Hohenesche, N. du Fresne; Friedrich, J.M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grabmuller, S.; Grasso, A.; Grosse-Perdekamp, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Haas, F.; Hahne, D.; von Harrach, D.; Hashimoto, R.; Heinsius, F.H.; Herrmann, F.; Hinterberger, F.; Horikawa, N.; d'Hose, N.; Hsieh, C.Yu; Huber, S.; Ishimoto, S.; Ivanov, A.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jary, V.; 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.; Kramer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z.V.; Kuchinski, N.; Kunne, F.; Kurek, K.; Kurjata, R.P.; Lednev, A.A.; Lehmann, A.; Levillain, M.; Levorato, S.; Lichtenstadt, J.; Longo, R.; Maggiora, A.; Magnon, A.; Makins, N.; 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.; Neyret, D.; Nikolaenko, V.I.; Novy, J.; Nowak, W.D.; Nunes, A.S.; Olshevsky, A.G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J.C.; Pereira, F.; Pesek, M.; Peshekhonov, D.V.; Platchkov, S.; Pochodzalla, J.; Polyakov, V.A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Rocco, E.; Rossiyskaya, N.S.; Ryabchikov, D.I.; Rychter, A.; Samoylenko, V.D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I.A.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schonning, K.; Schopferer, S.; Selyunin, A.; Shevchenko, O.Yu.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Sozzi, F.; Srnka, A.; Stolarski, M.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Takekawa, S.; Wolbeek, J. ter; Tessaro, S.; Tessarotto, F.; Thibaud, F.; Tosello, F.; Tskhay, V.; Uhl, S.; Veloso, J.; Virius, M.; Weisrock, T.; Wilfert, M.; Windmolders, R.; Zaremba, K.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.; Zink, A.

    2016-01-01

    New results for the double spin asymmetry $A_1^{\\rm p}$ and the proton longitudinal spin structure function $g_1^{\\rm p}$ are presented. They were obtained by the COMPASS collaboration using polarised 200 GeV muons scattered off a longitudinally polarised NH$_3$ target. The data were collected in 2011 and complement those recorded in 2007 at 160\\,GeV, in particular at lower values of $x$. They improve the statistical precision of $g_1^{\\rm p}(x)$ by about a factor of two in the region $x\\lesssim 0.02$. A next-to-leading order QCD fit to the $g_1$ world data is performed. It leads to a new determination of the quark spin contribution to the nucleon spin, $\\Delta \\Sigma$ ranging from 0.26 to 0.36, and to a re-evaluation of the first moment of $g_1^{\\rm p}$. The uncertainty of $\\Delta \\Sigma$ is mostly due to the large uncertainty in the present determinations of the gluon helicity distribution. A new evaluation of the Bjorken sum rule based on the COMPASS results for the non-singlet structure function $g_1^{\\rm...

  11. Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

    Directory of Open Access Journals (Sweden)

    Balder Lai

    2014-01-01

    Full Text Available An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins.

  12. The spin-dependent structure function $g_1(x)$ of the proton from polarized deep-inelastic muon scattering

    CERN Document Server

    Adeva, B; Arvidson, A; Badelek, B; Bardin, G; Baum, G; Berglund, P; Betev, L; Birsa, R; De Botton, N R; Bradamante, Franco; Bravar, A; Bressan, A; Bültmann, S; Burtin, E; Crabb, D; Cranshaw, J; Çuhadar-Dönszelmann, T; Dalla Torre, S; Van Dantzig, R; Derro, B R; Deshpande, A A; Dhawan, S K; Dulya, C M; Eichblatt, S; Fasching, D; Feinstein, F; Fernández, C; Forthmann, S; Frois, Bernard; Gallas, A; Garzón, J A; Gilly, H; Giorgi, M A; Görtz, S; Gracia, G; De Groot, N; Haft, K; Von Harrach, D; Hasegawa, T; Hautle, P; Hayashi, N; Heusch, C A; Horikawa, N; Hughes, V W; Igo, G; Ishimoto, S; Iwata, T; Kabuss, E M; Kageya, T; Karev, A G; Ketel, T; Kiryluk, J; Kiselev, Yu F; Krivokhizhin, V G; Kröger, W; Kukhtin, V V; Kurek, K; Kyynäräinen, J; Lamanna, M; Landgraf, U; Le Goff, J M; Lehár, F; de Lesquen, A; Lichtenstadt, J; Litmaath, M; Magnon, A; Mallot, G K; Marie, F; Martin, A; Martino, J; Matsuda, T; Mayes, B W; McCarthy, J S; Medved, K S; Meyer, W T; Van Middelkoop, G; Miller, D; Miyachi, Y; Mori, K; Moromisato, J H; Nassalski, J P; Naumann, Lutz; Niinikoski, T O; Oberski, J; Ogawa, A; Grosse-Perdekamp, M; Pereira, H; Perrot-Kunne, F; Peshekhonov, V D; Pinsky, L; Platchkov, S K; Pló, M; Pose, D; Postma, H; Pretz, J; Puntaferro, R; Rädel, G; Rijllart, A; Reicherz, G; Rodríguez, M; Rondio, Ewa; Roscherr, B; Sabo, I; Saborido, J; Sandacz, A; Savin, I A; Schiavon, R P; Schiller, A; Sichtermann, E P; Simeoni, F; Smirnov, G I; Staude, A; Steinmetz, A; Stiegler, U; Stuhrmann, H B; Szleper, M; Tessarotto, F; Thers, D; Tlaczala, W; Tripet, A; Ünel, G; Velasco, M; Vogt, J; Voss, Rüdiger; Whitten, C; Windmolders, R; Wislicki, W; Witzmann, A; Ylöstalo, J; Zanetti, A M; Zaremba, K

    1997-01-01

    We present a new measurement of the virtual photon proton asymmetry $A_1^{\\rm p}$ from deep inelastic scattering of polarized muons on polarized protons in the kinematic range $0.0008 1$ GeV$^{2}$. A perturbative QCD evolution in next-to-leading order is used to determine $g_1^{\\rm p}(x)$ at a constant $Q^2$. At $Q^{2} = 10$ GeV$^{2}$ we find, in the measured range, $\\int_{0.003}^{0.7} g_{1}^{\\rm p}(x){\\rm d}x = 0.139 \\pm 0.006~({\\rm stat})\\pm 0.008~({\\rm syst)} \\pm 0.006~({\\rm evol})$. The value of the first moment $\\Gamma_{1}^{\\rm p} = \\int_{0}^{1} g_{1}^{\\rm p}(x){\\rm d}x$ of $g_{1}^{\\rm p}$ depends on the approach used to describe the behaviour of $g_{1}^{\\rm p}$ at low $x$. We find that the Ellis-Jaffe sum rule is violated. With our published result for $\\Gamma_{1}^{\\rm d}$ we confirm the Bjorken sum rule with an accuracy of $\\approx 15\\%$ at the one standard deviation level.

  13. Precise determination of the spin structure function $\\mathbf{g_1}$ of the proton, deuteron and neutron

    CERN Document Server

    Airapetian, A; Akopov, Z; Andrus, A; Aschenauer, E C; Augustyniak, W; Avakian, R; Avetisian, A; Avetissian, E; Belostotskii, S; Bianchi, N; Blok, H P; Böttcher, H; Borisov, A; Borysenko, A; Brüll, A; Bryzgalov, V; Capiluppi, M; Capitani, G P; Ciullo, G; Contalbrigo, M; Dalpiaz, P F; Deconinck, W; De Leo, R; Demey, M; De Nardo, L; De Sanctis, E; Devitsin, E; Diefenthaler, M; Di Nezza, P; Dreschler, J; Düren, M; Ehrenfried, M; Elalaoui-Moulay, A; Elbakian, G; Ellinghaus, F; Elschenbroich, U; Fabbri, R; Fantoni, A; Felawka, L; Frullani, S; Funel, A; Gabbert, D; Gärber, Y; Gapienko, G; Gapienko, V; Garibaldi, F; Garrow, K; Gavrilov, G; Karibian, V; Giordano, F; Grebenyuk, O; Gregor, I M; Guler, H; Gute, A; Hadjidakis, C; Hartig, M; Hasch, D; Hasegawa, T; Hesselink, W H A; Hillenbrand, A; Hoek, M; Holler, Y; Hommez, B; Hristova, I; Iarygin, G; Ivanilov, A; Izotov, A; Jackson, H E; Jgoun, A; Kaiser, R; Keri, T; Kinney, E; Kiselev, A; Kobayashi, T; Kopytin, M; Korotkov, V; Kozlov, V; Krauss, B; Kravchenko, P; Krivokhizhin, V G; Lagamba, L; Lapikas, L; Lenisa, P; Liebing, P; Linden-Levy, L A; Lorenzon, W; Lü, J; Lu, S; Ma, B Q; Maiheu, B; Makins, N C R; Mao, Y; Marianski, B; Marukyan, H; Masoli, F; Mexner, V; Meyners, N; Michler, T; Miklukho, O; Miller, C A; Miyachi, Y; Muccifora, V; Murray, M; Nagaitsev, A; Nappi, E; Naryshkin, Yu; Negodaev, M; Nowak, Wolf-Dieter; Ohsuga, H; Osborne, A; Perez-Benito, R; Pickert, N; Raithel, M; Reggiani, D; Reimer, P E; Reischl, A; Reolon, A R; Riedl, C; Rith, K; Rosner, G; Rostomyan, A; Rubacek, L; Rubin, J; Ryckbosch, D; Salomatin, Y; Sanjiev, I; Savin, I; Schäfer, A; Schnell, G; Schüler, K P; Seele, J; Seitz, B; Shearer, C; Shibata, T A; Shutov, V; Sinram, K; Stancari, M; Statera, M; Steffens, E; Steijger, J J M; Stenzel, H; Stewart, J; Stinzing, F; Stösslein, U; Streit, J; Tait, P; Tanaka, H; Taroian, S P; Tchuiko, B; Terkulov, A R; Trzcinski, A; Tytgat, M; Vandenbroucke, A; Van der Nat, P B; van der Steenhoven, G; Van Haarlem, Y; Veretennikov, D; Vikhrov, V; Vogel, C; Wang, S; Weiskopf, C; Ye, Y; Ye, Z; Yen, S; Zihlmann, B; Zupranski, P

    2006-01-01

    Precise measurements of the spin structure functions of the proton $g_1^p(x,Q^2)$ and deuteron $g_1^d(x,Q^2)$ are presented over the kinematic range $0.0041 \\leq x \\leq 0.9$ and $0.18 $ GeV$^2$ $\\leq Q^2 \\leq 20$ GeV$^2$. The data were collected at the HERMES experiment at DESY, in deep-inelastic scattering of 27.6 GeV longitudinally polarized positrons off longitudinally polarized hydrogen and deuterium gas targets internal to the HERA storage ring. The neutron spin structure function $g_1^n$ is extracted by combining proton and deuteron data. The integrals of $g_1^{p,d}$ at $Q^2=5$ GeV$^2$ are evaluated over the measured $x$ range. Neglecting any possible contribution to the $g_1^d$ integral from the region $x \\leq 0.021$, a value of $0.330 \\pm 0.011\\mathrm{(theo.)}\\pm0.025\\mathrm{(exp.)}\\pm 0.028$(evol.) is obtained for the flavor-singlet axial charge $a_0$ in a leading-twist NNLO analysis.

  14. Stable Expression of Hantavirus H8205 Strain G1/IL-2 Gene and Immune Protection of the Fusion Gene

    Institute of Scientific and Technical Information of China (English)

    XIONG Ying; YUAN Yuan; JIA Min; YU Bing; HUANG Hanju

    2007-01-01

    To explore the feasibility of stable expression of Hantavirus H8205 strain G1 segment and human IL-2 fusion gene in Vero cells, and to examine the immune protection effects on mice vaccinated with this recombinant eukaryotic expression vector containing Hantavirus G1 gene and IL-2 gene. With the help of lipofectamine, the Vero cells were transfected with pcDNA3.1/HisB-IL-2-G1 and the positive cells were selected by G418. IFAT and SDS-PAGE electrophoresis were used to determine the stable transfection and expression of recombinant protein.Each mouse was inoculated with plasmids intramuscularly (i.m.) three times, 2 boosts were given at 2-week intervals, serum anti-hantavirus antibodies were detected by ELISA and neutralizing antibodies (NAb) were detected by Plaque Reduction Neutralization Test. The fusion protein expressed in Vero cells was 78 kD, corresponding to the estimated molecular size. The neutralizing antibody titers of mice with pcDNA3.1/HisB-IL-2-G1 were 1:20-1:80. IL-2/G1 fusion gene could be transferred in Vero cells and stably express the fusion protein. Specific humeral immune responses in mice can be induced with the recombinant eukaryotic expression vector containing the fusion gene, which lays the foundation for further development of therapeutic HTNV vaccine.

  15. 法国银行业的改革与困境%Réforme et difficulté dans le système bancaire fran(c)ais

    Institute of Scientific and Technical Information of China (English)

    王凡

    2003-01-01

    Le système bancaire francais a beaucoup changé à cause d'une série de réformes pendant ces demières décennles. Malgré I' amé1iomtion des structures et malgré la diversification des activités,les banques francaises ont besoin d' une transformation approfondiepour bien faire face à la concurrence internationale. Pourtant, cette évolufion est actuellement empechée par le ralentissement économique de la France, la concurrence accrue dans la zone-euro, les risquesfinanciers mondiaux, ainsi que les nouvelles règles de surveillance et de compte.

  16. Los terrores nocturnos: implicaciones educativas en el 2º ciclo de Educación Infantil

    OpenAIRE

    Parra-Peñafiel, Clara

    2014-01-01

    El presente trabajo trata el tema de los terrores nocturnos desde el ámbito educativo. Para ello, se ha planteado conocer estrategias relacionadas con los terrores nocturnos infantiles en el 2º ciclo de Educación Infantil. La metodología utilizada ha sido el análisis teórico de estudios relacionados con los terrores nocturnos para conocer el estado de la cuestión. Como conclusiones más relevantes, el docente debería conocer las principales características de este trastorno del sueño para pode...

  17. Precision measurements of $g_1$ of the proton and the deuteron with 6 GeV electrons

    CERN Document Server

    Prok, Y; Kvaltine, N; Adhikari, K P; Adikaram, D; Aghasyan, M; Amaryan, M J; Anderson, M D; Pereira, S Anefalos; Avakian, H; Baghdasaryan, H; Ball, J; Baltzell, N A; Battaglieri, M; Biselli, A S; Bono, J; Briscoe, W J; Brock, J; Brooks, W K; Bültmann, S; Burkert, V D; Carlin, C; Carman, D S; Celentano, A; Chandavar, S; Colaneri, L; Cole, P L; Contalbrigo, M; Cortes, O; Crabb, D; Crede, V; D'Angelo, A; Dashyan, N; De Vita, R; De Sanctis, E; Deur, A; Djalali, C; Dodge, G E; Doughty, D; Dupre, R; Alaoui, A El; Fassi, L El; Elouadrhiri, L; Fedotov, G; Fegan, S; Fersch, R; Fleming, J A; Forest, T A; Garcon, M; Gevorgyan, N; Ghandilyan, Y; Gilfoyle, G P; Girod, F X; Giovanetti, K L; Goetz, J T; Gohn, W; Gothe, R W; Griffioen, K A; Guegan, B; Guler, N; Haffidi, K; Hanretty, C; Harrison, N; Hattawy, M; Hicks, K; Ho, D; Holtrop, M; Ilieva, Y; Ireland, D G; Ishkhanov, B S; Isupov, E L; Jawalkar, S; Jiang, X; Jo, H S; Joo, K; Kalantarians, N; Keith, C; Keller, D; Khandaker, M; Kim, A; Kim, W; Klein, A; Klein, F J; Koirala, S; Kubarovsky, V; Kuhn, S E; Kuleshov, S V; Lenisa, P; Livingston, K; Lu, H Y; MacGregor, I J D; Markov, N; Mayee, M; McKinnon, B; Meekins, D; Mineeva, T; Mirazita, M; Mokeev, V; Montgomery, R A; Moutarde, H; Movsisyan, A; Munevar, E; Camacho, C Munoz; Nadel-Turonski, P; Niccolai, S; Niculescu, G; Niculescu, I; Osipenko, M; Ostrovidov, A I; Pappalardo, L L; Paremuzyan, R; Park, K; Peng, P; Phillips, J J; Pierce, J; Pisano, S; Pogorelko, O; Pozdniakov, S; Price, J W; Procureur, S; Protopopescu, D; Puckett, A J R; Raue, B A; Rimal, D; Ripani, M; Rizzo, A; Rosner, G; Rossi, P; Roy, P; Sabatié, F; Saini, M S; Salgado, C; Schott, D; Schumacher, R A; Seder, E; Sharabian, Y G; Simonyan, A; Smith, C; Smith, G; Sober, D I; Sokhan, D; Stepanyan, S S; Stepanyan, S; Strakovsky, I I; Strauch, S; Sytnik, V; Taiuti, M; Tang, W; Tkachenko, S; Ungaro, M; Vernarsky, B; Vlassov, A V; Voskanyan, H; Voutier, E; Walford, N K; Watts, D P; Weinstein, L B; Zachariou, N; Zana, L; Zhang, J; Zhao, B; Zhao, Z W; Zonta, I

    2014-01-01

    The inclusive polarized structure functions of the proton and deuteron, g1p and g1d, were measured with high statistical precision using polarized 6 GeV electrons incident on a polarized ammonia target in Hall B at Jefferson Laboratory. Electrons scattered at lab angles between 18 and 45 degrees were detected using the CEBAF Large Acceptance Spectrometer (CLAS). For the usual DIS kinematics, Q^2>1 GeV^2 and the final-state invariant mass W>2 GeV, the ratio of polarized to unpolarized structure functions g1/F1 is found to be nearly independent of Q^2 at fixed x. Significant resonant structure is apparent at values of W up to 2.3 GeV. In the framework of perturbative QCD, the high-W results can be used to better constrain the polarization of quarks and gluons in the nucleon, as well as high-twist contributions.

  18. Radiation-induced chromosomal hot spots at G 1 and G 2 stages of human lymphocytes in culture

    Directory of Open Access Journals (Sweden)

    Murugesan R

    2003-01-01

    Full Text Available Radiation-induced chromosomal break points in cultured lymphocytes of normal healthy individuals as well as of those with certain genetic disorders are reported to be localized at certain specific loci (hot spots. These reports are based on studies carried out in lymphocytes irradiated at G 1 stage. The present study examines whether the location of hot spots and the frequency seen in cells irradiated at G 1 are similar to those irradiated at G 2 stage of the cell cycle and also tests whether cells of patients exhibit hot spots on irradiation.The results showed that the radiation induced chromosomal break points to be similar in those irradiated are G 1 and G 2 stages of the cell cycle and also that cells of patients exhibited chromosomal hot spots.

  19. Mean time for the development of large workloads and large queue lengths in the GI/G/1 queue

    Directory of Open Access Journals (Sweden)

    Charles Knessl

    1996-01-01

    Full Text Available We consider the GI/G/1 queue described by either the workload U(t (unfinished work or the number of customers N(t in the system. We compute the mean time until U(t reaches excess of the level K, and also the mean time until N(t reaches N0. For the M/G/1 and GI/M/1 models, we obtain exact contour integral representations for these mean first passage times. We then compute the mean times asymptotically, as K and N0→∞, by evaluating these contour integrals. For the general GI/G/1 model, we obtain asymptotic results by a singular perturbation analysis of the appropriate backward Kolmogorov equation(s. Numerical comparisons show that the asymptotic formulas are very accurate even for moderate values of K and N0.

  20. The radio expansion and brightening of the very young supernova remnant G1.9+0.3

    CERN Document Server

    Green, D A; Borkowski, K J; Hwang, U; Harrus, I; Petre, R

    2008-01-01

    Recent radio observations of the small Galactic supernova remnant G1.9+0.3 made at 4.86 GHz with the VLA are presented, and compared with earlier observations at 1.49 GHz which have a comparable resolution (10 x 4 arcsec^2). These show that the radio emission from this remnant has expanded significantly, by about 15 per cent over 23 years, with a current outer diameter of approximately 92 arcsec. This expansion confirms that G1.9+0.3 is the youngest Galactic remnant yet identified, only about 150 years old at most. Recent, lower resolution, 1.43-GHz observations are also discussed, and the integrated flux densities from these and the 4.86-GHz observations are compared with earlier results. This shows that the integrated flux density of G1.9+0.3 has been increasing recently.

  1. Precision measurements of g1 of the proton and the deuteron with 6 GeV electrons

    Energy Technology Data Exchange (ETDEWEB)

    Prok, Yelena; Bosted, Peter; Kvaltine, Nicholas; Adhikari, Krishna; Adikaram-Mudiyanselage, Dasuni; Aghasyan, Mher; Amaryan, Moskov; Anderson, Mark; Anefalos Pereira, Sergio; Avagyan, Harutyun; Baghdasaryan, Hovhannes; Ball, Jacques; Baltzell, Nathan; Battaglieri, Marco; Biselli, Angela; Bono, Jason; Briscoe, William; Brock, Joseph; Brooks, William; Bueltmann, Stephen; Burkert, Volker; Carlin, Christopher; Carman, Daniel; Celentano, Andrea; Chandavar, Shloka; Colaneri, Luca; Cole, Philip; Contalbrigo, Marco; Cortes, Olga; Crabb, Donald; Crede, Volker; D' Angelo, Annalisa; Dashyan, Natalya; De Vita, Raffaella; De Sanctis, Enzo; Deur, Alexandre; Djalali, Chaden; Dodge, Gail; Doughty, David; Dupre, Raphael; El Alaoui, Ahmed; El Fassi, Lamiaa; Elouadrhiri, Latifa; Fedotov, Gleb; Fegan, Stuart; Fersch, Robert; Fleming, Jamie; Forest, Tony; Garcon, Michel; Gevorgyan, Nerses; Ghandilyan, Yeranuhi; Gilfoyle, Gerard; Girod-Gard, Francois-Xavier; Giovanetti, Kevin; Goetz, John; Gohn, Wesley; Gothe, Ralf; Griffioen, Keith; Guegan, Baptiste; Guler, Nevzat; Hafidi, Kawtar; Hanretty, Charles; Harrison, Nathan; Hattawy, Mohammad; Hicks, Kenneth; Ho, Dao; Holtrop, Maurik; Ilieva, Yordanka; Ireland, David; Ishkhanov, Boris; Isupov, Evgeny; Jawalkar, Sucheta; Jiang, Xiaodong; Jo, Hyon-Suk; Joo, Kyungseon; Kalantarians, Narbe; Keith, Christopher; Keller, Daniel; Khandaker, Mahbubul; Kim, Andrey; Kim, Wooyoung; Klein, Andreas; Klein, Franz; Koirala, Suman; Kubarovsky, Valery; Kuhn, Sebastian; Kuleshov, Sergey; Lenisa, Paolo; Livingston, Kenneth; Lu, Haiyun; MacGregor, Ian; Markov, Nikolai; Mayer, Michael; McKinnon, Bryan; Meekins, David; Mineeva, Taisiya; Mirazita, Marco; Mokeev, Viktor; Montgomery, Rachel; MOUTARDE, Herve; Movsisyan, Aram; Munevar Espitia, Edwin; Munoz Camacho, Carlos; Nadel-Turonski, Pawel; Niccolai, Silvia; Niculescu, Gabriel; Niculescu, Maria; Osipenko, Mikhail; Ostrovidov, Alexander; Pappalardo, Luciano; Paremuzyan, Rafayel; Park, K; Peng, Peng; Phillips, J J; Pierce, Joshua; Pisano, Silvia; Pogorelko, Oleg; Pozdniakov, Serguei; Price, John; Procureur, Sebastien; Protopopescu, Dan; Puckett, Andrew; Raue, Brian; Rimal, Dipak; Ripani, Marco; Rizzo, Alessandro; Rosner, Guenther; Rossi, Patrizia; Roy, Priyashree; Sabatie, Franck; Saini, Mukesh; Salgado, Carlos; Schott, Diane; Schumacher, Reinhard; Seder, Erin; Sharabian, Youri; Simonyan, Ani; Smith, Claude; Smith, Gregory; Sober, Daniel; Sokhan, Daria; Stepanyan, Stepan; Stepanyan, Samuel; Strakovski, Igor; Strauch, Steffen; Sytnik, Valeriy; Taiuti, Mauro; Tang, Wei; Tkachenko, Svyatoslav; Ungaro, Maurizio; Vernarsky, Brian; Vlasov, Alexander; Voskanyan, Hakob; Voutier, Eric; Walford, Natalie; Watts, Daniel; Weinstein, Lawrence; Zachariou, Nicholas; Zana, Lorenzo; Zhang, Jixie; Zhao, Bo; Zhao, Zhiwen; Zonta, Irene

    2014-08-01

    The inclusive polarized structure functions of the proton and deuteron, g1p and g1d, were measured with high statistical precision using polarized 6 GeV electrons incident on a polarized ammonia target in Hall B at Jefferson Laboratory. Electrons scattered at lab angles between 18 and 45 degrees were detected using the CEBAF Large Acceptance Spectrometer (CLAS). For the usual DIS kinematics, Q^2>1 GeV^2 and the final-state invariant mass W>2 GeV, the ratio of polarized to unpolarized structure functions g1/F1 is found to be nearly independent of Q^2 at fixed x. Significant resonant structure is apparent at values of W up to 2.3 GeV. In the framework of perturbative QCD, the high-W results can be used to better constrain the polarization of quarks and gluons in the nucleon, as well as high-twist contributions.

  2. Improvement of vascular function by acute and chronic treatment with the GPR30 agonist G1 in experimental diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Zi-lin Li

    Full Text Available The G-protein coupled estrogen receptor 30 (GPR30 is a seven-transmembrane domain receptor that mediates rapid estrogen responses in a wide variety of cell types. This receptor is highly expressed in the cardiovascular system, and exerts vasodilatory effects. The objective of the present study was to investigate the effects of GPR30 on vascular responsiveness in diabetic ovariectomized (OVX rats and elucidate the possible mechanism involved. The roles of GPR30 were evaluated in the thoracic aorta and cultured endothelial cells. The GPR30 agonist G1 induced a dose-dependent vasodilation in the thoracic aorta of the diabetic OVX rats, which was partially attenuated by the nitric oxide synthase (NOS inhibitor, nitro-L-arginine methylester (L-NAME and the GPR30-selective antagonist G15. Dose-dependent vasoconstrictive responses to phenylephrine were attenuated significantly in the rings of the thoracic aorta following the acute G1 administration in the diabetic OVX rats. This effect of G1 was abolished partially by L-NAME and G15. The acute administration of G1 increased significantly the eNOS activity and the concentration of NO in the endothelial cells exposed to high glucose. G1 treatment induced an enhanced endothelium-dependent relaxation to acetylcholine (Ach in the diabetic OVX rats. Further examination revealed that G1 induced vasodilation in the diabetic OVX rats by increasing the phosphorylation of eNOS. These findings provide preliminary evidence that GPR30 activation leads to eNOS activation, as well as vasodilation, to a certain degree and has beneficial effects on vascular function in diabetic OVX rats.

  3. A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

    Directory of Open Access Journals (Sweden)

    Ryuta Ueda

    Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

  4. Evaluation of Palm PCRTM G1-12 System: a portable battery-operated PCR thermal cycler

    Directory of Open Access Journals (Sweden)

    Siti Aminah Ahmed

    2016-08-01

    Full Text Available Polymerase chain reaction (PCR is the basis of recombinant and other molecular biological techniques. Availability of cheap and robust PCR platforms enables the tests to be performed easily, even in resource constrained settings. Herein we compared the efficacy of a portable thermal cycler ( Palm PCRTM G1-12 System for rapid DNA amplification against the standard Peltier-based thermal cycler using plasmid DNA and genomic DNA in single and multiplex PCR experiments. Our study revealed that the Palm PCRTM G1-12 System could be a portable DNA amplification system to conduct various molecular techniques, especially in places where resources are limited.

  5. Thermodynamic characterization of the PR-10 allergens Bet v 1, Api g 1 and Dau c 1 and pH-dependence of nApi g 1 and nDau c 1

    NARCIS (Netherlands)

    Bollen, M.A.; Wichers, H.J.; Helsper, J.P.F.G.; Savelkoul, H.F.J.; Boekel, van M.A.J.S.

    2010-01-01

    Natural and recombinant Bet v 1, the major birch pollen allergen, and homologous allergens, Api g 1 and Dau c 1, from celery and carrot, respectively, were studied by CD spectroscopy under conditions of varying denaturant concentration, pH and temperature to determine fundamental thermodynamic param

  6. Base substitution mutations in uridinediphosphate-dependent glycosyltransferase 76G1 gene of Stevia rebaudiana causes the low levels of rebaudioside A: mutations in UGT76G1, a key gene of steviol glycosides synthesis.

    Science.gov (United States)

    Yang, Yong-Heng; Huang, Su-Zhen; Han, Yu-Lin; Yuan, Hai-Yan; Gu, Chun-Sun; Zhao, Yan-Hai

    2014-07-01

    Steviol glycosides, extracted from the leaves of Stevia rebaudiana (Bert) Bertoni, are calorie-free sugar substitute of natural origin with intensely sweet (Boileau et al., 2012). Stevioside and rebaudioside A are the two main kinds of the diterpenic glycosides. We analyzed the concentration of stevioside and rebaudioside A in Stevia leaves of about 500 samples (hybrid progenies) and discovered a mutation plant "Z05" with very low levels of rebaudioside A. Because UGT76G1, a uridinediphosphate-dependent glycosyltransferases, is responsible for the conversion from stevioside to rebaudioside A (Richman et al., 2005), so mutation identification was done by sequencing the candidate gene, UGT76G1. In this study molecular analysis of two strains revealed a heterozygotic nonsense mutation of c.389T > G (p.L121X) in UGT76G1. Meanwhile, we found some amino acid substitutions significant change the protein structure. And the difference of enzyme activity between two strains proved the lack of functionality of UGT76G1 of the mutation "Z05". So the nonsense mutation and amino acid substitution mutation resulted in the low levels of rebaudioside A.

  7. 考虑驾驶员行为偏好的车辆最优路径选择的G1-TOPSIS法%Vehicle Optimal Path Selection Based on G1-TOPSIS method Considering the Behavior Preference of Driver

    Institute of Scientific and Technical Information of China (English)

    邢建平

    2015-01-01

    The previous optimal path selection of vehicles is mostly considered the shortest path or the least time. However, in practice, there is often a different behavior preference. The different requirements of the driver in the path selection are considered in this article, and the G1 method is used to determine the weight of the influence factors on the path selection. Further the optimal path method based on TOPSIS combining with G1 method is developed, which considers the driver's behavior preference. An example is used to show that the proposed method is effective and practical.%以前的车辆最优路径选择大多是考虑路程最短或时间最少。然而在实际的情形往往是伴随着驾驶员不同的行为偏好。充分考虑了驾驶员在路径选择中的不同要求,将G1法引入到驾驶员路径选择影响因素的权重确定,同时发展出基于G1-TOPSIS法车辆最优路径方法,并通过应用例子说明了方法的有效性和实用性。

  8. Thermodynamic characterization of the PR-10 allergens Bet v 1, Api g 1 and Dau c 1 and pH-dependence of nApi g 1 and nDau c 1

    NARCIS (Netherlands)

    Bollen, M.A.; Wichers, H.J.; Helsper, J.P.F.G.; Savelkoul, H.F.J.; Boekel, van M.A.J.S.

    2010-01-01

    Natural and recombinant Bet v 1, the major birch pollen allergen, and homologous allergens, Api g 1 and Dau c 1, from celery and carrot, respectively, were studied by CD spectroscopy under conditions of varying denaturant concentration, pH and temperature to determine fundamental thermodynamic param

  9. Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype.

    Science.gov (United States)

    Caldas, Ivo Santana; Diniz, Livia de Figueiredo; Guedes, Paulo Marcos da Matta; Nascimento, Álvaro Fernando da Silva do; Galvão, Lúcia Maria da Cunha; Lima, Wanderson Geraldo de; Caldas, Sérgio; Bahia, Maria Terezinha

    2017-03-01

    This study was designed to verify the relationship between IgG antibodies isotypes and myocarditis in Trypanosoma cruzi infection using mice and dogs infected with different T. cruzi strains. The animals were infected with benznidazole-susceptible Berenice-78 and benznidazole-resistant AAS and VL-10 strains. The IgG subtypes were measured in serum samples from dogs (IgG, IgG1, and IgG2) and mice (IgG, IgG1, IgG2a, and IgG2b). The infection of dogs with VL-10 strain induced the highest levels of heart inflammation while intermediate and lower levels were detected with Berenice-78 and AAS strains, respectively. Similar results were found in mice infected with VL-10, but not in those infected with AAS or Berenice-78 strains. The AAS strain induced higher levels of heart inflammation in mice, while Berenice-78 strain was not able to induce it. Correlation analysis between myocarditis and antibody reactivity index revealed very interesting results, mainly for IgG and IgG1, the latter being the most exciting. High IgG1 showed a significant correlation with myocarditis in both experimental models, being more significant in dogs (r=0.94, pmyocarditis intensity in Chagas disease.

  10. The structure of VgrG1 from Pseudomonas aeruginosa, the needle tip of the bacterial type VI secretion system.

    Science.gov (United States)

    Spínola-Amilibia, Mercedes; Davó-Siguero, Irene; Ruiz, Federico M; Santillana, Elena; Medrano, Francisco Javier; Romero, Antonio

    2016-01-01

    The type VI secretion system (T6SS) is a mechanism that is commonly used by pathogenic bacteria to infect host cells and for survival in competitive environments. This system assembles on a core baseplate and elongates like a phage puncturing device; it is thought to penetrate the target membrane and deliver effectors into the host or competing bacteria. Valine-glycine repeat protein G1 (VgrG1) forms the spike at the tip of the elongating tube formed by haemolysin co-regulated protein 1 (Hcp1); it is structurally similar to the T4 phage (gp27)3-(gp5)3 puncturing complex. Here, the crystal structure of full-length VgrG1 from Pseudomonas aeruginosa is reported at a resolution of 2.0 Å, which through a trimeric arrangement generates a needle-like shape composed of two main parts, the head and the spike, connected via a small neck region. The structure reveals several remarkable structural features pointing to the possible roles of the two main segments of VgrG1: the head as a scaffold cargo domain and the β-roll spike with implications in the cell-membrane puncturing process and as a carrier of cognate toxins.

  11. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 sw

  12. COST Actions G1 and G8: EU programs on the use of radiation in art and archaeometry

    Energy Technology Data Exchange (ETDEWEB)

    Adriaens, Annemie E-mail: annemie.adriaens@ugent.be; Demortier, Guy

    2004-11-01

    This paper gives an overview of the research activities within the European COST Actions G1 and G8. Both actions aim at achieving a better preservation and conservation of our cultural heritage by increasing the knowledge in art and archaeological objects through chemical and physical analyses.

  13. Antigenic differences between the EG95-related proteins from Echinococcus granulosus G1 and G6 genotypes: implications for vaccination.

    Science.gov (United States)

    Alvarez Rojas, C A; Gauci, C G; Lightowlers, M W

    2013-02-01

    Cystic echinococcosis caused by Echinococcus granulosus remains an important and neglected issue in public health. The study of the likely efficacy of the currently available EG95 vaccine against other genotypes of the parasite is important to improve the vaccine as a potential tool to be used in control programmes. The recombinant vaccine EG95-1G1 was developed based on the G1 genotype of E. granulosus. Characterization of the eg95 gene family in the G6 genotype by genomic DNA cloning previously produced the first unequivocal information about the composition of the gene family in a different genotype. The information was used in this study to predict and express two EG95-related proteins from the G6 genotype as recombinants, for assessment of their capacity to bind antibodies raised in sheep vaccinated with the EG95-1G1 vaccine. The proteins (EG95-1G6 and EG95-5G6) from the G6 genotype of E. granulosus were unable to bind all the antibodies raised by sheep vaccinated with EG95-1G1. Differences in the amino acid sequence of EG95-related proteins from G6 and likely the differences in the encoded FnIII domain may be responsible for changes in the conformation of these epitopes.

  14. The transient M/G/1/0 queue: some bounds and approximations for light traffic with application to reliability

    Directory of Open Access Journals (Sweden)

    J. Ben Atkinson

    1995-01-01

    Full Text Available We consider the transient analysis of the M/G/1/0 queue, for which Pn(t denotes the probability that there are no customers in the system at time t, given that there are n(n=0,1 customers in the system at time 0. The analysis, which is based upon coupling theory, leads to simple bounds on Pn(t for the M/G/1/0 and M/PH/1/0 queues and improved bounds for the special case M/Er/1/0. Numerical results are presented for various values of the mean arrival rate λ to demonstrate the increasing accuracy of approximations based upon the above bounds in light traffic, i.e., as λ→0. An important area of application for the M/G/1/0 queue is as a reliability model for a single repairable component. Since most practical reliability problems have λ values that are small relative to the mean service rate, the approximations are potentially useful in that context. A duality relation between the M/G/1/0 and GI/M/1/0 queues is also described.

  15. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 sw

  16. Draft Genome Sequence of Brucella melitensis Strain ADMAS-G1, Isolated from Placental Fluids of an Aborted Goat.

    Science.gov (United States)

    Shome, Rajeswari; Krithiga, Natesan; Muttannagouda, Revanasiddappa Biradar; Veeregowda, Belamaranahalli Muniveerappa; Swati, Sahay; Shome, Bibek Ranjan; Vishnu, Udayakumar; Sankarasubramanian, Jagadesan; Sridhar, Jayavel; Gunasekaran, Paramasamy; Rahman, Habibur; Rajendhran, Jeyaprakash

    2013-10-10

    Here, we report the draft genome sequence and annotation of the Brucella melitensis strain designated ADMAS-G1, isolated from placental fluids of an aborted goat. The length of the genome is 3,284,982 bp, with a 57.3% GC content. A total of 3,325 protein-coding genes and 63 RNA genes were predicted.

  17. Draft Genome Sequence of Brucella melitensis Strain ADMAS-G1, Isolated from Placental Fluids of an Aborted Goat

    OpenAIRE

    Shome, Rajeswari; Krithiga, Natesan; Muttannagouda, Revanasiddappa Biradar; Veeregowda, Belamaranahalli Muniveerappa; Swati, Sahay; Shome, Bibek Ranjan; Vishnu, Udayakumar; Sankarasubramanian, Jagadesan; Sridhar, Jayavel; Gunasekaran, Paramasamy; Rahman, Habibur; Rajendhran, Jeyaprakash

    2013-01-01

    Here, we report the draft genome sequence and annotation of the Brucella melitensis strain designated ADMAS-G1, isolated from placental fluids of an aborted goat. The length of the genome is 3,284,982 bp, with a 57.3% GC content. A total of 3,325 protein-coding genes and 63 RNA genes were predicted.

  18. Insensitive bounds for the moments of the sojourn time distribution in the M/G/1 processor-sharing queue

    NARCIS (Netherlands)

    Cheung, S.K.; Berg, J.L. van den; Boucherie, R.J.

    2006-01-01

    This paper studies the M/G/1 processor-sharing (PS) queue, in particular the sojourn time distribution conditioned on the initial job size. Although several expressions for the Laplace-Stieltjes transform (LST) are known, these expressions are not suitable for computational purposes. This paper deri

  19. A two-stage approach in solving the state probabilities of the multi-queue M/G/1 model

    Science.gov (United States)

    Chen, Mu-Song; Yen, Hao-Wei

    2016-04-01

    The M/G/1 model is the fundamental basis of the queueing system in many network systems. Usually, the study of the M/G/1 is limited by the assumption of single queue and infinite capacity. In practice, however, these postulations may not be valid, particularly when dealing with many real-world problems. In this paper, a two-stage state-space approach is devoted to solving the state probabilities for the multi-queue finite-capacity M/G/1 model, i.e. q-M/G/1/Ki with Ki buffers in the ith queue. The state probabilities at departure instants are determined by solving a set of state transition equations. Afterward, an embedded Markov chain analysis is applied to derive the state probabilities with another set of state balance equations at arbitrary time instants. The closed forms of the state probabilities are also presented with theorems for reference. Applications of Little's theorem further present the corresponding results for queue lengths and average waiting times. Simulation experiments have demonstrated the correctness of the proposed approaches.

  20. IgG1 adsorption to siliconized glass vials-influence of pH, ionic strength, and nonionic surfactants.

    Science.gov (United States)

    Höger, Kerstin; Mathes, Johannes; Frieß, Wolfgang

    2015-01-01

    In this study, the adsorption of an IgG1 antibody to siliconized vials was investigated with focus on the formulation parameters pH, ionic strength, and nonionic surfactants. Electrophoretic mobility measurements were performed to investigate the charge characteristics of protein and siliconized glass particles at different pH values. Calculation of the electrokinetic charge density allowed further insight into the energetic conditions in the protein-sorbent interface. Maximum adsorption of IgG1 was found at acidic pH values and could be correlated with energetically favorable minimal ion incorporation into the interface. The importance of electrostatic interactions for IgG1 adsorption at acidic pH values was also confirmed by the efficient adsorption reduction at decreased solution ionic strength. A second adsorption maximum around the pI of the protein was assigned to hydrophobic interactions with the siliconized surface. Addition of the nonionic surfactants poloxamer 188 or polysorbate 80 resulted in almost complete suppression of adsorption at pH 7.2, and a strong but less efficient effect at pH 4 on siliconized glass vials. This adsorption suppression was much less pronounced on borosilicate glass vials. From these results, it can be concluded that electrostatic interactions contribute substantially to IgG1 adsorption to siliconized glass vials especially at acidic formulation pH.

  1. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1

  2. Dynamic FoxG1 expression coordinates the integration of multipolar pyramidal neuron precursors into the cortical plate.

    Science.gov (United States)

    Miyoshi, Goichi; Fishell, Gord

    2012-06-21

    Pyramidal cells of the cerebral cortex are born in the ventricular zone and migrate through the intermediate zone to enter into the cortical plate. In the intermediate zone, these migrating precursors move tangentially and initiate the extension of their axons by transiently adopting a characteristic multipolar morphology. We observe that expression of the forkhead transcription factor FoxG1 is dynamically regulated during this transitional period. By utilizing conditional genetic strategies, we show that the downregulation of FoxG1 at the beginning of the multipolar cell phase induces Unc5D expression, the timing of which ultimately determines the laminar identity of pyramidal neurons. In addition, we demonstrate that the re-expression of FoxG1 is required for cells to transit out of the multipolar cell phase and to enter into the cortical plate. Thus, the dynamic expression of FoxG1 during migration within the intermediate zone is essential for the proper assembly of the cerebral cortex.

  3. Identification of up-regulated proteins potentially involved in the antagonism mechanism of Bacillus amyloliquefaciens G1.

    Science.gov (United States)

    Cao, Haipeng; Zheng, Weidong; He, Shan; Wang, Hao; Wang, Tu; Lu, Liqun

    2013-06-01

    The use of Bacillus probiotics has been demonstrated as a promising method in the biocontrol of bacterial diseases in aquaculture. However, the molecular antibacterial mechanism of Bacillus still remains unclear. In order to explore the antibacterial mechanism of the potential antagonistic Bacillus amyloliquefaciens strain G1, comparative proteomics between B. amyloliquefaciens strain G1 and its non-antagonistic mutant strain was investigated. The 2-dimensional electrophoresis gel maps of their total extracted proteins were described and 42 different proteins were found to be highly expressed in strain G1 in comparison with those in the mutant strain. 35 of these up-regulated proteins were successfully identified using MALDI-TOF-TOF MS and databank analysis, and their biological functions were analyzed through the KEGG database. The increased expression of these proteins suggested that high levels of energy metabolism, biosynthesis and stress resistance could play important roles in strain G1's antagonism. To our knowledge, this is the first report on the proteins involved in the antagonism mechanism of B. amyloliquefaciens using a proteomic approach and the proteomic data also contribute to a better understanding of the molecular basis for the antagonism of B. amyloliquefaciens.

  4. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.

    Directory of Open Access Journals (Sweden)

    Neel M Fofaria

    Full Text Available In this study, we determined the cytotoxic effects of piperine, a major constituent of black and long pepper in melanoma cells. Piperine treatment inhibited the growth of SK MEL 28 and B16 F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest by piperine treatment was associated with DNA damage as indicated by phosphorylation of H2AX at Ser139, activation of ataxia telangiectasia and rad3-related protein (ATR and checkpoint kinase 1 (Chk1. Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Similarly, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine. Piperine treatment caused down-regulation of E2F1 and phosphorylation of retinoblastoma protein (Rb. Apoptosis induced by piperine was associated with down-regulation of XIAP, Bid (full length and cleavage of Caspase-3 and PARP. Furthermore, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS by tiron protected the cells from piperine mediated cell cycle arrest and apoptosis. These results suggest that piperine mediated ROS played a critical role in inducing DNA damage and activation of Chk1 leading to G1 cell cycle arrest and apoptosis.

  5. Overestimated Oncologic Significance of Lymph Node Metastasis in G1 Nonfunctioning Neuroendocrine Tumor in the Left Side of the Pancreas.

    Science.gov (United States)

    Yoo, Young Jin; Yang, Seok Jeong; Hwang, Ho Kyoung; Kang, Chang Moo; Kim, Hogeun; Lee, Woo Jung

    2015-09-01

    Recent studies have expounded on the oncologic significance of lymph node metastasis in nonfunctioning (NF) neuroendocrine tumors (NETs) of the pancreas and suggest regional lymph node dissection for treating pancreatic NET. We tested this recommendation in NF pancreatic NET-G1, as these tumors are generally small and suitable for function-preserving minimally invasive pancreatectomy.From January 2005 to December 2014, medical records of patients who underwent pancreatectomy for pathologically confirmed NF NET-G1 of the left side of the pancreas were retrospectively reviewed. Oncologic outcomes were compared between limited pancreatectomy and distal pancreatosplenectomy.Thirty-five patients (14 males and 21 females) with a mean age of 55.9 ± 11.4 years were enrolled in this study. Six patients (17.1%) underwent distal pancreatosplenectomy. Limited pancreatectomies comprised 15 spleen-preserving distal pancreatectomies (42.8%), 10 enucleations (28.6%), and 4 central pancreatectomies (11.4%). Lymph node metastasis was not found in 6 patients who underwent distal pancreatectomy with a splenectomy; meanwhile, the others were regarded as pNx since no lymph node retrieval was attempted during the limited pancreatectomy. Overall disease-free survival was 36.5 months (95% confidence interval [CI]: 25.9-47.1) and no tumor-related mortality was noted. Minimally invasive pancreatectomy (P = 0.557) and limited pancreatectomy (P = 0.758) showed no adverse impact in treating NF NET-G1 of the left side of the pancreas.The oncologic significance of lymph node metastasis is overestimated in NF NET-G1 of the left side of the pancreas. Routine conventional distal pancreatosplenectomy to retrieve regional lymph nodes may be too excessive in treating NF NET-G1 of the distal pancreas.

  6. Transformation abrogates an early G1-phase arrest point required for specification of the Chinese hamster DHFR replication origin.

    Science.gov (United States)

    Wu, J R; Keezer, S M; Gilbert, D M

    1998-03-16

    The origin decision point (ODP) was originally identified as a distinct point during G1-phase when Chinese hamster ovary (CHO) cell nuclei experience a transition that is required for specific recognition of the dihydrofolate reductase (DHFR) origin locus by Xenopus egg extracts. Passage of cells through the ODP requires a mitogen-independent protein kinase that is activated prior to restriction point control. Here we show that inhibition of an early G1-phase protein kinase pathway by the addition of 2-aminopurine (2-AP) prior to the ODP arrests CHO cells in G1-phase. Transformation with simian virus 40 (SV40) abrogated this arrest point, resulting in the entry of cultured cells into S-phase in the presence of 2-AP and a disruption of the normal pattern of initiation sites at the DHFR locus. Cells treated with 2-AP after the ODP initiated replication specifically within the DHFR origin locus. Transient exposure of transformed cells to 2-AP during the ODP transition also disrupted origin choice, whereas non-transformed cells arrested in G1-phase and then passed through a delayed ODP after removal of 2-AP from the medium. We conclude that mammalian cells have many potential sites at which they can initiate replication. Normally, events occurring during the early G1-phase ODP transition determine which of these sites will be the preferred initiation site. However, if chromatin is exposed to S-phase-promoting factors prior to this transition, mammalian cells, like Xenopus and Drosophila embryos, can initiate replication without origin specification.

  7. Improved ENSO simulation from climate system model FGOALS-g1.0 to FGOALS-g2

    Science.gov (United States)

    Chen, Lin; Yu, Yongqiang; Zheng, Weipeng

    2016-10-01

    This study presents an overview of the improvement in the simulation of El Niño-Southern Oscillation (ENSO) in the latest generation of the Institute of Atmospheric Physics' coupled general circulation model (CGCM), the Flexible Global Ocean-Atmosphere-Land System model Grid-point Version 2 (FGOALS-g2; hereafter referred to as "g2") from its predecessor FGOALS-g1.0 (referred to as "g1"), including the more realistic amplitude, irregularity, and ENSO cycle. The changes have been analyzed quantitatively based on the Bjerknes stability index, which serves as a measure of ENSO growth rate. The improved simulation of ENSO amplitude is mainly due to the reasonable representation of the thermocline and thermodynamic feedbacks: On the one hand, the deeper mean thermocline results in a weakened thermocline response to the zonal wind stress anomaly, and the looser vertical stratification of mean temperature leads to a weakened response of anomalous subsurface temperature to anomalous thermocline depth, both of which cause the reduced thermocline feedback in g2; on the other hand, the alleviated cold bias of mean sea surface temperature leads to more reasonable thermodynamic feedback in g2. The regular oscillation of ENSO in g1 is associated with its unsuccessful representation of the role of atmospheric noise over the western-central equatorial Pacific (WCEP) in triggering ENSO events, which arises from the weak synoptic-intraseasonal variability of zonal winds over the WCEP in g1. The asymmetric transition of ENSO in g1 is attributed to the asymmetric effect of thermocline feedback, which is due to the annual cycle of mean upwelling in the eastern Pacific. This study highlights the great impact of improving the representation of mean states on the improved simulation of air-sea feedback processes and ultimately more reasonable depiction of ENSO behaviors in CGCMs.

  8. G1 condition for C-curves and application in surface modeling%C-曲线间G1拼接条件及在曲面造型中的应用

    Institute of Scientific and Technical Information of China (English)

    王刘强; 刘旭敏

    2007-01-01

    C-B样条无法精确表示半圆弧和半椭圆弧,在对C-B样条曲线和C-Bézier曲线基函数及端点特性分析的基础上,通过增加控制顶点使C-B样条曲线通过控制多边形的首末顶点并与首末边相切,给出了C-B样条曲线和C-Bézier曲线间G1拼接条件;利用C-Bézier曲线表示半圆弧和半椭圆弧,并与C-B样条曲线进行G1拼接,从而解决了C-B样条曲面造型中半圆弧和半椭圆弧的表示问题.

  9. 批量到达带启动时间的单重休假M/G/1排队系统%Single Vacation and Set-Up Time of M/G/1 Queueing System with Batch Arrival

    Institute of Scientific and Technical Information of China (English)

    高娃

    2005-01-01

    本文研究批量到达带启动时间的单重休假的M/G/1排队系统,给出稳态队长的母函数和等待时间分布的LST及其它们的随机分解结果,推导出忙期、闲期和线期母函数和均值.

  10. The Geomx/G/1 Queue with Batch Arrival and Second Optional Service%具有成批到达和二次可选服务的Geomx/G/1排队

    Institute of Scientific and Technical Information of China (English)

    赵媛; 田乃硕

    2011-01-01

    在经典Geom/G/1排队系统中引入成批到达和二次可选服务,研究了一个具有成批到达和二次可选服务的Geomx/G/1排队系统.通过引入广义服务时间,运用嵌入Markov链的方法研究了该排队系统的各项指标,得到了其稳态队长及等待时间分布的母函数,并给出了该模型的两个特例.%Batch arrival and second optional service were introduced in the classical Geom/G/1 queue system. Then the queue model was built and described. By using the method of imbedded Markov chains and leading into broad sense service time, the PGF of the steady state queue length and waiting time were derived. And two particular models were given.

  11. Isolation and partial identification of eight endogenous G1 inhibitors of JB-1 ascites tumor cell proliferation.

    Science.gov (United States)

    Barfod, N M

    1982-06-01

    Eight endogenous G1 inhibitors of the proliferation of JB-1 ascites tumor cells have been isolated and characterized. The activity of the inhibitors has been analyzed on synchronized JB-1 (murine plasmacytoma) and L1A2 (murine sarcoma) cells in vitro using flow cytometry. The purified inhibitors have been tested for in vivo activity on partially synchronized JB-1 and L1A2 ascites tumors in situ. Four of the inhibitors exhibited a high degree of cell specificity (chalone-like inhibitors) and were chemically related, whereas the other four showed no cell specificity. In most extractions, the amount of cell-specific activity is more than 50% of the total G1-inhibitory activity. Most of the inhibitors are low-molecular-weight peptides and glycopeptides.

  12. Crystal Structures of Glycosyltransferase UGT78G1 Reveal the Molecular Basis for Glycosylation and Deglycosylation of (Iso)flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Modolo, Luzia V.; Li, Lenong; Pan, Haiyun; Blount, Jack W.; Dixon, Richard A.; Wang, Xiaoqiang; (SRNF)

    2010-09-21

    The glycosyltransferase UGT78G1 from Medicago truncatula catalyzes the glycosylation of various (iso)flavonoids such as the flavonols kaempferol and myricetin, the isoflavone formononetin, and the anthocyanidins pelargonidin and cyanidin. It also catalyzes a reverse reaction to remove the sugar moiety from glycosides. The structures of UGT78G1 bound with uridine diphosphate or with both uridine diphosphate and myricetin were determined at 2.1 {angstrom} resolution, revealing detailed interactions between the enzyme and substrates/products and suggesting a distinct binding mode for the acceptor/product. Comparative structural analysis and mutagenesis identify glutamate 192 as a key amino acid for the reverse reaction. This information provides a basis for enzyme engineering to manipulate substrate specificity and to design effective biocatalysts with glycosylation and/or deglycosylation activity.

  13. Evolutionarily conserved transcription factor Apontic controls the G1/S progression by inducing cyclin e during eye development

    KAUST Repository

    Liu, Qingxin

    2014-06-16

    During Drosophila eye development, differentiation initiates in the posterior region of the eye disk and progresses anteriorly as a wave marked by the morphogenetic furrow (MF), which demarcates the boundary between anterior undifferentiated cells and posterior differentiated photoreceptors. However, the mechanism underlying the regulation of gene expression immediately before the onset of differentiation remains unclear. Here, we show that Apontic (Apt), which is an evolutionarily conserved transcription factor, is expressed in the differentiating cells posterior to the MF. Moreover, it directly induces the expression of cyclin E and is also required for the G1-to-S phase transition, which is known to be essential for the initiation of cell differentiation at the MF. These observations identify a pathway crucial for eye development, governed by a mechanism in which Cyclin E promotes the G1-to-S phase transition when regulated by Apt.

  14. TRANSIENT QUEUE SIZE DISTRIBUTION SOLUTION OF GEOM/G/1 QUEUE WITH FEEDBACK-A RECURSIVE METHOD

    Institute of Scientific and Technical Information of China (English)

    Chuanyi LUO; Yinghui TANG; Cailiang LI

    2009-01-01

    This paper considers the Geom/G/1 queueing model with feedback according to a late arrival system with delayed access (LASDA). Using recursive method, this paper studies the transient property of the queue size from the initial state N(0+) = I. Some new results about the recursive expression of the transient queue size distribution at any epoch n+ and the recursive formulae of the equilibrium distribution are obtained, Furthermore, the recursive formulae of the equilibrium queue size distribution at epoch n-, and n are obtained, too. The important relations between stationary queue size distributions at different epochs are discovered (being different from the relations given in M/G/1 queueing system). The model discussed in this paper can be widely applied in all kinds of communications and computer network.

  15. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

    DEFF Research Database (Denmark)

    Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

    2015-01-01

    mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise...... temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin...

  16. X-ray Spectral Variations in the Youngest Galactic Supernova Remnant G1.9+0.3

    CERN Document Server

    Reynolds, S P; Green, D A; Hwang, U; Harrus, I; Petre, R

    2009-01-01

    The discovery of the youngest Galactic supernova remnant (SNR) G1.9+0.3 has allowed a look at a stage of SNR evolution never before observed. We analyze the 50 ks Chandra observation with particular regard to spectral variations. The very high column density ($N_H \\sim 6 \\times 10^{22}$ cm$^{-2}$) implies that dust scattering is important, and we use a simple scattering model in our spectral analysis. The integrated X-ray spectrum of G1.9+0.3 is well described by synchrotron emission from a power-law electron distribution with an exponential cutoff. Using our measured radio flux and including scattering effects, we find a rolloff frequency of $5.4 (3.0, 10.2) \\times 10^{17}$ Hz ($h \

  17. The ($G' /G, 1/G$)-expansion method for solving nonlinear space–time fractional differential equations

    Indian Academy of Sciences (India)

    EMRULLAH YA¸SAR; ILKER BURAK GIRESUNLU

    2016-08-01

    In this work, we present ($G' /G, 1/G$)-expansion method for solving fractional differential equations based on a fractional complex transform. We apply this method for solving space–time fractional Cahn--Allen equation and space--time fractional Klein–Gordon equation. The fractional derivatives are described in the sense of modified Riemann--Lioville. As a result of some exact solution in the form of hyperbolic, trigonometric and rational solutions are deduced. The obtained solutions may be used for explaining of some physical problems.The($G' /G, 1/G$)-expansion method has a wider applicability for nonlinear equations. We have verified all the obtained solutions with the aid of Maple.

  18. 26 CFR 1.1033(g)-1 - Condemnation of real property held for productive use in trade or business or for investment.

    Science.gov (United States)

    2010-04-01

    ... productive use in trade or business or for investment. 1.1033(g)-1 Section 1.1033(g)-1 Internal Revenue... Nontaxable Exchanges § 1.1033(g)-1 Condemnation of real property held for productive use in trade or business... advertising displays as real property—(1) In general. Under section 1033(g)(3) of the Code, a taxpayer...

  19. Detailed petrographic descriptions and microprobe data for tertiary silicic volcanic rocks in drill hole USW G-1, Yucca Mountain, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Caporuscio, F.A.; Warren, R.G.; Broxton, D.E.

    1985-12-01

    This report contains detailed petrographic descriptions of 74 thin sections from drill hole USW G-1 at Yucca Mountain, Nevada. These descriptions are keyed to the distinctions between devitrified, vitrophyre, vitric, and zeolitized intervals below the Topopah Spring Member repository horizon. The petrographic features of the zeolitized intervals down through the Crater Flat tuff, as well as the sorption properties determined from these intervals, suggest that these zeolite occurrences may each have comparable sorptive capability.

  20. The hard X-ray view of the young supernova remnant G1.9+0.3

    DEFF Research Database (Denmark)

    Zoglauer, Andreas; Reynolds, Stephen P.; An, Hongjun

    2015-01-01

    NuSTAR observed G1.9+0.3, the youngest known supernova remnant in the Milky Way, for 350 ks and detected emission up to ~30 keV. The remnant's X-ray morphology does not change significantly across the energy range from 3 to 20 keV. A combined fit between NuSTAR and Chandra shows that the spectrum...

  1. Echinococcus ortleppi (G5) and Echinococcus granulosus sensu stricto (G1) loads in cattle from Southern Brazil.

    Science.gov (United States)

    Balbinotti, Helier; Santos, Guilherme B; Badaraco, Jeferson; Arend, Ana C; Graichen, Daniel Ângelo S; Haag, Karen L; Zaha, Arnaldo

    2012-09-10

    Echinococcus granulosus sensu stricto (G1) and Echinococcus ortleppi (G5) are haplotypes of the parasite formerly known as Echinococcus granulosus sensu lato, which in its larval stage causes cystic hydatid disease, endemic in Southern Brazil. Epidemiological and molecular knowledge about the haplotypes occurring in a region is essential to control the spread of the disease. The aim of this work was to analyze the haplotype frequency and fertility of hydatid cysts in cattle from the state of Rio Grande do Sul. Cysts were collected and classified according to their fertility status. DNA was extracted from protoscoleces and germinal layers and then used as template for the amplification of the cytochrome c oxidase subunit 1 gene by PCR. Amplicons were purified and sequenced, and the sequences were analyzed for haplotype identification. A total of 638 fertile cysts collected in the last ten years were genotyped. On average, G1 (56.6%) was more frequent than G5 (43.4%). In lungs, the G5 haplotype exhibited a higher parasite load (52.8%), whereas in the liver, G1 was more frequent (90.4%). The analysis revealed an increase in the frequency of G5 haplotype cysts during the period of sampling, and an increase in the abundance of fertile cysts has also been observed in the last several years. Most infertile cysts were genotyped as G1. The possible factors involved in the increase in the proportion of E. ortleppi (G5) and the consequences of this increase are discussed. This study suggests that the proportion of E. ortleppi (G5) loads in cattle may be increasing overtime.

  2. Sequence analysis of VP4 genes of wild type and culture adapted human rotavirus G1P[8] strains

    Institute of Scientific and Technical Information of China (English)

    Ritu Arora; Ganesh S Dhale; Pooja R Patil; Shobha D Chitambar

    2011-01-01

    Objective:To conduct a comparative analysis of the VP4gene sequences of Indian wild type (06361,0613158, 061060and0715880) and cell culture adapted (06361-CA, 0613158-CA, 061060-CAand0715880-CA) G1P[8] rotavirus strains.Methods: Full-length VP4 genes of each of the four wild type G1P[8] rotavirus strains and their cell culture adapted counterparts displaying consistent cytopathic effect were subjected toRT-PCRamplification and nucleotide sequencing. Results: All four cell culture adaptedG1P[8]rotavirus strains showed nucleotide and amino acid substitutions in theVP4 gene as compared to their wild type strains. The number of substitutions however, varied from1-64and 1-13 respectively. The substitutions were distributed in both VP5*andVP8* subunits ofVP4gene respectively of permeabilization and hemagglutinating activity. The presence of unique amino acid substitutions was identified in two of the four wild type (V377G, S387N in 061060and I644Lin0715880) and all four cell culture adapted (A46Vin0613158-CA, T60R in06361-CA, L237V, G389V andQ480H in061060-CA andS615G andT625Pin0715880-CA) strains for the first time in theVP4 gene ofP[8]specificity. Amino acid substitutions generated increase in the hydrophilicity in the cell culture adapted rotavirus strains as compared to their corresponding wild type strains.Conclusions: Amino acid substitutions detected in the VP4 genes ofG1P[8]rotavirus strains from this study together with those from other studies highlight occurrence of only strain and/or host specific substitutions during cell culture adaptation. Further evaluation of such substitutions for their role in attenuation, immunogenicity and conformation is needed for the development of newer rotavirus vaccines.

  3. MKP1 phosphatase mediates G1-specific dephosphorylation of H3Serine10P in response to DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Ajit K.; Khan, Shafqat A.; Sharda, Asmita; Reddy, Divya V; Gupta, Sanjay, E-mail: sgupta@actrec.gov.in

    2015-08-15

    Highlights: • Reversible reduction of H3S10 phosphorylation after DNA damage is G1 phase specific. • Dynamic balance between MAP kinases, MKP1 and MSK1 regulate H3S10P during DDR. • MKP1 associates with chromatin bearing γH2AX in response to DNA damage. • Inhibition of MKP1 activity with specific inhibitor promotes radiation-induced cell death. - Abstract: Histone mark, H3S10 phosphorylation plays a dual role in a cell by maintaining relaxed chromatin for active transcription in interphase and condensed chromatin state in mitosis. The level of H3S10P has also been shown to alter on DNA damage; however, its cell cycle specific behavior and regulation during DNA damage response is largely unexplored. In the present study, we demonstrate G1 cell cycle phase specific reversible loss of H3S10P in response to IR-induced DNA damage is mediated by opposing activities of phosphatase, MKP1 and kinase, MSK1 of the MAP kinase pathway. We also show that the MKP1 recruits to the chromatin in response to DNA damage and correlates with the decrease of H3S10P, whereas MKP1 is released from chromatin during recovery phase of DDR. Furthermore, blocking of H3S10 dephosphorylation by MKP1 inhibition impairs DNA repair process and results in poor survival of WRL68 cells. Collectively, our data proposes a pathway regulating G1 cell cycle phase specific reversible reduction of H3S10P on IR induced DNA damage and also raises the possibility of combinatorial modulation of H3S10P with specific inhibitors to target the cancer cells in G1-phase of cell cycle.

  4. A quadratic programming method for optimal degree reduction of Bézier curves with G1-conitnuity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper presents a quadratic programming method for optimal multi-degree reduction of Bézier curves with G1-continuity. The L2 and l2 measures of distances between the two curves are used as the objective functions. The two additional parameters, available from the coincidence of the oriented tangents, are constrained to be positive so as to satisfy the solvability condition. Finally, degree reduction is changed to solve a quadratic problem of two parameters with linear constraints. Applica

  5. G0-G1 cell cycle phase transition as revealed by fluorescence resonance energy transfer: analysis of human fibroblast chromatin.

    Science.gov (United States)

    Bottiroli, Giovanni; Croce, A C; Bottone, M G; Vaccino, S; Pellicciari, C

    2004-01-01

    In the present study, microspectrofluorometry and digital imaging procedures were used to investigate by fluorescence Resonance Energy Transfer (FRET) analysis the changes of chromatin organization during the transition from G0 quiescent stat to G1 phase. G0 transition is a key event in cell cycle progress depending on the activation of specific genes and the concomitant silencing of others, which both entail spatial chromatin rearrangement. Normal human fibroblasts arrested in G0-phase by culture in low-serum containing medium and stimulated to re-enter G1 by serum addition were used as cell model. To investigate the occurrence and timing of these supramolecular chromatin changes, we estimated the relative FRET efficiency in single cells after double-helical DNA. Hoechst 33258 amd propidium iodide were used as a donor-acceptor dye pair since they exhibit particularly favourable spectral characteristics, that allow the calculation procedure to be semplified. The results of FRET analysis were compared to those of the immunocytochemical labelling of two nuclear proteins (i.e., Ki-67 and statin) whose expression is an established marker of potentially proliferating G1 cells or resting G0 cells, respectively. FRET efficiency was lower in G0 than G1 fibroblasts: this is likely due to higher chromatin packaging in quiescent cells which especially hinders the interaction with the donor molecules less favourable, in terms of relative distance and spatial orientation. FRET efficiency significantly increased shortly (1h) after serum stimulation of quiescent fibroblasts, thus indicating that chromatin is rearranged in parallel with activation of cycle-related gene; it is worth noting that these signs largely preceded the occurrence of immunopositivity for Ki-67, which was detectable only 24h after serum stimulation. FRET-based analyses which already proved to be suitable for studying the overall chromatin organization in differentiated cells, may now be envisaged as a

  6. The Spin-dependent Structure Function of the Proton $g_{1}^p$ and a Test of the Bjorken Sum Rule

    CERN Document Server

    Alekseev, M G; Alexandrov, Yu; Alexeev, G D; Amoroso, A; Austregesilo, A; Badelek, B; Balestra, F; Ball, J; Barth, J; Baum, G; Bedfer, Y; Bernhard, J; Bertini, R; Bettinelli, M; Birsa, R; Bisplinghoff, J; Bordalo, P; Bradamante, F; Bravar, A; Bressan, A; Brona, G; Burtin, E; Bussa, M P; Chaberny, D; Cotic, D; Chiosso, M; Chung, S U; Cicuttin, A; Colantoni, M; Crespo, M L; Dalla Torre, S; Das, S; Dasgupta, S S; Denisov, O Yu; Dhara, L; Diaz, V; Donskov, S V; Doshita, N; Duic, V; Dünnweber, W; Efremov, A; El Alaoui, A; Eversheim, P D; Eyrich, W; Faessler, M; Ferrero, A; Filin, A; Finger, M; Finger, M Jr; Fischer, H; Franco, C; Friedrich, J M; Garfagnini, R; Gautheron, F; Gavrichtchouk, O P; Gazda, R; Gerassimov, S; Geyer, R; Giorgi, M; Gnesi, I; Gobbo, B; Goertz, S; Grabmüller, S; Grasso, A; Grube, B; Gushterski, R; Guskov, A; Haas, F; von Harrach, D; Hasegawa, T; Heinsius, F H; Hermann, R; Herrmann, F; Heß, C; Hinterberger, F; Horikawa, N; Höppner, Ch; d'Hose, N; Ilgner, C; Ishimoto, S; Ivanov, O; Ivanshin, Yu; Iwata, T; Jahn, R; Jasinski, P; Jegou, G; Joosten, R; Kabuß, E; Käfer, W; Kang, D; Ketzer, B; Khaustov, G V; Khokhlov, Yu A; Kisselev, Yu; Klein, F; Klimaszewski, K; Koblitz, S; Koivuniemi, J H; Kolosov, V N; Kondo, K; Königsmann, K; Konopka, R; Konorov, I; Konstantinov, V F; Korzenev, A; Kotzinian, A M; Kouznetsov, O; Kowalik, K; Krämer, M; Kral, A; Kroumchtein, Z V; Kuhn, R; Kunne, F; Kurek, K; Lauser, L; Le Goff, J M; Lednev, A A; Lehmann, A; Levorato, S; Lichtenstadt, J; Liska, T; Maggiora, A; Maggiora, M; Magnon, A; Mallot, G K; Mann, A; Marchand, C; Marroncle, J; Martin, A; Marzec, J; Massmann, F; Matsuda, T; Maximov, A N; W Meyer, W; Michigami, T; Mikhailov, Yu V; Moinester, M A; Mutter, A; Nagaytsev, A; Nagel, T; Nassalski, J; Negrini, T; Nerling, F; Neubert, S; Neyret, D; Nikolaenko, V I; Olshevsky, A G; Ostrick, M; Padee, A; Panknin, R; Panzieri, D; Parsamyan, B; Paul, S; Pawlukiewicz-Kaminska, B; Perevalova, E; Pesaro, G; Peshekhonov, D V; Piragino, G; Platchkov, S; Pochodzalla, J; Polak, J; Polyakov, V A; Pontecorvo, G; Pretz, J; Quintans, C; Rajotte, J F; Ramos, S; Rapatsky, V; Reicherz, G; Richter, A; Robinet, F; Rocco, E; Rondio, E; Ryabchikov, D I; Samoylenko, V D; Sandacz, A; Santos, H; Sapozhnikov, M G; Sarkar, S; Savin, I A; Sbrizzai, G; Schiavon, P; Schill, C; Schmitt, L; Schlüter, T; Schopferer, S; Schröder, W; Shevchenko, O Yu; Siebert, H W; Silva, L; Sinha, L; Sissakian, A N; Slunecka, M; Smirnov, G I; Sosio, S; Sozzi, F; Srnka, A; Stolarski, M; Sulc, M; Sulej, R; Takekawa, S; Tessaro, S; Tessarotto, F; Teufel, A; Tkatchev, L G; Uhl, S; Uman, I; Virius, M; Vlassov, N V; Vossen, A; Weitzel, Q; Windmolders, R; Wislicki, W; Wollny, H; Zaremba, K; Zavertyaev, M; Zemlyanichkina, E; Ziembicki, M; Zhao, J; Zhuravlev, N; Zvyagin, A

    2010-01-01

    The inclusive double-spin asymmetry, $A_{1}^{p}$, has been measured at COMPASS in deepinelastic polarised muon scattering off a large polarised NH3 target. The data, collected in the year 2007, cover the range Q2 > 1 (GeV/c)^2, 0.004 < x < 0.7 and improve the statistical precision of g_{1}^{p}(x) by a factor of two in the region x < 0.02. The new proton asymmetries are combined with those previously published for the deuteron to extract the non-singlet spin-dependent structure function g_1^NS(x,Q2). The isovector quark density, Delta_q_3(x,Q2), is evaluated from a NLO QCD fit of g_1^NS. The first moment of Delta_q3 is in good agreement with the value predicted by the Bjorken sum rule and corresponds to a ratio of the axial and vector coupling constants g_A/g_V = 1.28+-0.07(stat)+-0.10(syst).

  7. Glucosamine, a naturally occurring amino monosaccharide, inhibits A549 and H446 cell proliferation by blocking G1/S transition.

    Science.gov (United States)

    Ju, Yinghua; Yu, Aiming; Sun, Xiuhua; Wu, Didi; Zhang, Hongkai

    2013-09-01

    Uncontrolled proliferation is important in tumorigenesis. In the present study, the effects of glucosamine on lung cancer cell proliferation were investigated. The expression of cyclin E, one of the key cyclins in the G1/S transition, and Skp2, the ubiquitin ligase subunit that targets the negative cell cycle regulator, p27Kip1, were also assessed. Moreover, the underlying mechanisms of action of glucosamine were investigated in lung cancer cells. A549 and H446 cells were synchronized using thymidine in the presence or absence of glucosamine. The effect of glucosamine on lung cancer cell proliferation was determined by MTT assay. Cyclin E and p27Kip1 proteins and their phosphorylation levels were detected by western blot analysis. Furthermore, the effect of glucosamine on the cell cycle was evaluated by flow cytometry. Glucosamine was found to inhibit lung cancer cell proliferation and to suppress Skp2 and cyclin E expression. Notably, the phosphorylation levels of cyclin E (Thr62) and p27Kip1 (Thr187) were downregulated by glucosamine, and negatively correlated with degradation. Glucosamine was also found to arrest lung cancer cells in the G1/S phase. Thus, glucosamine may inhibit lung cancer cell proliferation by blocking G1/S transition through the inhibition of cyclin E and Skp2 protein expression.

  8. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

    DEFF Research Database (Denmark)

    Dou, Q P; Zhao, S; Levin, A H;

    1994-01-01

    By performing DNase I footprint analysis, we had identified three distinct protein binding sequences (MT1, MT2, and MT3) located on the mouse thymidine kinase (TK) upstream promoter (Dou, Q.-P., Fridovich-Keil, J. L., and Pardee, A.B. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1157-1161). Here we...... report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes....... (iii) Formation of both these DNA-protein complexes were cell cycle-dependent: a G0/G1 phase-specific complex (E2F.G0/G1) was replaced by an S phase-specific complex(es) (E2F.S), whereas "free" E2F increased after the G1/S transition. (iv) Pulse inhibition of protein synthesis with cycloheximide...

  9. Singularity-conquering ZG controllers of z2g1 type for tracking control of the IPC system

    Science.gov (United States)

    Zhang, Yunong; Yu, Xiaotian; Yin, Yonghua; Peng, Chen; Fan, Zhengping

    2014-09-01

    With wider investigations and applications of autonomous robotics and intelligent vehicles, the inverted pendulum on a cart (IPC) system has become more attractive for numerous researchers due to its concise and representative structure. In this article, the tracking-control problem of the IPC system is considered and investigated. Based on Zhang dynamics (ZD) and gradient dynamics (GD), a novel kind of ZG controllers are developed and investigated for achieving the tracking-control purpose, which contains controllers of z2g0 and z2g1 types according to the number of times of using the ZD and GD methods. Besides, theoretical analyses are presented to guarantee the global and exponential convergence performance of both z2g0 and z2g1 controllers. Computer simulations are further performed to substantiate the feasibility and effectiveness of ZG controllers. More importantly, comparative simulation results demonstrate that controllers of z2g1 type can conquer the singularity problem (i.e. the division-by-zero problem).

  10. Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation.

    Science.gov (United States)

    Wang, Entong; Yin, Yili; Zhao, Min; Forrester, John V; McCaig, Colin D

    2003-03-01

    Vascular endothelial cell (VEC) proliferation is a key event in angiogenesis and is tightly regulated. Electric potential differences exist around the vascular endothelium and give rise to endogenous electric fields (EFs), whether these EFs influence VEC proliferation is unclear. We exposed cultured VECs to applied EFs of physiological strengths for up to 72 h. EF at 50 or 100 mV/mm did not influence cell proliferation, but at 200 mV/mm, cell density, cell growth rate, and mitosis index decreased significantly. EF-induced reduction in VEC proliferation was not due to increased apoptosis, because caspase apoptosis inhibitor Z-VAD-FMK (20 microM), had no effect on this response. Rather, EF responses were mediated via decreased entry of cells into S phase from G1 phase, as shown by flow cytometry. Western blot showed that EFs decreased G1-specific cyclin E expression and increased cyclin/cyclin-dependent kinase complex inhibitor p27kipl expression. Thus EFs controlled VEC proliferation through induction of cell cycle arrest at G1 by down-regulation of cyclin E expression and up-regulation of p27kipl expression, rather than by promoting apoptosis. If control of the cell cycle by endogenous EFs extends beyond VECs, this would be of widespread biological significance in vivo.

  11. Impact of the GeoMIP G1 sunshade geoengineering experiment on the Atlantic meridional overturning circulation

    Science.gov (United States)

    Hong, Yu; Moore, John C.; Jevrejeva, Svetlana; Ji, Duoying; Phipps, Steven J.; Lenton, Andrew; Tilmes, Simone; Watanabe, Shingo; Zhao, Liyun

    2017-03-01

    We analyze the multi-earth system model responses of ocean temperatures and the Atlantic Meridional Overturning Circulation (AMOC) under an idealized solar radiation management scenario (G1) from the Geoengineering Model Intercomparison Project. All models simulate warming of the northern North Atlantic relative to no geoengineering, despite geoengineering substantially offsetting the increases in mean global ocean temperatures. Increases in the temperature of the North Atlantic Ocean at the surface (∼0.25 K) and at a depth of 500 m (∼0.10 K) are mainly due to a 10 Wm‑2 reduction of total heat flux from ocean to atmosphere. Although the AMOC is slightly reduced under the solar dimming scenario, G1, relative to piControl, it is about 37% stronger than under abrupt4 × CO2 . The reduction of the AMOC under G1 is mainly a response to the heat flux change at the northern North Atlantic rather than to changes in the water flux and the wind stress. The AMOC transfers heat from tropics to high latitudes, helping to warm the high latitudes, and its strength is maintained under solar dimming rather than weakened by greenhouse gas forcing acting alone. Hence the relative reduction in high latitude ocean temperatures provided by solar radiation geoengineering, would tend to be counteracted by the correspondingly active AMOC circulation which furthermore transports warm surface waters towards the Greenland ice sheet, warming Arctic sea ice and permafrost.

  12. Biochemical DSB-repair model for mammalian cells in G1 and early S phases of the cell cycle.

    Science.gov (United States)

    Taleei, Reza; Nikjoo, Hooshang

    2013-08-30

    The paper presents a model of double strand breaks (DSB) repair in G1 and early S phases of the cell cycle. The model is based on a plethora of published information on biochemical modification of DSB induced by ionizing radiation. So far, three main DSB repair pathways have been identified, including nonhomologous end-joining (NHEJ), homologous recombination (HR), and microhomology-mediated end-joining (MMEJ). During G1 and early S phases of the cell cycle, NHEJ and MMEJ repair pathways are activated dependent on the type of double strand breaks. Simple DSB are a substrate for NHEJ, while complex DSB and DSB in heterochromatin require further end processing. Repair of all DSB start with NHEJ presynaptic processes, and depending on the type of DSB pursue simple ligation, further end processing prior to ligation, or resection. Using law of mass action the model is translated into a mathematical formalism. The solution of the formalism provides the step by step and overall repair kinetics. The overall repair kinetics are compared with the published experimental measurements. Our calculations are in agreement with the experimental results and show that the complex types of DSBs are repaired with slow repair kinetics. The G1 and early S phase model could be employed to predict the kinetics of DSB repair for damage induced by high LET radiation.

  13. X-Ray Localization of the Intermediate-Mass Black Hole in the Globular Cluster G1 with Chandra

    CERN Document Server

    Kong, A K H; Di Stefano, R; Barmby, P; Lewin, W H G; Primini, F A

    2009-01-01

    We report the most accurate X-ray position of the giant globular cluster G1 in M31 by using the Chandra X-ray Observatory, Hubble Space Telescope (HST), and Canada-France-Hawaii Telescope (CFHT). G1 is clearly detected with Chandra and by cross-registering with HST and CFHT images, we derive a 1sigma error radius of 0.15", significantly smaller than the previous measurement by XMM-Newton. We conclude that the X-ray emission of G1 comes from within the core radius of the cluster. There are two possibilities for the origin of the X-ray emission: it could be due to either accretion of a central intermediate-mass black hole, or ordinary low-mass X-ray binaries. Based on the ratio of X-ray to the Eddington luminosity, an intermediate-mass black hole accreting from the cluster gas seems unlikely and we suggest that the X-rays are due to accretion from a companion. We also find that the X-ray emission may be offset from the radio emission. Future high-resolution and high-sensitivity radio imaging observations will r...

  14. Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles.

    Science.gov (United States)

    Kinoshita, Chika; Nagano, Tomohisa; Seki, Nobuyoshi; Tomita, Yoichi; Sugita, Tomonori; Aida, Yuta; Itagaki, Munenori; Satoh, Kenichi; Sutoh, Satoshi; Abe, Hiroshi; Tsubota, Akihito; Aizawa, Yoshio

    2016-08-07

    To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins. The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis. The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles. HCV

  15. G0-G1 cell cycle phase transition as revealed by fluorescence resonance energy transfer: analysis of human fibroblast chromatin

    Directory of Open Access Journals (Sweden)

    G Bottiroli

    2009-06-01

    Full Text Available In the present study, microspectrofluorometry and digital imaging procedures were used to investigate by fluorescence Resonance Energy Transfer (FRET analysis the changes of chromatin organization during the transition from G0 quiescent state to G1 phase. G0-G1 transition is a key event in cell cycle progress depending on the activation of specific genes and the concomitant silencing of others, which both entail spatial chromatin rearrangement. Normal human fibroblasts arrested in G0-phase by culture in low-serum contanining medium and stimulated to re-enter G1 by serum addition were used as cell model. To investigate the occurrence and timing of these supramolecular chromatin changes, we estimated the relative FRET efficiency in single cells after double-staining with two DNA-specific dyes which non-covalently bind to double-helical DNA. Hoechst 33258 and propidium iodide were used as a donor-acceptor dye pair since they exhibit particularly favourable spectral characteristics, that allow the calculation procedure to be semplified. The results of FRET analysis were compared to those of the immunocytochemical labelling of two nuclear proteins (i.e., Ki-67 and statin whose expression is an established marker of potentially proliferating G1 cells or resting G0 cells, respectively. FRET efficiency was lower in G0 than in G1 fibroblasts: this is likely due to a higher chromatin packaging in quiescent cells which especially hinders the intercalation of propidium iodide molecules, thus making the interaction with the donor molecules less favourable, in terms of relative distance and spatial orientation. FRET efficiency significantly increased shortly (1h after serum stimulation of quiescent fibroblasts, thus indicating that chromatin is rearranged in parallel with activation of cycle-related gene; it is worth noting that these signs largely preceded the occurrence of immunopositivity for Ki-67, which was detectable only 24h after serum stimulation

  16. Asteroid phase curve analysis with the H, G 1, G 2 photometric phase function: application to the PTF survey observations

    Science.gov (United States)

    Penttilä, Antti; Cellino, Alberto; Lu, Xiaoping; Shevchenko, Vasilij G.; Muinonen, Karri

    2016-10-01

    Estimation of an asteroid's absolute magnitude H from its photometry is extremely important. The absolute magnitude relates the brightness of the asteroid to its size, if the geometric albedo is known. The shape of the phase curve can serve as a proxy for the taxonomic type of the asteroid in cases with no spectral information available [1,2].In 2012, the IAU adopted the H,G1,G2 function to replace the H,G function for phase curve analysis [3]. This new function improves the backscattering behavior of the curve with high- and low-albedo asteroids. The phase function (PF) can be applied to asteroids with multiple high-quality observations. If the number of observations is small, or their accuracy is low, problems may arise. The most apparent problem is that the parameter G or the parameters G1, G2 might be poorly estimated. The solution has been to fix to value of G or values of G1, G2 and estimate only the H. In our recent work [4], we offer a solution that can improve the current situation with the photometric fits with a small number of low-accuracy observations. We present a constrained nonlinear least-squares method for fitting the H,G1,G2 function that can improve the possible bias with low-accuracy data. Then, we revisit the two-parameter PF with new data and offer a new version, the H,G12* PF. Finally, we assess the problem with fixed G or G1, G2 parameters by introducing one-parameter models that relate to five taxonomic asteroid groups. We tie all the models together with three or two parameters, or a single parameter, with a statistical model selection procedure to select the best version for a particular data set.We have developed practical tools for the abovementioned algorithms. We apply the tools to a dataset of 8,900 asteroids with almost 500,000 photometric observations from the Palomar Transient Factory survey [5]. We report the effect of the revised H estimates on the geometric albedos in cases where WISE-mission size estimates are available.[1] D

  17. EL2-related defects in neutron irradiated GaAs/sub 1//sub -x/P/sub x/ alloys

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, E.; Garcia, F.; Jimenez, B.; Calleja, E.; Gomez, A.; Alcober, V.

    1985-10-15

    The generation of EL2-related defects in GaAsP alloys by fast neutron irradiation has been studied through deep level transient spectroscopy and photocapacitance techniques. After irradiation p-n junctions were not annealed at high temperatures. In the composition range x>0.4, fast neutrons generate a broad center at E/sub c/-0.7 eV that it is suggested to belong to the EL2 family. The presence of photocapacitance quenching effects has been taken as a preliminary fingerprint to make the above assignment. From computer analysis of the nonexponential transient capacitance waveforms, evidence that neutron irradiation creates a family of midgap levels, EL2-related, is found.

  18. M/G/1 Queue with Single Working Vacation and Vacation Interruption%带单重工作休假和休假中断的M/G/1排队系统

    Institute of Scientific and Technical Information of China (English)

    卢国云; 徐秀丽; 王继利; 刘春平

    2011-01-01

    研究单重工作休假和休假中断的M/G/1排队系统,得到了其嵌入Markov链的转移概率矩阵,采用M/G/1型结构矩阵解析法,得到离去时刻稳态队长的母函数的解析表达式.采用经典随机分解方法,给出了队长的条件随机分解结构、条件等待时间的随机分解结果、稳态等待时间的LST变换及稳态下平均等待时间等性能指标.给出数值例子,并讨论了系统参数对几个主要性能指标的影响,从而验证了理论分析的合理性和有效性.%An M/G/1 queue system with a single working vacation and working interruption was studied. An M/G/l -type transition probability matrix of the embedded Markov chain was obtained. And using the M/G/l -type matrix analysis method, the PGF of the stationary queue length for the customers at departure epochs was derived. By the classic stochastic decomposition solution, the stochastic decomposition results of the stationary queue length and the conditional waiting time were presented. And some performance measures of the system such as the LST of the stationary waiting time and the expected waiting time were also obtained. Numerical examples were presented to show the influence of the system parametes on several main performance characteristics, and the rationality and the effectiveness of the theoretical analysis were proved.

  19. 研究M/G/1排队的一个新的向量马氏过程%A New Vector Markov Process for M/G/1 Queue

    Institute of Scientific and Technical Information of China (English)

    严庆强; 史定华; 郭兴国

    2005-01-01

    In this paper, by considering the stochastic process of the busy period and the idle period, and introducing the unfinished work as a supplementary variable, a new vector Markov process was presented to study the M/G/1 queue again. Through establishing and solving the density evolution equations, the busy-period distribution, and the stationary distributions of waiting time and queue length were obtained. In addition, the stability condition of this queue system was given by means of an imbedded renewal process.

  20. 具有二次可选服务的多重休假Geom/G/1离散排队%The Geom/G/1 queue with second optional service and multiple vacation

    Institute of Scientific and Technical Information of China (English)

    赵媛; 田乃硕; 原小娟; 靳晓青; 宁小虎

    2011-01-01

    通过引入广义服务时间,用嵌入Markov链的方法研究了具有二次可选服务的多重休假Geom/G/1排队模型,得到了其稳态队长和等待时间分布的母函数,并给出了该模型的两个特例,进一步验证了模型的正确性,最后通过数值例子说明该模型可以较好地模拟一些实际问题.%By leading into broad sense service time and using the method of imbedded Markov chains, the Geom/G/1 queue with second optional service and multiple vacation was studied.The PGF( probability generating function) of the steady state queue length and waiting time were derived.And then two particular models were given to further verify the correctness of the model.Finally, numerical examples proved that our model could reasonably represent some practical problems.

  1. Impacts, effectiveness and regional inequalities of the GeoMIP G1 to G4 solar radiation management scenarios

    Science.gov (United States)

    Yu, Xiaoyong; Moore, John C.; Cui, Xuefeng; Rinke, Annette; Ji, Duoying; Kravitz, Ben; Yoon, Jin-Ho

    2015-06-01

    We evaluate the effectiveness and the regional inequalities of solar radiation management (SRM) in compensating for simultaneous changes in temperature and precipitation caused by increased greenhouse gas concentrations. We analyze the results from Earth System Models under four Geoengineering Model Intercomparison Project (GeoMIP) experiments with a modified form of the Residual Climate Response approach. Each experiment produces 50 model yrs of simulations: 13 models completed experiment G1 (offsetting 4 × CO2 via solar reduction); 12 models completed experiment G2 (offsetting CO2 that increased by 1% per year); 3 models completed experiment G3 (offsetting increasing radiative forcing under RCP4.5 with increasing stratospheric aerosol); and 7 models completed experiment G4 (injection of 5 Tg SO2 a- 1 into the stratosphere). The regional inequalities in temperature and precipitation compensation for experiments G1, G3 and G4 are significantly different from their corresponding noise backgrounds for most models, but for G2 they are not significantly different from noise. Differences in the regional inequalities and the actual effectiveness among the four SRM scenarios are not significant for many models. However, in more than half of the models, the effectiveness for temperature in the solar dimming geoengineering scenarios (G1 and G2) is significantly higher than that in the SO2 geoengineering scenarios (G3 and G4). The effectiveness of the four SRM experiments in compensating for temperature change is considerably higher than for precipitation. The methodology used highlights that a large across-model variation in the treatment of key geoengineering processes (such as stratospheric aerosols) and the quantification of damage caused by climate change creates significant uncertainties in any strategies to achieve optimal compensation effectiveness across different regions.

  2. Binomial Schedule for an M/G/1 Type Queueing System with an Unreliable Server under N-Policy

    Directory of Open Access Journals (Sweden)

    Lotfi Tadj

    2014-01-01

    Full Text Available We consider in this paper an M/G/1 type queueing system with the following extensions. First, the server is unreliable and is subject to random breakdowns. Second, the server also implements the well-known N-policy. Third, instead of a Bernoulli vacation schedule, the more general notion of binomial schedule with K vacations is applied. A cost function with two decision variables is developed. A numerical example shows the effect of the system parameters on the optimal management policy.

  3. Approximation of the steady state system state distribution of the M/G/1 retrial queue with impatient customers

    Directory of Open Access Journals (Sweden)

    Stihi Nadjet

    2012-01-01

    Full Text Available For M/G/1 retrial queues with impatient customers, we review the results, concerning the steady state distribution of the system state, presented in the literature. Since the existing formulas are cumbersome (so their utilization in practice becomes delicate or the obtaining of these formulas is impossible, we apply the information theoretic techniques for estimating the above mentioned distribution. More concretely, we use the principle of maximum entropy which provides an adequate methodology for computing a unique estimate for an unknown probability distribution based on information expressed in terms of some given mean value constraints.

  4. Molecular basis for vulnerability to mitochondrial and oxidative stress in a neuroendocrine CRI-G1 cell line.

    Directory of Open Access Journals (Sweden)

    Natasha Chandiramani

    Full Text Available BACKGROUND: Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases are linked to mitochondrial dysfunction, which leads to impaired cellular bioenergetics and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types. METHODOLOGY/PRINCIPAL FINDINGS: Starting with an insulinoma cell line as a model for a neuronal/endocrine cell type, we isolated a novel subclonal line (named CRI-G1-RS that was more susceptible to cell death induced by mitochondrial respiratory chain inhibitors than the parental CRI-G1 line (renamed CRI-G1-RR for clarity. Compared to parental RR cells, RS cells were also more vulnerable to direct oxidative stress, but equally vulnerable to mitochondrial uncoupling and less vulnerable to protein kinase inhibition-induced apoptosis. Thus, differential vulnerability to mitochondrial toxins between these two cell types likely reflects differences in their ability to handle metabolically generated reactive oxygen species rather than differences in ATP production/utilization or in downstream apoptotic machinery. Genome-wide gene expression analysis and follow-up biochemical studies revealed that, in this experimental system, increased vulnerability to mitochondrial and oxidative stress was associated with (1 inhibition of ARE/Nrf2/Keap1 antioxidant pathway; (2 decreased expression of antioxidant and phase I/II conjugation enzymes, most of which are Nrf2 transcriptional targets; (3 increased expression of molecular chaperones, many of which are also considered Nrf2 transcriptional targets; (4 increased expression of β cell-specific genes and transcription factors that specify/maintain β cell fate; and (5 reconstitution of glucose-stimulated insulin secretion. CONCLUSIONS/SIGNIFICANCE: The molecular profile presented here will enable identification of individual genes or

  5. On the Discrete-Time GeoX/G/1 Queues under N-Policy with Single and Multiple Vacations

    Directory of Open Access Journals (Sweden)

    Sung J. Kim

    2013-01-01

    Full Text Available We consider the discrete-time GeoX/G/1 queue under N-policy with single and multiple vacations. In this queueing system, the server takes multiple vacations and a single vacation whenever the system becomes empty and begins to serve customers only if the queue length is at least a predetermined threshold value N. Using the well-known property of stochastic decomposition, we derive the stationary queue-length distributions for both vacation models in a simple and unified manner. In addition, we derive their busy as well as idle-period distributions. Some classical vacation models are considered as special cases.

  6. The Recursive Solution for Geom/G/1(E,SV) Queue with Feedback and Single Server Vacation

    Institute of Scientific and Technical Information of China (English)

    Chuan-yi Luo; Ying-hui Tang

    2011-01-01

    Using recursive method, this paper studies the queue size properties at any epoch n+ in Geom/G/i(E, SV) queueing model with feedback under LASDA (late arrival system with delayed access) setup. Some new results about the recursive expressions of queue size distribution at different epoch (n+, n, n-) are obtained.Furthermore the important relations between stationary queue size distribution at different epochs are discovered.The results are different from the relations given in M/G/1 queueing system. The model discussed in this paper can be widely applied in many kinds of communications and computer network.

  7. ANALYSIS AND COMPUTATIONAL ALGORITHM FOR QUEUES WITH STATE-DEPENDENT VACATIONS Ⅱ: M(n)/G/1/K

    Institute of Scientific and Technical Information of China (English)

    Xiuli CHAO; Ayyar RAHMAN

    2006-01-01

    We study a single-server queueing system with state-dependent arrivals and general service distribution, or simply M(n)/G/1/K, where the server follows an N policy and takes multiple vacations when the system is empty. We provide a recursive algorithm using the supplementary variable technique to numerically compute the stationary queue length distribution of the system. The only input requirements are the Laplace-Stieltjes transforms of the service time distribution and the vacation time distribution, and the state-dependent arrival rate. The computational complexity of the algorithm is O(K3).

  8. Some Reliability Problems Arising in the Mx/G(M/G)/1 Repairable Queueing System with Single Delay Vacation

    Institute of Scientific and Technical Information of China (English)

    TANG Ying-hui

    2001-01-01

    On the basis of Ref. [1], the Mx/G(M/G)/1 repairable queueing system with single delay vacation is discussed again. The following reliability problems of the service station are studied: (a) The probability that it fails at time t, i.e. its unavailability; (b) The expected failure number during the time interval (0,t]; (c) The expected failure number during the "server busy period"; (d) The expected downtime during the time interval (0,t]. Some reliability results of the service station are obtained. These results would be interest to reliability analysts.

  9. Assessment of the efficacy of Aspergillus sp. EL-2 in textile waste water treatment.

    Science.gov (United States)

    Gomaa, Ola M; Kareem, Hussein Abd El; Fatahy, Reham

    2012-04-01

    Fungal biomass has the ability to decolorize a wide variety of dyes successfully through a number of mechanisms. A brown rot isolate, previously identified as Aspergillus sp. EL-2, was used in the aerobic treatment of textile waste water efficiently. In the current work, the treated waste water was tested chemically using more than one combined treatment. Microbial toxicity, phytotoxicity, genotoxicity and cytotoxicity were also studied to assess the toxicity level for each treatment. The obtained data suggest that the contribution of more than one mode of treatment is essential to ensure complete destruction of the by-products. The use of gamma irradiation (25 kGy) after the bioremediation step led to the decrease of the by-products of biodegradation as observed by visible spectrum and Fourier transfer infra red spectroscopy (FT-IR). The toxicity assessment presented variable results indicating the need for more than one toxicity test to confirm the presence or absence of hazardous compounds. Brown rot fungus could be used efficiently in the treatment of textile waste water without the risk of obtaining high carcinogenic or genotoxic compounds, especially if combined treatment is employed.

  10. Endoscopic and pathologic features of neuroendocrine neoplasm G1 in the rectum%直肠神经内分泌肿瘤 G1内镜及病理学特征分析

    Institute of Scientific and Technical Information of China (English)

    吴林林; 胡艳萍; 刘凤阁

    2014-01-01

    Objective To investigate the endoscope and pathology characteristics of rectal neuroendocrine neoplasm (NEN) G1.Methods From January 2007 to December 2012, retrospective analyzed the clinical data of 18 cases with NEN in G1 which were underwent endoscopic biopsy and diagnosed according to the 2010 WHO classification of tumors of the diges-tive system of standard pathology .Combined with endoscopic observation and comprehensive analysis of tissue under a micro -scope for morphological change , immunohistochemical method were used to detect the cell cytokeratins (AE1/AE3), cytoke-ratin (CK8/18), chromogranin A (CgA), synaptophysin (Syn), neuron specific enolase (NSE), nuclear antigen (Ki-67) expression .Results NEN G1 under endoscopic were mostly submucosal tumors , can be moved with hard texture .The tumor cells under the microscope arranged in a sheet , nests, banded structure;small cells,consistent shape,hyperchromatic nuclei, no or few mitotic.The positive rate of AE1/AE3, CK8/18, CgA, Syn and NSE were 100.0%, 88.9%, 83.3%, 77.8%and 55.6%, Ki-67 positive rate is less than or equal to 2%.Conclusion NEN G1 lack of specific clinical manifestations , they are usually smaller , endoscopic observation is not easy to confirm the diagnosis , immunohistochemical detection of AE 1/AE3, CK8/18, CgA, Syn is very important for the pathological diagnosis .%目的:探讨直肠神经内分泌肿瘤( NEN) G1的内镜和病理学特征。方法回顾性分析2007年1月—2012年12月行内镜活检并参考2010年WHO消化系统肿瘤分类标准病理诊断为NEN G118例患者临床资料,结合内镜观察结果及显微镜下组织学形态变化进行综合分析,免疫组化方法检测细胞广谱角蛋白( AE1/AE3)、细胞角蛋白(CK8/18)、嗜铬粒素A(CgA)、突触素(Syn)、神经元特异性烯醇化酶(NSE)、核抗原(Ki-67)表达情况。结果NEN G1在内镜下多为黏膜隆起性肿物,活动度尚可,质地偏硬。

  11. The geology of uranium in the Saint-Sylvestre granite district (Limousin, Massif Central, France); La geologie de l'uranium dans le massif granitique de Saint-Sylvestre (Limousin - Massif Central Francais)

    Energy Technology Data Exchange (ETDEWEB)

    Marquaire, C.; Moreau, M.; Barbier, J.; Ranchin, G.; Carrat, H.G.; Coppens, R.; Senecal, J.; Koszotolanyi, C.; Dottin, H

    1969-07-01

    Nord Limousin et repartition des mineralisations uraniferes. 2. J. BARBIER, G. RANCHIN, H. G. CARRAT et R. COPPENS Geologie du massif de St-Sylvestre et geochimie de l'uranium - Introduction aux etudes de laboratoire - Problemes de methodologie. 3. J. BARBIER et G. RANCHIN Zonalite petrographique et geochimique dans le massif granitique de St-Sylvestre (Limousin - Massif Central francais). 4. J. BARBIER et G. RANCHIN Geochimie de l'uranium dans le massif de St-Sylvestre (Limousin - Massif Central francais) - Occurrences de l'uranium geochimique primaire et processus de remaniements. 5. J. SENEGAL Monographie du gisement du Brugeaud. 6. R. COPPENS, Ch. KOSZTOLANYI et H. DOTTIN Etude geochronologique de la mine du Brugeaud. (auteurs)

  12. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico

    Science.gov (United States)

    Molina-Mendoza, Pedro; Hernández-Guzmán, Karina; Olivares-Pérez, Jaime; Sarracent-Pérez, Jorge; Zumaquero-Ríos, José

    2016-01-01

    The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans. PMID:27563665

  13. Impact of Mitochondria-Mediated Apoptosis in U251 Cell Cycle Arrest in G1 Stage and Caspase Activation.

    Science.gov (United States)

    Zhang, Lei; Liang, Peng; Zhang, Rui

    2015-11-23

    BACKGROUND Most mitochondria-mediated apoptosis has some relevance to the cell cycle, but there is still a lack of investigations about U251 cell cycle in human brain glioma cells. In this study, we aimed to clarify the correlation of mitochondria-mediated apoptosis with the U251 cell cycle and its influence on apoptosis, through observing the impact of mitochondria-mediated apoptosis in U251cell specificity cycle arrest and Caspase activation. MATERIAL AND METHODS AnnexinV/PI and API were used to label the brain glioma cells for flow cytometry analysis of U251 cell apoptosis and cell cycle. RT-PCR and Western blot were performed to detect Caspase-3 and Caspase-9 activation. RESULTS Peripheral blood in stationary phase is not sensitive to apoptosis induction, but U251 cells have obvious apoptosis. Mitochondria-mediated apoptosis mainly occurs in the G1 phase of the cell cycle. Caspase-3 and Caspase-9 mRNAs and proteins expression increased significantly after the cells were treated by mitochondrial apoptosis-related gene Bax induction. CONCLUSIONS Mitochondria-mediated apoptosis is related to the U251 cell cycle with specific G1 stage arrest. Caspase activation occurs in the process of cell apoptosis.

  14. Hispolon from Phellinus linteus induces G0/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells.

    Science.gov (United States)

    Chen, Yi-Chuan; Chang, Heng-Yuan; Deng, Jeng-Shyan; Chen, Jian-Jung; Huang, Shyh-Shyun; Lin, I-Hsin; Kuo, Wan-Lin; Chao, Wei; Huang, Guan-Jhong

    2013-01-01

    Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.

  15. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells.

    Science.gov (United States)

    Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob; Oestergaard, Vibe H; Lisby, Michael

    2015-08-17

    Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis.

  16. Uncommon occurrence ratios of aflatoxin B1, B 2, G 1, and G 2 in maize and groundnuts from Malawi.

    Science.gov (United States)

    Matumba, Limbikani; Sulyok, Michael; Njoroge, Samuel M C; Njumbe Ediage, Emmanuel; Van Poucke, Christof; De Saeger, Sarah; Krska, Rudolf

    2015-02-01

    We report an unusual aflatoxin profile in maize and groundnuts from Malawi, with aflatoxin G1 found routinely at equal or even higher levels than aflatoxin B1. Aflatoxin B1 (AFB1) ratio in a contaminated sample is generally greater than 50% of total aflatoxin (sum of aflatoxin B1, B2, G1, and G2). In Malawi, the aflatoxin occurrence ratios were determined by examining LC-MS/MS and HPLC fluorescence detection (FLD) data of 156 naturally contaminated raw maize and 80 groundnut samples collected in 2011 and 2012. Results showed that natural aflatoxin occurrence ratio differed. In 47% of the samples, the concentration of AFG1 was higher than that of AFB1. The mean concentration percentages of AFB1/AFB2/AFG1/AFG2 in reference to total aflatoxins were found to be 47:5:43:5%, respectively. The AFG1 and AFB1 50/50 trend was observed in maize and groundnuts and was consistent for samples collected in both years. If the AFB1 measurement was used to check compliance of total aflatoxin regulatory limit set at 10, 20, 100, and 200 μg/kg with an assumption that AFB1≥50% of the total aflatoxin content, 8, 13, 24, and 26% false negative rates would have occurred respectively. It is therefore important for legislation to consider total aflatoxins rather than AFB1 alone.

  17. An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition.

    Science.gov (United States)

    Ondracka, Andrej; Robbins, Jonathan A; Cross, Frederick R

    2016-01-01

    B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C-Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition.

  18. Spin structure function g_1 at small x and arbitrary $Q^2: Total resummaion of leading logarithms vs Standard Approach

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2007-01-01

    The Standard Approach (SA) for description of the structure function g_1 combines the DGLAP evolution equations and Standard Fits for the initial parton densities. The DGLAP equations describe the region of large Q^2 and large x, so there are not theoretical grounds to exploit them at small x. In practice, extrapolation of DGLAP into the region of large Q^2 and small x is done with complementing DGLAP with special, singular (~x^{-a}) phenomenological fits for the initial parton densities. The factors x^{-a} are wrongly believed to be of the non-perturbative origin. Actually, they mimic the resummation of logs of x and should be expelled from the fits when the resummation is accounted for. Contrary to SA, the resummaton of logarithms of x is a straightforward and natural way to describe g_1 in the small-x region. This approach can be used at both large and small Q^2 where DGLAP cannot be used by definition. Confronting this approach and SA demonstrates that the singular initial parton densities and the power Q...

  19. RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

    Science.gov (United States)

    Russo, P; Ottoboni, C; Crippa, A; Riou, J F; O'Connor, P M

    2001-04-01

    A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

  20. The Polarised Photon $g_1^\\gamma$ Sum Rule at the Linear Collider and High Luminosity B Factories

    CERN Document Server

    Shore, G M

    2004-01-01

    The sum rule for the first moment of the polarised (virtual) photon structure function $g_1^\\gamma(x,Q^2;K^2)$ is revisited in the light of proposals for future $e^+ e^-$ colliders. The sum rule exhibits an array of phenomena characteristic of QCD: for real photons ($K^2=0$) electromagnetic gauge invariance constrains the first moment to vanish; the limit for asymptotic photon virtuality ($m_\\rho^2 \\ll K^2 \\ll Q^2$) is governed by the electromagnetic $U_A(1)$ axial anomaly and the approach to asymptopia by the gluonic anomaly; for intermediate values of $K^2$, it reflects the realisation of chiral symmetry and is determined by the off-shell radiative couplings of the pseudoscalar mesons; finally, like many polarisation phenomena in QCD, the first moment of $g_1^\\gamma$ involves the gluon topological susceptibility. In this paper, we review the original sum rule proposed by Narison, Shore and Veneziano and extend the relation with pseudoscalar mesons. The possibility of measuring the sum rule in future polaris...

  1. Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

    Directory of Open Access Journals (Sweden)

    Raja Kumar Vadivelu

    2012-01-01

    Full Text Available Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05. Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC.

  2. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico.

    Science.gov (United States)

    Villa-Mancera, Abel; Molina-Mendoza, Pedro; Hernández-Guzmán, Karina; Olivares-Pérez, Jaime; Sarracent-Pérez, Jorge; Zumaquero-Ríos, José

    2016-01-01

    The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans.

  3. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico

    Directory of Open Access Journals (Sweden)

    Abel Villa-Mancera

    2016-01-01

    Full Text Available The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P<0.01 for low seropositivity (r=0.93 and medium seropositivity (r=0.84. The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans.

  4. Characterization of upFc, a fragment of human immunoglobulin G1 produced by pepsin in urea.

    Science.gov (United States)

    Parr, D M; Hofmann, T; Connell, G E

    1976-09-01

    The digestion of human IgG1/K myeloma proteins with pepsin in the presence of 8 M-urea produces fragments that differ from those produced by aqueous peptic digestion, and from other characteristic immunoglobulin fragments. Fb'2, the larger urea/pepsin fragment, was previously shown to consist of the constant regions of the light chains, and the CH1 domains and hinge regions of the heavy chains. The smaller fragment, upFc, has now been characterized. After reduction, three peptides were released from fragment upFc. Amino acid sequencing, N- and C-terminal determinations and amino acid compositions have enabled these peptides to be identified as residues Ile-253 to Leu-306, residues Thr-307 to Asp-376 and residues Thr-411 to Gly-446 of the heavy chain. Fragment upFc therefore contains the entire Fc region, beginning at residue Ile-253, except for a 34-residue section from within the CH3-domain disulphide loop. Peptic digestion of IgG1/K proteins in 8M-urea therefore provides a method for isolating from gamma1 heavy chains five homogeneous peptides in good yield, which account for almost the entire constant region. Characterization of fragments Fb'2 and upFc has shown that the action of pepsin in urea is entirely different from that of aqueous pepsin. Two gamma1 heavy chains have been shown to differ in sequence at three positions from the sequence reported for protein Eu.

  5. An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition

    Science.gov (United States)

    Ondracka, Andrej; Robbins, Jonathan A.; Cross, Frederick R.

    2016-01-01

    B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C-Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition. PMID:27410035

  6. YOUNG REMNANTS OF TYPE Ia SUPERNOVAE AND THEIR PROGENITORS: A STUDY OF SNR G1.9+0.3

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborti, Sayan; Childs, Francesca; Soderberg, Alicia, E-mail: schakraborti@post.harvard.edu [Institute for Theory and Computation, Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2016-03-01

    SNe Ia, with their remarkably homogeneous light curves and spectra, have been used as standardizable candles to measure the accelerating expansion of the universe. Yet, their progenitors remain elusive. Common explanations invoke a degenerate star (white dwarf) that explodes upon almost reaching the Chandrasekhar limit, by either steadily accreting mass from a companion star or violently merging with another degenerate star. We show that circumstellar interaction in young Galactic supernova remnants can be used to distinguish between these single and double degenerate (DD) progenitor scenarios. Here we propose a new diagnostic, the surface brightness index, which can be computed from theory and compared with Chandra and Very Large Array (VLA) observations. We use this method to demonstrate that a DD progenitor can explain the decades-long flux rise and size increase of the youngest known galactic supernova remnant (SNR), G1.9+0.3. We disfavor a single degenerate scenario for SNR G1.9+0.3. We attribute the observed properties to the interaction between a steep ejecta profile and a constant density environment. We suggest using the upgraded VLA, ASKAP, and MeerKAT to detect circumstellar interaction in the remnants of historical SNe Ia in the Local Group of galaxies. This may settle the long-standing debate over their progenitors.

  7. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

    Science.gov (United States)

    Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

    2015-01-01

    Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. PMID:26283799

  8. Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment

    Science.gov (United States)

    Chalmers, Iain W.; Fitzsimmons, Colin M.; Brown, Martha; Pierrot, Christine; Jones, Frances M.; Wawrzyniak, Jakub M.; Fernandez-Fuentes, Narcis; Tukahebwa, Edridah M.; Dunne, David W.; Khalife, Jamal; Hoffmann, Karl F.

    2015-01-01

    Background The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored. Methodology/Principal Findings Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0

  9. Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

    Directory of Open Access Journals (Sweden)

    Iain W Chalmers

    Full Text Available The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29 containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study. While vaccination with SmLy6A (SmCD59a and SmLy6D (Sm29 induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K. Our examination extends the number of members to eleven (including three novel proteins and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE responses against two surface-bound representatives (SmLy6A and SmLy6B within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively, these values are both higher than IgG1 prevalence (2.7% for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively when compared to rising IgG

  10. Analysis of Hopf Bifurcation Caused by Leakage Conductance g1 in the H-H Model in Muscles%肌肉中的HH模型的漏电导g1Hopf分岔分析

    Institute of Scientific and Technical Information of China (English)

    王江; 邓斌; 曾启明; 张骅

    2003-01-01

    本文以肌肉中的Hodgkin-Huxley模型为研究对象,研究病理实验中有显著变化的漏电导参数g1对Hodgkin-Huxley模型的影响并分析其Hopf分岔.本文采用高维方程的代数判据进行Hodgkin-Huxley模型单参数动态分岔分析,简化了分析过程,并用研究结果解释相应的生理过程,试图从生物系统动态过程异变的角度探讨生理疾病的成因.

  11. A Discrete-Time Geo/G/1 Retrial Queue with Bernoulli Vacation and Second Optional Service%有Bernoulli休假和可选服务的Geo/G/1重试排队

    Institute of Scientific and Technical Information of China (English)

    陈佩树; 朱翼隽; 陈燕

    2011-01-01

    讨论了有Bernoulli休假策略和可选服务的离散时间Geo/G/1重试排队系统.假定一旦顾客发现服务台忙或在休假就进入重试区域,重试时间服从几何分布.顾客在进行第一阶段服务结束后可以离开系统或进一步要求可选服务.服务台在每次服务完毕后,可以进行休假,或者等待服务下一个顾客.还研究了在此模型下的马尔可夫链,并计算了在稳态条件下的系统的各种性能指标以及给出一些特例和系统的随机分解.%We analyze a discrete-time Geo/G/1retrial queue with Bernoulli vacation where all the arriving customers require a first essential service while only some of them demand a second optional service. If upon arrival, the server is busy or vacation, the CU8tomer is obliged to leave the service area and to orbit. Each customer in the orbit forms an independent retrial source and the retrial time follows a geometrical law. Just after completion of a customer's service the server may take a vacation of random length or may opt to continue staying in the system to serve the next customer. We study the Markov chain underlying the considered queuing system and some performance measures of the system in steady-state. Further, we give two stochastic decomposition laws and some examples.

  12. G0/G1 arrest and S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6).

    Science.gov (United States)

    El-Sherbiny, Y M; Cox, M C; Ismail, Z A; Shamsuddin, A M; Vucenik, I

    2001-01-01

    Inositol hexaphosphate (InsP6 or IP6) has shown a striking anti-cancer activity in both in vivo and in vitro models. In an attempt to elucidate the mechanism(s) underlying the anti-neoplastic potential of IP6, we investigated its effect on cell cycle progression of MCF-7 estrogen receptor (ER)-positive and MDA-MB 231 ER-negative human breast cancer cell lines and HT-29 human colon cancer cells. The anti-proliferative effect of IP6 was evaluated using dual-parameter flow cytometric measurements of DNA content, versus the incorporation of 5-bromo-2-deoxyuridine (BrdU) to determine cells actively synthesizing DNA. Combined analysis of the expression of cell cycle-related proteins, proliferation marker Ki-67 and proliferating cell nuclear antigen (PCNA) versus DNA content were used to determine the amount of proliferating cells in each phase, engaged in cell cycle transit. After 3 days of treatment with 5 mM IP6, S-phase, as estimated by BrdU uptake, was significantly decreased in all three cell lines (p = 0.002). MCF-7 and HT-29 cells accumulated in the G0/G1 range of DNA contents (p = 0.002 and p = 0.001, respectively). MDA MB-231 cells transiently accumulated in G0/G1 only after 2 days (p = 0.01). There was a significant decrease in the percentage of Ki-67 expression in IP6-treated cells, from 82.8+/-3.0% to 66.8+/-4.2% in MCF-7 (p = 0.007), from 93.4+/-4.6% to 71.7+/-3.3% in MDA-MB 231 (p = 0.004), and from 95.2+/-1.2% to 73.5+/-2.5% in HT-29 cells (p = 0.002) respectively. PCNA expression levels were also significantly decreased by IP6 in all three cell lines (MCF-7 p = 0.0007; MDA-MB 231 p = 0.0006; HT-29 p = 0.0001). These results show that IP6 controls the progression of cells through the cycle by decreasing S- phase and arresting cells in the G0/G1-phase of the cell cycle. A significant decrease in the expression of proliferation markers indicated that IP6 disengaged cells from actively cycling. Further investigations of cell cycle regulators may lead us to a

  13. Api5 contributes to E2F1 control of the G1/S cell cycle phase transition.

    Directory of Open Access Journals (Sweden)

    Marina Garcia-Jove Navarro

    Full Text Available BACKGROUND: The E2f transcription factor family has a pivotal role in controlling the cell fate in general, and in particular cancer development, by regulating the expression of several genes required for S phase entry and progression through the cell cycle. It has become clear that the transcriptional activation of at least one member of the family, E2F1, can also induce apoptosis. An appropriate balance of positive and negative regulators appears to be necessary to modulate E2F1 transcriptional activity, and thus cell fate. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show that Api5, already known as a regulator of E2F1 induced-apoptosis, is required for the E2F1 transcriptional activation of G1/S transition genes, and consequently, for cell cycle progression and cell proliferation. Api5 appears to be a cell cycle regulated protein. Removal of Api5 reduces cyclin E, cyclin A, cyclin D1 and Cdk2 levels, causing G1 cell cycle arrest and cell cycle delay. Luciferase assays established that Api5 directly regulates the expression of several G1/S genes under E2F1 control. Using protein/protein and protein/DNA immunoprecipitation studies, we demonstrate that Api5, even if not physically interacting with E2F1, contributes positively to E2F1 transcriptional activity by increasing E2F1 binding to its target promoters, through an indirect mechanism. CONCLUSION/SIGNIFICANCE: The results described here support the pivotal role of cell cycle related proteins, that like E2F1, may act as tumor suppressors or as proto-oncogenes during cancer development, depending on the behavior of their positive and negative regulators. According to our findings, Api5 contributes to E2F1 transcriptional activation of cell cycle-associated genes by facilitating E2F1 recruitment onto its target promoters and thus E2F1 target gene transcription.

  14. Optimal management for infinite capacity N-policy M/G/1 queue with a removable service station

    Science.gov (United States)

    Chang, Y. C.; Pearn, W. L.

    2011-07-01

    In this article, we consider an infinite capacity N-policy M/G/1 queueing system with a single removable server. Poisson arrivals and general distribution service times are assumed. The server is controllable that may be turned on at arrival epochs or off at service completion epochs. We apply a differential technique to study system sensitivity, which examines the effect of different system input parameters on the system. A cost model for infinite capacity queueing system under steady-state condition is developed, to determine the optimal management policy at minimum cost. Analytical results for sensitivity analysis are derived. We also provide extensive numerical computations to illustrate the analytical sensitivity properties obtained. Finally, an application example is presented to demonstrate how the model could be used in real applications to obtain the optimal management policy.

  15. In silico Sequence Analysis, Homology Modeling and Function Annotation of Ocimum basilicum Hypothetical Protein G1CT28_OCIBA

    Directory of Open Access Journals (Sweden)

    Sobia Idrees

    2012-07-01

    Full Text Available Ocimum basilicum is commonly known as sweet basil and belongs to the Lamiaceae Family. Ocimum basilicum has great therapeutic benefits and can be used for lowering blood pressure, as an antispasmodic as well as cleansing the blood. In the present study, subcellular localization prediction suggested that it is a cytoplasmic protein. We predicted the 3D structure of protein using homology modeling as 3D structure prediction approach. 3D structure of the protein was determined using Protein Structure Prediction Server (PS2 selecting MODELLER as 3D structure prediction method. Quality analysis of the model indicated that it is a reliable model. Furthermore, it was discovered that Ocimum basilicum hypothetical protein G1CT28_OCIBA is involved in two biological processes, oxidation reduction and metabolic process and the biochemical function of the protein is acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor, catalytic activity and oxidoreductase.

  16. mir-35 is involved in intestine cell G1/S transition and germ cell proliferation in C.elegans

    Institute of Scientific and Technical Information of China (English)

    Min Liu; Pengpeng Liu; Li Zhang; Qingchun Cai; Ge Gao; Wenxia Zhang; Dong Liu; Qichang Fan; Zuoyan Zhu

    2011-01-01

    MicroRNA (miRNA) regulates gene expression in many cellular events,yet functions of only a few miRNAs are known in C.elegans.We analyzed the function of mir-35-41 unique to the worm,and show here that mir-35 regulates the G1/S transition of intestinal cells and germ cell proliferation.Loss of mir-35 leads to a decrease of nuclei numbers in intestine and distal mitotic gonad,while re-introduction of mir-35 rescues the mutant phenotypes.Genetic analysis indicates that mir-35 may act through Rb/E2F and SCF pathways.Further bioinformatic and functional analyses demonstrate that mir-35 targets evolutionaily conserved lin-23 and gld-1.Together,our study reveals a novel function of mir-35 family in cell division regulation.

  17. A VLA ARCHIVE OBSERVATION OF THE YOUNGEST KNOWN GALACTIC SUPERNOVA REMNANT G1.9+0.3

    Directory of Open Access Journals (Sweden)

    Yolanda Gómez

    2009-01-01

    Full Text Available Presentamos el análisis de una observación de archivo sin publicar hecha con el Very Large Array a 1.49 GHz en 1989 hacia la remanente de supernova G1.9+0.3, la más joven conocida en la Galaxia. Esta observación concuerda con la evolución temporal del tama~no angular reportada anteriormente. Derivamos una tasa de expansión angular de 0:46 +- 0:11% por año y estimamos una edad de 220+-70/45 años comparando las imágenes de 1985 y 1989.

  18. Young Remnants of Type Ia Supernovae and Their Progenitors: A Study of SNR G1.9+0.3

    CERN Document Server

    Chakraborti, Sayan; Soderberg, Alicia

    2015-01-01

    Type Ia supernovae, with their remarkably homogeneous light curves and spectra, have been used as standardizable candles to measure the accelerating expansion of the Universe. Yet, their progenitors remain elusive. Common explanations invoke a degenerate star (white dwarf) which explodes upon reaching close to the Chandrasekhar limit, by either steadily accreting mass from a companion star or violently merging with another degenerate star. We show that circumstellar interaction in young Galactic supernova remnants can be used to distinguish between these single and double degenerate progenitor scenarios. Here we propose a new diagnostic, the Surface Brightness Index, which can be computed from theory and compared with Chandra and VLA observations. We use this method to demonstrate that a double degenerate progenitor can explain the decades-long flux rise and size increase of the youngest known Galactic SNR G1.9+0.3. We disfavor a single degenerate scenario. We attribute the observed properties to the interact...

  19. Phylogenetic relationships among Brazilian howler monkeys, genus Alouatta (Platyrrhini, Atelidae, based on g1-globin pseudogene sequences

    Directory of Open Access Journals (Sweden)

    Carla Maria Meireles

    1999-09-01

    Full Text Available The genus Alouatta (howler monkeys is the most widely distributed of New World primates, and has been arranged in three species groups: the Central American Alouatta palliata group and the South American Alouatta seniculus and Alouatta caraya groups. While the latter is monotypic, the A. seniculus group encompasses at least three species (A. seniculus, A. belzebul and A. fusca. In the present study, approximately 600 base pairs of the g1-globin pseudogene were sequenced in the four Brazilian species (A. seniculus, A. belzebul, A. fusca and A. caraya. Maximum parsimony and maximum likelihood methods yielded phylogenetic trees with the same arrangement: {A. caraya [A. seniculus (A. fusca, A. belzebul]}. The most parsimonious tree had bootstrap values greater than 82% for all groupings, and strength of grouping values of at least 2, supporting the sister clade of A. fusca and A. belzebul. The study also confirmed the presence of a 150-base pair Alu insertion element and a 1.8-kb deletion in the g1-globin pseudogene in A. fusca, features found previously in the remaining three species. The cladistic classification based on molecular data agrees with those of morphological studies, with the monospecific A. caraya group being clearly differentiated from the A. seniculus group.Os guaribas, do gênero Alouatta, que são os primatas do Novo Mundo com maior distribuição geográfica, têm sido colocados em três grupos de espécies: o grupo Alouatta palliata da América central, e os grupos sulamericanos Alouatta seniculus e Alouatta caraya. Este último é monotípico, mas o grupo A. seniculus inclui pelo menos três espécies (A. seniculus, A. belzebul e A. fusca. Neste estudo, foram seqüenciados aproximadamente 600 pares de base do pseudogene globina g1 nas quatro espécies brasileiras (A. seniculus, A. belzebul, A. fusca e A. caraya. Os métodos de máxima parcimônia e máxima verossimilhança produziram árvores filogenéticas com o mesmo arranjo

  20. Human RAD6 Promotes G1-S Transition and Cell Proliferation through Upregulation of Cyclin D1 Expression

    Science.gov (United States)

    Biskup, Ewelina; Liu, Yan; Chen, Pei-Chao; Chang, Jian-Feng; Jiang, Wenjie; Jing, Yuanya; Chen, Youwei; Jin, Hui; Chen, Su

    2014-01-01

    Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics. PMID:25409181

  1. Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression.

    Directory of Open Access Journals (Sweden)

    Fengfeng Cai

    Full Text Available Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1 in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.

  2. An M[x]/G/1 Retrial G-queue with Single Vacation Subject to the Server Breakdown and Repair

    Institute of Scientific and Technical Information of China (English)

    Shu-ping YANG; Jin-biao WU; Zai-ming LIU

    2013-01-01

    An M[X]/G/1 retrial G-queue with single vacation and unreliable server is investigated in this paper.Arrivals of positive customers form a compound Poisson process,and positive customers receive service immediately if the server is free upon their arrivals; Otherwise,they may enter a retrial orbit and try their luck after a random time interval.The arrivals of negative customers form a Poisson process.Negative customers not only remove the customer being in service,but also make the server under repair.The server leaves for a single vacation as soon as the system empties.In this paper,we analyze the ergodical condition of this model.By applying the supplementary variables method,we obtain the steady-state solutions for both queueing measures and reliability quantities.

  3. Lysocellin, a metabolite of the novel drug 'alopestatin', induces G1 arrest and prevents cytotoxicity induced by etoposide.

    Science.gov (United States)

    Takahara, Yoshinori; Yogosawa, Shingo; Maruyama, Sakiko; Watanabe, Noriko; Yokoyama, Hirofumi; Fukasawa, Kazuteru; Sukenaga, Yoshikazu; Kamiyama, Jun; Izumi, Moriatsu; Wakada, Miki; Zhang, Helin; Yoshizawa, Kaname; Kawa, Shigeyuki; Nikaido, Toshio; Sakai, Toshiyuki

    2006-04-01

    We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. In drug combination studies, we found that lysocellin treatment weakened the cytotoxic activity of etoposide in MG63 cells using a colony-formation assay. To study the in vivo efficacy of lysocellin, we isolated a novel compound related to lysocellin from the same streptomycete, and found that the novel drug is converted to lysocellin in vivo and decreases etoposide-induced alopecia in a neonatal rat model. We raise the possibility that this novel drug, named 'alopestatin', may be a promising agent against alopecia.

  4. Do comets C/1861 G1 (Thatcher) and C/1861 J1 (Great comet) have a common origin?

    Science.gov (United States)

    Branham, R. L.

    2015-10-01

    A new orbit is calculated for Comet C/1861 G1 (Thatcher), associated with the Lyrid meteor shower, to replace Oppolzer's orbit of 1864. The new orbit is based upon 649 observations, 326 in right ascension and 323 in declination, made between 11 April 1861 and 7 Sept. 1861. The final orbit uses residuals calculated with the Welsch weighting function. The comet's period of 416.87 ± 0.56 yr agrees with Oppolzer's period of 415 yr athough other elements such as the inclination differ. Although the post-perihelion residuals are relatively random, 52.1% probability of randomness, pre-perihelion residuals lack randomness indicating possible deviations from Keplerian motion caused by ejection of meteoritic material. Comet Thatcher is unrelated to the Great comet of 1861.

  5. (2S)-naringenin from Typha angustata inhibits vascular smooth muscle cell proliferation via a G0/G1 arrest.

    Science.gov (United States)

    Lee, Jung-Jin; Yi, Hyoseok; Kim, In-Su; Kim, Yohan; Nhiem, Nguyen Xuan; Kim, Young Ho; Myung, Chang-Seon

    2012-02-15

    Typha angustata is used in traditional Chinese medicine for a variety of clinical disorders. Its pharmacological actions include beneficial effects on hyperlipidemia and myocardial infarction, as well as labor-inducing and antibacterial effects. We investigated the mechanism underlying the ability of (2S)-naringenin, an active compound from Typha angustata, to inhibit the proliferation of vascular smooth muscle cells (VSMCs). After measuring the antiproliferative effect of (2S)-naringenin on VSMC proliferation using cell proliferation and viability assays, the possible involvement of a signaling pathway associated with platelet-derived growth factor receptor β (PDGF-Rβ), extracellular signal regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB), or phospholipase C-γ1 (PLCγ1) was investigated by immunoblotting. Moreover, the effect of (2S)-naringenin on DNA synthesis and the cell cycle was examined using a [(3)H]-thymidine incorporation assay and flow cytometry. (2S)-Naringenin significantly inhibited PDGF-BB-induced VSMC proliferation in a concentration-dependent manner, but did not affect signaling pathways associated with PDGF-Rβ, Akt/PKB, ERK1/2, or PLCγ1. However, (2S)-naringenin suppressed DNA synthesis via a G(0)/G(1) cell cycle arrest. Accordingly, the expression of cyclins D1 and E and cyclin-dependent kinases 2 and 4 was inhibited in a concentration-dependent manner; moreover, the phosphorylation of retinoblastoma protein was suppressed. Our results show that (2S)-naringenin inhibited the PDGF-BB-induced proliferation of VSMCs via a G(0)/G(1) arrest; thus, (2S)-naringenin may be valuable as a therapeutic agent for managing atherosclerosis and/or vascular restenosis. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Development of tetravalent IgG1 dual targeting IGF-1R-EGFR antibodies with potent tumor inhibition.

    Science.gov (United States)

    Croasdale, Rebecca; Wartha, Katharina; Schanzer, Juergen M; Kuenkele, Klaus-Peter; Ries, Carola; Mayer, Klaus; Gassner, Christian; Wagner, Martina; Dimoudis, Nikolaos; Herter, Sylvia; Jaeger, Christiane; Ferrara, Claudia; Hoffmann, Eike; Kling, Lothar; Lau, Wilma; Staack, Roland F; Heinrich, Julia; Scheuer, Werner; Stracke, Jan; Gerdes, Christian; Brinkmann, Ulrich; Umana, Pablo; Klein, Christian

    2012-10-15

    In this study we present novel bispecific antibodies that simultaneously target the insulin-like growth factor receptor type I (IGF-1R) and epidermal growth factor receptor (EGFR). For this purpose disulfide stabilized scFv domains of the EGFR/ADCC antibody GA201 were fused via serine-glycine connectors to the C-terminus of the heavy (XGFR2) or light chain (XGFR4), or the N-termini of the light (XGFR5) or heavy chain (XGFR3) of the IGF-1R antibody R1507 as parental IgG1 antibody. The resulting bispecific IGF-1R-EGFR antibodies XGFR2, XGFR3 and XGFR4 were successfully generated with yields and stability comparable to conventional IgG1 antibodies. They effectively inhibited IGF-1R and EGFR phosphorylation and 3D proliferation of H322M and H460M2 tumor cells, induced strong down-modulation of IGF-1R as well as enhanced EGFR down-modulation compared to the parental EGFR antibody GA201 and were ADCC competent. The bispecific XGFR derivatives showed a strong format dependent influence of N- or C-terminal heavy and light chain scFv attachment on ADCC activity and an increase in receptor downregulation over the parental combination in vitro. XGFR2 and XGFR4 were selected for in vivo evaluation and showed potent anti-tumoral efficacy comparable to the combination of monospecific IGF-1R and EGFR antibodies in subcutaneous BxPC3 and H322M xenograft models. In summary, we have managed to overcome issues of stability and productivity of bispecific antibodies, discovered important antibody fusion protein design related differences on ADCC activity and receptor downmodulation and show that IGF-1R-EGFR antibodies represent an attractive therapeutic strategy to simultaneously target two key components de-regulated in multiple cancer types, with the ultimate goal to avoid the formation of resistance to therapy.

  7. Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance

    Directory of Open Access Journals (Sweden)

    Thieffry Denis

    2009-01-01

    Full Text Available Abstract Background In breast cancer, overexpression of the transmembrane tyrosine kinase ERBB2 is an adverse prognostic marker, and occurs in almost 30% of the patients. For therapeutic intervention, ERBB2 is targeted by monoclonal antibody trastuzumab in adjuvant settings; however, de novo resistance to this antibody is still a serious issue, requiring the identification of additional targets to overcome resistance. In this study, we have combined computational simulations, experimental testing of simulation results, and finally reverse engineering of a protein interaction network to define potential therapeutic strategies for de novo trastuzumab resistant breast cancer. Results First, we employed Boolean logic to model regulatory interactions and simulated single and multiple protein loss-of-functions. Then, our simulation results were tested experimentally by producing single and double knockdowns of the network components and measuring their effects on G1/S transition during cell cycle progression. Combinatorial targeting of ERBB2 and EGFR did not affect the response to trastuzumab in de novo resistant cells, which might be due to decoupling of receptor activation and cell cycle progression. Furthermore, examination of c-MYC in resistant as well as in sensitive cell lines, using a specific chemical inhibitor of c-MYC (alone or in combination with trastuzumab, demonstrated that both trastuzumab sensitive and resistant cells responded to c-MYC perturbation. Conclusion In this study, we connected ERBB signaling with G1/S transition of the cell cycle via two major cell signaling pathways and two key transcription factors, to model an interaction network that allows for the identification of novel targets in the treatment of trastuzumab resistant breast cancer. Applying this new strategy, we found that, in contrast to trastuzumab sensitive breast cancer cells, combinatorial targeting of ERBB receptors or of key signaling intermediates does not

  8. Accurate Analytic Potential Energy Function and Spectroscopic Study for G1 ∏g State of Dimer 7Li2

    Institute of Scientific and Technical Information of China (English)

    SHI De-Heng; MA Heng; SUN Jin-Feng; ZHU Zun-Lue

    2007-01-01

    The reasonable dissociation limit for the G1∏g state of dimer 7Li2 is determined. The equilibrium internuclear distance, dissociation energy, harmonic frequency, vibrational zero energy, and adiabatic excitation energy are calculated using a symmetry-adapted-cluster configuration-interaction method in complete active space in Gaussian03 program package at such numerous basis sets as 6-311++G, 6-311++G(2df, 2pd), 6-311++G(2df, p), cc-PVTZ, 6-311++G(3df, 3pd), CEP-121G, 6-311++G(2df, pd), 6-311++G(d,p),6-311G(3df,3pd), D95(3df,3pd), 6-311++G(3df, 2p),6-311++G(2df), 6-311++G(df, pd) D95V++, and DGDZVP. The complete potential energy curves are obtained at these sets over a wide internuclear distance range and have least squares fitted to Murrell-Sorbie function. The conclusion shows that the basis set 6-311++G(2df, p) is a most suitable one for the G1∏g state. At this basis set, the calculated spectroscopic constants Te, De, Eo, Re, ωe, ωeXe, αe, and Be are of 3.9523 eV, 0.813 06 eV, 113.56 cm-1, 0.320 15 nm,227.96 cm-1, 1.6928 cm-1, 0.004 436 cm-1, and 0.4689 cm-1, respectively, which are in good agreement with measurements whenever available. The total 50 vibrational levels and corresponding inertial rotation constants are for the first time calculated and compared with available RKR data. And good agreement with measurements is obtained.

  9. Matrine promotes G0/G1 arrest and down-regulates cyclin D1 expression in human rhabdomyosarcoma cells.

    Science.gov (United States)

    Guo, L; Xue, T Y; Xu, W; Gao, J Z

    2013-09-01

    Matrine has a broad-spectrum of anti-cancer effects and is efficient in the inhibition of proliferation of hepatoma cells, leukemia cells and neuroblastoma cell. However, its efficacy and tentative mechanisms in rhabdomyosarcoma have not been addressed before. This study aimed to investigate the effects of Matrine on cell cycle and expression of cyclin D1 in human rhabdomyosarcoma cells (RD cell line). RD cell line was treated with different concentrations (0, 0.5, 1.0, and 1.5 mg/mL) of Matrine, and cell proliferation and cell cycle were evaluated using, respectively, MTT assay and flow cytometry. The effect of Matrine on cyclin D1 mRNA levels was measured by RT-PCR. There was a dose-dependent inhibition of proliferation in the matrine-treated group (inhibition of proliferation rate in control cells 12.70 ± 0.35%; Matrine-treated cells [0.5, 1.0, and 1.5 mg/mL]: 31.16 ± 0.11%, 42.96 ± 0.9%, and 57.26 ± 0.8%). The G0 / G1 ratio in study groups were, respectively, 58.44 ± 3.57%, 64.79 ± 2.03%, 69.97 ± 2.89% and 75.03 ± 1.23%.Cyclin D1 mRNA levels progressively diminished (control group ratio of cyclin D1 / β-actin: 0.59 ± 0.06; Matrine: 0.35 ± 0.05, 0.27 ± 0.02 and 0.04 ± 0.03). All aforementioned changes were significant (PMatrine markedly suppresses cell proliferation in RD cells by decreasing expression of cyclin D1 mRNA and blocking the cell cycle at the G0 / G1 stage.

  10. Asteroid observations at low phase angles. IV. Average parameters for the new H, G1, G2 magnitude system

    Science.gov (United States)

    Shevchenko, Vasilij G.; Belskaya, Irina N.; Muinonen, Karri; Penttilä, Antti; Krugly, Yurij N.; Velichko, Feodor P.; Chiorny, Vasilij G.; Slyusarev, Ivan G.; Gaftonyuk, Ninel M.; Tereschenko, Igor A.

    2016-04-01

    We present new observational data for selected main-belt asteroids of different compositional types. The detailed magnitude-phase dependences including small phase angles (Aurelia (0.1°, F-type), (596) Scheila (0.2°, D-type), (635) Vundtia (0.2°, B-type), (671) Carnegia (0.2°, P-type), (717) Wisibada (0.1°, T-type), (1021) Flammario (0.6°, B-type), and (1279) Uganda (0.5°, E-type). For several asteroids, the dependences of brightness on the phase angle were investigated in the BVRI bands. We found a great diversity in the opposition-effect behavior both in the magnitude and the width of the opposition surges, especially for low-albedo asteroids. Some low-albedo asteroids (e.g., (10) Hygiea) display a broad opposition effect with an amplitude of 0.15-0.20 mag relative to the extrapolation of the linear part of the phase curve. Other asteroids (e.g., (596) Scheila, (1021) Flammario) show linear magnitude-phase dependences down to small phase angles (0.1-0.2°). Using numerous data sets on the magnitude-phase dependences with extensive phase-angle coverage, we examined in more detail the new three-parameter H, G1, G2 magnitude system. We determined the values of the G1 and G2 parameters for magnitude phase dependences of individual asteroids and obtained the average parameters for main asteroid compositional types. The values obtained can be used for the estimation of the absolute magnitude of an asteroid from a single observed magnitude when the magnitude-phase dependency is unknown and/or to calculate a visible magnitude for the ephemerides.

  11. Identificación de los polimorfismos G1 y G8 del gen GDF9 en ovinos criollos Araucanos

    Directory of Open Access Journals (Sweden)

    E Paz

    2014-01-01

    Full Text Available En la especie ovina se han descrito una serie de polimorfismos en genes de efecto mayor relacionados con la actividad reproductiva. Las mutaciones ubicadas en el gen de efecto mayor GDF9 se han asociado con el incremento de la tasa ovulatoria y el tamaño de la camada. GDF9 es un factor celular secretado por el ovocito y es miembro de la familia de factores de crecimiento transformante (TGF-β localizado en el cromosoma 5 ovino. El objetivo de este trabajo fue identificar la presencia de los polimorfismos en los sitios G1 y G8 en el gen GDF9 en ovinos criollos Araucanos. Se extrajo el ADN de 100 muestras sanguíneas para posteriormente determinar la presencia de las mutaciones utilizando la técnica PCR-RFLP. Fue amplificada una región de 462 pb correspondiente al exón 1, la cuál fue digerida con la enzima de restricción HhaI, el siguiente fragmento amplificado fue de 139 pb correspondiente al exón 2, siendo digerido con la enzima Ddel. Se identificó la presencia del polimorfismo G1 con una frecuencia genotípica del 0,56 (genotipo GG, 0,44 (genotipo GA y una frecuencia alélica de 0,78 para el alelo (G y 0,22 para el alelo (A. No se detectó la presencia de polimorfismo G8. Este es el primer reporte de este polimorfismo en ovinos en Chile que podría servir como un marcador genético de prolificidad para la selección de ovinos criollos Araucanos.

  12. Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

    Science.gov (United States)

    Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

    2017-02-01

    The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G0/G1 phase and reduced the number of cells in the S phase, as compared with the control group (Parctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G0/G1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

  13. Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Seiko [Division of Infections and Molecular Biology, Kyushu Dental University (Japan); Division of Maxillofacial Surgery, Kyushu Dental University (Japan); Okinaga, Toshinori; Ariyoshi, Wataru [Division of Infections and Molecular Biology, Kyushu Dental University (Japan); Oral Biology Research Center, Kyushu Dental University (Japan); Takahashi, Osamu; Iwanaga, Kenjiro [Division of Maxillofacial Surgery, Kyushu Dental University (Japan); Nishino, Norikazu [Oral Biology Research Center, Kyushu Dental University (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Surgery, Kyushu Dental University (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Kyushu Dental University (Japan); Oral Biology Research Center, Kyushu Dental University (Japan)

    2013-05-10

    Highlights: •Novel histone deacetylase inhibitor Ky-2, remarkably inhibits myeloma cell growth. •Ky-2 demonstrates no cytotoxicity against normal lymphocytic cells. •Ky-2 induces cell cycle arrest through the cell cycle-associated proteins. •Ky-2 induces Bcl-2-inhibitable apoptosis through a caspase-dependent cascade. -- Abstract: Objectives: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. Materials and methods: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst’s staining was used to detect apoptotic cells. Results: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. Conclusion: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells.

  14. Enhanced translocation and growth of Rhodococcus erythropolis PR4 in the alkane phase of aqueous-alkane two phase cultures were mediated by GroEL2 overexpression.

    Science.gov (United States)

    Takihara, Hayato; Ogihara, Jun; Yoshida, Takao; Okuda, Shujiro; Nakajima, Mutsuyasu; Iwabuchi, Noriyuki; Sunairi, Michio

    2014-01-01

    We previously reported that R. erythropolis PR4 translocated from the aqueous to the alkane phase, and then grew in two phase cultures to which long-chain alkanes had been added. This was considered to be beneficial for bioremediation. In the present study, we investigated the proteins involved in the translocation of R. erythropolis PR4. The results of our proteogenomic analysis suggested that GroEL2 was upregulated more in cells that translocated inside of the pristane (C19) phase than in those located at the aqueous-alkane interface attached to the n-dodecane (C12) surface. PR4 (pK4-EL2-1) and PR4 (pK4-ΔEL2-1) strains were constructed to confirm the effects of the upregulation of GroEL2 in translocated cells. The expression of GroEL2 in PR4 (pK4-EL2-1) was 15.5-fold higher than that in PR4 (pK4-ΔEL2-1) in two phase cultures containing C12. The growth and cell surface lipophilicity of PR4 were enhanced by the introduction of pK4-EL2-1. These results suggested that the plasmid overexpression of groEL2 in PR4 (pK4-EL2-1) led to changes in cell localization, enhanced growth, and increased cell surface lipophilicity. Thus, we concluded that the overexpression of GroEL2 may play an important role in increasing the organic solvent tolerance of R. erythropolis PR4 in aqueous-alkane two phase cultures.

  15. Geology and uranium occurrences in the Forez tertiary plain (in the French 'Massif Central'); Geologie et mineralisations uraniferes de la plaine tertiaire du Forez (Massif Central francais)

    Energy Technology Data Exchange (ETDEWEB)

    Duclos, P. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses - 92 (France). Centre d' Etudes Nucleaires

    1967-01-01

    In the first part, the observations made during the geological survey of the Forez Tertiary plain (in the French 'Massif Central') are recalled. Then, using various methods, the author lists the formations according to chronology. Finally, a reconstitution of the geological history of this subsidence basin is attempted. In the second part, the occurrence of 17 uranium bearing geochemical anomalies is commented upon. Each of these various anomalies is given a place on the stratigraphic scale. This enables the author to put the successive phases of uranium deposition into their proper perspective in the history of the plain. In conclusion, the author points out the usefulness of these uraniferous geochemical anomalies. (author) [French] Dans la premiere partie, l'auteur rappelle les observations faites au cours de l'etude geologique de la plaine tertiaire du Forez (Massif Central francais). Puis se servant de differentes methodes, il etablit une chronologie des formations. Enfin, il termine par un essai de reconstitution de l'histoire geologique de ce bassin de subsidence. Dans la deuxieme partie, il commente la decouverte de 17 anomalies geochimiques uraniferes. Il situe ces differentes anomalies dans la serie stratigraphique. Ceci lui permet de replacer les depots successifs de l'uranium dans l'histoire de la plaine. Enfin, il indique l'interet de ces anomalies geochimiques uraniferes. (auteur)

  16. Radioprotection and the argon 41 formed in the reactors G-1 and G-2/G-3; La radioprotection et l'argon 41 forme dans les piles G-1 et G-2/G-3

    Energy Technology Data Exchange (ETDEWEB)

    Chassany, J.Ph.; Paillard, R.; Meffre, P. [Commissariat a l' Energie Atomique, Marcoule (France). Centre de Production de Plutonium de Marcoule

    1965-07-01

    The activation of argon 40 present in the air (9.3 l/m{sup 3}) or in trace form in CO{sub 2} is particularly important. In G-1 the cooling is effected by atmospheric air which passes through the reactor and is expelled through a chimney. The activity due to argon 41 of the expelled air is about l0{sup -4} Ci/m{sup 3}. For the reactors G-2 and G-3 the cooling is effected using CO{sub 2} in a closed circuit at a pressure of 15 kg/cm{sup 2}. Although the argon content of industrial CO{sub 2} is practically constant, it can be influenced by that of the residual air left in the circuits during the start-up. The activity due to argon 41 of the neat-carrying fluid is about 10{sup -3} Ci/m{sup 3}. (authors) [French] L'activation de l'argon 40 present dans l'air (9,3 l par m{sup 3}) ou a l'etat de trace dans CO{sub 2} est particulierement importante. A G-1, le refroidissement est effectue par de l'air atmospherique traversant la pile et rejete par une cheminee. L'activite en argon 41 de l'air a la sortie est de l'ordre de 10{sup -4} Ci/m{sup 3}. Pour les piles G-2 et G-3, le refroidissement est assure par du CO{sub 2}, en circuit ferme, sous une pression de 15 kg/cm{sup 2}. Si la teneur en argon du CO{sub 2} industriel est pratiquement constante, elle peut etre influencee par celle de l'air residuel laisse dans les circuits au moment du gonflage. L'activite en argon 41 du fluide caloporteur est de l'ordre de 10{sup -3} Ci/m{sup 3}. (auteurs)

  17. 带负顾客和不耐烦顾客的离散时间Geo/G/1重试排队%A discrete-time Geo/G/1 retrial queue with negative customers and impatient customers

    Institute of Scientific and Technical Information of China (English)

    彭懿; 杨向群; 吴锦标

    2011-01-01

    考虑了一个带负顾客和不耐烦顾客且重试时间为一般分布的离散时间Geo/G/1重试排队系统.负顾客带走一个正在服务的顾客,而对重试组中的顾客无影响.正顾客到达系统若遇服务器忙则可能进入重试组也可能离开系统.通过对此排队系统的嵌入马氏链进行分析,得到了重试组队长和系统队长的概率母函数.进而得到了一系列重要的排队指标.此外,还推导出了系统的稳态存在条件.以及对无负顾客和不耐烦顾客时的特例进行了分析.最后通过几个具体的数值实例演示了一些参数对系统关键性能指标的影响.%We consider a discrete-time Geo/G/1 retrial queue with negative customers and general retrial times. Negative customers will make the customer being in service lost but has no effect to the orbit. When the server is busy, the arriving positive customers either enter the orbit or leave the system. We analyze the Markov chain underlying the considered queueing system. The system state distribution as well as the orbit size and the system size distributions are obtained in terms of their generating functions. These generating functions yield exact expressions for some important performance measures. Besides, the stability condition of the system is derived. Further, the special case of no negative customers and no impatient customers is discussed. Finally, some numerical examples are provided to illustrate the impact of several parameters on some crucial performance characteristics of the system.

  18. An M~X/G/1 Retrial Queue with Starting Failures and Negative Customers%有启动失败和负顾客的M^X/G/1重试排队模型

    Institute of Scientific and Technical Information of China (English)

    高珊; 刘再明

    2011-01-01

    An MX/G/1 retrial queue with negative customers and starting failures is considered.Negative customers arrive according to a Poisson process with parameter δ when the positive customer is undergoing service,and a positive customer undergoing service gets annihilated with probability θ(0θ≤1) or survives the onslaught of an arriving negative customer with probability 1-θ and continues his service.By using embedded Markov chain,the necessary and sufficient condition for the system stability is derived and the stationary distribution of the embedded Markov chain is given.The steady-state distributions of the number of customers in the system and orbit and other performance measures are obtained through method of supplementary variables,and the stochastic decomposition property and some special cases are analyzed.At last some numerical examples are given to illustrate the impact of the parameters on the some performance characteristics.%研究有负顾客到达的MX/G/1重试排队模型,其中服务台有可能启动失败。负顾客在服务台忙时以到达率为δ的Po isson流进入系统,且以概率θ(0〈θ≤1)带走正在服务的正顾客,否则以概率1-θ正顾客继续接受服务。通过嵌入马尔可夫链法给出了系统稳态的充要条件并给出了嵌入马尔可夫链的稳态分布。利用补充变量法得到了稳态时系统和重试区域中队长以及系统的各种指标,并给出了系统队长的随机分解性和几种特例,最后给出了几个数值例子来说明各参数对一些系统性能指标的影响。

  19. p16INK4a, but not constitutively active pRb, can impose a sustained G1 arrest: molecular mechanisms and implications for oncogenesis

    DEFF Research Database (Denmark)

    Lukas, J; Sørensen, Claus Storgaard; Lukas, C

    1999-01-01

    p16ink4 and pRb, two components of a key G1/S regulatory pathway, and tumor suppressors commonly targeted in oncogenesis, are among the candidates for gene therapy of cancer. Wild-type p16 and a constitutively active pRb(delta cdk) mutant both blocked G1 in short-term experiments, but only p16...

  20. Well-Posedness of M/G/1 Queuing System with Multiple Working Vacation and Vacation Interruption%工作休假和休假中止的M/G/1排队模型的适定性

    Institute of Scientific and Technical Information of China (English)

    图尔逊艾力·尼亚孜; 艾合买提·阿不来提

    2012-01-01

    In this paper, we mainly study the M/G/l queuing system with multiple working vacation and vacation interruption. First, we convert the mathematical model corresponding to this system into an abstract Cauchy problem. Second, we prove that the operator corresponding this queuing model generates a positive contraction Co-semigroup T(t). Then we show that T(t) is isometric operator. Last, we conclude that this model has a unique nonnegative time-dependent solution.%主要研究工作休假和休假中止的M/G/1排队系统,首先将对应于此系统的数学模型转化为抽象Cauchy问题,其次证明对应于此排队模型的主算子生成正压缩C0半群T(t),然后证明T(t)是局部等距的,最后证明此模型存在唯一的非负时间依赖解.

  1. Drawing a Line in the Sand: Identifying the Borderzone between Self and Other in EL1 and EL2 Citation Practices

    Science.gov (United States)

    Hyland, Theresa Ann

    2009-01-01

    Current concerns about academic plagiarism in student writing assume qualitative and quantitative differences in the writing of students for whom English is a first language (EL1) and English is a second language (EL2), but lack precision in measuring those differences. I examined the citation practices of EL1 and EL2 students in a timed writing…

  2. Effect of synchronization of donor cells in early G1-phase using shake-off method on developmental potential of somatic cell nuclear transfer embryos in cattle.

    Science.gov (United States)

    Goto, Yuji; Hirayama, Muneyuki; Takeda, Kazuya; Tukamoto, Nobuyuki; Sakata, Osamu; Kaeriyama, Hiroshi; Geshi, Masaya

    2013-08-01

    In this study, we compared the developmental ability of somatic cell nuclear transfer (SCNT) embryos reconstructed with three bovine somatic cells that had been synchronized in G0-phase (G0-SCNT group) or early G1-phase (eG1-SCNT group). Furthermore, we investigated the production efficiency of cloned offspring for NT embryos derived from these donor cells. The G0-phase and eG1-phase cells were synchronized, respectively, using serum starvation and antimitotic reagent treatment combined with shaking of the plate containing the cells (shake-off method). The fusion rate in the G0-SCNT groups (64.2 ± 1.8%) was significantly higher than that of eG1-SCNT groups (39.2 ± 1.9%) (P cells in eG1-phase using the shake-off method improved the overall production efficiency of the clone offspring per transferred embryo.

  3. Comparison of SEC and CE-SDS methods for monitoring hinge fragmentation in IgG1 monoclonal antibodies.

    Science.gov (United States)

    Dada, Oluwatosin O; Rao, Romesh; Jones, Natalie; Jaya, Nomalie; Salas-Solano, Oscar

    2017-10-25

    Fragmentation of monoclonal antibodies is a critical quality attribute routinely monitored to assess the purity and integrity of the product from development to commercialization. Cleavage in the upper hinge region of IgG1 monoclonal antibodies is a common fragmentation pattern widely studied by size exclusion chromatography (SEC). Capillary electrophoresis with sodium dodecylsulfate (CE-SDS) is a well-established technique commonly used for monitoring antibody fragments as well, but its comparability to SEC in monitoring hinge fragments has not been established until now. We report a characterization strategy that establishes the correlation between hinge region fragments analyzed by SEC and CE-SDS. Monoclonal antibodies with elevated hinge fragments were generated under low pH stress conditions and analyzed by SEC and CE-SDS. The masses of the fragments generated were determined by LC-MS. Electrophoretic migration of the hinge fragmentation products in CE-SDS were determined based on their mass values. Comparative assessment of fragments by SEC, and CE-SDS showed similar correlation with incubation time. This study demonstrates that CE-SDS can be employed as a surrogate technique to SEC for monitoring hinge region fragments. Most importantly, combination of these techniques can be used to obtain comprehensive understanding of fragment related characteristics of therapeutic protein products. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.

    Science.gov (United States)

    Aregger, Michael; Kaskar, Aneesa; Varshney, Dhaval; Fernandez-Sanchez, Maria Elena; Inesta-Vaquera, Francisco A; Weidlich, Simone; Cowling, Victoria H

    2016-03-03

    The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Casein Kinase Iγ2 Impairs Fibroblasts Actin Stress Fibers Formation and Delays Cell Cycle Progression in G1

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    Mathieu Latreille

    2012-01-01

    Full Text Available Actin cytoskeleton remodeling is under the regulation of multiple proteins with various activities. Here, we demonstrate that the γ2 isoform of Casein Kinase I (CKIγ2 is part of a novel molecular path regulating the formation of actin stress fibers. We show that overexpression of CKIγ2 in fibroblasts alters cell morphology by impairing actin stress fibers formation. We demonstrate that this is concomitant with increased phosphorylation of the CDK inhibitor p27Kip and lower levels of activated RhoA, and is dependent on CKIγ2 catalytic activity. Moreover, we report that roscovitine, a potent inhibitor of cyclin-dependent kinases, including Cdk5, decreases p27Kip protein levels and restores actin stress fibers formation in CKIγ2 overexpressing cells, suggesting the existence of a CKIγ2-Cdk5-p27Kip-RhoA pathway in regulating actin remodeling. On the other hand, we also show that in a manner independent of its catalytic activity, CKIγ2 delays cell cycle progression through G1. Collectively our findings reveal that CKIγ2 is a novel player in the control of actin cytoskeleton dynamics and cell proliferation.

  6. Monitoring of aflatoxin G1, B1, G2, and B2 occurrence in some samples of walnut.

    Science.gov (United States)

    Habibipour, Reza; Tamandegani, Parisa Rahimi; Farmany, Abbas

    2016-12-01

    This research was conducted to monitor the aflatoxigenic fungi and aflatoxin contamination of walnut in the Hamedan province. For this purpose, 40 samples were analyzed. Aspergillus, Alternaria, Rhizopus, Cladosporium, Fusarium, yeast, and some different bacteria were isolated from walnuts. Aspergillus is the most frequent genus. Aspergillus flavus was predominantly isolated. HPLC was used for evaluation of aflatoxin contamination of walnut samples. Aflatoxins G1 (AFG1), B1 (AFB1), G2 (AFG2), and B2 (AFB2) were produced by 20 isolates. AFG1 and AFB1 were being predominant at concentration ranges of 1.7-18.2 and 0-8.2 ngg(-1), respectively. Highest levels were found in one sample that was highly contaminated with Aspergillus flavus/Aspergillus parasiticus. Methyl beta cyclodextrin also was performed for detection of aflatoxigenic Aspergillus isolates. The results showed that only 31.6% (p aflatoxin. A significant difference was shown between shielded and unshielded walnut in aflatoxin contamination. The content of aflatoxin in most of the walnut samples did not reach to maximum tolerable limit for aflatoxin B1 in EU standard (p > 0.05). Thus, systematic and continues monitoring of walnuts is recommended.

  7. DO COMETS C/1861 G1 (THATCHER AND C/1861 J1 (GREAT COMET HAVE A COMMON ORIGIN?

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    Richard L. Branham

    2015-01-01

    Full Text Available Con el objeto de mejorar la ́orbita de Oppolzer de 1864, se cal cula una nueva ́orbita para el Cometa C/1861 G1 (Thatcher, el cual es t ́a asociado a la lluvia de estrellas de las L ́ıridas. La nueva ́orbita se basa en 649 observaciones hechas entre el 11 de abril y el 7 de septiembre de 1861, 326 en a scensi ́on recta y 323 en declinaci ́on. La ́orbita final utiliza los residuos ca lculados con la funci ́on de ponderaci ́on de Welsch. El per ́ıodo del cometa, 416 ± 0.56 a ̃nos, concuerda con el de Oppolzer, 415 a ̃nos, pero otros elementos orbitale s, como la inclinaci ́on, discrepan. Si bien los residuos post-perihelio se presenta n relativamente al azar, con una probabilidad del 52.1% de serlo, los residuos pre-perih elio no son azarosos, lo cual indica posibles desviaciones del movimiento kepleria no debidas a la expulsi ́on de material meteor ́ıtico. El Cometa Thatcher no est ́a relac ionado con el Gran Cometa de 1861.

  8. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase.

    Science.gov (United States)

    Schweiger, Martina; Paar, Margret; Eder, Christina; Brandis, Janina; Moser, Elena; Gorkiewicz, Gregor; Grond, Susanne; Radner, Franz P W; Cerk, Ines; Cornaciu, Irina; Oberer, Monika; Kersten, Sander; Zechner, Rudolf; Zimmermann, Robert; Lass, Achim

    2012-11-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state.

  9. Effects of Sterigmatocystin, Deoxynivalenol and Aflatoxin G1 on Apoptosis of Human Peripheral Blood Lymphocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To explore the effects of Sterigmatocystin (ST), Deoxynivalenol (DON) and Aflatoxin G1 (AFG1) on apoptosis of human peripheral blood lymphocytes (HPBLs) in vitro and thus to further elucidate the putative roles of these three mycotoxins on human immunosystem. Methods The effects of ST, DON and AFG1 on apoptosis of HPBLs were studied with cell culture, flow cytometric (FCM) DNA analysis and DNA agarose gel electrophoresis. Results DNA agarose gel electrophoresis results showed the characteristic "ladder" pattern of apoptosis in HPBLs treated with ST, DON and AFG1. Flow cytometric DNA analysis revealed that typical subdiploid peaks of apoptosis in DNA histogram could be seen in all groups treated with the three mycotoxins. Significant time-effect and dose-effect relationships were found between the apoptosis rates and treatment time as well as concentrations of the three mycotoxins. Conclusion ST, DON and AFG1 can induce apoptosis of HPBLs in vitro and may have some negative effects on human immunosystem.

  10. Resibufogenin Induces G1-Phase Arrest through the Proteasomal Degradation of Cyclin D1 in Human Malignant Tumor Cells.

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    Masami Ichikawa

    Full Text Available Huachansu, a traditional Chinese medicine prepared from the dried toad skin, has been used in clinical studies for various cancers in China. Resibufogenin is a component of huachansu and classified as bufadienolides. Resibufogenin has been shown to exhibit the anti-proliferative effect against cancer cells. However, the molecular mechanism of resibufogenin remains unknown. Here we report that resibufogenin induces G1-phase arrest with hypophosphorylation of retinoblastoma (RB protein and down-regulation of cyclin D1 expression in human colon cancer HT-29 cells. Since the down-regulation of cyclin D1 was completely blocked by a proteasome inhibitor MG132, the suppression of cyclin D1 expression by resibufogenin was considered to be in a proteasome-dependent manner. It is known that glycogen synthase kinase-3β (GSK-3β induces the proteasomal degradation of cyclin D1. The addition of GSK-3β inhibitor SB216763 inhibited the reduction of cyclin D1 caused by resibufogenin. These effects on cyclin D1 by resibufogenin were also observed in human lung cancer A549 cells. These findings suggest that the anti-proliferative effect of resibufogenin may be attributed to the degradation of cyclin D1 caused by the activation of GSK-3β.

  11. High glucose decreases the expression of ATP-binding cassette transporter G1 in human vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Jiahong Xue; Zuyi Yuan; Yue Wu; Yan Zhao; Zhaofei Wan

    2008-01-01

    Objective:ATP-binding cassette transporters(ABC) A1 and G1 play an important role in mediating cholesterol efflux and preventing macrophage foam cell formation. In this study, we examined the regulation of ABC transporters by high glucose in human vascular smooth muscle cells(VSMCs), the other precursor of foam cells. Methods:Incubation of human VSMCs with D-ghicose(5 to 30 mM) for 1 to 7 days in the presence or absence of antioxidant and nuclear factor(NF)-kB inhibitors, the expressions of ABCA1 and ABCG1 were analyzed by real time PCR and Western blotting. Results:High glucose decreased ABCG1 mRNA and protein expression in cultured VSMCs, whereas the expression of ABCA1 was not significantly decreased. Down-regulation of ABCG1 mRNA expression by high glucose was abolished by antioxidant N-acetyl-L-cysteine(NAC) and NF-kB inhibitors, BAY 11-7085 and tosyl-phenylalanine chloromethyl-ketone(TPCK). Conclusion:High glucose suppresses the expression of ABCG1 in VSMCs, which is the possible mechanism of VSMC derived foam cell transformation.

  12. Studies on Middle-Phase Microemulsions of Green Surfactant n -Dodecyl Polyglucoside C12G1.46

    Institute of Scientific and Technical Information of China (English)

    CHAI,Jin-Ling; WU,Chang-Ju; LI,Gan-Zuo; ZHANG,Gao-Yong

    2003-01-01

    The three-phase behavior in the quaternary system ot n-dodecyl polyglucoside C12G1.46/1-butanol/cyclohexane/water has been studied at 40 ℃ in terms of the variables γ and δ. Increasing δ at constant γ causes a phase inversion from an oil-in-water microemulsion in contact with excess oil ( winsor Ⅰ or 2) to a water-in-oil microemulsion in contact with excess water (winsor Ⅱ or 2) via a middle-phase microemulsion in contact with excess oil and water (winsor Ⅲ or 3). By taking into account the different solubilities of alkyl polyglucoside and 1-butanol in the oil phase, the composition of the hydrophile-lipophile balanced interfacial film in the middle of the three-phase body can be calculated. The effects of different oils and aqueous media on the phase behavior and on the composition of the interfacial film and the efficiency for alkyl polyglucoside to make equal weights of water and oil to a single phase were investigated.It was found that the oil molecules with small molecular volumes can improve the solubilizing efficiency of the surfactant to form single-phase microemulsion. In inorganic salt (NaCl) and acid (HCl)solutions, less 1-butanol is needed than that in alkali (NaOH) solution to form middle-phase microemulsion.

  13. Liver X receptor α mediates hepatic triglyceride accumulation through upregulation of G0/G1 Switch Gene 2 expression

    Science.gov (United States)

    Heckmann, Bradlee L.; Zhang, Xiaodong; Saarinen, Alicia M.; Schoiswohl, Gabriele; Kershaw, Erin E.; Zechner, Rudolf

    2017-01-01

    Liver X receptors (LXRs) are transcription factors essential for cholesterol homeostasis and lipogenesis. LXRα has been implicated in regulating hepatic triglyceride (TG) accumulation upon both influx of adipose-derived fatty acids (FAs) during fasting and stimulation of de novo FA synthesis by chemical agonism of LXR. However, whether or not a convergent mechanism is employed to drive deposition of FAs from these 2 different sources in TGs is undetermined. Here, we report that the G0/G1 Switch Gene 2 (G0S2), a selective inhibitor of intracellular TG hydrolysis/lipolysis, is a direct target gene of LXRα. Transcriptional activation is conferred by LXRα binding to a direct repeat 4 (DR4) motif in the G0S2 promoter. While LXRα–/– mice exhibited decreased hepatic G0S2 expression, adenoviral expression of G0S2 was sufficient to restore fasting-induced TG storage and glycogen depletion in the liver of these mice. In response to LXR agonist T0901317, G0S2 ablation prevented hepatic steatosis and hypertriglyceridemia without affecting the beneficial effects on HDL. Thus, the LXRα-G0S2 axis plays a distinct role in regulating hepatic TG during both fasting and pharmacological activation of LXR.

  14. Inhibition of G1P3 expression found in the differential display study on respiratory syncytial virus infection

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    Li Lei

    2008-10-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the leading viral pathogen associated with bronchiolitis and lower respiratory tract disease in infants and young children worldwide. The respiratory epithelium is the primary initiator of pulmonary inflammation in RSV infections, which cause significant perturbations of global gene expression controlling multiple cellular processes. In this study, differential display reverse transcription polymerase chain reaction amplification was performed to examine mRNA expression in a human alveolar cell line (SPC-A1 infected with RSV. Results Of the 2,500 interpretable bands on denaturing polyacrylamide gels, 40 (1.6% cDNA bands were differentially regulated by RSV, in which 28 (70% appeared to be upregulated and another 12 (30% appeared to be downregulated. Forty of the expressed sequence tags (EST were isolated, and 20 matched homologs in GenBank. RSV infection upregulated the mRNA expression of chemokines CC and CXC and interfered with type α/β interferon-inducible gene expression by upregulation of MG11 and downregulation of G1P3. Conclusion RSV replication could induce widespread changes in gene expression including both positive and negative regulation and play a different role in the down-regulation of IFN-α and up-regulation of IFN-γ inducible gene expression, which suggests that RSV interferes with the innate antiviral response of epithelial cells by multiple mechanisms.

  15. MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D.

    Science.gov (United States)

    Georgantas, Robert W; Streicher, Katie; Luo, Xiaobing; Greenlees, Lydia; Zhu, Wei; Liu, Zheng; Brohawn, Philip; Morehouse, Christopher; Higgs, Brandon W; Richman, Laura; Jallal, Bahija; Yao, Yihong; Ranade, Koustubh

    2014-03-01

    Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa-miR-206 was down-regulated in melanoma (-75.4-fold, P = 1.7 × 10(-4)). MiR-206 has been implicated in a large number of cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role in tumor development remains largely unknown, its biologic function is poorly characterized, and its targets affecting cancer cells are largely unknown. MiR-206 reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3'UTR reporter gene assays revealed that miR-206 inhibited translation of CDK4, Cyclin D1, and Cyclin C. Additionally, hsa-miR-206 transfection induced G1 arrest in multiple melanoma cell lines. These observations support hsa-miR-206 as a tumor suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as miR-206 targets.

  16. Metabolism of methoxychlor by the P450-monooxygenase CYP6G1 involved in insecticide resistance of Drosophila melanogaster after expression in cell cultures of Nicotiana tabacum.

    Science.gov (United States)

    Joussen, Nicole; Schuphan, Ingolf; Schmidt, Burkhard

    2010-03-01

    Cytochrome P450 monooxygenase CYP6G1 of Drosophila melanogaster was heterologously expressed in a cell suspension culture of Nicotiana tabacum. This in vitro system was used to study the capability of CYP6G1 to metabolize the insecticide methoxychlor (=1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane, 1) against the background of endogenous enzymes of the corresponding non-transgenic culture. The Cyp6g1-transgenic cell culture metabolized 96% of applied methoxychlor (45.8 microg per assay) within 24 h by demethylation and hydroxylation mainly to trishydroxy and catechol methoxychlor (16 and 17%, resp.). About 34% of the metabolism and the distinct formation of trishydroxy and catechol methoxychlor were due to foreign enzyme CYP6G1. Furthermore, methoxychlor metabolism was inhibited by 43% after simultaneous addition of piperonyl butoxide (458 microg), whereas inhibition in the non-transgenic culture amounted to 92%. Additionally, the rate of glycosylation was reduced in both cultures. These results were supported by the inhibition of the metabolism of the insecticide imidacloprid (6; 20 microg, 24 h) in the Cyp6g1-transgenic culture by 82% in the presence of piperonyl butoxide (200 microg). Due to CYP6G1 being responsible for imidacloprid resistance of Drosophila or being involved in DDT resistance, it is likely that CYP6G1 conveys resistance to methoxychlor (1). Furthermore, treating Drosophila with piperonyl butoxide could weaken the observed resistance phenomena.

  17. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells

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    Xiang Y. Kong

    2014-03-01

    Full Text Available Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1gt/gt mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1gt/gt liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1gt/gt Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1gt/gt mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.

  18. Evolutionary changes in gene expression, coding sequence and copy-number at the Cyp6g1 locus contribute to resistance to multiple insecticides in Drosophila.

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    Thomas W R Harrop

    Full Text Available Widespread use of insecticides has led to insecticide resistance in many populations of insects. In some populations, resistance has evolved to multiple pesticides. In Drosophila melanogaster, resistance to multiple classes of insecticide is due to the overexpression of a single cytochrome P450 gene, Cyp6g1. Overexpression of Cyp6g1 appears to have evolved in parallel in Drosophila simulans, a sibling species of D. melanogaster, where it is also associated with insecticide resistance. However, it is not known whether the ability of the CYP6G1 enzyme to provide resistance to multiple insecticides evolved recently in D. melanogaster or if this function is present in all Drosophila species. Here we show that duplication of the Cyp6g1 gene occurred at least four times during the evolution of different Drosophila species, and the ability of CYP6G1 to confer resistance to multiple insecticides exists in D. melanogaster and D. simulans but not in Drosophila willistoni or Drosophila virilis. In D. virilis, which has multiple copies of Cyp6g1, one copy confers resistance to DDT and another to nitenpyram, suggesting that the divergence of protein sequence between copies subsequent to the duplication affected the activity of the enzyme. All orthologs tested conferred resistance to one or more insecticides, suggesting that CYP6G1 had the capacity to provide resistance to anthropogenic chemicals before they existed. Finally, we show that expression of Cyp6g1 in the Malpighian tubules, which contributes to DDT resistance in D. melanogaster, is specific to the D. melanogaster-D. simulans lineage. Our results suggest that a combination of gene duplication, regulatory changes and protein coding changes has taken place at the Cyp6g1 locus during evolution and this locus may play a role in providing resistance to different environmental toxins in different Drosophila species.

  19. Live imaging-based model selection reveals periodic regulation of the stochastic G1/S phase transition in vertebrate axial development.

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    Mayu Sugiyama

    2014-12-01

    Full Text Available In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1 fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1 notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of

  20. UVB-induced cell death signaling is associated with G1-S progression and transcription inhibition in primary human fibroblasts.

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    Tatiana Grohmann Ortolan

    Full Text Available DNA damage induced by ultraviolet (UV radiation can be removed by nucleotide excision repair through two sub-pathways, one general (GGR and the other specific for transcribed DNA (TCR, and the processing of unrepaired lesions trigger signals that may lead to cell death. These signals involve the tumor suppressor p53 protein, a central regulator of cell responses to DNA damage, and the E3 ubiquitin ligase Mdm2, that forms a feedback regulatory loop with p53. The involvement of cell cycle and transcription on the signaling to apoptosis was investigated in UVB-irradiated synchronized, DNA repair proficient, CS-B (TCR-deficient and XP-C (GGR-deficient primary human fibroblasts. Cells were irradiated in the G1 phase of the cell cycle, with two doses with equivalent levels of apoptosis (low and high, defined for each cell line. In the three cell lines, the low doses of UVB caused only a transient delay in progression to the S phase, whereas the high doses induced permanent cell cycle arrest. However, while accumulation of Mdm2 correlated well with the recovery from transcription inhibition at the low doses for normal and CS-B fibroblasts, for XP-C cells this protein was shown to be accumulated even at UVB doses that induced high levels of apoptosis. Thus, UVB-induced accumulation of Mdm2 is critical for counteracting p53 activation and apoptosis avoidance, but its effect is limited due to transcription inhibition. However, in the case of XP-C cells, an excess of unrepaired DNA damage would be sufficient to block S phase progression, which would signal to apoptosis, independent of Mdm2 accumulation. The data clearly discriminate DNA damage signals that lead to cell death, depending on the presence of UVB-induced DNA damage in replicating or transcribing regions.

  1. Identification of a Selective G1-Phase Benzimidazolone Inhibitor by a Senescence-Targeted Virtual Screen Using Artificial Neural Networks

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    Alan E. Bilsland

    2015-09-01

    Full Text Available Cellular senescence is a barrier to tumorigenesis in normal cells, and tumor cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning–based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. One hundred and forty-seven virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase assays. Among the found hits, a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced senescence-associated β-galactosidase activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1, and CDC25C. In addition, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long-term treatments. Preliminary structure-activity and structure clustering analyses are reported, and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor–like profile in normal cells, with different pathways affected in cancer cells.

  2. Nitration of Tyrosine 247 Inhibits Protein Kinase G-1α Activity by Attenuating Cyclic Guanosine Monophosphate Binding*

    Science.gov (United States)

    Aggarwal, Saurabh; Gross, Christine M.; Rafikov, Ruslan; Kumar, Sanjiv; Fineman, Jeffrey R.; Ludewig, Britta; Jonigk, Danny; Black, Stephen M.

    2014-01-01

    The cGMP-dependent protein kinase G-1α (PKG-1α) is a downstream mediator of nitric oxide and natriuretic peptide signaling. Alterations in this pathway play a key role in the pathogenesis and progression of vascular diseases associated with increased vascular tone and thickness, such as pulmonary hypertension. Previous studies have shown that tyrosine nitration attenuates PKG-1α activity. However, little is known about the mechanisms involved in this event. Utilizing mass spectrometry, we found that PKG-1α is susceptible to nitration at tyrosine 247 and 425. Tyrosine to phenylalanine mutants, Y247F- and Y425F-PKG-1α, were both less susceptible to nitration than WT PKG-1α, but only Y247F-PKG-1α exhibited preserved activity, suggesting that the nitration of Tyr247 is critical in attenuating PKG-1α activity. The overexpression of WT- or Y247F-PKG-1α decreased the proliferation of pulmonary artery smooth muscle cells (SMC), increased the expression of SMC contractile markers, and decreased the expression of proliferative markers. Nitrosative stress induced a switch from a contractile to a synthetic phenotype in cells expressing WT- but not Y247F-PKG-1α. An antibody generated against 3-NT-Y247 identified increased levels of nitrated PKG-1α in humans with pulmonary hypertension. Finally, to gain a more mechanistic understanding of how nitration attenuates PKG activity, we developed a homology model of PKG-1α. This model predicted that the nitration of Tyr247 would decrease the affinity of PKG-1α for cGMP, which we confirmed using a [3H]cGMP binding assay. Our study shows that the nitration of Tyr247 and the attenuation of cGMP binding is an important mechanism regulating in PKG-1α activity and SMC proliferation/differentiation. PMID:24469460

  3. Nitration of tyrosine 247 inhibits protein kinase G-1α activity by attenuating cyclic guanosine monophosphate binding.

    Science.gov (United States)

    Aggarwal, Saurabh; Gross, Christine M; Rafikov, Ruslan; Kumar, Sanjiv; Fineman, Jeffrey R; Ludewig, Britta; Jonigk, Danny; Black, Stephen M

    2014-03-14

    The cGMP-dependent protein kinase G-1α (PKG-1α) is a downstream mediator of nitric oxide and natriuretic peptide signaling. Alterations in this pathway play a key role in the pathogenesis and progression of vascular diseases associated with increased vascular tone and thickness, such as pulmonary hypertension. Previous studies have shown that tyrosine nitration attenuates PKG-1α activity. However, little is known about the mechanisms involved in this event. Utilizing mass spectrometry, we found that PKG-1α is susceptible to nitration at tyrosine 247 and 425. Tyrosine to phenylalanine mutants, Y247F- and Y425F-PKG-1α, were both less susceptible to nitration than WT PKG-1α, but only Y247F-PKG-1α exhibited preserved activity, suggesting that the nitration of Tyr(247) is critical in attenuating PKG-1α activity. The overexpression of WT- or Y247F-PKG-1α decreased the proliferation of pulmonary artery smooth muscle cells (SMC), increased the expression of SMC contractile markers, and decreased the expression of proliferative markers. Nitrosative stress induced a switch from a contractile to a synthetic phenotype in cells expressing WT- but not Y247F-PKG-1α. An antibody generated against 3-NT-Y247 identified increased levels of nitrated PKG-1α in humans with pulmonary hypertension. Finally, to gain a more mechanistic understanding of how nitration attenuates PKG activity, we developed a homology model of PKG-1α. This model predicted that the nitration of Tyr(247) would decrease the affinity of PKG-1α for cGMP, which we confirmed using a [(3)H]cGMP binding assay. Our study shows that the nitration of Tyr(247) and the attenuation of cGMP binding is an important mechanism regulating in PKG-1α activity and SMC proliferation/differentiation.

  4. PKCeta enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells.

    Science.gov (United States)

    Fima, E; Shtutman, M; Libros, P; Missel, A; Shahaf, G; Kahana, G; Livneh, E

    2001-10-11

    Protein kinase C encodes a family of enzymes implicated in cellular differentiation, growth control and tumor promotion. However, not much is known with respect to the molecular mechanisms that link protein kinase C to cell cycle control. Here we report that the expression of PKCeta in MCF-7 cells, under the control of a tetracycline-responsive inducible promoter, enhanced cell growth and affected the cell cycle at several points. The induced expression of another PKC isoform, PKCdelta, in MCF-7 cells had opposite effects and inhibited their growth. PKCeta expression activated cellular pathways in these cells that resulted in the increased expression of the G1 phase cyclins, cyclin D and cyclin E. Expression of the cyclin-dependent kinase inhibitor p21(WAF1) was also specifically elevated in PKCeta expressing cells, but its overall effects were not inhibitory. Although, the protein levels of the cyclin-dependent kinase inhibitor p27(KIP1) were not altered by the induced expression of PKCeta, the cyclin E associated Cdk2 kinase activity was in correlation with the p27(KIP1) bound to the cyclin E complex and not by p21(WAF1) binding. PKCeta expression enhanced the removal of p27(KIP1) from this complex, and its re-association with the cyclin D/Cdk4 complex. Reduced binding of p27(KIP1) to the cyclin D/Cdk4 complex at early time points of the cell cycle also enhanced the activity of this complex, while at later time points the decrease in bound p21(WAF1) correlated with its increased activity in PKCeta-expressing cells. Thus, PKCeta induces altered expression of several cell cycle functions, which may contribute to its ability to affect cell growth.

  5. Perturbation of thermal unfolding and aggregation of human IgG1 Fc fragment by Hofmeister anions.

    Science.gov (United States)

    Zhang-van Enk, Jian; Mason, Bruce D; Yu, Lei; Zhang, Le; Hamouda, Wael; Huang, Gang; Liu, Dingjiang; Remmele, Richard L; Zhang, Jifeng

    2013-02-04

    The thermal unfolding and subsequent aggregation of the unglycosylated Fc fragment of a human IgG1 antibody (Fc) were studied in the salt solutions of Na(2)SO(4), KF, KCl and KSCN at pH 4.8 and 7.2 below and at its pI of 7.2, respectively, using differential scanning calorimetry (DSC), far ultraviolet circular dichroism (far-UV CD), size exclusion chromatography (SE-HPLC) and light scattering. First, our experimental results demonstrated that the thermal unfolding of the C(H)2 domain of the Fc was sufficient to induce aggregation. Second, at both pH conditions, the anions (except F(-)) destabilized the C(H)2 domain where the effectiveness of SO(4)(2-) > SCN(-) > Cl(-) > F(-) was more apparent at pH 4.8. In addition, the thermal stability of the C(H)2 domain was less sensitive to the change in salt concentration at pH 7.2 than at pH 4.8. Third, at pH 4.8 when the Fc had a net positive charge, the anions accelerated the aggregation reaction with SO(4)(2-) > SCN(-) > Cl(-) > F(-) in effectiveness. But these anions slowed down the aggregation kinetics at pH 7.2 with similar effectiveness when the Fc was net charge neutral. We hypothesize that the effectiveness of the anion on destabilizing the C(H)2 domain could be attributed to its ability to perturb the free energy for both of the native and unfolded states. The effect of the anions on the kinetics of the aggregation reaction could be interpreted based on the modulation of the electrostatic protein-protein interactions by the anions.

  6. Squamocin modulates histone H3 phosphorylation levels and induces G1 phase arrest and apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Wu Yang-Chang

    2011-02-01

    Full Text Available Abstract Background Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected aurora B and MSK1 as representatives for testing various compounds and drugs, and found that squamocin, a bis-tetrahydrofuran annonaceous acetogenin, exerted a potent effect on histone H3 phosphorylation. Methods GBM8401, Huh-7, and SW620 cells were incubated with 15, 30, and 60 μM squamocin for 24 h. The expressions of mRNA and proteins were analyzed by qRT-PCR and Western blotting, respectively. The cell viability was determined by an MTT assay. Cell cycle distribution and apoptotic cells were analyzed by flow cytometry. Results Our results showed that squamocin inhibited the proliferation of GBM8401, Huh-7, and SW620 cells, arrested the cell cycle at the G1 phase, and activated both intrinsic and extrinsic pathways to apoptosis. In addition, we demonstrated that squamocin had the ability to modulate the phosphorylation levels of H3S10 (H3S10p and H3S28 (H3S28p in association with the downregulation of aurora B and pMSK1 expressions. Conclusions This study is the first to show that squamocin affects epigenetic alterations by modulating histone H3 phosphorylation at S10 and S28, providing a novel view of the antitumor mechanism of squamocin.

  7. Molecular Cloning and Expression an 8-kDa Subunit of Antigen B from G1 strain of Echinococcus granulosus

    Directory of Open Access Journals (Sweden)

    Hakim AZIZI

    2015-10-01

    Full Text Available Background: Echinococcosis or hydatidosis is a chronic, zoonotic worldwide infection caused by the larval stage of the dog taeniid tapeworm Echinococcus granulosus. Vaccination has been considered as one of the ways to prevent of hy-datidosis in recent decades. The aim of this study was to construct a pcDNA3.1 eukaryotic expression vector contain-ing the subunit 8-kDa antigen B (Hyd1 of E. granulosus (G1 strain and investigate its capability to induce protein ex-pression in mammalian cell line, as a basis toward developing a DNA vaccine against hydatidosis.Methods: The coding sequence of HydI was amplified by PCR with the specific PCR primers from pQE/HydI, and then was sub-cloned into pcDNA3.1 plasmid as expression vector. The pcHyd1 plasmid was digested by restriction enzymes and amplified with the specific PCR primers to confirm cloning of this gene in pcDNA3 plasmid. In last step, the sub-cloned gene was expressed in mammalian cell line (NIH 3T3 cells.Result: The subunit 8-kDa antigen B (Hyd1 was successfully sub-cloned in pcDNA3.1 and Hyd1 protein was ex-pressed in eukaryotic cell confirmed by SDS-PAGE and Western blot.Conclusion: Recombinant plasmid of pcDNA3.1 was successfully constructed and express of recombinant Hyd1 protein was confirmed. That is promising step for forthcoming measures on providing vaccine against human and animal hydatidosis.

  8. A general G1/S-phase cell-cycle control module in the flowering plant Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Xin'Ai Zhao

    Full Text Available The decision to replicate its DNA is of crucial importance for every cell and, in many organisms, is decisive for the progression through the entire cell cycle. A comparison of animals versus yeast has shown that, although most of the involved cell-cycle regulators are divergent in both clades, they fulfill a similar role and the overall network topology of G1/S regulation is highly conserved. Using germline development as a model system, we identified a regulatory cascade controlling entry into S phase in the flowering plant Arabidopsis thaliana, which, as a member of the Plantae supergroup, is phylogenetically only distantly related to Opisthokonts such as yeast and animals. This module comprises the Arabidopsis homologs of the animal transcription factor E2F, the plant homolog of the animal transcriptional repressor Retinoblastoma (Rb-related 1 (RBR1, the plant-specific F-box protein F-BOX-LIKE 17 (FBL17, the plant specific cyclin-dependent kinase (CDK inhibitors KRPs, as well as CDKA;1, the plant homolog of the yeast and animal Cdc2⁺/Cdk1 kinases. Our data show that the principle of a double negative wiring of Rb proteins is highly conserved, likely representing a universal mechanism in eukaryotic cell-cycle control. However, this negative feedback of Rb proteins is differently implemented in plants as it is brought about through a quadruple negative regulation centered around the F-box protein FBL17 that mediates the degradation of CDK inhibitors but is itself directly repressed by Rb. Biomathematical simulations and subsequent experimental confirmation of computational predictions revealed that this regulatory circuit can give rise to hysteresis highlighting the here identified dosage sensitivity of CDK inhibitors in this network.

  9. Pristimerin causes G1 arrest, induces apoptosis, and enhances the chemosensitivity to gemcitabine in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Yongwei Wang

    Full Text Available Despite rapid advances in chemotherapy and surgical resection strategies, pancreatic cancer remains the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 5%. Therefore, novel therapeutic agents for the prevention and treatment of pancreatic cancer are urgently needed. The aim of this study was to investigate the effect of pristimerin, a quinonemethide triterpenoid compound isolated from Celastraceae and Hippocrateaceae, on inhibition of cell proliferation and induction of apoptosis in three pancreatic cancer cells, BxPC-3, PANC-1 and AsPC-1, in both monotherapy and in combination with gemcitabine. Treatment with pristimerin decreased the cell proliferation of all three pancreatic cancer cells in a dose- and time-dependent manner. Treatment of pancreatic cancer cells with pristimerin also resulted in G1-phase arrest which was strongly associated with a marked decrease in the level of cyclins (D1 and E and cyclin-dependent kinases (cdk2, cdk4 and cdk6 with concomitant induction of WAF1/p21 and KIP1/p27. Pristimerin treatment also resulted in apoptotic cell death, cleavage of caspase-3, modulation in the expressions of Bcl-2 family proteins, inhibition of the translocation and DNA-binding activity of NF-κB. In addition, pristimerin potentiated the growth inhibition and apoptosis inducing effects of gemcitabine in all three pancreatic cancer cells, at least in part, by inhibiting constitutive as well as gemcitabine-induced activation of NF-κB in both its DNA-binding activity and transcriptional activity. Taken together, these data provide the first evidence that pristimerin has strong potential for development as a novel agent against pancreatic cancer.

  10. Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells.

    Science.gov (United States)

    Zhou, Jin; Li, L U; Fang, L I; Xie, Hua; Yao, Wenxiu; Zhou, Xiang; Xiong, Zhujuan; Wang, L I; Li, Zhixi; Luo, Feng

    2016-07-01

    Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated with quercetin was labeled as d3 by stable isotope labeling by amino acids in cell culture (SILAC). The isotope peaks of control HepG2 cells were compared with the d3-labeled HepG2 cells by mass spectrometry (MS) to identify significantly altered proteins. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were subsequently employed to verify the results of the MS analysis. A flow cytometry assay was designed to observe the influence of various quercetin treatment concentrations on the cell cycle distribution of HepG2 cells. The results indicated that quercetin is able to substantially inhibit proliferation of HepG2 cells and induce an obvious morphological alteration of cells. According to the MS results, the 70 credibly-changed proteins that were identified may play important roles in multiple cellular processes, including protein synthesis, signaling, cytoskeletal processes and metabolism. Among these functional proteins, the expression of cyclin D1 (CCND1) was found to be significantly decreased. RT-PCR and western blot analyses verified the SILAC-MS results of decreased CCND1 expression. In summary, flow cytometry revealed that quercetin is able to induce G1 phase arrest in HepG2 cells. Based on the aforementioned observations, it is suggested that quercetin exerts antitumor activity in HepG2 cells through multiple pathways, including interfering with CCND1 gene expression to disrupt the cell cycle and proliferation of HepG2 cells. In the future, we aim to explore this effect in vivo.

  11. Novel mutation in forkhead box G1 (FOXG1) gene in an Indian patient with Rett syndrome.

    Science.gov (United States)

    Das, Dhanjit Kumar; Jadhav, Vaishali; Ghattargi, Vikas C; Udani, Vrajesh

    2014-03-15

    Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by the progressive loss of intellectual functioning, fine and gross motor skills and communicative abilities, deceleration of head growth, and the development of stereotypic hand movements, occurring after a period of normal development. The classic form of RTT involves mutation in MECP2 while the involvement of CDKL5 and FOXG1 genes has been identified in atypical RTT phenotype. FOXG1 gene encodes for a fork-head box protein G1, a transcription factor acting primarily as transcriptional repressor through DNA binding in the embryonic telencephalon as well as a number of other neurodevelopmental processes. In this report we have described the molecular analysis of FOXG1 gene in Indian patients with Rett syndrome. FOXG1 gene mutation analysis was done in a cohort of 34 MECP2/CDKL5 mutation negative RTT patients. We have identified a novel mutation (p. D263VfsX190) in FOXG1 gene in a patient with congenital variant of Rett syndrome. This mutation resulted into a frameshift, thereby causing an alteration in the reading frames of the entire coding sequence downstream of the mutation. The start position of the frameshift (Asp263) and amino acid towards the carboxyl terminal end of the protein was found to be well conserved across species using multiple sequence alignment. Since the mutation is located at forkhead binding domain, the resultant mutation disrupts the secondary structure of the protein making it non-functional. This is the first report from India showing mutation in FOXG1 gene in Rett syndrome.

  12. G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle.

    Science.gov (United States)

    Laurens, Claire; Badin, Pierre-Marie; Louche, Katie; Mairal, Aline; Tavernier, Geneviève; Marette, André; Tremblay, Angelo; Weisnagel, S John; Joanisse, Denis R; Langin, Dominique; Bourlier, Virginie; Moro, Cedric

    2016-07-01

    Recent data suggest that adipose triglyceride lipase (ATGL) plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2), recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4) expression (5.4 fold, p < 0.001). Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro. Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism.

  13. Apprenez la Science en Francais?

    Science.gov (United States)

    Edmonds, Juliet; Jacobs, Pippa

    2011-01-01

    The authors explain why integrating the teaching of science and French is not as ridiculous as it may at first sound. They describe how this innovative integrated approach works in a primary school in Oxfordshire. The project involves Content and Language Integrated Learning (CLIL). CLIL is a method whereby a curriculum subject is planned and…

  14. Characterization of the NSP4 gene of group A human rotavirus G1P[8] strains circulating in Sapporo, Japan from 1987 to 2000.

    Science.gov (United States)

    Tatsumi, Masatoshi; Nagaoka, Yoshinobu; Tsugawa, Takeshi; Yoto, Yuko; Hori, Tsukasa; Tsutsumi, Hiroyuki

    2014-02-01

    The genetic diversity of the NSP4 gene of rotavirus G1P[8] strains obtained in Sapporo was analyzed, Japan from 1987 to 2000. Sixty-four strains, which were distributed across the whole study period, were included. All G1P[8] NSP4 genes detected in this study belonged to genotype E1, which divided into at least three lineages. The Sapporo rotavirus G1P[8] isolates were found in each lineage. The mean estimated substitution rate was 1.40 × 10(-3) nucleotide substitutions per site per year, which was comparable to that of the G1P[8] VP7 gene. Comparison of the deduced NSP4 amino acid sequences showed genetic diversity at the center of antigenic site II, but not in the enterotoxic domain. This report represents the first investigation of the genetic diversity and evolution of group A rotavirus NSP4 genes in Asia.

  15. Repression of the transcription factor Bach2 contributes to predisposition of IgG1 memory B cells toward plasma cell differentiation.

    Science.gov (United States)

    Kometani, Kohei; Nakagawa, Rinako; Shinnakasu, Ryo; Kaji, Tomohiro; Rybouchkin, Andrei; Moriyama, Saya; Furukawa, Koji; Koseki, Haruhiko; Takemori, Toshitada; Kurosaki, Tomohiro

    2013-07-25

    Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells.

  16. Differential chromosomal radiosensitivity within the first G1-phase of the cell cycle of early-dividing human leukocytes in vitro after stimulation with PHA

    Energy Technology Data Exchange (ETDEWEB)

    Beek, B.; Obe, G.

    1977-02-11

    Human leukocyte cultures were irradiated with 200 R X rays before the addition of phytohemagglutinin (PHA) in the Go-stage and at different times up to 25 h within the first G1-phase of the cell cycle after the addition of PHA. The results of the analysis of chromosomal aberrations show that the frequencies of dicentric chromosomes increase significantly when leukocytes leave the Go-stage, reaching a minimum yield of aberrations about halfway through the first G1-phase. After that, toward the end of the G1-phase, the frequencies of dicentric chromosomes decrease again to a level similar to that found in the Go-stage. Different possible explanations for the differential chromosomal radiosensitivity of human leukocytes within the first post-stimulation G1-phase are discussed.

  17. Locations of All Shotpoints for R/V GYRE Cruise G1-99-GM (99002) - GOM99SHTALLG.SHP

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — All shotpoint locations from multichannel seismics survey, USGS cruise G1-99-GM During June 1998 and April 1999, the U.S. Geological Survey (USGS) conducted two...

  18. Genetic diversity and phylogeography of highly zoonotic Echinococcus granulosus genotype G1 in the Americas (Argentina, Brazil, Chile and Mexico) based on 8279bp of mtDNA.

    Science.gov (United States)

    Laurimäe, Teivi; Kinkar, Liina; Andresiuk, Vanessa; Haag, Karen Luisa; Ponce-Gordo, Francisco; Acosta-Jamett, Gerardo; Garate, Teresa; Gonzàlez, Luis Miguel; Saarma, Urmas

    2016-11-01

    Echinococcus granulosus is a taeniid cestode and the etiological agent of an infectious zoonotic disease known as cystic echinococcosis (CE) or hydatid disease. CE is a serious public health concern in many parts of the world, including the Americas, where it is highly endemic in many regions. Echinococcus granulosus displays high intraspecific genetic variability and is divided into multiple genotypes (G1-G8, G10) with differences in their biology and etiology. Of these, genotype G1 is responsible for the majority of human and livestock infections and has the broadest host spectrum. However, despite the high significance to the public and livestock health, the data on genetic variability and regional genetic differences of genotype G1 in America are scarce. The aim of this study was to evaluate the genetic variability and phylogeography of G1 in several countries in America by sequencing a large portion of the mitochondrial genome. We analysed 8279bp of mtDNA for 52 E. granulosus G1 samples from sheep, cattle and pigs collected in Argentina, Brazil, Chile and Mexico, covering majority of countries in the Americas where G1 has been reported. The phylogenetic network revealed 29 haplotypes and a high haplotype diversity (Hd=0.903). The absence of phylogeographic segregation between different regions in America suggests the importance of animal transportation in shaping the genetic structure of E. granulosus G1. In addition, our study revealed many highly divergent haplotypes, indicating a long and complex evolutionary history of E. granulosus G1 in the Americas.

  19. Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model.

    Science.gov (United States)

    Li, Qiang; Ujiie, Hideyuki; Shibaki, Akihiko; Wang, Gang; Moriuchi, Reine; Qiao, Hong-jiang; Morioka, Hiroshi; Shinkuma, Satoru; Natsuga, Ken; Long, Heather A; Nishie, Wataru; Shimizu, Hiroshi

    2010-12-15

    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen 17 (hCOL17), which triggers blister formation via complement activation. Previous in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized mice, this mAb effectively reproduced a BP phenotype that included subepidermal blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell degranulation. Subsequently, alanine substitutions at various C1q binding sites were separately introduced to the Fc region of the IgG1 mAb. Among these mutated mAbs, the one that was mutated at the P331 residue completely failed to activate the complement in vitro and drastically lost pathogenic activity in COL17-humanized mice. These findings indicate that P331 is a key residue required for complement activation and that IgG1-dependent complement activation is essential for blister formation in BP. This study is, to our knowledge, the first direct evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and it raises the possibility that IgG1 mAbs with Fc modification may be used to block pathogenic epitopes in autoimmune diseases.

  20. Development of a single-nucleotide-polymorphism marker for specific authentication of Korean ginseng (Panax ginseng Meyer) new cultivar "G-1".

    Science.gov (United States)

    Yang, Dong-Uk; Kim, Min-Kyeoung; Mohanan, Padmanaban; Mathiyalagan, Ramya; Seo, Kwang-Hoon; Kwon, Woo-Saeng; Yang, Deok-Chun

    2017-01-01

    Korean ginseng (Panax ginseng) is a well-known medicinal plant of Oriental medicine that is still in practice today. Until now, a total of 11 Korean ginseng cultivars with unique features to Korean ginseng have been developed based on the pure-line-selection method. Among them, a new cultivar namely G-1 with different agricultural traits related to yield and content of ginsenosides, was developed in 2012. The aim of this study was to distinguish the new ginseng cultivar G-1 by identifying the unique single-nucleotide polymorphism (SNP) at its 45S ribosomal DNA and Panax quinquefolius region than other Korean ginseng cultivars using multiplex amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR). A SNP at position of 45S ribosomal DNA region between G-1, P. quinquefolius, and the other Korean ginseng cultivars was identified. By designing modified allele-specific primers based on this site, we could specifically identified G-1 and P. quinquefolius via multiplex PCR. The unique primer for the SNP yielded an amplicon of size 449 bp in G-1 cultivar and P. quinquefolius. This study presents an effective method for the genetic identification of the G-1 cultivar and P. quinquefolius. The results from our study shows that this SNP-based approach to identify the G-1 cultivar will be a good way to distinguish accurately the G-1 cultivar and P. quinquefolius from other Korean ginseng cultivars using a SNP at 45S ribosomal DNA region.

  1. Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells

    Directory of Open Access Journals (Sweden)

    Li HF

    2015-06-01

    Full Text Available Huai-Feng Li,1–3,* Xu-An Wang,1–3,* Shan-Shan Xiang,1–3,* Yun-Ping Hu,1–3 Lin Jiang,1–3 Yi-Jun Shu,1–3 Mao-Lan Li,1–3 Xiang-Song Wu,1–3 Fei Zhang,1–3 Yuan-Yuan Ye,1–3 Hao Weng,1–3 Run-Fa Bao,1–3 Yang Cao,1–3 Wei Lu,1–3 Qian Dong,1–3 Ying-Bin Liu1–3 1Department of General Surgery, 2Laboratory of General Surgery, 3Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Oleanolic acid (OA, a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma. Keywords: oleanolic acid, gallbladder carcinoma, apoptosis, cell cycle arrest, mitochondrial pathway

  2. Secreted cyclophilin A mediates G1/S phase transition of cholangiocarcinoma cells via CD147/ERK1/2 pathway.

    Science.gov (United States)

    Obchoei, Sumalee; Sawanyawisuth, Kanlayanee; Wongkham, Chaisiri; Kasinrerk, Watchara; Yao, Qizhi; Chen, Changyi; Wongkham, Sopit

    2015-02-01

    Cyclophilin A (CypA) was shown to be upregulated in human cholangiocarcinoma (CCA) tissues. Suppression of intracellular CypA (inCypA) significantly reduces cell proliferation in vitro and tumor growth in nude mice. In the present study, the effect and potential mechanism of secreted CypA (sCypA) on cell proliferation of CCA cell lines were further investigated. CCA cells were treated with sCypA-containing conditioned media (CM) or with purified recombinant human CypA (rhCypA). Cell proliferation, cell cycle, ERK1/2, p38 MAPK, NF-κB, and STAT3 activities were examined by MTS assay, flow cytometry, and Western blot. sCypA was detected in CM from MMNK1 (an immortalized human cholangiocyte cell line) and six CCA cell lines. The sCypA levels corresponded to the inCypA levels indicating the intracellular origin of sCypA. Both sCypA-containing CM and rhCypA significantly increased proliferation of CCA cells. CD147 depletion by shRNA-knockdown or neutralizing with a CD147-monoclonal antibody significantly reduced sCypA-, and rhCypA-mediated cell proliferation. Upon rhCypA treatment, ERK1/2 was rapidly phosphorylated; whereas neutralizing CD147 inhibited ERK1/2 phosphorylation. Cell cycle analysis showed a significant increase in S phase and decrease in G1 population in rhCypA-treated cells. The expression levels of cyclin D1 and phosphorylated-retinoblastoma protein in the rhCypA-treated cells were increased compared with those in the non-treated control cells. p38 MAPK pathway was shown to be suppressed in siCypA-treated cells. In summary, CypA is secreted from CCA cells and enhances cell proliferation in an autocrine/paracrine manner, at least via direct binding with CD147, which may activate the ERK1/2 and p38 MAPK signaling pathways.

  3. THE HARD X-RAY VIEW OF THE YOUNG SUPERNOVA REMNANT G1.9+0.3

    Energy Technology Data Exchange (ETDEWEB)

    Zoglauer, Andreas; Boggs, Steven E.; Craig, William W.; Krivonos, Roman A. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Reynolds, Stephen P. [Physics Department, North Carolina State University, Raleigh, NC 27695 (United States); An, Hongjun [Department of Physics, McGill University, Montreal, Quebec, H3A 2T8 (Canada); Christensen, Finn E. [DTU Space, National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Fryer, Chris L. [CCS-2, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Grefenstette, Brian W.; Harrison, Fiona A.; Madsen, Kristin K.; Miyasaka, Hiromasa [Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Hailey, Charles J. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Zhang, William W., E-mail: zog@ssl.berkeley.edu [Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2015-01-10

    NuSTAR observed G1.9+0.3, the youngest known supernova remnant in the Milky Way, for 350 ks and detected emission up to ∼30 keV. The remnant's X-ray morphology does not change significantly across the energy range from 3 to 20 keV. A combined fit between NuSTAR and Chandra shows that the spectrum steepens with energy. The spectral shape can be well fitted with synchrotron emission from a power-law electron energy distribution with an exponential cutoff with no additional features. It can also be described by a purely phenomenological model such as a broken power law or a power law with an exponential cutoff, though these descriptions lack physical motivation. Using a fixed radio flux at 1 GHz of 1.17 Jy for the synchrotron model, we get a column density of N {sub H} = (7.23 ± 0.07) × 10{sup 22} cm{sup –2}, a spectral index of α = 0.633 ± 0.003, and a roll-off frequency of ν{sub rolloff} = (3.07 ± 0.18) × 10{sup 17} Hz. This can be explained by particle acceleration, to a maximum energy set by the finite remnant age, in a magnetic field of about 10 μG, for which our roll-off implies a maximum energy of about 100 TeV for both electrons and ions. Much higher magnetic-field strengths would produce an electron spectrum that was cut off by radiative losses, giving a much higher roll-off frequency that is independent of magnetic-field strength. In this case, ions could be accelerated to much higher energies. A search for {sup 44}Ti emission in the 67.9 keV line results in an upper limit of 1.5 × 10{sup –5} photons cm{sup –2} s{sup –1} assuming a line width of 4.0 keV (1 sigma)

  4. Nucleotide mismatches between the VP7 gene and the primer are associated with genotyping failure of a specific lineage from G1 rotavirus strains

    Directory of Open Access Journals (Sweden)

    Espinola Emilio E

    2006-05-01

    Full Text Available Abstract In recent years it was reported that the accumulation of point mutations in VP4 and VP7 genes of rotavirus strains was the main cause of the failure of the G or P-typing. Failures in the correct genotyping of G1, G2, G8, G9 and G10 rotavirus strains were reported in the most commonly used reverse transcription (RT-PCR strategies. Collecting VP7 gene sequences of G1 rotavirus strains from databases we found that 74 (61.2 % out of 121 G1 strains from lineage I showed the four specific mismatches at the 5' end of the 9T1-1 primer, previously associated with the failure of G1-typing. Thus, a great percentage of the G1 strains from lineage I worldwide reported could not have been typed if the Das's RT-PCR strategy were used. This analysis shows that the failure on the detection of the G1 strains could be due to the diversification of rotavirus strains in phylogenetic lineages. Therefore, the use of different RT-PCR strategies with different primer binding locations on the VP7 gene or new typing methodologies -like microarrays procedures- could be a better option to avoid the failure of the G-typing of rotavirus strains detected during surveillance programs.

  5. Gene duplication and co-evolution of G1/S transcription factor specificity in fungi are essential for optimizing cell fitness.

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    Adi Hendler

    2017-05-01

    Full Text Available Transcriptional regulatory networks play a central role in optimizing cell survival. How DNA binding domains and cis-regulatory DNA binding sequences have co-evolved to allow the expansion of transcriptional networks and how this contributes to cellular fitness remains unclear. Here we experimentally explore how the complex G1/S transcriptional network evolved in the budding yeast Saccharomyces cerevisiae by examining different chimeric transcription factor (TF complexes. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. The difference in size and complexity of the G1/S transcriptional network across yeast species makes it well suited to investigate how TF paralogs (SBF and MBF and DNA binding sequences (SCB and MCB co-evolved after gene duplication to rewire and expand the network of G1/S target genes. Our data suggests that whilst SBF is the likely ancestral regulatory complex, the ancestral DNA binding element is more MCB-like. G1/S network expansion took place by both cis- and trans- co-evolutionary changes in closely related but distinct regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD with that from more distantly related fungi leads to a contraction of the SBF-regulated G1/S network in budding yeast, which also correlates with increased defects in cell growth, cell size, and proliferation.

  6. G1-4A, a polysaccharide from Tinospora cordifolia induces peroxynitrite dependent killer dendritic cell (KDC) activity against tumor cells.

    Science.gov (United States)

    Pandey, Vipul K; Amin, Prayag J; Shankar, Bhavani S

    2014-12-01

    Dendritic cells (DC) play a central role in the development of an adaptive immune response against tumor. In addition to its role in antigen presentation, DC also possesses cytotoxic activity against tumor cells. We have earlier shown phenotypic and functional maturation of bone marrow derived dendritic cells (BMDC) by G1-4A, an arabinogalactan derived from Tinospora cordifolia. In this study, we have investigated the killer phenotype of BMDC matured in the presence of G1-4A, [mBMDC (G1-4A)] on tumor cells. We have observed several fold increase in killing of tumor cells by mBMDC (G1-4A). The tumoricidal activity was not specific to syngeneic tumors cells but could kill xenogenic tumors also. Nitric oxide released by mBMDC (G1-4A) generates peroxynitrite in tumor cells and is responsible for killing of target cells. This killing was completely abrogated by inducible nitric oxide synthase (iNOS) inhibitor 1400W and NADPH oxidase inhibitor apocyanin. The killed target cells are phagocytosed by BMDC which further activate syngeneic cytotoxic T cells. These results thus show that G1-4A treated mBMDC acquire killer phenotype along with maturation which plays an important role in activation of cytotoxic T cells.

  7. Inhibition of the melanoma cell cycle and regulation at the G1/S transition by 12-O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity.

    Science.gov (United States)

    Coppock, D L; Buffolino, P; Kopman, C; Nathanson, L

    1995-11-01

    The growth of malignant melanoma cells is inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA) while the growth of normal melanocytes is stimulated. We previously demonstrated that TPA inhibits the growth of Demel melanoma cells and leads to arrest at both at the G1/S and G2/M cell cycle transitions. To investigate the mechanism by which TPA arrests melanoma cell growth at the G1/S transition we have examined its effects on the levels of cyclins and cyclin dependent kinases (CDKs) and activation of CDK2 kinase activity. Addition of TPA in G1 blocked the increase in the level of p34cdc2 mRNA, but not of CDK2 mRNA. When TPA was added in G1, it inhibited the mobility shift of CDK2 reflecting a change in phosphorylation state. This corresponded to inhibition of the increase in CDK2 histone H1 kinase activity. There was little effect on the level of CDK4. Treatment with TPA during G1 caused a three to four fold increase in cyclin D1 mRNA expression, but blocked the increase in the expression of cyclin A and cyclin B mRNAs later in the cell cycle. TPA caused a small increase in levels of cyclin D1 and had little effect on cyclin E, suggesting these G1 cyclins were not limiting. Addition of TPA in G1 prevented an increase in cyclin A levels, suggesting cyclin A might play an important role in mediating the growth inhibition. Examination of the levels of the CDK inhibitors p21Cip1 and p27Kip1 showed that the level of these inhibitors was higher in G1 and dropped as cells entered S phase. In the presence of TPA this decrease did not occur. These results demonstrate that TPA blocks the G1/S transition in Demel melanoma cells in late G1 by mechanisms which regulate phosphorylation and activation of the CDK2 kinase. These mechanisms include preventing the decrease in p21Cip1 and p27Kip1 kinase inhibitors and limiting the amount of cyclin A.

  8. Double-negative feedback between S-phase cyclin-CDK and CKI generates abruptness in the G1/S switch

    Directory of Open Access Journals (Sweden)

    Rainis eVenta

    2012-12-01

    Full Text Available The G1/S transition is a crucial decision point in the cell cycle. At G1/S, there is an abrupt switch from a state of high CDK inhibitor (CKI levels and low S-phase CDK activity to a state of high S-phase CDK activity and degraded CKI. In budding yeast, this transition is triggered by phosphorylation of the Cdk1 inhibitor Sic1 at multiple sites by G1-phase CDK (Cln1,2-Cdk1 and S-phase CDK (Clb5,6-Cdk1 complexes. Using mathematical modeling we demonstrate that the mechanistic basis for the abruptness and irreversibility of the G1/S transition is the highly specific phosphorylation of Sic1 by S-phase CDK complex. This switch is generated by a double negative feedback loop in which S-CDK1 phosphorylates Sic1, thus targeting it for destruction, and thereby liberating further S-CDK1 from the inhibitory Sic1-S-CDK1 complex. Our model predicts that the abruptness of the switch depends upon a strong binding affinity within the Sic1-S-CDK inhibitory complex. In vitro phosphorylation analysis using purified yeast proteins revealed that free Clb5-Cdk1 can create positive feedback by phosphorylating Sic1 that is bound in the inhibitory complex, and that Sic1 inhibits Clb5-Cdk1 with a sub-nanomolar inhibition constant. Our model also predicts that if the G1-phase CDK complex is too efficient at targeting Sic1 for destruction, then G1/S becomes a smooth and readily reversible transition. We propose that the optimal role for the G1-phase CDK in the switch would not be to act as a kinase activity directly responsible for abrupt degradation of CKI, but rather to act as a priming signal that initiates a positive feedback loop driven by emerging free S-phase CDK.

  9. Phylogenetic and computational structural analysis of VP7 gene of group a human rotavirus G1P[8] strains obtained in Sapporo, Japan from 1987 to 2000.

    Science.gov (United States)

    Nagaoka, Yoshinobu; Tatsumi, Masatoshi; Tsugawa, Takeshi; Yoto, Yuko; Tsutsumi, Hiroyuki

    2012-05-01

    Many studies indicate that G1P[8] genotypes are the most prevalent rotavirus strains worldwide. Although two vaccines have been licensed and their value proven in many countries, continuous surveillance for genetic evolution of circulating rotavirus strains before and after the introduction of the vaccines is desirable. G and P typing were carried out on all field strains isolated during 1987-2000 in Sapporo, Japan. Phylogenetic analysis for the VP7 gene of rotavirus G1P[8] strains was performed. Amino acid substitutions were mapped on the predicted three-dimensional VP7 protein image. G1P[8] genotype predominated. One hundred thirteen strains with G1P[8] genotype were analyzed. Phylogenetic studies of the VP7 gene classified these strains into three lineages. The mean estimated substitution rate was 7.25 × 10(-4) nucleotide substitutions per site per year. One predominant lineage contained the mutant strains which had VP7 amino acid substitutions at residue 91 and 212 that is in the neutralization domains. They were estimated to locate in or near intersubunit boundary of VP7 trimer. It is suggested that the most prevalent G1P[8] lineage strains in Sapporo obtained some survival advantages by changing the neutralization domains of VP7.

  10. Overexpression of a glycosyltransferase gene SrUGT74G1 from Stevia improved growth and yield of transgenic Arabidopsis by catechin accumulation.

    Science.gov (United States)

    Guleria, Praveen; Yadav, Sudesh Kumar

    2014-03-01

    Steviol glycoside and gibberellin biosynthetic routes are known as divergent branches of a common origin in Stevia. A UDP-glycosyltransferase encoded by SrUGT74G1 catalyses the conversion of steviolbioside into stevioside in Stevia rebaudiana leaves. In the present study, transgenic Arabidopsis thaliana overexpressing SrUGT74G1 cDNA from Stevia were developed to check the probability of stevioside biosynthesis in them. However, stevioside accumulation was not evident in transgenics. Also, the transgenic Arabidopsis showed no change in GA3 content on SrUGT74G1 overexpression. Surprisingly, significant accumulation of catechin was noticed in transgenics. The transgenics showed a considerable increase in shoot length, root length and rosette area. An increase in free radical scavenging activity of transgenics was noticed. Moreover, the seed yield of transgenics was also increased by 6-15% than control. Additionally, variation in trichome branching pattern on leaf surface of transgenics was observed. The trichome branching pattern was also validated by exogenous catechin exposure (10, 50, 100 ng ml(-1)) to control plants. Hence, present study reports the probable role of SrUGT74G1 from Stevia in catechin accumulation of transgenic Arabidopsis thaliana. Thus, detailed study in present perspective has revealed the role of Stevia SrUGT74G1 gene in trichome branching pattern, improved vegetative growth, scavenging potential and seed yield by catechin accumulation in transgenic Arabidopsis.

  11. ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

    Science.gov (United States)

    Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O

    2016-08-02

    ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

  12. Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination.

    Science.gov (United States)

    Svensson, Mattias N D; Andersson, Karin M E; Wasén, Caroline; Erlandsson, Malin C; Nurkkala-Karlsson, Merja; Jonsson, Ing-Marie; Brisslert, Mikael; Bemark, Mats; Bokarewa, Maria I

    2015-12-01

    Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6(+) germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 ligand-deficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells. On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family. B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of γ1 germ-line transcripts, resulting in impaired IgG1 production. Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile γ1 germ-line transcripts and CSR to IgG1.

  13. Radiolabeled novel mAb 4G1 for immunoSPECT imaging of EGFRvIII expression in preclinical glioblastoma xenografts

    Science.gov (United States)

    Liu, Xujie; Dong, Chengyan; Shi, Jiyun; Ma, Teng; Jin, Zhongxia; Jia, Bing; Liu, Zhaofei; Shen, Li; Wang, Fan

    2017-01-01

    Epidermal growth factor receptor mutant III (EGFRvIII) is exclusively expressed in tumors, such as glioblastoma, breast cancer and hepatocellular carcinoma, but never in normal organs. Increasing evidence suggests that EGFRvIII has clinical significance in glioblastoma prognosis due to its enhanced tumorigenicity and chemo/radio resistance, thus the development of an imaging approach to early detect EGFRvIII expression with high specificity is urgently needed. To illustrate this point, we developed a novel anti-EGFRvIII monoclonal antibody 4G1 through mouse immunization, cell fusion and hybridoma screening and then confirmed its specificity and affinity by a serial of assays. Following biodistribution and small animal single-photon emission computed tomography (SPECT/CT) imaging of 125I-4G1 in EGFRvIII positive/negative tumor-bearing mice were performed and evaluated to verify the tumor accumulation of this radiotracer. The biodistribution indicated that 125I-4G1 showed prominent tumor accumulation at 24 h post-injection, which reached maximums of 11.20 ± 0.75% ID/g and 13.98 ± 0.57% ID/g in F98npEGFRvIII and U87vIII xenografts, respectively. In contrast, 125I-4G1 had lower tumor accumulation in F98npEGFR and U87MG xenografts. Small animal SPECT/CT imaging revealed that 125I-4G1 had a higher tumor uptake in EGFRvIII-positive tumors than that in EGFRvIII-negative tumors. This study demonstrates that radiolabeled 4G1 can serve as a valid probe for the imaging of EGFRvIII expression, and would be valuable into the clinical translation for the diagnosis, prognosis, guiding therapy, and therapeutic efficacy evaluation of tumors. PMID:28031526

  14. An ultra-clean technique for accurately analysing Pb isotopes and heavy metals at high spatial resolution in ice cores with sub-pg g(-1) Pb concentrations.

    Science.gov (United States)

    Burn, Laurie J; Rosman, Kevin J R; Candelone, Jean-Pierre; Vallelonga, Paul; Burton, Graeme R; Smith, Andrew M; Morgan, Vin I; Barbante, Carlo; Hong, Sungmin; Boutron, Claude F

    2009-02-23

    Measurements of Pb isotope ratios in ice containing sub-pg g(-1) concentrations are easily compromised by contamination, particularly where limited sample is available. Improved techniques are essential if Antarctic ice cores are to be analysed with sufficient spatial resolution to reveal seasonal variations due to climate. This was achieved here by using stainless steel chisels and saws and strict protocols in an ultra-clean cold room to decontaminate and section ice cores. Artificial ice cores, prepared from high purity water were used to develop and refine the procedures and quantify blanks. Ba and In, two other important elements present at pg g(-1) and fg g(-1) concentrations in Polar ice, were also measured. The final blank amounted to 0.2+/-0.2 pg of Pb with (206)Pb/(207)Pb and (208)Pb/(207)Pb ratios of 1.16+/-0.12 and 2.35+/-0.16, respectively, 1.5+/-0.4 pg of Ba and 0.6+/-2.0 fg of In, most of which probably originates from abrasion of the steel saws by the ice. The procedure was demonstrated on a Holocene Antarctic ice core section and was shown to contribute blanks of only approximately 5%, approximately 14% and approximately 0.8% to monthly resolved samples with respective Pb, Ba and In concentrations of 0.12 pg g(-1), 0.3 pg g(-1) and 2.3 fg g(-1). Uncertainties in the Pb isotopic ratio measurements were degraded by only approximately 0.2%.

  15. Suppression of c-Myc enhances p21(WAF1/CIP1) -mediated G1 cell cycle arrest through the modulation of ERK phosphorylation by ascochlorin.

    Science.gov (United States)

    Jeong, Yun-Jeong; Hoe, Hyang-Sook; Cho, Hyun-Ji; Park, Kwan-Kyu; Kim, Dae-Dong; Kim, Cheorl-Ho; Magae, Junji; Kang, Dong Wook; Lee, Sang-Rae; Chang, Young-Chae

    2017-08-18

    Numerous anti-cancer agents inhibit cell cycle progression via a p53-dependent mechanism; however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy. In the present study, we provide evidence that ascochlorin, an isoprenoid antibiotic, is a non-toxic anti-cancer agent that induces G1 cell cycle arrest and p21(WAF1/CIP1) expression by downregulating of c-Myc protein expression. Ascochlorin promoted the G1 arrest, upregulated p53 and p21(WAF1/CIP1) , and downregulated c-Myc in HCT116 cells. In p53-deficient cells, ascochlorin enhanced the expression of G1 arrest-related genes except p53. Small interfering RNA (siRNA) mediated c-Myc silencing indicated that the transcriptional repression of c-Myc was related to ascochlorin-mediated modulation of p21(WAF1/CIP1) expression. Ascochlorin suppressed the stabilization of the c-Myc protein by inhibiting ERK and P70S6K/4EBP1 phosphorylation, whereas it had no effect on c-Myc degradation mediated by PI3K/Akt/GSK3β. The ERK inhibitor PD98059 and siRNA-mediated ERK silencing induced G1 arrest and p21(WAF1/CIP1) expression by downregulating c-Myc in p53-deficient cells. These results indicated that ascochlorin-induced G1 arrest is associated with the repression of ERK phosphorylation and c-Myc expression. Thus, we reveal a role for ascochlorin in inhibiting tumor growth via G1 arrest, and identify a novel regulatory mechanism for ERK /c-Myc. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Post-transcriptional regulation of cyclins D1, D3 and G1 and proliferation of human cancer cells depend on IMP-3 nuclear localization.

    Science.gov (United States)

    Rivera Vargas, T; Boudoukha, S; Simon, A; Souidi, M; Cuvellier, S; Pinna, G; Polesskaya, A

    2014-05-29

    RNA-binding proteins of the IMP family (insulin-like growth factor 2 (IGF2) mRNA-binding proteins 1-3) are important post-transcriptional regulators of gene expression. Multiple studies have linked high expression of IMP proteins, and especially of IMP-3, to an unfavorable prognosis in numerous types of cancer. The specific importance of IMP-3 for cancer transformation remains poorly understood. We here show that all three IMPs can directly bind the mRNAs of cyclins D1, D3 and G1 (CCND1, D3 and G1) in vivo and in vitro, and yet only IMP-3 regulates the expression of these cyclins in a significant manner in six human cancer cell lines of different origins. In the absence of IMP-3, the levels of CCND1, D3 and G1 proteins fall dramatically, and the cells accumulate in the G1 phase of the cell cycle, leading to almost complete proliferation arrest. Our results show that, compared with IMP-1 and IMP-2, IMP-3 is enriched in the nucleus, where it binds the transcripts of CCND1, D3 and G1. The nuclear localization of IMP-3 depends on its protein partner HNRNPM and is indispensable for the post-transcriptional regulation of expression of the cyclins. Cytoplasmic retention of IMP-3 and HNRNPM in human cancer cells leads to significant drop in proliferation. In conclusion, a nuclear IMP-3-HNRNPM complex is important for the efficient synthesis of CCND1, D3 and G1 and for the proliferation of human cancer cells.

  17. Cdc48 and cofactors Npl4-Ufd1 are important for G1 progression during heat stress by maintaining cell wall integrity in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Meng-Ti Hsieh

    Full Text Available The ubiquitin-selective chaperone Cdc48, a member of the AAA (ATPase Associated with various cellular Activities ATPase superfamily, is involved in many processes, including endoplasmic reticulum-associated degradation (ERAD, ubiquitin- and proteasome-mediated protein degradation, and mitosis. Although Cdc48 was originally isolated as a cell cycle mutant in the budding yeast Saccharomyces cerevisiae, its cell cycle functions have not been well appreciated. We found that temperature-sensitive cdc48-3 mutant is largely arrested at mitosis at 37°C, whereas the mutant is also delayed in G1 progression at 38.5°C. Reporter assays show that the promoter activity of G1 cyclin CLN1, but not CLN2, is reduced in cdc48-3 at 38.5°C. The cofactor npl4-1 and ufd1-2 mutants also exhibit G1 delay and reduced CLN1 promoter activity at 38.5°C, suggesting that Npl4-Ufd1 complex mediates the function of Cdc48 at G1. The G1 delay of cdc48-3 at 38.5°C is a consequence of cell wall defect that over-activates Mpk1, a MAPK family member important for cell wall integrity in response to stress conditions including heat shock. cdc48-3 is hypersensitive to cell wall perturbing agents and is synthetic-sick with mutations in the cell wall integrity signaling pathway. Our results suggest that the cell wall defect in cdc48-3 is exacerbated by heat shock, which sustains Mpk1 activity to block G1 progression. Thus, Cdc48-Npl4-Ufd1 is important for the maintenance of cell wall integrity in order for normal cell growth and division.

  18. Induction of interleukin-10 in the T helper type 17 effector population by the G protein coupled estrogen receptor (GPER) agonist G-1

    Science.gov (United States)

    Brunsing, Ryan L; Prossnitz, Eric R

    2011-01-01

    Interleukin-10 (IL-10) is a potent suppressor of the immune system, commonly produced by CD4+ T cells to limit ongoing inflammatory responses minimizing host damage. Many autoimmune diseases are marked by large populations of activated CD4+ T cells within the setting of chronic inflammation; therefore, drugs capable of inducing IL-10 production in CD4+ T cells would be of great therapeutic value. Previous reports have shown that the small molecule G-1, an agonist of the membrane-bound G-protein-coupled estrogen receptor GPER, attenuates disease in an animal model of autoimmune encephalomyelitis. However, the direct effects of G-1 on CD4+ T-cell populations remain unknown. Using ex vivo cultures of purified CD4+ T cells, we show that G-1 elicits IL-10 expression in T helper type 17 (Th17) -polarized cells, increasing the number of IL-10+ and IL-10+ IL-17A+ cells via de novo induction of IL-10. T-cell cultures differentiated in the presence of G-1 secreted threefold more IL-10, with no change in IL-17A, tumour necrosis factor-α, or interferon-γ. Moreover, inhibition of extracellular signal-regulated kinase (but not p38 or Jun N-terminal kinase) signalling blocked the response, while analysis of Foxp3 and RORγt expression demonstrated increased numbers of IL-10+ cells in both the Th17 (RORγt+) and Foxp3+ RORγt+ hybrid T-cell compartments. Our findings translated in vivo as systemic treatment of male mice with G-1 led to increased IL-10 secretion from splenocytes following T-cell receptor cross-linking. These results demonstrate that G-1 acts directly on CD4+ T cells, and to our knowledge provide the first example of a synthetic small molecule capable of eliciting IL-10 expression in Th17 or hybrid T-cell populations. PMID:21722102

  19. Measurement of the Deuteron Spin Structure Function $g_{1}^{d(x)}$ for $1(GeV/c)^{2} < Q^{2} < 40 (GeV/c)^{2}$

    CERN Document Server

    Anthony, P L; Averett, T; Band, H R; Berisso, M C; Borel, H; Bosted, P E; Bultmann, S L; Buénerd, M; Chupp, T E; Churchwell, S; Court, G R; Crabb, D; Day, D; Decowski, P; De Pietro, P; Erbacher, R; Erickson, R; Feltham, A; Fonvieille, H; Frlez, E; Gearhart, R A; Ghazikhanian, V; Gómez, J; Griffioen, K A; Harris, C; Houlden, M A; Hughes, E W; Hyde-Wright, C E; Igo, G; Incerti, S; Jensen, J; Johnson, J R; King, P M; Kolomensky, Yu G; Kuhn, S E; Lindgren, R; Lombard-Nelsen, R M; Marroncle, J; McCarthy, J; McKee, P; Meyer, Werner T; Mitchell, G; Mitchell, J; Olson, M; Penttila, S; Peterson, G; Petratos, G G; Pitthan, R; Pocanic, D; Prepost, R; Prescott, C; Qin, L M; Raue, B A; Reyna, D; Rochester, L S; Rock, S E; Rondon-Aramayo, O A; Sabatie, F; Sick, I; Smith, T; Sorrell, L; Staley, F; Lorant, S St; Stuart, L M; Szalata, Z M; Terrien, Y; Tobias, A; Todor, L; Toole, T; Trentalange, S; Walz, D; Welsh, R C; Wesselmann, F R; Wright, T R; Young, C C; Zeier, M; Zhu, H; Zihlmann, B

    1999-01-01

    New measurements are reported on the deuteron spin structure function g_1^d. These results were obtained from deep inelastic scattering of 48.3 GeV electrons on polarized deuterons in the kinematic range 0.01 < x < 0.9 and 1 < Q^2 < 40 (GeV/c)^2. These are the first high dose electron scattering data obtained using lithium deuteride (6Li2H) as the target material. Extrapolations of the data were performed to obtain moments of g_1^d, including Gamma_1^d, and the net quark polarization Delta Sigma.

  20. Phosphorylation on Thr-55 by TAF1 mediates degradation of p53: a role for TAF1 in cell G1 progression.

    Science.gov (United States)

    Li, Heng-Hong; Li, Andrew G; Sheppard, Hilary M; Liu, Xuan

    2004-03-26

    The largest subunit of TFIID, TAF1, possesses an intrinsic protein kinase activity and is important for cell G1 progression and apoptosis. Since p53 functions by inducing cell G1 arrest and apoptosis, we investigated the link between TAF1 and p53. We found that TAF1 induces G1 progression in a p53-dependent manner. TAF1 interacts with and phosphorylates p53 at Thr-55 in vivo. Substitution of Thr-55 with an alanine residue (T55A) stabilizes p53 and impairs the ability of TAF1 to induce G1 progression. Furthermore, both RNAi-mediated TAF1 ablation and apigenin-mediated inhibition of the kinase activity of TAF1 markedly reduced Thr-55 phosphorylation. Thus, phosphorylation and the resultant degradation of p53 provide a mechanism for regulation of the cell cycle by TAF1. Significantly, the Thr-55 phosphorylation was reduced following DNA damage, suggesting that this phosphorylation contributes to the stabilization of p53 in response to DNA damage.

  1. Comparison of Kil Goat and Saanen x Kil Goat Crosbred (F1, G1 Raised At The Farm Conditions In Terms of Fertility Characteristics

    Directory of Open Access Journals (Sweden)

    Hilal Tozlu Çelik

    2015-01-01

    Full Text Available This research Amasya Sarilar (40°54'23"N, 35°08'min5"E, a private business in the years 2011-2012 between the grown Saanen x Kil goat crosbred (F1, G1 and Kil goat in the fertility characteristics to detect and genotype on these features, year was conducted to determine the effects of such factors. In the study of reproductive traits for the year 2011 only twin goats giving birth rate among genotypes were found statistically difference. The twin birth rate of Kil goat was similar in F1 crosbred and G1 is different from both genotypes were found. In 2012, the remaining infertile among genotypes goat, dead goat giving birth and twin goats rate has been determined that there are statistical differences. Infertility rate, Saanen x Kil goat F1, G1 crosbred was found to be higher than in the Kil goat. Twin goat giving birth rate F1 genotypes in high, genotypes G1 and Kil goats find similar.

  2. 11 CFR 105.1 - Place of filing; House candidates and their authorized committees (2 U.S.C. 432(g)(1)).

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Place of filing; House candidates and their authorized committees (2 U.S.C. 432(g)(1)). 105.1 Section 105.1 Federal Elections FEDERAL ELECTION COMMISSION GENERAL DOCUMENT FILING (2 U.S.C. 432(g)) § 105.1 Place of filing; House candidates and their...

  3. Regulation of the G1/S Transition in Hepatocytes: Involvement of the Cyclin-Dependent Kinase Cdk1 in the DNA Replication

    Directory of Open Access Journals (Sweden)

    Anne Corlu

    2012-01-01

    Full Text Available A singular feature of adult differentiated hepatocytes is their capacity to proliferate allowing liver regeneration. This review emphasizes the literature published over the last 20 years that established the most important pathways regulating the hepatocyte cell cycle. Our article also aimed at illustrating that many discoveries in this field benefited from the combined use of in vivo models of liver regeneration and in vitro models of primary cultures of human and rodent hepatocytes. Using these models, our laboratory has contributed to decipher the different steps of the progression into the G1 phase and the commitment to S phase of proliferating hepatocytes. We identified the mitogen dependent restriction point located at the two-thirds of the G1 phase and the concomitant expression and activation of both Cdk1 and Cdk2 at the G1/S transition. Furthermore, we demonstrated that these two Cdks contribute to the DNA replication. Finally, we provided strong evidences that Cdk1 expression and activation is correlated to extracellular matrix degradation upon stimulation by the pro-inflammatory cytokine TNFα leading to the identification of a new signaling pathway regulating Cdk1 expression at the G1/S transition. It also further confirms the well-orchestrated regulation of liver regeneration via multiple extracellular signals and pathways.

  4. Ethanol extract of Kilkyung-baeksan, a traditional herbal formula, induces G0/G1 cell cycle arrest in human lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2015-09-01

    Conclusion: EE-KKBS exerted its cytostatic activity through regulating G1 cell cycle checkpoint in lung cancer cells, and this activity is mainly mediated by one of its component herbs, seeds of Croton tiglium. Collectively, our data suggest that EE-KKBS could be a novel candidate for adjuvant therapy for lung cancer.

  5. Intrinsic Properties of immunoglobulin IgG1 Isotype-Switched B Cell Receptors Promote Microclustering and the Initiation of Signaling

    Science.gov (United States)

    Liu, Wanli; Meckel, Tobias; Tolar, Pavel; Sohn, Hae Won; Pierce, Susan K.

    2010-01-01

    Summary Memory B cells express high affinity, immunoglobulin B cell receptors (IgG-BCRs) that enhance B cell responses giving rise to the rapid production of high affinity, IgG antibodies. Despite the central role of IgG-BCRs in memory responses, the mechanisms by which the IgG-BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging we showed that independent of affinity, IgG1-BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells’ encounter with membrane bound antigen including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1-BCR signaling. Thus, intrinsic properties of the IgG1-BCR enhance early antigen-driven events that ultimately translate into heightened signaling. PMID:20620943

  6. DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination.

    Science.gov (United States)

    Biehs, Ronja; Steinlage, Monika; Barton, Olivia; Juhász, Szilvia; Künzel, Julia; Spies, Julian; Shibata, Atsushi; Jeggo, Penny A; Löbrich, Markus

    2017-02-16

    Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cells with biphasic kinetics. We show that DSBs repaired with slow kinetics, including those localizing to heterochromatic regions or harboring additional lesions at the DSB site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ. Resection-dependent c-NHEJ represents an inducible process during which Plk3 phosphorylates CtIP, mediating its interaction with Brca1 and promoting the initiation of resection. Mre11 exonuclease, EXD2, and Exo1 execute resection, and Artemis endonuclease functions to complete the process. If resection does not commence, then repair can ensue by c-NHEJ, but when executed, Artemis is essential to complete resection-dependent c-NHEJ. Additionally, Mre11 endonuclease activity is dispensable for resection in G1. Thus, resection in G1 differs from the process in G2 that leads to homologous recombination. Resection-dependent c-NHEJ significantly contributes to the formation of deletions and translocations in G1, which represent important initiating events in carcinogenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. The nuclear position of pericentromeric DNA of chromosome 11 appears to be random in G0 and non-random in G1 human lymphocytes.

    Science.gov (United States)

    Hulspas, R; Houtsmuller, A B; Krijtenburg, P J; Bauman, J G; Nanninga, N

    1994-07-01

    The nuclear topography of pericentromeric DNA of chromosome 11 was analyzed in G0 (nonstimulated) and G1 [phytohemagglutinin (PHA) stimulated] human lymphocytes by confocal microscopy. In addition to the nuclear center, the centrosome was used as a second point of reference in the three-dimensional (3D) analysis. Pericentromeric DNA of chromosome 11 and the centrosome were labeled using a combination of fluorescent in situ hybridization (FISH) and immunofluorescence. To preserve the 3D morphology of the cells, these techniques were performed on whole cells in suspension. Three-dimensional images of the cells were analyzed with a recently developed 3D software program (Interactive Measurement of Axes and Positioning in 3 Dimensions). The distribution of the chromosome 11 centromeres appeared to be random during the G0 stage but clearly non-random during the G1 stage, when the nuclear center was used as a reference point. Further statistical analysis of the G1 cells revealed that the centromeres were randomly distributed in a shell underlying the nuclear membrane. A topographical relationship between the centrosome and the centromeres appeared to be absent during the G0 and G1 stages of the cell cycle.

  8. A method for the low-level (ng g(-1)) determination of perfluorooctanoate in paper and textile by liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Stadalius, Marilyn; Connolly, Paul; L'Empereur, Karen; Flaherty, John M; Isemura, Tsuguhide; Kaiser, Mary A; Knaup, Wolfgang; Noguchi, Masahiro

    2006-08-04

    The determination of perfluorooctanoate (PFO) in articles of commerce has become increasingly important to understand if treated products are a possible source of PFO. An LC-MS/MS method for the determination of PFO in paper and textile using a dual labeled 13C-PFOA internal standard was successfully developed and validated. Residues of PFO were determined using an isocratic, reversed-phase high-performance liquid chromatography (HPLC) method with an ammonium acetate/methanol buffer. Ions monitored were 413 (parent) and 369 (daughter) for PFO and 415 (parent) and 370 (daughter) for dual labeled 13C-PFOA internal standard. As a precaution against ubiquitous PFO that occasionally occurs in mobile phase or instrument components, two Hypercarb cartridges (4 mm) were placed before the HPLC injector. Any PFO that was captured by the cartridges was removed before each injection by flushing the system with 100% methanol prior to equilibration with the isocratic mobile phase. Overall recovery and standard deviation over a 3 day validation regimen for samples (n=54-55) fortified with PFOA at 5, 50, and 200 ng g(-1) were 114+/-4.9% for textile and 110+/-7.6% for paper. The results also established a limit of detection (LOD) of 1 ng g(-1) in textile and 2 ng g(-1) in paper based upon S/N of the 5.0 ng g(-1) fortification versus the untreated paper and textile.

  9. Regulation of P21cip1 Expression by Growth Factors and the Extracellular Matrix Reveals a Role for Transient ERK Activity in G1 Phase

    Science.gov (United States)

    Bottazzi, Maria Elena; Zhu, Xiaoyun; Böhmer, Ralph M.; Assoian, Richard K.

    1999-01-01

    We have examined the regulation of p21cip1 by soluble mitogens and cell anchorage as well as the relationship between the expression of p21cip1 and activation of the ERK subfamily of MAP kinases. We find that p21cip1 expression in G1 phase can be divided into two discrete phases: an initial induction that requires growth factors and the activation of ERK, and then a subsequent decline that is enhanced by cell anchorage in an ERK-independent manner. In contrast to the induction of cyclin D1, the induction of p21cip1 is mediated by transient ERK activity. Comparative studies with wild-type and p21cip1-null fibroblasts indicate that adhesion-dependent regulation of p21cip1 is important for proper control of cyclin E–cdk2 activity. These data lead to a model in which mitogens and anchorage act in a parallel fashion to regulate G1 phase expression of p21cip1. They also show that (a) growth factors and growth factor/extracellular matrix cooperation can have different roles in regulating G1 phase ERK activity and (b) both transient and sustained ERK signals have functionally significant roles in controlling cell cycle progression through G1 phase. PMID:10491389

  10. Extensive Chemical Modifications in the Primary Protein Structure of IgG1 Subvisible Particles Are Necessary for Breaking Immune Tolerance.

    Science.gov (United States)

    Boll, Björn; Bessa, Juliana; Folzer, Emilien; Ríos Quiroz, Anacelia; Schmidt, Roland; Bulau, Patrick; Finkler, Christof; Mahler, Hanns-Christian; Huwyler, Jörg; Iglesias, Antonio; Koulov, Atanas V

    2017-04-03

    A current concern with the use of therapeutic proteins is the likely presence of aggregates and submicrometer, subvisible, and visible particles. It has been proposed that aggregates and particles may lead to unwanted increases in the immune response with a possible impact on safety or efficacy. The aim of this study was thus to evaluate the ability of subvisible particles of a therapeutic antibody to break immune tolerance in an IgG1 transgenic mouse model and to understand the particle attributes that might play a role in this process. We investigated the immunogenic properties of subvisible particles (unfractionated, mixed populations, and well-defined particle size fractions) using a transgenic mouse model expressing a mini-repertoire of human IgG1 (hIgG1 tg). Immunization with proteinaceous subvisible particles generated by artificial stress conditions demonstrated that only subvisible particles bearing very extensive chemical modifications within the primary amino acid structure could break immune tolerance in the hIgG1 transgenic mouse model. Protein particles exhibiting low levels of chemical modification were not immunogenic in this model.

  11. Purification and characterization of two phospho-β-galactosidases, LacG1 and LacG2, from Lactobacillus gasseri ATCC33323T

    NARCIS (Netherlands)

    Honda, Hiroyuki; Nagaoka, Seiji; Kawai, Yasushi; Kemperman, Robèr; Kok, Jan; Yamazaki, Yukiko; Tateno, Yoshio; Kitazawa, Haruki; Saito, Tadao

    2012-01-01

    Lactobacillus gasseri ATCC33323T expresses four enzymes showing phospho-β-galactosidase activity (LacG1, LacG2, Pbg1 and Pbg2). We previously reported the purification and characterization of two phospho-β-galactosidases (Pbg1 and Pbg2) from Lactobacillus gasseri JCM1031 cultured in lactose medium.

  12. Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry.

    Science.gov (United States)

    Vergés, Emili; Colomina, Neus; Garí, Eloi; Gallego, Carme; Aldea, Martí

    2007-06-08

    G1 cyclin Cln3 plays a key role in linking cell growth and proliferation in budding yeast. It is generally assumed that Cln3, which is present throughout G1, accumulates passively in the nucleus until a threshold is reached to trigger cell cycle entry. We show here that Cln3 is retained bound to the ER in early G1 cells. ER retention requires binding of Cln3 to the cyclin-dependent kinase Cdc28, a fraction of which also associates to the ER. Cln3 contains a chaperone-regulatory Ji domain that counteracts Ydj1, a J chaperone essential for ER release and nuclear accumulation of Cln3 in late G1. Finally, Ydj1 is limiting for release of Cln3 and timely entry into the cell cycle. As protein synthesis and ribosome assembly rates compromise chaperone availability, we hypothesize that Ydj1 transmits growth capacity information to the cell cycle for setting efficient size/ploidy ratios.

  13. The Cln3 cyclin is down-regulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast.

    Science.gov (United States)

    Gallego, C; Garí, E; Colomina, N; Herrero, E; Aldea, M

    1997-12-01

    Nutrients are among the most important trophic factors in all organisms. When deprived of essential nutrients, yeast cells use accumulated reserves to complete the current cycle and arrest in the following G1 phase. We show here that the Cln3 cyclin, which has a key role in the timely activation of SBF (Swi4-Swi6)- and MBF (Mbp1-Swi6)-dependent promoters in late G1, is down-regulated rapidly at a post-transcriptional level in cells deprived of the nitrogen source. In addition to the fact that Cln3 is degraded faster by ubiquitin-dependent mechanisms, we have found that translation of the CLN3 mRNA is repressed approximately 8-fold under nitrogen deprivation conditions. As a consequence, both SBF- and MBF-dependent expression is strongly down-regulated. Mainly because of their transcriptional dependence on SBF, and perhaps with the contribution of similar post-transcriptional mechanisms to those found for Cln3, the G1 cyclins Cln1 and 2 become undetectable in starved cells. The complete loss of Cln cyclins and the sustained presence of the Clb-cyclin kinase inhibitor Sic1 in starved cells may provide the molecular basis for the G1 arrest caused by nitrogen deprivation.

  14. G protein-coupled receptor 30 ligand G-1 increases aryl hydrocarbon receptor signalling by inhibition of tubulin assembly and cell cycle arrest in human MCF-7 cells.

    Science.gov (United States)

    Tarnow, Patrick; Tralau, Tewes; Luch, Andreas

    2016-08-01

    Regulatory crosstalk between the aryl hydrocarbon receptor (AHR) and oestrogen receptor α (ERα) is well established. Apart from the nuclear receptors ERα and ERβ, oestrogen signalling further involves an unrelated G protein-coupled receptor termed GPR30. In order to investigate potential regulatory crosstalk, this study investigated the influence of G-1 as one of the few GPR30-specific ligands on the AHR regulon in MCF-7 cells. As a well-characterised model system, these human mammary carcinoma cells co-express all three receptors (AHR, ERα and GPR30) and are thus ideally suited to study corresponding regulatory pathway interactions on transcript level. Indeed, treatment with micromolar concentrations of the GPR30-specific agonist G-1 resulted in up-regulation of AHR as well as the transcripts for cytochromes P450 1A1 and 1B1, two well-known targets of the AHR regulon. While this was partly attributable to G-1-mediated inhibition of tubulin assembly and subsequent cell cycle arrest in the G2/M phase, the effects nevertheless required functional AHR. However, G-1-induced up-regulation of CYP 1A1 was not mediated by GPR30, as G15 antagonist treatment as well as a knockdown of GPR30 and AHR failed to inhibit this effect.

  15. Responses of IgE, IgG1, and IgG4 to concanavalin A-binding Blomia tropicalis antigens in allergic patients

    Directory of Open Access Journals (Sweden)

    K.C. Almeida

    2006-11-01

    Full Text Available Blomia tropicalis (Bt and Dermatophagoides pteronyssinus (Dp are the prevalent house dust mites in tropical countries and are associated with allergic diseases. Glycosylated antigens are highly immunogenic and involved in different pathologies. We evaluated the presence of IgE, IgG1, and IgG4 to concanavalin A-binding antigens (Bt-Con-A isolated from Bt-total extract in sera of allergic and non-allergic subjects. Bt-total and Bt-Con-A extracts were evaluated by SDS-PAGE and ELISA for reacting with IgE, IgG1, and IgG4 in sera of 121 patients with allergic rhinitis and 36 non-allergic individuals. All subjects were skin prick tested with Bt-total extract and inhibition tests were performed for IgE, IgG1, and IgG4 using both extracts (Bt-total and Bt-Con-A. Skin prick test showed that 58% of the patients were sensitized to Bt (Bt+, with 52% reactive to both mites (Bt and Dp and 6% to Bt only. A broad spectrum of proteins (14-152 kDa was visualized in Bt-total and components >27 kDa for the Bt-Con-A extract. ELISA showed a similar profile of IgE, IgG1 and IgG4 levels in response to Bt-total and Bt-Con-A extracts in different groups, although Bt+ patients showed a lower IgG4 reactivity to Bt-Con-A extract. Specific IgG1 levels were higher in Bt+ patients than in control subjects, and IgG4 levels showed no significant difference among groups. ELISA inhibition showed a partial IgE and total IgG1 and IgG4 cross-reactivity with Dp extract for Bt-total and Bt-Con-A extracts. We conclude that Con-A-binding components isolated from Bt constitute major allergens and are involved in both allergen sensitization (IgE response and homeostasis maintenance (IgG1 and IgG4 responses.

  16. Human rotavirus strains circulating in Venezuela after vaccine introduction: predominance of G2P[4] and reemergence of G1P[8].

    Science.gov (United States)

    Vizzi, Esmeralda; Piñeros, Oscar A; Oropeza, M Daniela; Naranjo, Laura; Suárez, José A; Fernández, Rixio; Zambrano, José L; Celis, Argelia; Liprandi, Ferdinando

    2017-03-21

    Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] rotaviruses, but they were rather distant from Rotarix(®) vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence

  17. Direct determination of platinum group elements and their distributions in geological and environmental samples at the ng g(-1) level using LA-ICP-IDMS.

    Science.gov (United States)

    Boulyga, Sergei F; Heumann, Klaus G

    2005-10-01

    Laser ablation inductively coupled plasma isotope dilution mass spectrometry (LA-ICP-IDMS) was applied to the direct and simultaneous determination of the platinum group elements (PGEs) Pt, Pd, Ru, and Ir in geological and environmental samples. A special laser ablation system with high ablation rates was used, along with sector field ICP-MS. Special attention was paid to deriving the distributions of PGEs in the pulverized samples. IDMS could not be applied to the (mono-isotopic) Rh, but the similar ablation behavior of Ru and Rh allowed Rh to be simultaneously determined via relative sensitivity coefficients. The laser ablation process produces hardly any oxide ions (which usually cause interference in PGE analysis with liquid sample injection), so the ICP-MS can be run in its low mass resolution but high-sensitivity mode. The detection limits obtained for the geological samples were 0.16 ng g(-1), 0.14 ng g(-1), 0.08 ng g(-1), 0.01 ng g(-1) and 0.06 ng g(-1) for Ru, Rh, Pd, Ir and Pt, respectively. LA-ICP-IDMS was applied to different geological reference materials (TDB-1, WGB-1, UMT-1, WMG-1, SARM-7) and the road dust reference material BCR-723, which are only certified for some of the PGEs. Comparisons with certified values as well as with indicative values from the literature demonstrated the validity of the LA-ICP-IDMS method. The PGE concentrations in subsamples of the road dust reference material correspond to a normal distribution, whereas the distributions in the geological reference materials TDB-1, WGB-1, UMT-1, WMG-1, and SARM-7 are more complex. For example, in the case of Ru, a logarithmic normal distribution best fits the analyzed concentrations in TDB-1 subsamples, whereas a pronounced nugget effect was found for Pt in most geological samples.

  18. Analysis of Gene Evolution, Protein Expression and Identification of Echinococcus granulosus EgG1Y162%细粒棘球蚴EgG1Y162基因进化分析、表达及鉴定

    Institute of Scientific and Technical Information of China (English)

    祖力皮也·吐尔逊; 曹春宝; 温浩; 丁剑冰; 德力夏提·依米提

    2016-01-01

    目的:克隆和鉴定细粒棘球蚴的EgG1 Y162基因,分析其蛋白表达和适应性进化并鉴定抗原性.方法:根据emY162基因序列设计引物,分别从细粒棘球绦虫原头蚴、囊壁生发层、成虫和虫卵四个发育阶段,提取基因组DNA和总RNA,mRNA反转录为cDNA,利用PCR的方法以基因组DNA和cDNA为模板扩增EgG1Y162基因;构建PUCm-T/EgG1Y162重组质粒,经PCR、酶切及测序鉴定后,测序确定其正确性.利用DNAman软件与MEGA4软件对EgG1Y162基因特点进行分析并构建EgG1Y162核酸序列的进化树进一步探讨其同源性.荧光定量PCR检测EgG1Y162基因在细粒棘球绦虫原头蚴、囊壁生发层、成虫和虫卵四个不同发育阶段的表达情况.利用定向克隆技术将EgG1Y162抗原基因片段克隆至原核表达质粒PET-41a上,通过酶切分析和PCR鉴定筛选出阳性克隆,测序确定序列.IPTG初步诱导和表达EgG1Y162-GST重组蛋白,通过SDS-PAGE电泳和Westernblot试验分析鉴定.结果:从细粒棘球绦虫的两个不同发育阶段均克隆出EgG1Y162基因,从总DNA克隆得到片段长度1 680bp,从cDNA克隆得到片段长度459bp.相似性比较表明,EgG1Y162基因序列与emY162相似性为91%,而EgG1Y162基因cDNA与emY162相似性为95%.进一步分析显示,EgG1Y162基因序列由3个外显子和2个内含子组成,外显子区域分别为1~70,1064~1 380和1 577 ~1 648.位于疏水端1~16位氨基酸构成EgG1Y162信号肽序列,35~ 115位氨基酸形成一个大的纤黏连蛋白剪接体FN3,133 ~ 152位氨基酸构成羧基端跨膜区域.测序结果显示EgG1Y162抗原基因长度为360bp,编码120个氨基酸.通过荧光定量PCR检测,发现EgG1Y162在成虫、生发层阶段、原头蚴和虫卵阶段均有不同程度的表达.但是EgG1Y162在成虫中的表达量最多,相对值为19.526,差异有统计学意义(P<0.01),其次生发层阶段,为5.122,再次在原头蚴阶段,相对值为5.083,

  19. Promoter polymorphism MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) in development of HAND and modulation of pathogenesis of HAND

    Indian Academy of Sciences (India)

    HARI OM SINGH; SHRUTI D MARATHE; SUMITRA NAIN; DHARMESH SAMANI; VIJAY NEMA; MANISHAV GHATE; R R GANGAKHEDKAR

    2017-09-01

    The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by host genetic susceptibility factorssuch as Matrix metalloproteinases (MMPs). Promoter polymorphism of MMP-1 and MMP-3 may modify the expression ofthe gene. Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A polymorphisms withdevelopment of HAND and the modulation of pathogenesis of HAND. We enrolled a total of 180 individuals, 50 HIVinfectedindividuals with HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607 1G allele were associatedwith the development of HAND (OR = 1.64, P = 0.05; OR = 1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1-16071G1G, MMP-3-16125A5A genotypes increased the risk for the development of HAND (OR = 1.78, P = 0.25;OR = 2.39, P = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were associated with thereduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P = 0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increasedthe risk of development of HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-16071G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P = 0.89). MMP-3-1612 6A5A genotypeshowed higher risk for development of HAND in alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have aninfluence on development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for pathogenesis of HAND.

  20. IgM, IgA, IgG1 and IgG2 specific responses in blood and gut secretion of calves fed soyabean products.

    Science.gov (United States)

    Dréau, D; Lallès, J P; Salmon, H; Toullec, R

    1995-07-01

    Calves fed soya proteins may develop severe gastrointestinal disorders. Whether these are predominantly associated with particular Ig subclasses and (or) dietary proteins remains unclear. Therefore, antibody responses to soyabean protein were analysed by dot- and blot-immunobinding in plasma and intestinal mucous secretions. One-month-old calves were fed for 2.5 months liquid diets based on skim milk powder (SMP) or a mixture (2:3, protein basis) of whey and soyabean products including a low antigenic hydrolysed soya protein isolate (HSPI) and a highly antigenic heated soya flour (HSF). Specific antibodies (Abs) of the main isotypes (IgM, IgA, IgG1, IgG2) were characterised by immunostaining of samples which had been previously incubated with nitrocellulose sheets coated with SMP, HSPI or HSF extracts. Plasma collected before feeding experimental diets showed very little specific Abs. By contrast, 2.5 months later, a three-fold increase (P IgA titres against HSF antigens was observed in calves fed HSF compared with those fed the control or HSPI diet. IgG1 immunoblotting revealed many protein bands from soya in the molecular range of 22-32 and 38-42 kDa. Immunorecognition of specific proteins from SMP and HSPI remained low and similar among animal groups. Specific IgM, IgA and IgG1 titres against HSF, and to a lesser extent HSPI, were significantly higher (P IgA and IgG1. By contrast, only weak bands were found for IgM and IgG2 in all groups of calves. Thus, calves fed antigenic HSF do present specific Abs including IgG1 and IgA isotypes, both systemically and locally. Therefore, IgG1 and (or) IgA rather than IgM and IgG2 Abs may be preferred for assessing the immunogenicity of soyabean products in calves. Interestingly, soyabean immunogenicity was drastically reduced by adequate proteolysis.

  1. Detection of IgG1 antibodies against Mycobacterium tuberculosis DosR and Rpf antigens in tuberculosis patients before and after chemotherapy.

    Science.gov (United States)

    Mattos, Ana Márcia Menezes; Chaves, Alexandre Silva; Franken, Kees L M C; Figueiredo, Bárbara Bruna Muniz; Ferreira, Ana Paula; Ottenhoff, Tom H M; Teixeira, Henrique Couto

    2016-01-01

    Diagnosis of tuberculosis (TB) remains challenging. Serum IgG1 antibodies against Mycobacterium tuberculosis active growth phase antigens (ESAT-6/CFP-10, Rv0717 and Rv3353), DosR regulon-encoded proteins (Rv1733, Rv1737, Rv2628 and Rv2029), and resuscitation-promoting factors (Rv0867 and Rv2389) were evaluated in TB patients using ELISA. Active TB patients showed elevated levels of IgG1 antibodies against ESAT-6/CFP-10, Rv0717, Rv3353, Rv1733, Rv2628, Rv2029 and Rv0867 in comparison to healthy controls (p tuberculosis antigens, including DosR and Rpf proteins, may represent an additional tool in the diagnosis of tuberculosis.

  2. Comparison of IgM, IgG1 and IgG2 responses to Trichinella spiralis and Trichinella britovi in swine

    Directory of Open Access Journals (Sweden)

    Serrano F.J

    2001-06-01

    Full Text Available Pigs infected with T. spiralis and T. britovi were followed by double (lgG and triple antibody ELISA (IgG1, lgG 2 and IgM during a 12-week-period. Specific IgG and IgG1 responses were similar and showed a significant relation with the infecting doses and intensity of infection. Response to T. britovi was slightly lower than in groups infected with the same dose of T. spiralis. lgG 2 response was weak and almost undetectable in the lowest infected pigs, but relationship with the intensity of infection was unclear. IgM antibodies showed rapid but transient increases, generally simultaneous to peaks of IgG response.

  3. Generation of Discrete Bicubic G1 B-Spline Ship Hullform Surfaces from a Given Curve Network Using Virtual Iso-Parametric Curves

    Institute of Scientific and Technical Information of China (English)

    Joong-Hyun Rhim; Doo-Yeoun Cho; Kyu-Yeul Lee; Tae-Wan Kim

    2006-01-01

    We propose a method that automatically generates discrete bicubic G1 continuous B-spline surfaces that interpolate the curve network of a ship hullform. First, the curves in the network are classified into two types: boundary curves and "reference curves". The boundary curves correspond to a set of rectangular (or triangular) topological type that can be represented with tensor-product (or degenerate) B-spline surface patches. Next, in the interior of the patches,surface fitting points and cross boundary derivatives are estimated from the reference curves by constructing "virtual" isoparametric curves. Finally, a discrete G1 continuous B-spline surface is generated by a surface fitting algorithm. Several smooth ship hullform surfaces generated from curve networks corresponding to actual ship hullforms demonstrate the quality of the method.

  4. Draft Genome Sequence of Geobacillus icigianus Strain G1w1T Isolated from Hot Springs in the Valley of Geysers, Kamchatka (Russian Federation).

    Science.gov (United States)

    Bryanskaya, Alla V; Rozanov, Aleksey S; Logacheva, Maria D; Kotenko, Anastasia V; Peltek, Sergey E

    2014-10-23

    The Geobacillus icigianus G1w1(T) strain was isolated from sludge samples of unnamed vaporing hydrothermal (97°С) outlets situated in a geyser in the Troinoy region (Valley of Geysers, Kronotsky Nature Reserve, Kamchatka, Russian Federation; 54°25'51.40″N, 160°7'41.40″E). The sequenced and annotated genome is 3,457,810 bp and encodes 3,342 genes.

  5. Characterization of pH dependent Mn(II oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    Directory of Open Access Journals (Sweden)

    Tsing eBohu

    2015-07-01

    Full Text Available Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB isolates limits our understanding of how pH influences biological Mn(II oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction (XRD, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase (MCO expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS, particularly superoxide, appeared to be more important for T-G1 mediated Mn(II oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  6. Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway.

    Directory of Open Access Journals (Sweden)

    Chao-Ying Huang

    Full Text Available In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2 was suppressed by specific small interfering RNA (siRNA. These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.

  7. Analysis of the APX, PGD1 and R1G1B constitutive gene promoters in various organs over three homozygous generations of transgenic rice plants.

    Science.gov (United States)

    Park, Su-Hyun; Bang, Seung Woon; Jeong, Jin Seo; Jung, Harin; Redillas, Mark Christian Felipe Reveche; Kim, Hyung Il; Lee, Kang Hyun; Kim, Youn Shic; Kim, Ju-Kon

    2012-06-01

    We have previously characterized the constitutively active promoters of the APX, PGD1 and R1G1B genes in rice (Park et al. 2010 in J Exp Bot 61:2459-2467). To have potential crop biotechnology applications, gene promoters must be stably active over many generations. In our current study, we report our further detailed analysis of the APX, PGD1 and R1G1B gene promoters in various organs and tissues of transgenic rice plants for three (T₃₋₅) homozygous generations. The copy numbers in 37 transgenic lines that harbor promoter:gfp constructs were determined and promoter activities were measured by real-time qPCR. Analysis of the 37 lines revealed that 15 contained a single copy of one of the three promoter:gfp chimeric constructs. The promoter activity levels were generally higher in multi-copy lines, whereas variations in these levels over the T₃₋₅ generations studied were observed to be smaller in single-copy than in multi-copy lines. The three promoters were further found to be highly active in the whole plant body at both the vegetative and reproductive stages of plant growth, with the exception of the APX in the ovary and R1G1B in the pistil and filaments where zero or very low levels of activity were detected. Of note, the spatial activities of the PGD1 promoter were found to be strikingly similar to those of the ZmUbi1, a widely used constitutive promoter. Our comparison of promoter activities between T₃, T₄ and T₅ plants revealed that the APX, PGD1 and R1G1B promoters maintained their activities at comparable levels in leaves and roots over three homozygous generations and are therefore potentially viable alternative promoters for crop biotechnology applications.

  8. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1.

    Science.gov (United States)

    Bohu, Tsing; Santelli, Cara M; Akob, Denise M; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  9. Lengthening the G(1) phase of neural progenitor cells is concurrent with an increase of symmetric neuron generating division after stroke.

    Science.gov (United States)

    Zhang, Rui L; Zhang, Zheng G; Roberts, Cynthia; LeTourneau, Yvonne; Lu, Mei; Zhang, Li; Wang, Ying; Chopp, Michael

    2008-03-01

    The proportion of neural progenitors that remain in (P fraction) and exit from (Q fraction) the cell cycle determines the degree of neurogenesis. Using S-phase labeling with 5-bromo-2'-deoxyuridine and a double nucleoside analog-labeling scheme, we measured the cell-cycle kinetics of neural progenitors and estimated the proportion of P and Q fractions in the subventricular zone (SVZ) of adult rats subjected to stroke. Stroke increased SVZ cell proliferation, starting 2 days, reaching a maximum 4 and 7 days after stroke. The cell-cycle length (T(C)) of SVZ cells changed dynamically over a period of 2 to 14 days after stroke, with the shortest length of 11 h at 2 days after stroke. The reduction of the T(C) resulted from a decrease of the G(1) phase because the G(2), M, and S phases were unchanged. In addition, during this period, reduction of the G(1) phase was concomitant with an increase in the P fraction, whereas an augmentation of the Q fraction was associated with lengthening of the G(1) phase. Furthermore, approximately 90% of cells that exited the cell cycle were neurons and the population of a pair of dividing daughter cells with a neuronal marker increased from 9% at 2 days to 26% at 14 days after stroke. These data suggest that stroke triggers early expansion of the progenitor pool via shortening the cell-cycle length and retaining daughter cells within the cell cycle, and the lengthening of G(1) leads to daughter cells exiting the cell cycle and differentiating into neurons.

  10. Application of isotope-dilution laser ablation ICP-MS for direct determination of Pu concentrations in soils at pg g(-1) levels.

    Science.gov (United States)

    Boulyga, Sergei F; Tibi, Markus; Heumann, Klaus G

    2004-01-01

    The methods available for determination of environmental contamination by plutonium at ultra-trace levels require labor-consuming sample preparation including matrix removal and plutonium extraction in both nuclear spectroscopy and mass spectrometry. In this work, laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was applied for direct analysis of Pu in soil and sediment samples. Application of a LINA-Spark-Atomizer system (a modified laser ablation system providing high ablation rates) coupled with a sector-field ICP-MS resulted in detection limits as low as 3x10(-13) g g(-1) for Pu isotopes in soil samples containing uranium at a concentration of a few microg g(-1). The isotope dilution (ID) technique was used for quantification, which compensated for matrix effects in LA-ICP-MS. Interferences by UH+ and PbO2+ ions and by the peak tail of 238U+ ions were reduced or separated by use of dry plasma conditions and a mass resolution of 4000, respectively. No other effects affecting measurement accuracy, except sample inhomogeneity, were revealed. Comparison of results obtained for three contaminated soil samples by use of alpha-spectrometry, ICP-MS with sample decomposition, and LA-ICP-IDMS showed, in general, satisfactory agreement of the different methods. The specific activity of (239+240)Pu (9.8 +/- 3.0 mBq g(-1)) calculated from LA-ICP-IDMS analysis of SRM NIST 4357 coincided well with the certified value of 10.4 +/- 0.2 mBq g(-1). However, the precision of LA-ICP-MS for determination of plutonium in inhomogeneous samples, i.e. if "hot" particles are present, is limited. As far as we are aware this paper reports the lowest detection limits and element concentrations yet measured in direct LA-ICP-MS analysis of environmental samples.

  11. ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

    Science.gov (United States)

    Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

    2016-01-01

    Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

  12. Co-immunization of cattle with a vaccine against babesiosis and Lactobacillus casei increases specific IgG1 levels to Babesia bovis and B. bigemina.

    Science.gov (United States)

    Bautista-Garfias, Carlos Ramón; Lozano, Astrid Rodríguez; Martínez, Carmen Rojas; Martínez, Jesús Antonio Álvarez; Millán, Julio Vicente Figueroa; García, Gustavo Román Reyes; Castañeda-Arriola, Roberto; Aguilar-Figueroa, Blanca Rosa

    2015-10-01

    The effect of Lactobacillus casei administered along with a live attenuated vaccine vs. bovine babesiosis (VAC) on induction of IgG1 and IgG2 antibodies to Babesia bovis and Babesia bigemina was assessed by the indirect fluorescent antibody test (IFAT) in bovines of an endemic babesiosis area before (day 0) and after vaccination (days 15 and 30). We previously reported that L. casei increases the efficiency of VAC under controlled conditions and under extreme conditions in the field; however, the levels of IgG1 and IgG2 antibodies to B. bovis and B. bigemina are not known in vaccinated animals. Twenty-one dairy cows were allocated into three groups (seven animals per group): unvaccinated, vaccinated with VAC and vaccinated simultaneously with VAC and L. casei (VAC-LC). All animals were kept in a babesiosis endemic area at Tlalixcoyan, Veracruz. At days 15 and 30 after vaccination, the average levels of IgG1 to B. bovis and to B. bigemina were significantly higher in VAC-LC group than levels observed in VAC and control groups (P<0.01). Levels of IgG2 were similar in VAC and VAC-LC groups but higher than in the control group (P<0.01). When tested in in vitro cultures of B. bovis, sera from VAC-LC group significantly inhibited parasite growth as compared with the sera of the other two groups. It is suggested that the efficiency improvement of VAC, in part, is due to the L. casei boost of IgG1 over IgG2 antibodies to B. bovis and B. bigemina when the bacteria is co-inoculated with this vaccine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. β2-adrenoceptor blockage induces G1/S phase arrest and apoptosis in pancreatic cancer cells via Ras/Akt/NFκB pathway

    Directory of Open Access Journals (Sweden)

    Zhang Dong

    2011-11-01

    Full Text Available Abstract Background Smoking and stress, pancreatic cancer (PanCa risk factors, stimulate nitrosamine 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK and catecholamines production respectively. NNK and catecholamine bind the β-adrenoceptors and induce PanCa cell proliferation; and we have previously suggested that β-adrenergic antagonists may suppress proliferation and invasion and stimulate apoptosis in PanCa. To clarify the mechanism of apoptosis induced by β2-adrenergic antagonist, we hypothesize that blockage of the β2-adrenoceptor could induce G1/S phase arrest and apoptosis and Ras may be a key player in PanCa cells. Results The β1 and β2-adrenoceptor proteins were detected on the cell surface of PanCa cells from pancreatic carcinoma specimen samples by immunohistochemistry. The β2-adrenergic antagonist ICI118,551 significantly induced G1/S phase arrest and apoptosis compared with the β1-adrenergic antagonist metoprolol, which was determined by the flow cytometry assay. β2-adrenergic antagonist therapy significantly suppressed the expression of extracellular signal-regulated kinase, Akt, Bcl-2, cyclin D1, and cyclin E and induced the activation of caspase-3, caspase-9 and Bax by Western blotting. Additionally, the β2-adrenergic antagonist reduced the activation of NFκB in vitro cultured PanCa cells. Conclusions The blockage of β2-adrenoceptor markedly induced PanCa cells to arrest at G1/S phase and consequently resulted in cell death, which is possibly due to that the blockage of β2-adrenoceptor inhibited NFκB, extracellular signal-regulated kinase, and Akt pathways. Therefore, their upstream molecule Ras may be a key factor in the β2-adrenoceptor antagonist induced G1/S phase arrest and apoptosis in PanCa cells. The new pathway discovered in this study may provide an effective therapeutic strategy for PanCa.

  14. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    Science.gov (United States)

    Bohu, Tsing; Santelli, Cara M; Akob, Denise M.; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  15. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    Science.gov (United States)

    Bohu, Tsing; Santelli, Cara M.; Akob, Denise M.; Neu, Thomas R.; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling. PMID:26236307

  16. Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability.

    Science.gov (United States)

    Gao, Guangxun; Chen, Liang; Li, Jingxia; Zhang, Dongyun; Fang, Yong; Huang, Haishan; Chen, Xiequn; Huang, Chuanshu

    2014-05-15

    The cancer chemopreventive property of Chinese herb new isolate isorhapontigenin (ISO) and mechanisms underlying its activity have never been explored. Here we demonstrated that ISO treatment with various concentrations for 3 weeks could dramatically inhibit TPA/EGF-induced cell transformation of Cl41 cells in Soft Agar assay, whereas co-incubation of cells with ISO at the same concentrations could elicit G0/G1 cell-cycle arrest without redundant cytotoxic effects on non-transformed cells. Further studies showed that ISO treatment resulted in cyclin D1 downregulation in dose- and time-dependent manner. Our results indicated that ISO regulated cyclin D1 at transcription level via targeting JNK/C-Jun/AP-1 activation. Moreover, we found that ISO-inhibited JNK/C-Jun/AP-1 activation was mediated by both upregulation of MKP-1 expression through increasing its mRNA stability and deactivating MKK7. Most importantly, MKP-1 knockdown could attenuate ISO-mediated suppression of JNK/C-Jun activation and cyclin D1 expression, as well as G0/G1 cell cycle arrest and cell transformation inhibition, while ectopic expression of FLAG-cyclin D1 T286A mutant also reversed ISO-induced G0/G1 cell-cycle arrest and inhibition of cell transformation. Our results demonstrated that ISO is a promising chemopreventive agent via upregulating mkp-1 mRNA stability, which is distinct from its cancer therapeutic effect with downregulation of XIAP and cyclin D1 expression.

  17. MiR-92a mediates AZD6244 induced apoptosis and G1-phase arrest of lymphoma cells by targeting Bim.

    Science.gov (United States)

    Lv, Xiao-Bin; Zhang, Xing; Deng, Lan; Jiang, Ling; Meng, Wei; Lu, Zhigang; Wang, Xiuju

    2014-04-01

    AZD6244, an ATP-uncompetitive inhibitor of mitogen-activated protein kinase 1/2 (MEK1/2), has shown activity in several malignant tumours. However, whether AZD6244 has a function in lymphoma cells is not known. We report that AZD6244 treatment represses the growth of Raji and MOLT4 cells by inducing apoptosis and G1-phase arrest. Using miRNAs array and quantitative RT-PCR, miR-92a was downregulated byAZD6244 treatment through the ERK1/2-AP1 signalling pathway. Overexpression of miR-92a abrogated AZD6244-induced apoptosis and G1-phase arrest, indicating that it is involved in the cytotoxicity of AZD6244 in lymphoma cells. A luciferase reporter assay showed that miR-92a directly targetsthe 3'-UTRs of Bim. Overexpression of miR-92a mimics downregulated Bim mRNA and protein expression level, indicating that miR-92a negatively regulates its expression at both levels. Silencing Bim decreases AZD6244-induced apoptosis and G1-phase arrest, suggesting that Bim contributes to the growth arrest. Thus, miR-92a mediates AZD6244-induced cytotoxicity of lymphoma cells by targeting Bim. Downregulation of miR-92a by AZD6244 is mediated by the ERK1/2-AP1 signalling pathway.

  18. RABL6A promotes G1-S phase progression and pancreatic neuroendocrine tumor cell proliferation in an Rb1-dependent manner.

    Science.gov (United States)

    Hagen, Jussara; Muniz, Viviane P; Falls, Kelly C; Reed, Sara M; Taghiyev, Agshin F; Quelle, Frederick W; Gourronc, Francoise A; Klingelhutz, Aloysius J; Major, Heather J; Askeland, Ryan W; Sherman, Scott K; O'Dorisio, Thomas M; Bellizzi, Andrew M; Howe, James R; Darbro, Benjamin W; Quelle, Dawn E

    2014-11-15

    Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression and metastatic disease are limited. We found amplification of a putative oncogene, RABL6A, in primary human pancreatic NETs (PNET) that correlated with high-level RABL6A protein expression. Consistent with those results, stable silencing of RABL6A in cultured BON-1 PNET cells revealed that it is essential for their proliferation and survival. Cells lacking RABL6A predominantly arrested in G1 phase with a moderate mitotic block. Pathway analysis of microarray data suggested activation of the p53 and retinoblastoma (Rb1) tumor-suppressor pathways in the arrested cells. Loss of p53 had no effect on the RABL6A knockdown phenotype, indicating that RABL6A functions independent of p53 in this setting. By comparison, Rb1 inactivation partially restored G1 to S phase progression in RABL6A-knockdown cells, although it was insufficient to override the mitotic arrest and cell death caused by RABL6A loss. Thus, RABL6A promotes G1 progression in PNET cells by inactivating Rb1, an established suppressor of PNET proliferation and development. This work identifies RABL6A as a novel negative regulator of Rb1 that is essential for PNET proliferation and survival. We suggest RABL6A is a new potential biomarker and target for anticancer therapy in PNET patients.

  19. Mitofusin-2-mediated tethering of mitochondria and endoplasmic reticulum promotes cell cycle arrest of vascular smooth muscle cells in G0/G1 phase.

    Science.gov (United States)

    Li, Dan; Li, Xiaolan; Guan, Yang; Guo, Xiaomei

    2015-06-01

    Mitofusin-2 (Mfn-2) is a hyperplasia suppressor. Changes in Mfn-2 expression are thought to reflect mitochondrial remodeling during cell proliferation. However, it is unclear how the participation of Mfn-2 in mitochondrial remodeling prevents cellular proliferation. Here we show that arresting vascular smooth muscle cells (VSMCs) in the G0/G1 phase by serum starvation up-regulates Mfn-2 expression and causes mitochondria to assemble into a tubular network and to attach to the endoplasmic reticulum (ER). In the S phase, short rod-shaped mitochondrial structures that were dissociated from the ER were observed. Levels of glucose, ATP, l-amino acid, and NADP(+) did not vary throughout the cell cycle. However, NAD(+) level was lower and NADH level was higher in the G0/G1 phase than in the S phase. Mitochondrial membrane potential was lower in the S phase than in the G0/G1 phase. Infecting VSMCs with an adenovirus encoding full-length Mfn-2 increased NADH level and reduced NAD(+) level, while infecting the cells with an adenovirus that silences the p21(ras) signature motif produced opposite effects. These results suggest that Mfn-2 up-regulation causes mitochondrial fusion into tubular networks and attachment to the ER, which in turn halts proliferation of VSMCs. © The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  20. p21 Inhibits Cdk1 in the absence of Cdk2 to maintain the G1/S phase DNA damage checkpoint.

    Science.gov (United States)

    Satyanarayana, Ande; Hilton, Mary Beth; Kaldis, Philipp

    2008-01-01

    Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2(-/-) mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2(-/-) mice, arrest promptly at the G1/S checkpoint in response to gamma-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2(-/-) cells due to prolonged and impaired DNA repair activity. In addition, Cdk2(-/-) mice were more sensitive to lethal irradiation compared to wild-type and displayed delayed resumption of DNA replication in regenerating liver cells. Our results suggest that the G1/S DNA damage checkpoint is intact in the absence of Cdk2, but Cdk2 is important for proper repair of the damaged DNA.

  1. NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through HDAC6 Inhibition in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jih-Tung Pai

    2015-05-01

    Full Text Available Disrupting lung tumor growth via histone deacetylases (HDACs inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90 mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA, a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4.

  2. Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells.

    Science.gov (United States)

    Park, Cheol; Choi, Young-Whan; Hyun, Sook Kyung; Kwon, Hyun Ju; Hwang, Hye Jin; Kim, Gi-Young; Choi, Byung Tae; Kim, Byung-Woo; Choi, Il-Whan; Moon, Sung-Kwon; Kim, Wun-Jae; Choi, Yung Hyun

    2009-10-01

    We isolated two phytochemical lignans, schisandrin and schisandrin C, from Schizandra chinensis Baill and investigated their anti-cancer effects in human leukemia U937 cells. Schisandrin C inhibited cell growth in a dose-dependent manner, which was associated with the induction of G1 arrest of the cell cycle and apoptosis; schisandrin did not inhibit growth. Schisandrin C induced G1 arrest was correlated with down-regulation of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk) 4 and E2Fs expression, inhibition of phosphorylation of retinoblastoma protein (pRB), and up-regulation of the Cdk inhibitor p21(WAF1/CIP1). In addition, schisandrin C-induced apoptosis was associated with down-regulation of expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, proteolytic activation of caspase-3 and -9, and a concomitant degradation of poly(ADP-ribose) polymerase (PARP). Furthermore, schisandrin C-induced apoptosis was significantly inhibited by a caspase-3 specific inhibitor z-DEVD-fmk, indicating an important role for caspase-3 in the schisandrin C mechanism. In summary, growth inhibition by schisandrin C is related to cell cycle arrest at G1 and induction of caspase-3-dependent apoptosis in U937 cells; these findings suggest that schisandrin C may be a useful chemotherapeutic agent.

  3. Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

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    Lijian Yang

    Full Text Available Based on interactions among transcription factors, oncogenes, tumor suppressors and microRNAs, a Boolean model of cancer network regulated by miR-17-92 cluster is constructed, and the network is associated with the control of G1/S transition in the mammalian cell cycle. The robustness properties of this regulatory network are investigated by virtue of the Boolean network theory. It is found that, during G1/S transition in the cell cycle process, the regulatory networks are robustly constructed, and the robustness property is largely preserved with respect to small perturbations to the network. By using the unique process-based approach, the structure of this network is analyzed. It is shown that the network can be decomposed into a backbone motif which provides the main biological functions, and a remaining motif which makes the regulatory system more stable. The critical role of miR-17-92 in suppressing the G1/S cell cycle checkpoint and increasing the uncontrolled proliferation of the cancer cells by targeting a genetic network of interacting proteins is displayed with our model.

  4. Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning during G1 Phase and Assembly of the Origin Recognition Complex in Human Cells.

    Science.gov (United States)

    Kara, Nihan; Hossain, Manzar; Prasanth, Supriya G; Stillman, Bruce

    2015-05-08

    Replication of eukaryotic chromosomes occurs once every cell division cycle in normal cells and is a tightly controlled process that ensures complete genome duplication. The origin recognition complex (ORC) plays a key role during the initiation of DNA replication. In human cells, the level of Orc1, the largest subunit of ORC, is regulated during the cell division cycle, and thus ORC is a dynamic complex. Upon S phase entry, Orc1 is ubiquitinated and targeted for destruction, with subsequent dissociation of ORC from chromosomes. Time lapse and live cell images of human cells expressing fluorescently tagged Orc1 show that Orc1 re-localizes to condensing chromatin during early mitosis and then displays different nuclear localization patterns at different times during G1 phase, remaining associated with late replicating regions of the genome in late G1 phase. The initial binding of Orc1 to mitotic chromosomes requires C-terminal amino acid sequences that are similar to mitotic chromosome-binding sequences in the transcriptional pioneer protein FOXA1. Depletion of Orc1 causes concomitant loss of the mini-chromosome maintenance (Mcm2-7) helicase proteins on chromatin. The data suggest that Orc1 acts as a nucleating center for ORC assembly and then pre-replication complex assembly by binding to mitotic chromosomes, followed by gradual removal from chromatin during the G1 phase.

  5. A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins.

    Science.gov (United States)

    Fisher, D L; Nurse, P

    1996-02-15

    Deletion of the fission yeast mitotic B-type cyclin gene cdc13 causes cells to undergo successive rounds of DNA replication. We have used a strain which expresses cdc13 conditionally to investigate re-replication. Activity of Start genes cdc2 and cdc10 is necessary and p34cdc2 kinase is active in re-replicating cells. We tested to see whether other cyclins were required for re-replication using cdc13delta. Further deletion of cig1 and puc1 had no effect, but deletion of cig2/cyc17 caused a severe delay in re-replication. Deletion of cig1 and cig2/cyc17 together abolished re-replication completely and cells arrested in G1. This, and analysis of the temperature sensitive cdc13-117 mutant, suggests that cdc13 can effectively substitute for the G1 cyclin activity of cig2/cyc17. We have characterized p56cdc13 activity and find evidence that in the absence of G1 cyclins, S-phase is delayed until the mitotic p34cdc2-p56cdc13 kinase is sufficiently active. These data suggest that a single oscillation of p34cdc2 kinase activity provided by a single B-type cyclin can promote ordered progression into both DNA replication and mitosis, and that the level of cyclin-dependent kinase activity may act as a master regulator dictating whether cells undergo S-phase or mitosis.

  6. Importance of trivalency and the e(g)(1) configuration in the photocatalytic oxidation of water by Mn and Co oxides.

    Science.gov (United States)

    Maitra, Urmimala; Naidu, B S; Govindaraj, A; Rao, C N R

    2013-07-16

    Prompted by the early results on the catalytic activity of LiMn2O4 and related oxides in the photochemical oxidation of water, our detailed study of several manganese oxides has shown that trivalency of Mn is an important factor in determining the catalytic activity. Thus, Mn2O3, LaMnO3, and MgMn2O4 are found to be very good catalysts with turnover frequencies of 5 × 10(-4) s(-1), 4.8 × 10(-4) s(-1), and 0.8 × 10(-4) s(-1), respectively. Among the cobalt oxides, Li2Co2O4 and LaCoO3--especially the latter--exhibit excellent catalytic activity, with the turnover frequencies being 9 × 10(-4) s(-1) and 1.4 × 10(-3) s(-1), respectively. The common feature among the catalytic Mn and Co oxides is not only that Mn and Co are in the trivalent state, but Co(3+) in the Co oxides is in the intermediate t2g(5)e(g)(1) state whereas Mn(3+) is in the t2g(3e(g)(1) state. The presence of the e(g)(1) electron in these Mn and Co oxides is considered to play a crucial role in the photocatalytic properties of the oxides.

  7. The transcriptomic G1-G6 signature of hepatocellular carcinoma in an Asian population: Association of G3 with microvascular invasion.

    Science.gov (United States)

    Allen, John Carson; Nault, Jean-Charles; Zhu, Guili; Khor, Andrew Yu Keat; Liu, Jin; Lim, Tony Kiat Hon; Zucman-Rossi, Jessica; Chow, Pierce K H

    2016-11-01

    In this study, a transcriptomic group classification based on a European population is tested on a Singapore cohort. The results highlight the genotype/phenotype correlation in a Southeast Asian population. The G1-G6 transcriptomic classification derived from hepatocellular carcinoma (HCC) resected from European patients, robustly reflected group-specific clinical/pathological features. We investigated the application of this molecular classification in Southeast Asian HCC patients.Gene expression analysis was carried out on HCC surgically resected in Singapore patients who were grouped into G1-G6 transcriptomic categories according to expression of 16 predictor genes (illustrated in Supplementary Table 1, http://links.lww.com/MD/B413 and Supplementary Fig. 1, http://links.lww.com/MD/B413) using quantitative reverse transcription polymerase chain reaction (RT-PCR). Univariate and multivariate polytomous logistic regression was used to investigate association between clinical variables and pooled transcriptomic classes G12, G3, and G456.HCC from Singapore (n = 82) were distributed (%) into G1 (13.4), G2 (24.4), G3 (15.9), G4 (24.4), G5 (14.6), and G6 (7.3) subgroups. Compared to the European data, the Singapore samples were relatively enriched in G1-G3 versus G4-G6 tumors (53.7% vs 46.3%) reflecting the higher proportion of hepatitis B virus (HBV) patients in Singapore versus Europe samples (43% vs 30%). Pooled classes were defined as G12, G3, and G456. G12 was associated with higher alpha-fetoprotein (AFP) concentrations (OR = 1.69, 95% CI: 1.30-2.20; P Singapore cohorts were generally similar relative to associations between transcriptomic groups and clinical features. This lends credence to the G1-G6 transcriptomic classifications being applicable regardless of the ethnic origin of HCC patients. The G3 group was associated with microvascular invasion and holds potential for investigation into the underlying mechanisms and selection for therapeutic

  8. G0 Seed Potential of The Aeroponics Potatoes Seed In The Lowlands With A Root Zone Cooling Into G1 In The Highlands

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    Eni Sumarni

    2016-04-01

    Full Text Available Abstract. In tropical country likes in Indonesia, potato seeds that originated from temperate zone can only be produced in low temperature of highland. Besides this way has many limitation of productivity, it often causes soil erosion. To minimize environment destroying risk tuber seed production in lowland is a challenge. This research was done to trace that modified root zone cooling method of aerophonic system can be applied to produce high quality of tuber seeds in lowland. The First Generations (G0 of var. Atlantic and var. Granola were used as plant materials, and randomized block design (RBD with four replications was applied in this research. Data regarding with vegetative as well as tuber production parameters were analyzed using Coefficient of variance (ANOVA and continued with the least significant difference test (LSD; p = 5%. The results showed that aerophonic generated seeds (G0 had vigorous growth and could produce the normal G1. In term of tuber yield component and number of leaves var. Atlantic showed higher than var. Granola did. The comparison of seed weight between G0 and G1 was about 10 grams and 54 g on average, respectively. Since the size and weight of such G1 could be categorized as Large (L in term of commercial seed market, It’s implied that the lowland modified aerophonic system could be nominated as a prospective method for producing G0 tuber seed in the future.    Potensi Bibit G0 Dari Bibit Kentang Aeroponik Di Dataran Rendah Dengan Akar Zona Pendingin Menjadi G1 Di Dataran Tinggi  Abstrak. Di negara tropis seperti di Indonesia, bibit kentang yang berasal dari zona sedang hanya dapat diproduksi pada suhu rendah di dataran tinggi. Selain itu cara ini memiliki banyak keterbatasan produktivitas dan sering menyebabkan erosi tanah. Meminimalkan resiko dampak kerusakan lingkungan akibat produksi benih umbi di dataran rendah adalah sebuah tantangan. Penelitian ini dilakukan untuk mengkaji bahwa metode zona akar

  9. HPLC法测定150种中药材中黄曲霉毒素G2、G1、B2、B1的含量%Determination of Aflatoxin G2,G1,B2 and B1 in 150 Chinese Herbs by HPLC

    Institute of Scientific and Technical Information of China (English)

    郭巧技; 高咏莉; 王淑红

    2012-01-01

    Objective: To establish an HPLC method for the determination of aflatoxin G2 , G1 , B2 and B1 in 150 Chinese herbs. Method: After extracted by 70% methanol and purified by immunoafinity column, the aflatoxins were determined by fluorescence detection. Result: The calibration curves for aflatoxin G2 and B2 were linear within the range of 0. 15-6.00 ng · ml-1 , and those for aflatoxin G1 and B1 were linear within the range of 0. 5-20.00 ng · ml-1 . The recoveries were within the range of 85. 6% -92. 0% . Conclusion : The method is reliable, accurate and specific, and can be used in the determination of aflatoxin G2 , G1 , B2 and B1.%目的:建立了HPLC法测定150种中药材中的黄曲霉毒素G2、G1、B2、B1含量.方法:样品经70% 甲醇提取、免疫亲和色谱柱净化后,用HPLC-柱后衍生-荧光检测器测定.结果:黄曲霉毒素G2、B2在0.15~6.00 ng·ml-1范围内,黄曲霉毒素G1、B1在0.5~20.00 ng·ml-1范围内线性关系良好.回收率为85.6%~92.0%.结论:本法操作简便,结果准确、重复性好,可用于中药材中黄曲霉毒素G2、G1、B2、B1的测定.

  10. Correlation between Progesterone Dependent Cyclin G1 and PRA/PRB Expression in Endometrial Adenocarcinoma and the Related Clinical Significance%子宫内膜腺癌中孕激素依赖的cyclin G1与PRA/PRB表达的相关性及临床意义

    Institute of Scientific and Technical Information of China (English)

    方明; 于海礼; 袁东智; 徐倩; 张金虎; 何亚平; 岳利民

    2011-01-01

    Objective : To study the correlation hetween cyclin G1 and progesterone receptor isoforms PRA / PRB in endometrial adenocarcinoma in order to explore the reason for the low expression of cyclin G1 in this kind of disease. Methods : Immunohistochemistry was used to test the expression of cyclin G1 and progesterone receptor PRA / PRB in 48 cases of adenocarcinoma of endometrium including 17 cases of well-differentiated carcinoma, 19 cases of mid-differentiated carcinoma and 12 cases of poor-differentiated carcinoma. The correlation between cyclin G1 protein expression and PRA or PRB expression was analyzed. Results: In well. mid and poor differentiated adenocarcinoma of endometrium, PRA positive rates were 88. 2% ( 15/17 ), 79. 0% ( 15/19 ) and 66. 7%( 8/12 )respectively. Statistical analysis showed that there was no correlation between PRA expression and histological grade of endometrial adenocarcinoma( P>0. 05 ); PRB positive rates were 47. 1%( 8/17 ), 15. 8%( 3/19 )and 8. 3%( 1/12 ) respectively and cyclin G1 positive rates were 35. 3% ( 6/17 ), 10. 5% ( 2/19 ) and 0% ( 0/12 )respectively. The expression of both PRB and cyclin Gl were positively correlated with histological grade of endometrialadenocarcinoma( P < 0. 05 ). There was no correlation hetweencyclin G1 expression and PRA while relationship was found between cyclin G1 expression and PRB( P < 0. 05 ). Conclusion : In endometrial adenocarcinoma, the expressions of PRB and cyclin Gl protein decrease with the descending of tumor histological grade , and the expressions of both proteins are positively correlated. Thus it can be deduced that low expression of progesterone dependent cyclin G1 may he related to low expression of PRB in endometrial adenocarcinoma.%目的:探讨孕激素依赖的cyclin G1与孕激素受体亚型PRA和PRB在子宫内膜腺癌中表达的相关性及cyclin G1在子宫内膜腺癌中低表达的原因.方法:采用免疫组化SP法分别检测48例子宫内

  11. Cell cycle arrest by prostaglandin A1 at the G1/S phase interface with up-regulation of oncogenes in S-49 cyc- cells

    Science.gov (United States)

    Hughes-Fulford, M.

    1994-01-01

    Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the -49 lymphoma variant (cyc-) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc- cells. DNA synthesis is inhibited 42% by dmPGA1 (50 microM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the alpha, beta unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc- cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30-50 microns) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc- cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block.(ABSTRACT TRUNCATED AT 250 WORDS).

  12. 1-(2-Hydroxy-5-methylphenyl-3-phenyl-1,3-propanedione Induces G1 Cell Cycle Arrest and Autophagy in HeLa Cervical Cancer Cells

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    Jie-Heng Tsai

    2016-08-01

    Full Text Available The natural agent, 1-(2-hydroxy-5-methylphenyl-3-phenyl-1,3-propanedione (HMDB, has been reported to have growth inhibitory effects on several human cancer cells. However, the role of HMDB in cervical cancer remains unclear. Herein, we found that HMDB dose- and time-dependently inhibited growth of HeLa cervical cancer cells, accompanied with G1 cell cycle arrest. HMDB decreased protein expression of cyclins D1/D3/E and cyclin-dependent kinases (CDKs 2/4/6 and reciprocally increased mRNA and protein levels of CDK inhibitors (p15, p16, p21, and p27, thereby leading to the accumulation of hypophosphorylated retinoblastoma (Rb protein. HMDB also triggered the accumulation of acidic vesicles and formation of microtubule-associated protein-light chain 3 (LC3, followed by increased expression of LC3 and Beclin-1 and decreased expression of p62, suggesting that HMDB triggered autophagy in HeLa cells. Meanwhile, suppression of the expression of survivin and Bcl-2 implied that HMDB-induced autophagy is tightly linked to apoptosis. Exploring the action mechanism, HMDB induced autophagy via the modulation of AMP-activated protein kinase (AMPK and mTOR signaling pathway rather than the class III phosphatidylinositol 3-kinase pathway. These results suggest that HMDB inhibits HeLa cell growth by eliciting a G1 arrest through modulation of G1 cell cycle regulators and by concomitantly inducing autophagy through the mediation of AMPK-mTOR and Akt-mTOR pathways, and may be a promising antitumor agent against cervical cancer.

  13. 1-(2-Hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione Induces G1 Cell Cycle Arrest and Autophagy in HeLa Cervical Cancer Cells.

    Science.gov (United States)

    Tsai, Jie-Heng; Hsu, Li-Sung; Huang, Hsiu-Chen; Lin, Chih-Li; Pan, Min-Hsiung; Hong, Hui-Mei; Chen, Wei-Jen

    2016-08-05

    The natural agent, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB), has been reported to have growth inhibitory effects on several human cancer cells. However, the role of HMDB in cervical cancer remains unclear. Herein, we found that HMDB dose- and time-dependently inhibited growth of HeLa cervical cancer cells, accompanied with G1 cell cycle arrest. HMDB decreased protein expression of cyclins D1/D3/E and cyclin-dependent kinases (CDKs) 2/4/6 and reciprocally increased mRNA and protein levels of CDK inhibitors (p15, p16, p21, and p27), thereby leading to the accumulation of hypophosphorylated retinoblastoma (Rb) protein. HMDB also triggered the accumulation of acidic vesicles and formation of microtubule-associated protein-light chain 3 (LC3), followed by increased expression of LC3 and Beclin-1 and decreased expression of p62, suggesting that HMDB triggered autophagy in HeLa cells. Meanwhile, suppression of the expression of survivin and Bcl-2 implied that HMDB-induced autophagy is tightly linked to apoptosis. Exploring the action mechanism, HMDB induced autophagy via the modulation of AMP-activated protein kinase (AMPK) and mTOR signaling pathway rather than the class III phosphatidylinositol 3-kinase pathway. These results suggest that HMDB inhibits HeLa cell growth by eliciting a G1 arrest through modulation of G1 cell cycle regulators and by concomitantly inducing autophagy through the mediation of AMPK-mTOR and Akt-mTOR pathways, and may be a promising antitumor agent against cervical cancer.

  14. FC-TRIPLEX Chagas/Leish IgG1: a multiplexed flow cytometry method for differential serological diagnosis of chagas disease and leishmaniasis.

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    Andréa Teixeira-Carvalho

    Full Text Available Differential serological diagnosis of Chagas disease and leishmaniasis is difficult owing to cross-reactivity resulting from the fact that the parasites that cause these pathologies share antigenic epitopes. Even with optimized serological assays that use parasite-specific recombinant antigens, inconclusive test results continue to be a problem. Therefore, new serological tests with high sensitivity and specificity are needed. In the present work, we developed and evaluated the performance of a new flow cytometric serological method, referred to as FC-TRIPLEX Chagas/Leish IgG1, for the all-in-one classification of inconclusive tests. The method uses antigens for the detection of visceral leishmaniasis, localized cutaneous leishmaniasis, and Chagas disease and is based on an inverted detuned algorithm for analysis of anti-Trypanosomatidae IgG1 reactivity. First, parasites were label with fluorescein isothiocyanate or Alexa Fluor 647 at various concentrations. Then serum samples were serially diluted, the dilutions were incubated with suspensions of mixed labeled parasites, and flow cytometric measurements were performed to determine percentages of positive fluorescent parasites. Using the new method, we obtained correct results for 76 of 80 analyzed serum samples (95% overall performance, underscoring the outstanding performance of the method. Moreover, we found that the fluorescently labeled parasite suspensions were stable during storage at room temperature, 4 °C, and -20 °C for 1 year. In addition, two different lots of parasite suspensions showed equivalent antigen recognition; that is, the two lots showed equivalent categorical segregation of anti-Trypanosomatidae IgG1 reactivity at selected serum dilutions. In conclusion, we have developed a sensitive and selective method for differential diagnosis of Chagas disease, visceral leishmaniasis, and localized cutaneous leishmaniasis.

  15. 1-(2-Hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione Induces G1 Cell Cycle Arrest and Autophagy in HeLa Cervical Cancer Cells

    Science.gov (United States)

    Tsai, Jie-Heng; Hsu, Li-Sung; Huang, Hsiu-Chen; Lin, Chih-Li; Pan, Min-Hsiung; Hong, Hui-Mei; Chen, Wei-Jen

    2016-01-01

    The natural agent, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB), has been reported to have growth inhibitory effects on several human cancer cells. However, the role of HMDB in cervical cancer remains unclear. Herein, we found that HMDB dose- and time-dependently inhibited growth of HeLa cervical cancer cells, accompanied with G1 cell cycle arrest. HMDB decreased protein expression of cyclins D1/D3/E and cyclin-dependent kinases (CDKs) 2/4/6 and reciprocally increased mRNA and protein levels of CDK inhibitors (p15, p16, p21, and p27), thereby leading to the accumulation of hypophosphorylated retinoblastoma (Rb) protein. HMDB also triggered the accumulation of acidic vesicles and formation of microtubule-associated protein-light chain 3 (LC3), followed by increased expression of LC3 and Beclin-1 and decreased expression of p62, suggesting that HMDB triggered autophagy in HeLa cells. Meanwhile, suppression of the expression of survivin and Bcl-2 implied that HMDB-induced autophagy is tightly linked to apoptosis. Exploring the action mechanism, HMDB induced autophagy via the modulation of AMP-activated protein kinase (AMPK) and mTOR signaling pathway rather than the class III phosphatidylinositol 3-kinase pathway. These results suggest that HMDB inhibits HeLa cell growth by eliciting a G1 arrest through modulation of G1 cell cycle regulators and by concomitantly inducing autophagy through the mediation of AMPK-mTOR and Akt-mTOR pathways, and may be a promising antitumor agent against cervical cancer. PMID:27527160

  16. Allergen-specific regulation of allergic rhinitis in mice by intranasal exposure to IgG1 monoclonal antibody Fab fragments against pathogenic allergen.

    Science.gov (United States)

    Matsuoka, Daiko; Mizutani, Nobuaki; Sae-Wong, Chutha; Yoshino, Shin

    2014-09-01

    Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28-30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1-10) with papain were also intranasally administered 15min before each OVA challenge. The results showed that treatment with O1-10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1-10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen.

  17. Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats.

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    Jewell A Jessup

    Full Text Available INTRODUCTION: The G protein-coupled estrogen receptor (GPER is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days or vehicle (VEH, DMSO/EtOH on cardiac function and structure. METHODS: Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS diet or a high salt (4% sodium; HS diet for 10 weeks beginning at 5 weeks of age. RESULTS: Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope, increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e'] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05 as determined by tissue Doppler. CONCLUSION: Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.

  18. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Hung, Chein-Hui [Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Puizi City, Chiayi 613, Taiwan, ROC (China); Chang, Nai Wen [Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, ROC (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China)

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  19. Clearance of human IgG1-sensitised red blood cells in vivo in humans relates to the in vitro properties of antibodies from alternative cell lines.

    Directory of Open Access Journals (Sweden)

    Kathryn L Armour

    Full Text Available We previously produced a recombinant version of the human anti-RhD antibody Fog-1 in the rat myeloma cell line, YB2/0. When human, autologous RhD-positive red blood cells (RBC were sensitised with this IgG1 antibody and re-injected, they were cleared much more rapidly from the circulation than had been seen earlier with the original human-mouse heterohybridoma-produced Fog-1. Since the IgG have the same amino acid sequence, this disparity is likely to be due to alternative glycosylation that results from the rat and mouse cell lines. By comparing the in vitro properties of YB2/0-produced Fog-1 IgG1 and the same antibody produced in the mouse myeloma cell line NS0, we now have a unique opportunity to pinpoint the cause of the difference in ability to clear RBC in vivo. Using transfected cell lines that express single human FcγR, we showed that IgG1 made in YB2/0 and NS0 cell lines bound equally well to receptors of the FcγRI and FcγRII classes but that the YB2/0 antibody was superior in FcγRIII binding. When measuring complexed IgG binding, the difference was 45-fold for FcγRIIIa 158F, 20-fold for FcγRIIIa 158V and approximately 40-fold for FcγRIIIb. The dissimilarity was greater at 100-fold in monomeric IgG binding assays with FcγRIIIa. When used to sensitise RBC, the YB2/0 IgG1 generated 100-fold greater human NK cell antibody-dependent cell-mediated cytotoxicity and had a 103-fold advantage over the NS0 antibody in activating NK cells, as detected by CD54 levels. In assays of monocyte activation and macrophage adherence/phagocytosis, where FcγRI plays major roles, RBC sensitised with the two antibodies produced much more similar results. Thus, the alternative glycosylation profiles of the Fog-1 antibodies affect only FcγRIII binding and FcγRIII-mediated functions. Relating this to the in vivo studies confirms the importance of FcγRIII in RBC clearance.

  20. Three-dimensional parton distribution functions $g_{1T}$ and $h_{1L}^\\perp$ in the polarized proton-antiproton Drell-Yan process

    CERN Document Server

    Zhu, Jiacai

    2011-01-01

    We present predictions of the unweighted and weighted double spin asymmetries related to the transversal helicity distribution $g_{1T}$ and the longitudinal transversity distribution $h_{1L}^\\perp$, two of eight leading-twist transverse momentum dependent parton distributions (TMDs) or 3-dimensional parton distribution functions (3dPDFs), in the polarized proton-antiproton Drell-Yan process at typical kinematics on the Facility for Antiproton and Ion Research (FAIR). We conclude that FAIR is ideal to access the new 3dPDFs towards a detailed picture of the nucleon structure.

  1. Circadian variation in expression of G1 phase cyclins D1 and E and cyclin-dependent kinase inhibitors p16 and p21 in human bowel mucosa

    Institute of Scientific and Technical Information of China (English)

    John Griniatsos; George Marinos; John Bramis; Panayiotis O Michail; Othon P Michail; Stamatios Theocharis; Antonios Arvelakis; Ioannis Papaconstantinou; Evangelos Felekouras; Emmanouel Pikoulis; Ioannis Karavokyros; Chris Bakoyiannis

    2006-01-01

    AIM: To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm.METHODS: Between January 2003 and December 2004,twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism,underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalinfixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours (00:00,06:00, 12:00, 18:00 and 24:00), we studied the expression of G1 phase cydins (D1 and E) as well as the expression of the G1 phase cyclin-dependent kinase (CDK)inhibitors p16 and p21 as indicators of cell cycle progression in colonic epithelial cells using immunohistochemical methods.RESULTS: The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00:00 and 18:00, respectively (P< 0.001).A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12:00 and 18:00 (P<0.001), respectively. When the complexes cyclins D1-p21 and E-p21were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D1-p16 and E-p16were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00:00, 06:00and 24:00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18:00.CONCLUSION: Colonic epithelial cells seem to enter the G1 phase of the cell cycle during afternoon (between 12:00 and 18:00) with the highest rates obtained at 18:00. From a clinical point of view, the present results suggest that G1-phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.

  2. S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and distributed multipoles. Proof of concept and first applications to metal cations.

    Science.gov (United States)

    Chaudret, Robin; Gresh, Nohad; Narth, Christophe; Lagardère, Louis; Darden, Thomas A; Cisneros, G Andrés; Piquemal, Jean-Philip

    2014-09-04

    We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar

  3. Situation analysis of physical independence of the equipment and safety circuits of Almaraz NPP regarding R.G. 1.75 rev.3 (2005); Analisis de la situacion de la independencia fisica de los equipos y circuitos electricos de seguridad de C. N. Almaraz respecto a la R. G. 1.75 rev 3 (2005)

    Energy Technology Data Exchange (ETDEWEB)

    Seijas Portela, S.

    2010-07-01

    Situation analysis of physical independence of the electrical equipment and circuits CN safety Almaraz about R.G. 1.75 rev. 3. (2005) The aim of this paper is to present the work done in the analysis of the physical separation of redundant safety electrical equipment (emergency diesel generators, medium voltage, electrical cabinets, etc.) and physical separation of circuits and electrical conduits.

  4. Study of the extraction of residual heat for a steam generator in the presence of incondensables modeling with TRACE: PKL experiment III G1.1; Estudio de la extraccion del calor residual por un generador de vapor en presencia de incondensables modelado con TRACE: experimento PKL III G1.1

    Energy Technology Data Exchange (ETDEWEB)

    Berna, C.; Escriva, A.; Munuz-Cobo, J. L.; Romero, A.

    2012-07-01

    This paper made the simulation of the PKL III G1.1 experiment using SNAP interface and the TRACE code. This experiment aims to essentially the study of the extraction of the residual heat of the steam generator in the presence of gases incondensables.

  5. The Queue Mξ/G/1 with Different Arrival Rates on the Multiple Adaptive Vacations and Setup Times%具有不同到达率的带有启动时间的多级适应性休假Mξ/G/1排队模型

    Institute of Scientific and Technical Information of China (English)

    孙微; 李世勇; 田乃硕

    2007-01-01

    In this paper, we discuss the queue Mξ/G/1 with different arrival rates on the multiple adaptive vacations and setup times. We derive the probability generating function (p.g.f.)of the steady-state queue length by the method of embedded Markov chain and the Laplace-Stieltjes transform (LST)of the steady-state waiting time (FCFS). From the results, we obtain the conclusion that the steady-state queue length and waiting time have the property of stochastic decomposition. And we also get the LST of busy period and give several special cases. Many discussed models as to Mξ/G/1 are special cases of the model.%本文研究具有不同到达率的带有启动时间的多级适应性休假Mξ/G/1排队模型,应用嵌入马尔可夫链方法推导出了稳态队长和等待时间(先到先服务规则)分布,并验证了稳态队长和稳态等待时间具有随机分解性,而且给出了忙期分布.许多关于Mξ/G/1的排队模型都可以看作是此模型的特例.

  6. Overexpression of the promyelocytic leukemia gene suppresses growth of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis

    Institute of Scientific and Technical Information of China (English)

    HE Dalin 贺大林; NAN Xunyi 南勋义; Chang Kun-Song; WANG Yafeng 王亚峰; Chung Leland W.K.

    2003-01-01

    Objectives To examine the anti-oncogenic effects of promyelocytic leukemia (PML) on bladder cancer and to explore its molecular mechanisms of growth suppression.Methods Wild-type PML was transfected into bladder cancer cells (5637 cell) and expressed in a replication-deficient adenovirus-mediated gene delivery system and introduced into human bladder cancer cells (5637 cell) in vitro and in vivo. The effect and mechanisms of the PML gene in cell growth, clonogenicity, and tumorigenicity of bladder cancer cells were studied using in vitro and in vivo growth assays, soft agar colony-forming assay, cell cycle analysis, apoptosis assay and in vivo tumorigenicity assay.Results Overexpression of PML in 5637 cells significantly reduced their growth rate and clonogenicity on soft agar. PML suppressed bladder cancer cell growth by inducing G1 cell cycle arrest and apoptosis. Adenovirus-mediated PML (Ad-PML) significantly suppressed the tumorigenicity and growth of bladder cancer cells. Intratumoral injection of Ad-PML into tumors induced by 5637 cells dramatically suppressed their growth. Conclusions The results indicated that overexpression of PML protein may promote efficient growth inhibition of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis, and adenovirus-mediated PML (Ad-PML) expression efficiently suppresses human bladder cancer growth.

  7. Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

    Science.gov (United States)

    Davidsson, Pia; Söderling, Ann-Sofi; Svensson, Lena; Ahnmark, Andrea; Flodin, Christine; Wanag, Ewa; Screpanti-Sundqvist, Valentina; Gennemark, Peter

    2015-05-01

    Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax ) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. ROLE OF PI3K-AKT-mTOR AND Wnt SIGNALING PATHWAYS IN G1-S TRANSITION OF CELL CYCLE IN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    LAKSHMIPATHI eVADLAKONDA

    2013-04-01

    Full Text Available The PI3K–Akt pathway together with one of its downstream targets, the mechanistic target of rapamycin (mTOR is a highly deregulated pathway in cancers. There is a reciprocal relation between the Akt phosphorylation and mTOR complexes. Akt phosphorylated at T308 activates mTORC1 by inhibition of the tuberous sclerosis complex (TSC1/2, where as mTORC2 is recognized as the kinase that phosphorylates Akt at S473. Recent developments in the research on regulatory mechanisms of autophagy places mTORC1 mediated inhibition of autophagy at the central position in activation of proliferation and survival pathways in cells. Autophagy is a negative regulator of Wnt signaling pathway and the downstream effectors of Wnt signaling pathway, cyclin D1 and the c-Myc, are the key players in initiation of cell cycle and regulation of the G1-S transition in cancer cells. Production of reaction oxygen species (ROS, a common feature of a cancer cell metabolism, activates several downstream targets like the transcription factors FoxO, which play key roles in promoting the progression of cell cycle. A model is presented on the role of PI3K -Akt - mTOR and Wnt pathways in regulation of the progression of cell cycle through Go-G1-and S phases.

  9. Roscovitine treatment improves synchronization of donor cell cycle in G0/G1 stage and in vitro development of handmade cloned buffalo (Bubalus bubalis) embryos.

    Science.gov (United States)

    Selokar, Naresh L; Saini, Monika; Muzaffer, Mushariffa; Krishnakanth, G; Saha, Ambika P; Chauhan, Manmohan S; Manik, Radheysham; Palta, Prabhat; Madan, Pavneesh; Singla, Suresh K

    2012-04-01

    This study investigated the effects of serum-starvation, total confluence, and roscovitine treatment on cell-cycle synchronization of buffalo ear skin fibroblasts to the G0/G1 stage and on the developmental competence of cloned embryos. Serum starvation of total confluence cultures for 24 h had a higher (proscovitine treatment than that with 10 μM (94.4, 96.4, and 86.6%, respectively), which was similar to that for total confluence (86.0%). MTT assay showed that cell viability decreased as dose of roscovitine increased. The blastocyst rate was significantly higher (proscovitine-treated (20 and 30 μM) groups (48.8, 48.9, 57.9, and 62.9%, respectively) compared to nontreated cyclic cells (20.2%). However, the cleavage rate and total cell number of cloned embryos were similar for all the groups. The number of ICM cells was improved by 30 μM roscovitine treatment (45.25 ± 2.34). The cryosurvival rate of blastocysts derived from cells synchronized with 20 or 30 μM roscovitine was higher compared to that for total confluence group (33.6, 37.8 vs. 23.8%). In conclusion, treatment with 30 μM roscovitine is optimal for harvesting G0/G1 stage cells for producing high quality cloned buffalo embryos, and that it is better than serum-starvation or total confluence for cell synchronization.

  10. Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes.

    Directory of Open Access Journals (Sweden)

    Monika Sharma

    Full Text Available BACKGROUND: Cystic echinococcosis (CE caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s of the parasite responsible for human hydatidosis in North India. METHODOLOGY/PRINCIPAL FINDINGS: To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1 sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32 were found to be infected with hydatid cyst of either G3 (53.1% or G1 (40.62% genotype and one each of G5 (cattle strain and G6 (camel strain genotype. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate the zoonotic potential of G1 (sheep strain and G3 (buffalo strain genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain in an Asian country and presence of G6 genotype (camel strain in India. The results may have important implications in the planning of control strategies for human hydatidosis.

  11. 7-Epiclusianone, a Benzophenone Extracted from Garcinia brasiliensis (Clusiaceae), Induces Cell Cycle Arrest in G1/S Transition in A549 Cells.

    Science.gov (United States)

    Ionta, Marisa; Ferreira-Silva, Guilherme A; Niero, Evandro L; Costa, Éderson D'Martin; Martens, Adam A; Rosa, Welton; Soares, Marisi G; Machado-Santelli, Gláucia M; Lago, João Henrique G; Santos, Marcelo H

    2015-07-15

    Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 μM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies.

  12. Effects of Cyclin D1 Antisense Oligodeoxyneucleotides on the Growth and Expression of G1 Phase Regulators in Gastric Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    帅晓明; 韩高雄; 王国斌

    2003-01-01

    To investigate the effects of Cyclin D1 antisense oligodeoxyneucleotides (ASODN) on the growth, cell cycle progression and expression of G1 phase regulators in human gastric carcinoma cell lines SGC7901 and HS746T, phosphorothioate-modified Cyclin D1 ASODN were encapsulated by LipofectAMINE2000 and transfected into gastric carcinoma cells. Dose-dependent inhibitory effects were induced by Cyclin D1 ASODN in two gastric carcinoma cell lines. Treatment of gastric carcinoma cells with 0.2 μmol/L Cyclin D1 ASODN for 24 h could significantly inhibit their growth in vitro and in vivo, reduce expression of Cyclin DlmRNA to 26.3 % (SGC7901) and 17.3 %(HS746T) respectively. The percentage of cells in G0/G1 phase was increased as revealed by flow cytometry. Immunohistochemical staining showed that the expression of p21 was increased and the expression of Cyclin D1 and pRb was decreased in the two cell lines; the expression of p27 was increased in HS746T, but unchanged in SGC7901. Cyclin D1 ASODN could inhibit the growth and the expression of Cyclin D1 mRNA in gastric carcinoma cells, influence the cell cycle and expression of its regulators.

  13. Comparison of Saanen x Hair Goat Crossbred (F1, G1 and Hair Goat Raised at The Farm Conditions in Terms of Milk Yield Characteristics

    Directory of Open Access Journals (Sweden)

    Hilal Tozlu Çelik

    2015-01-01

    Full Text Available This study was conducted to determine milk yield characteristics and its effect on genotypes, years and ages Hair goat x Saanen crossbred and Hair goat breed between 2011-2012 years in private enterprise which is located in Amasya province Sarılar village. In this study, the effect of genotypes was found significant on average daily milk yield, lactation length and lactation milk yield in 2011 and 2012 years. In 2011, the effect of goat ages were determined on average daily milk yield (ADMY and lactation milk yield (LMY for all goat genotypes. In 2012, the effect of goat ages was determined on average daily milk yield and lactation length (LL for all goat genotypes. The effect of year F1 and Hair goat were found significant on ADMY, LMY, and LL. The effect of year was found significant on only LL for G1 genotype. As a result it can be say that Saanen goat x Hair goat crossbred F1 and G1 genotype milk yield was higher than Hair goat reared in farmer conditions.

  14. Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding

    Energy Technology Data Exchange (ETDEWEB)

    Oganesyan, Vaheh, E-mail: oganesyanv@medimmune.com; Mazor, Yariv; Yang, Chunning; Cook, Kimberly E.; Woods, Robert M. [MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878 (United States); Ferguson, Andrew [AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Mailstop E3, Waltham, MA 02451 (United States); Bowen, Michael A.; Martin, Tom; Zhu, Jie; Wu, Herren; Dall’Acqua, William F., E-mail: oganesyanv@medimmune.com [MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878 (United States)

    2015-10-31

    In an effort to identify the critical structural features responsible for the high-affinity interaction of IgG1 Fc with FcγRI, the structure of the corresponding complex was solved at a resolution of 2.4 Å. The three-dimensional structure of a human IgG1 Fc fragment bound to wild-type human FcγRI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 Å using molecular replacement; this is the highest resolution achieved for an unmutated FcγRI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of FcγRI. It also explains the long-known major energetic contribution of the Fc ‘LLGG’ motif at positions 234–237, and particularly of Leu235, via a ‘lock-and-key’ mechanism. Finally, a previously held belief is corrected and a differing view is offered on the recently proposed direct role of Fc carbohydrates in the corresponding interaction. Structural evidence is provided that such glycan-related effects are strictly indirect.

  15. Evaluation of the nature, origin and potentiality of the subsurface Middle Jurassic and Lower Cretaceous source rocks in Melleiha G-1x well, North Western Desert, Egypt

    Directory of Open Access Journals (Sweden)

    Mohamed M. El Nady

    2015-09-01

    Full Text Available The present work aims to evaluate the nature and origin of the source rock potentiality of subsurface Middle Jurassic and Lower Cretaceous source rocks in Melleiha G-1x well. This target was achieved throughout the evaluation of total organic carbon, rock Eval pyrolysis and vitrinite reflectance for fifteen cutting samples and three extract samples collected from Khatatba, Alam El Bueib and Kharita formations in the studied well. The result revealed that the main hydrocarbon of source rocks, for the Middle Jurassic (Khatatba Fm. is mainly mature, and has good capability of producing oil and minor gas. Lower Cretaceous source rocks (Alam El Bueib Fm. are mature, derived from mixed organic sources and have fair to good capability to generate gas and oil. Kharita Formation of immature source rocks originated from terrestrial origin and has poor to fair potential to produce gas. This indicates that Khatatba and Alam El Bueib formations take the direction of increasing maturity far away from the direction of biodegradation and can be considered as effective source potential in the Melleiha G-1x well.

  16. Ursolic acid benzaldehyde chalcone leads to inhibition of cell proliferation and arrests cycle in G1/G0 phase in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Yan Jia

    2015-06-01

    Full Text Available In the present study, the effect of ursolic acid benzaldehyde chalcone (UABC on ovarian carcinoma cells was studied. The results revealed that ovarian carcinoma cells on UABC treatment increased Sub-G1 cell population, increased rate of cell apoptosis and morphological changes in mitochondrial membrane. In OVCAR 432 cells treatment with UABC increased the Sub-G1 cell population to 72.3% and growth inhibition rate of >72%. Treatment with 20 µM of UABC for 48 hours, led to an induction of apoptosis in 67.2% and induced morphological changes in OVCAR 432 cells. The Western blot results showed high concentration of cytochrome c in the cell cytosol after 48 hours of UABC treatment. Treatment of RMS-13 cells with UABC resulted in inhibition of GLI1, GLI2, PTCH1, and IGF2 genes. In addition, we found a significant reduction in hedgehog activity of RMS-13 cells after UABC treatment by means of a hedgehog-responsive reporter assay. Therefore, UABC can be a promising agent for the treatment of ovarian carcinoma.

  17. Human IgG1 Cγ1 Domain Is Crucial for the Bioactivity of the Engineered Anti-CD20 Antibodies

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Jiannan Feng; Yan Li; Xianjiang Kang; Yingxun Sun; Xin Gu; Ying Huang; Hong Chang; Beifen Shen

    2007-01-01

    In this study, we discussed the necessity of human IgG1 Cγ1 domain for recombinant antibody using computeraided homology modeling method and experimental studies. The heavy (VH) and light (VL) chain variable regions of 1-28, a murine IgM-type anti-CD20 mAb, were ligated by linker peptide (Gly4Ser)3 to form the single-chain Fv fragment (scFv). Then, the engineered antibody (LH1-3) was generated by fusing scFv with the entire IgG1 heavy constant regions. The 3-D structure of LH1-3 was modeled using computer-aided homology modeling method and the binding activity of LH1-3 was evaluated theoretically. Compared to the 3-D structure of the Fv fragment of the parent antibody, the conformation of the active pocket of LH1-3 was remained because of the rigid support of Cγ1.Further experimental results of flow cytometry showed that the engineered anti-CD20 antibody possessed specifically binding activity to CD20-expressing target cells. The anti-CD20 antibody fragments could also mediate complement-dependent cytotoxicity (CDC) of human B-lymphoid cell lines. Our study highlights some interests and advantages of a methodology based on the homology modeling and analysis of molecular structural properties.

  18. Overexpression of p27KIP1 induced cell cycle arrest in G1 phase and subsequent apoptosis in HCC-9204 cell line

    Institute of Scientific and Technical Information of China (English)

    Jiang Li; Wen Liang Wang; Xin Ke Yang; Xin Xin Yu; Yun De Hou; Meng Liang Ge; Jie Zhang

    2000-01-01

    AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-9204 cells. This study is to investigate whether p27KIP1 plays an important role in this process. MEHODS In order to elucidate the exact function of p27KIP1 in this process, a zinc inducible p27KIP1 stable transfectant and transient p27KIP1- GFP fusion transfectant were constructed. The effects of inducible p27KIP1 on cell growth, cell cycle arrest and apoptosis were examined in the mock, control pMD vector, and pMD-KIP1 transfected HCC-9204 cells. RESULTS This p27KIP1-GFP transfectant may transiently express the fusion gene. The cell growth was reduced by 35% at 48 h of p27KIP1 induction with zinc treatment as determined by trypan blue exclusion assay. These differences remained the same after 72 h of p27KIP1 expression, p27KIP1 caused cell cycle arrest after 24 h of induction, with 40% increase in G1 population. Prolonged p27KIP1 expression in this cell line induced apoptotic cell death reflected by TUNEL assay. Fourty-eight h and 72 h of p27KIP1 expression showed a characteristic DNA ladder on agarose gel electrophoresis.

  19. The non-homologous end-joining pathway of S. cerevisiae works effectively in G1-phase cells, and religates cognate ends correctly and non-randomly.

    Science.gov (United States)

    Gao, Shujuan; Honey, Sangeet; Futcher, Bruce; Grollman, Arthur P

    2016-06-01

    DNA double-strand breaks (DSBs) are potentially lethal lesions repaired by two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). Homologous recombination preferentially reunites cognate broken ends. In contrast, non-homologous end-joining could ligate together any two ends, possibly generating dicentric or acentric fragments, leading to inviability. Here, we characterize the yeast NHEJ pathway in populations of pure G1 phase cells, where there is no possibility of repair using a homolog. We show that in G1 yeast cells, NHEJ is a highly effective repair pathway for gamma-ray induced breaks, even when many breaks are present. Pulsed-field gel analysis showed chromosome karyotypes following NHEJ repair of cells from populations with multiple breaks. The number of reciprocal translocations was surprisingly low, perhaps zero, suggesting that NHEJ preferentially re-ligates the "correct" broken ends instead of randomly-chosen ends. Although we do not know the mechanism, the preferential correct ligation is consistent with the idea that broken ends are continuously held together by protein-protein interactions or by larger scale chromatin structure. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Multiple B-cell epitope vaccine induces a Staphylococcus enterotoxin B-specific IgG1 protective response against MRSA infection.

    Science.gov (United States)

    Zhao, Zhuo; Sun, He-Qiang; Wei, Shan-Shan; Li, Bin; Feng, Qiang; Zhu, Jiang; Zeng, Hao; Zou, Quan-Ming; Wu, Chao

    2015-01-01

    No vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has been currently approved for use in humans. Staphylococcus enterotoxin B (SEB) is one of the most potent MRSA exotoxins. In the present study, we evaluated the efficacy and immunologic mechanisms of an SEB multiple B-cell epitope vaccine against MRSA infection. Synthetic overlapping peptide ELISA identified three novel B-cell immunodominant SEB epitopes (in addition to those previously known): SEB31-48, SEB133-150, and SEB193-210. Six B-cell immunodominant epitopes (amino acid residues 31-48, 97-114, 133-150, 193-210, 205-222, and 247-261) were sufficient to induce robust IgG1/IgG2b-specific protective responses against MRSA infection. Therefore, we constructed a recombinant MRSA SEB-specific multiple B-cell epitope vaccine Polypeptides by combining the six SEB immunodominant epitopes and demonstrated its ability to induce a robust SEB-specific IgG1 response to MRSA, as well as a Th2-directing isotype response. Moreover, Polypeptides-induced antisera stimulated synergetic opsonophagocytosis killing of MRSA. Most importantly, Polypeptides was more effective at clearing the bacteria in MRSA-infected mice than the whole SEB antigen, and was able to successfully protect mice from infection by various clinical MRSA isolates. Altogether, these results support further evaluation of the SEB multiple B-cell epitope-vaccine to address MRSA infection in humans.