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Sample records for 10-11 sv bq-1

  1. Molecular cloning, characterization and antigenicity of Babesia sp. BQ1 (Lintan) (Babesia cf. motasi) apical membrane antigen-1 (AMA-1).

    PubMed

    Niu, Qingli; Liu, Zhijie; Yang, Jifei; Guan, Guiquan; Pan, Yuping; Luo, Jianxun; Yin, Hong

    2016-12-12

    Apical membrane antigen-1 (AMA-1) has been described as a potential vaccine candidate in apicomplexan parasites. Here we characterize the ama-1 gene. The full-length ama-1 gene of Babesia sp. BQ1 (Lintan) (BLTAMA-1) is 1785 bp, which contains an open reading frame (ORF) encoding a 65-kDa protein of 594 amino acid residues; by definition, the 5' UTR precedes the first methionine of the ORF. Phylogenetic analysis based on AMA-1 amino acid sequences clearly separated Piroplasmida from other Apicomplexa parasites. The Babesia sp. BQ1 (Lintan) AMA-1 sequence is most closely associated with that of B. ovata and B. bigemina, with high bootstrap value. A recombinant protein encoding a conserved region and containing ectodomains I and II of BLTAMA-1 was constructed. BLTrAMA-1-DI/DII proteins were tested for reactivity with sera from sheep infected by Babesia sp. BQ1 (Lintan). In Western-blot analysis, native Babesia sp. BQ1 (Lintan) AMA-1 proteins were recognized by antibodies raised in rabbits against BLTrAMA-1 in vitro. The results of this study are discussed in terms of gene characterization, taxonomy and antigenicity.

  2. 10 CFR 10.11 - Criteria.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Criteria. 10.11 Section 10.11 Energy NUCLEAR REGULATORY... Restricted Data or National Security Information or an Employment Clearance § 10.11 Criteria. (a) The... indicating poor judgment, unreliabilty, or untrustworthiness. (10) Is a user of alcohol habitually and...

  3. 10 CFR 10.11 - Criteria.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Criteria. 10.11 Section 10.11 Energy NUCLEAR REGULATORY... Restricted Data or National Security Information or an Employment Clearance § 10.11 Criteria. (a) The... indicating poor judgment, unreliabilty, or untrustworthiness. (10) Is a user of alcohol habitually and...

  4. 10 CFR 10.11 - Criteria.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Criteria. 10.11 Section 10.11 Energy NUCLEAR REGULATORY... Restricted Data or National Security Information or an Employment Clearance § 10.11 Criteria. (a) The... indicating poor judgment, unreliabilty, or untrustworthiness. (10) Is a user of alcohol habitually and...

  5. 10 CFR 10.11 - Criteria.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Criteria. 10.11 Section 10.11 Energy NUCLEAR REGULATORY... Restricted Data or National Security Information or an Employment Clearance § 10.11 Criteria. (a) The... indicating poor judgment, unreliabilty, or untrustworthiness. (10) Is a user of alcohol habitually and...

  6. 10 CFR 10.11 - Criteria.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Criteria. 10.11 Section 10.11 Energy NUCLEAR REGULATORY... Restricted Data or National Security Information or an Employment Clearance § 10.11 Criteria. (a) The... indicating poor judgment, unreliabilty, or untrustworthiness. (10) Is a user of alcohol habitually and...

  7. Maintenance Downtime January 10 - 11, 2015

    Atmospheric Science Data Center

    2015-01-05

    ... outage this weekend, January 10-11,  all our external websites hosted on-Center will be impacted. You may experience sporadic accessibility to these websites during the maintenance period. Please plan your data orders and ...

  8. 44 CFR 10.11 - Environmental information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Environmental information. 10... OF HOMELAND SECURITY GENERAL ENVIRONMENTAL CONSIDERATIONS Agency Implementing Procedures § 10.11 Environmental information. Interested persons may contact the Environmental Officer or the...

  9. 44 CFR 10.11 - Environmental information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Environmental information. 10... OF HOMELAND SECURITY GENERAL ENVIRONMENTAL CONSIDERATIONS Agency Implementing Procedures § 10.11 Environmental information. Interested persons may contact the Environmental Officer or the...

  10. 19 CFR 10.11 - General.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... States Components § 10.11 General. (a) Sections 10.12 through 10.23 set forth definitions and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), for American-made fabricated components... impartial and uniform assessment of duties upon merchandise claimed to be partially exempt from duty...

  11. Sequence and organization of the rhoptry-associated-protein-1 (rap-1) locus for the sheep hemoprotozoan Babesia sp. BQ1 Lintan (B. motasi phylogenetic group).

    PubMed

    Niu, Qingli; Bonsergent, Claire; Guan, Guiquan; Yin, Hong; Malandrin, Laurence

    2013-11-15

    Babesiosis is a frequent infection of animals worldwide by tick borne pathogen Babesia, and several species are responsible for ovine babesiosis. Recently, several Babesia motasi-like isolates were described in sheep in China. In this study, we sequenced the multigenic rap-1 gene locus of one of these isolates, Babesia sp. BQ1 Lintan. The RAP-1 proteins are involved in the process of red blood cells invasion and thus represent a potential target for vaccine development. A complex composition and organization of the rap-1 locus was discovered with: (1) the presence of 3 different types of rap-1 sequences (rap-1a, rap-1b and rap-1c); (2) the presence of multiple copies of rap-1a and rap-1b; (3) polymorphism among the rap-1a copies, with two classes (named rap-1a61 and rap-1a67) having a similarity of 95.7%, each class represented by two close variants; (4) polymorphism between rap-1a61-1 and rap-1a61-2 limited to three nucleotide positions; (5) a difference of eight nucleotides between rap-1a67-1 and rap-1a67-2 from position 1270 to the putative stop site of rap-1a67-1 which might produce two putative proteins of slightly different sizes; (6) the ratio of rap-1a copies corresponding to one rap-1a67, one rap-1a61-1 and one rap-1a61-2; (7) the presence of three different intergenic regions separating rap-1a, rap-1b and rap-1c; (8) interspacing of the rap-1a copies with rap-1b copies; and (9) the terminal position of rap-1c in the locus. A 31kb locus composed of 6 rap-1a sequences interspaced with 5 rap-1b sequences and with a terminal rap-1c copy was hypothesized. A strikingly similar sequence composition (rap-1a, rap-1b and rap-1c), as well as strong gene identities and similar locus organization with B. bigemina were found and highlight the conservation of synteny at this locus in this phylogenetic clade.

  12. 1 CFR 10.11 - Scope and sources.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Scope and sources. 10.11 Section 10.11 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER PRESIDENTIAL PAPERS Annual Publication § 10.11 Scope and sources. The basic text of the Public Papers...

  13. 1 CFR 10.11 - Scope and sources.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Scope and sources. 10.11 Section 10.11 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER PRESIDENTIAL PAPERS Annual Publication § 10.11 Scope and sources. The basic text of the Public Papers...

  14. 27 CFR 10.11 - Meaning of terms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Meaning of terms. 10.11 Section 10.11 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS COMMERCIAL BRIBERY Definitions § 10.11 Meaning of terms. As used in this...

  15. 46 CFR 188.10-11 - Chemistry laboratory.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Chemistry laboratory. 188.10-11 Section 188.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 188.10-11 Chemistry laboratory. This term...

  16. 46 CFR 188.10-11 - Chemistry laboratory.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Chemistry laboratory. 188.10-11 Section 188.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 188.10-11 Chemistry laboratory. This term...

  17. 46 CFR 188.10-11 - Chemistry laboratory.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Chemistry laboratory. 188.10-11 Section 188.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 188.10-11 Chemistry laboratory. This term...

  18. 46 CFR 188.10-11 - Chemistry laboratory.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Chemistry laboratory. 188.10-11 Section 188.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 188.10-11 Chemistry laboratory. This term...

  19. 46 CFR 188.10-11 - Chemistry laboratory.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Chemistry laboratory. 188.10-11 Section 188.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 188.10-11 Chemistry laboratory. This term...

  20. 46 CFR 30.10-11 - Coastwise-TB/C.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Coastwise-TB/C. 30.10-11 Section 30.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-11 Coastwise—TB/C. Under this designation shall be included all tank vessels normally navigating the waters of...

  1. 46 CFR 30.10-11 - Coastwise-TB/C.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Coastwise-TB/C. 30.10-11 Section 30.10-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-11 Coastwise—TB/C. Under this designation shall be included all tank vessels normally navigating the waters of...

  2. Heavy ion collision dynamics of 10,11B+10,11B reactions

    NASA Astrophysics Data System (ADS)

    Singh, BirBikram; Kaur, Manpreet; Kaur, Varinderjit; Gupta, Raj K.

    2015-01-01

    The dynamical cluster-decay model (DCM) of Gupta and collaborators has been applied successfully to the decay of very-light (A ˜ 30), light (A ˜ 40-80), medium, heavy and super-heavy mass compound nuclei for their decay to light particles (evaporation residues, ER), fusion-fission (ff), and quasi-fission (qf) depending on the reaction conditions. We intend to extend here the application of DCM to study the extreme case of decay of very-light nuclear systems 20,21,22Ne∗ formed in 10,11B+10,11B reactions, for which experimental data is available for their binary symmetric decay (BSD) cross sections, i.e., σBSD. For the systems under study, the calculations are presented for the σBSD in terms of their preformation and barrier penetration probabilities P0 and P. Interesting results are that in the decay of such lighter systems there is a competing reaction mechanism (specifically, the deep inelastic orbiting of non-compound nucleus (nCN) origin) together with ff. We have emipirically estimated the contribution of σnCN. Moreover, the important role of nuclear structure characteristics via P0 as well as angular momentum ℓ in the reaction dynamics are explored in the study.

  3. 37 CFR 10.11 - Removing names from the register.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... register. 10.11 Section 10.11 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE... from the register. A letter may be addressed to any individual on the register, at the address of which... desires to remain on the register. The name of any individual failing to reply and give any...

  4. 37 CFR 10.11 - Removing names from the register.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... register. 10.11 Section 10.11 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE... from the register. A letter may be addressed to any individual on the register, at the address of which... desires to remain on the register. The name of any individual failing to reply and give any...

  5. 37 CFR 10.11 - Removing names from the register.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... register. 10.11 Section 10.11 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE... from the register. A letter may be addressed to any individual on the register, at the address of which... desires to remain on the register. The name of any individual failing to reply and give any...

  6. 47 CFR 10.11 - CMAS implementation timeline.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false CMAS implementation timeline. 10.11 Section 10.11 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM General... Federal Alert Aggregator and Alert Gateway makes the Government Interface Design specifications available....

  7. RAP-1a is the main rhoptry-associated-protein-1 (RAP-1) recognized during infection with Babesia sp. BQ1 (Lintan) (B. motasi-like phylogenetic group), a pathogen of sheep in China.

    PubMed

    Niu, Qingli; Bonsergent, Claire; Rogniaux, Hélène; Guan, Guiquan; Malandrin, Laurence; Moreau, Emmanuelle

    2016-12-15

    Babesia sp. BQ1 (Lintan) is one of the parasites isolated from infected sheep in China that belongs to the B. motasi-like phylogenetic group. The rhoptry-associated-protein 1 (rap-1) locus in this group consists of a complex organization of 12 genes of three main types: 6 rap-1a variants intercalated with 5 identical copies of rap-1b and a single 3' ending rap-1c gene. In the present study, transcription analysis performed by standard RT-PCR demonstrated that the three different rap-1 gene types and the four rap-1a variants were transcribed by the parasite cultivated in vitro. Peptides, specific for each rap-1 type gene, were selected in putative linear B-epitopes and used to raise polyclonal rabbit antisera. Using these sera, the same expression pattern of RAP-1 proteins was found in parasites cultivated in vitro or collected from acute infection whereas only RAP-1a67 was detectable in merozoite extracts. However, ELISA performed with recombinant RAP-1a67, RAP-1b or RAP-1c and sera from infected sheep demonstrated that RAP-1a67 is the main RAP-1 recognized during infection, even if some infected sheep also recognized RAP-1b and/or RAP-1c.

  8. Breadboard RL10-11B low thrust operating mode

    NASA Technical Reports Server (NTRS)

    Kmiec, Thomas D.; Galler, Donald E.

    1987-01-01

    Cryogenic space engines require a cooling process to condition engine hardware to operating temperature before start. This can be accomplished most efficiently by burning propellants that would otherwise be dumped overboard after cooling the engine. The resultant low thrust operating modes are called Tank Head Idle and Pumped Idle. During February 1984, Pratt & Whitney conducted a series of tests demonstrating operation of the RL10 rocket engines at low thrust levels using a previously untried hydrogen/oxygen heat exchanger. The initial testing of the RL10-11B Breadboard Low Thrust Engine is described. The testing demonstrated operation at both tank head idle and pumped idle modes.

  9. Cosmic Ray Telescope Experiment (CRT), Pioneer 10/11 Program

    NASA Technical Reports Server (NTRS)

    McDonald, Frank B.

    1999-01-01

    In May 1996 the electrical power on Pioneer 10 was no longer adequate to support the Cosmic Ray Telescope Experiment (CRT). In March 1997 ground based operations for the mission were terminated. The 25 years of Pioneer 10 were a remarkable voyage of discovery as it ventured into a vast new unexplored region of space. These observations by the Pioneer experiments led in the development of a new discipline of space science - heliospheric physics. For cosmic ray studies it was an incredible era, leading to the identification of new energetic particle populations and processes and initiating the study of the dynamics and large-scale structure and began the study of the dynamics and large-scale structure of the outer heliosphere. A summary of some of the principal scientific findings of the CRT experiment over this period is given in the next section. Even with the cessation of data from the Pioneer 10/11 mission there remained a great deal of scientific analysis and data archiving that required on the order of an additional three years of effort on the part of the CRT team. We have tried to select those tasks where the P10/11 CRT data have an important role to play. Special emphasis is placed on long-term synoptic studies that make use of the extended temporal and spatial coverage of the missions and the full capabilities of the CRT experiment. The major scientific objectives of this study are: (1) A phenomenological study of the modulation process in the heliosphere, thereby laying the foundation for developing a unified model of cosmic ray modulation over a complete 22 year heliomagnetic cycle; (2) These modulation studies and the temporal changes in the cosmic ray intensities also provide information on the large-scale structure and dynamics of the outer heliosphere; (3) use the galactic and anomalous cosmic ray data from Pioneer 10 to obtain a more accurate estimate of the distance to the modulation boundary and to the termination shock; (4) Use the results from (2

  10. LP/SV Bladder Buoyancy Test Comparison

    DTIC Science & Technology

    2011-07-01

    The buoyant force of the British MK 30 LCX is also unknown; however, this flotation device utilizes a large bladder and may replace the LP/SV. Aim...following inflation using a 45g CO2 canister. Conclusion: In all trials, both flotation devices produced buoyant forces greater that 35 lbs. The British...2. The British use a very similar aircrew flotation device called the MK 30 LCX. It differs from the currently used LP/SV because it utilizes a

  11. SV40-mediated immortalization of human fibroblasts.

    PubMed

    Ozer, H L; Banga, S S; Dasgupta, T; Houghton, J; Hubbard, K; Jha, K K; Kim, S H; Lenahan, M; Pang, Z; Pardinas, J R; Patsalis, P C

    1996-01-01

    We have identified a multistep mechanism by which the DNA virus SV40 overcomes cellular senescence. Expression of SV40 T antigen is required for both transient extension of life span and unlimited life span or immortalization. These effects are mediated through inactivation of function of growth suppressors pRB and p53 via complex formation with T antigen. However, immortalization additionally requires inactivation of a novel growth suppressor gene, which has recently been identified to be on the distal portion of the long arm of chromosome 6, designated SEN6. We propose that SEN6 is responsible for cellular senescence in fibroblasts and other cells.

  12. 43 CFR 10.11 - Disposition of culturally unidentifiable human remains.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... human remains. 10.11 Section 10.11 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or... unidentifiable human remains. (a) General. This section implements section 8(c)(5) of the Act and applies...

  13. 43 CFR 10.11 - Disposition of culturally unidentifiable human remains.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... human remains. 10.11 Section 10.11 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or... unidentifiable human remains. (a) General. This section implements section 8(c)(5) of the Act and applies...

  14. Evidence of SV40 infections in hospitalized children

    NASA Technical Reports Server (NTRS)

    Butel, J. S.; Jafar, S.; Wong, C.; Arrington, A. S.; Opekun, A. R.; Finegold, M. J.; Adam, E.

    1999-01-01

    Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

  15. First HPLC-UV method for rapid and simultaneous quantification of phenobarbital, primidone, phenytoin, carbamazepine, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine, lamotrigine, oxcarbazepine and licarbazepine in human plasma.

    PubMed

    Serralheiro, Ana; Alves, Gilberto; Fortuna, Ana; Rocha, Marília; Falcão, Amílcar

    2013-04-15

    A sensitive and fast high-performance liquid chromatographic method coupled with ultraviolet detection is herein reported for the simultaneous determination of human plasma concentration of six antiepileptic drugs frequently used in clinical practice [phenobarbital (PB), primidone (PRM), phenytoin (PHT), carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC)] and some of their main metabolites, carbamazepine-10,11-epoxide (CBZ-E), 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (trans-diol) and licarbazepine (Lic). Sample preparation consisted of a deproteinization step with methanol followed by a solid-phase extraction procedure. Chromatographic separation was achieved in approximately 15 min on a reversed-phase C18 column using a mobile phase composed by water-methanol-acetonitrile-triethylamine (68.7:25:6:0.3, v/v/v/v; pH 6.5) pumped isocratically at 1.0 mL/min. The detector was set at 237 nm. Calibration curves were linear with regression coefficients greater than 0.992 over the concentration ranges 0.25-100 μg/mL for PB, 0.4-50 μg/mL for PRM, 0.5-50 μg/mL for PHT, 0.1-50 μg/mL for CBZ, LTG and CBZ-E, 0.1-25 μg/mL for OXC, 0.25-10 μg/mL for trans-diol and 0.15-80 μg/mL for Lic. Inter- and intra-day imprecision did not exceed 12.15% and inaccuracy was within ±14.91%. Absolute mean recoveries ranged from 78.49 to 101.04% and no interferences were observed at the retention times of the analytes and internal standard (ketoprofen). This bioanalytical method was successfully applied to real plasma samples from epileptic patients and it seems to be a suitable tool for routine therapeutic drug monitoring and also to support other clinical pharmacokinetic-based studies.

  16. Easy Growth Experiment on Peas Stimulates Interest in Biology for 10-11 Year Old Pupils

    ERIC Educational Resources Information Center

    McEwen, Birgitta

    2007-01-01

    How do we support the enthusiasm children show for biology in school? Unfortunately, lack of exciting practical work and boring biology lessons seem to make science less popular. As a senior lecturer in plant physiology at Karlstad University I have simplified experiments intended for students at university and then tested them on 10-11 year old…

  17. 43 CFR 10.11 - Disposition of culturally unidentifiable human remains.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony in Museums and Federal Collections § 10.11 Disposition of culturally... control. (4) A museum or Federal agency may also transfer control of funerary objects that are...

  18. 43 CFR 10.11 - Disposition of culturally unidentifiable human remains.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Objects of Cultural Patrimony in Museums and Federal Collections § 10.11 Disposition of culturally... unidentifiable human remains and associated funerary objects. (1) A museum or Federal agency that is unable to... that none of them has objected to the proposed transfer of control. (4) A museum or Federal agency...

  19. 43 CFR 10.11 - Disposition of culturally unidentifiable human remains.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony in Museums and Federal Collections § 10.11 Disposition of culturally... control. (4) A museum or Federal agency may also transfer control of funerary objects that are...

  20. 15 CFR 10.11 - Revision or amendment of a standard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.11 Revision or amendment of a standard. (a) A published... Committee serves in the development of a new standard. The processing of a revision of a standard shall be... or the design characteristics of the product being standardized, or which cannot reasonably...

  1. 46 CFR 39.10-11 - Personnel training-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.10-11.... Training must include drills or demonstrations using the installed vapor control system covering normal... cover the following subjects: (1) Purpose of a vapor control system; (2) Principles of the vapor...

  2. 46 CFR 39.10-11 - Personnel training-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.10-11.... Training must include drills or demonstrations using the installed vapor control system covering normal... cover the following subjects: (1) Purpose of a vapor control system; (2) Principles of the vapor...

  3. Synthesis and biological evaluation of 10,11-methylenedioxy-14-azacamptothecin.

    PubMed

    Elban, Mark A; Sun, Wenyue; Eisenhauer, Brian M; Gao, Rong; Hecht, Sidney M

    2006-08-03

    [reaction: see text] 10,11-Methylenedioxy-14-azacamptothecin, a potent analogue of the antitumor agent camptothecin (CPT), has been prepared via a key condensation between AB and DE ring precursors. The biological testing of this compound validated a strategy for modulation of the off-rate of camptothecin analogues from the topoisomerase-DNA-CPT ternary complex via structural modification.

  4. 25 CFR 10.11 - How would someone detained or incarcerated, or their representative, get the BIA policies and...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... representative, get the BIA policies and standards? 10.11 Section 10.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY DETENTION FACILITIES AND PROGRAMS § 10.11 How would someone detained or incarcerated, or their representative, get the BIA policies and standards? At...

  5. 25 CFR 10.11 - How would someone detained or incarcerated, or their representative, get the BIA policies and...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... representative, get the BIA policies and standards? 10.11 Section 10.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY DETENTION FACILITIES AND PROGRAMS § 10.11 How would someone detained or incarcerated, or their representative, get the BIA policies and standards? At...

  6. 25 CFR 10.11 - How would someone detained or incarcerated, or their representative, get the BIA policies and...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... representative, get the BIA policies and standards? 10.11 Section 10.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY DETENTION FACILITIES AND PROGRAMS § 10.11 How would someone detained or incarcerated, or their representative, get the BIA policies and standards? At...

  7. 25 CFR 10.11 - How would someone detained or incarcerated, or their representative, get the BIA policies and...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... representative, get the BIA policies and standards? 10.11 Section 10.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY DETENTION FACILITIES AND PROGRAMS § 10.11 How would someone detained or incarcerated, or their representative, get the BIA policies and standards? At...

  8. 25 CFR 10.11 - How would someone detained or incarcerated, or their representative, get the BIA policies and...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... representative, get the BIA policies and standards? 10.11 Section 10.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY DETENTION FACILITIES AND PROGRAMS § 10.11 How would someone detained or incarcerated, or their representative, get the BIA policies and standards? At...

  9. c-myc protein can be substituted for SV40 T antigen in SV40 DNA replication.

    PubMed Central

    Iguchi-Ariga, S M; Itani, T; Yamaguchi, M; Ariga, H

    1987-01-01

    Replicating activity of SV40 origin-containing plasmid was tested in human cells as well as in monkey CosI cells. All the plasmids possessing SV40 ori sequences could replicate, even in the absence of SV40 T antigen, in human HL-60 and Raji cells which are expressing c-myc gene at high level. The copy numbers of the replicated plasmids in these human cells were 1/100 as high as in monkey CosI cells which express SV40 T antigen constitutively. Exactly the same plasmids as the transfected original ones were recovered from the Hirt supernatant of the transfected HL-60 cells. Furthermore, replication of the SV40 ori-containing plasmids in HL-60 cells was inhibited by anti-c-myc antibody co-transfected into the cells. These results indicate that the c-myc protein can be substituted for SV40 T antigen in SV40 DNA replication. Images PMID:3037484

  10. Differential activation of human constitutive androstane receptor and its SV23 and SV24 splice variants by rilpivirine and etravirine

    PubMed Central

    Sharma, Devinder; Lau, Aik Jiang; Sherman, Matthew A; Chang, Thomas K H

    2015-01-01

    Background and Purpose Rilpivirine and etravirine are second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) indicated for the treatment of HIV/AIDS. The constitutive androstane receptor (CAR) regulates the expression of genes involved in various biological processes, including the transport and biotransformation of drugs. We investigated the effect of rilpivirine and etravirine on the activity of the wild-type human CAR (hCAR-WT) and its hCAR-SV23 and hCAR-SV24 splice variants, and compared it with first-generation NNRTIs (efavirenz, nevirapine, and delavirdine). Experimental Approach Receptor activation, ligand-binding domain (LBD) transactivation, and co-activator recruitment were investigated in transiently transfected, NNRTI-treated HepG2 cells. Nuclear translocation of green fluorescent protein-tagged hCAR-WT and CYP2B6 gene expression were assessed in NNRTI-treated human hepatocytes. Key Results Rilpivirine and etravirine activated hCAR-WT, but not hCAR-SV23 or hCAR-SV24, and without transactivating the LBD or recruiting steroid receptor coactivators SRC-1, SRC-2, or SRC-3. Among the first-generation NNRTIs investigated, only efavirenz activated hCAR-WT, hCAR-SV23, and hCAR-SV24, but none of them transactivated the LBD of these receptors or substantively recruited SRC-1, SRC-2, or SRC-3. Rilpivirine, etravirine, and efavirenz triggered nuclear translocation of hCAR-WT and increased hCAR target gene (CYP2B6) expression. Conclusion and Implications NNRTIs activate hCAR-WT, hCAR-SV23, and hCAR-SV24 in a drug-specific and isoform-selective manner. The activation occurs by a mechanism that does not appear to involve binding to the LBD or recruitment of SRC-1, SRC-2, or SRC-3. PMID:25363652

  11. Study of 11Li and 10,11Be nuclei through elastic scattering and breakup reactions

    NASA Astrophysics Data System (ADS)

    Gaidarov, M. K.; Lukyanov, V. K.; Kadrev, D. N.; Zemlyanaya, E. V.; Antonov, A. N.; Lukyanov, K. V.; Spasova, K.

    2016-01-01

    The hybrid model of the microscopic optical potential (OP) is applied to calculate the 11Li+p, 10,11Be+p, and 10,11Be+12C elastic scattering cross sections at energies E < 100 MeV/nucleon. The OP's contain the folding-model real part (ReOP) with the direct and exchange terms included, while its imaginary part (ImOP) is derived within the high-energy approximation (HEA) theory. For the 11Li+p elastic scattering, the microscopic large-scale shell model (LSSM) density of 11Li is used, while the density distributions of 10,11Be nuclei obtained within the quantum Monte Carlo (QMC) model and the generator coordinate method (GCM) are utilized to calculate the microscopic OPs and cross sections of elastic scattering of these nuclei on protons and 12C. The depths of the real and imaginary parts of OP are fitted to the elastic scattering data, being simultaneously adjusted to reproduce the true energy dependence of the corresponding volume integrals. Also, the cluster models, in which 11Li consists of 2n-halo and the 9Li core having its own LSSM form of density and 11Be consists of a n-halo and the 10Be core, are adopted. Within the latter, we give predictions for the longitudinal momentum distributions of 9Li fragments produced in the breakup of 11Li at 62 MeV/nucleon on a proton target. It is shown that our results for the diffraction and stripping reaction cross sections in 11Be scattering on 9Be, 93Nb, 181Ta, and 238U targets at 63 MeV/nucleon are in a good agreement with the available experimental data.

  12. Design of a Two-Stage Light Gas Gun for Muzzle Velocities of 10 - 11 kms

    NASA Technical Reports Server (NTRS)

    Bogdanoff, David W.

    2016-01-01

    Space debris poses a major risk to spacecraft. In low earth orbit, impact velocities can be 10 11 kms and as high as 15 kms. For debris shield design, it would be desirable to be able to launch controlled shape projectiles to these velocities. The design of the proposed 10 11 kmsec gun uses, as a starting point, the Ames 1.280.22 two stage gun, which has achieved muzzle velocities of 10 11.3 kmsec. That gun is scaled up to a 0.3125 launch tube diameter. The gun is then optimized with respect to maximum pressures by varying the pump tube length to diameter ratio (LD), the piston mass and the hydrogen pressure. A pump tube LD of 36.4 is selected giving the best overall performance. Piezometric ratios for the optimized guns are found to be 2.3, much more favorable than for more traditional two stage light gas guns, which range from 4 to 6. The maximum powder chamber pressures are 20 to 30 ksi. To reduce maximum pressures, the desirable range of the included angle of the cone of the high pressure coupling is found to be 7.3 to 14.6 degrees. Lowering the break valve rupture pressure is found to lower the maximum projectile base pressure, but to raise the maximum gun pressure. For the optimized gun with a pump tube LD of 36.4, increasing the muzzle velocity by decreasing the projectile mass and increasing the powder loads is studied. It appears that saboted spheres could be launched to 10.25 and possibly as high as 10.7 10.8 kmsec, and that disc-like plastic models could be launched to 11.05 kms. The use of a tantalum liner to greatly reduce bore erosion and increase muzzle velocity is discussed. With a tantalum liner, CFD code calculations predict muzzle velocities as high as 12 to 13 kms.

  13. Neutron dosimetry and damage calculation for the JP-10, 11, 13, and 16 experiments in HFIR

    SciTech Connect

    Greenwood, L.R.; Ratner, R.T.

    1996-04-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint U.S./Japanese experiments JP-10, 11, 13, and 16 in the target of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Lab (ORNL). These experiments were irradiated at 85 MW for 238.5 EFPD. The maximum fast neutron fluence >0.1 MeV was about 2.1E + 22 n/cm{sup 2} for all of the experiments resulting in about 17.3 dpa in 316 stainless steel.

  14. Pioneer 10/11 data analysis of the magnetic field experiment

    NASA Technical Reports Server (NTRS)

    Jones, D. E.

    1982-01-01

    Work conducted in support of the Pioneer missions to Jupiter (10,11), and Saturn (11) as well as the reduction, analysis and interpretation of magnetic field data obtained by the vector helium magnetometer on the Pioneer 10 and 11 spacecraft is summarized. Initial efforts concentrated primarily on the interplanetary data, and those aspcts of the data of relevance to obtaining a better understanding of the interaction of the magnetized solar wind with the terrestrial magnetic field. After encounters of Jupiter and Saturn, the emphasis of research was directed primarily to an analysis of the planetary data. In particular, it soon became clear that there was a need for modelling of the various candidate magnetospheric currents suggested by the data. Results not published as yet, are also summarized.

  15. Sperm FISH and chromatin integrity in spermatozoa from a t(6;10;11) carrier.

    PubMed

    Olszewska, Marta; Huleyuk, Nataliya; Fraczek, Monika; Zastavna, Danuta; Wiland, Ewa; Kurpisz, Maciej

    2014-05-01

    Complex chromosome rearrangements (CCRs) are structurally balanced or unbalanced aberrations involving more than two breakpoints on two or more chromosomes. CCRs can be a potential reason for genomic imbalance in gametes, which leads to a drastic reduction in fertility. In this study, the meiotic segregation pattern, aneuploidy of seven chromosomes uninvolved in the CCR and chromatin integrity were analysed in the ejaculated spermatozoa of a 46,XY,t(6;10;11)(q25.1;q24.3;q23.1)mat carrier with asthenozoospermia and a lack of conception. The frequency of genetically unbalanced spermatozoa was 78.8% with a prevalence of 4:2 segregants of 38.2%, while the prevalence of the adjacent 3:3 mode was 35.3%. Analysis of the aneuploidy of chromosomes 13, 15, 18, 21, 22, X and Y revealed an approximately fivefold increased level in comparison with that of the control group, indicating the presence of an interchromosomal effect. Sperm chromatin integrity status was evaluated using chromomycin A3 and aniline blue staining (deprotamination), acridine orange test and TUNEL assay (sperm DNA fragmentation). No differences were found when comparisons were made with a control group. We suggest that the accumulation of genetically unbalanced spermatozoa, significantly increased sperm aneuploidy level and decreased sperm motility (20%, progressive) were not responsible for the observed lack of reproductive success in the analysed infertile t(6;10;11) carrier. Interestingly, in the case described herein, a high level of sperm chromosomal imbalance appears not to be linked to sperm chromatin integrity status.

  16. [Possible relation between viruses and oromaxillofacial tumors. III. Demonstration of the SV40 antigen and anti-SV40 antibodies in patients with tumors of the parotid gland].

    PubMed

    Stoian, M; Zaharia, O; Suru, M; Goldstein, I; Nastac, E

    1987-01-01

    SV40 antigen was detected in 7 of 13 malignant tumors developed in the head and neck region. Specific complement fixing antibodies were found in all the patients with the SV40 antigen present in the parotid gland tumoral cells. Incidence of the anti-SV40 complement fixing antibodies in parotid gland tumor bearing patients was of 69.6%.

  17. Acaricidal activity of 9-oxo-10,11-dehydroageraphorone extracted from Eupatorium adenophorum in vitro.

    PubMed

    Liao, Fei; Hu, Yanchun; Tan, Hui; Wu, Lei; Wang, Yunfei; Huang, Yue; Mo, Quan; Wei, Yahui

    2014-05-01

    The acaricidal activity of the 9-oxo-10,11-dehydroageraphorone (euptox A), a cadenine sesquiterpene from Eupatorium adenophorum (E. adenophorum) against Sarcoptes scabiei and Psoroptes cuniculi was tested in vitro. A complementary log-log (CLL) model was used to analyze the data of the toxicity tests in vitro. The results showed euptox A had strong toxicity against mites, killing all S. scabiei at 3 and 4 mg/ml (m/v) concentration, while 4 mg/ml euptox A was also found to kill all P. cuniculi within a 4 h period. Similarly, 2, 3 and 4 mg/ml concentration of euptox A had strong toxicity against S. scabiei, with median lethal time (LT50) values at 0.687, 0.526, 0.326 h, respectively. 3 mg/ml and 4 mg/ml showed strong acaricidal action against P. cuniculi; the LT50 values were 0.693 and 0.493 h, respectively. The median lethal concentration (LC50) values were 1.068 mg/ml for Scabies mite and 0.902 mg/ml for P. cuniculi in 2 h. The results indicate that euptox A has strong acaricidal activity and may exploit as novel drugs for the effective control of animal acariasis.

  18. Geomagnetic activity during 10 - 11 solar cycles that has been observed by old Russian observatories.

    NASA Astrophysics Data System (ADS)

    Seredyn, Tomasz; Wysokinski, Arkadiusz; Kobylinski, Zbigniew; Bialy, Jerzy

    2016-07-01

    A good knowledge of solar-terrestrial relations during past solar activity cycles could give the appropriate tools for a correct space weather forecast. The paper focuses on the analysis of the historical collections of the ground based magnetic observations and their operational indices from the period of two sunspot solar cycles 10 - 11, period 1856 - 1878 (Bartels rotations 324 - 635). We use hourly observations of H and D geomagnetic field components registered at Russian stations: St. Petersburg - Pavlovsk, Barnaul, Ekaterinburg, Nertshinsk, Sitka, and compare them to the data obtained from the Helsinki observatory. We compare directly these records and also calculated from the data of the every above mentioned station IHV indices introduced by Svalgaard (2003), which have been used for further comparisons in epochs of assumed different polarity of the heliospheric magnetic field. We used also local index C9 derived by Zosimovich (1981) from St. Petersburg - Pavlovsk data. Solar activity is represented by sunspot numbers. The correlative and continuous wavelet analyses are applied for estimation of the correctness of records from different magnetic stations. We have specially regard to magnetic storms in the investigated period and the special Carrington event of 1-2 Sep 1859. Generally studied magnetic time series correctly show variability of the geomagnetic activity. Geomagnetic activity presents some delay in relation to solar one as it is seen especially during descending and minimum phase of the even 11-year cycle. This pattern looks similarly in the case of 16 - 17 solar cycles.

  19. [Socioeconomic differences in nutrition and nutritional status in 10-11-year-old boys].

    PubMed

    van Poppel, G; Schneijder, P; Maas, I A; Schrijver, J; Sluiter-van Nies, A A; Kok, F J

    1989-06-17

    The relation between socio-economic status and food consumption and nutritional status was investigated in boys aged 10-11 yr (n = 125) who participated in a survey in 1987. Based on the parents' education and profession, boys were categorized in three levels of socio-economic status. In the lower socio-economic category (n = 59) body mass index and skinfold thickness are higher (p less than 0.05) than in the highest category (n = 41) and caries is more prevalent (83% vs 51%). In comparison with both higher groups, dairy products, vegetables and fruit are less frequently used in the lower category, and consumption of protein, calcium and riboflavin is lower (p less than 0.05). These results indicate an increased risk of caries and obesity in the lower socio-economic group. The other differences clearly have an unfavourable tendency, but do not indicate directly increased risk of nutritional deficiencies or nutrition-related diseases in the lower socio-economic group.

  20. Genome Sequence of the Arctic Methanotroph Methylobacter tundripaludum SV96

    SciTech Connect

    Svenning, Mette M; Hestnes, Anne Grethe; Wartiainen, Ingvild; Stein, Lisa Y.; Klotz, Martin G; Kalyuzhnaya, Marina G.; Spang, Anja; Bringel, Francoise O.; Vuilleumier, Stephane; Lajus, Aurelie; Cheng, Jan-Fang; Goodwin, Lynne A.; Ivanova, N; Han, James; Han, Cliff; Hauser, Loren John; Held, Brittany; Land, Miriam L; Lapidus, Alla L.; Lucas, Susan; Nolan, Matt; Pitluck, Sam; Woyke, Tanja

    2011-01-01

    Methylobacter tundripaludum SV96(T) (ATCC BAA-1195) is a psychrotolerant aerobic methane-oxidizing gammaproteobacterium (Methylococcales, Methylococcaceae) living in High Arctic wetland soil. The strain was isolated from soil harvested in July 1996 close to the settlement Ny-Alesund, Svalbard, Norway (78 degrees 56'N, 11 degrees 53'E), and described as a novel species in 2006. The genome includes pmo and pxm operons encoding copper membrane monooxygenases (Cu-MMOs), genes required for nitrogen fixation, and the nirS gene implicated in dissimilatory nitrite reduction to NO but no identifiable inventory for further processing of nitrogen oxides. These genome data provide the basis to investigate M. tundripaludum SV96, identified as a major player in the biogeochemistry of Arctic environments.

  1. ER Operations Installation of Three FLUTe Soil-Vapor Monitoring Wells (MWL-SV03 MWL-SV04 and MWL-SV05) at the Mixed Waste Landfill.

    SciTech Connect

    Copland, John Robin

    2014-09-01

    This installation report describes the May through July 2014 drilling activities performed for the installation of three multi-port soil-vapor monitoring wells (MWL-SV03, MWL-SV04, and MWL-SV05) at the Mixed Waste Landfill (MWL), which is located at Sandia National Laboratories, New Mexico (SNL/NM). SNL/NM is managed and operated by Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy (DOE)/National Nuclear Security Administration. The MWL is designated as Solid Waste Management Unit (SWMU) 76 and is located in Technical Area (TA) III (Figure 1-1). The locations of the three soil-vapor monitoring wells (MWL-SV03, MWL-SV04, and MWL-SV05) are shown in Figure 1-2

  2. A New SV2A Ligand for Epilepsy.

    PubMed

    Rogawski, Michael A

    2016-10-20

    Since the 1970s, racetams have been in use as cognitive enhancers. Levetiracetam was discovered to have antiseizure activity in animal models and was then found to bind to SV2A in synaptic and endocrine vesicles. Brivaracetam, an analog of levetiracetam, was identified in a medicinal chemistry campaign with the objective of discovering analogs with higher affinity at racetam-binding sites and greater antiseizure potency.

  3. Effect of homologous tumor DNA on the evolution of SV40-induced hamster sarcoma.

    PubMed

    Nastac, E; Stoian, M; Iosipenco, M; Suru, M; Hozoc, M; Repanovici, R

    1985-01-01

    DNA extracted from SV40-induced hamster sarcoma (SV40--HS DNA) increased the survival length of animals carrying the homologous tumor and--in some cases--inhibited the development of the tumor. The efficacy of the preparation was directly proportional to the number of administrations; it did not necessarily depend on the amount of SV40--HS DNA per dose. SV40 DNA had no favourable effect on the evolution of the SV40-induced tumor, which suggests that viral DNA does not represent the active component of the SV40--HS DNA preparations. Some possible mechanisms of the effect of homologous tumor preparations are discussed.

  4. A "tsunami" in the protoplanetary disk of SV Cep

    NASA Astrophysics Data System (ADS)

    Shenavrin, V. I.; Grinin, V. P.; Rostopchina-Shakhovskaya, A. N.; Demidova, T. V.; Shakhovskoi, D. N.; Belan, S. P.

    2017-01-01

    The results of 15 years of photometric observations of the UX Ori star SV Cep in the near-infrared ( JHKL) are presented. They demonstrate the presence of a cyclic component with a period of 7 years in the variations of the IR fluxes. This is clearly seen in all four IR bands, but is absent in the optical. The variation amplitude is highest in the K band: Δ K ≈ 0.68 m . The shape of the variations differs slightly in the transition from J to L. However, it is reproduced with good accuracy during two cycles, suggesting a periodic process is observed. If the periodic perturbations in the circumstellar disk of SV Cep are due to a companion's orbitalmotion, the orbital semi-major axis should be 5AU, foramass of SVCep of 2.6 M ⊙. The absence of a seven-year period in the optical light curve of SV Cep means that the observed period cannot be due to variations in the circumstellar extinction. The IR brightness variations could be due to the companion's motion along an eccentric orbit, resulting in a periodic modulation of the rate of accretion onto the star.

  5. Molecular analysis of SV-40-CAL, a new slow growing SV-40 strain from the kidney of a caged New World monkey with fatal renal disease.

    PubMed

    Zdziarski, Jacqueline M; Sarich, Nicolene A; Witecki, Kelley E; Lednicky, John A

    2004-10-01

    A decline of the Callimico goeldii population in American zoos is presently occurring due to glomerulonephritis of unknown etiology. We hypothesized that this emerging idiopathic fatal renal disease (IFRD) was caused by a virus. We therefore attempted to isolate virus from the kidneys three C. goeldi in Illinois that had IFRD. Along with other viruses, Simian virus 40 (SV-40) strain CAL was isolated. SV-40-CAL is currently the slowest-growing natural isolate of SV-40 in CV-1 cells. Inefficient SV-40-CAL growth in CV-1 cells stems from two features: a suboptimal protoarchetypal regulatory region, and a Large tumor antigen gene sequence like that of SV-40 strain T302, previously considered the slow-growing natural isolate of SV-40. To our knowledge, this is the first documented isolation of SV-40 from a New World monkey outside of a laboratory setting. Though SV-40 is renaltropic, the role of SV-40-CAL in IFRD is uncertain. Transmission of SV-40 to C. goeldii through anthropogenic activity is suspected.

  6. No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.

    PubMed

    Lynch, J M; Tate, S K; Kinirons, P; Weale, M E; Cavalleri, G L; Depondt, C; Murphy, K; O'Rourke, D; Doherty, C P; Shianna, K V; Wood, N W; Sander, J W; Delanty, N; Goldstein, D B; Sisodiya, S M

    2009-01-01

    Levetiracetam (LEV), a newer antiepileptic drug (AED) useful for several epilepsy syndromes, binds to SV2A. Identifying genetic variants that influence response to LEV may allow more tailored use of LEV. Obvious candidate genes are SV2A, SV2B and SV2C, which encode the only known binding site, synaptic vesicle protein 2 (SV2), with LEV binding to the SV2A isoform. SV2A is an essential protein as homozygous SV2A knockout mice appear normal at birth but fail to grow, experience severe seizures and die by 3 weeks. We addressed characterising AED response issues in pharmacogenetics and whether variation in these genes associates with response to LEV in two independent cohorts with epilepsy. We also investigated whether variation in these three genes associated with epilepsy predisposition in two larger cohorts of patients with various epilepsy phenotypes. Common genetic variation in SV2A, encoding the actual binding site of LEV, was fully represented in this study whereas SV2B and SV2C were not fully covered. None of the polymorphisms tested in SV2A, SV2B or SV2C influence LEV response or predisposition to epilepsy. We found no association between genetic variation in SV2A, SV2B or SV2C and response to LEV or epilepsy predisposition. We suggest this study design may be used in future pharmacogenetic work examining AED or LEV efficacy. However, different study designs would be needed to examine common variation with minor effect sizes, or rare variation, influencing AED or LEV response or epilepsy predisposition.

  7. Shorter intervals at peak SV vs.V̇O2max may yield high SV with less physiological stress.

    PubMed

    Colakoglu, Muzaffer; Ozkaya, Ozgur; Balci, Gorkem Aybars; Yapicioglu, Bulent

    2015-01-01

    The purpose of this study was to evaluate whether greater and sustainable stroke volume (SV) responses may be obtained by exercise intensities corresponding to peak SV (SVpeak) vs. maximal O2 consumption (VO2max), and short vs. long intervals (SI vs. LI). Nine moderate- to well-trained male athletes competing at regional level specialists of cyclist, track and field volunteered to take part in the study (VO2max: 59.7 ± 7.4 mL·min(-1)·kg(-1)). Following familiarisation sessions, VO2max was determined, and then SVpeak was evaluated using exercise intensities at 40%-100% of VO2max by nitrous-oxide rebreathing (N2ORB) method. Then each separate participant exercised wattages corresponding to individual VO2max and SVpeak during both SI (SIVO2max and SI(SVpeak)) and LI (LIVO2max and LI(SVpeak)) workouts on a cycle ergometer. Main results showed that both SIVO2max and SI(SVpeak) yielded greater SV responses than LIVO2max and LI(SVpeak) (p ≤ 0.05). Mean SV responses were greater in LI(SVpeak) than in LIVO2max (p ≤ 0.05), but there was no statistical difference between SI(SVpeak) and SIVO2max. However, there was significantly less physiological stress based on VO2, respiratory exchange ratio, heart rate and rate of perceived exhaustion in SVpeak than in [Formula: see text] intensities (p ≤ 0.05). Moreover, SV responses at exercise phases increased in the early stages and remain stable until the end of SIVO2max and SI(SVpeak) workouts (p > 0.05), while they were gradually decreasing in LIVO2max and LI(SVpeak) sessions (p ≤ 0.05). In conclusion, if the aim of a training session is to improve SVpeak with less physiological stress, SI(SVpeak) seems a better alternative than other modalities tested in the present study.

  8. RAPTR-SV: a hybrid method for the detection of structural variants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Motivation: Identification of Structural Variants (SV) in sequence data results in a large number of false positive calls using existing software, which overburdens subsequent validation. Results: Simulations using RAPTR-SV and another software package that uses a similar algorithm for SV detection...

  9. Insecticidal potency of bacterial species Bacillus thuringiensis SV2 and Serratia nematodiphila SV6 against larvae of mosquito species Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus.

    PubMed

    Patil, Chandrashekhar D; Patil, Satish V; Salunke, Bipinchandra K; Salunkhe, Rahul B

    2012-05-01

    The tremendous worldwide efforts to isolate novel mosquito larvicidal bacteria with improved efficacy present significant promise to control vector-borne diseases of public health importance. In the present study, two native bacterial isolates, Bacillus thuringiensis (Bt SV2) and Serratia species (SV6) were evaluated for mosquito larvicidal potential against the early fourth instar larvae of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus with reference to B. thuringiensis subsp. israelensis (Bti) H 14. The native Gram-positive, spore-forming Bt SV2 isolate showed 100% mortality against early fourth instars of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus, in parallel to Bti H14 strain. After 24 h, Bt SV2 showed 98%, 89%, and 80.67%, and Bti H14 showed 92%, 98.33%, and 60% mortality against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus, respectively. Serratia SV6 showed highest activity against Culex quinquefasciatus (100%) followed by Anopheles stephensi (95%) and Aedes aegypti (91%) after 48 h of exposure. The Gram-negative Serratia SV6 showed delayed toxicity compared to Bti H14 and Bt SV2 against early fourth instars of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. The relative mortality of all treatments after 12-h exposures showed the varied toxicity with respect to exposure time, bacterial treatment, and mosquito species. Genetic relatedness of the strains was confirmed on the basis of phylogenetic reconstructions based on alignment of 16S rRNA gene sequences which indicated a strong clustering of the strain SV2 with B. thuringiensis and the strain SV6 with Serratia nematodiphila. In conclusion, the native isolate B. thuringiensis SV2 showed significant toxicity while Serratia SV6 showed less and delayed toxicity against several mosquito species compared with BtiH14. They may be used as novel bacterial insecticidal agents in mosquito vector-borne disease control. To our knowledge, this is the

  10. Evaluation of Low-Cost, Objective Instruments for Assessing Physical Activity in 10-11-Year-Old Children

    ERIC Educational Resources Information Center

    Hart, Teresa L.; Brusseau, Timothy; Kulinna, Pamela Hodges; McClain, James J.; Tudor-Locke, Catrine

    2011-01-01

    This study compared step counts detected by four, low-cost, objective, physical-activity-assessment instruments and evaluated their ability to detect moderate-to-vigorous physical activity (MVPA) compared to the ActiGraph accelerometer (AG). Thirty-six 10-11-year-old children wore the NL-1000, Yamax Digiwalker SW 200, Omron HJ-151, and Walk4Life…

  11. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    PubMed

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

  12. Evidence, from Pioneer 10/11, Galileo, and Ulysses Data, for an Anomalous, Weak, Long-Range Acceleration

    NASA Technical Reports Server (NTRS)

    Anderson, J. D.; Laing, P. A.; Lau, E. L.; Liu, A. S.; Nieto, M. M.; Turyshev, S. G.

    1998-01-01

    Radio metric data from the Pioneer 10/11, Galileo, and Ulysses Spacecraft indicate an apparent anomalous, constant, acceleration acting on the spacecraft with a magnitude 8.5 x 10(sup -8) cm/s(sup 2), directed towards the Sun.

  13. A Teacher's Guide to Folksinging: A Mini-Elective for Students in Grades 9, 10, 11, and 12.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    To help meet the needs of nonmusic-major students in grade 9, 10, 11, and 12, this teacher's guide offers guidelines for a course to stimulate students' interest and involvement in folksinging. Guidelines are provided on the role of the teacher, methods of instruction, and suggested time allotments. Brief descriptions and comments on some typical…

  14. Systematic analysis of above-barrier fusion of {sup 9,10,11}Be+{sup 209}Bi

    SciTech Connect

    Hinde, D. J.; Dasgupta, M.

    2010-06-15

    Measurements of fusion for {sup 9,10,11}Be allow testing of the relative importance to fusion and breakup of the alpha-cluster structure found in all these Be isotopes, compared with the neutron-halo structure only present for {sup 11}Be. However, disagreements exist among different published experimental data sets for the reactions of {sup 9,10,11}Be with {sup 209}Bi. Accurate measurements of above-barrier cross sections for the products of complete fusion (fission and evaporation residues) in the reaction of {sup 9}Be with {sup 209}Bi and {sup 208}Pb provide the basis for a reanalysis of above-barrier fusion for {sup 10,11}Be+{sup 209}Bi. This includes procedures making full use of the higher precision stable beam data and resolves many of the disagreements. The improved self-consistency of the analysis allows investigation of the experimental average fusion barriers. Although showing some scatter, these suggest a higher barrier for the neutron halo nucleus {sup 11}Be. Comparison of published cross sections for fusion associated with capture of all the charge of the projectile suggest that all these Be isotopes show significant suppression of complete fusion, a surprising result given that the alpha-breakup threshold energies are 1.57 MeV for {sup 9}Be but over 7 MeV for {sup 10,11}Be. Further experimental studies to investigate in more detail the division between complete and incomplete fusion for reactions of {sup 10,11}Be are needed.

  15. Tissue-specific regulation of CXCL9/10/11 chemokines in keratinocytes: Implications for oral inflammatory disease

    PubMed Central

    Marshall, Alison; Celentano, Antonio; Cirillo, Nicola; McCullough, Michael; Porter, Stephen

    2017-01-01

    The IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 play a key role in many inflammatory conditions, particularly those mediated by T cells. Therefore, the production of these chemokines in peripheral tissues could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus (OLP). In the present study, we assessed the production of keratinocyte-derived CXCL9/10/11 under basal and inflammatory conditions and investigated whether these chemokines were involved in the pathogenesis of OLP. We used semi-quantitative PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting (FACS) to assess the expression and functional role of CXCL9/10/11 in oral keratinocytes (three strains of normal human oral keratinocytes (NHOK), and the H357 oral cancer cell line) in the presence or absence of IFN-γ. CXCL9/10/11 were also assessed in tissues from normal patients and those with oral lichen planus (OLP). The time course study in oral keratinocytes treated with IFN-γ showed that expression of CXCL9/10/11 chemokines was significantly enhanced by IFN-γ in a time-dependent manner. In particular, CXCL10, a prominent chemokine that was overexpressed by IFN-γ-stimulated NHOK, was able to effectively recruit CD4 lymphocytes, mainly CD4+CD45RA- cells. Significantly higher levels of CXCL9/10/11 were found in tissues from patients with OLP compared to normal oral mucosa. Taken together, the results demonstrate that normal oral keratinocytes produce chemotactic molecules that mediate T cell recruitment. This study furthers understanding of chemokine production in oral keratinocytes and their role in the pathophysiology of oral mucosa, with particular relevance to OLP. PMID:28253295

  16. SV Cam spot activity in February 2001 - March 2002

    NASA Astrophysics Data System (ADS)

    Zboril, M.; Djurašević, G.

    2003-07-01

    We present the analysis of new BVR light curves for the active star SV Cam. The Roche model with spotted areas on the hotter primary component fits satisfactorily all filter observations yielding two spots in intermediate latitudes and covering about 1.5% each of the stellar surface. Both are ~ 1000 K cooler than surrounding photosphere. The comparison with an earlier season (January/February 2000) suggests that the spots probably evolved in area longitude and latitude but basic and preferred orientation from previous season is confirmed. Data are available only in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/406/193

  17. Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission

    PubMed Central

    Tokudome, Kentaro; Okumura, Takahiro; Shimizu, Saki; Mashimo, Tomoji; Takizawa, Akiko; Serikawa, Tadao; Terada, Ryo; Ishihara, Shizuka; Kunisawa, Naofumi; Sasa, Masashi; Ohno, Yukihiro

    2016-01-01

    Synaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2aL174Q rat) carrying a Sv2a-targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2aL174Q mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures. In addition, development of kindling associated with repeated PTZ treatments or focal stimulation of the amygdala was markedly facilitated by the Sv2aL174Q mutation. Neurochemical studies revealed that the Sv2aL174Q mutation specifically reduced depolarization-induced GABA, but not glutamate, release in the hippocampus without affecting basal release or the SV2A expression level in GABAergic neurons. In addition, the Sv2aL174Q mutation selectively reduced the synaptotagmin1 (Syt1) level among the exocytosis-related proteins examined. The present results demonstrate that dysfunction of SV2A due to the Sv2aL174Q mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development, illustrating the crucial role of SV2A-GABA system in modulating kindling epileptogenesis. PMID:27265781

  18. Evaluation of eye irritation by S-(-)-10,11-dihydroxyfarnesic acid methyl ester secreted by Beauveria bassiana CS1029.

    PubMed

    Son, Hyeong-U; Lee, Sang-Han

    2013-10-01

    The aim of this study was to investigate whether S-(-)-10,11-dihydroxyfarnesic acid methyl ester produced by cell subtype Beauveria bassiana CS1029 causes acute toxicity when used for cosmetic purposes by performing an eye irritation test. New Zealand white (NZW) rabbits were treated with a 100 mg/dose of S-(-)-10,11-dihydroxyfarnesic acid methyl ester according to standard procedure guidelines. No significant changes in terms of ocular lesions of the cornea, turbidity of the cornea, swelling of the eyelid or ocular discharge were observed in the methyl ester-treated groups, while sodium dioctyl sulfosuccinate, a positive control, caused severe toxicity. The anatomical and pathological observations indicate that the methyl ester produced by Beauveria bassiana CS1029 did not induce eye irritation in the lenses of the rabbits. The data suggest that the methyl ester evaluated in this study has promising potential as a cosmetic ingredient that does not irritate the eye.

  19. The characterization of ficaprenol-10, -11 and 12 from the leaves of Ficus elastica (decorative rubber plant).

    PubMed

    Stone, K J; Wellburn, A R; Hemming, F W; Pennock, J F

    1967-01-01

    Evidence from mass, nuclear-magnetic-resonance and infrared spectrometry and from gas-liquid and thin-layer chromatography is presented in favour of the presence of cis-trans-decaprenol, -undecaprenol and -dodecaprenol in the mixture of polyprenols (2.6mg./g.) isolated from leaf tissue of Ficus elastica. The trivial names ficaprenol-10, -11 and -12 are proposed. Nuclear-magnetic-resonance studies showed that each of these prenols contains three trans internal isoprene residues and a cis ;OH-terminal' isoprene residue. Ficaprenol-11 is the major component of the mixture. Chromatographic evidence suggests the presence also of small amounts of ficaprenol-9 and -13. The precise position of the three trans internal isoprene residues was not determined but it is suggested that these are adjacent to the omega-terminal isoprene residue and that the ficaprenols are formed from all-trans-geranylgeranyl pyrophosphate. It is also suggested that ficaprenol-10, -11, -12 and -13 are probably the same compounds as castaprenol-10, -11, -12 and -13.

  20. DETECTION OF SPECIFIC ANTIGEN IN SV40-TRANSFORMED CELLS BY IMMUNOFLUORESCENCE

    PubMed Central

    Pope, John H.; Rowe, Wallace P.

    1964-01-01

    With an immunofluorescent technique involving the use of serum of hamsters with SV40 tumors, nuclear fluorescence was detected in each of five cell lines, derived from four mammalian species, transformed by SV40 virus. Essentially all nuclei, including those of multinuclear cells, were fluorescent-stainable. Serum of hamsters bearing SV40 tumors was also found to give nuclear fluorescence in susceptible cells (AGMK or BSC-1) acutely infected with SV40 virus. These findings provide further evidence that cellular incorporation of the SV40 viral genome, with partial expression of the genome by synthesis of at least one virus-specific antigen, is an integral property of all SV40 transformed cells. PMID:14206435

  1. The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses

    NASA Technical Reports Server (NTRS)

    Kohli, M.; Jorgensen, T. J.

    1999-01-01

    The simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses. Copyright 1999 Academic Press.

  2. The human synaptic vesicle protein, SV2A, functions as a galactose transporter in Saccharomyces cerevisiae.

    PubMed

    Madeo, Marianna; Kovács, Attila D; Pearce, David A

    2014-11-28

    SV2A is a synaptic vesicle membrane protein expressed in neurons and endocrine cells and involved in the regulation of neurotransmitter release. Although the exact function of SV2A still remains elusive, it was identified as the specific binding site for levetiracetam, a second generation antiepileptic drug. Our sequence analysis demonstrates that SV2A has significant homology with several yeast transport proteins belonging to the major facilitator superfamily (MFS). Many of these transporters are involved in sugar transport into yeast cells. Here we present evidence showing, for the first time, that SV2A is a galactose transporter. We expressed human SV2A in hexose transport-deficient EBY.VW4000 yeast cells and demonstrated that these cells are able to grow on galactose-containing medium but not on other fermentable carbon sources. Furthermore, the addition of the SV2A-binding antiepileptic drug levetiracetam to the medium inhibited the galactose-dependent growth of hexose transport-deficient EBY.VW4000 yeast cells expressing human SV2A. Most importantly, direct measurement of galactose uptake in the same strain verified that SV2A is able to transport extracellular galactose inside the cells. The newly identified galactose transport capability of SV2A may have an important role in regulating/modulating synaptic function.

  3. P-SV-wave propagation in heterogeneous media: grid method

    NASA Astrophysics Data System (ADS)

    Jianfeng, Zhang; Tielin, Liu

    1999-02-01

    We present a new numerical modelling algorithm for P-SV-wave propagation in heterogeneous media, which is named the grid method in this paper. Similar to the finite-element method in the discretization of a numerical mesh, the grid method is flexible in incorporating surface topography and curved interfaces. The grid method, in the same way as the staggered-grid finite-difference scheme, is developed from the first-order velocity-stress hyperbolic system of elastic wave equations. The free-surface conditions are satisfied naturally for the grid method. The method, with its small numerical dispersion and good stability, is of high accuracy and low computational cost. Each time step needs 34M+N multiplication operations and 26M+N addition operations for N nodes and M triangular grids. In this paper, the triangular grid method is discussed in detail, and the numerical dispersion, stability criterion and numerical simulations are presented. The grid method based on triangular grids and quadrangular grids is also studied here.

  4. Goddard High Resolution Spectrograph SV/GTO Project

    NASA Technical Reports Server (NTRS)

    Ebbets, Dennis

    1999-01-01

    Contract number NAS5-30433, known at Ball Aerospace as the GHRS SV/GTO project, supported our participation in the post-launch activities of the Goddard High Resolution Spectrograph aboard the Hubble Space Telescope. The period of performance was December 1988 through December 1998. The contract supported the involvement of Dr Dennis Ebbets in the work of the GHRS Investigation Definition Team, and several of the Ball people in the documentation and publication of results. Three main categories of tasks were covered by this contract; in-orbit calibration of the GHRS, guaranteed time observations, and education and public outreach. The nature and accomplishments of these tasks are described in the report. This summary makes many references to publications in the scientific and technical literature. Appendix A is extracted from a complete bibliography, and lists those papers that are directly related to work performed under this GHRS contract. The tasks related to the in-orbit calibration of the GHRS were by far the largest responsibility during the first six years of the project. During this period Dr. Ebbets was responsible for the definition of calibration requirements, design of experiments, preparation of observing proposals, tracking their implementation and execution, and coordinating the analysis and publication of the results. Prior to the launch of HST in 1990 the observing proposals were developed in cooperation with the scientists on the GHRS DDT, engineers at Ball Aerospace, the operations staff at the STScI, and project coordinators at GSFC.

  5. Disassociation of the SV40 Genome from Capsid Proteins Prior to Nuclear Entry

    PubMed Central

    2012-01-01

    Background Previously, we demonstrated that input SV40 particles undergo a partial disassembly in the endoplasmic reticulum, which exposes internal capsid proteins VP2 and VP3 to immunostaining. Then, in the cytoplasm, disassembly progresses further to also make the genomic DNA accessible to immune detection, as well as to detection by an ethynyl-2-deoxyuridine (EdU)-based chemical reaction. The cytoplasmic partially disassembled SV40 particles retain some of the SV40 capsid proteins, VP1, VP2, and VP3, in addition to the viral genome. Findings In the current study, we asked where in the cell the SV40 genome might disassociate from capsid components. We observed partially disassembled input SV40 particles around the nucleus and, beginning at 12 hours post-infection, 5-Bromo-2-deoxyuridine (BrdU)-labeled parental SV40 DNA in the nucleus, as detected using anti-BrdU antibodies. However, among the more than 1500 cells examined, we never detected input VP2/VP3 in the nucleus. Upon translocation of the BrdU-labeled SV40 genomes into nuclei, they were transcribed and, thus, are representative of productive infection. Conclusions Our findings imply that the SV40 genome disassociates from the capsid proteins before or at the point of entry into the nucleus, and then enters the nucleus devoid of VP2/3. PMID:22882793

  6. A Taxometric Analysis of the Psychopathy Checklist: Screening Version (PCL:SV): Further Evidence of Dimensionality

    ERIC Educational Resources Information Center

    Walters, Glenn D.; Gray, Nicola S.; Jackson, Rebecca L.; Sewell, Kenneth W.; Rogers, Richard; Taylor, John; Snowden, Robert J.

    2007-01-01

    A taxometric analysis of the Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995) was performed on a group of 2,250 male and female forensic/psychiatric patients and jail/prison inmates. The 4 PCL:SV facet scores (Interpersonal, Affective, Impulsive Lifestyle, Antisocial Behavior) served as indicators in…

  7. Detection of antibodies to polyomavirus SV40 in two central European countries.

    PubMed

    Butel, J S; Wong, C; Vilchez, R A; Szücs, G; Dömök, I; Kríz, B; Slonim, D; Adam, E

    2003-03-01

    Simian virus 40 (SV40) is significantly associated with some human cancers. However, the frequency of tumor-associated virus detection differs by geographic regions, so it is important to understand the status of SV40 infections in different populations. Poliovaccines potentially containing live SV40 were used in well-documented nationwide vaccination programs in Hungary and the Czech Republic that are reported here. We analyzed serum samples from periodic surveillance programs in those two countries for antibodies to SV40 using a specific plaque reduction neutralization assay. The prevalence of antibodies was between 1.3 and 8.7% in Hungary and from 1.0 to 4.0% in the Czech Republic. Females had a higher rate of antibodies than males, reaching in certain age groups 15.6% in Hungary and 8.3% in the Czech Republic. Antibodies to SV40 were found in similar proportions in both countries among persons not directly exposed to poliovaccines and subjects vaccinated in the era of SV40-free vaccines. Complexities and limitations of current serological approaches to epidemiological studies of SV40 in humans are discussed. These data suggest that SV40 may be present in these populations and emphasize the importance of follow-up studies to determine the pathogenesis of infections by this emerging human agent.

  8. Early cytoplasmic vacuolization of African green monkey kidney cells by SV40.

    PubMed

    Miyamura, T; Kitahara, T

    1975-01-01

    As early as 3--4 hours after infection with SV40 at a high input multiplicity, African green monkey (Cercopithecus aethiops) kidney (AGMK) cells developed cytoplasmic vacuolization. At 10--20 hours after infection, the vacuolization reached its maximal level, then disappeared and SV40 specific cytopathic change followed. This vacuolization developed before the synthesis of the specific T and V antigens. This early cytoplasmic vacuolization (ECV) was prevented by preincubating the virus with specific antiserum, or by heating the virus with MgCl2. The ECV could be induced by UV-irradiated SV40. Addition of metabolic inhibitors had no effect on the induction of the ECV. These results suggest that the capacity to induce the ECV resides in a structural component(s) of SV40 virion and the vacuolization is not associated with the replication of SV40.

  9. Nuclear factor of activated T-cells (NFAT) plays a role in SV40 infection

    SciTech Connect

    Manley, Kate; O'Hara, Bethany A.; Atwood, Walter J.

    2008-03-01

    Recent evidence highlighted a role for the transcription factor, nuclear factor of activated T-cells (NFAT), in the transcription of the human polyomavirus JCV. Here we show that NFAT is also important in the transcriptional control of the related polyomavirus, Simian Virus 40 (SV40). Inhibition of NFAT activity reduced SV40 infection of Vero, 293A, and HeLa cells, and this block occurred at the stage of viral transcription. Both NFAT3 and NFAT4 bound to the SV40 promoter through {kappa}B sites located within the 72 bp repeated enhancer region. In Vero cells, NFAT was involved in late transcription, but in HeLa and 293A cells both early and late viral transcription required NFAT activity. SV40 large T-Ag was found to increase NFAT activity and provided a positive feedback loop to transactivate the SV40 promoter.

  10. In vivo exposure of marine mussels to carbamazepine and 10-hydroxy-10,11-dihydro-carbamazepine: Bioconcentration and metabolization.

    PubMed

    Boillot, C; Martinez Bueno, M J; Munaron, D; Le Dreau, M; Mathieu, O; David, A; Fenet, H; Casellas, C; Gomez, E

    2015-11-01

    Aquatic organisms are exposed to pharmaceuticals present in natural waters, but few data are available on the accumulation of these substances in such organisms. The present study evaluated the in vivo bioconcentration of two anticonvulsants--carbamazepine (CBZ) and 10-hydroxy-10,11-dihydro-carbamazepine (10 OH)--in marine mussels (Mytilus galloprovincialis) exposed to nominal 10 μg L(-1) concentrations for one week. The bioconcentration factors (BCFs) were 3.9 and 4.5 L kg(-1) dry weight (dw) for CBZ and 10 OH, respectively. CBZ accumulation reached an average tissue concentration of 29.3 ± 4.8 ng g(-1) dw, and 10 OH accumulated up to 40.9 ± 4.6 ng g(-1) dw in tissues within one week, showing first-order kinetics. BCF obtained with linear QSAR models correctly estimated the CBZ bioconcentration and overestimated the 10 OH bioconcentration to some extent. The detection of two metabolites (carbamazepine-10,11-epoxide and acridine) among the five sought suggested an active metabolism for CBZ. In contrast, none of the 10 OH metabolites were detected in mussels exposed to 10 OH. CBZ showed higher accumulation in the digestive gland, where some relevant metabolites were detected, than in other studied tissues. The implication of those findings on field biomonitoring is discussed.

  11. Combating childhood obesity: Reactions of children aged 10-11 years towards the National Child Measurement Programme.

    PubMed

    Nnyanzi, Lawrence Achilles

    2015-10-06

    The aim of this study was to explore the reactions of children aged 10-11 years towards being weighed and measured and subsequently told their correct weight as part of the National Child Measurement Programme (NCMP). The study was undertaken in primary schools in a Primary Care Trust (PCT) in the North East of England, UK. One-to-one semi-structured interviews were conducted post-NCMP measurement (and the feedback) with a sample of 21 children, aged 10-11 years, conveniently sampled from the primary schools in the PCT. Findings from the study indicate that the NCMP, especially the weight feedback letter caused annoyance, panic and worry among children who were indicated to have weight problems and oversensitised all children about weight issues, regardless of their weight category. The NCMP is a potentially useful 'wake-up call' to the fact that something needs to be done for children identified to be overweight or obese but needs to be delivered with a sensitivity to the impact of the news on the child.

  12. Control of Floret Symmetry by RAY3, SvDIV1B, and SvRAD in the Capitulum of Senecio vulgaris1[OPEN

    PubMed Central

    2016-01-01

    All members of Asteraceae, the largest flowering family, have a unique compressed inflorescence known as a capitulum, which resembles a solitary flower. The capitulum often consists of bilateral (zygomorphic) ray florets and radial (actinomorphic) disc florets. In Antirrhinum majus, floral zygomorphy is established by the interplay between dorsal petal identity genes, CYCLOIDEA (CYC) and RADIALIS (RAD), and a ventral gene DIVARICATA (DIV). To investigate the role of CYC, RAD, and DIV in the development of ray and disc florets within a capitulum, we isolated homologs of these genes from an Asteraceae species, Senecio vulgaris (common groundsel). After initial uniform expression of RAY3 (CYC), SvRAD, and SvDIV1B in ray florets only, RAY3 and SvRAD were exclusively expressed in the ventral petals of the ray florets. Our functional analysis further showed that RAY3 promotes and SvDIV1B represses petal growth, confirming their roles in floral zygomorphy. Our results highlight that while floral symmetry genes such as RAY3 and SvDIV1B appear to have a conserved role in petal growth in both Senecio and Antirrhinum, the regulatory relationships and expression domains are divergent, allowing ventral petal elongation in Senecio versus dorsal petal elongation in Antirrhinum. In S. vulgaris, diversification of CYC genes has led to novel interactions; SvDIV1B inhibits RAY3 and SvRAD, and may activate RAY2. This highlights how recruitment of floral symmetry regulators into dynamic networks was crucial for creating a complex and elaborate structure such as the capitulum. PMID:27208229

  13. Effect of pressure on the semipolar GaN (10-11) growth mode on patterned Si substrates

    NASA Astrophysics Data System (ADS)

    Liu, Jian-Ming; Zhang, Jie; Lin, Wen-Yu; Ye, Meng-Xin; Feng, Xiang-Xu; Zhang, Dong-Yan; Steve, Ding; Xu, Chen-Ke; Liu, Bao-Lin

    2015-05-01

    In this paper, we investigate the effect of pressure on the growth mode of high quality (10-11) GaN using an epitaxial lateral over growth (ELO) technique by metal organic chemical vapor deposition (MOCVD). Two pressure growth conditions, high pressure (HP) 1013 mbar and low pressure growth (LP) 500 mbar, are employed during growth. In the high pressure growth conditions, the crystal quality is improved by decreasing the dislocation and stack fault density in the strip connection locations. The room temperature photoluminescence measurement also shows that the light emission intensity increases three times using the HP growth condition compared with that using the LP growth conditions. In the low temperature (77 K) photoluminescence, the defects-related peaks are very obvious in the low pressure growth samples. This result also indicates that the crystal quality is improved using the high pressure growth conditions. Project support by the National High Technology Research and Development Program of China (Green Laser).

  14. Revisiting the Chemistry of Guaiacwood Oil: Identification and Formation Pathways of 5,11- and 10,11-Epoxyguaianes.

    PubMed

    Tissandié, Loïc; Gaysinski, Marc; Brévard, Hugues; Meierhenrich, Uwe J; Filippi, Jean-Jacques

    2017-02-24

    Guaiacwood oil from Bulnesia sarmientoi Lorentz ex. Griseb is a common natural ingredient of the perfume industry used in both domestic and luxury fragrances for its highly appreciated woody-rosy odor, as well as its excellent fixative properties. Despite its long and traditional use as a perfume ingredient, guaiacwood oil has not been extensively studied. Thus, the chemical characterization of its constituents by using a full array of GC-hyphenated techniques (GC-MS, GC × GC-MS, and pc-GC) combined with conventional chemical fractionation was undertaken. In the course of this work, 15 new sesquiterpenoids mostly belonging to the 5,11- and 10,11-epoxyguaiane families were identified. Each isolated compound was fully characterized by NMR and MS. Collectively, the specific chemical relationships observed between sesquiterpene oxides and alcohols permitted the formulation of probable formation pathways regarding their presence as natural constituents of guaiacwood extracts.

  15. Absolute frequency list of the ν3-band transitions of methane at a relative uncertainty level of 10(-11).

    PubMed

    Okubo, Sho; Nakayama, Hirotaka; Iwakuni, Kana; Inaba, Hajime; Sasada, Hiroyuki

    2011-11-21

    We determine the absolute frequencies of 56 rotation-vibration transitions of the ν(3) band of CH(4) from 88.2 to 90.5 THz with a typical uncertainty of 2 kHz corresponding to a relative uncertainty of 2.2 × 10(-11) over an average time of a few hundred seconds. Saturated absorption lines are observed using a difference-frequency-generation source and a cavity-enhanced absorption cell, and the transition frequencies are measured with a fiber-laser-based optical frequency comb referenced to a rubidium atomic clock linked to the international atomic time. The determined value of the P(7) F(2)((2)) line is consistent with the International Committee for Weights and Measures recommendation within the uncertainty.

  16. Kindling-associated SV2A expression in hilar GABAergic interneurons of the mouse dentate gyrus.

    PubMed

    Ohno, Yukihiro; Okumura, Takahiro; Terada, Ryo; Ishihara, Shizuka; Serikawa, Tadao; Sasa, Masashi

    2012-02-29

    Immunohistochemical studies were performed to analyze the expressional changes in hippocampal synaptic vesicle protein 2A (SV2A) following pentylenetetrazole (PTZ) kindling. Repeated treatments of mice with sub-convulsive PTZ (40 mg/kg, i.p.) for 15 days progressively enhanced seizure susceptibility and induced clonic convulsions in most animals examined. Topographical analysis of hippocampal SV2A-immunoreactivity revealed that SV2A was densely expressed in the hilar region of the dentate gyrus, stratum lucidum of the CA3 field and around the periphery of CA3 pyramidal neurons. PTZ kindling region-specifically increased SV2A expression in the dentate hilus without affecting that in the stratum lucidum or the pyramidal cell layer of the CA3 field. Confocal laser microscopic analysis using PTZ-kindled mice illustrated that most SV2A was co-expressed with glutamic acid decarboxylase 67 in the cell bodies and dendrites of hilar interneurons. However, SV2A-immunoreactivity was negligibly observed in the hilar glutamatergic nerve terminals (mossy fibers) probed with the anti-vesicular glutamate transporter 1 antibody. The present study suggests that SV2A specifically regulates hilar GABAergic neurotransmission in the kindled hippocampus probably as a compensatory or prophylactic mechanism against kindling epileptogenesis.

  17. A longitudinal study of grapheme-color synesthesia in childhood: 6/7 years to 10/11 years.

    PubMed

    Simner, Julia; Bain, Angela E

    2013-01-01

    Grapheme-color synesthesia is a condition characterized by enduring and consistent associations between letter/digits and colors. This study is the continuation of longitudinal research begun by Simner et al. (2009) which aimed to explore the development of this condition in real time within a childhood population. In that earlier study we randomly sampled over 600 children and tested them aged 6/7 and 7/8 years. We identified the child synesthetes within that cohort and measured their development over 1 year, in comparison to a group of non-synesthetic children with both average and superior memories. We were able to show the beginnings of a developmental progression in which synesthetic associations (e.g., A = red) mature over time from relatively chaotic pairings into a system of fixed consistent associations. In the current study we return to this same population three years later when participants are now 10/11 years. We used the same paired-association memory task to determine the synesthetic status of our participants and to also establish synesthetes' inventories of grapheme-color associations. We compared their inventories to those from age 6/7 and 7/8 years to examine how synesthesia matures over time. Together with earlier findings, our study shows that grapheme-color synesthesia emerges with a protracted trajectory, with 34% of letters/digits fixed at age 6/7 years, 48% fixed at 7/8 years and 71% fixed at 10/11 years. We also show several cases where synesthesia is not developing in the same time-frame as peers, either because it has died out at an older age, or because it was slower to develop than other cases. Our study paints the first picture of the emergence of synesthesia in real-time over four years within a randomly sampled population of child synesthetes.

  18. High efficiency of replication and expression of foreign genes in SV40-transformed human fibroblasts.

    PubMed Central

    Boast, S; La Mantia, G; Lania, L; Blasi, F

    1983-01-01

    Human fibroblasts (HF) were transformed in vitro with origin-defective SV40 DNA (ori-) using the calcium phosphate co-precipitation technique. The SV40 ori- transformed human cells (HSF) were able to replicate efficiently a recombinant DNA molecule containing the ori sequence of SV40 DNA. Transfection of HFS with pTBC1, a recombinant pi vx plasmid containing the herpes simplex virus thymidine kinase (HSV-TK) gene and the ori SV40 sequences, results in high levels of TK mRNA of correct size. The pTBC1 plasmid does not appear to contain 'poison' sequences and can be efficiently re-established in Escherichia coli after replication in human cells. This host vector system may be of great usefulness in studying the expression of human genes in human cells. Images Fig. 2. Figure 3. PMID:6321161

  19. Relaxin has anti-apoptotic effects on human trophoblast-derived HTR-8/SV neo cells.

    PubMed

    Lodhi, Romana S Z; Nakabayashi, Koji; Suzuki, Kaho; Yamada, Ai Y; Hazama, Rhoichi; Ebina, Yasuhiko; Yamada, Hideto

    2013-12-01

    The study was conducted to evaluate the effects of human relaxin on apoptosis in the human trophoblast derived HTR-8/SV neo cell line, which is a possible model of human extravillous trophoblasts (EVTs). HTR-8/SV neo cells, cultured in phenol red free RPMI1640 medium, were treated with different doses of human recombinant (rH2) relaxin in serum-deprived conditions. RT-PCR was used for evaluating relaxin receptor: RXFP1 and RXFP2 expression in HTR-8/SV neo cells. The cell death was examined by TUNEL assay. Furthermore, we investigated caspase-3, cleaved PARP and Bcl-2 expressions by Western blot analysis to recognize the translational effects of anti-apoptotic and pro-apoptotic proteins. RXFP1 and RXFP2 mRNA expression was observed in HTR-8/SV neo cells. Compared with untreated control cultures, treatment with rH2 relaxin, decreased TUNEL-positive rate in HTR-8/SV neo cells was observed. Western blot analysis revealed that treatment with rH2 relaxin decreased the expression of caspase-3 and cleaved PARP, but in contrast increased Bcl-2 expression in those cells. These results suggest that rH2 relaxin has anti-apoptotic effects on HTR8/SV neo cells by decreasing pro-apoptotic caspase-3 and cleaved PARP expression and up-regulating anti-apoptotic Bcl-2 expression.

  20. Preferential increase in the hippocampal synaptic vesicle protein 2A (SV2A) by pentylenetetrazole kindling.

    PubMed

    Ohno, Yukihiro; Ishihara, Shizuka; Terada, Ryo; Kikuta, Miki; Sofue, Nobumasa; Kawai, Yoshiko; Serikawa, Tadao; Sasa, Masashi

    2009-12-18

    The present study evaluated the expressional levels of synaptic vesicle protein 2A (SV2A) and other secretary machinery proteins (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, Munc18-1, N-ethylmaleimide-sensitive factor (NSF) and soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP)) in a pentylenetetrazole (PTZ) kindling model. Repeated administration of sub-convulsive PTZ (40 mg/kg, i.p.) progressively increased seizure susceptibility in mice and consistently induced clonic seizures in most animals tested at 15 days after the treatment. Western blot analysis revealed that, among the secretary machinery proteins examined, hippocampal SV2A was selectively elevated by PTZ kindling. PTZ kindling-induced SV2A expression appeared region-specific and the SV2A levels in the cerebral cortex or cerebellum were unaltered. In addition, SV2A expression by PTZ kindling was prominent in the hilar region of the dentate gyrus (DG) where GABAergic interneurons are located, but not in other hippocampal regions (e.g., the stratum lucidum of the CA3 and synaptic layers surrounding CA1 or CA3 pyramidal neurons). These findings suggest that PTZ kindling preferentially elevates SV2A expression in the hippocampus probably as a compensatory mechanism to activate the inhibitory neurotransmission.

  1. Plasmalemmal vesicle associated protein (PV1) modulates SV40 virus infectivity in CV-1 cells.

    PubMed

    Tse, Dan; Armstrong, David A; Oppenheim, Ariella; Kuksin, Dmitry; Norkin, Leonard; Stan, Radu V

    2011-08-26

    Plasmalemmal vesicle associated protein (Plvap/PV1) is a structural protein required for the formation of the stomatal diaphragms of caveolae. Caveolae are plasma membrane invaginations that were implicated in SV40 virus entry in primate cells. Here we show that de novo Plvap/PV1 expression in CV-1 green monkey epithelial cells significantly reduces the ability of SV40 virus to establish productive infection, when cells are incubated with low concentrations of the virus. However, in presence of high viral titers PV1 has no effect on SV40 virus infectivity. Mechanistically, PV1 expression does not reduce the cell surface expression of known SV40 receptors such as GM1 ganglioside and MHC class I proteins. Furthermore, PV1 does not reduce the binding of virus-like particles made by SV40 VP1 protein to the CV-1 cell surface and does not impact their internalization when cells are incubated with either high or low VLP concentrations. These results suggest that PV1 protein is able to block SV40 infectivity at low but not at high viral concentration either by interfering with the infective internalization pathway at the cell surface or at a post internalization step.

  2. Plasmalemmal vesicle associated protein (PV1) modulates SV40 virus infectivity in CV-1 cells

    PubMed Central

    Tse, Dan; Armstrong, David A.; Oppenheim, Ariella; Kuksin, Dimitry; Norkin, Leonard; Stan, Radu V.

    2011-01-01

    Plasmalemmal vesicle associated protein (Plvap/PV1) is a structural protein required for the formation of the stomatal diaphragms of caveolae. Caveolae are plasma membrane invaginations that were implicated in SV40 virus entry in primate cells. Here we show that de novo Plvap/PV1 expression in CV-1 green monkey epithelial cells significantly reduces the ability of SV40 virus to establish productive infection, when cells are incubated with low concentrations of the virus. However, in presence of high viral titers PV1 has no effect on SV40 virus infectivity. Mechanistically, PV1 expression does not reduce the cell surface expression of known SV40 receptors such as GM1 ganglioside and MHC class I proteins. Furthermore, PV1 does not reduce the binding of virus-like particles made by SV40 VP1 protein to the CV-1 cell surface and does not impact their internalization when cells are incubated with either high or low VLP concentrations. These results suggest that PV1 protein is able to block SV40 infectivity at low but not at high viral concentration either by interfering with the infective internalization pathway at the cell surface or at a post internalization step. PMID:21827737

  3. Luni-solar 18.6- and solar cycle 10 - 11-year signals in USA air temperature records.

    NASA Astrophysics Data System (ADS)

    Currie, R. G.

    1993-02-01

    Spectrum analysis of 1197 USA air temperature records yields evidence for two peaks with periods 18.8±1.7 and 10.4±0.5 years. Tests by the t-statistic show that both are significant at confidence levels of 99.9 per cent, and both account for 23 per cent of total variance in the raw data. They are identified as the luni-solar 18.6 year Mn and solar cycle Sc 10 - 11 year signals in climate, induced by the twelfth largest constituent tide acting on the Earth and a variation of 10 to 11 years in the Sun's luminosity of the order of 0.1 per cent. Amplitude and phase of Mn wavetrains are highly non-stationary with respect to both time and geography; in particular, abrupt 180° phase changes in wave polarity are often observed. Amplitude and phase of the Sc waves are also highly non-stationary.

  4. False carbamazepine positives due to 10,11-dihydro-10-hydroxycarbamazepine breakdown in the GC-MS injector port.

    PubMed

    Lewis, Russell J; Angier, Mike K; Johnson, Robert D

    2014-10-01

    During the investigation of aviation accidents, postmortem specimens from accident victims are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. A case recently received by CAMI screened positive for the anticonvulsant medication carbamazepine (CBZ; Tegretol(®)) by gas chromatography-mass spectrometry (GC-MS). The CBZ found during this routine screening procedure was subsequently confirmed using a CBZ-specific GC-MS procedure. It was later discovered that the accident victim had been prescribed oxcarbazepine (OXCBZ; Trileptal(®)). OXCBZ is structurally similar to CBZ and is metabolized by cytosolic enzymes in the liver to an active metabolite, 10,11-dihydro-10-hydroxycarbamazepine (DiCBZ). It was determined that the CBZ initially found in this case was present due to the thermal breakdown of DiCBZ in the GC-MS injector port. In the current study, this conversion was investigated and the percentage of CBZ formed at various injector port temperatures was determined. Additionally, these three compounds were quantified in nine fluid and tissue specimens from the case in question. Liquid chromatography-mass spectrometry was also incorporated to further demonstrate the absence/presence of CBZ in these samples.

  5. Transdermal delivery of 10,11-methylenedioxycamptothecin by hyaluronic acid based nanoemulsion for inhibition of keloid fibroblast.

    PubMed

    Gao, Yuanyuan; Cheng, Xiaojie; Wang, Zhiguo; Wang, Juan; Gao, Tingting; Li, Peng; Kong, Ming; Chen, Xiguang

    2014-11-04

    This study designs an alternative transdermal delivery system for 10,11-methylenedioxycamptothecin(MD-CPT) to inhibit keloid. Hyaluronic acid nanoemulsions (HANs) with nano size, negative charge and good stability were prepared as transdermal carriers. The MD-CPT loaded HANs performed desirable skin permeable capacity across human keloid skin and the drug was transferred directly to keloid lesion area. MD-CPT was delivered percutaneously higher than the control group. FITC-HANs could be successfully internalized by keloid fibroblast (KF) and deliver MD-CPT toward nucleus, inhibited the proliferation of KF, while there was no serious toxicity to normal skin fibroblasts. The growth-inhibitory effect was further clarified upon cell cycle regulation, which arrested cells at G1/S and prevented them entry into mitosis. KF gene expression demonstrated plasminogen activator inhibitor-1 (PAI-1) was significantly down-regulated and Smad7 up-regulated, which was beneficial to inhibit keloid. The study demonstrated that as transdermal delivery of MD-CPT by HANs has potential for inhibition of keloid fibroblast.

  6. SV40 and p53 as team players in childhood lymphoproliferative disorders.

    PubMed

    Heinsohn, Susanne; Scholz, Roswitha; Kabisch, Hartmut

    2011-05-01

    Simian virus 40 (SV40) is known to be potently oncogenic and can induce several types of tumours, such as lymphoma. p53 was discovered as a cellular partner of the SV40 large T-antigen, the oncoprotein of this virus. There have not been many studies on SV40 and p53 in lymphomas and the ones that exist, are controversial. A comparison of these two components in lymphoma has not been reported previously. We examined 91 lymphomas [60 B-cell non-Hodgkin's lymphomas (B-NHLs), 19 B-cell acute lymphoblastic leukemias (B-ALLs), 7 B-cell precursor acute lymphoblastic leukemias and 5 T-cell acute lymphoblastic leukemias] for the presence of SV40. Overall, 40 samples from 12 B-NHL/19 B-ALL patients were additionally investigated for p53 mutation in the hot-spot exons 5 to 8. Overall, we found 62/91 lymphomas to be SV40-positive, among them 16/19 B-ALLs and 38/60 B-NHLs. SV40 was absent in 147 of the 149 blood control samples. We found 11 p53 mutations in 19 B-ALL patients: 5 in exon 5 (codons 132, 141, 143, 155 and 181), 4 in exon 7 (codons 236, 238 and 248), 2 in exon 8 (codon 273). In B-NHL patients we found p53-mutations in 9/12 samples: 6 of these in 3 lymph nodes (LNs). One LN harboured 3 different p53 mutations: Exon 5 (codon 132), exon 6 (codon 213) and exon 8 (codon 288). Another LN showed 2 different p53 mutations: Exon 6 (codon 213) and exon 8 (codon 285). Except for 1 nonsense mutation in an LN of a B-NHL patient, all 20 mutations were missense mutations, 2 were homozygous, both found in B-NHL-samples, and one of these (codon 175) is known to cause the global denaturation of p53. All occur in the DNA-binding domain of p53. All specimens showing a p53 mutation, were SV40-positive. p53 mutaions found in LNs of B-NHL patients harbour high SV40 copy numbers. Our data strongly support an important role for SV40, as well as a strong association of SV40 and p53 in childhood lympho-proliferative disorders.

  7. Development and Validation of a New Mouse Model to Investigate the Role of SV2A in Epilepsy

    PubMed Central

    Bartholome, Odile; Sánchez Gil, Judit; Neirinckx, Virginie; Wislet, Sabine; Becker, Guillaume; Plenevaux, Alain; Van den Ackerveken, Priscilla; Rogister, Bernard

    2016-01-01

    SV2A is a glycoprotein present in the membranes of most synaptic vesicles. Although it has been highly conserved throughout evolution, its physiological role remains largely unknown. Nevertheless, Levetiracetam, a very effective anti-epileptic drug, has been recently demonstrated to bind to SV2A. At present, our understanding of the normal function of SV2A and its possible involvement in diseases like epilepsy is limited. With this study, we sought to develop a relevant model enabling analysis of SV2A’s role in the occurrence or progression of epilepsy. For this purpose, we generated a floxed SV2A mouse model with conditional alleles carrying LoxP sites around exon 3 by means of a gene-targeting strategy. The SV2A lox/lox mouse line is indistinguishable from wild-type mice. When the recombination was observed in all cells, a model of mice with both SV2A alleles floxed around exon 3 recapitulated the phenotype of SV2A KO mice, including seizures. However, the specific invalidation of SV2A in the CA3 hippocampal region was not followed by epileptic seizures or decrease in the epileptic threshold on pentylenetetrazol (PTZ) test. These results demonstrate that the floxed SV2A mouse line has been successfully established. This transgenic mouse model will be useful for investigating SV2A functions related to cell types and developmental stages. PMID:27861538

  8. p53 elevation in human cells halt SV40 infection by inhibiting T-ag expression

    PubMed Central

    Drayman, Nir; Ben-nun-Shaul, Orly; Butin-Israeli, Veronika; Srivastava, Rohit; Rubinstein, Ariel M.; Mock, Caroline S.; Elyada, Ela; Ben-Neriah, Yinon; Lahav, Galit; Oppenheim, Ariella

    2016-01-01

    SV40 large T-antigen (T-ag) has been known for decades to inactivate the tumor suppressor p53 by sequestration and additional mechanisms. Our present study revealed that the struggle between p53 and T-ag begins very early in the infection cycle. We found that p53 is activated early after SV40 infection and defends the host against the infection. Using live cell imaging and single cell analyses we found that p53 dynamics are variable among individual cells, with only a subset of cells activating p53 immediately after SV40 infection. This cell-to-cell variabilty had clear consequences on the outcome of the infection. None of the cells with elevated p53 at the beginning of the infection proceeded to express T-ag, suggesting a p53-dependent decision between abortive and productive infection. In addition, we show that artificial elevation of p53 levels prior to the infection reduces infection efficiency, supporting a role for p53 in defending against SV40. We further found that the p53-mediated host defense mechanism against SV40 is not facilitated by apoptosis nor via interferon-stimulated genes. Instead p53 binds to the viral DNA at the T-ag promoter region, prevents its transcriptional activation by Sp1, and halts the progress of the infection. These findings shed new light on the long studied struggle between SV40 T-ag and p53, as developed during virus-host coevolution. Our studies indicate that the fate of SV40 infection is determined as soon as the viral DNA enters the nucleus, before the onset of viral gene expression. PMID:27462916

  9. Immunoprecipitation of SV40 replicating minichromosomes complexed with bacteriophage T4 gene 32 protein.

    PubMed Central

    Miranda, E I; Garrido-Guerrero, E; Garcia-Carranca, A; Gariglio, P

    1992-01-01

    Simian Virus 40 (SV40) DNA replication is a useful model to study eukaryotic cell DNA replication because it encodes only one replication protein and its genome has a nucleoprotein structure ('minichromosome') indistinguishable from cellular chromatin. Late after infection SV40 replicating DNA molecules represent about 5% of total viral minichromosomes. Since gene 32 protein (P32) from bacteriophage T4 interacts with single-stranded DNA and SV40 replication complexes are expected to contain single-stranded regions at the replication forks, we asked whether P32 might be used to isolate replicating SV40 minichromosomes. When nuclear extracts from SV40 infected cells were treated sequentially with P32 and anti-P32 antibodies, pulse-labeled minichromosomes were selectively immunoprecipitated. Agarose gel electrophoresis analysis confirmed that immunoprecipitated material corresponded to SV40 replicative intermediates. Protein analysis of the pelleted material revealed several proteins of viral and cellular origin. Among them, T antigen and histones were found to be complexed with at least other three proteins from cellular origin, to the replicative complexes. Additionally, anti-P32 antibodies were able to detect three cellular proteins of approximately 70, 32 and 13 kDa in western blots. These proteins could correspond to those found as part of an eukaryotic multisubunit single-stranded DNA binding protein. The use of P32 and anti-P32 antibodies thus allows the separation of replicating from mature SV40 minichromosomes and can constitute a novel method to enrich and to study replicative active chromatin. Images PMID:1311833

  10. Associations between sleeping habits and food consumption patterns among 10-11-year-old children in Finland.

    PubMed

    Westerlund, Lisa; Ray, Carola; Roos, Eva

    2009-11-01

    The increasing prevalence of overweight and obesity among children is of special concern. Inverse associations between sleep length and overweight have been found in children. Short sleeping hours result in hormonal changes, which increase perceived hunger and appetite. This could affect food intake, and consequently lead to overweight. The aim is to find out whether there is an association between adequate sleep and food consumption among 10-11-year-old school children in Finland. One thousand two hundred and sixty-five children (response rate 79 %), aged 9-11, from thirty-one schools filled in a questionnaire about their health behaviour. Inadequate sleep was measured as short sleeping hours during school nights and weekend nights, difficulties in waking up in the morning and tiredness during the day. Food consumption patterns were measured by two consumption indices, energy-rich foods and nutrient-dense foods, based on a short FFQ (sixteen items). Inadequate sleep is associated with food consumption patterns. Boys with shorter sleep duration during school nights, and who were felt tired during the day, were more likely to consume energy-rich foods. Girls with shorter sleep duration during school nights consumed more likely energy-rich foods and less likely nutrient-dense foods. Adjusting for physical activity and screen time weakened the explored associations. The associations with energy-rich foods were stronger for boys than for girls. Sleeping habits are associated with food consumption patterns. Shorter sleep duration during school nights in school children is associated with higher consumption of energy-rich foods.

  11. Visualization of SV2A conformations in situ by the use of Protein Tomography

    SciTech Connect

    Lynch, Berkley A.; Matagne, Alain; Braennstroem, Annika; Euler, Anne von; Jansson, Magnus; Hauzenberger, Elenor; Soederhaell, J. Arvid

    2008-10-31

    The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography{sup TM}. We identified two major conformations of SV2A in mouse brain tissue: first, a compact, funnel-structure with a pore-like opening towards the cytoplasm; second, a more open, V-shaped structure with a cleft-like opening towards the intravesicular space. The large differences between these conformations suggest a high degree of flexibility and support a valve-like mechanism consistent with the postulated transporter role of SV2A. These two conformations are represented both in samples treated with LEV, and in saline-treated samples, which indicates that LEV binding does not cause a large-scale conformational change of SV2A, or lock a specific conformational state of the protein. This study provides the first direct structural data on SV2A, and supports a transporter function suggested by sequence homology to MFS class of transporter proteins.

  12. The Utility of the YLS/CMI-SV for Assessing Youth Offenders in Singapore

    PubMed Central

    Yu, Hui; Lee, Yirong; Zeng, Gerald

    2014-01-01

    The Youth Level of Service/Case Management Inventory–Screening Version (YLS/CMI-SV) is designed to provide a preliminary estimate of the level of risk for antisocial behaviors as well as an indication of areas for intervention in youth offenders. This study examined the predictive validity of the YLS/CMI-SV for violent, nonviolent, and general recidivism in a sample of 3,264 youth offenders within a Singaporean context (Mfollow-up = 1,764.5 days; SDfollow-up = 521.5). Cox regression and Receiver Operating Characteristic analyses revealed that the YLS/CMI-SV is significantly predictive of general, violent, and nonviolent recidivism for the male youth offenders, but there were mixed results for the female youth offenders. Overall, these results indicated that the YLS/CMI-SV is a useful measure for assessing the levels of risk for male youth offenders, and more investigation is needed to determine the suitability of the YLS/CMI-SV for the female youth offenders. Its implications for clinical practice and policy are discussed. PMID:25983353

  13. Exposure to light at night accelerates aging and spontaneous uterine carcinogenesis in female 129/Sv mice

    PubMed Central

    Popovich, Irina G.; Zabezhinski, Mark A.; Panchenko, Andrei V.; Piskunova, Tatiana S.; Semenchenko, Anna V.; Tyndyk, Maragriata L.; Yurova, Maria N.; Anisimov, Vladimir N.

    2013-01-01

    The effect of the constant illumination on the development of spontaneous tumors in female 129/Sv mice was investigated. Forty-six female 129/Sv mice starting from the age of 2 mo were kept under standard light/dark regimen [12 h light (70 lx):12hr dark; LD, control group], and 46 of 129/Sv mice were kept under constant illumination (24 h a day, 2,500 lx, LL) from the age of 5 mo until to natural death. The exposure to the LL regimen significantly accelerated body weight gain, increased body temperature as well as acceleration of age-related disturbances in estrous function, followed by significant acceleration of the development of the spontaneous uterine tumors in female 129/Sv mice. Total tumor incidence as well as a total number of total or malignant tumors was similar in LL and LD group (p > 0.05). The mice from the LL groups survived less than those from the LD group (χ2 = 8.5; p = 0.00351, log-rank test). According to the estimated parameters of the Cox’s regression model, constant light regimen increased the relative risk of death in female mice compared with the control (LD) group (p = 0.0041). The data demonstrate in the first time that the exposure to constant illumination was followed by the acceleration of aging and spontaneous uterine tumorigenesis in female 129/Sv mice. PMID:23656779

  14. Induction of ermSV by 16-membered-ring macrolide antibiotics.

    PubMed Central

    Kamimiya, S; Weisblum, B

    1997-01-01

    The erm family of 23S rRNA adenine-N6-methyltransferases confers resistance to all macrolide-lincosamide-streptograminB (MLS) antibiotics, but not all MLS antibiotics induce synthesis of Erm methyltransferase with equal efficiency in a given organism. The induction efficiency of a test panel of MLS antibiotics was studied by using two translational attenuator-lac reporter gene fusion constructs, one based on ermSV from Streptomyces viridochromogenes NRRL 2860 and the other based on ermC from Staphylococcus aureus RN2442. Four types of responses which were correlated with the macrolide ring size were seen, as follows: group 1, both ermSV and ermC were induced by the 14-membered-ring macrolides erythromycin, lankamycin, and matromycin, as well as by the lincosamide celesticetin; group 2, neither ermSV nor ermC was induced by the 12-membered-ring macrolide methymycin or by the lincosamide lincomycin or the streptogramin type B antibiotic ostreogrycin B; group 3, ermSV was selectively induced over ermC by the 16-membered-ring macrolides carbomycin, chalcomycin, cirramycin, kitasamycin, maridomycin, and tylosin; and group 4, ermC was selectively induced over ermSV by the 14-membered-ring macrolide megalomicin. These data suggest that the leader peptide determines the specificity of induction by different classes of MLS antibiotics and that for a given attenuator, a major factor which determines whether a given macrolide induces resistance is its size. PMID:9055987

  15. Prediction of drug-drug interactions with carbamazepine-10,11-epoxide using a new in vitro assay for epoxide hydrolase inhibition.

    PubMed

    Rosa, Maria; Bonnaillie, Pierre; Chanteux, Hugues

    2016-12-01

    1. Carbamazepine is an antiepileptic drug which is metabolized by CYP3A4 into carbamazepine-10,11-epoxide. This metabolite is then detoxified by epoxide hydrolase. As carbamazepine-10,11-epoxide has been associated with neurotoxicity, it is critical to identify whether a new antiepileptic drug has the potential to inhibit epoxide hydrolase and therefore increase carbamazepine-10,11-epoxide plasma levels. 2. In this study, an in vitro assay was developed to evaluate epoxide hydrolase activity by using carbamazepine-10,11-epoxide as probe substrate. The ability of this assay to predict drug-drug interactions (DDI) at the epoxide hydrolase level was also investigated. 3. To this aim, known inhibitors of epoxide hydrolase for which in vivo data are available were used. Firstly, carbamazepine-10,11-epoxide hydrolase activity was determined in liver microsomes, cytosol and hepatocytes. Thereafter, the IC50 of epoxide hydrolase inhibitors (progabide, valproic acid, valpromide and valnoctamide) was determined in liver microsomes and hepatocytes. Finally, prediction of AUC increase was performed using the in vitro data generated. 4. Interestingly, epoxide hydrolase activity was found to be much higher in human hepatocytes compared to liver microsomes/cytosol. Even though assessed on a limited number of compounds, this study demonstrated that the use of hepatocytes seems to be a more relevant model to assess and predict DDI at the epoxide hydrolase level.

  16. Pelvis width associated with bone mass distribution at the proximal femur in children 10-11 years old.

    PubMed

    Cardadeiro, Graça; Baptista, Fátima; Janz, Kathleen F; Rodrigues, Luís A; Sardinha, Luís B

    2014-03-01

    Differences in skeletal geometry may generate different patterns of mechanical loading to bone. Impact and muscle loading during physical activity have been shown to influence skeletal geometry. The purpose of this study was to compare geometric measures of the pelvis and proximal femur (PF) of young children and to analyze the contribution and potential interaction of these geometric measures with physical activity on PF bone mass distribution. Participants were 149 girls and 145 boys, aged 10-11 years. Total body and left hip DXA scans were used to derive pelvic and PF geometric measures and PF bone mineral density (BMD) at the femoral neck (FN), trochanter (TR), and intertrochanter (IT). These subregions were used to represent bone mass distribution via three BMD ratios: FN:PF, TR:PF, and IT:PF. Physical activity was objectively measured using accelerometry, and maturity was estimated as the years of distance from peak height velocity. When compared to boys, girls had a wider pelvic diameter and greater interacetabular distances (p < 0.001), lower BMD at FN, TR, and IT (p < 0.05), and higher TR:PF (p < 0.001). After controlling for maturity, body height, and lean body mass, the interacetabular distance in girls explained 21.1 % (β = 0.713, p < 0.001) in TR:PF and 2.9 % (β = -0.179, p = 0.031) in the IT:PF. Neck-shaft angle explained 5.6 % (β = -0.265, p = 0.001) of the IT:PF and 3.1 % (β = 0.194, p = 0.018) of the FN:PF. In boys, FN axis length explained 2.9 % (β = 0.195, p = 0.040) of TR:PF. There was no main effect of physical activity or interaction effect with pelvic geometry in explaining BMD differences among the subregions of the PF. Even before sexual dimorphism, girls have a wider pelvis than boys, which accounted for proportionally greater BMD of the TR than other subregions of the PF.

  17. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease.

    PubMed

    Dunn, Amy R; Stout, Kristen A; Ozawa, Minagi; Lohr, Kelly M; Hoffman, Carlie A; Bernstein, Alison I; Li, Yingjie; Wang, Minzheng; Sgobio, Carmelo; Sastry, Namratha; Cai, Huaibin; Caudle, W Michael; Miller, Gary W

    2017-03-14

    Members of the synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, although SV2C with its restricted basal ganglia distribution is poorly characterized. SV2C is emerging as a potentially relevant protein in Parkinson disease (PD), because it is a genetic modifier of sensitivity to l-DOPA and of nicotine neuroprotection in PD. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of PD. Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fast-scan cyclic voltammetry, reduced striatal dopamine content, disrupted α-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Furthermore, SV2C expression is dramatically altered in postmortem brain tissue from PD cases but not in Alzheimer disease, progressive supranuclear palsy, or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction.

  18. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease

    PubMed Central

    Stout, Kristen A.; Ozawa, Minagi; Lohr, Kelly M.; Hoffman, Carlie A.; Bernstein, Alison I.; Li, Yingjie; Wang, Minzheng; Sgobio, Carmelo; Sastry, Namratha; Cai, Huaibin; Caudle, W. Michael

    2017-01-01

    Members of the synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, although SV2C with its restricted basal ganglia distribution is poorly characterized. SV2C is emerging as a potentially relevant protein in Parkinson disease (PD), because it is a genetic modifier of sensitivity to l-DOPA and of nicotine neuroprotection in PD. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of PD. Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fast-scan cyclic voltammetry, reduced striatal dopamine content, disrupted α-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Furthermore, SV2C expression is dramatically altered in postmortem brain tissue from PD cases but not in Alzheimer disease, progressive supranuclear palsy, or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction. PMID:28246328

  19. Cellular factors required for multiple stages of SV40 DNA replication in vitro.

    PubMed Central

    Fairman, M P; Stillman, B

    1988-01-01

    Plasmids containing the SV40 origin replicate in the presence of SV40 T antigen and a cell free extract derived from human 293 cells. Upon fractionation of this extract, two essential replication factors have been identified. One of these is a multi-subunit DNA binding protein containing polypeptides of 70,000, 34,000 and 11,000 daltons which may function as a eukaryotic single strand DNA binding protein (SSB). The other partially purified fraction is required with T antigen for the first stage of DNA replication, the formation of a pre-synthesis complex at the replication origin. These results, and others, define multiple stages of SV40 DNA replication in vitro which are analogous to multiple stages of Escherichia coli and phage lambda replication, and may reflect similar events in the replication of cellular chromosomes. Images PMID:2841119

  20. High electrical conductivity in Ni₃(2,3,6,7,10,11-hexaiminotriphenylene)₂, a semiconducting metal-organic graphene analogue.

    PubMed

    Sheberla, Dennis; Sun, Lei; Blood-Forsythe, Martin A; Er, Süleyman; Wade, Casey R; Brozek, Carl K; Aspuru-Guzik, Alán; Dincă, Mircea

    2014-06-25

    Reaction of 2,3,6,7,10,11-hexaaminotriphenylene with Ni(2+) in aqueous NH3 solution under aerobic conditions produces Ni3(HITP)2 (HITP = 2,3,6,7,10,11-hexaiminotriphenylene), a new two-dimensional metal-organic framework (MOF). The new material can be isolated as a highly conductive black powder or dark blue-violet films. Two-probe and van der Pauw electrical measurements reveal bulk (pellet) and surface (film) conductivity values of 2 and 40 S·cm(-1), respectively, both records for MOFs and among the best for any coordination polymer.

  1. Low prevalence of SV40 in Swiss mesothelioma patients after elimination of false-positive PCR results.

    PubMed

    Ziegler, Annemarie; Seemayer, Christian A; Hinterberger, Marc; Vogt, Peter; Bigosch, Colette; Gautschi, Oliver; Tornillo, Luigi; Betticher, Daniel C; Moch, Holger; Stahel, Rolf A

    2007-09-01

    The association of simian virus 40 (SV40) with malignant pleural mesothelioma is currently under debate. In some malignancies of viral aetiology, viral DNA can be detected in the patients' serum or plasma. To characterize the prevalence of SV40 in Swiss mesothelioma patients, we optimized a real-time PCR for quantitative detection of SV40 DNA in plasma, and used a monoclonal antibody for immunohistochemical detection of SV40 in mesothelioma tissue microarrays. Real-time PCR was linear over five orders of magnitude, and sensitive to a single gene copy. Repeat PCR determinations showed excellent reproducibility. However, SV40 status varied for independent DNA isolates of single samples. We noted that SV40 detection rates by PCR were drastically reduced by the implementation of strict room compartmentalization and decontamination procedures. Therefore, we systematically addressed common sources of contamination and found no cross-reactivity with DNA of other polyomaviruses. Contamination during PCR was rare and plasmid contamination was infrequent. SV40 DNA was reproducibly detected in only 4 of 78 (5.1%) plasma samples. SV40 DNA levels were low and not consistently observed in paired plasma and tumour samples from the same patient. Immunohistochemical analysis revealed a weak but reproducible SV40 staining in 16 of 341 (4.7%) mesotheliomas. Our data support the occurrence of non-reproducible SV40 PCR amplifications and underscore the importance of proper sample handling and analysis. SV40 DNA and protein were found at low prevalence (5%) in plasma and tumour tissue, respectively. This suggests that SV40 does not appear to play a major role in the development of mesothelioma.

  2. Transformation of Hamster Embryo Cells and Tumor Induction in Newborn Hamsters by Simian Adenovirus SV11

    PubMed Central

    Casto, Bruce C.

    1969-01-01

    Simian adenovirus, SV11, readily transformed hamster embryo cell cultures in vitro and produced tumors in vivo when inoculated into newborn hamsters. Foci consisting of small, loosely attached, rounded cells could be seen as early as 7 days postinoculation. Many of these cells contained several nuclei or the nucleus was multilobed. The cells grew without extensive cell to cell contact or formed small chains or clusters when passaged in vitro. This pattern of cell morphology and growth has not been reported with other simian or human adenovirus-transformed cells. Linearity of foci formation with virus dilution was observed when the virus multiplicity was less than 3 plaque-forming units (PFU)/cell. The PFU to focus-forming units ratio for SV11 was found to be 2 × 104 to 4 × 104, which is approximately 5- to 10-fold and 50- to 100-fold lower than those reported for simian adenovirus, SA7, and human adenovirus type 12, respectively. Cells transformed by SV11: (i) produced tumors when inoculated into young hamsters, (ii) contained tumor antigen which reacts with serum obtained from hamsters bearing SV11 passaged tumors, and (iii) could be propagated in vitro through an indefinite number of generations. Images PMID:5786181

  3. The Budding SV3: Estimating the Cost of Architectural Growth Early in the Life Cycle

    DTIC Science & Technology

    2014-04-30

    Systems Engineering Cost Model ) and the SV3. Based on its stochastic nature, this procedure is further implemented as a Monte Carlo simulation ...ABSTRACT As the systems engineering community continues to mature model -based approaches exciting opportunities for sophisticated, computational analysis...we estimate the marginal increase in systems engineering effort via an explicit connection between the open academic cost model COSYSMO (Constructive

  4. Chromosome fragility and susceptibility of Bloom's syndrome fibroblasts to SV40 transformation.

    PubMed

    Lin, M S; Alfi, O S

    1980-03-15

    A comparison of the frequencies of chromosomal aberrations and the rates of SV40 transformation was made using fibroblasts obtained from 2 patients with Bloom's syndrome (BS) and from a normal individual. BS cells were found to be more susceptible to chromosome damage, in confirmation of earlier reports, but surprisingly, BS cells were distinctly less prone to transformation.

  5. An Inmate Classification System Based on PCL: SV Factor Scores in a Sample of Prison Inmates

    ERIC Educational Resources Information Center

    Wogan, Michael; Mackenzie, Marci

    2007-01-01

    Psychopaths represent a significant management challenge in a prison population. A sample of ninety-five male inmates from three medium security prisons was tested using the Hare Psychopathy Checklist: Screening Version (PCL:SV). Using traditional criteria, 22% of the inmates were classified as psychopaths. Scores on the two factor dimensions of…

  6. Malignant progression of an SV40-transformed human epidermal keratinocyte cell line.

    PubMed Central

    Brown, K. W.; Gallimore, P. H.

    1987-01-01

    Human foetal keratinocytes were transfected with a recombinant plasmid (pSV6-1) which contained an origin defective SV40 genome. The resulting transformed cell line had many properties in common with previously described SV40-transformed keratinocytes, including expression of simple epithelial-type keratins. It was non-tumourigenic in nude mice at early passages, forming small benign cysts, however, after approximately 46 in vitro passages, these transformed keratinocytes formed invasive squamous cell carcinomas in athymic nude mice. Several in vitro changes were associated with this acquisition of tumourigenicity (a) an alteration in cellular morphology, (b) development of a cytogenetically marked clone and (c) loss of cell surface fibronectin. The loss of fibronectin was also observed in vivo; cysts formed by SV6-1 Bam/HFK produced human fibronectin whereas tumours did not, although both tumours and cysts were laminin- and keratin-positive. These results indicate that the spontaneous development of secondary events in immortalised human cells may lead to the acquisition of a malignant phenotype. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2447927

  7. Current Explorations of Adult Learner: Implications for Mentoring and More. Adult Higher Education Alliance Annual Conference Proceedings (36th, Orlando, Florida, March 10-11, 2016)

    ERIC Educational Resources Information Center

    Elufiede, Kemi, Ed.; Flynn, Bonnie, Ed.

    2016-01-01

    The 36th Annual Adult Higher Education Alliance (AHEA) Conference was held on March 10-11, 2016 in Orlando, Florida, on the campus of the University of Central Florida. There were 48 presentations from scholars and practitioners from 20 states who participated in the conference. The contributions to these proceedings represent the best of the…

  8. Studio in Advertising Design, Fashion Design and Illustration, Product Design, Stage Design. Volume 3: Advanced Elective Courses in Art for Grades 10, 11, or 12.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    The document provides teaching guidelines and information on advance elective courses in a studio art program for grades 10, 11, and 12. The courses are presented in four sections: (1) studio in advertising design--advertising and production, lettering, illustrating, and color reproduction; (2) studio in fashion design and illustration--elements…

  9. Health Curriculum Materials: Grades 10, 11, and 12. Strand IV, Environmental and Community Health; Consumer Health. Special Edition for Evaluation and Discussion.

    ERIC Educational Resources Information Center

    Van Hooft, Gordon E.; And Others

    This publication contains curriculum suggestions for teaching Environmental and Community Health - Consumer Health for grades 10, 11 and 12. Emphasis is placed on the psychological dimension of contemporary quackery and pseudo-scientific practices, and sources of health information and health counsel. In general, the grade 10 through 12 materials…

  10. Behavioral responses of the invasive Halyomorpha halys (Stål) to traps baited with stereoisomeric mixtures of 10,11-epoxy-1-bisabolen-3-OL.

    PubMed

    Leskey, Tracy C; Khrimian, Ashot; Weber, Donald C; Aldrich, Jeffrey C; Short, Brent D; Lee, Doo-Hyung; Morrison, William R

    2015-04-01

    The brown marmorated stink bug, Halyomorpha halys, is an invasive insect in the United States that is capable of inflicting significant yield losses for fruit, vegetable, and soybean growers. Recently, a male-produced aggregation pheromone of H. halys was identified as a 3.5:1 mixture of (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol, two stereoisomers of a natural sesquiterpene with a bisabolane skeleton, potentially existing in 16 stereoisomeric forms. In this study, we assessed attraction to pheromonal and non-pheromonal stereoisomeric mixtures of 10,11-epoxy-1-bisabolen-3-ol, which are easier to synthesize than single isomers, and evaluated dose-dependent responses to attractive mixtures in field trials. Some treatments not containing the natural pheromone components were moderately active in field-trapping studies, signifying that some stereoisomers of 10,11-epoxy-1-bisabolen-3-ol are sufficiently similar to the true pheromone in structure to trigger behavioral responses. Importantly, we found that mixtures of stereoisomers containing pheromone components were also highly attractive to H. halys, even in the presence of multiple "unnatural" stereoisomers. Further, adult and nymphal captures were dose-dependent, regardless of whether the lure contained pheromonal or non-pheromonal components. Our findings of attraction to pheromonal and non-pheromonal stereoisomers and lack of inhibition from non-pheromonal stereoisomers of 10,11-epoxy-1-bisabolen-3-ol increase the flexibility of developing pheromone-based products for H. halys.

  11. Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin

    PubMed Central

    Weisemann, Jasmin; Stern, Daniel; Mahrhold, Stefan; Dorner, Brigitte G.; Rummel, Andreas

    2016-01-01

    Botulinum neurotoxins (BoNTs) exhibit extraordinary potency due to their exquisite neurospecificity, which is achieved by dual binding to complex polysialo-gangliosides and synaptic vesicle proteins. The luminal domain 4 (LD4) of the three synaptic vesicle glycoprotein 2 isoforms, SV2A‐C, identified as protein receptors for the most relevant serotype BoNT/A, binds within the 50 kDa cell binding domain HC of BoNT/A. Here, we deciphered the BoNT/A‐SV2 interactions in more detail. In pull down assays, the binding of HCA to SV2-LD4 isoforms decreases from SV2C >> SV2A > SV2B. A binding constant of 200 nM was determined for BoNT/A to rat SV2C-LD4 in GST pull down assay. A similar binding constant was determined by surface plasmon resonance for HCA to rat SV2C and to human SV2C, the latter being slightly lower due to the substitution L563F in LD4. At pH 5, as measured in acidic synaptic vesicles, the binding constant of HCA to hSV2C is increased more than 10-fold. Circular dichroism spectroscopy reveals that the quadrilateral helix of SV2C-LD4 already exists in solution prior to BoNT/A binding. Hence, the BoNT/A‐SV2C interaction is of different nature compared to BoNT/B‐Syt-II. In particular, the preexistence of the quadrilateral β-sheet helix of SV2 and its pH-dependent binding to BoNT/A via backbone–backbone interactions constitute major differences. Knowledge of the molecular details of BoNT/A‐SV2 interactions drives the development of high affinity peptides to counteract BoNT/A intoxications or to capture functional BoNT/A variants in innovative detection systems for botulism diagnostic. PMID:27196927

  12. High Electrical Conductivity in Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2, a Semiconducting Metal-Organic Graphene Analogue

    SciTech Connect

    Sheberla, Dennis; Sun, Lei; Blood-Forsythe, Martin A.; Er, Süleyman; Wade, Casey R.; Brozek, Carl K.; Aspuru-Guzik, Alán; Dinc,; #259; Mircea,

    2014-09-22

    Reaction of 2,3,6,7,10,11-hexaaminotriphenylene with Ni2+ in aqueous NH3 solution under aerobic conditions produces Ni3(HITP)2 (HITP = 2,3,6,7,10,11-hexaiminotriphenylene), a new two-dimensional metal–organic framework (MOF). The new material can be isolated as a highly conductive black powder or dark blue-violet films. Two-probe and van der Pauw electrical measurements reveal bulk (pellet) and surface (film) conductivity values of 2 and 40 S·cm–1, respectively, both records for MOFs and among the best for any coordination polymer.

  13. Line-profile and continuum variations of the contact binary SV Centauri

    NASA Technical Reports Server (NTRS)

    Rahe, J.; Drechsel, H.; Wargau, W.

    1982-01-01

    A total of five high and ten low dispersion UV spectra of the interacting contact binary SV Centauri obtained between 1979 and 1982 are analyzed. The low resolution observations cover the whole phase range, while a few selected phases were observed in high dispersion. The UV data were complemented with optical photometric and spectroscopic observations, in order to determine the tructure and absolute dimensions of the system. The profiles of prominent UV resonance and metastable lines undergo drastic changes with phase angle and time. Their overall appearance indicates relatively strong mass loss from the system, exhibiting pronounced variations of the stellar wind. The far UV continuum distribution suggests the presence of a luminous hot radiation source with maximum emission in the soft X-ray range, which is most apparently seen during the first quadrature phase, while it is weakest close to primary minimum. The case exchange and mass loss process as well as the evolutionary stage of SV Centauri are discussed.

  14. Kinetic behavior of the reaction between hydroxyl radical and the SV40 minichromosome

    NASA Astrophysics Data System (ADS)

    Ly, A.; Aguilera, J. A.; Milligan, J. R.

    2007-06-01

    Aqueous solutions containing the minichromosomal form of the virus SV40 and the radical scavenger DMSO were subjected to γ-irradiation, and the resulting formation of single-strand breaks (SSB) was quantified. Under the irradiation conditions, most SSBs were produced as a consequence of hydroxyl radical ( rad OH) reactions. By controlling the competition between DMSO and the viral DNA substrate for rad OH, we are able to estimate the rate coefficient for the reaction of rad OH with the SV40 minichromosome. The results cannot be described adequately by homogeneous competition kinetics, but it is possible to describe the rate coefficient for the reaction as a function of the scavenging capacity of the solution. The experimentally determined rate coefficient lies in the range 1×10 9-2×10 9 L mol -1 s -1 at 10 7 s -1, and increases with increasing scavenging capacity.

  15. SV40 DNA in a carrier system of human glioblastoma cells.

    PubMed

    Steinberg, V I; Norkin, L C

    1988-04-01

    The state of the SV40 DNA in a stable carrier system of A172 human glioblastoma cells was examined by Southern blot hybridization analysis. At a sensitivity of 0.1 viral genome equivalents per cell, we detected only free, apparently nondefective, viral genomes. However, when we overexposed our autoradiograms or examined cloned cell populations, integrated viral sequences were observed. Furthermore, aberrant forms of free viral DNA were seen as well. Four clones, isolated at 15 weeks, produced T antigen and displayed enhanced saturation density and plating efficiency characteristic of SV40 transformation. None of these clones produced capsid proteins or infectious virus, even upon fusion with CV-1 cells, Viral DNA in the clones ranged from 0.5 to 50 equivalents per cell, on the average. Two of the Week-15 clones contained a similar (but not identical) predominant truncated SV40 sequence which was present both in a free state and integrated at a single major site in a reiterated head-to-tail array. These clones also contained other minor integrated sequences. Another Week-15 clone contained viral sequences integrated at two major sites as well as heterogeneous free DNA. Only free aberrant DNA was detected in the fourth Week-15 clone. Seven of eight clones isolated at 23 weeks produced no infectious virus or T antigen. No viral DNA was detected in those clones. The eighth clone did produce infectious virus and contained a predominance of free viral DNA. All of the clones were susceptible to superinfection with wild-type SV40, although less so than uninfected A172 cultures.

  16. High Cooperativity of the SV40 Major Capsid Protein VP1 in Virus Assembly

    PubMed Central

    Mukherjee, Santanu; Abd-El-Latif, Mahmoud; Bronstein, Michal; Ben-nun-Shaul, Orly; Kler, Stanislav; Oppenheim, Ariella

    2007-01-01

    SV40 is a small, non enveloped DNA virus with an icosahedral capsid of 45 nm. The outer shell is composed of pentamers of the major capsid protein, VP1, linked via their flexible carboxy-terminal arms. Its morphogenesis occurs by assembly of capsomers around the viral minichromosome. However the steps leading to the formation of mature virus are poorly understood. Intermediates of the assembly reaction could not be isolated from cells infected with wt SV40. Here we have used recombinant VP1 produced in insect cells for in vitro assembly studies around supercoiled heterologous plasmid DNA carrying a reporter gene. This strategy yields infective nanoparticles, affording a simple quantitative transduction assay. We show that VP1 assembles under physiological conditions into uniform nanoparticles of the same shape, size and CsCl density as the wild type virus. The stoichiometry is one DNA molecule per capsid. VP1 deleted in the C-arm, which is unable to assemble but can bind DNA, was inactive indicating genuine assembly rather than non-specific DNA-binding. The reaction requires host enzymatic activities, consistent with the participation of chaperones, as recently shown. Our results demonstrate dramatic cooperativity of VP1, with a Hill coefficient of ∼6. These findings suggest that assembly may be a concerted reaction. We propose that concerted assembly is facilitated by simultaneous binding of multiple capsomers to a single DNA molecule, as we have recently reported, thus increasing their local concentration. Emerging principles of SV40 assembly may help understanding assembly of other complex systems. In addition, the SV40-based nanoparticles described here are potential gene therapy vectors that combine efficient gene delivery with safety and flexibility. PMID:17712413

  17. Wf/pc Cycle 1 Cal: Non-Sv WFC Flats 1

    NASA Astrophysics Data System (ADS)

    MacKenty, John

    1990-12-01

    This program takes "uniform illuminated" pictures of the earth to obtain the "instrument signature" for flat field corrections. This proposal contains observations for all WFC filters used by GOs and GTOs during Cycle 1 which were not included in the SV program. The camera - filter combinations done in this proposal are: WFC: F469N, F1042M, F1083N. These are the WFC flats which are not expected to saturate on the bright earth.

  18. High cooperativity of the SV40 major capsid protein VP1 in virus assembly.

    PubMed

    Mukherjee, Santanu; Abd-El-Latif, Mahmoud; Bronstein, Michal; Ben-nun-Shaul, Orly; Kler, Stanislav; Oppenheim, Ariella

    2007-08-22

    SV40 is a small, non enveloped DNA virus with an icosahedral capsid of 45 nm. The outer shell is composed of pentamers of the major capsid protein, VP1, linked via their flexible carboxy-terminal arms. Its morphogenesis occurs by assembly of capsomers around the viral minichromosome. However the steps leading to the formation of mature virus are poorly understood. Intermediates of the assembly reaction could not be isolated from cells infected with wt SV40. Here we have used recombinant VP1 produced in insect cells for in vitro assembly studies around supercoiled heterologous plasmid DNA carrying a reporter gene. This strategy yields infective nanoparticles, affording a simple quantitative transduction assay. We show that VP1 assembles under physiological conditions into uniform nanoparticles of the same shape, size and CsCl density as the wild type virus. The stoichiometry is one DNA molecule per capsid. VP1 deleted in the C-arm, which is unable to assemble but can bind DNA, was inactive indicating genuine assembly rather than non-specific DNA-binding. The reaction requires host enzymatic activities, consistent with the participation of chaperones, as recently shown. Our results demonstrate dramatic cooperativity of VP1, with a Hill coefficient of approximately 6. These findings suggest that assembly may be a concerted reaction. We propose that concerted assembly is facilitated by simultaneous binding of multiple capsomers to a single DNA molecule, as we have recently reported, thus increasing their local concentration. Emerging principles of SV40 assembly may help understanding assembly of other complex systems. In addition, the SV40-based nanoparticles described here are potential gene therapy vectors that combine efficient gene delivery with safety and flexibility.

  19. HSC70 interactions with SV40 viral proteins differ between permissive and nonpermissive mammalian cells

    PubMed Central

    Sainis, Ioannis; Angelidis, Charalambos; Pagoulatos, Gerasimos N.; Lazaridis, Ioannis

    2000-01-01

    SV40 belongs to a group of DNA tumor viruses which induce the expression of the 70 Kd heat shock proteins, but the meaning of this induction remains unclear. Investigating the role of hsc70 in the SV40 life cycle, we found that the protein translocates to the nucleus late in infection of permissive CV1 cells, in contrast to infected nonpermissive BALB/3T3 and NIH/3T3 cells in which hsc70 remains cytoplasmic. Moreover, the pattern of hsc70 nuclear staining was diffused and clearly distinguishable from that observed after heat shock. In addition hsc70 late in infection coimmunoprecipitated with the viral capsid protein VP1, suggesting a role in the process of viral packaging. Interactions of hsc70 with the early viral oncoprotein T antigen were observed only in nonpermissive cells, indicating that the binding of the above proteins is specific to cells that do not support viral propagation. Finally, treatment of permissive CV1 cells with interferon γ, a known antiviral cytokine, resulted in hsc70 binding to T antigen. Our results suggest that the role of hsc70 in the process of SV40 infection is directly related to the ability of the host cells to support viral propagation and is clearly different between permissive and nonpermissive cell lines. PMID:11147964

  20. In vitro transformation of Li-Fraumeni syndrome fibroblasts by SV40 large T antigen mutants.

    PubMed

    Maclean, K; Rogan, E M; Whitaker, N J; Chang, A C; Rowe, P B; Dalla-Pozza, L; Symonds, G; Reddel, R R

    1994-03-01

    Transfection of SV40 early region DNA into normal human diploid fibroblasts (NHDFs) increases their proliferative potential to a limited extent. We have investigated the roles of the SV40 large T antigen (LTAg) regions responsible for binding to the protein products of the retinoblastoma (Rb) and p53 genes in this temporary escape from senescence. Patients encoding LTAg mutants were transfected into NHDFs and into Li-Fraumeni syndrome (LFS) fibroblasts which are heterozygous wild-type (wt)/null-mutant for p53. A LTAg mutated in the p53-binding region (T402DE) had greatly reduced efficiency of focus formation, and a p110Rb-binding mutant was unable to induce any foci. T402DE-induced NHDF foci senesced at the same time as untransfected cells, but the equivalent LFS foci all had increased proliferative potentials, with the greatest increase being seen in clones that lost the wt p53 allele. One LFS clone expressed the T402DE mutant during focus formation, but later lost both the T402DE DNA and the wt p53 allele. We conclude that SV40-induced focus formation in NHDFs requires the LTAg p110Rb-binding region, and is enhanced by loss of normal p53 function. In contrast, increased proliferative potential is primarily due to loss of p53 function.

  1. Effect of trimethyllead chloride on slowly activating (SV) channels in red beet (Beta vulgaris L.) taproots.

    PubMed

    Trela, Zenon; Burdach, Zbigniew; Przestalski, Stanisław; Karcz, Waldemar

    2012-12-01

    The patch-clamp technique was used to examine the effect of trimethyllead chloride (Met(3)PbCl) on SV channel activity in red beet (Beta vulgaris L.) taproot vacuoles. It was found that in the control bath the macroscopic currents showed the typical slow activation and a strong outward rectification of the steady-state currents. An addition of Met(3)PbCl to the bath solution blocked, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant τ increased several times in the presence of 100 μM trimethyllead chloride at all voltages tested. When single channel properties were analyzed, only little channel activity could be recorded in the presence of 100 μM Met(3)PbCl. Trimethyllead chloride decreased significantly (by about one order of magnitude) the open probability of single channels. The recordings of single channel activity obtained in the presence and absence of Met(3)PbCl showed that organolead only slightly (by ca. 10%) decreased the unitary conductance of single channels. It was also found that Met(3)PbCl diminished significantly the number of SV channel openings, whereas it did not change the opening times of the channels. Taken together, these results suggest that Met(3)PbCl binding site is located outside the channel selectivity filter.

  2. Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

    PubMed Central

    Padi, Megha; Korkhin, Anna; James, Robert L.; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A.; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A.; Hill, David E.; Cusick, Michael E.; Vidal, Marc; Florens, Laurence; Washburn, Michael P.; Litovchick, Larisa; DeCaprio, James A.

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  3. SV40 late protein VP4 forms toroidal pores to disrupt membranes for viral release

    PubMed Central

    Raghava, Smita; Giorda, Kristina M.; Romano, Fabian B.; Heuck, Alejandro P.; Hebert, Daniel N.

    2014-01-01

    Nonenveloped viruses are generally released from the cell by the timely lysis of host cell membranes. SV40 has been used as a model virus for the study of the lytic nonenveloped virus life cycle. The expression of SV40 VP4 at later times during infection is concomitant with cell lysis. To investigate the role of VP4 in viral release and its mechanism of action, VP4 was expressed and purified from bacteria as a fusion protein for use in membrane disruption assays. Purified VP4 perforated membranes as demonstrated by the release of fluorescent markers encapsulated within large unilamellar vesicles or liposomes. Dynamic light scattering results found that VP4 treatment did not cause membrane lysis or change the size of the liposomes. Liposomes encapsulated with bodipy-labeled streptavidin were used to show that VP4 formed stable pores in membranes. These VP4 pores had an inner diameter of between 1 and 5 nm. Asymmetrical liposomes containing pyrene-labeled lipids in the outer monolayer were employed to monitor transbilayer lipid diffusion. Consistent with VP4 forming toroidal pore structures in membranes, VP4 induced transbilayer lipid diffusion or lipid flip-flop. Altogether, these studies support a central role for VP4 acting as a viroporin in the disruption of cellular membranes to trigger SV40 viral release by forming toroidal pores that unite the outer and inner leaflets of membrane bilayers. PMID:23651212

  4. Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.

    PubMed Central

    Mayall, F G; Jacobson, G; Wilkins, R

    1999-01-01

    AIM: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. METHODS: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre. RESULTS: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level. CONCLUSIONS: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further. Images PMID:10474522

  5. De Par en Par, 10 & 11. (Wide Open, 10 & 11.)

    ERIC Educational Resources Information Center

    De Par en Par, 1997

    1997-01-01

    These two magazines, written entirely in Spanish, are designed for classroom use in the elementary grades. Number 10, focuses on ecology, discussing such topics as the greenhouse effect, endangered species, protecting the natural environment, tree planting, earthworms, natural waste, books on environmental subjects, saving the earth, and…

  6. Intrathecal administration of AAV/GALC vectors in 10-11-day-old twitcher mice improves survival and is enhanced by bone marrow transplant.

    PubMed

    Karumuthil-Melethil, Subha; Marshall, Michael S; Heindel, Clifford; Jakubauskas, Benas; Bongarzone, Ernesto R; Gray, Steven J

    2016-11-01

    Globoid cell leukodystrophy (GLD), or Krabbe disease, is an autosomal recessive neurodegenerative disease caused by the deficiency of the lysosomal enzyme galactocerebrosidase (GALC). Hematopoietic stem cell transplantation (HSCT) provides modest benefit in presymptomatic patients but is well short of a cure. Gene transfer experiments using viral vectors have shown some success in extending the survival in the mouse model of GLD, twitcher mice. The present study compares three single-stranded (ss) AAV serotypes, two natural and one engineered (with oligodendrocyte tropism), and a self-complementary (sc) AAV vector, all packaged with a codon-optimized murine GALC gene. The vectors were delivered via a lumbar intrathecal route for global CNS distribution on PND10-11 at a dose of 2 × 10(11) vector genomes (vg) per mouse. The results showed a similar significant extension of life span of the twitcher mice for all three serotypes (AAV9, AAVrh10, and AAV-Olig001) as well as the scAAV9 vector, compared to control cohorts. The rAAV gene transfer facilitated GALC biodistribution and detectable enzymatic activity throughout the CNS as well as in sciatic nerve and liver. When combined with BMT from syngeneic wild-type mice, there was significant improvement in survival for ssAAV9. Histopathological analysis of brain, spinal cord, and sciatic nerve showed significant improvement in preservation of myelin, with ssAAV9 providing the greatest benefit. In summary, we demonstrate that lumbar intrathecal delivery of rAAV/mGALCopt can significantly enhance the life span of twitcher mice treated at PND10-11 and that BMT synergizes with this treatment to improve the survival further. © 2016 Wiley Periodicals, Inc.

  7. Androgens act synergistically to enhance estrogen-induced upregulation of human tissue kallikreins 10, 11, and 14 in breast cancer cells via a membrane bound androgen receptor.

    PubMed

    Paliouras, Miltiadis; Diamandis, Eleftherios P

    2008-04-01

    The regulation of gene expression by steroid hormones plays an important role in the normal development and function of many organs, as well as in the pathogenesis of endocrine-related cancers, especially breast cancer. However, clinical data suggest that combined testosterone and estrogen treatments on post-menopausal women increase the risk of breast cancer. Experiments have shown that many, if not all kallikreins are under steroid hormone regulation in breast cancer cell lines. Their implication as prognostic and diagnostic markers has also been well-documented. Thus, we investigated the effect of combined hormone stimulation with androgens and 17beta-estradiol on the ductal caricinoma cell line BT474. This cell line has been shown to be sensitive to both, androgens (secreting PSA) and estrogens (secreting a number of kallikreins including KLK10, 11, and KLK14). We found that PSA expression was downregulated upon combined hormone stimulation, confirming reports that estrogen can antagonize and block the activity of the androgen receptor. Upon analysis of estrogen-sensitive kallikreins 10, 11, and 14, all showed to be synergistically enhanced in their expression three- to fourfold, upon joint hormone treatment versus individual hormone stimulation. The enhancement is dependent upon the action of androgens as treatment with the androgen receptor antagonist cyproterone actetate normalized the expression of KLK10, 11, and KLK14 to estrogen-stimulation levels. The synergistic effects between estrogens and androgens on estrogen-sensitive genes may have implications on the role of the kallikreins in associated risk of breast cancer and progression.

  8. Direct single-molecule observations of DNA unwinding by SV40 large tumor antigen under a negative DNA supercoil state.

    PubMed

    Takahashi, Shunsuke; Motooka, Shinya; Kawasaki, Shohei; Kurita, Hirofumi; Mizuno, Takeshi; Matsuura, Shun-Ichi; Hanaoka, Fumio; Mizuno, Akira; Oshige, Masahiko; Katsura, Shinji

    2017-01-05

    Superhelices, which are induced by the twisting and coiling of double-helical DNA in chromosomes, are thought to affect transcription, replication, and other DNA metabolic processes. In this study, we report the effects of negative supercoiling on the unwinding activity of simian virus 40 large tumor antigen (SV40 TAg) at a single-molecular level. The supercoiling density of linear DNA templates was controlled using magnetic tweezers and monitored using a fluorescent microscope in a flow cell. SV40 TAg-mediated DNA unwinding under relaxed and negative supercoil states was analyzed by the direct observation of both single- and double-stranded regions of single DNA molecules. Increased negative superhelicity stimulated SV40 TAg-mediated DNA unwinding more strongly than a relaxed state; furthermore, negative superhelicity was associated with an increased probability of SV40 TAg-mediated DNA unwinding. These results suggest that negative superhelicity helps to regulate the initiation of DNA replication.

  9. 77 FR 13318 - SV Hydro, LLC, Coffeeville, LLC, FFP Project 99, LLC; Notice Announcing Filing Priority for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-06

    ... Energy Regulatory Commission SV Hydro, LLC, Coffeeville, LLC, FFP Project 99, LLC; Notice Announcing Filing Priority for Preliminary Permit Applications On February 28, 2012, the Commission held a drawing to determine priority between three competing preliminary permit applications with identical...

  10. SV40 host-substituted variants: a new look at the monkey DNA inserts and recombinant junctions.

    PubMed

    Singer, Maxine; Winocour, Ernest

    2011-04-10

    The available monkey genomic data banks were examined in order to determine the chromosomal locations of the host DNA inserts in 8 host-substituted SV40 variant DNAs. Five of the 8 variants contained more than one linked monkey DNA insert per tandem repeat unit and in all cases but one, the 19 monkey DNA inserts in the 8 variants mapped to different locations in the monkey genome. The 50 parental DNAs (32 monkey and 18 SV40 DNA segments) which spanned the crossover and flanking regions that participated in monkey/monkey and monkey/SV40 recombinations were characterized by substantial levels of microhomology of up to 8 nucleotides in length; the parental DNAs also exhibited direct and inverted repeats at or adjacent to the crossover sequences. We discuss how the host-substituted SV40 variants arose and the nature of the recombination mechanisms involved.

  11. A Mitochondrial Role of SV2a Protein in Aging and Alzheimer's Disease: Studies with Levetiracetam.

    PubMed

    Stockburger, Carola; Miano, Davide; Baeumlisberger, Marion; Pallas, Thea; Arrey, Tabiwang N; Karas, Michael; Friedland, Kristina; Müller, Walter E

    2016-01-01

    Aberrant neuronal network activity associated with neuronal hyperexcitability seems to be an important cause of cognitive decline in aging and Alzheimer's disease (AD). Out of many antiepileptics, only levetiracetam improved cognitive dysfunction in AD patients and AD animal models by reducing hyperexcitability. As impaired inhibitory interneuronal function, rather than overactive neurons, seems to be the underlying cause, improving impaired neuronal function rather than quieting overactive neurons might be relevant in explaining the lack of activity of the other antiepileptics. Interestingly, improvement of cognitive deficits by levetiracetam caused by small levels of soluble Aβ was accompanied by improvement of synaptic function and plasticity. As the negative effects of Aβ on synaptic plasticity strongly correlate with mitochondrial dysfunction, wehypothesized that the effect of levetiracetam on synaptic activity might be raised by an improved mitochondrial function. Accordingly, we investigated possible effects of levetiracetam on neuronal deficits associated with mitochondrial dysfunction linked to aging and AD. Levetiracetam improved several aspects of mitochondrial dysfunction including alterations of fission and fusion balance in a cell model for aging and early late-onset AD. We demonstrate for the first time, using immunohistochemistry and proteomics, that the synaptic vesicle protein 2A (SV2a), the molecular target of levetiracetam, is expressed in mitochondria. In addition, levetiracetam shows significant effect on the opening of the mitochondrial permeability transition pore. Importantly, the effects of levetiracetam were significantly abolished when SV2a was knockdown using siRNA. In conclusion, interfering with the SV2a protein at the mitochondrial level and thereby improving mitochondrial function might represent an additional therapeutic effect of levetiracetam to improve symptoms of late-onset AD.

  12. Durable cytotoxic immune responses against gp120 elicited by recombinant SV40 vectors encoding HIV-1 gp120 +/- IL-15.

    PubMed

    McKee, Hayley J; T'sao, Patricia Y; Vera, Maria; Fortes, Puri; Strayer, David S

    2004-08-23

    BACKGROUND: A vaccine that elicits durable, powerful anti-HIV immunity remains an elusive goal. In these studies we tested whether multiple treatments with viral vector-delivered HIV envelope antigen (gp120), with and without IL-15, could help to approach that goal. For this purpose, we used recombinant Tag-deleted SV40-derived vectors (rSV40s), since they do not elicit neutralizing antibody responses, and so can be given multiply without loss of transduction efficiency. METHODS: SV(gp120) carried the coding sequences for HIV-1NL4-3 Env, and SV(mIL-15) carried the cDNA for mouse IL-15. Singly, and in combination, these two vectors were given monthly to BALB/cJ mice. Cytotoxic immunity and cytotoxic memory were tested in direct cytotoxicity assays using unselected effector cells. Antibody vs. gp120 was measured in a binding assay. In both cases, targets were P815 cells that were stably transfected with gp120. RESULTS: Multiple injections of SV(gp120) elicited powerful anti-gp120 cytolytic activity (>70% specific lysis) by unselected spleen cells. Cells from multiply-immunized mice that were rested 1 year after their last injections still showed >60% gp120-specific lysis. Anti-gp120 antibody was first detected after 2 monthly injections of SV(gp120) and remained elevated thereafter. Adding SV(mIL-15) to the immunization regimen dramatically accelerated the development of memory cytolytic responses, with >/= 50% specific lysis seen 1 month after two treatments. IL-15 did not alter the development of antibody responses. CONCLUSIONS: Thus, rSV40s encoding antigens and immunostimulatory cytokines may be useful tools for priming and/or boosting immune responses against HIV.

  13. Wf/pc Cycle 1 Cal: Non-Sv PC Flats 1

    NASA Astrophysics Data System (ADS)

    MacKenty, John

    1990-12-01

    This program takes "uniform illuminated" pictures of the earth to obtain the "instrument signature" for flat field corrections. This proposal contains observations for all PC filters used by GOs and GTOs during Cycle 1 which were not included in the SV program. The camera - filter combinations done in this proposal are: PC: F368M,F588N,F631N,F648M,F875M,F1042M These are the PC flats which are not expected to saturate on the bright earth.

  14. Differential gene expression in SV40-mediated immortalization of human fibroblasts.

    PubMed

    Pardinas, J; Pang, Z; Houghton, J; Palejwala, V; Donnelly, R J; Hubbard, K; Small, M B; Ozer, H L

    1997-06-01

    Normal human diploid fibroblasts (HF) have a limited life span, undergo senescence, and rarely, if ever, spontaneously immortalize in culture. Introduction of the gene for T antigen encoded by the DNA virus SV40 extends the life span of HF and increases the frequency of immortalization; however, immortalization requires both T-dependent and T-independent functions. We previously generated independent SV40-transformed non-immortal (pre-immortal) HF cell lines from which we then obtained immortal sublines as part of a multifaceted approach to identify functions responsible for immortalization. In this study we undertook a search for cellular mRNAs which are differentially expressed upon immortalization. A lambda cDNA library was prepared from a pre-immortal SV40-transformed HF (HF-C). We screened the library with a subtracted probe enriched for sequences present in HF-C and reduced in immortal AR5 cells. A more limited screen was also employed for sequences overexpressed in AR5 using a different strategy. Alterations in the level of mRNAs in AR5 encoding functions relevant to signal transduction pathways were identified; however, most cDNAs encoded novel sequences. In an effort to clarify which of the altered mRNAs are most relevant to immortalization, we performed Northern analysis with RNA prepared from three paired sets of independent pre-immortal and immortal (4 cell lines) SV40-transformants using eight cloned cDNAs which show reduced expression in AR5. Three of these were reduced in additional immortal cell lines as well; one, J4-4 (unknown function) is reduced in all the immortal cell lines tested; a second, J4-3 (possible PP2C type phosphatase) is reduced in 2 of the 3 matched sets; and a third, J2-2 (unknown function) is reduced in 2 unrelated immortal cell lines. Although the roles of these genes are as yet unclear, their further analysis should extend our understanding of the molecular bases for immortalization. In particular, the patterns of expression of

  15. A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors.

    PubMed

    Louboutin, Jean-Pierre; Agrawal, Lokesh; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

    2009-05-01

    Human immunodeficiency virus 1 (HIV-1) encephalopathy is thought to result in part from the toxicity of HIV-1 envelope glycoprotein gp120 for neurons. Experimental systems for studying the effects of gp120 and other HIV proteins on the brain have been limited to the acute effects of recombinant proteins in vitro or in vivo in simian immunodeficiency virus-infected monkeys. We describe an experimental rodent model of ongoing gp120-induced neurotoxicity in which HIV-1 envelope is expressed in the brain using an SV40-derived gene delivery vector, SV(gp120). When it is inoculated stereotaxically into the rat caudate putamen, SV(gp120) caused a partly hemorrhagic lesion in which neuron and other cell apoptosis continues for at least 12 weeks. Human immunodeficiency virus gp120 is expressed throughout this time, and some apoptotic cells are gp120 positive. Malondialdehyde and 4-hydroxynonenal assays indicated that there was lipid peroxidation in these lesions. Prior administration of recombinant SV40 vectors carrying antioxidant enzymes, copper/ zinc superoxide dismutase or glutathione peroxidase, was protective against SV(gp120)-induced oxidative injury and apoptosis. Thus, in vivo inoculation of SV(gp120) into the rat caudate putamen causes ongoing oxidative stress and apoptosis in neurons and may therefore represent a useful animal model for studying the pathogenesis and treatment of HIV-1 envelope-related brain damage.

  16. Homologous SV40 RNA trans-splicing: a new mechanism for diversification of viral sequences and phenotypes.

    PubMed

    Eul, Joachim; Patzel, Volker

    2013-11-01

    Simian Virus 40 (SV40) is a polyomavirus found in both monkeys and humans, which causes cancer in some animal models. In humans, SV40 has been reported to be associated with cancers but causality has not been proven yet. The transforming activity of SV40 is mainly due to its 94-kD large T antigen, which binds to the retinoblastoma (pRb) and p53 tumor suppressor proteins, and thereby perturbs their functions. Here we describe a 100 kD super T antigen harboring a duplication of the pRB binding domain that was associated with unusual high cell transformation activity and that was generated by a novel mechanism involving homologous RNA trans-splicing of SV40 early transcripts in transformed rodent cells. Enhanced trans-splice activity was observed in clones carrying a single point mutation in the large T antigen 5' donor splice site (ss). This mutation impaired cis-splicing in favor of an alternative trans-splice reaction via a cryptic 5'ss within a second cis-spliced SV40 pre-mRNA molecule and enabled detectable gene expression. Next to the cryptic 5'ss we identified additional trans-splice helper functions, including putative dimerization domains and a splice enhancer sequence. Our findings suggest RNA trans-splicing as a SV40-intrinsic mechanism that supports the diversification of viral RNA and phenotypes.

  17. Analytical performance evaluation of ADVIA Chemistry Carbamazepine_2 assay: minimal cross-reactivity with carbamazepine 10, 11-epoxide and none with hydroxyzine or cetirizine.

    PubMed

    Dasgupta, Amitava; Reyes, Meredith A; Davis, Barbara G; Marlow, Anne M; Johnson, Myrtle

    2010-01-01

    Carbamazepine is an anticonvulsant requiring routine therapeutic drug monitoring. Recently, Siemens Healthcare Diagnostic Division released a new carbamazepine assay: ADVIA Chemistry Carbamazepine_2 (Carbamazepine_2) for application on ADVIA analyzers. We evaluated the analytical performance of this assay as well as its potential cross-reactivities with carbamazepine 10, 11-epoxide, hydroxyzine, and cetirizine. The within-run and between-run precisions of the Carbamzepine-2 assay were <6% and limit of detection was 0.5 microg/ml using ADVIA 1800 analyzer. The assay was linear up to a carbamazepine concentration of 20.0 microg/ml. The new method compared well with a widely used carbamazepine EMIT 2000 assay on the Hitachi 917 analyzer. Using 75 patients' specimens (where carbamazepine concentrations varied from 0.5 to 21.7 microg/ml) and carbamazepine EMIT 2000 as the reference method (x-axis), we observed the following regression equation: y=1.04 x+0.32 (r=0.99). The new carbazepine_2 method was not affected by a hemoglobin concentration of 1,000 mg/dl, conjugated or unconjugated bilirubin concentration of 60 mg/dl, and triglyceride concentration of 1,000 mg/dl. In addition, this assay showed no cross-reactivity with hydroxyzine or cetirizine and demonstrated minimal cross-reactivity with carbamazepine 10, 11-epoxide. We conclude that the ADVIA Chemistry carbamazepine_2 assay has adequate precision and accuracy for routine therapeutic drug monitoring of carbamazepine in clinical laboratories.

  18. Expression of SV40 T antigen polypeptides in cells biochemically transformed by plasmids containing the herpes simplex virus thymidine kinase gene and the genome of an SV40tsA mutant.

    PubMed

    Kit, S; Otsuka, H; Qavi, H; Trkula, D; Dubbs, D R

    1981-10-15

    To study the expression of SV40 tsA genomes that had been non-selectively introduced into mouse cells, SV40 tsA207 DNA was cleaved with BamH I and ligated to BamH I-cleaved plasmid pAGO DNA, which contains a functional HSV-1 thymidine kinase (TK) gene in the form of 2 kbp Pvu II fragment inserted at the Pvu II site of pBR322. Recombinant plasmids (11-12 kbp) were isolated and amplified in E. coli K12 strain RRI. Restriction nuclease analyses demonstrated that recombinant plasmids pSB15 and pSB10 contained intact SV40 genomes with the polarity of transcription oriented in the same direction (clockwise) or the opposite direction (counterclockwise), respectively, in relation to that of the HSV-1 TK gene. Cla I-cleaved pSB10 and pSB15 DNAs were used to transform LM(TK-) cells to TK+. Serological and disc PAGE analyses showed that clonal lines transformed by these plasmids all expressed the selected marker, HSV-1 TK. Molecular hybridization experiments showed that transformed clonal lines TF pSB10 C7 and TF pSB15 C10 had integrated intact SV40 genomes at one integration site, TF pSB10 C3 had integrated an SV40 genome with a small deletion near the BamH I site, but TF pSB15 Cl had integrated a plasmid from which most of the SV40 nucleotide sequences had been deleted. IF assays with hamster anti-SV40 tumor sera showed that TF pSB10 C7 and TF pSB15 C10 strongly expressed SV40 T antigens in over 90% of the cells, TF pSB10 C3 expressed SV40 T antigens in a minority of the cells, and TF pSB15 C1 did not express SV40 T antigens at all. [35S]-methionine labelling and immunoprecipitation experiments showed that, at 36.5 degrees C: (1) TF pSB10 C7 and TF pSB15 C10 expressed 92K and 20K mol. wt. species of SV40 T antigens and 50-55K cellular protein; (2) expression of all three was reduced in TF pSB10 C3 cells; and (3) TF pSB15 C1 expressed none of the SV40 T antigens, nor did parental LM(TK-) or TF 8-2 transformed cells (which contained the HSV-1 TK gene but not SV40 DNA). At 40

  19. Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities.

    PubMed Central

    Ondek, B; Shepard, A; Herr, W

    1987-01-01

    The SV40 enhancer contains three genetically defined elements, called A, B and C, that can functionally compensate for one another. By using short, synthetic DNA oligonucleotides, we show that each of these elements can act autonomously as an enhancer when present as multiple tandem copies. Analysis of a progressive series of B element oligomers shows a single element is ineffective as an enhancer and that the activity of two or more elements increases with copy number. Assay in five different cell lines of two separate enhancers containing six tandem copies of either the B or C element shows that these elements possess different cell-specific activities. Parallel oligomer enhancer constructs containing closely spaced double point mutations display no enhancer activity in any of the cell lines tested, indicating that these elements represent single units of enhancer function. These elements contain either a 'core' or 'octamer' consensus sequence but these consensus sequences alone are not sufficient for enhancer activity. The different cell-specific activities of the B and C elements are consistent with functional interactions with different trans-acting factors. We discuss how tandem duplication of such dissimilar elements, as in the wild-type SV40 72-bp repeats, can serve to expand the conditions under which an enhancer can function. Images Fig. 2. Fig. 3. Fig. 4. PMID:3036487

  20. Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.

    PubMed

    Douaud, Marine; Feve, Katia; Pituello, Fabienne; Gourichon, David; Boitard, Simon; Leguern, Eric; Coquerelle, Gérard; Vieaud, Agathe; Batini, Cesira; Naquet, Robert; Vignal, Alain; Tixier-Boichard, Michèle; Pitel, Frédérique

    2011-01-01

    Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans.

  1. Vulnerability to chronic subordination stress-induced depression-like disorders in adult 129SvEv male mice.

    PubMed

    Dadomo, Harold; Sanghez, Valentina; Di Cristo, Luisana; Lori, Andrea; Ceresini, Graziano; Malinge, Isabelle; Parmigiani, Stefano; Palanza, Paola; Sheardown, Malcolm; Bartolomucci, Alessandro

    2011-08-01

    Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders.

  2. SV40 transformation of Swiss 3T3 cells can cause a stable reduction in the calcium requirement for growth

    PubMed Central

    1984-01-01

    A well-characterized SV40-transformed Swiss 3T3 line, SV101, and its revertants were tested for the ability to grow in reduced Ca++ (0.01 mM). Transformants and revertants did not differ from the parent 3T3 line in their Ca++ requirements. All three classes of cells grew less well in low Ca++ than in regular Ca++ (2.0 mM). SV40 transformants were then selected for the ability to grow in reduced Ca++. This new class of transformants was found to grow in 1% serum, grow in soft agarose, have a reorganized actin cytoskeleton, and express viral T antigens, as well as grow well in low Ca++. One of the selected clones was found to be T antigen-negative, yet was transformed in the serum, anchorage, actin, and Ca++ assays. It is possible that this clone was a spontaneous transformant. However, Southern blot analysis revealed the presence of integrated SV40 DNA. In addition, this analysis revealed the absence of an intact early region fragment, which codes for the viral T antigens. One explanation of this result may be that the mechanism of viral transformation for growth in low Ca++ involves viral- host DNA interactions that may not require a fully functional T antigen. In this case SV40 integration may be acting as a nonspecific cellular mutagen. PMID:6094595

  3. Immortalization of neuronal progenitors using SV40 large T antigen and differentiation towards dopaminergic neurons

    PubMed Central

    Alwin Prem Anand, A; Gowri Sankar, S; Kokila Vani, V

    2012-01-01

    Transplantation is common in clinical practice where there is availability of the tissue and organ. In the case of neurodegenerative disease such as Parkinson's disease (PD), transplantation is not possible as a result of the non-availability of tissue or organ and therefore, cell therapy is an innovation in clinical practice. However, the availability of neuronal cells for transplantation is very limited. Alternatively, immortalized neuronal progenitors could be used in treating PD. The neuronal progenitor cells can be differentiated into dopaminergic phenotype. Here in this article, the current understanding of the molecular mechanisms involved in the differentiation of dopaminergic phenotype from the neuronal progenitors immortalized with SV40 LT antigen is discussed. In addition, the methods of generating dopaminergic neurons from progenitor cells and the factors that govern their differentiation are elaborated. Recent advances in cell-therapy based transplantation in PD patients and future prospects are discussed. PMID:22863662

  4. Wf/pc Cycle 1 Calib: Non-Sv WFC Flats 2

    NASA Astrophysics Data System (ADS)

    MacKenty, John

    1990-12-01

    This program takes "uniform illuminated" pictures of the earth to obtain the "instrument signature" for flat field corrections. This proposal series contains observations for all WFC filters used by GOs and GTOs during Cycle 1 which were not included in the SV program. The camera - filter combinations done in this proposal are: WFC: F492M,F569W,F606W,F675W,F725LP,F791W,F814W,F850LP,F875M (these are done in combination with F122M) These are the PC flats which are expected to saturate on the bright earth without a neutral density filter. The following observations are also included with and without the F122M filter to permit correction: F502N,F588N,F673N,F889N

  5. Wf/pc Cycle 1 Calib: Non-Sv PC Flats 2

    NASA Astrophysics Data System (ADS)

    MacKenty, John

    1990-12-01

    This program takes "uniform illuminated" pictures of the earth to obtain the "instrument signature" for flat field corrections. This proposal series contains observations for all PC filters used by GOs and GTOs during Cycle 1 which were not included in the SV program. The camera - filter combinations done in this proposal are: PC: F569W, F606W, F675W, F725LP, F791W, F814W, F850LP (these are done in combination with F122M) These are the PC flats which are expected to saturate on the bright earth without a neutral density filter. The following observations are also included to permit correction for the F122M filter: F517N+F122M, F517N, F664N+F122M, F664N, F718M+F122M, F718M, F875M+F122M, F875M

  6. Maintenance of telomeres in SV40-transformed pre-immortal and immortal human fibroblasts.

    PubMed

    Small, M B; Hubbard, K; Pardinas, J R; Marcus, A M; Dhanaraj, S N; Sethi, K A

    1996-09-01

    Shortening of telomeres has been hypothesized to contribute to cellular senescence and may play a role in carcinogenesis of human cells. Furthermore, activation of telomerase has frequently been demonstrated in tumor-derived and in vitro immortalized cells. In this study, we have assessed these phenomena during the life span of simian virus 40 (SV40)-transformed preimmortal and immortal human fibroblasts. We observed progressive reduction in telomere length in preimmortal transformed cells with extended proliferative capacity, with the most dramatic shortening at late passage. Telomere lengths became stabilized (or increased) in immortal fibroblasts accompanied, in one case, by the activation of telomerase. However, an independent immortal cell line that displayed stable telomeres did not have detectable telomerase activity. Furthermore, we found significant telomerase activity in two preimmortal derivatives. Our results provide further evidence for maintenance of telomeres in immortalized human fibroblasts, but they suggest a lack of causal relationship between telomerase activation and immortalization.

  7. Biochemical analysis of SV40 small t mediated theophylline resistance in CV-1 cells

    SciTech Connect

    Renz, C.D.

    1986-01-01

    The papovavirus SV40 encodes for the two tumor antigens, large T and small t. While much is known about large T, little information is available about the role of small t in the viral life cycle. The authors have developed a system for studying small t antigen based on its ability to overcome the G/sub 0/ growth arrest induced by the methylxanthine, theophylline. Uninfected CV-1 cells, the permissive host for SV40, are arrested by 1-2mM theophylline. In contrast, Wt-infected cells are not arrested by the same concentrations of this drug. Biochemical studies were designed to analyze the effects of theophylline and the means by which small t can overcome the growth arrest of CV-1 cells. Theophylline, a cyclic AMP analogue, does not appear to arrest CV-1 cells by a cAMP-dependent mechanism. Theophylline appears to arrest CV-1 cells by inhibiting sodium influx. Both /sub 86/Rb/sup +/ and /sup 22/Na/sup +/ uptake were inhibited by theophylline. Amiloride and TMB-8, drugs which are known to inhibit the plasma membrane Na/sup +//H/sup +/ antiporter, decreased /sup 86/Rb/sup +/ and /sup 22/Na/sup +/ uptake to the same degree as theophylline. Because these drugs also arrested mock and D1- but not Wt-infected cells it is possible that theophylline inhibits sodium uptake by inhibiting this antiporter. Furthermore, because Wt-infected cells are resistant to the growth arrest induced by these drugs, it is possible that small t acts either by directly altering this antiporter or by bypassing the step which requires the activity of the antiporter.

  8. The SV40 large T-antigen origin binding domain directly participates in DNA unwinding.

    PubMed

    Foster, Erin C; Simmons, Daniel T

    2010-03-16

    The origin binding domain (OBD) of SV40 large T-ag serves a critical role during initiation of DNA replication to position T-ag on the origin. After origin recognition, T-ag forms a double hexamer over the origin. Within each hexamer, the OBD adopts a lock washer structure where the origin recognizing A1 and B2 loops face toward the helicase domain and likely become unavailable for binding DNA. In this study, we investigated the role of the central channel of the OBD hexamer in DNA replication by analyzing the effects of mutations of residues lining the channel. All mutants showed binding defects with origin DNA and ssDNA especially at low protein concentrations, but only half were defective at supporting DNA replication in vitro. All mutants were normal in unwinding linear origin DNA fragments. However, replication defective mutants failed to unwind a small origin containing circular DNA whereas replication competent mutants did so normally. The presence of RPA and/or pol/prim restored circular DNA unwinding activity of compromised mutants probably by interacting with the separated DNA strands on the T-ag surface. We interpret these results to indicate a role for the OBD central channel in binding and threading ssDNA during unwinding of circular SV40 DNA. Mixing experiments suggested that only one monomer in an OBD hexamer was necessary for DNA unwinding. We present a model of DNA threading through the T-ag complex illustrating how single-stranded DNA could pass close to a trough generated by key residues in one monomer of the OBD hexamer.

  9. A Missense Mutation of the Gene Encoding Synaptic Vesicle Glycoprotein 2A (SV2A) Confers Seizure Susceptibility by Disrupting Amygdalar Synaptic GABA Release

    PubMed Central

    Tokudome, Kentaro; Okumura, Takahiro; Terada, Ryo; Shimizu, Saki; Kunisawa, Naofumi; Mashimo, Tomoji; Serikawa, Tadao; Sasa, Masashi; Ohno, Yukihiro

    2016-01-01

    Synaptic vesicle glycoprotein 2A (SV2A) is specifically expressed in the membranes of synaptic vesicles and modulates action potential-dependent neurotransmitter release. To explore the role of SV2A in the pathogenesis of epileptic disorders, we recently generated a novel rat model (Sv2aL174Q rat) carrying a missense mutation of the Sv2a gene and showed that the Sv2aL174Q rats were hypersensitive to kindling development (Tokudome et al., 2016). Here, we further conducted behavioral and neurochemical studies to clarify the pathophysiological mechanisms underlying the seizure vulnerability in Sv2aL174Q rats. Sv2aL174Q rats were highly susceptible to pentylenetetrazole (PTZ)-induced seizures, yielding a significantly higher seizure scores and seizure incidence than the control animals. Brain mapping analysis of Fos expression, a biological marker of neural excitation, revealed that the seizure threshold level of PTZ region-specifically elevated Fos expression in the amygdala in Sv2aL174Q rats. In vivo microdialysis study showed that the Sv2aL174Q mutation preferentially reduced high K+ (depolarization)-evoked GABA release, but not glutamate release, in the amygdala. In addition, specific control of GABA release by SV2A was supported by its predominant expression in GABAergic neurons, which were co-stained with antibodies against SV2A and glutamate decarboxylase 1. The present results suggest that dysfunction of SV2A by the missense mutation elevates seizure susceptibility in rats by preferentially disrupting synaptic GABA release in the amygdala, illustrating the crucial role of amygdalar SV2A-GABAergic system in epileptogenesis. PMID:27471467

  10. The effects of progesterone on apoptosis in the human trophoblast-derived HTR-8/SV neo cells.

    PubMed

    Liu, Jin; Matsuo, Hiroya; Laoag-Fernandez, Jovelle B; Xu, Qin; Maruo, Takeshi

    2007-12-01

    Progesterone (P4) is frequently used in the treatment of threatened abortion, prevention of recurrent miscarriage and threatened preterm labor. However, little is known about the molecular mechanism of P4 in the regulation of extravillous trophoblasts' (EVTs) function. This study was designed to examine the presence of progesterone receptor (PR) in the human trophoblast-derived HTR-8/SV neo cell line, which is a possible model of EVTs, and the effects of P4 on apoptosis in those cells. The HTR-8/SV neo cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 microg/ml streptomycin. When the cell the population reached 50% confluency, the cells were stepped down to serum-free conditions in the presence or absence of graded concentrations of P4 (1, 10 and 100 ng/ml) for 48 h. The cultured cells were used for RT-PCR, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay, immunocytochemistry and western blot analyses. Immunocytochemistry and western blot analyses revealed that PR was evident in HTR-8/SV neo cells. Compared with untreated cultures, treatment with P4 (10 and 100 ng/ml) resulted in significant decreases in the TUNEL-positive rate, Fas, Fas ligand (Fas-L), caspase-8, caspase-3 and poly (ADP-ribose) polymerase (PARP) expression in HTR-8/SV neo cells, and a significant increase in Bcl-2 expression in those cells. Consistently, Fas mRNA expression in those cells was significantly inhibited by the treatment with 10 ng/ml P4 compared with untreated cultures. This study suggests that PR exists in HTR-8/SV neo cells and that P4 inhibits apoptosis by down-regulating Fas, Fas-L, caspase-8, caspase-3 and PARP expression as well as up-regulating Bcl-2 expression in HTR-8/SV neo cells.

  11. Exploring the Interaction of SV2A with Racetams Using Homology Modelling, Molecular Dynamics and Site-Directed Mutagenesis

    PubMed Central

    Lee, Joanna; Daniels, Veronique; Sands, Zara A.; Lebon, Florence; Shi, Jiye; Biggin, Philip C.

    2015-01-01

    The putative Major Facilitator Superfamily (MFS) transporter, SV2A, is the target for levetiracetam (LEV), which is a successful anti-epileptic drug. Furthermore, SV2A knock out mice display a severe seizure phenotype and die after a few weeks. Despite this, the mode of action of LEV is not known at the molecular level. It would be extremely desirable to understand this more fully in order to aid the design of improved anti-epileptic compounds. Since there is no structure for SV2A, homology modelling can provide insight into the ligand-binding site. However, it is not a trivial process to build such models, since SV2A has low sequence identity to those MFS transporters whose structures are known. A further level of complexity is added by the fact that it is not known which conformational state of the receptor LEV binds to, as multiple conformational states have been inferred by tomography and ligand binding assays or indeed, if binding is exclusive to a single state. Here, we explore models of both the inward and outward facing conformational states of SV2A (according to the alternating access mechanism for MFS transporters). We use a sequence conservation analysis to help guide the homology modelling process and generate the models, which we assess further with Molecular Dynamics (MD). By comparing the MD results in conjunction with docking and simulation of a LEV-analogue used in radioligand binding assays, we were able to suggest further residues that line the binding pocket. These were confirmed experimentally. In particular, mutation of D670 leads to a complete loss of binding. The results shed light on the way LEV analogues may interact with SV2A and may help with the on-going design of improved anti-epileptic compounds. PMID:25692762

  12. Development of a highly-efficient CHO cell line generation system with engineered SV40E promoter.

    PubMed

    Fan, Lianchun; Kadura, Ibrahim; Krebs, Lara E; Larson, Jeffery L; Bowden, Daniel M; Frye, Christopher C

    2013-12-01

    Chinese hamster ovary (CHO) cells have been one of the most widely used host cells for the manufacture of therapeutic recombinant proteins. An effective and efficient clinical cell line development process, which could quickly identify those rare, high-producing cell lines among a large population of low and non-productive cells, is of considerable interest to speed up biological drug development. In the glutamine synthetase (GS)-CHO expression system, selection of top-producing cell lines is based on controlling the balance between the expression level of GS and the concentration of its specific inhibitor, l-methionine sulfoximine (MSX). The combined amount of GS expressed from plasmids that have been introduced through transfection and the endogenous CHO GS gene determine the stringency and efficiency of selection. Previous studies have shown significant improvement in selection stringency by using GS-knockout CHO cells, which eliminate background GS expression from the endogenous GS gene in CHOK1SV cells. To further improve selection stringency, a series of weakened SV40E promoters have been generated and used to modulate plasmid-based GS expression with the intent of manipulating GS-CHO selection, finely adjusting the balance between GS expression and GS inhibitor (MSX) levels. The reduction of SV40E promoter activities have been confirmed by TaqMan RT-PCR and GFP expression profiling. Significant productivity improvements in both bulk culture and individual clonal cell line have been achieved with the combined use of GS-knockout CHOK1SV cells and weakened SV40E promoters driving GS expression in the current cell line generation process. The selection stringency was significantly increased, as indicated by the shift towards higher distribution of producing-cell populations, even with no MSX added into cell culture medium. The potential applications of weakened SV40E promoter and GS-knockout cells in development of targeted integration and transient CHO

  13. Simultaneous stereoselective high-performance liquid chromatographic determination of 10-hydroxycarbazepine and its metabolite carbamazepine-10,11-trans-dihydrodiol in human urine.

    PubMed

    Volosov, A; Bialer, M; Xiaodong, S; Perucca, E; Sintov, A; Yagen, B

    2000-02-11

    An enantioselective HPLC method for the simultaneous determination of the concentration of the enantiomers of the oxcarbazepine metabolites 10-hydroxycarbazepine (MHD) and carbamazepine-10,11-trans-dihydrodiol (DHD) in human urine is described. The method is based on extraction with tert.-butylmethyl ether-dichloromethane (2:1, v/v) under alkaline conditions, separation and evaporation of the organic phase and dissolution of the residue in the mobile phase. Enantiomers are resolved on a Diacel Chiralcel OD column (250 mm x 4.6 mm I.D.) under isocratic conditions using as mobile phase n-hexane-ethanol-2-propanol (18:2:1, v/v/v) with addition of glacial acetic acid (0.1%). The enantiomers are detected by UV at 215 nm. The method allows reliable determination of the MHD and DHD enantiomers in human urine with limits of quantification of 0.2 mg/l and 0.4 mg/l, respectively.

  14. Comparison of in vitro and in vivo phototoxicity tests with S-(-)-10,11-dihydroxyfarnesic acid methyl ester produced by Beauveria bassiana KACC46831.

    PubMed

    Kim, Min-A; Son, Hyeong-U; Yoon, Cheol-Sik; Nam, Sung-Hee; Choi, Young-Cheol; Lee, Sang-Han

    2014-09-01

    Beauveria bassiana is a fungi that is well-known for demonstrating a resistance to environmental change. To confirm whether S-(-)-10,11-dihydroxyfarnesic acid methyl ester (DHFAME) produced by Beauveria bassiana KACC46831 causes phototoxicity when used for cosmetic purposes due to its anti-tyrosinase activity, we conducted in vitro and in vivo phototoxicity tests. There were no significant changes or damage observed in the compound-treated group with regards to skin phototoxicity, while 8-methoxypsoralen, which served as a positive control, induced toxic effects. The in vitro 3T3 neutral red uptake assay, an alternative assessment, was used for further confirmation of the phototoxicity. The results showed that DHFAME did not exhibit phototoxicity at the designated concentrations, with or without UV irradiation in the 3T3 cells. These results indicated that the methyl ester produced by Beauveria bassiana KACC46831 does not induce phototoxicity in the skin. Therefore, the results of the present study indicate that DHFAME shows potential for use as a cosmetic ingredient that does not cause skin phototoxicity.

  15. Microscopic analysis of 10,11Be elastic scattering on protons and 12C and breakup processes of 11Be within the 10Be+n cluster model

    NASA Astrophysics Data System (ADS)

    Spasova, K.; Lukyanov, V. K.; Kadrev, D. N.; Antonov, A. N.; Zemlyanaya, E. V.; Lukyanov, K. V.; Gaidarov, M. K.

    2016-06-01

    The elastic scattering cross-sections of 10,11Be on protons and 12C at energy E < 100 MeV/nucleon using microscopically calculated optical potentials (OP) are presented. The real OP is obtained by a folding procedure with effective NN interactions, while the imaginary OP is estimated within the high energy approximation (HEA). The spin-orbit part of the OP is also included. The characteristics of the breakup processes of 11Be on different nuclear targets are also considered. The cross-sections of diffractive breakup and stripping reactions of 11Be on 9Be, 93Nb, 181Ta and 238U at energy E = 63 MeV/nucleon and the longitudinal momentum distributions of 10Be fragments produced in the breakup of 11Be on these nuclei are presented. The results are in a good agreement with the available experimental data, in particular the obtained widths of about 50 MeV/c are closed to the empirical ones.

  16. Quantification of carbamazepine and its 10,11-epoxide metabolite in rat plasma by UPLC-UV and application to pharmacokinetic study.

    PubMed

    Beig, Avital; Dahan, Arik

    2014-07-01

    A rapid, selective and sensitive UPLC-UV method was developed and validated for the quantitative analysis of carbamazepine and its epoxide metabolite in rat plasma. A relatively small volume of plasma sample (200 μL) is required for the described analytical method. The method includes simple protein precipitation, liquid-liquid extraction, evaporation, and reconstitution steps. Samples were separated on a Waters Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) with a gradient mobile phase consisted of 60:40 going to 40:60 (v/v) water-acetonitrile at a flow rate of 0.5 mL/min. The total run time was as low as 6 min, representing a significant improvement in comparison to existing methods. Excellent linearity (r(2)  > 0.999) was achieved over a wide concentration range. Close to complete recovery, short analysis time, high stability, accuracy, precision and reproducibility, and low limit of quantitation were demonstrated. Finally, we successfully applied this analytical method to a pre-clinical oral pharmacokinetic study, revealing the plasma profiles of both carbamazepine and carbamazepine-10,11-epoxide following oral administration of carbamazepine to rats. The advantages demonstrated in this work make this analytical method both time- and cost-efficient approach for drug and metabolite monitoring in the pre-clinical/clinical laboratory.

  17. Metal-organic Kagome lattices M3(2,3,6,7,10,11-hexaiminotriphenylene)2 (M = Ni and Cu): from semiconducting to metallic by metal substitution.

    PubMed

    Chen, Shuang; Dai, Jun; Zeng, Xiao Cheng

    2015-02-28

    Motivated by recent experimental synthesis of a semiconducting metal-organic graphene analogue (J. Am. Chem. Soc., 2014, 136, 8859), i.e., Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 [Ni3(HITP)2], a new Kagome lattice, Cu3(HITP)2, is designed by substituting the coordination of Ni by Cu. Such substitution results in interesting changes in electronic properties of the M3(HITP)2 bulk and two-dimensional (2D) sheets. In Ni3(HITP)2, each Ni atom adopts the dsp(2) hybridization, forming a perfect 2D conjugation, whereas in Cu3(HITP)2, each Cu atom adopts the sp(3) hybridization, resulting in a distorted 2D sheet. The M3(HITP)2 bulks, assembled from M3(HITP)2 sheets via both strong π-π interaction and weak metal-metal interaction, are metallic. However, the 2D Ni3(HITP)2 sheet is a semiconductor with a narrow band gap whereas the 2D Cu3(HITP)2 sheet is a metal. Remarkably, both the 2D M3(HITP)2 Kagome lattices possess Dirac bands in the vicinity of the Fermi level. Additional ab initio molecular dynamics simulations show that both sheets exhibit high thermal stability at elevated temperatures. Our theoretical study offers new insights into tunability of electronic properties for the 2D metal-organic frameworks (MOFs).

  18. Comorbidity of 9/11-related PTSD and depression in the World Trade Center Health Registry 10-11 years postdisaster.

    PubMed

    Caramanica, Kimberly; Brackbill, Robert M; Liao, Tim; Stellman, Steven D

    2014-12-01

    Many studies report elevated prevalence of posttraumatic stress disorder (PTSD) and depression among persons exposed to the September 11, 2001 (9/11) disaster compared to those unexposed; few have evaluated long-term PTSD with comorbid depression. We examined prevalence and risk factors for probable PTSD, probable depression, and both conditions 10-11 years post-9/11 among 29,486 World Trade Center Health Registry enrollees who completed surveys at Wave 1 (2003-2004), Wave 2 (2006-2007), and Wave 3 (2011-2012). Enrollees reporting physician diagnosed pre-9/11 PTSD or depression were excluded. PTSD was defined as scoring ≥ 44 on the PTSD Checklist and depression as scoring ≥ 10 on the 8-item Patient Health Questionnaire. We examined 4 groups: comorbid PTSD and depression, PTSD only, depression only, and neither. Among enrollees, 15.2% reported symptoms indicative of PTSD at Wave 3, 14.9% of depression, and 10.1% of both. Comorbid PTSD and depression was associated with high 9/11 exposures, low social integration, health-related unemployment, and experiencing ≥ 1 traumatic life event post-9/11. Comorbid persons experienced poorer outcomes on all PTSD-related impairment measures, life satisfaction, overall health, and unmet mental health care need compared to those with only a single condition. These findings highlight the importance of ongoing screening and treatment for both conditions, particularly among those at risk for mental health comorbidity.

  19. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    SciTech Connect

    Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya; Ohno, Naohito; Matsushita, Sho; Akatsuka, Toshitaka; Handa, Hiroshi; Matsui, Masanori

    2014-01-05

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.

  20. Oil Sands Characteristics and Time-Lapse and P-SV Seismic Steam Monitoring, Athabasca, Canada

    NASA Astrophysics Data System (ADS)

    Takahashi, A.; Nakayama, T.; Kashihara, K.; Skinner, L.; Kato, A.

    2008-12-01

    -injection. The differences of the seismic responses between the time-lapse seismic volumes can be quantitatively explained by P-wave velocity decrease of the oil sands layers due to steam-injection. In addition, the data suggests that a larger area would be influenced by pressure than temperature. We calculate several seismic attributes such as RMS values of amplitude difference, maximum cross correlations, and interval velocity differences. These attributes are integrated by using self-organization maps (SOM) and K-means methods. By this analysis, we are able to distinguish areas of steam chamber growth from transitional and non-affected areas. In addition, 3D P-SV converted-wave processing and analysis are applied on the second 3D data set (recorded with three-component digital sensor). Low Vp/Vs values in the P-SV volume show areas of steam chamber development, and high Vp/Vs values indicate transitional zones. Our analysis of both time-lapse 3D seismic and 3D P-SV data along with the rock physics model can be used to monitor qualitatively and quantitatively the rock property changes of the inter-well reservoir sands in the field.

  1. Virus--tumor host cell relationships. In vivo cocultivation of adenovirus type 5 and of SV40 in mouse Ehrlich ascites carcinoma.

    PubMed

    Nastac, E; Chira, M; Hozoc, M; Athanasiu, P; Teleguţă, L; Suru, M; Stoian, M; Pirvu, C

    1982-01-01

    Mouse Ehrlich ascites carcinoma (EAC) cells proved to be a semipermissive substrate for in vivo cultivation of adenovirus 5 (Ad5) and SV40. The multiplication of SV40 in EAC cells was facilitated by the coinfection with Ad5. As demonstrated by ID and EID reactions, the virus progens isolated at the first passage after the mixed infection of EAC cells with Ad5 and SV40 possess an antigenic mosaic with fractions characteristic of the parental viruses and of the cell substrate in which they had cultivated in vitro and in vivo. The progens gave positive seroneutralization and complement fixation reactions only with antiserum to SV40.

  2. Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F

    SciTech Connect

    Fu, Zhuji; Chen, Chen; Barbieri, Joseph T.; Kim, Jung-Ja P.; Baldwin, Michael R.

    2010-02-22

    Botulinum neurotoxin causes rapid flaccid paralysis through the inhibition of acetylcholine release at the neuromuscular junction. The seven BoNT serotypes (A-G) have been proposed to bind motor neurons via ganglioside-protein dual receptors. To date, the structure-function properties of BoNT/F host receptor interactions have not been resolved. Here, we report the crystal structures of the receptor binding domains (HCR) of BoNT/A and BoNT/F and the characterization of the dual receptors for BoNT/F. The overall polypeptide fold of HCR/A is essentially identical to the receptor binding domain of the BoNT/A holotoxin, and the structure of HCR/F is very similar to that of HCR/A, except for two regions implicated in neuronal binding. Solid phase array analysis identified two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core. Using affinity chromatography, HCR/F bound native synaptic vesicle glycoproteins as part of a protein complex. Deglycosylation of glycoproteins using {alpha}(1-3,4)-fucosidase, endo-{beta}-galactosidase, and PNGase F disrupted the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, was unaffected. These data indicate that the HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2. The interaction of HCR/F with gangliosides was also investigated. HCR/F bound specifically to gangliosides that contain {alpha}2,3-linked sialic acid on the terminal galactose of a neutral saccharide core (binding order GT1b = GD1a GM3; no binding to GD1b and GM1a). Mutations within the putative ganglioside binding pocket of HCR/F decreased binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons. Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons.

  3. SvSXP: a Strongylus vulgaris antigen with potential for prepatent diagnosis

    PubMed Central

    2013-01-01

    Background Strongyle parasites are ubiquitous in grazing horses. Strongylus vulgaris, the most pathogenic of the large strongyles, is known for its extensive migration in the mesenteric arterial system. The lifecycle of S. vulgaris is characterised by a long prepatent period where the migrating larvae are virtually undetectable as there currently is no test available for diagnosing prepatent S. vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes endarteritis and thrombosis with a risk of non-strangulating intestinal infarctions. Emergence of anthelmintic resistance among cyathostomins has led to recommendations of reduced treatment intensity by targeting horses that exceed a predetermined strongyle faecal egg count threshold. One study suggests an apparent increase in prevalence of S. vulgaris on farms where reduced anthelmintic treatment intensity has been implemented. These issues highlight the need for an accurate and reliable assay for diagnosing prepatent S. vulgaris infection. Methods Immunoscreening of a larval S. vulgaris cDNA library using hyperimmune serum raised against S. vulgaris excretory/secretory antigens was performed to identify potential diagnostic antigens. Immunoreactive clones were sequenced, one potential antigen was characterised, expressed as a recombinant protein, initially evaluated by western blot (WB) analysis, the diagnostic potential of the IgG subclasses was evaluated by ELISA, and the diagnostic accuracy evaluated using serum from 102 horses with known S. vulgaris infection status. Results The clone expressing the potential antigen encoded a S. vulgaris SXP/RAL2 homologue. The recombinant protein, rSvSXP, was shown to be a potential diagnostic antigen by WB analysis, and a target of serum IgGa, IgG(T) and total IgG in naturally infected horses, with IgG(T) antibodies being the most reliable indicator of S. vulgaris infection in horses. Evaluation of diagnostic accuracy of the ELISA resulted in a

  4. Preclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H

    PubMed Central

    2013-01-01

    Background [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared. Methods Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors. Results Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation. Conclusions This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient

  5. SV40-IMMORTALIZED NON-TUMORIGENIC AND TUMORIGENIC CELL LINES DIFFER IN EXPRESSION OF HALLMARK VIRAL RESPONSE MRNAS

    EPA Science Inventory

    SV40-Immortalized Non-Tumorigenic and Tumorigenic Cell Lines Differ in Expression of Hallmark Viral Response mRNAs.

    Prior to the use of an in vitra/in viva transformation system to examine the tumorigenic activity of environmental contaminants, in vitra gene expression pa...

  6. 77 FR 10739 - SV Hydro, LLC, Coffeeville, LLC, FFP Project 99, LLC; Notice Announcing Preliminary Permit Drawing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... Energy Regulatory Commission SV Hydro, LLC, Coffeeville, LLC, FFP Project 99, LLC; Notice Announcing Preliminary Permit Drawing . The Commission has received three preliminary permit applications deemed filed on October 3, 2011, at 8:30 a.m.,\\1\\ for proposed projects to be located at the U.S. Army Corps of...

  7. Gene expression promoted by the SV40 DNA targeting sequence and the hypoxia-responsive element under normoxia and hypoxia.

    PubMed

    Sacramento, C B; Moraes, J Z; Denapolis, P M A; Han, S W

    2010-08-01

    The main objective of the present study was to find suitable DNA-targeting sequences (DTS) for the construction of plasmid vectors to be used to treat ischemic diseases. The well-known Simian virus 40 nuclear DTS (SV40-DTS) and hypoxia-responsive element (HRE) sequences were used to construct plasmid vectors to express the human vascular endothelial growth factor gene (hVEGF). The rate of plasmid nuclear transport and consequent gene expression under normoxia (20% O2) and hypoxia (less than 5% O2) were determined. Plasmids containing the SV40-DTS or HRE sequences were constructed and used to transfect the A293T cell line (a human embryonic kidney cell line) in vitro and mouse skeletal muscle cells in vivo. Plasmid transport to the nucleus was monitored by real-time PCR, and the expression level of the hVEGF gene was measured by ELISA. The in vitro nuclear transport efficiency of the SV40-DTS plasmid was about 50% lower under hypoxia, while the HRE plasmid was about 50% higher under hypoxia. Quantitation of reporter gene expression in vitro and in vivo, under hypoxia and normoxia, confirmed that the SV40-DTS plasmid functioned better under normoxia, while the HRE plasmid was superior under hypoxia. These results indicate that the efficiency of gene expression by plasmids containing DNA binding sequences is affected by the concentration of oxygen in the medium.

  8. N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A

    PubMed Central

    Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan; Lam, Kwok-ho; Stern, Daniel; Bagramyan, Karine; Perry, Kay; Kalkum, Markus; Rummel, Andreas; Dong, Min; Jin, Rongsheng

    2016-01-01

    Botulinum neurotoxin serotype A1 (BoNT/A1) is one of the most dangerous potential bioterrorism agents, and exerts its action by invading motoneurons. It is also a licensed drug widely used for medical and cosmetic applications. Here we report a 2.0 Å resolution crystal structure of BoNT/A1 receptor-binding domain in complex with its neuronal receptor, the glycosylated human SV2C. We find that the neuronal tropism of BoNT/A1 requires recognition of both the peptide moiety and an N-linked glycan on SV2. This N-glycan—conserved in all SV2 isoforms across vertebrates—is essential for BoNT/A1 binding to neurons and its potent neurotoxicity. The glycan-binding interface on SV2 is targeted by a human BoNT/A1-neutralizing antibody currently licensed as an anti-botulism drug. Our studies reveal a new paradigm of host-pathogen interactions, in which pathogens exploit conserved host post-translational modifications to achieve highly specific receptor binding while also tolerating genetic changes across multiple isoforms of receptors. PMID:27294781

  9. Reliability and Validity Evaluation of the Psychopathy Checklist: Screening Version (PCL:SV) in Swedish Correctional and Forensic Psychiatric Samples

    ERIC Educational Resources Information Center

    Douglas, Kevin S.; Strand, Susanne; Belfrage, Henrik; Fransson, Goran; Levander, Sten

    2005-01-01

    This study evaluated the structural reliability, construct-related validity, and cultural validity generalization of the Hare Psychopathy Checklist: Screening Version (PCL:SV) in a sample of more than 560 male and female Swedish forensic psychiatric treatment patients, forensic evaluation patients, and criminal offenders. Structural reliability…

  10. Examining the Utility of the PCL:SV as a Screening Measure Using Competing Factor Models of Psychopathy

    ERIC Educational Resources Information Center

    Guy, Laura S.; Douglas, Kevin S.

    2006-01-01

    The correspondence between the Hare Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995) and the Hare Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991, 2003) was examined in forensic (N = 175) and correctional (N = 188) samples. Intermeasure correlations for Total scores (0.95 forensic, 0.94…

  11. Examining the utility of the PCL:SV as a screening measure using competing factor models of psychopathy.

    PubMed

    Guy, Laura S; Douglas, Kevin S

    2006-06-01

    The correspondence between the Hare Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995) and the Hare Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991, 2003) was examined in forensic (N = 175) and correctional (N = 188) samples. Intermeasure correlations for Total scores (.95 forensic, .94 correctional) and the original 2-factor, D. J. Cooke and C. Michie's (2001) 3-factor, and R. D. Hare's (2003) 4-facet models (range = .87-.95) were high. Area under the curve values for the PCL:SV were .98 in both samples (cutoff = PCL-R Total score of 25). The PCL:SV performed well as a screen, maximizing false positive relative to false negative errors. Close correlations for prediction of violent recidivism in the correctional sample were obtained for the PCL-R (.42) and PCL:SV (.37). Results indicate the robust relation between the measures is maintained whether they are completed on the basis of file review only or file plus interview and whether the same or different raters score the measures.

  12. P-SV conversions at a shallow boundary beneath Campi Flegrei caldera (Italy) - evidence for the magma chamber

    SciTech Connect

    Ferrucci, F.; Hirn, A.; De Natale, G.; Virieux, J.; Mirabile, L. Inst. de Physique du Globe, Paris Osservatorio Vesuviano, Naples CNRS, Inst. de Geodynamique, Valbonne Ist. Universitario Navale, Naples )

    1992-10-01

    Seismograms from an active seismic experiment carried out at Campi Flegrei caldera (near Naples, Italy), show a large-amplitude SV-polarized shear wave, following by less than 1.5-s P waves reflected at wide angle from a deep crustal interface. Early arriving SV-polarized waves, with the same delay to direct P waves, are also observed in seismograms from a regional 280 km-deep, magnitude 5.1 earthquake. Such short delays of S to P waves are consistent with a P-SV conversion on transmission occurring at a shallow boundary beneath the receivers. The large amplitude of the converted-SV phase, along with that the P waves are near vertical, requires a boundary separating a very low rigidity layer from the upper caldera fill. The converted phases are interpreted as a seismic marker of a magma chamber. The top of this magma chamber is located slightly deeper than the deepest earthquakes observed during the 1982-1984 unrest of Campi Flegrei. 8 refs.

  13. Structure and properties of 9,10,11,12,13,14-hexahydro-9,10[1‧,4‧]-benzenoanthracene and 9,10,11,12,13,14,15,16-octahydro-9,10[1‧,4‧]-benzenoanthracene

    NASA Astrophysics Data System (ADS)

    Masnovi, Michelle E.; Schildcrout, Steven M.; Masnovi, John

    2015-01-01

    The title compounds were prepared by 4πs + 4πs photochemical cycloaddition between anthracene and 1,3-cyclohexadiene, followed by catalytic hydrogenation. The results confirm the structure of the initial cycloadduct, 9,10,11,12,13,14-hexahydro-9,10[1‧,4‧]-benzenoanthracene (1), which in the crystal exhibits positional disorder about the cyclohexadiene-derived fragment that is only partially resolved. The origin of the disorder is considered in light of the crystallographic packing interactions and compared with intermolecular contacts in the hydrogenated derivative, 9,10,11,12,13,14,15,16-octahydro-9,10[1‧,4‧]-benzenoanthracene (2), which is not disordered. The asymmetric unit of 2 contains one-half of a molecule situated about a two-fold symmetry axis. Both structures contain relatively long interannular bonds between the bridgehead carbons of the anthracene- and cyclohexadiene-derived fragments, in agreement with ab initio calculations and considered in terms of bond strain in the carbon framework of these compounds.

  14. Cryo-electron microscopy of vitrified SV40 minichromosomes: the liquid drop model.

    PubMed Central

    Dubochet, J; Adrian, M; Schultz, P; Oudet, P

    1986-01-01

    The structure of SV40 minichromosomes has been studied by cryo-electron microscopy of vitrified thin layers of solution. In high-salt buffer (130 mM NaCl), freshly prepared minichromosomes are condensed into globules 30 nm or more in diameter. On the micrograph, they appear to be formed by the close packing of 10 nm granules which give rise to a 10 nm reflection in the optical diffractogram. The globules can adopt many different conformations. At high concentration, they fuse into a homogeneous 'sea' of closely packed 10 nm granules. In low-salt buffer (less than 10 mM NaCl), the globules open, first into 10 nm filaments, and then into nucleosome-strings. The 'liquid drop' model is proposed to explain the condensed structure of the minichromosome in high-salt buffer: nucleosomes stack specifically on top of one another, thus forming the 10 nm filaments. 10 nm filaments in turn, tend to aggregate laterally. Optimizing both these interactions results in the condensation of 10 nm filaments or portions thereof into a structure similar to that of a liquid. Some implications of this model for the structure of cellular chromatin are discussed. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 11. Fig. 13. Fig. 14. PMID:3011410

  15. Adsorptive stripping voltammetry of antibiotics rifamycin SV and rifampicin at renewable pencil electrodes.

    PubMed

    Kawde, Abdel-Nasser; Temerk, Yassein; Farhan, Nasser

    2014-01-01

    Adsorptive stripping voltammetry of antibiotics of rifamycin SV (RSV) and rifampicin (RIF) was investigated by cyclic voltammetry and differential pulse voltammetry using a renewable pencil graphite electrode (PGE). The nature of the oxidation process of RSV and RIF taking place at the PGE was characterized. The results show that the determination of highly sensitive oxidation peak current is the basis of a simple, accurate and rapid method for quantification of RSV and RIF in bulk forms, pharmaceutical formulations and biological fluids by differential pulse adsorptive stripping voltammetry (DPASV). Factors influencing the trace measurement of RSV and RIF at PGE are assessed. The limits of detection for the determination of RSV and RIF in bulk forms are 6.0 × 10(-8) mol/L and 1.3 × 10(-8) mol/L, respectively. Moreover, the proposed procedure was successfully applied to assay both RSV and RIF in pharmaceutical formulations and in biological fluids. The capability of the proposed procedure for simultaneous assay of antibiotics RSV-isoniazid and RIF-isoniazid was achieved. The statistical analysis and calibration curve data for trace determination of RSV and RIF are reported.

  16. Defined single-gene and multi-gene deletion mutant collections in Salmonella enterica sv Typhimurium.

    PubMed

    Porwollik, Steffen; Santiviago, Carlos A; Cheng, Pui; Long, Fred; Desai, Prerak; Fredlund, Jennifer; Srikumar, Shabarinath; Silva, Cecilia A; Chu, Weiping; Chen, Xin; Canals, Rocío; Reynolds, M Megan; Bogomolnaya, Lydia; Shields, Christine; Cui, Ping; Guo, Jinbai; Zheng, Yi; Endicott-Yazdani, Tiana; Yang, Hee-Jeong; Maple, Aimee; Ragoza, Yury; Blondel, Carlos J; Valenzuela, Camila; Andrews-Polymenis, Helene; McClelland, Michael

    2014-01-01

    We constructed two collections of targeted single gene deletion (SGD) mutants and two collections of targeted multi-gene deletion (MGD) mutants in Salmonella enterica sv Typhimurium 14028s. The SGD mutant collections contain (1), 3517 mutants in which a single gene is replaced by a cassette containing a kanamycin resistance (KanR) gene oriented in the sense direction (SGD-K), and (2), 3376 mutants with a chloramphenicol resistance gene (CamR) oriented in the antisense direction (SGD-C). A combined total of 3773 individual genes were deleted across these SGD collections. The MGD collections contain mutants bearing deletions of contiguous regions of three or more genes and include (3), 198 mutants spanning 2543 genes replaced by a KanR cassette (MGD-K), and (4), 251 mutants spanning 2799 genes replaced by a CamR cassette (MGD-C). Overall, 3476 genes were deleted in at least one MGD collection. The collections with different antibiotic markers permit construction of all viable combinations of mutants in the same background. Together, the libraries allow hierarchical screening of MGDs for different phenotypic followed by screening of SGDs within the target MGD regions. The mutants of these collections are stored at BEI Resources (www.beiresources.org) and publicly available.

  17. Effect of Trimethyltin Chloride on Slow Vacuolar (SV) Channels in Vacuoles from Red Beet (Beta vulgaris L.) Taproots.

    PubMed

    Trela, Zenon; Burdach, Zbigniew; Siemieniuk, Agnieszka; Przestalski, Stanisław; Karcz, Waldemar

    2015-01-01

    In the present study, patch-clamp techniques have been used to investigate the effect of trimethyltin chloride (Met3SnCl) on the slow vacuolar (SV) channels in vacuoles from red beet (Beta vulgaris L.) taproots. Activity of SV channels has been measured in whole-vacuole and cytosolic side-out patch configurations. It was found that addition of trimethyltin chloride to the bath solution suppressed, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant, τ, increased significantly in the presence of the organotin. When single channel activity was analyzed, only little channel activity could be recorded at 100 μM Met3SnCl. Trimethyltin chloride added to the bath medium significantly decreased (by ca. threefold at 100 μM Met3SnCl and at 100 mV voltage, as compared to the control medium) the open probability of single channels. Single channel recordings obtained in the presence and absence of trimethyltin chloride showed that the organotin only slightly (by <10%) decreased the unitary conductance of single channels. It was also found that Met3SnCl significantly diminished the number of SV channel openings, whereas it did not change the opening times of the channels. Taking into account the above and the fact that under the here applied experimental conditions (pH = 7.5) Met3SnCl is a non-dissociated (more lipophilic) compound, we suggest that the suppression of SV currents observed in the presence of the organotin results probably from its hydrophobic properties allowing this compound to translocate near the selectivity filter of the channel.

  18. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    PubMed

    Sowd, Gregory A; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L; Fanning, Ellen

    2014-12-01

    Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs) kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs) and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  19. Effect of Trimethyltin Chloride on Slow Vacuolar (SV) Channels in Vacuoles from Red Beet (Beta vulgaris L.) Taproots

    PubMed Central

    Trela, Zenon; Burdach, Zbigniew; Siemieniuk, Agnieszka; Przestalski, Stanisław; Karcz, Waldemar

    2015-01-01

    In the present study, patch-clamp techniques have been used to investigate the effect of trimethyltin chloride (Met3SnCl) on the slow vacuolar (SV) channels in vacuoles from red beet (Beta vulgaris L.) taproots. Activity of SV channels has been measured in whole-vacuole and cytosolic side-out patch configurations. It was found that addition of trimethyltin chloride to the bath solution suppressed, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant, τ, increased significantly in the presence of the organotin. When single channel activity was analyzed, only little channel activity could be recorded at 100 μM Met3SnCl. Trimethyltin chloride added to the bath medium significantly decreased (by ca. threefold at 100 μM Met3SnCl and at 100 mV voltage, as compared to the control medium) the open probability of single channels. Single channel recordings obtained in the presence and absence of trimethyltin chloride showed that the organotin only slightly (by <10%) decreased the unitary conductance of single channels. It was also found that Met3SnCl significantly diminished the number of SV channel openings, whereas it did not change the opening times of the channels. Taking into account the above and the fact that under the here applied experimental conditions (pH = 7.5) Met3SnCl is a non-dissociated (more lipophilic) compound, we suggest that the suppression of SV currents observed in the presence of the organotin results probably from its hydrophobic properties allowing this compound to translocate near the selectivity filter of the channel. PMID:26317868

  20. Preliminary report on the July 10-11, 2015 eruption at Volcán de Colima: Pyroclastic density currents with exceptional runouts and volume

    NASA Astrophysics Data System (ADS)

    Capra, L.; Macías, J. L.; Cortés, A.; Dávila, N.; Saucedo, R.; Osorio-Ocampo, S.; Arce, J. L.; Gavilanes-Ruiz, J. C.; Corona-Chávez, P.; García-Sánchez, L.; Sosa-Ceballos, G.; Vázquez, R.

    2016-01-01

    On July 10-11, 2015 an eruption occurred at Colima volcano produced 10.5 km long pyroclastic density currents (PDCs) along the Montegrande, and 6.5 km long along the San Antonio ravines. The summit dome was destroyed and a new crater excavated and breached to the south. This new breach connects to a narrow channel that descends along Colima's southern flank and was used by a subsequent lava flow. The Montegrande PDCs represent the longest and hottest flow of this type recorded during the past 30 years but are still smaller in comparison to the 15-km long PDCs produced during the 1913 Plinian eruption. Data obtained from field reconnaissance, lahar monitoring stations, and satellite imagery suggest that at least six PDCs occurred. The two largest PDCs (H/L 0.2) were able to surmount topographic barriers or bends. Based on field reconnaissance and digital elevation models extracted from SPOT satellite imageries we estimate a minimum volume for the valley-pond and distal fan deposits of 4.5 × 106 m3. After one week, the deposits were still hot with burning trees on the surface and millimeter-sized holes from which fumes were emanating. The juvenile components of the deposits consist of gray dense blocks and vesicular dark-gray blocks and bombs with bread-crust textures and cooling joints. The mineral association of these rocks consists of plagioclase + clinopyroxene + orthopyroxene + FeTi-oxides ± olivine and resorbed hornblende in a dark glassy matrix that corresponds to an andesitic composition.

  1. Definition and evolution of a new symbiovar, sv. rigiduloides, among Ensifer meliloti efficiently nodulating Medicago species.

    PubMed

    Gubry-Rangin, Cécile; Béna, Gilles; Cleyet-Marel, Jean-Claude; Brunel, Brigitte

    2013-10-01

    Understanding functional diversity is one of the main goals of microbial ecology, and definition of new bacterial ecotypes contributes significantly to this objective. Nitrogen-fixing bacteria provide a good system for investigation of ecotypes/biovars/symbiovars, as they present different specific associations with several host plants. This specific symbiosis is reflected both in the nodulation and fixation efficiency and in genetic characters of the bacteria, and several biovars have already been described in the bacterial species Ensifer meliloti. In the present study, the species affiliation of E. meliloti strains trapped from nodules sampled from Medicago rigiduloïdes roots was analyzed using housekeeping recA genes and DNA-DNA hybridization. The genetic diversity of these isolates was also investigated using several symbiotic markers: nodulation (nodA, nodB, nodC) and nitrogen fixation (nifH) genes, as well as the performance of phenotypic tests of nodulation capacity and nitrogen fixation efficiency. These analyses led to the proposal of a new bacterial symbiovar, E. meliloti sv. rigiduloides, that fixed nitrogen efficiently on M. rigiduloïdes, but not on Medicago truncatula. Using phylogenetic reconstructions, including the different described symbiovars, several hypotheses of lateral gene transfer and gene loss are proposed to explain the emergence of symbiovars within this species. The widespread geographical distribution of this symbiovar around the Mediterranean Basin, in contrast to restriction of M. rigiduloïdes to Eastern European countries, suggests that these isolates might also be associated with other plant species. The description of a new symbiovar within E. meliloti confirms the need for accurate bacterial ecological classification, especially for analysis of bacterial populations.

  2. Analytic performance evaluation of a new turbidimetric immunoassay for carbamazepine on the ADVIA 1650 analyzer: effect of carbamazepine 10,11-epoxide.

    PubMed

    Dasgupta, Amitava; Datta, Pradip

    2005-02-01

    Carbamazepine, an anticonvulsant, requires therapeutic drug monitoring. Recently Bayer HealthCare, Diagnostics Division released a turbidimetric immunoassay of carbamazepine on the ADVIA 1650 analyzer. We evaluated the analytic performance of this assay by comparing values obtained with this new assay in sera of 54 patients receiving carbamazepine with the values obtained by using a widely used fluorescence polarization immunoassay (FPIA) and a chemiluminescent immunoassay (CLIA). The new turbidimetric immunoassay for carbamazepine showed excellent precision. The low control showed a total CV of 4.9% (mean 2.86, SD 0.14 microg/mL), the medium control demonstrated a total CV of 3.5% (mean 7.79, SD 0.27 microg/mL), and the high control showed a total CV of 4.8% (mean 16.15, SD 0.78 microg/mL). The assay was linear up to a carbamazepine concentration of 20 microg/mL. The assay showed excellent dilution recovery and recovery of samples supplemented with carbamazepine (mean recovery 102.2%). We observed an excellent correlation between the values obtained by the FPIA (x-axis) assay and the new turbidimetric (y-axis) assay (y = 0.96 x - 0.46, r = 0.99, n = 54). We also observed excellent correlation between the values obtained by the CLIA (x-axis) and the turbidimetric (y-axis) assay (y = 1.10 x -0.32, r = 0.99, n = 54). However, the slope of 1.10 was higher than the slope of 0.96 observed with the regression equation obtained by using values obtained by the FPIA and the turbidimetric assay. The positive bias obtained with the new turbidimetric assay compared with the CLIA assay resulted from lower cross reactivity of carbamazepine 10,11-epoxide, the active metabolite of carbamazepine, with CLIA. On the other hand, the cross reactivity of the metabolite is similar between the new turbidimetric assay and the FPIA assay. We conclude that the new turbidimetric assay can be used for routine monitoring of carbamazepine in clinical laboratories.

  3. Removal of a small C-terminal region of JCV and SV40 large T antigens has differential effects on transformation.

    PubMed

    Seneca, Nicole T M; Sáenz Robles, Maria Teresa; Pipas, James M

    2014-11-01

    The large T antigen (LT) protein of JCV and SV40 polyomaviruses is required to induce tumors in rodents and transform cells in culture. When both LTs are compared side-by-side in cell culture assays, SV40 shows a more robust transformation phenotype even though the LT sequences are highly conserved. A complete understanding of SV40׳s enhanced transforming capabilities relative to JCV is lacking. When the least conserved region of the LT proteins, the variable linker and host range region (VHR), was removed, changes in T antigen expression and cellular p53 post-translational modifications occurred, but interaction with the pRB pathway was unaffected. Transformation assessed by growth in low serum was reduced after VHR truncation of the SV40, but not the JCV, T antigen. Conversely, anchorage independent transformation was enhanced only by truncation of the JCV VHR. This is the first report to link the SV40 or JCV VHR region to transformation potential.

  4. Serum antibodies to papova viruses (BK and SV 40) in subjects from the area with Balkan endemic nephropathy.

    PubMed

    Stoian, M; Hozoc, M; Iosipenco, M; Nastac, E; Melencu, M

    1983-01-01

    The presence of antibodies to BK virus and SV40 was investigated in 63 patients with Balkan endemic nephropathy (BEN) and in 83 apparently healthy subjects from the endemic area. Serum antibodies to BK virus were detected in 95.2% of the former and in 74.7% of the latter, high antibody levels being prevalent in the age groups 41-60 years. Antibodies to SV40 were absent in the BEN patients and their frequency in the healthy subjects (27.7%) was much lower than that previously recorded in healthy persons from other zones of Romania (40%). The results obtained plead for a prevalence of BK virus infection in the endemic area with BEN.

  5. Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen

    PubMed Central

    Chang, Y. Paul; Xu, Meng; Machado, Ana Carolina Dantas; Yu, Xian Jessica; Rohs, Remo; Chen, Xiaojiang S.

    2013-01-01

    SUMMARY The DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two multidomain LTag subunits bound to origin DNA. The structure reveals that the origin binding domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and assembly. Notably, the OBDs recognize the origin in an unexpected manner. The histidine residues of the AAA+ domains insert into a narrow minor groove region with enhanced negative electrostatic potential. Computational analysis indicates that this region is intrinsically narrow, demonstrating the role of DNA shape readout in origin recognition. Our results provide important insights into the assembly of the LTag initiator/ helicase at the replication origin and suggest that histidine contacts with the minor groove serve as a mechanism of DNA shape readout. PMID:23545501

  6. Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment.

    PubMed

    Klitgaard, Henrik; Matagne, Alain; Nicolas, Jean-Marie; Gillard, Michel; Lamberty, Yves; De Ryck, Marc; Kaminski, Rafal M; Leclercq, Karine; Niespodziany, Isabelle; Wolff, Christian; Wood, Martyn; Hannestad, Jonas; Kervyn, Sophie; Kenda, Benoit

    2016-04-01

    Despite availability of effective antiepileptic drugs (AEDs), many patients with epilepsy continue to experience refractory seizures and adverse events. Achievement of better seizure control and fewer side effects is key to improving quality of life. This review describes the rationale for the discovery and preclinical profile of brivaracetam (BRV), currently under regulatory review as adjunctive therapy for adults with partial-onset seizures. The discovery of BRV was triggered by the novel mechanism of action and atypical properties of levetiracetam (LEV) in preclinical seizure and epilepsy models. LEV is associated with several mechanisms that may contribute to its antiepileptic properties and adverse effect profile. Early findings observed a moderate affinity for a unique brain-specific LEV binding site (LBS) that correlated with anticonvulsant effects in animal models of epilepsy. This provided a promising molecular target and rationale for identifying selective, high-affinity ligands for LBS with potential for improved antiepileptic properties. The later discovery that synaptic vesicle protein 2A (SV2A) was the molecular correlate of LBS confirmed the novelty of the target. A drug discovery program resulted in the identification of anticonvulsants, comprising two distinct families of high-affinity SV2A ligands possessing different pharmacologic properties. Among these, BRV differed significantly from LEV by its selective, high affinity and differential interaction with SV2A as well as a higher lipophilicity, correlating with more potent and complete seizure suppression, as well as a more rapid brain penetration in preclinical models. Initial studies in animal models also revealed BRV had a greater antiepileptogenic potential than LEV. These properties of BRV highlight its promising potential as an AED that might provide broad-spectrum efficacy, associated with a promising tolerability profile and a fast onset of action. BRV represents the first selective SV2A

  7. Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostate Cancer Development and Metastasis

    DTIC Science & Technology

    2011-09-01

    suppressor gene mutated in prostate cancer. Science. 294, 2563-2566. 2. Chen, C, Hyytinen, ER, Sun, X, Helin, HJ, Koivisto, PA, et al. (2003) Deletion ...transcription factor family which was first identified as a tumor suppressor gene frequently inactivated in prostate cancer (PCa). A single germline SNP...increases PCa risk and KLF6 gene alternative splicing to produce KLF6-SV1, which promotes tumor cell growth and metastasis. Since their original

  8. A novel coumarin-quinone derivative SV37 inhibits CDC25 phosphatases, impairs proliferation, and induces cell death.

    PubMed

    Bana, Emilie; Sibille, Estelle; Valente, Sergio; Cerella, Claudia; Chaimbault, Patrick; Kirsch, Gilbert; Dicato, Mario; Diederich, Marc; Bagrel, Denyse

    2015-03-01

    Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation by regulating CDK/cyclin complexes. Overexpression of these enzymes is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, targeting CDC25 by compounds, able to inhibit their activity, appears a good therapeutic approach. Here, we describe the synthesis of a new inhibitor (SV37) whose structure is based on both coumarin and quinone moieties. An analytical in vitro approach shows that this compound efficiently inhibits all three purified human CDC25 isoforms (IC50 1-9 µM) in a mixed-type mode. Moreover, SV37 inhibits growth of breast cancer cell lines. In MDA-MB-231 cells, reactive oxygen species generation is followed by pCDK accumulation, a mark of CDC25 dysfunction. Eventually, SV37 treatment leads to activation of apoptosis and DNA cleavage, underlining the potential of this new type of coumarin-quinone structure.

  9. The L-arabinose-resistance test with Salmonella typhimurium strain SV3 selects forward mutations at several ara genes.

    PubMed

    Pueyo, C; Lopez-Barea, J

    1979-08-01

    A new assay has been described for mutagenicity testing using an L-arabinose-sensitive strain of Salmonella typhimurium. The test strain SV3 and several L-arabinose-resistant mutants selected therefrom are characterized in the present study by 3 different criteria: inhibition of growth by L-arabinose, accumulation of keto-sugars, and activities of the enzymes involved in L-arabinose catabolism. Strain SV3 (ara-531) shows high levels of inducible L-arabinose isomerase (EC 5.3.1.4) and L-ribulokinase (EC 2.7.1.16) activities, but is deficient in L-ribulose-5-phosphate 4-epimerase (EC 5.1.3.4), the enzyme encoded in Escherichia coli by gene D in the araBAD operon. Addition of L-arabinose to SV3 growing in glycerol or casamino acids stops growth. D-Glucose only partially reverses this inhibition. Reversion of the ara-531 mutation restores different levels of epimerase activity and resistance to L-arabinose. However, the great majority of the L-arabinose-resistant mutants do not utilize L-arabinose. The physiological and enzymatic properties of these L-arabinose non-utilizing mutants suggest that L-arabinose resistance is due to forward mutations in at least 3 other genes, araA, araB and araC, blocking steps prior to L-ribulose 5-phosphate accumulation.

  10. Transformation of human neonatal prostate epithelial cells by strontium phosphate transfection with a plasmid containing SV40 early region genes.

    PubMed

    Kaighn, M E; Reddel, R R; Lechner, J F; Peehl, D M; Camalier, R F; Brash, D E; Saffiotti, U; Harris, C C

    1989-06-01

    Neonatal human prostatic epithelial cells (NP-2s) were transfected by strontium phosphate coprecipitation with a plasmid (pRSV-T) containing the SV40 early region genes. The cells transfected with pRSV-T, but not the sham-transfected controls, formed rapidly growing, multilayered colonies within 2 weeks at a frequency of 1 x 10(-4) in a serum-free medium (P4-8F). In all, 28 colonies of transformed cells were isolated. Three of these have been cultured for a sufficient length of time to show that their growth potentials are well beyond that of the normal progenitor cells (NP-2s). There is also little or no indication of the culture "crisis" commonly seen in SV40-transformed cells in these transfected lines. All contain cytokeratins and SV40 T-antigen as revealed by immunofluorescence, have ultrastructural features of epithelial cells, and are pseudodiploid. None have produced tumors within 1 year after s.c. injection into nude mice. The transformed as well as the parental NP-2s cells require bovine pituitary extract for growth in serum-free medium and are stimulated by transforming growth factor beta 1 (TGF-beta 1) and epidermal growth factor in clonal growth assays. In contrast, a prostatic carcinoma cell line (PC-3) is inhibited by TGF-beta 1. This serum-free system and immortalized transfected clones will be useful for studying the action of putative prostatic carcinogens and tumor-promoting agents.

  11. Targeted expression of SV40 T antigen in the hair follicle of transgenic mice produces an aberrant hair phenotype.

    PubMed

    Keough, R; Powell, B; Rogers, G

    1995-03-01

    Directed expression of SV40 large T antigen (TAg) in transgenic mice can induce tissue-specific tumorigenesis and useful cell lines exhibiting differentiated characteristics can be established from resultant tumor cells. In an attempt to produce an immortalised mouse hair follicle cortical cell line for the study of hair keratin gene control, SV40 TAg expression was targeted to the hair follicles of transgenic mice using a sheep hair gene promoter. Expression of SV40 TAg in the follicle cortex disrupted normal fiber ultrastructure, producing a marked phenotypic effect. Affected hairs were wavy or severely kinked (depending on the severity of the phenotype) producing an appearance ranging from a ruffled coat to a stubble covering the back of the mouse. The transgenic hairs appeared to be weakened at the base of the fibers, leading to premature hair-loss and a thinner pelage, or regions of temporary nudity. No follicle tumors or neoplasia were apparent and immortalisation of cortical cells could not be established in culture. In situ hybridisation studies in the hair follicle using histone H3 as a cell proliferation marker suggested that cell proliferation had ceased prior to commencement of K2.10-TAg expression and was not re-established in the differentiating cortical cells. Hence, TAg was unable to induce cell immortalisation at that stage of cortical cell differentiation. However, transgenic mice developed various other abnormalities including vertebral abnormalities and bladder, liver and intestinal tumors, which resulted in reduced life expectancy.

  12. Disposable electrochemical flow cells for catalytic adsorptive stripping voltammetry (CAdSV) at a bismuth film electrode (BiFE)

    PubMed Central

    Gharib Naseri, Nahid; Economou, Anastasios; Goddard, Nicholas J.; Fielden, Peter R.

    2008-01-01

    Catalytic adsorptive stripping voltammetry (CAdSV) has been demonstrated at a bismuth film electrode (BiFE) in an injection-moulded electrochemical micro-flow cell. The polystyrene three-electrode flow cell was fabricated with electrodes moulded from a conducting grade of polystyrene containing 40% carbon fibre, one of which was precoated with Ag to enable its use as an on-chip Ag/AgCl reference electrode. CAdSV of Co(II) and Ni(II) in the presence of dimethylglyoxime (DMG) with nitrite employed as the catalyst was performed in order to assess the performance of the flow cell with an in-line plated BiFE. The injection-moulded electrodes were found to be suitable substrates for the formation of BiFEs. Key parameters such as the plating solution matrix, plating flow rate, analysis flow rate, solution composition and square-wave parameters have been characterised and optimal conditions selected for successful and rapid analysis of Co(II) and Ni(II) at the ppb level. The analytical response was linear over the range 1 to 20 ppb and deoxygenation of the sample solution was not required. The successful coupling of a microfluidic flow cell with a BiFE, thereby forming a “mercury-free” AdSV flow analysis sensor, shows promise for industrial and in-the-field applications where inexpensive, compact, and robust instrumentation capable of low-volume analysis is required. PMID:18351328

  13. Disposable electrochemical flow cells for catalytic adsorptive stripping voltammetry (CAdSV) at a bismuth film electrode (BiFE).

    PubMed

    Naseri, Nahid Gharib; Baldock, Sara J; Economou, Anastasios; Goddard, Nicholas J; Fielden, Peter R

    2008-06-01

    Catalytic adsorptive stripping voltammetry (CAdSV) has been demonstrated at a bismuth film electrode (BiFE) in an injection-moulded electrochemical micro-flow cell. The polystyrene three-electrode flow cell was fabricated with electrodes moulded from a conducting grade of polystyrene containing 40% carbon fibre, one of which was precoated with Ag to enable its use as an on-chip Ag/AgCl reference electrode. CAdSV of Co(II) and Ni(II) in the presence of dimethylglyoxime (DMG) with nitrite employed as the catalyst was performed in order to assess the performance of the flow cell with an in-line plated BiFE. The injection-moulded electrodes were found to be suitable substrates for the formation of BiFEs. Key parameters such as the plating solution matrix, plating flow rate, analysis flow rate, solution composition and square-wave parameters have been characterised and optimal conditions selected for successful and rapid analysis of Co(II) and Ni(II) at the ppb level. The analytical response was linear over the range 1 to 20 ppb and deoxygenation of the sample solution was not required. The successful coupling of a microfluidic flow cell with a BiFE, thereby forming a "mercury-free" AdSV flow analysis sensor, shows promise for industrial and in-the-field applications where inexpensive, compact, and robust instrumentation capable of low-volume analysis is required.

  14. SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

    PubMed Central

    Di Micco, Biagio; Lepretti, Marilena; Rota, Lidia; Quaglia, Ilaria; Ferrazzi, Paola; Di Micco, Gianluca; Di Micco, Pierpaolo

    2007-01-01

    Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL) disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1–16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV) to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL). We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1–16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1–16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1–16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1–16. Thus our study demonstrates that Peptide 1–16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation. PMID:18154667

  15. The Completion Agenda: A Call to Action. Summary Report from the November 10-11, 2010, Meeting of the American Association of Community Colleges Commissions and Board of Directors

    ERIC Educational Resources Information Center

    McPhail, Christine Johnson

    2011-01-01

    At its annual joint board and commission meeting (Washington, DC, November 10-11, 2010), American Association of Community Colleges (AACC) focused attention on college completion by presenting two panel discussions on the completion agenda, followed by breakout sessions in which participants were assigned to focus groups tasked with providing…

  16. Adult and Higher Education in the Contemporary World: Its Role in Cultural Literacy. Conference Proceedings of the Adult Higher Education Alliance Annual Conference (35th, Orlando, Florida, March 10-11, 2015)

    ERIC Educational Resources Information Center

    Elufiede, Oluwakemi, Ed.; Flynn, Bonnie, Ed.

    2015-01-01

    This document is Conference Proceedings Of The Adult Higher Education Alliance, 35th Annual Conference. The theme of the conference was Adult And Higher Education In The Contemporary World: Its Role In Cultural Literacy. Conference was March 10-11, 2015. The event was hosted by and held at the College Of Education And Human Performance, Morgridge…

  17. Induction of Duplication Reversion in Human Fibroblasts, by Wild-Type and Mutated Sv40 T Antigen, Covaries with the Ability to Induce Host DNA Synthesis

    PubMed Central

    Shammas, M. A.; Xia, S. J.; Reis, RJS.

    1997-01-01

    Intrachromosomal homologous recombination, manifest as reversion of a 14-kbp duplication in the hypoxanthine phosphoribosyl transferase (HPRT) gene, is elevated in human cells either stably transformed or transiently transfected by the SV40 (simian virus 40) large T antigen gene. Following introduction of wild-type SV40, or any of several T-antigen point mutations in a constant SV40 background, we observed a strong correlation between the stimulation of chromosomal recombination and induction of host-cell DNA synthesis. Moreover, inhibitors of DNA replication (aphidicolin and hydroxyurea) suppress SV40-induced homologous recombination to the extent that they suppress DNA synthesis. Stable integration of plasmids encoding T antigen also augments homologous recombination, which is suppressed by aphidicolin. We infer that the mechanism by which T antigen stimulates homologous recombination in human fibroblasts involves DNA replicative synthesis. PMID:9258684

  18. Correction: Zinc is required to ensure the expression of flagella and the ability to form biofilms in Salmonella enterica sv Typhimurium.

    PubMed

    Ammendola, Serena; D'Amico, Ylenia; Chirullo, Barbara; Drumo, Rosanna; Ciavardelli, Domenico; Pasquali, Paolo; Battistoni, Andrea

    2016-11-09

    Correction for 'Zinc is required to ensure the expression of flagella and the ability to form biofilms in Salmonella enterica sv Typhimurium' by Serena Ammendola et al., Metallomics, 2016, DOI: 10.1039/c6mt00108d.

  19. Effects of Enrichment and Litter Parity on Reproductive Performance and Behavior in BALB/c and 129/Sv Mice

    PubMed Central

    Whitaker, Julia W; Moy, Sheryl S; Pritchett-Corning, Kathleen R; Fletcher, Craig A

    2016-01-01

    We examined the effect of adding species-appropriate environmental enrichment items to breeding cages of BALB/cAnNCrl and 129S2/SvPasCrl mice. The 3 enrichment conditions were: 1) cotton nesting material; 2) nesting material plus a paper shelter and rolled paper bedding; and 3) an igloo dome with an exercise wheel in addition to the shelter-group enrichments. We measured litter size, litter survival to weaning age, average pup weight at 21 d, and the interlitter interval to evaluate reproductive performance. A random subset of the first- or second-litter offspring from each enrichment condition and strain was assessed in multiple behavioral tests. Enrichment significantly affected anxiety-like behavior and sociability, with the direction of change dependent on strain and sex. Litter parity had greater effects on some reproductive parameters than did the enrichment condition, and this effect was not solely due to a difference between the first compared with subsequent litters. The significant effects of litter parity on the number of pups born and weaned, female pup weight, and interlitter interval were dependent on the enrichment condition in BALB/c but not 129/Sv mice. Offspring from the first or second litter were included in a generational component to investigate whether enrichment effects on reproduction persist in adult offspring after transfer to a different facility for breeding. Natal cage enrichment had no effect on any reproductive parameter in the transferred mice. Overall, additional enrichment beyond nesting material had a beneficial effect on the interlitter interval in BALB/c mice and on the number of pups weaned in 129/Sv mice. PMID:27423144

  20. Observational Constraints on Terpene Oxidation with and without Anthropogenic Influence in the Amazon using Speciated Measurements from SV-TAG

    NASA Astrophysics Data System (ADS)

    Yee, L.; Isaacman, G. A.; Kreisberg, N. M.; Liu, Y.; McKinney, K. A.; de Sá, S. S.; Martin, S. T.; Alexander, M. L.; Palm, B. B.; Hu, W.; Campuzano Jost, P.; Day, D. A.; Jimenez, J. L.; Viegas, J.; Springston, S. R.; Wurm, F.; Ferreira De Brito, J.; Artaxo, P.; Manzi, A. O.; Machado, L.; Longo, K.; Oliveira, M. B.; Souza, R. A. F. D.; Hering, S. V.; Goldstein, A. H.

    2014-12-01

    Biogenic volatile organic compounds (BVOCs) from the Amazon forest represent the largest regional source of organic carbon emissions to the atmosphere. These BVOC emissions dominantly consist of volatile and semi-volatile terpenoid compounds that undergo chemical transformations in the atmosphere to form oxygenated condensable gases and secondary organic aerosol (SOA). However, the oxidation pathways of these compounds are still not well understood, and are expected to differ significantly between "pristine" conditions, as is common in Amazonia, and polluted conditions caused by emissions from growing cities. Our focus is to elucidate how anthropogenic emissions influence BVOC chemistry and BSOA formation through speciated measurements of their oxidation products. We have deployed the Semi-Volatile Thermal desorption Aerosol Gas Chromatograph (SV-TAG) at the rural T3 site located west of the urban center of Manaus, Brazil as part of the Green Ocean Amazon (GoAmazon) 2014 field campaign to measure hourly concentrations of semi-volatile BVOCs and their oxidation products during the wet and dry seasons. Primary BVOC concentrations measured by the SV-TAG include sesquiterpenes and diterpenes, which have rarely been speciated with high time-resolution. We observe sesquiterpenes to be anti-correlated with ozone, indicative of sesquiterpene oxidation playing a major role in the regional oxidant budget. The role of sesquiterpenes in atmospheric SOA formation are of interest due to their high aerosol yields and high reactivity with ozone, relative to more commonly measured BVOCs (e.g. monoterpenes). We explore relative concentrations of sesquiterpenes and monoterpenes and their roles as precursors to SOA formation by combining SV-TAG measurements with those from an additional suite of VOC and particle measurements deployed in the Amazon. We also report the first ever hourly observations of the gas-particle partitioning of speciated terpene oxidation products in the Amazon

  1. Effects of Enrichment and Litter Parity on Reproductive Performance and Behavior in BALB/c and 129/Sv Mice.

    PubMed

    Whitaker, Julia W; Moy, Sheryl S; Pritchett-Corning, Kathleen R; Fletcher, Craig A

    2016-01-01

    We examined the effect of adding species-appropriate environmental enrichment items to breeding cages of BALB/cAnNCrl and 129S2/SvPasCrl mice. The 3 enrichment conditions were: 1) cotton nesting material; 2) nesting material plus a paper shelter and rolled paper bedding; and 3) an igloo dome with an exercise wheel in addition to the shelter-group enrichments. We measured litter size, litter survival to weaning age, average pup weight at 21 d, and the interlitter interval to evaluate reproductive performance. A random subset of the first- or second-litter offspring from each enrichment condition and strain was assessed in multiple behavioral tests. Enrichment significantly affected anxiety-like behavior and sociability, with the direction of change dependent on strain and sex. Litter parity had greater effects on some reproductive parameters than did the enrichment condition, and this effect was not solely due to a difference between the first compared with subsequent litters. The significant effects of litter parity on the number of pups born and weaned, female pup weight, and interlitter interval were dependent on the enrichment condition in BALB/c but not 129/Sv mice. Offspring from the first or second litter were included in a generational component to investigate whether enrichment effects on reproduction persist in adult offspring after transfer to a different facility for breeding. Natal cage enrichment had no effect on any reproductive parameter in the transferred mice. Overall, additional enrichment beyond nesting material had a beneficial effect on the interlitter interval in BALB/c mice and on the number of pups weaned in 129/Sv mice.

  2. Effect of the 21-bp repeat upstream element on in vitro transcription from the early and late SV40 promoters.

    PubMed Central

    Vigneron, M; Barrera-Saldana, H A; Baty, D; Everett, R E; Chambon, P

    1984-01-01

    The role of the 21-bp repeat region [simian virus 40 (SV40) coordinates 40-103] on early and late SV40 promoter functions has been investigated in vitro using a variety of mutated templates. Using either a HeLa whole cell extract or a S100 extract, we analyzed the transcripts by quantitative S1 nuclease mapping. GC-rich motifs contained in the 21-bp direct repeat constituted an essential element for efficient early transcription in vitro in agreement with previous in vivo results. These GC-rich motifs act in a non-polar fashion, since inversion of the 21-bp region did not reduce early transcription. Some point mutations in the 22-bp imperfectly repeated sequence, that drastically reduce initiations from the early promoter in vivo, had little effect in vitro, indicating that all the functions of these GC-rich motifs cannot be reproduced in vitro at present. The requirement for the 21-bp repeat region was less stringent when the concentration of the early promoter sequence was increased, which suggests that its function may be to facilitate the recognition of the 'weak' SV40 early TATA box. The multiple late start sites were accurately used in vitro and the GC-rich motifs contained in the 21-bp repeat region were an important element for efficient in vitro initiation of transcription from the late promoter, irrespective of their orientation. However, the effect of the 21-bp repeat region on late initiations decreased strikingly with increasing distance to the start sites, although it was still detectable over a distance of 220 bp. Under the present in vitro conditions, the 72-bp repeat region stimulates weakly both early and late transcription. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:6094181

  3. Establishment and characterisation of a novel bovine SV40 large T-antigen-transduced foetal hepatocyte-derived cell line.

    PubMed

    Gleich, Alexander; Kaiser, Bastian; Schumann, Julia; Fuhrmann, Herbert

    2016-06-01

    Due to lack of in vitro models for bovine hepatocytes apart from primary cells, there is demand for a bovine hepatocyte-derived cell line. Transduction of bovine foetal hepatocytes with SV40 large T-antigen was performed using the vector pRetro-E2 SV40. Phase contrast microscopy was carried out to evaluate morphology. Immunofluorescence staining was conducted to study expression of keratins, tight junction proteins zona occludens-1 and claudin-1, glucose transporter-2 and P-glycoprotein as well as phosphoenolpyruvate carboxykinase. Urea and triglyceride production was quantified photometrically. Histochemical staining of glycogen by Periodic acid-Schiff stain and of lipids with Oil red O was performed after 24 h incubation with 20 mM glucose and 85 μM palmitic acid, respectively. Gene expression analysis of hepatocyte-typical genes was conducted by reverse transcription PCR. We obtained a SV40LTAg-transduced extended passage cell line, referred to as BFH12. Polygonal growth, keratins, tight junction proteins zona occludens-1 and claudin-1 and glucose transporter-2 as well as P-glycoprotein and phosphoenolpyruvate carboxykinase were attested positively. Urea production calculated as cell-specific rate was 14.2 ± 2.0 fmol/h (early passage) and 17.6 ± 3.7 fmol/h (late passage). Cell-specific triglyceride production was 1.6 ± 0.5 fmol/h (early passage) and 2.1 ± 0.3 fmol/h (late passage). Additionally, cells were positive for glycogen and lipid storage and showed a gene expression pattern resembling foetal hepatocytes. With the properties described here, the novel cell line BFH12 is a hepatocyte-derived cell line which can be used as an in vitro whole cell model.

  4. [Possible relation between viruses and oromaxillofacial tumors. II. Research on the presence of the SV40 antigen and specific antibodies in patients with oromaxillofacial tumors].

    PubMed

    Stoian, M; Suru, M; Zaharia, O; Constantinescu, E; Fleshler, B A; Nastac, E

    1987-01-01

    SV40 antigen was detected on sections through malignant oromaxillofacial tumors in 47.8% of the cases, with a higher incidence among the epithelium originating tumors. Anti-SV40 CF antibodies were detected in 83.6% of the examined subjects with cancer, but only in 57.9% of the blood donors. The titers were quite low in general. The results are discussed from the point of view of the immunologic status of the patients.

  5. Modulation of the conformational state of the SV2A protein by an allosteric mechanism as evidenced by ligand binding assays

    PubMed Central

    Daniels, V; Wood, M; Leclercq, K; Kaminski, R M; Gillard, M

    2013-01-01

    Background and Purpose Synaptic vesicle protein 2A (SV2A) is the specific binding site of the anti-epileptic drug levetiracetam (LEV) and its higher affinity analogue UCB30889. Moreover, the protein has been well validated as a target for anticonvulsant therapy. Here, we report the identification of UCB1244283 acting as a SV2A positive allosteric modulator of UCB30889. Experimental Approach UCB1244283 was characterized in vitro using radioligand binding assays with [3H]UCB30889 on recombinant SV2A expressed in HEK cells and on rat cortex. In vivo, the compound was tested in sound-sensitive mice. Key Results Saturation binding experiments in the presence of UCB1244283 demonstrated a fivefold increase in the affinity of [3H]UCB30889 for human recombinant SV2A, combined with a twofold increase of the total number of binding sites. Similar results were obtained on rat cortex. In competition binding experiments, UCB1244283 potentiated the affinity of UCB30889 while the affinity of LEV remained unchanged. UCB1244283 significantly slowed down both the association and dissociation kinetics of [3H]UCB30889. Following i.c.v. administration in sound-sensitive mice, UCB1244283 showed a clear protective effect against both tonic and clonic convulsions. Conclusions and Implications These results indicate that UCB1244283 can modulate the conformation of SV2A, thereby inducing a higher affinity state for UCB30889. Our results also suggest that the conformation of SV2A per se might be an important determinant of its functioning, especially during epileptic seizures. Therefore, agents that act on the conformation of SV2A might hold great potential in the search for new SV2A-based anticonvulsant therapies. PMID:23530581

  6. AP-1/σ1B-Dependent SV Protein Recycling Is Regulated in Early Endosomes and Is Coupled to AP-2 Endocytosis.

    PubMed

    Kratzke, Manuel; Candiello, Ermes; Schmidt, Bernhard; Jahn, Olaf; Schu, Peter

    2015-08-01

    Adaptor protein (AP)-1/σ1B(-/-) mice have reduced synaptic-vesicle (SV) recycling and increased endosomes. Mutant mice have impaired spatial memory, and σ1B-deficient humans have a severe mental retardation. In order to define these σ1B(-/-) 'bulk' endosomes and to determine their functions in SV recycling, we developed a protocol to separate them from the majority of the neuronal endosomes. The σ1B(-/-) 'bulk' endosomes proved to be classic early endosomes with an increase in the phospholipid phosphatidylinositol 3-phosphate (PI-3-P), which recruits proteins mediating protein sorting out of early endosomes into different routes. σ1B deficiency induced alterations in the endosomal proteome reveals two major functions: SV protein storage and sorting into endolysosomes. Alternative endosomal recycling pathways are not up-regulated, but certain SV proteins are misrouted. Tetraspanins are enriched in σ1B(-/-) synaptosomes, but not in their endosomes or in their clathrin-coated-vesicles (CCVs), indicating AP-1/σ1B-dependent sorting. Synapses contain also more AP-2 CCV, although it is expected that they contain less due to reduced SV recycling. Coat composition of these AP-2 CCVs is altered, and thus, they represent a subpopulation of AP-2 CCVs. Association of calmodulin-dependent protein kinase (CaMK)-IIα, -δ and casein kinase (CK)-IIα with the endosome/SV pool is altered, as well as 14-3-3η, indicating changes in specific signalling pathways regulating synaptic plasticity. The accumulation of early endosomes and endocytotic AP-2 CCV indicates the regulation of SV recycling via early endosomes by the interdependent regulation of AP-2-mediated endocytosis and AP-1/σ1B-mediated SV reformation.

  7. Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostrate Cancer Development and Metastasis

    DTIC Science & Technology

    2010-09-01

    gene   frequently   inactivated  in  prostate  cancer  (PCa).  A  single  germline  SNP  increases  PCa...risk  and  KLF6   gene  alternative  splicing  to  produce  KLF6-­‐SV1,   which   promotes   tumor   cell   growth   and...of  c-­‐Myc  target   genes .   In   sum,   these   results   when   taken   together   begin   to  

  8. Simulations of P-SV wave scattering due to cracks by the 2-D finite difference method

    NASA Astrophysics Data System (ADS)

    Suzuki, Yuji; Shiina, Takahiro; Kawahara, Jun; Okamoto, Taro; Miyashita, Kaoru

    2013-12-01

    We simulate P-SV wave scattering by 2-D parallel cracks using the finite difference method (FDM). Here, special emphasis is put on simplicity; we apply a standard FDM (second-order velocity-stress scheme with a staggered grid) to media including traction-free, infinitesimally thin cracks, which are expressed in a simple manner. As an accuracy test of the present method, we calculate the displacement discontinuity along an isolated crack caused by harmonic waves using the method, which is compared with the corresponding results based on a reliable boundary integral equation method. The test resultantly indicates that the present method yields sufficient accuracy. As an application of this method, we also simulate wave propagation in media with randomly distributed cracks. We experimentally determine the attenuation and velocity dispersion induced by scattering from the synthetic seismograms, using a waveform averaging technique. It is shown that the results are well explained by a theory based on the Foldy approximation, if the crack density is sufficiently low. The theory appears valid with a crack density up to at least 0.1 for SV wave incidence, whereas the validity limit appears lower for P wave incidence.

  9. The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA

    PubMed Central

    Gai, Dahai; Wang, Damian; Li, Shu-Xing; Chen, Xiaojiang S

    2016-01-01

    DNA replication is a fundamental biological process. The initial step in eukaryotic DNA replication is the assembly of the pre-initiation complex, including the formation of two head-to-head hexameric helicases around the replication origin. How these hexameric helicases interact with their origin dsDNA remains unknown. Here, we report the co-crystal structure of the SV40 Large-T Antigen (LT) hexameric helicase bound to its origin dsDNA. The structure shows that the six subunits form a near-planar ring that interacts with the origin, so that each subunit makes unique contacts with the DNA. The origin dsDNA inside the narrower AAA+ domain channel shows partial melting due to the compression of the two phosphate backbones, forcing Watson-Crick base-pairs within the duplex to flip outward. This structure provides the first snapshot of a hexameric helicase binding to origin dsDNA, and suggests a possible mechanism of origin melting by LT during SV40 replication in eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.18129.001 PMID:27921994

  10. A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen.

    PubMed Central

    Eibl, R. H.; Kleihues, P.; Jat, P. S.; Wiestler, O. D.

    1994-01-01

    Using retrovirus-mediated transfer of the SV40 virus large T antigen into neural transplants, we have observed a high incidence of primitive neuroectodermal tumors (PNET). These neoplasms developed in 8 of 14 (57%) neural grafts after latency periods of 176 to 311 days. Histopathologically, the tumors exhibited features of human PNET such as formation of neuroblastic rosettes and immunocytochemical evidence for neuronal differentiation, synaptogenesis, and focal astrocytic differentiation. All neoplasms showed a striking migratory potential. The presence of the large T gene in the tumors was demonstrated by polymerase chain reaction-mediated amplification of a specific 242 bp segment of large T and DNA sequence analysis. Large T antigen was identified in tissue sections using an immunocytochemical reaction with the monoclonal antibody Pab 108. Cell lines were established from several tumors and subjected to G418 selection. Secondary tumors induced by intracerebral transplantation of these cells retained the characteristic morphological and immunocytochemical properties of PNETs. These experiments demonstrate a considerable transforming potential of SV40 large T antigen for neural precursor cells. The long latency period suggests that neoplastic transformation initiated by the large T gene requires additional spontaneous mutations of cooperating cellular genes. Because the mechanism of transformation by large T antigen appears to involve complex formation with and inactivation of cellular tumor suppressor gene products, these cell lines may serve as an interesting tool to search for novel neural tumor suppressor genes. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8129041

  11. In vitro chromatin remodelling by chromatin accessibility complex (CHRAC) at the SV40 origin of DNA replication.

    PubMed Central

    Alexiadis, V; Varga-Weisz, P D; Bonte, E; Becker, P B; Gruss, C

    1998-01-01

    DNA replication is initiated by binding of initiation factors to the origin of replication. Nucleosomes are known to inhibit the access of the replication machinery to origin sequences. Recently, nucleosome remodelling factors have been identified that increase the accessibility of nucleosomal DNA to transcription regulators. To test whether the initiation of DNA replication from an origin covered by nucleosomes would also benefit from the action of nucleosome remodelling factors, we reconstituted SV40 DNA into chromatin in Drosophila embryo extracts. In the presence of T-antigen and ATP, a chromatin-associated cofactor allowed efficient replication from a nucleosomal origin in vitro. In search of the energy-dependent cofactor responsible we found that purified 'chromatin accessibility complex' (CHRAC) was able to alter the nucleosomal structure at the origin allowing the binding of T-antigen and efficient initiation of replication. These experiments provide evidence for the involvement of a nucleosome remodelling machine in structural changes at the SV40 origin of DNA replication in vitro. PMID:9628878

  12. SV-Bay: structural variant detection in cancer genomes using a Bayesian approach with correction for GC-content and read mappability

    PubMed Central

    Iakovishina, Daria; Janoueix-Lerosey, Isabelle; Barillot, Emmanuel; Regnier, Mireille; Boeva, Valentina

    2016-01-01

    Motivation: Whole genome sequencing of paired-end reads can be applied to characterize the landscape of large somatic rearrangements of cancer genomes. Several methods for detecting structural variants with whole genome sequencing data have been developed. So far, none of these methods has combined information about abnormally mapped read pairs connecting rearranged regions and associated global copy number changes automatically inferred from the same sequencing data file. Our aim was to create a computational method that could use both types of information, i.e. normal and abnormal reads, and demonstrate that by doing so we can highly improve both sensitivity and specificity rates of structural variant prediction. Results: We developed a computational method, SV-Bay, to detect structural variants from whole genome sequencing mate-pair or paired-end data using a probabilistic Bayesian approach. This approach takes into account depth of coverage by normal reads and abnormalities in read pair mappings. To estimate the model likelihood, SV-Bay considers GC-content and read mappability of the genome, thus making important corrections to the expected read count. For the detection of somatic variants, SV-Bay makes use of a matched normal sample when it is available. We validated SV-Bay on simulated datasets and an experimental mate-pair dataset for the CLB-GA neuroblastoma cell line. The comparison of SV-Bay with several other methods for structural variant detection demonstrated that SV-Bay has better prediction accuracy both in terms of sensitivity and false-positive detection rate. Availability and implementation: https://github.com/InstitutCurie/SV-Bay Contact: valentina.boeva@inserm.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26740523

  13. The signal for clathrin-mediated endocytosis of the paramyxovirus SV5 HN protein resides at the transmembrane domain-ectodomain boundary region.

    PubMed

    Leser, G P; Ector, K J; Ng, D T; Shaughnessy, M A; Lamb, R A

    1999-09-15

    The hemagglutinin-neuraminidase (HN) glycoprotein of the paramyxovirus SV5 is internalized from the cell surface via clathrin-coated pits. However, the cytoplasmic domain of SV5 HN does not contain a previously characterized internalization motif. A cell-surface-expressed chimeric protein (APK), consisting of the cytoplasmic tail, transmembrane (TM) domain, and 12 residues of the ectodomain of HN joined to the cytoplasmic protein pyruvate kinase is internalized, indicating that the N-terminal region of HN contains an internalization signal. Although SV5 HN is internalized at a rate similar to that of influenza virus hemagglutinin (HA) mutant Y543, which contains a degenerate tyrosine-based signal in its cytoplasmic tail, the elimination of the majority of the HN cytoplasmic tail, or substitution of the HN TM domain with leucine residues, did not affect the rate of HN internalization. The HN protein of the closely related virus, Newcastle disease virus (NDV), is not internalized from the cell surface. Working under the usual convention that the TM domain consists of the hydrophobic residues bounded by two charged residues, analysis of internalization of mutant and chimeric NDV HN molecules indicates that the first seven SV5 HN ectodomain residues are critical for internalization of HN. A glutamic acid residue (E37) that abuts this presumptive HN TM domain/ectodomain boundary is important for SV5 HN internalization.

  14. Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice

    PubMed Central

    Wu, Ruirui; Wu, Xiafang; Wang, Huihui; Fang, Xin; Li, Yongfang; Gao, Lanyue; Sun, Guifan; Pi, Jingbo; Xu, Yuanyuan

    2017-01-01

    Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains. PMID:28303940

  15. Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C

    PubMed Central

    Benoit, Roger M.; Schärer, Martin A.; Wieser, Mara M.; Li, Xiaodan; Frey, Daniel; Kammerer, Richard A.

    2017-01-01

    A detailed molecular understanding of botulinum neurotoxin (BoNT)/host-cell-receptor interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications. The X-ray crystal structure of the receptor-binding domain (HC) of BoNT/A1 in complex with the luminal domain (LD) of its neuronal receptor SV2C revealed only few specific side-chain – side-chain interactions that are important for binding. Notably, two BoNT/A1 residues, Arg 1156 and Arg 1294, that are crucial for the interaction with SV2, are not conserved among subtypes. Because it has been suggested that differential receptor binding of subtypes might explain their differences in biological activity, we determined the crystal structure of BoNT/A2-HC in complex with SV2C-LD. Although only few side-chain interactions are conserved between the two BoNT/A subtypes, the overall binding mode of subtypes A1 and A2 is virtually identical. In the BoNT/A2-HC – SV2C complex structure, a missing cation-π stacking is compensated for by an additional salt bridge and an anion-π stacking interaction, which explains why the binding of BoNT/A subtypes to SV2C tolerates variable side chains. These findings suggest that motif extensions and a shallow binding cleft in BoNT/A-HC contribute to binding specificity. PMID:28252640

  16. Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice

    NASA Astrophysics Data System (ADS)

    Wu, Ruirui; Wu, Xiafang; Wang, Huihui; Fang, Xin; Li, Yongfang; Gao, Lanyue; Sun, Guifan; Pi, Jingbo; Xu, Yuanyuan

    2017-03-01

    Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.

  17. Cat odor exposure induces distinct changes in the exploratory behavior and Wfs1 gene expression in C57Bl/6 and 129Sv mice.

    PubMed

    Raud, Sirli; Sütt, Silva; Plaas, Mario; Luuk, Hendrik; Innos, Jürgen; Philips, Mari-Anne; Kõks, Sulev; Vasar, Eero

    2007-10-16

    129Sv and C57Bl/6 (Bl6) strains are two most widely used inbred mice strains for generation of transgenic animals. The present study confirms the existence of substantial differences in the behavior of these two mice strains. The exploratory behavior of Bl6 mice in a novel environment was significantly higher compared to 129Sv mice. The exposure of mice to cat odor-induced an anxiety-like state in Bl6, but not in 129Sv mice. The levels of Wfs1 gene expression did not differ in the prefrontal cortex, mesolimbic area and temporal lobe of experimentally naive Bl6 and 129Sv mice. However, after cat odor exposure the expression of Wfs1 gene was significantly lower in the mesolimbic area and temporal lobe of Bl6 mice compared to 129Sv strain. Dynamics of Wfs1 gene expression and exploratory behavior suggest that the down-regulation of Wfs1 gene in Bl6 mice might be related to the increased anxiety. Further studies are needed to test the robustness and possible causal relationship of this finding.

  18. Experiences in the Performance Analysis and Optimization of a Deterministic Radiation Transport Code on the Cray SV1

    SciTech Connect

    Peter Cebull

    2004-05-01

    The Attila radiation transport code, which solves the Boltzmann neutron transport equation on three-dimensional unstructured tetrahedral meshes, was ported to a Cray SV1. Cray's performance analysis tools pointed to two subroutines that together accounted for 80%-90% of the total CPU time. Source code modifications were performed to enable vectorization of the most significant loops, to correct unfavorable strides through memory, and to replace a conjugate gradient solver subroutine with a call to the Cray Scientific Library. These optimizations resulted in a speedup of 7.79 for the INEEL's largest ATR model. Parallel scalability of the OpenMP version of the code is also discussed, and timing results are given for other non-vector platforms.

  19. Mode-Converted (P-SV) Waves for Imaging Thin Intercalated Basaltic Layers and Their Possible Geologic Implications

    SciTech Connect

    Pandey, D. K.; Pandey, A.; Rajan, S.

    2010-06-15

    The subsurface imaging using conventional seismic reflection technique is challenging in areas where high velocity rocks such as basalts are underlain by low velocity rocks. The seismic image quality worsens in the presence of intercalated sediments within the basaltic layers. In the recent years, the multicomponent seismic exploration technique has drawn great attention because it reduces the ambiguity in seismic imaging, enlarges the S-wave information, and improves the prediction and identification of reservoir fluids. Improvements in sub-basalt imaging techniques could hold highly significant geologic implications such as resource exploration and identifying permanent geochemical trapping potential (such as for carbon sequestration studies). In this article, we examine the possibility of utilizing mode-converted (P-SV) waves for sub-basalt imaging as well as likely complicacies one may expect in such processes.

  20. Influenza virus hemagglutinin expression is polarized in cells infected with recombinant SV40 viruses carrying cloned hemagglutinin DNA.

    PubMed

    Roth, M G; Compans, R W; Giusti, L; Davis, A R; Nayak, D P; Gething, M J; Sambrook, J

    1983-06-01

    Primary cell cultures of African Green monkey kidney (AGMK) contain polarized epithelial cells in which influenza virus matures predominantly at the apical surfaces above tight junctions. Influenza virus glycoproteins were found to be localized at the same membrane domain from which the virus budded. When polarized primary AGMK cells were infected with recombinant SV40 viruses containing DNA coding for either an influenza virus H1 or H2 subtype hemagglutinin (HA), the HA proteins were preferentially expressed at the apical surface in a manner identical to that observed in influenza virus-infected cells. Thus, cellular mechanisms for sorting membrane glycoproteins recognize some structural feature of the HA glycoprotein itself, and other viral proteins are not necessary for this process.

  1. Topographic effects on seismic response of long-span rigid-frame bridge under SV seismic wave

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Zhao, Cheng-Gang; Qu, Tie-Jun

    2008-05-01

    Seismic ground motions of two neighboring mountains and the free surface between them are calculated under the SV seismic waves with three different incident angles. The results are then taken as the inputs of multi-point seismic excitations for the foundation of a long-span bridge built over the valley in the analysis considering the integrated influence of traveling wave and topography. On the basis of a dynamic analytical method, a finite element model is created for the seismic responses of a four-span rigid-frame bridge of 440 m. The pier-top displacement and the pier-bottom internal force of the bridge are calculated. Then the results are compared with those considering traveling-wave effect only. The conclusions can serve as a seismic design reference for the structures located on the complex mountain topography.

  2. Expression of gamma-glutamyl transpeptidase in adult rat liver cells after transformation with SV40 virus.

    PubMed

    Lafarge-Frayssinet, C; Estrade, S; Rosa-Loridon, B; Frayssinet, C; Cassingena, R

    1984-02-01

    By the use of histochemical techniques we have shown that the transformation of rat hepatocytes with simian virus 40 resulted in a large majority of cells producing gamma-glutamyl transpeptidase (gamma GT). Using a temperature-sensitive mutant of this virus we have shown that the percentage of cells exhibiting this enzyme in a temperature-sensitive SV40 mutant is much higher in cells grown at the permissive temperature of 33 degrees C than at the nonpermissive temperature of 40.5 degrees C. We thus conclude that, the correlation between gamma GT expression and chemical or spontaneous transformation of hepatocytes, previously described by other authors, can now be extended to viral transformation and that the enzyme activity is dependent on the expression of a transformed cell phenotype.

  3. Kava chalcone, flavokawain A, inhibits urothelial tumorigenesis in the UPII-SV40T transgenic mouse model.

    PubMed

    Liu, Zhongbo; Xu, Xia; Li, Xuesen; Liu, Shuman; Simoneau, Anne R; He, Feng; Wu, Xue-Ru; Zi, Xiaolin

    2013-12-01

    Flavokawain A (FKA) is the predominant chalcone identified from the kava plant. We have previously shown that FKA preferentially inhibits the growth of p53 defective bladder cancer cell lines. Here, we examined whether FKA could inhibit bladder cancer development and progression in vivo in the UPII-SV40T transgenic model that resembles human urothelial cell carcinoma (UCC) with defects in the p53 and the retinoblastoma (Rb) protein pathways. Genotyped UPII-SV40T mice were fed orally with vehicle control (AIN-93M) or FKA (6 g/kg food; 0.6%) for 318 days starting at 28 days of age. More than 64% of the male mice fed with FKA-containing food survived beyond 318 days of age, whereas only about 38% of the male mice fed with vehicle control food survived to that age (P = 0.0383). The mean bladder weights of surviving male transgenic mice with the control diet versus the FKA diet were 234.6 ± 72.5 versus 96.1 ± 69.4 mg (P = 0.0002). FKA was excreted primarily through the urinary tract and concentrated in the urine up to 8.4 μmol/L, averaging about 38 times (males) and 15 times (females) more concentrated than in the plasma (P = 0.0001). FKA treatment inhibited the occurrence of high-grade papillary UCC, a precursor to invasive urothelial cancer, by 42.1%. A decreased expression of Ki67, survivin, and X-linked inhibitor of apoptotic proteins (XIAP) and increased expression of p27 and DR5, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were observed in the urothelial tissue of FKA-fed mice. These results suggest a potential of FKA in preventing the recurrence and progression of non-muscle-invasive UCC.

  4. Inter Comparison of Atmospheric Correction Models - SACRS2, FLAASH and 6SV Using Resourcesat-2 AWiFS Data

    NASA Astrophysics Data System (ADS)

    Pathak, V. N.; Pandya, M. R.; Shah, D. B.; Trivedi, H. J.; Patel, K. D.; Sridhar, V. N.; Singh, R. P.

    2014-11-01

    Remote sensing measurements from space born sensors are strongly attenuated by the scattering and absorption processes through atmospheric molecules, aerosols and gases (ozone, water vapour, oxygen etc). The process of removing the atmospheric interference from the satellite-level signal is called atmospheric correction. Atmospheric correction can be performed through various methods such as, empirical method, semi-physical method, detailed radiative transfer models. Various methods exist for atmospheric correction of available global sensors such as NOAA-AVHRR, MODIS-Terra/Aqua, MERIS, Landsat-TM/ETM etc. However, there was no method available for atmospheric correction of the IRS data sets. A new physics-based model called Scheme for Atmospheric Correction of ResourceSat-2 AWiFS data (SACRS2) has been developed at Space Applications Centre (SAC) specifically tuned for the RS2-AWiFS sensor. This model has been developed from theoretical signal simulations using the 6SV (The Second Simulation of the Satellite Signal in the Solar Spectrum vector version) code. A detail analysis was carried out to perform inter comparison of the results of SACRS2 model with standard atmospheric correction models such as FLAASH (Fast Line-of-sight Atmospheric Analysis of Spectral Hypercube) and 6SV on RS2-AWiFS data. In turn, the performance of all three models was compared to in-situ measurements carried out over an experimental site located in the Kutch desert for seven RS2-AWiFS overpasses. The results showed a fairly good match of reflectance derived by all three correction models with the in-situ measurements.

  5. DJ-1, an oncogene and causative gene for familial Parkinson's disease, is essential for SV40 transformation in mouse fibroblasts through up-regulation of c-Myc.

    PubMed

    Kim, Yun Chul; Kitaura, Hirotake; Iguchi-Ariga, Sanae M M; Ariga, Hiroyoshi

    2010-09-24

    Simian virus 40 (SV40) is a tumor virus and its early gene product large T-antigen (LT) is responsible for the transforming activity of SV40. Parkinson's disease causative gene DJ-1 is also a ras-dependent oncogene, but the mechanism of its oncogene function is still not known. In this study, we found that there were no transformed foci when fibroblasts from DJ-1-knockout mice were transfected with LT. We also found that DJ-1 directly bound to LT and that the expression level of c-Myc in transformed cells was parallel to that of DJ-1. These findings indicate that DJ-1 is essential for SV40 transformation.

  6. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

    PubMed Central

    Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

    1996-01-01

    The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

  7. Fetal bovine serum and human constitutive androstane receptor: Evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system

    SciTech Connect

    Lau, Aik Jiang; Chang, Thomas K.H.

    2014-06-01

    The naturally occurring SV23 splice variant of human constitutive androstane receptor (hCAR-SV23) is activated by di-(2-ethylhexyl)phthalate (DEHP), which is detected as a contaminant in fetal bovine serum (FBS). In our initial experiment, we compared the effect of dialyzed FBS, charcoal-stripped, dextran-treated FBS (CS-FBS), and regular FBS on the basal activity and ligand-activation of hCAR-SV23 in a cell-based reporter gene assay. In transfected HepG2 cells cultured in medium supplemented with 10% FBS, basal hCAR-SV23 activity varied with the type of FBS (regular > dialyzed > CS). DEHP increased hCAR-SV23 activity when 10% CS-FBS, but not regular FBS or dialyzed FBS, was used. With increasing concentrations (1–10%) of regular FBS or CS-FBS, hCAR-SV23 basal activity increased, whereas in DEHP-treated cells, hCAR-SV23 activity remained similar (regular FBS) or slightly increased (CS-FBS). Subsequent experiments identified a serum-free culture condition to detect DEHP activation of hCAR-SV23. Under this condition, artemisinin, artemether, and arteether increased hCAR-SV23 activity, whereas they decreased it in cells cultured in medium supplemented with 10% regular FBS. By comparison, FBS increased the basal activity of the wild-type isoform of hCAR (hCAR-WT), whereas it did not affect the basal activity of the SV24 splice variant (hCAR-SV24) or ligand activation of hCAR-SV24 and hCAR-WT by 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO). The use of serum-free culture condition was suitable for detecting CITCO activation of hCAR-WT and hCAR-SV24. In conclusion, FBS leads to erroneous classification of pharmacological ligands of hCAR-SV23 in cell-based assays, but investigations on functional ligands of hCAR isoforms can be conducted in serum-free culture condition. - Highlights: • FBS leads to erroneous pharmacological classification of hCAR-SV23 ligands. • Artemisinin, artemether, and arteether activate hCAR-SV

  8. An Investigation of the Validity and Reliability of the Adapted Mathematics Anxiety Rating Scale-Short Version (MARS-SV) among Turkish Students

    ERIC Educational Resources Information Center

    Baloglu, Mustafa

    2010-01-01

    This study adapted the Mathematics Anxiety Rating Scale-Short Version (MARS-SV) into Turkish and investigated the validity and reliability of the adapted instrument. Twenty-five bilingual experts agreed on the language validity, and 49 Turkish language experts agreed on the conformity and understandability of the scale's items. Thirty-two subject…

  9. Relationship between posttranslational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient xeroderma pigmentosum fibroblasts and SV40-transformed human cells.

    PubMed

    Lachaise, F; Martin, G; Drougard, C; Perl, A; Vuillaume, M; Wegnez, M; Sarasin, A; Daya-Grosjean, L

    2001-06-15

    Xeroderma Pigmentosum (XP) is a rare recessively inherited human disease associated with a hypersensitivity to ultraviolet radiation. The ultraviolet component of sunlight can initiate and promote the formation of cutaneous tumors as seen in the skin cancer-prone XP patients. Previously, we have found that the low activity of the NADPH-dependent antioxydant enzyme, catalase, which we have observed in XP diploid fibroblasts and SV40-tranformed cells, could be restored by the addition of NADPH. Here we have analyzed transaldolase, which regulates NADPH levels produced by the pentose phosphate pathway in order to examine how it influences the catalase activity regulated in XP and SV40-transformed cells. We find that transaldolase activity is high in XP and SV40-transformed human fibroblasts, whereas transaldolase transcription is unchanged, suggesting that modification of transaldolase activity is due to a posttranslational modification of the protein. Two-dimensional electrophoresis analysis has allowed us to identify a complex set of transaldolase isoforms and to postulate that the phosphorylation of specific isoforms could be correlated with the different enzymatic activities seen. Our results show that high transaldolase activity corresponds to a low catalase activity in SV40-transformed cells and in fibroblasts from XP patients who have a high predisposition to develop skin cancer.

  10. New Molecular Targets for Antiepileptic Drugs: α2δ, SV2A, and Kv7/KCNQ/M Potassium Channels

    PubMed Central

    Rogawski, Michael A.; Bazil, Carl W.

    2008-01-01

    Many currently prescribed antiepileptic drugs (AEDs) act via voltage-gated sodium channels, through effects on γ-aminobutyric acid–mediated inhibition, or via voltage-gated calcium channels. Some newer AEDs do not act via these traditional mechanisms. The molecular targets for several of these nontraditional AEDs have been defined using cellular electrophysiology and molecular approaches. Here, we describe three of these targets: α2δ, auxiliary subunits of voltage-gated calcium channels through which the gabapentinoids gabapentin and pregabalin exert their anticonvulsant and analgesic actions; SV2A, a ubiquitous synaptic vesicle glycoprotein that may prepare vesicles for fusion and serves as the target for levetiracetam and its analog brivaracetam (which is currently in late-stage clinical development); and Kv7/KCNQ/M potassium channels that mediate the M-current, which acts a brake on repetitive firing and burst generation and serves as the target for the investigational AEDs retigabine and ICA-105665. Functionally, all of the new targets modulate neurotransmitter output at synapses, focusing attention on presynaptic terminals as critical sites of action for AEDs. PMID:18590620

  11. [Effects of histone deacetylase inhibitor sodium valproate on the physical and behavioral development of 129SV mice].

    PubMed

    Burenkova, O V; Aleksandrova, E A; Zarayskaya, I Yu

    2015-01-01

    Sodium valproate is a widely used antiepileptic drug at high dosage levels, but it has been shown to produce a variety of toxic side-effects when used during perinatal period. These effects include increased risk of congenital anomalies and autism. For this reason, valproate is commonly employed in animal model of autism. Sodium valproate has multiple molecular targets including histone deacetylases. Therefore valproate can be utilized as a tool for the modulation of epigenetic modifications of the genome via inhibition of histone deacetylases. It is known that administration of sodium valproate at a dose of 50 mg/kg during early postnatal period leads to increase of the histone H3 acetylation level in the brain. The aim of the present study was to evaluate the effects of multiple valproate injections from 3rd to 6th postnatal day (50 mg/kg s.c.) on physical and sensorimotor development of 129Sv mice. The standard battery of tests was used. Our results show that valproate have no negative effect on physical development, sensorimotor function, and social behavior. The obtained results support the applicability of sodium valproate in our dosing schedule for further experimental modulation of histone acetulation level in the developing brain.

  12. Export-deficient monoubiquitinated PEX5 triggers peroxisome removal in SV40 large T antigen-transformed mouse embryonic fibroblasts

    PubMed Central

    Nordgren, Marcus; Francisco, Tânia; Lismont, Celien; Hennebel, Lore; Brees, Chantal; Wang, Bo; Van Veldhoven, Paul P; Azevedo, Jorge E; Fransen, Marc

    2015-01-01

    Peroxisomes are ubiquitous cell organelles essential for human health. To maintain a healthy cellular environment, dysfunctional and superfluous peroxisomes need to be selectively removed. Although emerging evidence suggests that peroxisomes are mainly degraded by pexophagy, little is known about the triggers and molecular mechanisms underlying this process in mammalian cells. In this study, we show that PEX5 proteins fused to a bulky C-terminal tag trigger peroxisome degradation in SV40 large T antigen-transformed mouse embryonic fibroblasts. In addition, we provide evidence that this process is autophagy-dependent and requires monoubiquitination of the N-terminal cysteine residue that marks PEX5 for recycling. As our findings also demonstrate that the addition of a bulky tag to the C terminus of PEX5 does not interfere with PEX5 monoubiquitination but strongly inhibits its export from the peroxisomal membrane, we hypothesize that such a tag mimics a cargo protein that cannot be released from PEX5, thus keeping monoubiquitinated PEX5 at the membrane for a sufficiently long time to be recognized by the autophagic machinery. This in turn suggests that monoubiquitination of the N-terminal cysteine of peroxisome-associated PEX5 not only functions to recycle the peroxin back to the cytosol, but also serves as a quality control mechanism to eliminate peroxisomes with a defective protein import machinery. PMID:26086376

  13. [Gender-dependent effects of histone deacetylase inhibitor sodium valproate on early olfactory learning in 129Sv mice].

    PubMed

    Burenkova, O V; Aleksandrova, E A; Zaraĭskaia, I Iu

    2013-02-01

    In the brain, histone acetylation underlies both learning and the maintenance of long-term sustained effects of early experience which is further epigenetically inherited. However, the role of acetylation in learning previously has only been studied in adult animals: high level of learning could be dependent on high levels of histone H3 acetylation in the brain. The role of acetylation in the mechanisms of early learning has not been studied. In the present work, we were interested whether histone deacetylase inhibitor sodium valproate which increases the level of histone H3 acetylation will affect early olfactory discrimination learning in 8-day-old pups of 129Sv mice that are characterized by low efficiency of learning with imitation of maternal grooming. Multiple valproate injections from 3rd to 6th postnatal day had a gender-dependent effect: learning was selectively improved in male but not in female pups. In the female pups, learning improvement was observed after multiple injections of saline. Possible epigenetic mechanisms underlying these sex differences are discussed.

  14. Late SV40 factor (LSF) enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (MMP-9).

    PubMed

    Santhekadur, Prasanna K; Gredler, Rachel; Chen, Dong; Siddiq, Ayesha; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Fisher, Paul B; Sarkar, Devanand

    2012-01-27

    The transcription factor late SV40 factor (LSF) is overexpressed in human hepatocellular carcinoma (HCC) fostering a highly aggressive and metastatic phenotype. Angiogenesis is an essential component of cancer aggression and metastasis and HCC is a highly aggressive and angiogenic cancer. In the present studies, we analyzed the molecular mechanism of LSF-induced angiogenesis in HCC. Employing human umbilical vein endothelial cells (HUVEC) differentiation assay and chicken chorioallantoic membrane (CAM) assay we document that stable LSF overexpression augments and stable dominant negative inhibition of LSF (LSFdn) abrogates angiogenesis by human HCC cells. A quest for LSF-regulated factors contributing to angiogenesis, by chromatin immunoprecipitation-on-chip (ChIP-on-chip) assay, identified matrix metalloproteinase-9 (MMP-9) as a direct target of LSF. MMP-9 expression and enzymatic activity were higher in LSF-overexpressing cells and lower in LSFdn-expressing cells. Deletion mutation analysis identified the LSF-responsive regions in the MMP-9 promoter and ChIP assay confirmed LSF binding to the MMP-9 promoter. Inhibition of MMP-9 significantly abrogated LSF-induced angiogenesis as well as in vivo tumorigenesis, thus reinforcing the role of MMP-9 in facilitating LSF function. The present findings identify a novel target of LSF contributing to its oncogenic properties.

  15. StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

    SciTech Connect

    Zemla, A; Lang, D; Kostova, T; Andino, R; Zhou, C

    2010-11-29

    Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitate the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected

  16. Differences in memory development among C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl mice after delay and trace fear conditioning.

    PubMed

    March, Amelia; Borchelt, David; Golde, Todd; Janus, Christopher

    2014-02-01

    Fear-conditioning testing paradigms have been used to study differences in memory formation between inbred mouse strains, including numerous mouse models of human diseases. In this study, we characterized the conditioned fear memory of 3 inbred strains: C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl, obtained from Charles River Laboratories. We used 2 training paradigms: delay conditioning, in which an unconditional stimulus coterminates with the presentation of a conditional stimulus, and trace conditioning, in which the conditional and unconditional stimuli are separated by a trace interval. In each paradigm, we evaluated the recent (3 d) and remote (25 d) memory of the mice by using a longitudinal design. Our results showed that both C57BL/6NCrl and 129S2/SvPasCrl mice developed strong and long-lasting context and tone memories in both paradigms, but FVB/NCrl mice showed a weaker but nevertheless consistent tone memory after delay training. Tone memory in the FVB strain was stronger in male than female mice. The remote tone memory of 129S2/SvPasCrl mice diminished after delay training but was stable and stronger than that of C57BL/6NCrl mice after trace training. In conclusion, both C57BL/6NCrl and 129S2/SvPasCrl mice showed reliable and long-lasting fear memory after delay or trace training, with 129 mice showing particularly strong tone memory after trace conditioning. The FVB/NCrl strain, especially male mice, showed reliable tone fear memory after delay training. Our findings confirm that both C57BL/6NCrl and 129S2/SvPasCrl mice develop strong context and tone memory in delay and trace fear-conditioning paradigms.

  17. Measurements of developing teeth, and carpals and epiphyses of the ulna and radius for assessing new cut-offs at the age thresholds of 10, 11, 12, 13 and 14 years.

    PubMed

    Cameriere, R; De Luca, S; Cingolani, M; Ferrante, L

    2015-08-01

    The minimum age of criminal responsibility is the youngest age at which children may be held liable for infringements of penal laws. New cut-offs at the age thresholds of 10, 11, 12, 13 and 14 years were determined by applying three different methods: measurement of open apices in tooth roots (T); the ratio between the total area of carpal bones and epiphyses of the ulna and radius (HW); and the combined method (THW). The sample consisted of 291 Italian children (152 boys, 139 girls), aged between 5 and 15 years. The sensitivity and specificity were established. As regards THW, specificity reached the maximum of 95% in boys aged 10, and the minimum of 87% in boys aged 11. The best score of the Positive Predictive Value (PPV) was obtained in boys at 10 years with the THW method and the worst in girls of 12 with the HW method.

  18. Efficient Catalyst One-Pot Synthesis of 7-(Aryl)-10,10-dimethyl-10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione Derivatives Complemented by Antibacterial Activity

    PubMed Central

    Al-Majedy, Yasameen K.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2016-01-01

    The problem of bacteria resistance to many known agents has inspired scientists and researchers to discover novel efficient antibacterial drugs. Three rapid, clean, and highly efficient methods were developed for one-pot synthesis of 7-(aryl)-10,10-dimethyl-10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione derivatives. Three components are condensed in the synthesis, 4-hydroxycoumarin, 5,5-dimethyl-1,3-cyclohexanedione, and aromatic aldehydes, using tetrabutylammonium bromide (TBAB), diammonium hydrogen phosphate (DAHP), or ferric chloride (FeCl3), respectively. Each method has different reaction mechanisms according to the catalyst. The present methods have advantages, including one-pot synthesis, excellent yields, short reaction times, and easy isolation of product. All catalysts utilized in our study could be reused several times without losing their catalytic efficiency. All synthesized compounds were fully characterized and evaluated for their antibacterial activity. PMID:27563671

  19. Isolation and expression analysis of peanut chlorotic streak caulimovirus (PClSV) full-length transcript (FLt) promoter in transgenic plants.

    PubMed

    Maiti, I B; Shepherd, R J

    1998-03-17

    A promoter fragment from peanut chlorotic streak caulimovirus (PClSV) full-length transcript (FLt) was identified and later modified to have duplicated enhancer domain. The FLt promoter with its single or double enhancer domains, fused with the GUS reporter gene to form chimeric gene constructs, showed a high level of expression of these genes in cells and transgenic plants. The FLt promoter with its double enhancer domain gives an average threefold greater expression of genes compared to the FLt promoter with its single enhancer domain in transgenic plants. In young seedlings the expression was in the order root > leaf > stem. The histochemical GUS assay in young seedlings showed more activity in root tips and leaf midribs, veins, and other vascular tissues. The expression from the PClSV FLt promoter was compared with that from the figwort mosaic virus promoter in transgenic plants. These constitutive promoters were comparable in respect to GUS expression level.

  20. Measurement of vibrational energy transfer of OH (A2S+,v'=1?0) in low-pressure flames

    NASA Astrophysics Data System (ADS)

    Hartlieb, A. T.; Markus, D.; Kreutner, W.; Kohse-Höinghaus, K.

    1997-07-01

    Vibrational energy transfer (VET) and electronic quenching of OH (A2D+) was measured in a low-pressure H2/O2 flame for three rotational levels of OH (v'=1). Rate coefficients for collisions with H2O and N2 were determined. At 1600 K, kVET (N2) is (in 10-11 cm3s-1) 10.1DŽ, 6.1ǃ.8, and 3.8ǃ.3 for N'=0, 5, and 13, respectively. The kVET (H2O) is <1.1ǃ.8. The kQ (N2) is <2.4NJ for both vibrational levels. The kQ (H2O) in v'=1 is 59.1Lj.5, 54.7Lj.4, and 54.9Lj.6 for N'=0, 5, and 13, respectively, and, determined indirectly, 74.6ᆞ.4, 70.6ᆞ.3, and 63.4lj.3 for N'=0, 5, and 13 in v'=0. A multi-level model of OH population dynamics, which is being developed for the quantitative simulation of experimental LIF spectra, was extended to include VET. It was attempted to simulate state-to-state-specific VET coefficients for N2 collisions. From these simulations it appears that angular momentum conservation does not determine the N dependence of the vibrational relaxation step.

  1. STX140, but not paclitaxel, inhibits mammary tumour initiation and progression in C3(1)/SV40 T/t-antigen transgenic mice.

    PubMed

    Meyer-Losic, Florence; Newman, Simon P; Day, Joanna M; Reed, Michael J; Kasprzyk, Philip G; Purohit, Atul; Foster, Paul A

    2013-01-01

    Despite paclitxael's clinical success, treating hormone-refractory breast cancer remains challenging. Paclitaxel has a poor pharmacological profile, characterized by a low therapeutic index (TIX) caused by severe dose limiting toxicities, such as neutropenia and peripheral neuropathy. Consequently, new drugs are urgently required. STX140, a compound previously shown to have excellent efficacy against many tumors, is here compared to paclitaxel in three translational in vivo breast cancer models, a rat model of peripheral neuropathy, and through pharmacological testing. Three different in vivo mouse models of breast cancer were used; the metastatic 4T1 orthotopic model, the C3(1)/SV40 T-Ag model, and the MDA-MB-231 xenograft model. To determine TIX and pharmacological profile of STX140, a comprehensive dosing regime was performed in mice bearing MDA-MD-231 xenografts. Finally, peripheral neuropathy was examined using a rat plantar thermal hyperalgesia model. In the 4T1 metastatic model, STX140 and paclitaxel significantly inhibited primary tumor growth and lung metastases. All C3(1)/SV40 T-Ag mice in the control and paclitaxel treated groups developed palpable mammary cancer. STX140 blocked 47% of tumors developing and significantly inhibited growth of tumors that did develop. STX140 treatment caused a significant (P<0.001) survival advantage for animals in early and late intervention groups. Conversely, in C3(1)/SV40 T-Ag mice, paclitaxel failed to inhibit tumor growth and did not increase survival time. Furthermore, paclitaxel, but not STX140, induced significant peripheral neuropathy and neutropenia. These results show that STX140 has a greater anti-cancer efficacy, TIX, and reduced neurotoxicity compared to paclitaxel in C3(1)/SV40 T-Ag mice and therefore may be of significant benefit to patients with breast cancer.

  2. B-DNA to Z-DNA structural transitions in the SV40 enhancer: stabilization of Z-DNA in negatively supercoiled DNA minicircles

    NASA Technical Reports Server (NTRS)

    Gruskin, E. A.; Rich, A.

    1993-01-01

    During replication and transcription, the SV40 control region is subjected to significant levels of DNA unwinding. There are three, alternating purine-pyrimidine tracts within this region that can adopt the Z-DNA conformation in response to negative superhelix density: a single copy of ACACACAT and two copies of ATGCATGC. Since the control region is essential for both efficient transcription and replication, B-DNA to Z-DNA transitions in these vital sequence tracts may have significant biological consequences. We have synthesized DNA minicircles to detect B-DNA to Z-DNA transitions in the SV40 enhancer, and to determine the negative superhelix density required to stabilize the Z-DNA. A variety of DNA sequences, including the entire SV40 enhancer and the two segments of the enhancer with alternating purine-pyrimidine tracts, were incorporated into topologically relaxed minicircles. Negative supercoils were generated, and the resulting topoisomers were resolved by electrophoresis. Using an anti-Z-DNA Fab and an electrophoretic mobility shift assay, Z-DNA was detected in the enhancer-containing minicircles at a superhelix density of -0.05. Fab saturation binding experiments demonstrated that three, independent Z-DNA tracts were stabilized in the supercoiled minicircles. Two other minicircles, each with one of the two alternating purine-pyrimidine tracts, also contained single Z-DNA sites. These results confirm the identities of the Z-DNA-forming sequences within the control region. Moreover, the B-DNA to Z-DNA transitions were detected at superhelix densities observed during normal replication and transcription processes in the SV40 life cycle.

  3. The AT-rich tract of the SV40 ori core: negative synergism and specific recognition by single stranded and duplex DNA binding proteins.

    PubMed Central

    Galli, I; Iguchi-Ariga, S M; Ariga, H

    1992-01-01

    The SV40 origin of replication comprises a run of thymine and adenine residues. Integrity of this AT-rich sequence is known to be essential for replication. We set out to study whether or not these elements can work synergistically to sustain replication. Quite surprisingly, additional copies of the AT stretch linked to a functional SV40 ori core dramatically reduce its replication in Cosl cells, probably by creating some physical block. Interestingly, the same inhibiting effect can be observed with the addition in cis of the yeast ARS consensus, which is homologous to the SV40 AT stretch. This modulation is possibly due to the action of cellular factors that recognize either of the two sequences. In fact, we demonstrate the existence of factor(s) in Cosl crude nuclear extracts that in vitro can specifically bind to either of them. Moreover, we show that these sequence-specific factor(s) (MW about 50 kDa), named SOAP, recognize both single (T-rich strand) and double stranded forms of the AT tracts. Binding to single stranded AT stretches can be specifically inhibited by the corresponding duplex form, but not vice versa. Images PMID:1321411

  4. Isolation of a monoclonal antibody that recognizes the origin binding domain of JCV, but not SV40, large T-antigen.

    PubMed

    Grubman, Shelley A; Shin, Jong; Phelan, Paul J; Gong, Aaron; Can, Hande; Dilworth, Ryan; Kini, Sandeep Kuntadi; Gagnon, David; Archambault, Jacques; Meinke, Gretchen; Bohm, Andrew; Jefferson, Douglas M; Bullock, Peter A

    2016-10-01

    Within immunocompromised populations, the JC polyomavirus is the cause of the often-fatal disease Progressive Multifocal Leukoencephalopathy (PML). JC virus encodes a protein, termed T-antigen (T-ag), which is essential for its replication and pathogenicity. Previous studies of JCV T-ag have, in general, used antibodies raised against SV40 T-ag. Unfortunately, SV40 T-ag is also detected in humans and therefore there have been concerns about cross-reactivity. To address this issue, we have isolated a monoclonal antibody that binds to the JCV, but not the SV40, T-ag origin-binding domain (OBD). Furthermore, the region on the surface of the JCV T-ag OBD that is recognized by the "anti-JCV OBD mAb" has been mapped. We also demonstrate that the "anti-JCV OBD mAb" will be a useful reagent for standard techniques (e.g., Westerns blots and ELISAs). Finally, we note that additional monoclonal Abs that are specific for the T-ags encoded by the other human polyomaviruses could be generated by adopting the approach described herein.

  5. DNA-Free Recombinant SV40 Capsids Protect Mice from Acute Renal Failure by Inducing Stress Response, Survival Pathway and Apoptotic Arrest

    PubMed Central

    Abd-El-Latif, Mahmoud; Pizov, Galina; Eden, Arieh; Haviv, Yosef S.; Oppenheim, Ariella

    2008-01-01

    Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses. PMID:18714386

  6. Photometry and Spectroscopy of ES Aql, SV Sge, and Z UMi, Cool Stars with Variability of the R Coronae Borealis Type

    NASA Astrophysics Data System (ADS)

    Rosenbush, A. E.

    2013-12-01

    UBVR c I c photometric measurements are made of three cool stars with R Coronae Borealis type variability, ES Aql, SV Sge, and Z UMi. During their visual light minima ES Aql and Z UMi manifested brightness and color behavior typical of this type of variability: a decrease or increase in the color indices as the brightness decreases and an increase as the normal state is recovered. The molecular spectrum of Z UMi during the second half of the minimum with an weakness by about 4m was already normal, but the Na I D doublet lines were still filled with emission. High resolution profiles of the Na I D lines for SV Sge reveal a systematic shift to -10 km/s and an extended blue wing, which can be regarded as a consequence of a constant outflow of matter from the star's atmosphere that has not led to minima in the visual brightness even over a time of 9 years. Identification of the interstellar Na I D lines in the high resolution spectra has made it possible to verify the known color excess E(B-V) for Z UMi at a level 0m.02 ± 0m.11 and substantially reduce its value to 0m.03 for SV Sge. For the latter star this also opens up the possibility of a substantially lower absolute magnitude, M V ≤ 2m, than assumed previously.

  7. Seasonal radon measurements in Darbandikhan Lake water resources at Kurdistan region-northeastern of Iraq

    NASA Astrophysics Data System (ADS)

    Jafir, Adeeb Omer; Ahmad, Ali Hassan; Saridan, Wan Muhamad

    2016-03-01

    A total of 164 water samples were collected from Darbandikhan Lake with their different resources (spring, stream, and lake) during the four seasons, and the measurements were carried out using the electronic RAD 7 detector. For spring water the average radon concentration for spring, summer, autumn and summer were found to be 8.21 Bq/1, 8.94 Bq/1, 7.422 Bq/1, and 8.06 Bq/1, respectively, while for lake and streams the average values were found to be 0.43 Bq/1, 0.877 Bq/1, 0.727 Bq/1, 0.575 Bq/1 respectively. The radon concentration level was higher in summer and lower in spring, and only two samples from spring water have radon concentrations more than 11.1 Bq/1 recommended by the EPA. Total annual effective dose due to ingestion and inhalation has been estimated, the mean annual effective dose during the whole year for spring water was 0.022 mSv/y while for lake with streams was 0.00157 mSv/y. The determined mean annual effective dose in water was lower than the 0.1 mSv/y recommended by WHO. Some physicochemical parameters were measured and no correlation was found between them and radon concentration except for the conductivity of the spring drinking water which reveals a strong correlation for the four seasons.

  8. Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin

    PubMed Central

    Anisimov, Vladimir N; Popovich, Irina G; Zabezhinski, Mark A; Egormin, Peter A; Yurova, Maria N; Semenchenko, Anna V; Tyndyk, Margarita L; Panchenko, Andrey V; Trashkov, Alexandr P; Vasiliev, Andrey G; Khaitsev, Nikolai V

    2015-01-01

    The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone – IGF-1 – insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (+20%, P < 0.05) and slightly increased the maximum life span (+3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (−9.1% and −13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice. PMID:25483062

  9. Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

    PubMed Central

    Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

    2017-01-01

    After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only

  10. Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

    PubMed

    Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

    2017-01-01

    After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and

  11. Synthesis and characterization of a cyclobutane duocarmycin derivative incorporating the 1,2,10,11-tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) alkylation subunit.

    PubMed

    Lajiness, James P; Boger, Dale L

    2010-10-06

    The synthesis of 1,2,10,11-tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (17, CbBI), which contains a deep-seated fundamental structural modification in the CC-1065 and duocarmycin alkylation subunit consisting of the incorporation of a ring-expanded fused cyclobutane (vs cyclopropane), its chemical and structural characterization, and its incorporation into a key analogue of the natural products are detailed. The approach to the preparation of CbBI was based on a precedented (Ar-3' and Ar-5') but previously unknown Ar-4' spirocyclization of a phenol onto a tethered alkyl halide to form the desired cyclobutane. The conditions required for the implementation of the Ar-4' spirocyclization indicate that the entropy of activation substantially impacts the rate of reaction relative to that for the much more facile Ar-3' spirocyclization, while the higher enthalpy of activation slows the reaction relative to an Ar-5' spirocyclization. The characterization of the CbBI-based agents revealed their exceptional stability and exquisite reaction regioselectivity, and a single-crystal X-ray structure analysis of N-Boc-CbBI (13) revealed their structural origins. The reaction regioselectivity may be attributed to the stereoelectronic alignment of the two available cyclobutane bonds with the cyclohexadienone π-system, which resides in the bond that extends to the less substituted cyclobutane carbon for 13. The remarkable stability of N-Boc-CbBI (which is stable even at pH 1) relative to N-Boc-CBI containing a cyclopropane (t(1/2) = 133 h at pH 3) may be attributed to a combination of the increased extent of vinylogous amide conjugation, the nonoptimal geometric alignment of the cyclobutane with the activating cyclohexadienone, and the intrinsic but modestly lower strain energy (1.8 kcal/mol) of a cyclobutane versus a cyclopropane.

  12. Liquid chromatographic assay based on microextraction by packed sorbent for therapeutic drug monitoring of carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin and the active metabolites carbamazepine-10,11-epoxide and licarbazepine.

    PubMed

    Ferreira, Ana; Rodrigues, Márcio; Oliveira, Paula; Francisco, Joana; Fortuna, Ana; Rosado, Luísa; Rosado, Pedro; Falcão, Amílcar; Alves, Gilberto

    2014-11-15

    A new, sensitive and fast high-performance liquid chromatography-diode-array detection assay based on microextraction by packed sorbent (MEPS/HPLC-DAD) is herein reported, for the first time, to simultaneously quantify carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), and the active metabolites carbamazepine-10,11-epoxide (CBZ-E) and licarbazepine (LIC) in human plasma. Chromatographic separation of analytes and ketoprofen, used as internal standard (IS), was achieved in less than 15min on a C18-column, at 35°C, using acetonitrile (6%) and a mixture (94%) of water-methanol-triethylamine (73.2:26.5:0.3, v/v/v; pH 6.5) pumped at 1mL/min. The analytes and IS were detected at 215, 237 or 280nm. The method showed to be selective, accurate [bias ±14.8% (or ±17.8% in the lower limit of quantification)], precise [coefficient variation ≤9.7% (or ≤17.7% in the lower limit of quantification)] and linear (r(2)≥0.9946) over the concentration ranges of 0.1-15μg/mL for CBZ; 0.1-20μg/mL for LTG; 0.1-5μg/mL for OXC and CBZ-E; 0.2-40μg/mL for PB; 0.3-30μg/mL for PHT; and 0.4-40μg/mL for LIC. The absolute extraction recovery of the analytes ranged from 57.8 to 98.1% and their stability was demonstrated in the studied conditions. This MEPS/HPLC-DAD assay was successfully applied to real plasma samples from patients, revealing to be a cost-effective tool for routine therapeutic drug monitoring of CBZ, LTG, OXC, PB and/or PHT.

  13. Source locations of teleseismic P, SV, and SH waves observed in microseisms recorded by a large aperture seismic array in China

    NASA Astrophysics Data System (ADS)

    Liu, Qiaoxia; Koper, Keith D.; Burlacu, Relu; Ni, Sidao; Wang, Fuyun; Zou, Changqiao; Wei, Yunhao; Gal, Martin; Reading, Anya M.

    2016-09-01

    Transversely polarized seismic waves are routinely observed in ambient seismic energy across a wide range of periods, however their origin is poorly understood because the corresponding source regions are either undefined or weakly constrained, and nearly all models of microseism generation incorporate a vertically oriented single force as the excitation mechanism. To better understand the origin of transversely polarized energy in the ambient seismic wavefield we make the first systematic attempt to locate the source regions of teleseismic SH waves observed in microseismic (2.5-20 s) noise. We focus on body waves instead of surface waves because the source regions can be constrained in both azimuth and distance using conventional array techniques. To locate microseismic sources of SH waves (as well as SV and P waves) we continuously backproject the vertical, radial, and transverse components of the ambient seismic wavefield recorded by a large-aperture array deployed in China during 2013-2014. As expected, persistent P wave sources are observed in the North Atlantic, North Pacific, and Indian Oceans, mainly at periods of 2.5-10 s, in regions with the strong ocean wave interactions needed to produce secondary microseisms. SV waves are commonly observed to originate from locations indistinguishable from the P wave sources, but with smaller signal-to-noise ratios. We also observe SH waves with about half or less the signal-to-noise ratio of SV waves. SH source regions are definitively located in deep water portions of the Pacific, away from the sloping continental shelves that are thought to be important for the generation of microseismic Love waves, but nearby regions that routinely generate teleseismic P waves. The excitation mechanism for the observed SH waves may therefore be related to the interaction of P waves with small-wavelength bathymetric features, such as seamounts and basins, through some sort of scattering process.

  14. An oxidant- and solvent-stable protease produced by Bacillus cereus SV1: application in the deproteinization of shrimp wastes and as a laundry detergent additive.

    PubMed

    Manni, Laila; Jellouli, Kemel; Ghorbel-Bellaaj, Olfa; Agrebi, Rym; Haddar, Anissa; Sellami-Kamoun, Alya; Nasri, Moncef

    2010-04-01

    The current increase in amount of shrimp wastes produced by the shrimp industry has led to the need in finding new methods for shrimp wastes disposal. In this study, an extracellular organic solvent- and oxidant-stable metalloprotease was produced by Bacillus cereus SV1. Maximum protease activity (5,900 U/mL) was obtained when the strain was grown in medium containing 40 g/L shrimp wastes powder as a sole carbon source. The optimum pH, optimum temperature, pH stability, and thermal stability of the crude enzyme preparation were pH 8.0, 60 degrees C, pH 6-9.5, and <55 degrees C, respectively. The crude protease was extremely stable toward several organic solvents. No loss of activity was observed even after 60 days of incubation at 30 degrees C in the presence of 50% (v/v) dimethyl sulfoxide and ethyl ether; the enzyme retained more than 70% of its original activity in the presence of ethanol and N,N-dimethylformamide. The protease showed high stability toward anionic (SDS) and non-ionic (Tween 80, Tween 20, and Triton X-100) surfactants. Interestingly, the activity of the enzyme was significantly enhanced by oxidizing agents. In addition, the enzyme showed excellent compatibility with some commercial liquid detergents. The protease of B. cereus SV1, produced under the optimal culture conditions, was tested for shrimp waste deproteinization in the preparation of chitin. The protein removal with a ratio E/S of 20 was about 88%. The novelties of the SV1 protease include its high stability to organic solvents and surfactants. These unique properties make it an ideal choice for application in detergent formulations and enzymatic peptide synthesis. In addition, the enzyme may find potential applications in the deproteinization of shrimp wastes to produce chitin.

  15. The Ansamycin Antibiotic, Rifamycin SV, Inhibits BCL6 Transcriptional Repression and Forms a Complex with the BCL6-BTB/POZ Domain

    PubMed Central

    Evans, Sian E.; Goult, Benjamin T.; Fairall, Louise; Jamieson, Andrew G.; Ko Ferrigno, Paul; Ford, Robert; Schwabe, John W. R.; Wagner, Simon D.

    2014-01-01

    BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ∼40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor. PMID:24595451

  16. All six GC-motifs of the SV40 early upstream element contribute to promoter activity in vivo and in vitro.

    PubMed Central

    Barrera-Saldana, H; Takahashi, K; Vigneron, M; Wildeman, A; Davidson, I; Chambon, P

    1985-01-01

    Recombinants in which the six GC-motifs (I-VI) present in the upstream element of the SV40 early promoter region have been point mutated either individually or in pairs were used to determine the possible contribution of each GC-motif to the function of the overlapping early-early and late-early SV40 promoters. GC-motif I, and to a lesser extent, GC-motifs II and III, are critical for initiation at the early-early start sites. GC-motifs IV-VI play a subsidiary role. Mutations in GC-motifs I and II do not decrease the activity of the late-early promoter, whereas mutations in the GC-motifs III-VI have a moderate effect on it. The in vivo phenotype of the GC-motif mutants can be almost fully reproduced in vitro using a nuclear extract. DNase I protection footprinting experiments using wild-type or mutated templates and nuclear extracts indicate that each GC-motif behaves principally as an independent protein-binding site, presumably for transcription factor Sp1. The effect of changing the position of the 21-bp repeat region on initiation from the early-early and late-early start sites indicates that there is little flexibility in the position in which this upstream element can efficiently activate initiation of transcription from these start sites. Images Fig. 3. Fig. 4. Fig. 7. Fig. 8. Fig. 9. PMID:3004974

  17. Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice results in abnormal skeletal development

    PubMed Central

    1995-01-01

    The ability of SV40 T antigen to cause abnormalities in cartilage development in transgenic mice and chimeras has been tested. The cis- regulatory elements of the COL2A1 gene were used to target expression of SV40 T antigen to differentiating chondrocytes in transgenic mice and chimeras derived from embryonal stem (ES) cells bearing the same transgene. The major phenotypic consequences of transgenic (pAL21) expression are malformed skeleton, disproportionate dwarfism, and perinatal/neonatal death. Expression of T antigen was tissue specific and in the main characteristic of the mouse alpha 1(II) collagen gene. Chondrocyte densities and levels of alpha 1(II) collagen mRNAs were reduced in the transgenic mice. Islands of cells which express cartilage characteristic genes such as type IIB procollagen, long form alpha 1(IX) collagen, alpha 2(XI) collagen, and aggrecan were found in the articular and growth cartilages of pAL21 chimeric fetuses and neonates. But these cells, which were expressing T antigen, were not properly organized into columns of proliferating chondrocytes. Levels of alpha 1(II) collagen mRNA were reduced in these chondrocytes. In addition, these cells did not express type X collagen, a marker for hypertrophic chondrocytes. The skeletal abnormality in pAL21 mice may therefore be due to a retardation of chondrocyte maturation or an impaired ability of chondrocytes to complete terminal differentiation and an associated paucity of some cartilage matrix components. PMID:7822417

  18. Establishment of renal proximal tubule cell lines by targeted oncogenesis in transgenic mice using the L-pyruvate kinase-SV40 (T) antigen hybrid gene.

    PubMed

    Cartier, N; Lacave, R; Vallet, V; Hagege, J; Hellio, R; Robine, S; Pringault, E; Cluzeaud, F; Briand, P; Kahn, A

    1993-03-01

    Targeted oncogenesis allowed us to obtain two cell lines which have been derived from the proximal tubule of kidney from transgenic mice harbouring the simian virus (SV40) large T and small t antigens placed under the control of the 5' regulatory sequence from the rat L-type pyruvate kinase (L-PK) gene. The cell lines (PKSV-PCT and PKSV-PR cells) were derived from early (PCT) and late (Pars Recta, PR) microdissected proximal tubules grown in D-glucose-enriched medium. In such conditions of culture, both cell lines exhibited L-PK transcripts, a stable expression of SV40-encoded nuclear large T antigen, a prolonged life span but failed to induce tumors when injected sub-cutaneously into athymic (nu-nu) mice. Confluent cells, grown on plastic support or porous filters, were organized as monolayers of polarized cuboid cells with well developed apical microvilli and formed domes. Both cell lines exhibited morphological features of proximal tubule cells with villin located in the apical brush-border and substantial amounts of hydrolase activity. By immunofluorescence studies using specific antibodies, aminopeptidase N appeared restricted to the apical microvillar domain, whereas the H2 histocompatibility antigen was distributed in the cytoplasm and lateral membranes. These results demonstrate that the proximal morphological phenotype has been fully preserved in these cultured cells derived from tissue-specific targeted oncogenesis in transgenic mice.

  19. Diagnostic accuracy of sub-mSv prospective ECG-triggering cardiac CT in young infant with complex congenital heart disease.

    PubMed

    Gao, Wei; Zhong, Yu Min; Sun, Ai Min; Wang, Qian; Ouyang, Rong Zhen; Hu, Li Wei; Qiu, Han Sheng; Wang, Shi Yu; Li, Jian Ying

    2016-06-01

    To explore the clinical value and evaluate the diagnostic accuracy of sub-mSv low-dose prospective ECG-triggering cardiac CT (CCT) in young infants with complex congenital heart disease (CHD). A total of 102 consecutive infant patients (53 boys and 49 girls with mean age of 2.9 ± 2.4 m and weight less than 5 kg) with complex CHD were prospectively enrolled. Scans were performed on a 64-slice high definition CT scanner with low dose prospective ECG-triggering mode and reconstructed with 80 % adaptive statistical iterative reconstruction algorithm. All studies were performed during free breathing with sedation. The subjective image quality was evaluated by 5-point grading scale and interobserver variability was calculated. The objective image noise (standard deviation, SD) and contrast to noise ratio (CNR) was calculated. The effective radiation dose from the prospective ECG-triggering mode was recorded and compared with the virtual conventional retrospective ECG-gating mode. The detection rate for the origin of coronary artery was calculated. All patients also underwent echocardiography before CCT examination. 81 patients had surgery and their preoperative CCT and echocardiography findings were compared with the surgical results and sensitivity, specificity, positive and negative predictive values and accuracy were calculated for separate cardiovascular anomalies. Heart rates were 70-161 beats per minute (bpm) with mean value of 129.19 ± 14.52 bpm. The effective dose of 0.53 ± 0.15 mSv in the prospective ECG-triggering cardiac CT was lower than the calculated value in a conventional retrospective ECG-gating mode (2.00 ± 0.35 mSv) (p < 0.001). The mean CNR and SD were 28.19 ± 13.00 and 15.75 ± 3.61HU, respectively. The image quality scores were 4.31 ± 0.36 and 4.29 ± 0.41 from reviewer 1 and 2 respectively with an excellent agreement between them (Kappa = 0.85). The detection rate for the origins of the left and right coronary

  20. Detection and chromosomal assignment of SV40-DNA integration in Chinese hamster cell lines by chromosome sorting and dot blot hybridization.

    PubMed

    Hutter, K J; Klefenz, H; Goerttler, K

    1990-01-01

    A combination of cytometric (chromosome sorting), molecular (dot blot hybridization using radio-active and/or biotinylated DNA probes) and cytogenetic (G-banding) evaluation is described which allows the rapid identification of single copy and repetitive viral integrates and their assignment to chromosome groups or even individual chromosomes. In the case of Chinese hamster cell line CO 631 it could be demonstrated that SV40 DNA was solely integrated into a submetacentric marker chromosome. Such a cytometric/molecular/cytogenetic "identogram" may prove to be a useful tool in many areas of cell and tumor biology. Furthermore, amounts of chromosomes sufficient for analysis as well as subsequent cloning experiments can be accumulated.

  1. Accelerated Progression of Gastritis to Dysplasia in the Pyloric Antrum of TFF2−/− C57BL6 × Sv129 Helicobacter pylori-Infected Mice

    PubMed Central

    Fox, James G.; Rogers, Arlin B.; Whary, Mark T.; Ge, Zhongming; Ohtani, Masa; Jones, Evelyn Kurt; Wang, Timothy C.

    2007-01-01

    Trefoil factor family 2 (TFF2) is up-regulated in Helicobacter spp.-infected gastric tissues of both humans and mice. To ascertain the biological effects of TFF2 in vivo, TFF2−/− C57BL/6 × Sv129 and wild-type (WT) C57BL/6 × Sv129 mice were orally infected with Helicobacter pylori SS1. Mice were evaluated for gastric H. pylori colonization, pathology, and cytokine profiles at 6 and 19 months post inoculation (pi). At 6 months pi, there was a significant difference (P < 0.05) for epithelial criteria (mucosal defects, atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia) in the corpus of TFF2−/− versus WT mice. At 19 months pi, a similar statistical difference in epithelial parameters was noted in the antrum of TFF2−/− versus WT mice (P < 0.01). All of the TFF2−/− H. pylori-infected mice had high-grade antral dysplasia, including gastric intraepithelial neoplasia, which was statistically significant (P < 0.05) compared with the infected WT mice. Levels of interferon-γ were markedly elevated in the gastric mucosa of infected TFF2−/− mice at both 6 and 19 months pi. TFF2 provided a cytoprotective and/or anti-inflammatory effect against the progression of premalignant lesions of the gastric corpus at 6 months pi and in the pyloric antrum in H. pylori-infected mice at 19 months pi. These data support a protective role for TFF2 in part by modulating levels of gastric interferon-γ in the development of H. pylori-associated premalignancy of the distal stomach. PMID:17982128

  2. Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

    PubMed

    Mead, Emma J; Masterton, Rosalyn J; Feary, Marc; Obrezanova, Olga; Zhang, Lin; Young, Robert; Smales, C Mark

    2015-12-15

    Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilize knowledge of the amounts of these factors to build predictive models for and use cluster analysis to identify, high-producing cell lines. The present study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity.

  3. Effect of seawater on incident plane P and SV waves at ocean bottom and engineering characteristics of offshore ground motion records off the coast of southern California, USA

    NASA Astrophysics Data System (ADS)

    Diao, Hongqi; Hu, Jinjun; Xie, Lili

    2014-06-01

    The effect of seawater on vertical ground motions is studied via a theoretical method and then actual offshore ground motion records are analyzed using a statistical method. A theoretical analysis of the effect of seawater on incident plane P and SV waves at ocean bottom indicate that on one hand, the affected frequency range of vertical ground motions is prominent due to P wave resonance in the water layer if the impedance ratio between the seawater and the underlying medium is large, but it is greatly suppressed if the impedance ratio is small; on the other hand, for the ocean bottom interface model selected herein, vertical ground motions consisting of mostly P waves are more easily affected by seawater than those dominated by SV waves. The statistical analysis of engineering parameters of offshore ground motion records indicate that: (1) Under the influence of softer surface soil at the seafloor, both horizontal and vertical spectral accelerations of offshore motions are exaggerated at long period components, which leads to the peak spectral values moving to a longer period. (2) The spectral ratios (V/H) of offshore ground motions are much smaller than onshore ground motions near the P wave resonant frequencies in the water layer; and as the period becomes larger, the effect of seawater becomes smaller, which leads to a similar V/H at intermediate periods (near 2 s). These results are consistent with the conclusions of Boore and Smith (1999), but the V/H of offshore motion may be smaller than the onshore ground motions at longer periods (more than 5 s).

  4. Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model.

    PubMed

    Cranford, Taryn L; Velázquez, Kandy T; Enos, Reilly T; Bader, Jackie E; Carson, Meredith S; Chatzistamou, Ioulia; Nagarkatti, Mitzi; Murphy, E Angela

    2017-02-01

    Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a major modulator in the progression of mammary tumorigenesis, largely due to its ability to recruit macrophages to the tumor microenvironment. Macrophages are key mediators in the connection between inflammation and cancer progression and have been shown to play an important role in tumorigenesis. Thus, MCP-1 may be a potential therapeutic target in inflammatory and difficult-to-treat cancers such as triple negative breast cancer (TNBC). We examined the effect of MCP-1 depletion on mammary tumorigenesis in a model of TNBC. Tumor measurements were conducted weekly (until 22 weeks of age) and at sacrifice (23 weeks of age) in female C3(1)/SV40Tag and C3(1)/SV40Tag MCP-1 deficient mice to determine tumor numbers and tumorvolumes. Histopathological scoring was performed at 12 weeks of age and 23 weeks of age. Gene expression of macrophage markers and inflammatory mediators were measured in the mammary gland and tumor microenvironment at sacrifice. As expected, MCP-1 depletion resulted in decreased tumorigenesis, indicated by reduced primary tumor volume and multiplicity, and a delay in tumor progression represented by histopathological scoring (12 weeks of age). Deficiency in MCP-1 significantly downregulated expression of macrophage markers in the mammary gland (Mertk and CD64) and the tumor microenvironment (CD64), and also reduced expression of inflammatory cytokines in the mammary gland (TNFα and IL-1β) and the tumor microenvironment (IL-6). These data support the hypothesis that MCP-1 expression contributes to increased tumorigenesis in a model of TNBC via recruitment of macrophages and subsequent increase in inflammatory mediators.

  5. Investigations on the presence of antibodies to papova viruses in patients with different forms of cancer and in other categories of patients or apparently healthy subjects. Note I. Neutralizing antibodies to SV-40 in the cerebrospinal fluid of patients with brain tumors and chronic neurological diseases.

    PubMed

    Nastac, E; Stoian, M; Hozoc, M; Suru, M; Serban, A; Alexianu, D; Carp, N

    1981-01-01

    Neutralizing antibodies to SV-40 were detected in cerebrospinal fluid samples from 16 out of 43 patients with brain tumors and in 6 out of 20 patients with different nonmalignant chronic neurological diseases. The patients' age excluded the correlation with a vaccine-associated or occupational contact with SV-40. The results ascertain the occurrence of SV-40 or of an antigenically related virus in the population of Romania.

  6. SHEAR WAVE SEISMIC STUDY COMPARING 9C3D SV AND SH IMAGES WITH 3C3D C-WAVE IMAGES

    SciTech Connect

    John Beecherl; Bob A. Hardage

    2004-07-01

    The objective of this study was to compare the relative merits of shear-wave (S-wave) seismic data acquired with nine-component (9-C) technology and with three-component (3-C) technology. The original proposal was written as if the investigation would be restricted to a single 9-C seismic survey in southwest Kansas (the Ashland survey), on the basis of the assumption that both 9-C and 3-C S-wave images could be created from that one data set. The Ashland survey was designed as a 9-C seismic program. We found that although the acquisition geometry was adequate for 9-C data analysis, the source-receiver geometry did not allow 3-C data to be extracted on an equitable and competitive basis with 9-C data. To do a fair assessment of the relative value of 9-C and 3-C seismic S-wave data, we expanded the study beyond the Ashland survey and included multicomponent seismic data from surveys done in a variety of basins. These additional data were made available through the Bureau of Economic Geology, our research subcontractor. Bureau scientists have added theoretical analyses to this report that provide valuable insights into several key distinctions between 9-C and 3-C seismic data. These theoretical considerations about distinctions between 3-C and 9-C S-wave data are presented first, followed by a discussion of differences between processing 9-C common-midpoint data and 3-C common-conversion-point data. Examples of 9-C and 3-C data are illustrated and discussed in the last part of the report. The key findings of this study are that each S-wave mode (SH-SH, SV-SV, or PSV) involves a different subsurface illumination pattern and a different reflectivity behavior and that each mode senses a different Earth fabric along its propagation path because of the unique orientation of its particle-displacement vector. As a result of the distinct orientation of each mode's particle-displacement vector, one mode may react to a critical geologic condition in a more optimal way than do

  7. Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer

    PubMed Central

    Steiner, JL; Davis, JM; McClellan, JL; Enos, RT; Carson, JA; Fayad, R; Nagarkatti, M; Nagarkatti, PS; Altomare, D; Creek, KE; Murphy, EA

    2014-01-01

    Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15–16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted ‘U’ dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3-Con: 2061.8 ± 977.0 mm3; and C3-0.2%: 462.9 ± 75.9 mm3). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm3; C3-0.02%: 1401.5 ± 555.6 mm3), as was tumor number (C3-2%: 10.7 ± 1.3 mm3; C3-0.02%: 8.1 ± 1.1 mm3). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment. PMID:25482952

  8. Protein phosphatase 2A is a critical regulator of protein kinase C zeta signaling targeted by SV40 small t to promote cell growth and NF-kappaB activation.

    PubMed Central

    Sontag, E; Sontag, J M; Garcia, A

    1997-01-01

    We have reported that inhibition of protein phosphatase 2A (PP2A) by expression of SV40 small t stimulates the mitogenic MAP kinase cascade. Here, we show that SV40 small t can substitute for tumor necrosis factor-alpha (TNF-alpha) or serum and stimulate atypical protein kinase C zeta (PKC zeta) activity, resulting in MEK activation, cell proliferation and NF-kappaB-dependent gene transcriptional activation in CV-1 and NIH 3T3 cells. These effects were abrogated by co-expression of kinase-deficient PKC zeta and inhibition of phosphatidylinositol 3-kinase p85alpha-p110 by wortmannin, LY294002 and a dominant-negative mutant of p85alpha. In contrast, expression of kinase-inactive ERK2 inhibited small t-dependent cell growth but was unable to abolish small t-induced NF-kappaB transactivation. Our results provide the first in vivo evidence for a critical regulatory role of PP2A in bifunctional PKC zeta signaling pathways controlled by phosphatidylinositol 3-kinase. Constitutive activation of PKC zeta and NF-kappaB following inhibition of PP2A supports new mechanisms by which SV40 small t promotes cell growth and transformation. By establishing PP2A as a key player in the response of cells to growth factors and stress signals like TNF-alpha, our findings could explain why PP2A is a primary target utilized during SV40 infection to alter cellular behavior. PMID:9312025

  9. Nucleosome positioning in the regulatory region of SV40 chromatin correlates with the activation and repression of early and late transcription during infection.

    PubMed

    Kumar, Meera Ajeet; Christensen, Kendra; Woods, Benjamin; Dettlaff, Ashley; Perley, Danielle; Scheidegger, Adam; Balakrishnan, Lata; Milavetz, Barry

    2017-03-01

    The location of nucleosomes in SV40 virions and minichromosomes isolated during infection were determined by next generation sequencing (NGS). The patterns of reads within the regulatory region of chromatin from wild-type virions indicated that micrococcal nuclease-resistant nucleosomes were specifically positioned at nt 5223 and nt 363, while in minichromosomes isolated 48 h post-infection we observed nuclease-resistant nucleosomes at nt 5119 and nt 212. The nucleosomes at nt 5223 and nt 363 in virion chromatin would be expected to repress early and late transcription, respectively. In virions from the mutant cs1085, which does not repress early transcription, we found that these two nucleosomes were significantly reduced compared to wild-type virions confirming a repressive role for them. In chromatin from cells infected for only 30min with wild-type virus, we observed a significant reduction in the nucleosomes at nt 5223 and nt 363 indicating that the potential repression by these nucleosomes appeared to be relieved very early in infection.

  10. The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations.

    PubMed Central

    Hu, Q J; Dyson, N; Harlow, E

    1990-01-01

    The protein product of the retinoblastoma (RB) gene is thought to function in a pathway that restricts cell proliferation. Recently, transforming proteins from three different classes of DNA tumor viruses have been shown to form complexes with the RB protein. Genetic studies suggest that these interactions with the RB protein are important steps in transformation by these viruses. In order to understand better the function of the RB-viral oncoprotein complexes, we have mapped the regions of the RB protein that are necessary for these associations. Two non-contiguous regions of RB were found to be essential for complex formation with adenovirus E1A or SV40 large T antigen. These two regions are found between amino acids 393 and 572 and 646 and 772. Interestingly, these binding sites on RB overlap with the positions of naturally occurring, inactivating mutations of the RB gene. These results strongly suggest that these viral oncoproteins are targeting a protein domain that is an important site in the normal function of the RB protein. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 9. PMID:2138977

  11. Truncation of the COOH-terminal region of the paramyxovirus SV5 fusion protein leads to hemifusion but not complete fusion

    PubMed Central

    1996-01-01

    The role of the simian virus 5 (SV5) fusion (F) protein 20 residue COOH- terminal region, thought to represent the cytoplasmic tail, in fusion activity was examined by constructing a series of COOH-terminal truncation mutants. When the altered F proteins were expressed in eukaryotic cells, by using the vaccinia virus-T7 transient expression system, all the F proteins exhibited similar intracellular transport properties and all were expressed abundantly on the cell surface. Quantitative and qualitative cell fusion assays indicated that all of the F protein COOH-terminal truncation mutants mediated lipid mixing with similar kinetics and efficiency as that of wild-type F protein. However, the cytoplasmic content mixing activity decreased in parallel with the extent of the deletion in the F protein COOH-terminal truncation mutants. These data indicate that it is possible to separate the presumptive early step in the fusion reaction, hemifusion, and the final stage of fusion, content mixing, and that the presence of the F protein COOH-terminal region is important for the final steps of fusion. PMID:8858164

  12. Study of combined effects of sediment rheology and basement focusing in an unbounded viscoelastic medium using P-SV-wave finite-difference modelling

    NASA Astrophysics Data System (ADS)

    Narayan, Jay; Kumar, Vinay

    2014-12-01

    This paper consists of two parts. First, a fourth-order-accurate staggered-grid finite-difference (FD) program for simulation of P-SV-wave in viscoelastic medium is presented. The incorporated realistic damping is based on GMB-EK-model. The accuracy of program is validated by comparing computed phase-velocity and quality-factors with same based on GMB-EK-model and Futterman's relations. The second part of paper presents the combined effects of sediment damping and synclinal basement focusing (SBT) on ground motion. The results reveal SBT focusing, mode conversion and diffraction of incident waves. The response of elastic SBT model reveals an increase of spectral amplification with increasing frequency. The viscoelastic response of SBT model reveals that a particular frequency may get largest amplification for a particular set of values for damping, focal-length and distance from tip of the SBT. This frequency-dependent amplification may explain mysterious damage reported in some past earthquakes if predominantly amplified frequency matches natural frequency of damaged structures.

  13. Cell adhesion markers are expressed by a stable human endothelial cell line transformed by the SV40 large T antigen under vimentin promoter control.

    PubMed

    Vicart, P; Testut, P; Schwartz, B; Llorens-Cortes, C; Perdomo, J J; Paulin, D

    1993-10-01

    Markers of endothelium have been studied in a new endothelial cell line derived from human umbilical cord vein cells by microinjection of a recombinant gene that includes a deletion mutant of the human vimentin gene regulatory region controlling the large T and small t antigen coding region of the SV40 virus. In culture, this immortalized venous endothelial cell line (IVEC) demonstrated morphological characteristics of endothelium; uptake of acetylated low density lipoprotein and presence of the Factor VIII-related antigen. Treatment of IVEC cells with Interleukin-1 beta (IL-1 beta) at 10 U.ml-1 activates the expression of cell adhesion molecules such as endothelial leucocyte adhesion molecule (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), as observed in primary culture. Prostacyclin secretion was induced in the IVEC cells by 100 nM PMA treatment and thrombin at 0.5 U/ml. Angiotensin converting enzyme (ACE) activity detected in IVEC cells was present but lower than ACE activity in primary endothelial cells and was completely blocked by enalaprilat (1 microM), a specific ACE inhibitor. The presence of ACE mRNA was also demonstrated in IVEC cells by RT-PCR amplification. Our data demonstrate that endothelial cells immortalized by use of this recombinant gene retain the morphological organization and numerous differentiated properties of endothelium.

  14. Interphase fish analysis of cell cycle genes in asbestos-treated human mesothelial cells (HMC), SV40-transformed HMC (MeT-5A) and mesothelioma cells (COLO).

    PubMed

    Dopp, Elke; Poser, Ina; Papp, Thilo

    2002-01-01

    The epidemiologic association between asbestos exposure and human malignant mesothelioma is well established. However, the molecular mechanisms linking asbestos exposure of humans and the subsequent mesothelioma formation is not well understood. The most frequent genetic changes found so far in human malignant mesothelioma (HMM) are deletions and point mutations in the tumor suppressor genes p16INK4a and NF2. Whereas homozygous deletions appear to be the predominant mechanism leading to p16/CDKN2A inactivation, inactivating point mutations coupled with allelic loss mainly occur at the NF2 locus. In the present study, asbestos-treated human mesothelial cells (HMC), SV40-transformed human mesothelial cells (MeT-5A) and a human mesothelioma cell line (COLO) were investigated for genetic changes of cell cycle genes (cyclin D1, p16INK4a, RB1, CDK2) using multicolor fluorescence in situ hybridization (mFISH) in interphase cells. The results show that cyclin D1 is unaffected in all investigated cells. The p16INK4a gene locus was shown to be mutated in COLO cells but not in HMC. After labeling of CDK2 and RB1, hemizygous loss of one allele of each gene was observed in asbestos-treated HMC whereas gene amplification of these genes was detectable in MeT-5A and COLO cells. Our data indicate that disarrangement of the RB1 dependent pathway seems to be involved in mesothelioma formation.

  15. First molecular data and the phylogenetic position of the millipede-like centipede Edentistoma octosulcatum Tömösváry, 1882 (Chilopoda: Scolopendromorpha: Scolopendridae).

    PubMed

    Vahtera, Varpu; Edgecombe, Gregory D

    2014-01-01

    Edentistoma octosulcatum Tömösváry, 1882, is a rare, superficially millipede-like centipede known only from Borneo and the Philippines. It is unique within the order Scolopendromorpha for its slow gait, robust tergites, and highly modified gizzard and mandible morphology. Not much is known about the biology of the species but it has been speculated to be arboreal with a possibly vegetarian diet. Until now its phylogenetic position within the subfamily Otostigminae has been based only on morphological characters, being variably ranked as a monotypic tribe (Arrhabdotini) or classified with the Southeast Asian genus Sterropristes Attems, 1934. The first molecular data for E. octosulcatum sourced from a newly collected specimen from Sarawak were analysed with and without morphology. Parsimony analysis of 122 morphological characters together with two nuclear and two mitochondrial loci resolves Edentistoma as sister group to three Indo-Australian species of Rhysida, this clade in turn grouping with Ethmostigmus, whereas maximum likelihood and parsimony analyses of the molecular data on their own ally Edentistoma with species of Otostigmus. A position of Edentistoma within Otostigmini (rather than being its sister group as predicted by the Arrhabdotini hypothesis) is consistently retrieved under different analytical conditions, but support values within the subfamily remain low for most nodes. The species exhibits strong pushing behaviour, suggestive of burrowing habits. Evidence against a suggested vegetarian diet is provided by observation of E. octosulcatum feeding on millipedes in the genus Trachelomegalus.

  16. Host proteins that bind to or mimic SV40 large T antigen: using antibodies to look at protein interactions and their significance

    PubMed Central

    Mole, S. E.; Gannon, J. V.; Anton, I. A.; Ford, M. J.; Lane, D. P.

    1989-01-01

    The papovavirus SV40 is able to induce tumours in susceptible hosts and will transform cells in vitro. Its major early protein, large T antigen, is required for viral DNA synthesis, both in vivo and in vitro, and is also responsible for the oncogenic action of the virus. We have made use of an extensive library of anti-T monoclonal antibodies to investigate the cellular effects of T. Large T shares an antigenic determinant with a growth-regulated host protein, p68, which is a member of an expanding super-family of helicases with particular homology to the translation initiation factor elF-4A. We have also studied the binding and interaction of large T with two particular host components: the replicative enzyme DNA polymerase α and the proto-oncogene p53. These two proteins bind to similar regions of T and exert similar effects on its antigenic structure. We found that p53 can block the binding of DNA polymerase α to T as well as co-existing with DNA polymerase α in a trimeric complex with T. This suggests that these interactions may be important in the oncogenic and replicative action of large T.

  17. Uncatalyzed assembly of spherical particles from SV40 VP1 pentamers and linear dsDNA incorporates both low and high cooperativity elements

    SciTech Connect

    Mukherjee, Santanu; Kler, Stanislav; Oppenheim, Ariella; Zlotnick, Adam

    2010-02-05

    The capsid of SV40 virion is comprised of 72 pentamers of the major capsid protein, VP1. We examined the synergism between pentamer-pentamer interaction and pentamer-DNA interaction using a minimal system of purified VP1 and a linear dsDNA 600-mer, comparing electrophoresis with electron microscopy and size exclusion chromatography. At low VP1/DNA ratios, large tubes were observed that apparently did not survive native agarose gel electrophoresis. As the VP1 concentration increased, electrophoretic migration was slower and tubes were replaced by 200 A diameter particles and excess free pentamer. At high VP1/DNA ratios, a progressively larger fraction of particles was similar to 450 A diameter virions. VP1 association with DNA is very strong compared to the concentrations in these experiments yet, paradoxically, stable complexes appear only at high ratios of VP1 to DNA. These data suggest a DNA saturation-dependent nucleation event based on non-specific pentamer-DNA interaction that controls assembly and the ultimate capsid geometry.

  18. Effects of postirradiation temperature on the yields of radiation-induced single- and double-strand breakage in SV40 DNA

    SciTech Connect

    Jones, G.D.D.; Boswell, T.V.; Ward, J.F.

    1994-05-01

    The effects of postirradiation holding temperature on the yields of radiation-induced single- and double-strand breaks (SSBs and DSBs) in SV40 DNA have been measured by agarose gel electrophoresis. When the DNA is held at low temperatures ({<=}2{degrees}C) before and during electrophoresis, the measured yields of radiation-induced SSBs and DSBs are twofold less than in samples exposed to room temperature. In contrast, if the DNA is incubated at 37{degrees}C overnight, the yield of DSB`s increases twofold over the room temperature assay, while the SSB yield increases only to a small extent ({<=}20%). From a comparison of the various yields, we suggest that low temperature stabilizes radiation-induced labile sites, and that the increased yield of DSBs at 37{degrees}C is due either to the recruitment of spatially separate SSBs as DSBs by duplex melting, or to labile sites generating DSBs. The different routes to DSB formation are kinetically distinct. We conclude that room-temperature electrophoresis measures all SSBs including those from labile sites. 16 refs., 4 figs., 1 tab.

  19. PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities.

    PubMed

    Hu, Meng; Yuan, Shuofeng; Ye, Zi-Wei; Singh, Kailash; Li, Cun; Shuai, Huiping; Fai, Ng; Chow, Billy K C; Chu, Hin; Zheng, Bo-Jian

    2017-01-22

    Substitutions in the PA N-terminus (PAN) of influenza A viruses (IAVs) are associated with viral pathogenicity. During our previous study that identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase activity and the endonuclease activity when compared to those of the wild type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 IAV.

  20. Carbon nanotube IR detectors (SV)

    SciTech Connect

    Leonard, F. L.

    2012-03-01

    Sandia National Laboratories (Sandia) and Lockheed Martin Corporation (LMC) collaborated to (1) evaluate the potential of carbon nanotubes as channels in infrared (IR) photodetectors; (2) assemble and characterize carbon nanotube electronic devices and measure the photocurrent generated when exposed to infrared light;(3) compare the performance of the carbon nanotube devices with that of traditional devices; and (4) develop and numerically implement models of electronic transport and opto-electronic behavior of carbon nanotube infrared detectors. This work established a new paradigm for photodetectors.

  1. Sensitivity of clear-sky direct radiative effect of the aerosol to micro-physical properties by using 6SV radiative transfer model: preliminary results

    NASA Astrophysics Data System (ADS)

    Bassani, Cristiana; Tirelli, Cecilia; Manzo, Ciro; Pietrodangelo, Adriana; Curci, Gabriele

    2015-04-01

    The aerosol micro-physical properties are crucial to analyze their radiative impact on the Earth's radiation budget [IPCC, 2007]. The 6SV model, last generation of the Second Simulation of a Satellite Signal in the Solar Spectrum (6S) radiative transfer code [Kotchenova et al., 2007; Vermote et al., 1997] has been used to perform physically-based atmospheric correction of hyperspectral airborne and aircraft remote sensing data [Vermote et al., 2009; Bassani et al. 2010; Tirelli et al., 2014]. The atmospheric correction of hyperspectral data has been shown to be sensitive to the aerosol micro-physical properties, as reported in Bassani et al., 2012. The role of the aerosol micro-physical properties on the accuracy of the atmospheric correction of hyperspectral data acquired over water and land targets is investigated within the framework of CLAM-PHYM (Coasts and Lake Assessment and Monitoring by PRISMA HYperspectral Mission) and PRIMES (Synergistic use of PRISMA products with high resolution meteo-chemical simulations and their validation on ground and from satellite) projects, both funded by Italian Space Agency (ASI). In this work, the results of the radiative field of the Earth/Atmosphere coupled system simulated by using 6SV during the atmospheric correction of hyperspectral data are presented. The analysis of the clear-sky direct radiative effect is performed considering the aerosol micro-physical properties used to define the aerosol model during the atmospheric correction process. In particular, the AERONET [Holben et al., 1998] and FLEXAOD [Curci et al., 2014] micro-physical properties are used for each image to evaluate the contribution of the size distribution and refractive index of the aerosol type on the surface reflectance and on the direct radiative forcing. The results highlight the potential of the hyperspectral remote sensing data for atmospheric studies as well as for environmental studies. Currently, the future hyperspectral missions, such as the

  2. Geophysical fingerprints of shallow cultural structures from microgravity and GPR measurements in the Church of St. George, Svätý Jur, Slovakia

    NASA Astrophysics Data System (ADS)

    Panisova, Jaroslava; Murín, Igor; Pašteka, Roman; Haličková, Jana; Brunčák, Peter; Pohánka, Vladimír; Papčo, Juraj; Milo, Peter

    2016-04-01

    Recording of the historic edifice using the state-of-the-art geodetic and geophysical techniques brings easier visualisation in form of a three-dimensional (3D) model, thus allowing better understanding of its historical construction by the public and non-experts. We have applied this approach at the Church of St. George, one of the most significant religious buildings in south-western Slovakia, which dominates a silhouette of the town Svätý Jur. The geodetic survey allowed to record the actual state of the church. The church exterior was surveyed using a total station. Due to the intricate shape of the interior components of the church, it was decided to use a terrestrial laser scanner to generate the point cloud data, which were processed into floor plan, elevations, sectional 2D drawings and 3D model. The geophysical survey was carried out in the interior of the church in order to identify potential subsurface anthropogenic structures. Microgravity and ground penetrating radar (GPR) methods were selected as the most effective geophysical tools for such task. In microgravity data processing we focused on the calculation and removal of the gravitational effects of the building masses. The main negative gravity anomalies of interest in the nave, which also have been confirmed by GPR measurements, are interpreted as medieval crypts. Another very important outcome of the geophysical survey is the discovery of the west wall foundations of the oldest Romanesque construction. From each geophysical data acquired we derived 3D polygonal models, which are compared to achieve more realistic picture of the subsurface structures. Verification of these structures by means of archaeological excavation has not been carried out yet.

  3. Immortalization of multipotent growth-factor dependent hemopoietic progenitors from mice transgenic for GATA-1 driven SV40 tsA58 gene.

    PubMed Central

    Cairns, L A; Crotta, S; Minuzzo, M; Moroni, E; Granucci, F; Nicolis, S; Schiró, R; Pozzi, L; Giglioni, B; Ricciardi-Castagnoli, P

    1994-01-01

    The transcription factor GATA-1 is required for the normal development of erythroid cells. GATA-1 is also expressed in other hemopoietic cells, suggesting that it might be initially activated in a multipotent progenitor. To immortalize GATA-1-expressing progenitors, we generated mice transgenic for a thermosensitive SV40 T gene, driven by the GATA-1 promoter-enhancer. Immortalized marrow cells grow in culture at 32 degrees C but not at 38 degrees C, and are dependent on erythropoietin (Epo) or interleukin 3 (IL-3). Epo dependent cells express hemoglobin, high levels of GATA-1, GATA-2 and NF-E2 p45 mRNAs, and are positive for stem cell antigen 2 (Sca-2) and the early myeloid marker ER-MP12. IL-3 dependent cells can be derived from Epo dependent lines, and are hemoglobin-, Sca-2- and ER-MP12-negative, have low GATA-1 and NF-E2 p45 mRNA levels, and express myeloid markers Mac-1, F4/80 and Gr-1. Brief treatment of Epo dependent cells with myeloid growth factors (plus Epo) leads to the induction of Mac-1, F4/80 and Gr-1, concomitant with the disappearance from most cells of Sca-2, ER-MP12 and GATA-1 driven T antigen nuclear expression. Thus, the immortalized Epo dependent cells have the property of a progenitor capable of differentiation towards either the erythroid or myeloid lineages. These cells initiate transcription of a proportion of GATA-1 RNA molecules at an upstream promoter, previously known to be expressed only in testis cells. Images PMID:7925299

  4. Establishment of SV40 large T antigen-immortalized bovine liver sinusoidal cell lines and their immunological responses to deoxynivalenol and lipopolysaccharide.

    PubMed

    Yoshioka, Miyako; Takenouchi, Takato; Kitani, Hiroshi; Okada, Hiroyuki; Yamanaka, Noriko

    2016-12-01

    Immortalized bovine sinusoidal cell lines provide useful tools to study the immunological responses in the liver to the gastrointestinal tract-derived toxic substances, which may cause systemic symptoms in the affected livestock. Here, we established two immortalized bovine liver sinusoidal cell lines, endothelial-like B46, and myofibroblast-like A26, from primary cultures of bovine liver cells by the transfection with SV40 large T antigen. The pro-inflammatory cytokine responses in these cell lines to deoxynivalenol (DON) and lipopolysaccharide (LPS) were then compared to those in the primary bovine Kupffer cells (BKC). BKC were highly responsive to LPS, showing increased levels of IL-1α, IL-1β, IL-6, and TNF-α mRNA 3 h after stimulation. DON induced similar pro-inflammatory cytokine responses in BKC, except for IL-6. The endothelial B46 cells exhibited upregulation of IL-1α, IL-1β, and IL-6 3 h after stimulation by LPS. In contrast to the stimulation by LPS, B46 had relatively low pro-inflammatory cytokine responses to DON, except for IL-1α, which was moderately induced at 3 h and increased at 24 h after stimulation. The myofibroblast-like A26 cells exhibited low responses in the induction of pro-inflammatory cytokines to LPS or DON; however, the expression of IL-6 was significantly observed 3 h after DON stimulation. Our results suggest that bovine liver sinusoidal cells have distinctive pro-inflammatory cytokine responses against harmful substances, and these immune responses might determine the consequence of systemic inflammations in the diseased animal.

  5. Home cage activity and activity-based measures of anxiety in 129P3/J, 129X1/SvJ and C57BL/6J mice.

    PubMed

    Tang, Xiangdong; Sanford, Larry D

    2005-01-31

    We investigated the home cage activity and emotional behavior in mouse strains used as background for many studies of altered genes [C57BL/6J (B6, n=20), 129X1/SvJ (X1, n=20) and 129P3/J (P3, n=19)]. In their home cages, X1 and P3 mice exhibited less locomotion than did B6 mice, and the X1 mice showed significantly greater rearing than B6 and P3 mice did. A battery of three tests conducted in an open field (open field, emergence and novel object) revealed strain rankings of B6>X1>P3 or B6>X1=P3 in most activity variables. Significant correlations were found between home cage activity and activity in each of three tests, but not in all observation periods. Strain rankings on the elevated zero maze test were B6=X1>P3 in the number of stretched-attend body postures (SAPS) during the initial 6-min exposure for naive mice. Naive and nonnaive mice showed significantly different behaviors on the elevated zero maze. The results suggest that rankings on anxiety are P3>X1>B6 and that B6 mice have greater exploration in a novel environment compared with X1 and P3 mice. However, anxiety-like behaviors differed among strains in open-field-based tests and in the zero maze, and testing experience impacted performance on the zero maze. The findings illustrate that test variations and experience can influence performance and suggest the need for the consideration of how these factors interact with background strains in assessing gene-altered mice.

  6. Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A

    PubMed Central

    Matagne, A; Margineanu, D-G; Kenda, B; Michel, P; Klitgaard, H

    2008-01-01

    Background and purpose: Screening of 12 000 compounds for binding affinity to the synaptic vesicle protein 2A (SV2A), identified a high-affinity pyrrolidone derivative, brivaracetam (ucb 34714). This study examined its pharmacological profile in various in vitro and in vivo models of seizures and epilepsy, to evaluate its potential as a new antiepileptic drug. Experimental approach: The effects of brivaracetam and levetiracetam on epileptiform activity and seizure expression were examined in rat hippocampal slices, corneally kindled mice, audiogenic seizure–susceptible mice, maximal electroshock and pentylenetetrazol seizures in mice, hippocampal-kindled rats, amygdala-kindled rats and genetic absence epilepsy rats. Key results: Brivaracetam and levetiracetam reduced epileptiform responses in rat hippocampal slices, brivaracetam being most potent. Brivaracetam also differed from levetiracetam by its ability to protect against seizures in normal mice induced by a maximal electroshock or maximal dose of pentylenetetrazol. In corneally kindled mice and hippocampal-kindled rats, brivaracetam induced potent protection against secondarily generalized motor seizures and showed anti-kindling properties superior to levetiracetam. In amygdala-kindled rats, brivaracetam induced a significant suppression in motor-seizure severity and, contrary to levetiracetam, reduced the after-discharge at a higher dose. Audiogenic seizure–susceptible mice were protected more potently against the expression of clonic convulsions by brivaracetam than by levetiracetam. Brivaracetam induced a more complete suppression of spontaneous spike-and-wave discharges in genetic absence epilepsy rats than levetiracetam. Conclusions and implications: Brivaracetam has higher potency and efficacy than levetiracetam as an anti-seizure and anti-epileptogenic agent in various experimental models of epilepsy, and a wide therapeutic index. PMID:18500360

  7. Computerized segmentation algorithm with personalized atlases of murine MRIs in a SV40 large T-antigen mouse mammary cancer model

    NASA Astrophysics Data System (ADS)

    Sibley, Adam R.; Markiewicz, Erica; Mustafi, Devkumar; Fan, Xiaobing; Conzen, Suzanne; Karczmar, Greg; Giger, Maryellen L.

    2016-03-01

    Quantities of MRI data, much larger than can be objectively and efficiently analyzed manually, are routinely generated in preclinical research. We aim to develop an automated image segmentation and registration pipeline to aid in analysis of image data from our high-throughput 9.4 Tesla small animal MRI imaging center. T2-weighted, fat-suppressed MRIs were acquired over 4 life-cycle time-points [up to 12 to 18 weeks] of twelve C3(1) SV40 Large T-antigen mice for a total of 46 T2-weighted MRI volumes; each with a matrix size of 192 x 256, 62 slices, in plane resolution 0.1 mm, and slice thickness 0.5 mm. These image sets were acquired with the goal of tracking and quantifying progression of mammary intraepithelial neoplasia (MIN) to invasive cancer in mice, believed to be similar to ductal carcinoma in situ (DCIS) in humans. Our segmentation algorithm takes 2D seed-points drawn by the user at the center of the 4 co-registered volumes associated with each mouse. The level set then evolves in 3D from these 2D seeds. The contour evolution incorporates texture information, edge information, and a statistical shape model in a two-step process. Volumetric DICE coefficients comparing the automatic with manual segmentations were computed and ranged between 0.75 and 0.58 for averages over the 4 life-cycle time points of the mice. Incorporation of these personalized atlases with intra and inter mouse registration is expected to enable locally and globally tracking of the morphological and textural changes in the mammary tissue and associated lesions of these mice.

  8. The rate of nuclear cytoplasmic protein transport is determined by the casein kinase II site flanking the nuclear localization sequence of the SV40 T-antigen.

    PubMed Central

    Rihs, H P; Jans, D A; Fan, H; Peters, R

    1991-01-01

    We have previously demonstrated [Rihs, H.-P. and Peters, R. (1989) EMBO J., 8, 1479-1484] that the nuclear transport of recombinant proteins in which short fragments of the SV40 T-antigen are fused to the amino terminus of Escherichia coli beta-galactosidase is dependent on both the nuclear localization sequence (NLS, T-antigen residues 126-132) and a phosphorylation-site-containing sequence (T-antigen residues 111-125). While the NLS determines the specificity, the rate of transport is controlled by the phosphorylation-site-containing sequence. The present study furthers this observation and examines the role of the various phosphorylation sites. Purified, fluorescently labeled recombinant proteins were injected into the cytoplasm of Vero or hepatoma (HTC) cells and the kinetics of nuclear transport measured by laser microfluorimetry. By replacing serine and threonine residues known to be phosphorylated in vivo, we identified the casein kinase II (CK-II) site S111/S112 to be the determining factor in the enhancement of the transport. Either of the residues 111 or 112 was sufficient to elicit the maximum transport enhancement. The other phosphorylation sites (S120, S123, T124) had no influence on the transport rate. Examination of the literature suggested that many proteins harboring a nuclear localization sequence also contain putative CK-II sites at a distance of approximately 10-30 amino acid residues from the NLS. CK-II has been previously implicated in the transmission of growth signals to the nucleus. Our results suggest that CK-II may exert this role by controlling the rate of nuclear protein transport. Images PMID:1848177

  9. Online derivatization for hourly measurements of gas- and particle-phase semi-volatile oxygenated organic compounds by thermal desorption aerosol gas chromatography (SV-TAG)

    NASA Astrophysics Data System (ADS)

    Isaacman, G.; Kreisberg, N. M.; Yee, L. D.; Worton, D. R.; Chan, A. W. H.; Moss, J. A.; Hering, S. V.; Goldstein, A. H.

    2014-12-01

    Laboratory oxidation studies have identified a large number of oxygenated organic compounds that can be used as tracers to understand sources and oxidation chemistry of atmospheric particulate matter. Quantification of these compounds in ambient environments has traditionally relied on low-time-resolution collection of filter samples followed by offline sample treatment with a derivatizing agent to allow analysis by gas chromatography of otherwise non-elutable organic chemicals with hydroxyl groups. We present here an automated in situ instrument for the measurement of highly polar organic semi-volatile and low-volatility compounds in both the gas- and particle-phase with hourly quantification of mass concentrations and gas-particle partitioning. The dual-cell semi-volatile thermal desorption aerosol gas chromatograph (SV-TAG) with derivatization collects particle-only and combined particle-plus-vapor samples on two parallel sampling cells that are analyzed in series by thermal desorption into helium saturated with derivatizing agent. Introduction of MSTFA (N-methyl-N-(trimethylsilyl)trifluoroacetamide), a silylating agent, yields complete derivatization of all tested compounds, including alkanoic acids, polyols, diacids, sugars, and multifunctional compounds. In laboratory tests, derivatization is found to be highly reproducible (< 3% variability). During field deployment, a regularly injected internal standard is used to correct for variability in detector response, consumption of the derivatization agent, desorption efficiency, and transfer losses. Error in quantification from instrument fluctuations is found to be less than 10% for hydrocarbons and less than 15% for all oxygenates for which a functionally similar internal standard is available, with an uncertainty of 20-25% in measurements of particle fraction. After internal standard corrections, calibration curves are found to be linear for all compounds over the span of 1 month, with comparable response on

  10. On-line derivatization for hourly measurements of gas- and particle-phase Semi-Volatile oxygenated organic compounds by Thermal desorption Aerosol Gas chromatography (SV-TAG)

    NASA Astrophysics Data System (ADS)

    Isaacman, G.; Kreisberg, N. M.; Yee, L. D.; Worton, D. R.; Chan, A. W. H.; Moss, J. A.; Hering, S. V.; Goldstein, A. H.

    2014-07-01

    Laboratory oxidation studies have identified a large number of oxygenated organic compounds that can be used as tracers to understand sources and oxidation chemistry of atmospheric particulate matter. Quantification of these compounds in ambient environments has traditionally relied on low time-resolution collection of filter samples followed by offline sample treatment with a derivatizing agent to allow analysis by gas chromatography of otherwise non-elutable organic chemicals with hydroxyl groups. We present here an automated in situ instrument for the measurement of highly polar organic semi-volatile and low-volatility compounds in both the gas- and particle-phase with hourly time-resolution. The dual-cell Semi-Volatile Thermal desorption Aerosol Gas chromatograph (SV-TAG) with derivatization collects particle-only and combined particle-plus-vapor samples on two parallel sampling cells that are analyzed in series by thermal desorption into helium saturated with derivatizing agent. Introduction of MSTFA, a silylating agent, yields complete derivatization of all tested compounds, including alkanoic acids, polyols, diacids, sugars, and multifunctional compounds. In laboratory tests, derivatization is found to be highly reproducible (< 3% variability). During field deployment, a regularly injected internal standard is used to correct for variability in detector response, derivatization efficiency, desorption efficiency, and transfer efficiency. Error in quantification from instrument fluctuations is found to be less than 10% for hydrocarbons and less than 15% for all oxygenates for which a functionally similar internal standard is available. After internal standard corrections, calibration curves are found to be linear for all compounds over the span of one month with comparable response on both of the parallel sampling cells.

  11. The mdx Mutation in the 129/Sv Background Results in a Milder Phenotype: Transcriptome Comparative Analysis Searching for the Protective Factors

    PubMed Central

    Calyjur, Priscila Clara; Almeida, Camila de Freitas; Ayub-Guerrieri, Danielle; Ribeiro, Antonio Fernando; Fernandes, Stephanie de Alcântara; Ishiba, Renata; dos Santos, Andre Luis Fernandes; Onofre-Oliveira, Paula; Vainzof, Mariz

    2016-01-01

    The mdx mouse is a good genetic and molecular murine model for Duchenne Muscular Dystrophy (DMD), a progressive and devastating muscle disease. However, this model is inappropriate for testing new therapies due to its mild phenotype. Here, we transferred the mdx mutation to the 129/Sv strain with the aim to create a more severe model for DMD. Unexpectedly, functional analysis of the first three generations of mdx129 showed a progressive amelioration of the phenotype, associated to less connective tissue replacement, and more regeneration than the original mdxC57BL. Transcriptome comparative analysis was performed to identify what is protecting this new model from the dystrophic characteristics. The mdxC57BL presents three times more differentially expressed genes (DEGs) than the mdx129 (371 and 137 DEGs respectively). However, both models present more overexpressed genes than underexpressed, indicating that the dystrophic and regenerative alterations are associated with the activation rather than repression of genes. As to functional categories, the DEGs of both mdx models showed a predominance of immune system genes. Excluding this category, the mdx129 model showed a decreased participation of the endo/exocytic pathway and homeostasis categories, and an increased participation of the extracellular matrix and enzymatic activity categories. Spp1 gene overexpression was the most significant DEG exclusively expressed in the mdx129 strain. This was confirmed through relative mRNA analysis and osteopontin protein quantification. The amount of the 66 kDa band of the protein, representing the post-translational product of the gene, was about 4,8 times higher on western blotting. Spp1 is a known DMD prognostic biomarker, and our data indicate that its upregulation can benefit phenotype. Modeling the expression of the DEGs involved in the mdx mutation with a benign course should be tested as a possible therapeutic target for the dystrophic process. PMID:26954670

  12. Activation of histamine H4 receptor inhibits TNFα/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells.

    PubMed

    Stegajev, Vasili; Kouri, Vesa-Petteri; Salem, Abdelhakim; Rozov, Stanislav; Stark, Holger; Nordström, Dan C E; Konttinen, Yrjö T

    2014-12-01

    Apoptosis is involved in the pathogenesis of Sjögren's syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H₄R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H₄R signaling affect apoptosis of human salivary gland epithelial cell. Simian virus 40-immortalized acinar NS-SV-AC cells were cultured in serum-free keratinocyte medium ± histamine H₄R agonist HST-10. Expression and internalization of H₄R were studied by immunofluorescence staining ± clathrin inhibitor methyl-β-cyclodextrin (MβCD). Apoptosis induced using tumor necrosis factor-α with nuclear factor-κB inhibitor IMD-0354 was studied using phase contrast microscopy, Western blot, flow cytometry and polymerase chain reaction (qRT-PCR). HST-10-stimulated H₄R internalization was inhibited by MβCD. Western blotting revealed diminished phosphorylated c-Jun N-terminal kinase JNK, but unchanged levels of phosphorylated extracellular signal regulated kinase pERK1/2 in H₄R-stimulated samples compared to controls. qRT-PCR showed up-regulated expression of anti-apoptotic B cell lymphoma-extra large/Bcl-xL mRNAs and proteins, whereas pro-apoptotic Bcl-2-associated X protein/BAX remained unchanged in H4R-stimulated samples. H₄R stimulation diminished cleavage of PARP and flow cytometry showed significant dose-dependent inhibitory effect of H₄R stimulation on apoptosis. As far as we know this is the first study showing inhibitory effect of H₄R activation on apoptosis of human salivary gland cells. Diminished H₄R-mediated activation may contribute to loss of immune tolerance in autoimmune diseases and in SS in particular.

  13. Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain

    SciTech Connect

    Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A.

    2011-06-01

    With the aim of forming the ‘lock-washer’ conformation of the origin-binding domain of SV40 large T antigen in solution, using structure-based analysis an intermolecular disulfide bridge was engineered into the origin-binding domain to generate higher order oligomers in solution. The 1.7 Å resolution structure shows that the mutant forms a spiral in the crystal and has the de novo disulfide bond at the protein interface, although structural rearrangements at the interface are observed relative to the wild type. The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS–PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner.

  14. Application of SV40 T-transformed human corneal epithelial cells to evaluate potential irritant chemicals for in vitro alternative eye toxicity.

    PubMed

    Kim, Cho-Won; Park, Geon-Tae; Bae, Ok-Nam; Noh, Minsoo; Choi, Kyung-Chul

    2016-01-01

    Assessment of eye irritation potential is important to human safety, and it is necessary for various cosmetics and chemicals that may contact the human eye. Until recently, the Draize test was considered the standard method for estimating eye irritation, despite its disadvantages such as the need to sacrifice many rabbits for subjective scoring. Thus, we investigated the cytotoxicity and inflammatory response to standard eye irritants using SV40 T-transformed human corneal epithelial (SHCE) cells as a step toward development of an animal-free alternative eye irritation test. MTT and NRU assays of cell viability were performed to investigate the optimal experimental conditions for SHCE cell viability when cells were exposed to sodium dodecyl sulfate (SDS) as a standard eye irritant at 6.25×10(-3) to 1×10(-1)%. Additionally, cell viability of SHCE cells was examined in response to six potential eye irritants, benzalkonium chloride, dimethyl sulfoxide, isopropanol, SDS, Triton X-100 and Tween 20 at 5×10(-3) to 1×10(-1)%. Finally, we estimated the secretion level of cytokines in response to stimulation by eye irritants in SHCE cells. SHCE cells showed a good response to potential eye irritants when the cells were exposed to potential irritants for 10min at room temperature (RT), and cytokine production increased in a concentration-dependent manner, indicating that cytotoxicity and cytokine secretion from SHCE cells may be well correlated with the concentrations of irritants. Taken together, these results suggest that SHCE cells could be an excellent alternative in vitro model to replace in vivo animal models for eye irritation tests.

  15. Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism.

    PubMed

    Zhao, Wei; Zhong, Yi; Yuan, Hua; Wang, Jin; Zheng, Huajun; Wang, Ying; Cen, Xufeng; Xu, Feng; Bai, Jie; Han, Xiaobiao; Lu, Gang; Zhu, Yongqiang; Shao, Zhihui; Yan, Han; Li, Chen; Peng, Nanqiu; Zhang, Zilong; Zhang, Yunyi; Lin, Wei; Fan, Yun; Qin, Zhongjun; Hu, Yongfei; Zhu, Baoli; Wang, Shengyue; Ding, Xiaoming; Zhao, Guo-Ping

    2010-10-01

    Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimycobacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10,236,715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9,228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel 'quasi-core' with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.

  16. Update on Program Review Activities. Report 10-11

    ERIC Educational Resources Information Center

    Jones, Jessika

    2010-01-01

    Review of new degree and certificate programs proposed by the public higher education systems is a major California Postsecondary Education Commission (CPEC) activity. The Legislature, Administration, and the Legislative Analyst's Office consider program review to be one of CPEC's most important responsibilities. In the past six months, staff have…

  17. European Scientific Notes. Volume 37, Numbers 10/11.

    DTIC Science & Technology

    1983-11-01

    percent decrease in the intensity of space-geodetic methods for monitoring solar radiation reachipg the earth’s local crustal deformations. surface, the...1983) - and solids. The average power available 35-nm range at the Comitato Nazionale and the predicted high efficiency of Energia Nucleare laboratory in...the David W. Taylor Naval gated for transmittance. These measure- Ship Research and Development Center, ments are important for solar energy Bethesda

  18. Environmental Scanning Workshop (Lansing, Michigan, June 10-11, 1992).

    ERIC Educational Resources Information Center

    Morrison, James L.

    This publication presents an environmental scanning workshop for administrators in higher education institutions to help them incorporate environmental scanning into their planning and anticipation of future events. In particular, the workshop shows how to establish and sustain a comprehensive environmental scanning system and how to use the…

  19. Assessment of root uptake and systemic vine-transport of Salmonella enterica sv. Typhimurium by melon (Cucumis melo) during field production.

    PubMed

    Lopez-Velasco, Gabriela; Sbodio, Adrian; Tomás-Callejas, Alejandro; Wei, Polly; Tan, Kin Hup; Suslow, Trevor V

    2012-08-01

    Among melons, cantaloupes are most frequently implicated in outbreaks and surveillance-based recalls due to Salmonella enterica. There is limited but compelling evidence that associates irrigation water quality as a significant risk of preharvest contamination of melons. However, the potential for root uptake from water and soil and subsequent systemic transport of Salmonella into melon fruit is uncharacterized. The aim of this work was to determine whether root uptake of S. enterica results in systemic transport to fruit at high doses of applied inoculum through sub-surface drip and furrow irrigation during field production of melons. Cantaloupe and honeydew were grown under field conditions, in a silt clay loam soil using standard agronomic practices for California. An attenuated S. enterica sv. Typhimurium strain was applied during furrow irrigation and, in separate plots, buried drip-emitter lines delivered the inoculum directly into the established root zone. Contamination of the water resulted in soil contamination within furrows however Salmonella was not detected on top of the beds or around melon roots of furrow-irrigated rows demonstrating absence of detectable lateral transfer across the soil profile. In contrast, positive detection of the applied isolate occurred in soil and the rhizosphere in drip injected plots; survival of Salmonella was at least 41 days. Despite high populations of the applied bacteria in the rhizosphere, after surface disinfection, internalized Salmonella was not detected in mature melon fruit (n=485). Contamination of the applied Salmonella was detected on the rind surface of melons if fruit developed in contact with soil on the sides of the inoculated furrows. Following an unusual and heavy rain event during fruit maturation, melons collected from the central area of the beds, were shown to harbor the furrow-applied Salmonella. Delivery of Salmonella directly into the peduncle, after minor puncture wounding, resulted in detection

  20. Boletin de Informacion Educativa, Ano VI, No. 10/11 (Educational Information Bulletin, Volume VI, No. 10/11).

    ERIC Educational Resources Information Center

    Ministerio de Educacion y Cultura, Santa Fe (Argentina). Centro de Documentacion e Informacion Educativa de la Provincia de Santa Fe.

    This information bulletin is published by the Documentation and Educational Information Center in the Argentine province of Santa Fe. The bulletin reports on educational developments in the province and abroad, educational problems, statistics, legislation, documentation and information techniques, and information from international organizations.…

  1. Computed tomography coronary angiography with a consistent dose below 2 mSv using double prospectively ECG-triggered high-pitch spiral acquisition in patients with atrial fibrillation: initial experience.

    PubMed

    Wang, Qi; Qin, Jing; He, Bai; Zhou, Yin; Yang, Jun-jie; Hou, Xiao-ling; Yang, Xiao-bo; Chen, Jiu-hong; Chen, Yun-dai

    2013-08-01

    To evaluate the feasibility and imaging quality of double prospectively ECG-triggered high-pitch spiral acquisition mode (double flash mode) for coronary computed tomography angiography (CTCA) in patients with atrial fibrillation (AF). 47 patients (11 women, 36 men; mean age 64.5 ± 12.1 years) were enrolled for CTCA examinations using a dual-source CT with 2 × 128 × 0.6 mm collimation, 0.28 s rotation time and a pitch of 3.4. Double flash mode was prospectively triggered first at 60 % and later at 30 % of the R-R interval within two cardiac cycles. Image quality was evaluated using a four-point scale (1 = excellent, 4 = non-assessable). From 672 coronary artery segments, 77.5 % (521/672) was rated as score of 1, 20.8 % (140/672) as score of 2, 1.2 % (8/672) as score of 3 and 0.4 % (3/672) was rated as 'non-assessable'. The average image quality score was 1.25 ± 0.38 on a per segment basis. Mean dose-length product for CTCA was 92.6 ± 28.2 mGy cm, the effective dose was 1.30 ± 0.39 mSv (0.64-1.97 mSv). In patients with AF, double prospectively ECG-triggered high-pitch spiral acquisition mode could be a feasible and valuable scan mode for CTCA with a consistent dose below 2 mSv as well as diagnostic imaging quality.

  2. Pathologic progression of mammary carcinomas in a C3(1)/SV40 T/t-antigen transgenic rat model of human triple-negative and Her2-positive breast cancer.

    PubMed

    Hoenerhoff, M J; Shibata, M A; Bode, A; Green, J E

    2011-04-01

    The C3(1) component of the rat prostate steroid binding protein has been used to target expression of the SV40 T/t-antigen to the mammary epithelium of mice resulting in pre-neoplastic lesions that progress to invasive and metastatic cancer with molecular features of human basal-type breast cancer. However, there are major differences in the histologic architecture of the stromal and epithelial elements between the mouse and human mammary glands. The rat mammary gland is more enriched with epithelial and stromal components than the mouse and more closely resembles the cellular composition of the human gland. Additionally, existing rat models of mammary cancer are typically estrogen receptor positive and hormone responsive, unlike most genetically engineered mouse mammary cancer models. In an attempt to develop a mammary cancer model that might more closely resemble the pathology of human breast cancer, we generated a novel C3(1)/SV40 T/t-antigen transgenic rat model that developed progressive mammary lesions leading to highly invasive adenocarcinomas. However, aggressive tumor development prevented the establishment of transgenic lines. Characterization of the tumors revealed that they were primarily estrogen receptor and progesterone receptor negative, and either her2/neu positive or negative, resembling human triple-negative or Her2 positive breast cancer. Tumors expressed the basal marker K14, as well as the luminal marker K18, and were negative for smooth muscle actin. The triple negative phenotype has not been previously reported in a rat mammary cancer model. Further development of a C3(1)SV40 T/t-antigen based model could establish valuable transgenic rat lines that develop basal-type mammary tumors.

  3. Ethanol-Induced Increase of Agouti-Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J, but not 129/SvJ, Inbred Mice

    PubMed Central

    Cubero, Inmaculada; Navarro, Montserrat; Carvajal, Francisca; Lerma-Cabrera, Jose Manuel; Thiele, Todd E.

    2011-01-01

    Background The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro-opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti-related protein (AgRP), causes reductions of ethanol-reinforced lever pressing and binge-like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol-containing diet causes significant reductions of α-melanocyte stimulating hormone (α-MSH) immunoreactivity in specific brain regions of Sprague-Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and α-MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice. Methods Mice received an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg or 3.5 g/kg; mixed in 0.9% saline) or an equivolume of 0.9% saline. Two hours after injection, animals were sacrificed and their brains were processed for AgRP and α-MSH immunoreactivity. Results Results indicated that acute ethanol administration triggered a dose-dependent increase in AgRP immunoreactivity in the arcuate (ARC) of C57BL/6J mice, an effect that was not evident in the 129/SvJ strain. Although acute administration of ethanol did not influence α-MSH immunoreactivity, C57BL/6J mice had significantly greater overall α-MSH immunoreactivity in the ARC, dorsomedial, and lateral regions of the hypothalamus relative to the 129/SvJ strain. In contrast, C57BL/6J mice displayed significantly lower α-MSH immunoreactivity in the medial amygdala. Conclusions The results show that acute ethanol

  4. Guidance on the Use of Hand-Held Survey Meters for radiological Triage: Time-Dependent Detector Count Rates Corresponding to 50, 250, and 500 mSv Effective Dose for Adult Males and Adult Females

    SciTech Connect

    Bolch, W.E.; Hurtado, J.L.; Lee, C.; Manger, Ryan P; Hertel, Nolan; Burgett, E.; Dickerson, W.

    2012-01-01

    In June 2006, the Radiation Studies Branch of the Centers for Disease Control and Prevention held a workshop to explore rapid methods of facilitating radiological triage of large numbers of potentially contaminated individuals following detonation of a radiological dispersal device. Two options were discussed. The first was the use of traditional gamma cameras in nuclear medicine departments operated as makeshift wholebody counters. Guidance on this approach is currently available from the CDC. This approach would be feasible if a manageable number of individuals were involved, transportation to the relevant hospitals was quickly provided, and the medical staff at each facility had been previously trained in this non-traditional use of their radiopharmaceutical imaging devices. If, however, substantially larger numbers of individuals (100 s to 1,000 s) needed radiological screening, other options must be given to first responders, first receivers, and health physicists providing medical management. In this study, the second option of the workshop was investigated by the use of commercially available portable survey meters (either NaI or GM based) for assessing potential ranges of effective dose (G50, 50Y250, 250Y500, and 9500 mSv). Two hybrid computational phantoms were used to model an adult male and an adult female subject internally contaminated with 241Am, 60Cs, 137Cs, 131I, or 192Ir following an acute inhalation or ingestion intake. As a function of time following the exposure, the net count rates corresponding to committed effective doses of 50, 250, and 500 mSv were estimated via Monte Carlo radiation transport simulation for each of four different detector types, positions, and screening distances. Measured net count rates can be compared to these values, and an assignment of one of four possible effective dose ranges could be made. The method implicitly assumes that all external contamination has been removed prior to screening and that the measurements be

  5. Guidance on the Use of Hand-Held Survey Meters for Radiological Triage: Time-Dependent Detector Count Rates Corresponding to 50, 250, and 500 mSv Effective Dose for Adult Males and Adult Females

    PubMed Central

    Bolch, Wesley E.; Hurtado, Jorge L.; Lee, Choonsik; Manger, Ryan; Hertel, Nolan; Dickerson, William

    2013-01-01

    In June of 2006, the Radiation Studies Branch of the Centers for Disease Control and Prevention held a workshop to explore rapid methods of facilitating radiological triage of large numbers of potentially contaminated individuals following detonation of a radiological dispersal device. Two options were discussed. The first was the use of traditional gamma-cameras in nuclear medicine departments operated as make-shift whole-body counters. Guidance on this approach is currently available from the CDC. This approach is feasible if a manageable number of individuals were involved, transportation to the relevant hospitals was quickly provided, and the medical staff at each facility had been previously trained in this non-traditional use of their radiopharmaceutical imaging devices. If, however, substantially large numbers of individuals (100s to 1000s) needed radiological screening, other options must be given to first responders, first receivers, and health physicists providing medical management. In this study, the second option of the workshop was investigated – the use of commercially available portable survey meters (either NaI or GM based) for assessing potential ranges of effective dose (<50, 50–250, 250–500, and >500 mSv). Two hybrid computational phantoms were used to model an adult male and an adult female subject internally contaminated with either 241Am, 60Cs, 137Cs, 131I, and 192Ir following an acute inhalation or ingestion intake. As a function of time following the exposure, the net count rates corresponding to committed effective doses of 50, 250, and 500 mSv were estimated via Monte Carlo radiation transport simulation for each of four different detectors types, positions, and screening distances. Measured count rates can be compared to these values and an assignment of one of four possible effective dose ranges could be made. The method implicitly assumes that all external contamination has been removed prior to screening, and that the

  6. Guidance on the use of handheld survey meters for radiological triage: time-dependent detector count rates corresponding to 50, 250, and 500 mSV effective dose for adult males and adult females.

    PubMed

    Bolch, Wesley E; Hurtado, Jorge L; Lee, Choonsik; Manger, Ryan; Burgett, Eric; Hertel, Nolan; Dickerson, William

    2012-03-01

    In June 2006, the Radiation Studies Branch of the Centers for Disease Control and Prevention held a workshop to explore rapid methods of facilitating radiological triage of large numbers of potentially contaminated individuals following detonation of a radiological dispersal device. Two options were discussed. The first was the use of traditional gamma cameras in nuclear medicine departments operated as makeshift wholebody counters. Guidance on this approach is currently available from the CDC. This approach would be feasible if a manageable number of individuals were involved, transportation to the relevant hospitals was quickly provided, and the medical staff at each facility had been previously trained in this non-traditional use of their radiopharmaceutical imaging devices. If, however,substantially larger numbers of individuals (100’s to 1,000’s) needed radiological screening, other options must be given to first responders, first receivers, and health physicists providing medical management. In this study, the second option of the workshop was investigated--the use of commercially available portable survey meters (either NaI or GM based) for assessing potential ranges of effective dose (< 50, 50-250, 250-500,and >500 mSv). Two hybrid computational phantoms were used to model an adult male and an adult female subject internally contaminated with 241Am, 60Cs, 137Cs, 131I, or 192Ir following an acute inhalation or ingestion intake. As a function of time following the exposure, the net count rates corresponding to committed effective doses of 50, 250, and 500 mSv were estimated via Monte Carlo radiation transport simulation for each of four different detector types, positions, and screening distances.Measured net count rates can be compared to these values, and an assignment of one of four possible effective dose ranges could be made. The method implicitly assumes that all external contamination has been removed prior to screening and that the measurements be

  7. Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage.

    PubMed Central

    Shibata, M A; Liu, M L; Knudson, M C; Shibata, E; Yoshidome, K; Bandey, T; Korsmeyer, S J; Green, J E

    1999-01-01

    The dramatic increase in apoptosis observed during the development of preneoplastic mammary lesions is associated with a significant elevation in Bax expression in C3(1)/SV40 large T antigen (TAg) transgenic mice. The significance of Bax expression during tumor progression in vivo was studied by generating double-transgenic mice carrying the C3(1)/TAg transgene and mutant alleles for bax. C3(1)/TAg transgenic mice carrying mutant bax alleles exhibited accelerated rates of tumor growth, increased tumor numbers, larger tumor mass and decreased survival rates compared with mice carrying wild-type bax. Accelerated tumorigenesis associated with the bax+/- genotype did not require the loss of function of the second bax allele. Thus, haploid insufficiency of bax is enough to accelerate tumor progression, suggesting that the protective effect of Bax is dose-dependent. While levels of apoptosis in the preneoplastic lesions, but not carcinomas, were reduced in bax+/- or bax-/- mice compared with bax+/+ mice, rates of cellular proliferation in mammary lesions were similar among all bax genotypes. These data demonstrate that bax is a critical suppressor of mammary tumor progression at the stage of preneoplastic mammary lesion development through the upregulation of apoptosis, but that this protective effect is lost during the transition from preneoplasia to invasive carcinoma. PMID:10329616

  8. Self-assembled nanolaminate coatings (SV)

    SciTech Connect

    Fan, H.

    2012-03-01

    Sandia National Laboratories (Sandia) and Lockheed Martin Aeronautics (LM Aero) are collaborating to develop affordable, self-assembled, nanocomposite coatings and associated fabrication processes that will be tailored to Lockheed Martin product requirements. The purpose of this project is to develop a family of self-assembled coatings with properties tailored to specific performance requirements, such as antireflective (AR) optics, using Sandia-developed self-assembled techniques. The project met its objectives by development of a simple and economic self-assembly processes to fabricate multifunctional coatings. Specifically, materials, functionalization methods, and associated coating processes for single layer and multiple layers coatings have been developed to accomplish high reflective coatings, hydrophobic coatings, and anti-reflective coatings. Associated modeling and simulations have been developed to guide the coating designs for optimum optical performance. The accomplishments result in significant advantages of reduced costs, increased manufacturing freedom/producibility, improved logistics, and the incorporation of new technology solutions not possible with conventional technologies. These self-assembled coatings with tailored properties will significantly address LMC's needs and give LMC a significant competitive lead in new engineered materials. This work complements SNL's LDRD and BES programs aimed at developing multifunctional nanomaterials for microelectronics and optics as well as structure/property investigations of self-assembled nanomaterials. In addition, this project will provide SNL with new opportunities to develop and apply self-assembled nanocomposite optical coatings for use in the wavelength ranges of 3-5 and 8-12 micrometers, ranges of vital importance to military-based sensors and weapons. The SANC technologies will be applied to multiple programs within the LM Company including the F-35, F-22, ADP (Future Strike Bomber, UAV, UCAV, etc.). The SANC technologies will establish LMA and related US manufacturing capability for commercial and military applications therefore reducing reliance on off-shore development and production of related critical technologies. If these technologies are successfully licensed, production of these coatings in manufactory will create significant technical employment opportunities.

  9. Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL/6 and 129S1/Sv mice and comparisons with congenic strains

    PubMed Central

    Johnson, Kenneth R.; Tian, Cong; Gagnon, Leona H.; Jiang, Haiyan; Ding, Dalian; Salvi, Richard

    2017-01-01

    A single nucleotide variant (SNV) of the cadherin 23 gene (Cdh23c.753A), common to many inbred mouse strains, accelerates age-related hearing loss (AHL) and can worsen auditory phenotypes of other mutations. We used homologous recombination in C57BL/6 NJ (B6N) and 129S1/SvImJ (129S1) embryonic stem cells to engineer mouse strains with reciprocal single base pair substitutions (B6-Cdh23c.753A>G and 129S1-Cdh23c.753G>A). We compared ABR thresholds and cochlear pathologies of these SNV mice with those of congenic (B6.129S1-Cdh23Ahl+ and 129S1.B6-Cdh23ahl) and parental (B6N and 129S1) strain mice. Results verified the protective effect of the Cdh23c.753G allele, which prevented high frequency hearing loss in B6 mice to at least 18 months of age, and the AHL-inducing effect of the Cdh23c.753A allele, which worsened hearing loss in 129S1 mice. ABR thresholds differed between 129S-Cdh23c.753A SNV and 129S1.B6-Cdh23ahl congenic mice, and a linkage backcross involving these strains localized a Chr 10 QTL contributing to the difference. These results illustrate the large effects that strain background and congenic regions have on the hearing loss associated with Cdh23c.753alleles. Importantly, the B6-Cdh23c.753Gstrain can be used to eliminate the confounding influence of the Cdh23c.753Avariant in hearing studies of B6 mice and mutant mice on the B6 background. PMID:28287619

  10. Relationship between hemodynamics and atherosclerosis in aortic arches of apolipoprotein E-null mice on 129S6/SvEvTac and C57BL/6J genetic backgrounds

    PubMed Central

    Tomita, Hirofumi; Hagaman, John; Friedman, Morton H.; Maeda, Nobuyo

    2011-01-01

    Objective We investigated the relationships between hemodynamics and differential plaque development at the aortic arch of apolipoprotein E (apoE)-null mice on 129S6/SvEvTac (129) and C57BL/6J (B6) genetic backgrounds. Methods Mean flow velocities at the ascending and descending aorta (mVAA and mVDA) were measured by Doppler ultrasound in wild type and apoE-null male mice at 3 and 9 months of age. Following dissection of the aortic arches, anatomical parameters and plaque areas were evaluated. Results Arch plaques were five times bigger in 129-apoE than in B6-apoE mice at 3 months, and twice as large at 9 months. The geometric differences, namely larger vessel diameter in the B6 strain and broader inner curvature of the aortic arch in the 129 strain, were exaggerated in 9-month-old apoE-null mice. Cardiac output and heart rate under anesthesia were significantly higher in the B6 strain than in the 129 strain. The values of mVAA were similar in the two strains, while mVDA was lower in the 129 strain. However, there was a 129-apoE-specific reduction of flow velocities with age, and both mVAA and mVDA were significantly lower in 129-apoE than in B6-apoE mice at 9 months. The mean relative wall shear stress (rWSS) over the aortic arch in 129-apoE and B6-apoE mice were not different, but animals with lower mean rWSS had larger arch plaques within each strain. Conclusions The plaque formation in the arch of apoE-null mice is accompanied by strain-dependent changes in both arch geometry and hemodynamics. While arch plaque sizes negatively correlate with mean rWSS, additional factors are necessary to account for the strain differences in arch plaque development. PMID:22078246

  11. Copper, zinc-superoxide dismutase protects from ultraviolet B-induced apoptosis of SV40-transformed human keratinocytes: the protection is associated with the increased levels of antioxidant enzymes.

    PubMed

    Takahashi, H; Hashimoto, Y; Aoki, N; Kinouchi, M; Ishida-Yamamoto, A; Iizuka, H

    2000-05-01

    It has been reported that cellular oxidative stress induces apoptosis. Ultraviolet radiation that generates reactive oxygen intermediates (ROIs) also induces apoptosis. Superoxide dismutase (SOD) is among the most active scavengers of ROIs, providing defense against the cellular oxidative stress. Mammalian cells express two isozymes of SOD, copper, zinc-SOD (Cu, Zn-SOD) and manganese-SOD (Mn-SOD). Using SV40-transformed human keratinocytes (SVHK cells), we investigated the role of SODs in the ultraviolet B (UVB) irradiation-induced apoptosis. UVB irradiation decreased transiently Cu, Zn- and Mn-SOD activities and their protein levels, with subsequent recovery to the basal levels by 24 h. The UVB-induced decrease in SOD activity was dose-dependent and the maximal effect was obtained at 75 mJ/cm(2). The decrease in Cu, Zn-SOD was more marked than that in Mn-SOD. The cell death assay, annexin-V/propidium iodide flow cytometry, and DNA fragmentation analysis revealed that UVB irradiation induces apoptosis in SVHK cells. The UVB-induced apoptosis was suppressed by the treatment of antioxidants, catalase, glutathione, and alpha-tochopherol. The stable transfection of Cu, Zn-SOD expression vectors into SVHK cells was accompanied by the increased activities of antioxidant enzymes, catalase, and glutathione reductase, as well as glutathione and the cells were shown to be more resistant to UVB-induced apoptosis. In contrast, the transfection of Mn-SOD affected neither activities of antioxidant enzymes nor the UVB-induced apoptosis. The transfection of Cu, Zn-SOD antisense oligomers but not sense oligomers into SVHK or Cu, Zn-SOD cDNA-transfected SVHK (C2) cells significantly decreased the antioxidant enzyme activities and increased the UVB-induced apoptosis. On the other hand, the transfection of Mn-SOD antisense oligomers did not affect the UVB-induced apoptosis. These results suggest that the transfection of Cu, Zn-SOD expression vector, which is accompanied by the

  12. 13C and 15N CP/MAS, 1H-15N SCT CP/MAS and FTIR spectroscopy as tools for qualitative detection of the presence of zwitterionic and non-ionic forms of ansa-macrolide 3-formylrifamycin SV and its derivatives in solid state.

    PubMed

    Przybylski, Piotr; Pyta, Krystian; Klich, Katarzyna; Schilf, Wojciech; Kamieński, Bohdan

    2014-01-01

    (13)C, (15)N CP/MAS, including (1)H-(13)C and (1)H-(15)N short contact time CP/MAS experiments, and FTIR methods were applied for detailed structural characterization of ansa-macrolides as 3-formylrifamycin SV (1) and its derivatives (2-6) in crystal and in powder forms. Although HPLC chromatograms for 2/CH3 OH and 2/CH3 CCl3 were the same for rifampicin crystals dissolved in respective solvents, the UV-vis data recorded for them were different in 300-375 nm region. Detailed solid state (13)C and (15)N CP/MAS NMR and FTIR studies revealed that rifampicin (2), in contrast to 3-formylrifamycin SV (1) and its amino derivatives (3-6), can occur in pure non-ionic or zwitterionic forms in crystal and in pure these forms or a mixture of them in a powder. Multinuclear CP/MAS and FTIR studies demonstrated also that 3-6 derivatives were present exclusively in pure zwitterionic forms, both in powder and in crystal. On the basis of the solid state NMR and FTIR studies, two conformers of 3-formylrifamycin SV were detected in powder form due to the different orientations of carbonyl group of amide moiety. The PM6 molecular modeling at the semi-empirical level of theory, allowed visualization the most energetically favorable non-ionic and zwitterionic forms of 1-6 antibiotics, strongly stabilized via intramolecular H-bonds. FTIR studies indicated that the originally adopted forms of these type antibiotics in crystal or in powder are stable in standard laboratory conditions in time. The results presented point to the fact that because of a possible presence of two forms of rifampicin (compound 2), quantification of the content of this antibiotic in relevant pharmaceuticals needs caution.

  13. Evaluation of total effective dose due to certain environmentally placed naturally occurring radioactive materials using a procedural adaptation of RESRAD code.

    PubMed

    Beauvais, Z S; Thompson, K H; Kearfott, K J

    2009-07-01

    Due to a recent upward trend in the price of uranium and subsequent increased interest in uranium mining, accurate modeling of baseline dose from environmental sources of radioactivity is of increasing interest. Residual radioactivity model and code (RESRAD) is a program used to model environmental movement and calculate the dose due to the inhalation, ingestion, and exposure to radioactive materials following a placement. This paper presents a novel use of RESRAD for the calculation of dose from non-enhanced, or ancient, naturally occurring radioactive material (NORM). In order to use RESRAD to calculate the total effective dose (TED) due to ancient NORM, a procedural adaptation was developed to negate the effects of time progressive distribution of radioactive materials. A dose due to United States' average concentrations of uranium, actinium, and thorium series radionuclides was then calculated. For adults exposed in a residential setting and assumed to eat significant amounts of food grown in NORM concentrated areas, the annual dose due to national average NORM concentrations was 0.935 mSv y(-1). A set of environmental dose factors were calculated for simple estimation of dose from uranium, thorium, and actinium series radionuclides for various age groups and exposure scenarios as a function of elemental uranium and thorium activity concentrations in groundwater and soil. The values of these factors for uranium were lowest for an adult exposed in an industrial setting: 0.00476 microSv kg Bq(-1) y(-1) for soil and 0.00596 microSv m(3) Bq(-1) y(-1) for water (assuming a 1:1 234U:238U activity ratio in water). The uranium factors were highest for infants exposed in a residential setting and assumed to ingest food grown onsite: 34.8 microSv kg Bq(-1) y(-1) in soil and 13.0 microSv m(3) Bq(-1) y(-1) in water.

  14. PROCEEDINGS: 1989 INTERNATIONAL CONFERENCE ON MUNICIPAL WASTE COMBUSTION - VOLUME 4: SESSIONS 9, 10, 11, AND 12

    EPA Science Inventory

    The proceedings document presentations at the International Conference on Municipal Waste Combustion (MWC), held on April 11-14, 1989, in Hollywood, Florida. The objective of the Conference was to provide an effective international forum for the exchange and transfer of informati...

  15. Newton's Apple Teachers Guides. Seasons 9-10-11-12: A Collection of Lessons and Activities.

    ERIC Educational Resources Information Center

    Twin Cities Public Television, St. Paul, MN.

    Newton's Apple is a PBS family science program that explores basic science through high-energy, hands-on demonstrations. This volume is a collection of the teacher's guides from four seasons of Newton's Apple which were originally broadcast from 1991 through 1994. Each of the four seasons in the volume contains 26 lessons and a combination of…

  16. Strand IV Environmental and Community Health, World Health, Grades 10, 11, and 12.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    Special attention to the implications of world health problems and the effectiveness of international understanding and cooperation in alleviating harmful health conditions is given in this prototype curriculum for grades 10-12. The importance of student participation and ultimate involvement and commitment to world health problems is reflected.…

  17. Health Education: Cancer Prevention and Control. Curriculum Guides, Grades 10, 11, and 12.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Curriculum Development Center.

    These curriculum guidelines for tenth-, eleventh-, and twelfth-grade students discuss the prevention, early detection and treatment, and control of cancer. The nature of cancer, the epidemiological factors related to it, the types of treatments available, and rehabilitation of cancer victims are discussed. Finally, the unit discusses personal and…

  18. 15 CFR 10.11 - Revision or amendment of a standard.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... established public policy; or (3) The standard or any part of it is being used to mislead users or consumers or is determined to be against the interest of users, consumers, or the public in general. (b) A... to the standard with appropriate dissemination and public notice of the addendum; and (iii) If...

  19. A Report on the 1972 Interim Meetings of CCIR Study Groups 10, 11, and CMTT.

    ERIC Educational Resources Information Center

    Remley, Frederick M., Jr.

    The activities of the International Radio Consultative Committee (CCIR), the radio-communications arm of the International Telecommunications Union (ITU), serve the goal of standardizing practices and techniques useful in the broad field of telecommunications. In between the plenary meetings held every three years, the work of the committee is…

  20. Theory and modeling in nanoscience: Report of the May 10-11, 2002Workshop

    SciTech Connect

    McCurdy, C. William; Stechel, Ellen; Cummings, Peter; Hendrickson, Bruce; Keyes, David

    2002-06-28

    On May 10 and 11, 2002, a workshop entitled ''Theory and Modeling in Nanoscience'' was held in San Francisco, California, sponsored by the offices of Basic Energy Science and Advanced Scientific Computing Research of the Department of Energy. The Basic Energy Sciences Advisory Committee and the Advanced Scientific Computing Advisory Committee convened the workshop to identify challenges and opportunities for theory, modeling, and simulation in nanoscience and nanotechnology, and additionally to investigate the growing and promising role of applied mathematics and computer science in meeting those challenges. This report is the result of those contributions and the discussions at the workshop.

  1. CWEX-10/11: Overview of Results From the First Two Crop/Wind-Energy Experiments

    NASA Astrophysics Data System (ADS)

    Takle, E. S.; Rajewski, D. A.; Prueger, J. H.; Oncley, S.; Lundquist, J. K.; Horst, T. W.; Rhodes, M. E.; Pfeiffer, R.; Hatfield, J.; Spoth, K. K.; Doorenbos, R.

    2012-12-01

    We have conducted experiments in a 200-turbine operating wind farm in Iowa to measure aerodynamic and microclimate properties of the environment in and around turbines in an area of intensely managed agricultural crops. Surface measurements at multiple locations were made of temperature, humidity, wind speed, wind direction, turbulence, and fluxes of heat, momentum, moisture and CO2. These together with remotely sensed wind speed, wind direction and turbulence at hub height accumulated over the growing seasons of 2010 and 2011 enable us to begin understanding of how turbines influence microclimate conditions in a wind-farm. SCADA data from 13 turbines enable studies of wakes and their interactions with each other and with the surface. Our studies corroborate published results that report reduction in wind speed, increased night-time temperature and decreased the daytime temperature in regions leeward of leading turbines in a wind farm. Our microclimate measurements enable us to go beyond previous reports to investigate spatial structures of mean wind, turbulence kinetic energy, thermal stability, and fluxes of heat, moisture and CO2 at the surface. Control cases are provided by evaluating surface conditions under a wide variety of wind directions and evaluating surface conditions at times when turbines were turned off or abrupt wind shifts were documented. Careful delineation of wind directions from the SCADA data reveal lateral characteristics of wakes and allow comparisons of power reduction for multiple interacting turbines with comparable results reported for off-shore wind farms. Our studies suggest that near-surface conditions are influenced by the presence of overlying wakes, wakes that impinge on the surface, and an irregular standing wave pressure field created by lines of turbines presenting an obstacle to the flow. Surface stability observed concurrently with wake interactions provides some insights on diurnal variability of wind farm performance.

  2. 10/11/2001, Flood Disaster. Analyse and Solution For Algiers City

    NASA Astrophysics Data System (ADS)

    Iddir, R.; Saoula, S.; Laradi, N.

    In space of 24 hours on November 10, 2001, continuously torrential rainfall reaching 211mm (500.000 m3) on Algiers City made of this last one a dead City. Several dis- tricts of the capital, notably Bab El Oued and the municipality of Oued Koriche as well as the district of the Cool Valley were totally Flooded and plunged into the mud. The damages of this flood are very important. It takes to indicate that the human losses have affected the terrible figure of 750 died, more than 115 missing persons and 4.000 stricken families. Economical damage was estimated at more than 3 Billions Dollars. This study had for objective and direct orientation the analysis of the main causes of this disaster. At the beginning, a coverage of geomorphologic and anthropological Factors that were able to aggravate the situation were analysed with an outline on the domains of the town planning, the architecture, the domain of infrastructures and the behavior aggravating. Finally after a critical study, some propositions of Preventive management of the risk of floods in big Algiers were elaborated, to protect the very rich patrimony in this region, and to foresee economically profitable solutions and protectress.

  3. Spaceborne Ocean Intelligence Network: SOIN - Fiscal Year 10/11 Year-End Summary

    DTIC Science & Technology

    2011-10-01

    2010-2011 et du plan de travail pour l’exercice 2011-2012. Résultats: Outre le BT 1 ( gestion de projet, livraison et communication), le RSRO comptait...les procédures d’ordonnancement des données RADARSAT-2 et d’évitement des conflits (avec le Service canadien des glaces [SCG], R & D pour la défense

  4. Shuttle cryogenic supply system optimization study. Volume 3: Technical report, section 10, 11 and 12

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The evaluation of candidate cryogenic fuel systems for space shuttle vehicles is discussed. A set of guidelines was used to establish a matrix of possible combinations for the integration of potential cryogenic systems. The various concepts and combinations which resulted from the integration efforts are described. The parameters which were considered in developing the matrix are: (1) storage of cryogenic materials, (2) fuel lines, (3) tank pressure control, (4) thermal control, (5) fluid control, and (6) fluid conditioning. Block diagrams and drawings of the candidate systems are provided. Performance predictions for the systems are outlined in tables of data.

  5. Widely tunable, narrow linewidth external-cavity gain chip laser for spectroscopy between 10 - 11 µm

    NASA Astrophysics Data System (ADS)

    Shin, Dong K.; Henson, Bryce M.; Khakimov, Roman I.; Ross, Jacob A.; Dedman, Colin J.; Hodgman, Sean S.; Baldwin, Kenneth G. H.; Truscott, Andrew G.

    2016-11-01

    We have developed and characterised a stable, narrow linewidth external-cavity laser (ECL) tunable over 100 nm around 1080 nm, using a single-angled-facet gain chip. We propose the ECL as a low-cost, high-performance alternative to fibre and diode lasers in this wavelength range and demonstrate its capability through the spectroscopy of metastable helium. Within the coarse tuning range, the wavelength can be continuously tuned over 30 pm (7.8 GHz) without mode-hopping and modulated with bandwidths up to 3 kHz (piezo) and 37(3) kHz (current). The spectral linewidth of the free-running ECL was measured to be 22(2) kHz (Gaussian) and 4.2(3) kHz (Lorentzian) over 22.5 ms, while a long-term frequency stability better than 40(20) kHz over 11 hours was observed when locked to an atomic reference.

  6. REPORT OF NATIONAL ADVISORY COMMITTEE ON HEALTH OCCUPATIONS EDUCATION (MARCH 10-11, 1966).

    ERIC Educational Resources Information Center

    Office of Education (DHEW), Washington, DC.

    COMMITTEE MEMBERS AND OFFICE OF EDUCATION STAFF MET WITH RESOURCE PERSONS IN HEALTH OCCUPATIONS AREA. HIGHLIGHTS OF THE SPECIALISTS REPORTS ARE--BY 1970, 60 TO 70 THOUSAND MEDICAL TECHNOLOGISTS WILL BE NEEDED. PROGRAMS DEVELOPED IN TECHNICAL AND HIGH SCHOOLS AND COMMUNITY COLLEGES ARE ALL NEEDED TO REACH THIS GOAL. SHORTAGES OF QUALIFIED TEACHERS…

  7. Adaptive optics; Proceedings of the Meeting, Arlington, VA, April 10, 11, 1985

    NASA Astrophysics Data System (ADS)

    Ludman, J. E.

    Papers are presented on the directed energy program for ballistic missile defense, a self-referencing wavefront interferometer for laser sources, the effects of mirror grating distortions on diffraction spots at wavefront sensors, and the optical design of an all-reflecting, high-resolution camera for active-optics on ground-based telescopes. Also considered are transverse coherence length observations, time dependent statistics of upper atmosphere optical turbulence, high altitude acoustic soundings, and the Cramer-Rao lower bound on wavefront sensor error. Other topics include wavefront reconstruction from noisy slope or difference data using the discrete Fourier transform, acoustooptic adaptive signal processing, the recording of phase deformations on a PLZT wafer for holographic and spatial light modulator applications, and an optical phase reconstructor using a multiplier-accumulator approach. Papers are also presented on an integrated optics wavefront measurement sensor, a new optical preprocessor for automatic vision systems, a model for predicting infrared atmospheric emission fluctuations, and optical logic gates and flip-flops based on polarization-bistable semiconductor lasers.

  8. Pioneer 10/11 data analysis of the plasma analyzer experiment

    NASA Technical Reports Server (NTRS)

    Intriligator, D. S.

    1982-01-01

    The Pioneer 10 plasma analyzer detected the 10 plasma torus. Evidence was found of corotating ions which appear to be primarily S (++) and O (++) in the Pioneer 10 plasma data as the spacecraft moved inward from 6.9 to 5.4 R sub J. The Pioneer plasma analyzer was effective in obtaining information on the heavy ion populations in the Jovian magnetosphere. Interplanetary solar wind plasma shocks can trap energetic particles (cosmic rays) for weeks and out to distances of 17 AU. Energetic particles (o.5 MeV to 20 MeV) were confined between two plasma shocks from solar flares as the shocks propagated outward in the solar system.

  9. Mobile robots III; Proceedings of the Meeting, Cambridge, MA, Nov. 10, 11, 1988

    SciTech Connect

    Wolfe, W.J.

    1989-01-01

    Topics discussed include path planning, terrain classification, planetary rovers, navigation, architecture and control, three-dimensional sensing, and behavior specification. Particular papers are presented on a minimum path algorithm among three-dimensional polyhedral objects, parallel off-road perception processing on the autonomous land vehicle, hazard avoidance for a Mars rover, color vision for road following, a pipeline architecture for near real-time stereo range detection, a computational structure for enforcing reactive behavior in a mobile robot, and homeostatic control for a mobile robot.

  10. Thermal dissipation force modeling with preliminary results for Pioneer 10/11

    NASA Astrophysics Data System (ADS)

    Rievers, Benny; Bremer, Stefanie; List, Meike; Lämmerzahl, Claus; Dittus, Hansjörg

    2010-02-01

    The dissipation of thermal energy can produce disturbance forces on spacecraft surfaces if the energy is not dissipated in a symmetric pattern. This force can be computed as the quotient of the radiated power and the speed of light for a plate surface element. Depending on mission and spacecraft design the resulting surface forces have to be included into the disturbance budget. At ZARM (Center of Applied Space Technology and Microgravity) a raytracing algorithm was developed that allows the computation of the resulting force for complex spacecraft geometries. The method is based on the modeling of the spacecraft geometry in finite elements (FEs). Using an FE-solver the surface temperatures of the satellite can be derived with geometry and material parameters using heat sources/sinks as constraints. The outgoing radiation force is computed including reflectivity and absorption between all elements of the model. As an example for the method a test case model of the radio isotope thermal generators (RTGs) of Pioneer 11 is processed with this force computing method. The results show that detailed thermal modeling for the whole craft is necessary as the simplified test case results in a force that is non-negligible with respect to the pioneer anomaly.

  11. Environmental I.D.E.A.S. Clusters 10, 11, 12, Physical Sciences. Preliminary Edition.

    ERIC Educational Resources Information Center

    Helmick, Robert; And Others

    Approximately 30 experiments related to environmental problems comprise this manual. The three conceptual themes under which these lessons are organized deal with: (1) change; (2) the interaction of custom, rule, and law in society; and (3) economy, life style, and individual attitudes. Provided are materials for both students and teachers.…

  12. Conference on Uncertainty in Engineering Design (May 10-11, 1988)

    DTIC Science & Technology

    1988-05-11

    but rather N a coach who encourages and facilitates the work f his quality teams. N 7 Ishikawa’s Seven Tools At a slightly more sophisticated level the...PROGRAM PROJECT TASK WORK UNIT Office of Naval Research, CODE 1511:P.MD ELEMENT NO. No. NO.NO Arlington, Virginia 22217-5000 Conference on Uncertainty...was greatly enhanced by the work of Shepp and Vardi (1982) on the use of maximu, m likelihood (ML) methods. There are earlier instances of suggestions

  13. Pioneer 10/11 data analysis of the trapped radiation experiment

    NASA Technical Reports Server (NTRS)

    Fillius, W.

    1982-01-01

    The data handling operations and the database produced by the Trapped Radiation Experiment on the NASA Pioneer 10 and 11 spacecraft are outlined. In situ measurements of trapped radiation at both Jupiter and Saturn, the extension of cosmic ray observations to the outer heliosphere, the presence of Jovian electrons in interplanetary space, analyses of the interaction between planetary satellites and the trapped radiation that engulfs them, and further investigations of the radiation enviroments of both planets are reported.

  14. Dexa Body Composition Assessment in 10-11 Year Healthy Children

    PubMed Central

    Doodeman, H. J.; Struijf, E.; Houdijk, A. P. J.

    2016-01-01

    Introduction Obesity is a growing health problem associated with metabolic derangements and cardiovascular disease. Accumulating evidence links the accumulation of visceral adipose tissue (VAT) to these obesity related health risks in adults. Childhood obesity is associated with a lifetime risk of cardiovascular disease and poses a serious challenge to future health care. In children, there is much less data on the prevalence and gender differences of visceral obesity than in adults. This study aims to provide reference values for VAT in children 10–11 years of age. Methods In a cross-sectional study performed in the north western part of theNetherlands, healthy children of 10–11 years of age, were recruited from primary schools. Anthropometric data consisting of height, weight, waist circumference (WC) and BMI were measured. Body composition was measured using DXA, providing measures for bone mineral content, total fat mass (TFM), lean body mass (LBM) and VAT. Results 217 children were eligible for this study. Girls appeared to have a greater TFM (31.4% vs 27.5% of total body weight (TBW); P < .01) but lower VAT (0.3% vs 0.5% of TBW;P < .01) than boys, whereas boys had higher LBM (65.4% vs 69.3% TBW;P < .01). Median VAT area (cm2) was 41.1 for boys and 22.4 for girls (P < .01). Moderate to strong correlations were found for WC and BMI with VAT (boys: r = .664 and r = .630; Girls r = .699 and r = .546 respectively all P < .001). Discussion This study shows gender specific differences in VAT percentiles in healthy non-obese 10–11 year old children as measured by DXA that may serve as reference values in children. Independent of BMI and WC, girls tend to have more TFM but less VAT and LBM than boys. PMID:27788168

  15. Optical space communication II; Proceedings of the Meeting, Munich, Germany, June 10, 11, 1991

    NASA Astrophysics Data System (ADS)

    Franz, Juergen

    1991-05-01

    The present conference discusses the European SILEX project for optical space communications (OSP), Japanese activities in OSPs, deep-space OSP, a high data-rate interorbit link based on diode-pumped Nd:YAG laser technology, an electrooptic modulator for high-speed Nd:YAG laser communications, an unobscured mirror telescope for telecommunications, and optical carrier modulation by integrated optical devices in lithium niobate. Also discussed are micromachined scanning mirrors for laser-beam deflection, coherent optical fiber communications, a 90-deg optical hybrid for coherent receivers, economic factors relevant to an OSP, the effect of microaccelerations on an OSP terminal, and a novel fiber-optics-based conical scan-tracking device.

  16. Ultraviolet technology III; Proceedings of the Meeting, San Diego, CA, Aug. 10, 11, 1989

    NASA Astrophysics Data System (ADS)

    Huffman, Robert E.

    1989-12-01

    The present conference discusses topics in atmospheric UV radiance, UV detectors, and UV airborne sensors. Attention is given to a UV limb imaging experiment, UV ionospheric remote sensing with the Polar BEAR satellite, photon counting by means of microchannel plate (MCP) intensified electrographic cameras, the use of electron-bombarded virtual-phase CCDs and UV imaging detectors, results of dynamic range measurements on multianode microchannel-array detectors, and confined quantum state photomultiplier design. Also discussed are linear array-based UV spectrographs, a multianode MCP for plasma diagnostics, neutral-density UV filters obeying Beer's law, calibration and performance of the UV plume instrument, a magnetic-focus MCP image tube's evaluation, large CCD arrays with enhanced UV performance, images from a UV solar-blind photon-counting camera, and the design of high power laser polarizers.

  17. Modeling Nonignorable Missing Data with Item Response Theory (IRT). Research Report. ETS RR-10-11

    ERIC Educational Resources Information Center

    Rose, Norman; von Davier, Matthias; Xu, Xueli

    2010-01-01

    Large-scale educational surveys are low-stakes assessments of educational outcomes conducted using nationally representative samples. In these surveys, students do not receive individual scores, and the outcome of the assessment is inconsequential for respondents. The low-stakes nature of these surveys, as well as variations in average performance…

  18. Proceedings of the 1981 RADC Microwave Magnetics Technology Workshop, June 10-11, 1981,

    DTIC Science & Technology

    1983-01-01

    Acting Chief Antennas & RF Components Branch Electromagnetic Sciences Division APPROVED: ALLAN C. SCHELL Chief, Electromagnetic Sciences Division FOR...RADC Microwave Magnetics Technology Workshop Program 4 Opening Remarks J.C. Sethares, Workshop Chairman, RADC/EEAC, Hanscom AFB, MA 6 A.C. Schell , Chief...make it so. .-- F4 K b o 7K - .o.._ ALLAN C. SCHELL Chief Electromagnetic Sciences Division, RADC I Our interests and concerns in the area of microwave

  19. Materials for defense/aerospace applications (NON-SV)

    SciTech Connect

    Ellis, A. R.

    2012-03-01

    Through this effort, Sandia and Lockheed Martin Aeronautics Company (LM Aero) sought to assess the feasibility of (1) applying special materials to a defense application; (2) developing a piezoelectric-based micro thermophotovoltaic (TPV) cell; and (3) building and delivering a prototype laboratory emission measurement system. This project supported the Stockpile Research & Development Program by contributing to the development of radio frequency (RF) MEMS- and optical MEMS-based components - such as switches, phase shifters, oscillators, and filters - with improved performance and reduced weight and size. Investigation of failure mechanisms and solutions helped to ensure that MEMS-based technology will meet performance requirements and long term reliability goals in the specified environments dictated by Lockheed Martin's commercial and defense applications. The objectives of this project were to (1) fabricate and test materials for military applications; (2) perform a feasibility study of a piezoelectric-based micro TPV cell; and (3) build and deliver a prototype laboratory emission measurement system. Sandia fabricated and tested properties of materials, studied options for manufacturing scale-up, and delivered a prototype IR Emissometer. LM Aero provided material requirements and designs. Both participated in the investigation of attachment methods and environmental effects on material performance, a feasibility study of piezoelectric TPV cells, an investigation and development of new approaches to implement the required material functionality, and analysis and validation of material performance physics, numerical models, and experimental metrology.

  20. Overlapping Plate Field Distortion Calibration AST-SV-02

    NASA Astrophysics Data System (ADS)

    Jefferys, William

    1991-07-01

    The goal of these activities is to determine the optical field angle distortions of FGS units #3 to within an arbitrary scale factor, with a level of accuracy sufficient to support an overall astrometry error budget of +/- 0.0027 arcseconds rms. The actual solutions will provide the Project Data Base with the significant terms, their values, and their covariances including errors, which may then be applied to general FGS observations to reduce them for field angle distortions, except scale, alignment, and color corrections. THIS PROPOSAL ASSUMES THAT FGS#3 IS THE PRIME UNIT.

  1. Sub-mSV breast XACT scanner: concept and design

    NASA Astrophysics Data System (ADS)

    Tang, Shanshan; Ren, Liqiang; Samant, Pratik; Chen, Jian; Liu, Hong; Xiang, Liangzhong

    2016-04-01

    Excessive exposure to radiation increases the risk of cancer. We present the concept and design of a new imaging paradigm, X-ray induced acoustic computed tomography (XACT). Applying this innovative technology to breast imaging, one single X-ray exposure can generate a 3D acoustic image, which dramatically reduces the radiation dose to patients when compared to beast CT. A theoretical model is developed to analyze the sensitivity of XACT. A noise equivalent pressure model is used for calculating the minimal radiation dose in XACT imaging. Furthermore, K-Wave simulation is employed to study the acoustic wave propagation in breast tissue. Theoretical analysis shows that the X-ray induced acoustic signal has a 100% relative sensitivity to the X-ray absorption (given that the percentage change in the X-ray absorption coefficient yields the same percentage change in the acoustic signal amplitude), but not to X-ray scattering. The final detection sensitivity is primarily limited by the thermal noise. The radiation dose can be reduced by a factor of 100 compared with the newly FDA approved breast CT. Reconstruction result shows that breast calcification with diameter of 80 μm can be observed in XACT image by using ultrasound transducers with 5.5 MHz center frequency. Therefore, with the proposed innovative technology, one can potentially reduce radiation dose to patient in breast imaging as compared with current x-ray modalities.

  2. Extracting and Applying SV-SV Shear Modes from Vertical Vibrator Data Across Geothermal Prospects Final Report

    SciTech Connect

    Hardage, Bob

    2013-07-01

    This 3-year project was terminated at the end of Year 1 because the DOE Geothermal project-evaluation committee decided one Milestone was not met and also concluded that our technology would not be successful. The Review Panel recommended a ?no-go? decision be implemented by DOE. The Principal Investigator and his research team disagreed with the conclusions reached by the DOE evaluation committee and wrote a scientifically based rebuttal to the erroneous claims made by the evaluators. We were not told if our arguments were presented to the people who evaluated our work and made the ?no-go? decision. Whatever the case regarding the information we supplied in rebuttal, we received an official letter from Laura Merrick, Contracting Officer at the Golden Field Office, dated June 11, 2013 in which we were informed that project funding would cease and instructed us to prepare a final report before September 5, 2013. In spite of the rebuttal arguments we presented to DOE, this official letter repeated the conclusions of the Review Panel that we had already proven to be incorrect. This is the final report that we are expected to deliver. The theme of this report will be another rebuttal of the technical deficiencies claimed by the DOE Geothermal Review Panel about the value and accomplishments of the work we did in Phase 1 of the project. The material in this report will present images made from direct-S modes produced by vertical-force sources using the software and research findings we developed in Phase 1 that the DOE Review Panel said would not be successful. We made these images in great haste when we were informed that DOE Geothermal rejected our rebuttal arguments and still regarded our technical work to be substandard. We thought it was more important to respond quickly rather than to take additional time to create better quality images than what we present in this Final Report.

  3. Middle School Mathematics: 2006-07 to 2008-09. Impact Evaluation. E&R Report No. 10.11

    ERIC Educational Resources Information Center

    Paeplow, Colleen

    2010-01-01

    In 2006-07, seven Wake County Public School System (WCPSS) middle schools piloted Algebraic Thinking as an alternate approach to teaching middle school mathematics. Algebraic Thinking was developed to help students in grade 6 reach higher mathematics courses by combining the regular and advanced middle school mathematics courses into one…

  4. Wake Characteristics of a Single Turbine During the CWEX-10/11 Crop Wind-Energy EXperiments

    NASA Astrophysics Data System (ADS)

    Rajewski, D. A.; Takle, E. S.; Lundquist, J. K.; Rhodes, M. E.; Prueger, J. H.; Oncley, S. O.; Horst, T. W.; Pfeiffer, R.; Hatfield, J.; Spoth, K. K.; Doorenbos, R. K.

    2013-12-01

    In the summer of 2010 and 2011 for the Crop Wind-energy EXperiment (CWEX), flux stations measured differences in micrometeorology upstream and downstream of a single turbine within a large wind farm in Iowa. Profiling LiDARs were positioned upwind and downwind of a single turbine for two months in 2011 to document the wake profiles of mean wind speed and turbulent kinetic energy (TKE). Nacelle-based measurements of wind speed, wind direction, and power produced verified the likely presence of a wake above the downwind flux station. As described in the CWEX overview paper (Rajewski et al. 2013) the flux stations detected (1) turbine-wake events for wakes overhead but not intersecting the surface, (2) wakes with a direct surface influence, and (3) flow perturbations caused by the static pressure field around a line of turbines. We refine our conceptual model of wind turbine flow by comparing downwind-upwind flux and profile station differences for categories of waked and non-waked flow according to turbine hub-height speed and direction, ambient thermal stratification, and the operating status of the turbines. For nighttime stable conditions (some for which a low level jet is present) we measured both within the rotor depth and at the surface higher turbulence and stronger intermittency of the flow on the wake edges as compared to the wake core. We additionally observe frequent periods with 20-30° of directional shear from the surface to the top of the rotor as evidenced by a downwind flux station in non-waked flow with concurrent LiDAR measurement of a wake in the rotor layer. Momentum power spectra and co-spectra of 20-Hz surface data corroborate with previous wind tunnel and numerical simulations of wake turbulence with higher energy intensity but at reduced scales than for non-waked conditions. The spectra demonstrate a return to ambient flow when the wind farm is brought offline.

  5. Guiding Age 10-11 Students to Notice the Salient Features of Physical Change Models in Chemistry Digital Learning Objects

    ERIC Educational Resources Information Center

    Gustafson, Brenda; Mahaffy, Peter; Martin, Brian

    2015-01-01

    This paper focuses on one Grade 5 class (9 females; 9 males) who worked in student-pairs to view five digital learning object (DLO) lessons created by the authors and meant to introduce students to the nature of models, the particle nature of matter, and physical change. Specifically, the paper focuses on whether DLO design elements could assist…

  6. Strand I - Physical Health; Disease Prevention and Control for Grades 10, 11, and 12. Special Edition for Evaluation and Discussion.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    This health curriculum guide, intended for use in grades ten through twelve, addresses itself to disease prevention and control concepts which are particularly relevant to the adolescent's physical health needs. The contents of the guide are presented in outline form and cover source of injection, preventing the spread of communicable diseases,…

  7. Proceedings of the Conference on Nutrition and Mental Retardation (Ann Arbor, Michigan, February 10-11, 1971).

    ERIC Educational Resources Information Center

    Springer, Ninfa Saturnino, Ed.

    The conference, planned primarily for nutritionists and dieticians, dealt with the role of nutrition in the prevention and management of mental retardation. Proceedings include an overview of mental retardation, an examination of nutrition manpower needs in the fields of mental health and mental retardation on both the national and state levels,…

  8. Medical Service Specialist, Blocks III, V, VI, 10-11. Military Curriculum Materials for Vocational and Technical Education.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This second course of a two-course, postsecondary-level series for medical service specialist is one of a number of military-developed curriculum packages selected for adaptation to vocational instruction and curriculum development in a civilian setting. The purpose stated for the 89-hour course is to provide training in the basic theory and…

  9. Antifungal drug discovery and development--fourth international summit. 10-11 March 1999, Princeton, New Jersey, USA.

    PubMed

    Ryder, N

    1999-05-01

    Genetic and genomic approaches to discovery, selection and evaluation of antifungal targets were extensively discussed by several speakers at this meeting. Experimental targets with early lead compounds available from screening programs include translation (Ribogene Inc), transcription (SCRIPTGEN Pharmaceuticals Inc), and protein geranylgeranylation (Mitotix Inc). Classes of compounds which are more advanced in preclinical evaluation include the sordarins, inhibitors of fungal elongation factor 2 under development by Glaxo Wellcome plc and Merck and Co Inc, and a series of fungicidal peptides originally derived from a domain of the human neutrophil bactericidal permeability-increasing protein (BPI, Xoma Ltd). Preclinical and early clinical data were presented for two compounds: caspofungin (MK-0991, Merck and Co Inc), an echinocandin with a broad-spectrum of activity for parenteral application, and Sch-56592 (Schering-Plough Corp), an orally active triazole. The oral antimycotic, terbinafine (Novartis AG), primarily used in dermatological infections, shows potent synergy with azoles and has potential applications against several serious and drug-resistant fungal pathogens. Amphotericin B, which has long been the gold standard for therapy of life-threatening infections, is now available in several liposomal formulations, including AmBisome (Fujisawa Pharmaceutical Co Ltd) and Abelcet (The Liposome Company Inc) which show a reduced incidence of adverse events.

  10. Proceedings of the Eastern Region Annual Research Conference in Agricultural Education (Easton, Maryland, May 10-11, 1985).

    ERIC Educational Resources Information Center

    1985

    Twelve major papers delivered during this conference on agricultural education in the Northeastern states are included in this volume: (1) "Status of Pennsylvania Special Needs Students in Vocational Agriculture: Phase IV--Job Performance Follow-Up," by Dennis C. Scanlon and Connie D. Baggett; (2) "Education, Age and Experience:…

  11. Fundamentals of Tribology Workshop Held at the University of Florida, Gainesville, Florida on 10-11 May 2010: Project Summary

    DTIC Science & Technology

    2010-05-01

    Emerging characterization tools entailing elements of both microscopy and spectroscopy (nanoIR, X-ray microtomography, MALDI TOF -MS, TOF -SIMS...technologies. • Development of mechanical models of soft materials ( polymers ) will be required to allow their greater incorporation into tribological...systems; viscoelastic models are needed to describe the deformation of polymers from initiation to fracture; • Expansion of mechanical models to

  12. Advanced On-The-Job Training System: User’s Handbook (Sections 10-11). Volume 3

    DTIC Science & Technology

    1990-05-01

    A LABORATORY AIR FORCE SYSTEMS COMMAND BROOKS AIR FORCE BASE, TEXAS 78235-5601 NOTICE When Government drawings, specifications, or other data are...any obligation whatsoever. The fact that the Government may have formulated or in any way supplied the said drawings, specifications, or other data ...I provides information on the types and the operation of equipment used by the system. Volume II contains information on accessing and reviewing data

  13. Proceedings of the Annual Conference of the Midwest Philosophy of Education Society (Ann Arbor, Michigan, November 10-11, 1978).

    ERIC Educational Resources Information Center

    Merritt, James, Ed.; And Others

    The Midwest Philosophy of Education Society strives to enhance and deepen the level of conversation about education in the modern world and to evaluate, in moral terms, the relationship of education to the larger society. The following papers were presented at the 1978 annual meeting of the Society: "Educational Evaluation and Emancipation" (Gary…

  14. The Effects of Playground Markings on the Physical Self-Perceptions of 10-11-Year-Old School Children

    ERIC Educational Resources Information Center

    Crust, Lee; McKenna, Jim; Spence, Jon; Thomas, Catherine; Evans, Donna; Bishop, Daniel

    2014-01-01

    Background: Significant proportions of school children in the UK do not meet the minimum recommended daily requirements of 60-min moderate-intensity physical activity. Beyond taught classes, playtimes offer the opportunity for children to play and be physically active. Painted markings are one recent addition to school playgrounds that are…

  15. Interdisciplinary Student/Teacher Materials in Energy, the Environment, and the Economy: Agriculture, Energy, and Society, Grades 10, 11, 12.

    ERIC Educational Resources Information Center

    Brock, Phyllis; And Others

    This interdisciplinary instructional unit contains eleven lessons for grades 10-12 which focus on the energy component of food production. There are lessons which contrast food production systems in various cultures and also lessons which look at different systems and techniques in use in this country. There are lessons dealing with organic…

  16. Proceedings of the National Seminar for State Directors of Community-Junior Colleges (January 10-11, 1972). Final Report.

    ERIC Educational Resources Information Center

    Daugherty, Ronald, Comp.; And Others

    This 3-day seminar was specifically designed to acquaint state leaders with those trends in occupational education having direct and indirect implications for the post-secondary level and to provide a forum for identification and discussion of problems. Thus, 49 participants met and responded to presentations on the following topics: (1) "Improved…

  17. The Resources and Strategies that 10--11-Year-Old Boys Use to Construct Masculinities in the School Setting

    ERIC Educational Resources Information Center

    Swain, Jon

    2004-01-01

    The data in this article come from an ethnographic exploration into the construction of masculinities in three junior schools in the UK between 1998 and 1999. The author argues that the construction and performance of masculinity is inextricably linked to the acquisition of status within the school peer group, and he delineates the specific series…

  18. Manpower Planning and Forecasting, Proceedings of the Annual Research Conference (10th, Beverly Hills, California, April 10-11, 1967).

    ERIC Educational Resources Information Center

    California Univ., Los Angeles. Inst. of Industrial Relations.

    Five conference papers covering research studies and problems related to effective utilization of manpower in southern California are presented. "The Impact of Technological Change on Employees in the Southern California Aerospace Industry," by Paul Prasow, reports a longitudinal study of social and psychological adjustment factors…

  19. Proceedings on Combating the Unrestricted Warfare Threat: Integrating Strategy, Analysis, and Technology, 10-11 March 2008

    DTIC Science & Technology

    2008-03-01

    combined because that is force pro- tection. L.A./Long Beach brings in 43% of all the containers and 50% of all the energy west of the Rocky ... Mountains . If I am an adversary in Southern California, do I go south to San Diego or do I go to L.A.? By hardening the Port of San Diego, we created an...Chapter 3 Roundtable 2 Denying Access to and Use of WMD The dog spots the tiger with the monkey on his back as they emerge from the jungle. He says

  20. A Synopsis of the National Conference on Fitness and Aging (Washington, DC, September 10-11, 1981).

    ERIC Educational Resources Information Center

    President's Council on Physical Fitness and Sports, Washington, DC.

    This report contains presentations and program descriptions given at a conference on physical fitness and older adults. Included are: (1) Keynote Address (Richard S. Schweiker); (2) "Government's Role in Fitness for the Aging" (Pete V. Domenici and Beverly B. Byron); (3) "What Is Aging?" (James Skinner); (4) Medical Implications of Fitness and…

  1. The Major Project in the Field of Education in the Latin American and Caribbean Region. Bulletin 10-11.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Santiago (Chile). Regional Office for Education in Latin America and the Caribbean.

    The Major Project in the Field of Education stresses renewed and intensive efforts by Latin American and Caribbean Island countries to provide the resources and training necessary to meet basic education needs by the year 2000. This document examines project achievements, innovations, and problems through 1986 in the areas of rural education,…

  2. Oregon Statewide Writing Assessment: Results, Analysis, and Sample Student Writings, 1993-1997. Grades 8, 10, 11.

    ERIC Educational Resources Information Center

    Hill, Bonnie

    Noting that statewide writing assessment shows the achievements of Oregon students over the last decade, this booklet explains the results for the 1993-1997 assessments and provides papers illustrating the work that Oregon students in grades 8, 10, and 11 produce on the state test. The booklet's chapters are: (1) The History of Writing Assessment…

  3. Proceedings of a Conference--"The Future of Grammar in American Schools" (Winchester, VA, August 10-11, 1990).

    ERIC Educational Resources Information Center

    National Council of Teachers of English, Urbana, IL. Assembly for the Teaching of English Grammar.

    Providing alternatives to the way grammar is taught, this proceedings includes every paper (or summary) except one delivered at a conference on the future of grammar in American schools. Papers in the proceedings are: "Keynote: The Future of Grammar in American Schools" (Martha Kolln); "Approaches to Grammar: Teaching &…

  4. Report of the Yale Conference on the Teaching of English (16th, Yale University, April 10-11, 1970).

    ERIC Educational Resources Information Center

    Yale Univ., New Haven, CT. Graduate School.

    Four speeches illustrating important principles in the teaching of English are collected in this booklet: (1) "The Teaching of Writing as Art" by William E. Coles, Jr., who, in posing ambiguous, provocative questions as writing assignments, compels the student to explore language in its relationship to his experience and his persona; (2)…

  5. Portable TXRF Spectrometer with 10-11g Detection Limit and Portable XRF Spectromicroscope with Sub-mm Spatial Resolution

    NASA Astrophysics Data System (ADS)

    Kunimura, Shinsuke; Hatakeyama, So; Sasaki, Nobuharu; Yamamoto, Takashi; Kawai, Jun

    2010-04-01

    A portable total reflection X-ray fluorescence (TXRF) spectrometer that we have developed is applied to trace elemental analysis of water solutions. Although a 5 W X-ray tube is used in the portable TXRF spectrometer, detection limits of several ppb are achieved for 3d transition metal elements and trace elements in a leaching solution of soils, a leaching solution of solder, and alcoholic beverages are detected. Portable X-ray fluorescence (XRF) spectromicroscopes with a 1 W X-ray tube and an 8 W X-ray tube are also presented. Using the portable XRF spectromicroscope with the 1 W X-ray tube, 93 ppm of Cr is detected with an about 700 μm spatial resolution. Spatially resolved elemental analysis of a mug painted with blue, red, green, and white is performed using the two portable spectromicroscopes, and the difference in elemental composition at each paint is detected.

  6. Seeking Sustainable Public Universities: The Legacy of the Great Recession. Research & Occasional Paper Series: CSHE.10.11

    ERIC Educational Resources Information Center

    Lyall, Katharine

    2011-01-01

    The business models under which most public universities in the U.S. operate have become unsustainable. They were put in place when state economies were stronger and there were fewer programs making competing claims on state funds. The current Great Recession has made things worse, but the unsustainability of current business models derives from…

  7. The future of aeronautical transportation; Proceedings of the Princeton University Conference, Princeton, N.J., November 10, 11, 1975

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Papers are presented on first and second generation supersonic transports, the Supersonic Cruise Aircraft Research Program, wide-body subsonic transports and vertical and short takeoff and landing transports. Aspects of aircraft design are examined including the airframe, propulsion and electronics. Government regulation, cost/benefit analysis of research and development, airline economics and aircraft financing are also considered. The environmental impact of air transportation is discussed with emphasis on atmospheric emissions (including stratospheric pollution) and noise pollution. Individual items are announced in this issue.

  8. Radiological implications of inhaled 239Pu and 241Am in dusts at the former nuclear test site in Maralinga.

    PubMed

    Stradling, G N; Stather, J W; Gray, S A; Moody, J C; Ellender, M; Pearce, M J; Collier, C G

    1992-12-01

    The biokinetics of 239Pu and 241Am present in three dust samples obtained from Maralinga were investigated after their deposition in the rat lung. Results were used as an experimental basis for assessing the radiological implications for human exposure. The transfer rates of these actinides to blood in the various dusts differed by 50-fold. The most transportable forms were compatible with a material that had 25% class W and 75% class Y characteristics. The doses per unit intake for adults, children, and infants exposed to an aerosol of 5 microns AMAD were calculated to be, respectively, 0.059, 0.076, and 0.140 mSv Bq-1. The corresponding doses for the least transportable forms were the same as those calculated for a class Y compound, namely 0.036, 0.049, and 0.096 mSv Bq-1. The behavior of the actinides in humans was predicted by combining the transfer rates to blood with mechanical clearance data obtained after volunteers had inhaled 85Sr or 88Y labeled fused aluminosilicate particles. The results suggested that monitoring of 241Am in the chest could be used to advantage for assessing intakes incurred by workers involved with any further decontamination procedures but would be of little practical value for assessing inadvertent public exposure. The paper includes comments on the relevance of the 1990 ICRP recommendations and the proposed new dosimetric model for the respiratory tract.

  9. Reconstruction and forecast of doses due to ingestion of 137Cs and 90Sr after the Chernobyl accident.

    PubMed

    Kravets, A P; Pavlenko, Yu A

    2008-04-01

    The assessment doses due to ingestion of (137)Cs and (90)Sr for the population suffering from the Chernobyl accident was performed on the basis of the new mechanistic ecological model for assessment of radiological consequences of agricultural lands contamination (EMARC). The EMARC model allows estimation of internal doses based on ecological factors influencing the contamination of foodstuff, for the post-accidental years in the countries of the former Soviet Union. The EMARC model allows estimation of all quantities required in radiation hygiene practice. For example, the proposed analytical method may be used for both retrospective dose reconstruction and prospective estimates of annual dose and integrated "life-time" dose, for different age intervals. According to the EMARC model, estimated reference "life-time" doses for adults are between 7 and 269 microSv kBq(-1) m(2) for (137)Cs, and between 25 and 235 microSv kBq(-1) m(2) for (90)Sr. Maximal doses were estimated for persons who were 3, 9 and 11 years old, at the time of the accident and these doses exceed those for adults by a factors of 1, 5 for (90)Sr, and 1.4 for (137)Cs.

  10. Minutes of the Explosives Safety Seminar (19th) Held at Los Angeles, California on 9-10-11 September 1980. Volume II

    DTIC Science & Technology

    1980-09-01

    using 3M Co. polonium 210 as source of alpha particles. The air ionizers were used for approximately six (6) months. Their use was stopped since the...FRAGMNTS/BO F I ** Figure 15/ Fragment Areal Densities NRHbo - ~ 1-12191 02L3) (OSS4l) I’lU) 700𔄀 / __ 3s21? 210 t (.40) ( .0-0) o𔃻 t 80 IJ1 * f.UM...ABL-917 707 # 210 -9-70 1630 ABL-917 707 #110-13-70 1730 ABL-917 707 #111-5-70 040 ABL-1362 706 #112-23-70 1745 ABL-1362 706 #112-28-70 1655 ABL-1362

  11. IEEE Workshop on Real-Time Operating Systems and Software (7th) Held in Charlottesville, Virginia on May 10-11, 1990. Revision

    DTIC Science & Technology

    1990-10-01

    LeBlanc and E. P. Markatos, University of Rochester CHAOS arc A Kernelfor Predictable Programs in Dynamic R eal-Tim e System s...11 K. Schwan and A. Gheith Georgia Institute of Technology Implementing a Predictable Real...62 P. Gopinath and R. Gupta, Philips Laboratories Developing Software with Predictable Timing Behavior

  12. Proceedings of the Workshop on Unsteady Separated Flow Held at the United States Air Force Academy on August 10-11, 1983

    DTIC Science & Technology

    1984-05-01

    30309 (303) 492-7611 Dr. Mohamed Gad-El-Hak Flow Industries , Inc. 21414 - 68th Avenue South Kenth, WA 93032 (206) 872-8500 Major Eric Jumper Dept...Thru3t dependar.ce of the time advantage in a minimum time maneuver with limited PST capability. Results of trajectory optimisations . Fig. 15...through an analog to digital converter. The probe positioning has been automated in one direction and is driven by the microcomputer. The velocity

  13. Partnering for Vaccine Emerging Markets--Berlin, June 10-11, 2013: balancing vaccine quality, capacity, and cost-of-goods in emerging markets.

    PubMed

    Onraedt, Annelies

    2013-09-01

    Phacilitates 1st Partnering event for Vaccine Emerging Markets brought together approximately 100 attendees from developed and developing world vaccine manufacturers, leading non-profit organizations and industry suppliers. The goal was to discuss the vaccine needs in the developing world and how these needs can be met by leveraging collaboration and partnership models, by improving access to existing, new and next generation vaccines, by using novel technologies to drive competitive advantage and economics of vaccine manufacturing and by investing in localized capacity, including capacity for pandemic vaccines. The present article summarizes insights out of 30 oral contributions on how quality and capacity requirements can be balanced with cost by using novel manufacturing technologies and operating models.

  14. Proceedings of the Symposium on GPS Applications in Space (2nd) Held in Bedford, Massachusetts on 10-11 October 1989. Volume 1

    DTIC Science & Technology

    1990-02-13

    Advanced Spacecraft Applications, Triveni N. Upadhyay, George J. Priovolos, Harley Rhodehamel . . . 245 An Experiment In Attitude, Position And Velocity...Priovolos*, Harley Rhodehamel*, A. Wayne Deaton** (*Mayflower Communications, **NASA Marshall SFC): "Autonomous Integrated GPS/INS Navigation Filter for...optical path (for example, due to splices or connectors, nicks in the fiber cladding, impurities in the fiber core, etc.) will cause small-scale (1

  15. Proceedings of the Annual Conference of the Midwest Philosophy of Education Society (Chicago, Illinois, November 10-11, 1989, and November 9-10, 1990).

    ERIC Educational Resources Information Center

    Annis, David B., Ed.; Oliker, Michael A., Ed.

    Proceedings from two conferences of a society of specialists in the philosophy of education comprise this document. Fourteen papers are included from the 1989 conference program. They are: (1) "George S. Counts: Dare Educators Inspire World Vision?" (C. A. Ryan); (2) "Political Activities of George S. Counts and John L. Childs"…

  16. RESEARCH AND DEVELOPMENT PRIORITIES IN TECHNICAL EDUCATION, A REPORT OF A NATIONAL RESEARCH PLANNING CONFERENCE IN TECHNICAL EDUCATION (THE OHIO STATE UNIVERSITY, JANUARY 10-11, 1967).

    ERIC Educational Resources Information Center

    MILLER, AARON J.

    A SELECT GROUP OF PARTICIPANTS REPRESENTING NATIONAL LEADERSHIP IN BUSINESS, INDUSTRY, RESEARCH, GOVERNMENT, AND EDUCATION MET TO IDENTIFY SOME OF THE MOST OBVIOUS NEW EMERGING TECHNICAL OCCUPATIONS WHICH MIGHT REQUIRE RESEARCH AND DEVELOPMENT EFFORTS AND SOME OF THE MOST PRESSING RESEARCHABLE PROBLEM AREAS IN TECHNICAL EDUCATION. THE NEW OR…

  17. Evaluation of surface energy and carbon fluxes within a large wind farm during the CWEX-10/11 Crop Wind-energy EXperiments

    NASA Astrophysics Data System (ADS)

    Rajewski, D. A.; Takle, E. S.; Prueger, J. H.; Oncley, S.; Horst, T. W.; Pfeiffer, R.; Hatfield, J.; Spoth, K. K.; Doorenbos, R.

    2012-12-01

    The Crop Wind-energy EXperiment conducted in summer 2010 (very moist conditions) and summer 2011 (abnormally dry) included measurements of wind speed, temperature, relative humidity, turbulence kinetic energy, H2O, and CO2 at stations north and south of a line of turbines at the southwest edge of a large-scale 200-turbine wind farm (prevailing wind from the south). In contrast to previous studies that have reported turbine influences on surface wind speed and temperature, this report focuses on scalar fluxes of heat, H2O, and CO2. From previous measurements in agricultural fields we recognize the importance of non-turbine factors in analysis of the flux differences: variability of soil characteristics, moisture content, crop cultivar, management practices, planting dates, etc., which can create differences in what looks like a uniform field of maize (corn). We conceptualize the influences of turbines at canopy height at a given location in the field to arise from (1) wakes of reduced wind speed and turbulence conditions different from ambient that intersect the surface, (2) wakes that are passing overhead and interrupt the ambient turbulence that scales with height, or (3) changes in static pressure upwind and downwind of lines of turbines that create small-scale pressure gradients, localized flows, and changes to the vertical exchange of scalar variables. The turbine SCADA wind speed and wind direction provided by the wind farm operator facilitated our comparison of surface fluxes upwind and downwind as wakes moved laterally throughout the day and night. We report multiple levels of evidence that wind turbines increase vertical exchange of carbon dioxide and water vapor over the canopy. Latent heat and carbon fluxes are responsive to slight changes in the turbine wake position, and the flux differences are maximized when the periphery of the wake edge is above the station. The flux stations north of the turbine line report a larger net ecosystem exchange accumulation over both the 2010 and 2011 measurement periods than for the reference towers south of the turbine line. Future experiments however, must address if and to what extent this enhanced CO2 flux is assimilated to the crop and whether or not the bio-physiological response to this effect among many other turbine-related factors (e.g. higher nighttime temperature and higher daytime transpiration) modifies overall crop yield.

  18. Military History of the American Revolution. Proceedings of the Military History Symposium (6th) Held at the Air Force Academy, Colo. on 10-11 October 1974,

    DTIC Science & Technology

    1976-01-01

    in 1776 and not maintained subsequently because forces were dispersed ."• Evidence that the timing of the Dcclaratior. wi independence was in part...that it was determined to make them submit by taking or sinking their ships, devastating their ports, destroying their armed forces, and dispersing ...Still, it was confident that such a force of regulars would be able to disperse any number of untrained colonists and that Britain would gain a

  19. Submillimetre galaxies reside in dark matter haloes with masses greater than 3 × 10(11) solar masses.

    PubMed

    Amblard, Alexandre; Cooray, Asantha; Serra, Paolo; Altieri, B; Arumugam, V; Aussel, H; Blain, A; Bock, J; Boselli, A; Buat, V; Castro-Rodríguez, N; Cava, A; Chanial, P; Chapin, E; Clements, D L; Conley, A; Conversi, L; Dowell, C D; Dwek, E; Eales, S; Elbaz, D; Farrah, D; Franceschini, A; Gear, W; Glenn, J; Griffin, M; Halpern, M; Hatziminaoglou, E; Ibar, E; Isaak, K; Ivison, R J; Khostovan, A A; Lagache, G; Levenson, L; Lu, N; Madden, S; Maffei, B; Mainetti, G; Marchetti, L; Marsden, G; Mitchell-Wynne, K; Nguyen, H T; O'Halloran, B; Oliver, S J; Omont, A; Page, M J; Panuzzo, P; Papageorgiou, A; Pearson, C P; Pérez-Fournon, I; Pohlen, M; Rangwala, N; Roseboom, I G; Rowan-Robinson, M; Portal, M Sánchez; Schulz, B; Scott, Douglas; Seymour, N; Shupe, D L; Smith, A J; Stevens, J A; Symeonidis, M; Trichas, M; Tugwell, K; Vaccari, M; Valiante, E; Valtchanov, I; Vieira, J D; Vigroux, L; Wang, L; Ward, R; Wright, G; Xu, C K; Zemcov, M

    2011-02-24

    The extragalactic background light at far-infrared wavelengths comes from optically faint, dusty, star-forming galaxies in the Universe with star formation rates of a few hundred solar masses per year. These faint, submillimetre galaxies are challenging to study individually because of the relatively poor spatial resolution of far-infrared telescopes. Instead, their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations. A previous attempt at measuring this power spectrum resulted in the suggestion that the clustering amplitude is below the level computed with a simple ansatz based on a halo model. Here we report excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500 μm. From this excess, we find that submillimetre galaxies are located in dark matter haloes with a minimum mass, M(min), such that log(10)[M(min)/M(⊙)] = 11.5(+0.7)(-0.2) at 350 μm, where M(⊙) is the solar mass. This minimum dark matter halo mass corresponds to the most efficient mass scale for star formation in the Universe, and is lower than that predicted by semi-analytical models for galaxy formation.

  20. IMPERATIVES FOR CHANGE, NEW YORK STATE EDUCATION CONFERENCE ON COLLEGE AND UNIVERSITY PROGRAMS FOR TEACHERS OF THE DISADVANTAGED (YESHIVA UNIVERSITY, APRIL 10-11, 1967).

    ERIC Educational Resources Information Center

    JABLONSKY, ADELAIDE; AND OTHERS

    THESE PROCEEDINGS REPORT 19 DISCUSSION DEBATES, EACH REPRESENTED BY A NUMBER OF PAPERS IN FOUR MAJOR AREAS--(1) CONCERN FOR ATTITUDES AND BEHAVIOR (ADMINISTRATIVE COMMITMENT, COOPERATIVE COLLEGE-SCHOOL SYSTEM EFFORTS, CULTURE SHOCK, STAFF AND STUDENT ATTITUDES AND BEHAVIOR, AND SENSITIVITY TRAINING), (2) CONCERN FOR PEOPLE (TEACHING ETHNIC GROUPS,…

  1. IMPERATIVES FOR CHANGE, PROCEEDINGS OF THE NEW YORK STATE EDUCATION CONFERENCE ON COLLEGE AND UNIVERSITY PROGRAMS FOR TEACHERS OF THE DISADVANTAGED (YESHIVA UNIVERSITY, APRIL 10-11, 1967).

    ERIC Educational Resources Information Center

    JABLONSKY, ADELAIDE; AND OTHERS

    THESE PROCEEDINGS REPORT 19 DISCUSSION DEBATES, EACH REPRESENTED BY A NUMBER OF PAPERS IN FOUR MAJOR AREAS--(1) CONCERN FOR ATTITUDES AND BEHAVIOR (ADMINISTRATIVE COMMITMENT, COOPERATIVE COLLEGE-SCHOOL SYSTEM EFFORTS, CULTURE SHOCK, STAFF AND STUDENT ATTITUDES AND BEHAVIOR, AND SENSITIVITY TRAINING), (2) CONCERN FOR PEOPLE (TEACHING ETHNIC GROUPS,…

  2. USGS Workshop on Scientific Aspects of a Long-Term Experimental Plan for Glen Canyon Dam, April 10-11, 2007, Flagstaff, Arizona

    USGS Publications Warehouse

    ,

    2008-01-01

    Executive Summary Glen Canyon Dam is located in the lower reaches of Glen Canyon National Recreation Area on the Colorado River, approximately 15 miles upriver from Grand Canyon National Park (fig. 1). In 1992, Congress passed and the President signed into law the Grand Canyon Protection Act (GCPA; title XVIII, sec. 1801?1809, of Public Law 102-575), which seeks ?to protect, mitigate adverse impacts to, and improve the values for which Grand Canyon National Park and Glen Canyon National Recreation Area were established.? The Glen Canyon Dam Adaptive Management Program (GCDAMP) was implemented as a result of the 1996 Record of Decision on the Operation of Glen Canyon Dam Final Environmental Impact Statement to ensure that the primary mandate of the GCPA is met through advances in information and resources management (U.S. Department of the Interior, 1995). On November 3, 2006, the Bureau of Reclamation (Reclamation) announced it would develop a long-term experimental plan environmental impact statement (LTEP EIS) for operational activities at Glen Canyon Dam and other management actions on the Colorado River. The purpose of the long-term experimental plan is twofold: (1) to increase the scientific understanding of the ecosystem and (2) to improve and protect important downstream resources. The proposed plan would implement a structured, longterm program of experimentation to include dam operations, potential modifications to Glen Canyon Dam intake structures, and other management actions such as removal of nonnative fish species. The development of the long-term experimental plan continues efforts begun by the GCDAMP to protect resources downstream of Glen Canyon Dam, including Grand Canyon, through adaptive management and scientific experimentation. The LTEP EIS will rely on the extensive scientific studies that have been undertaken as part of the adaptive management program by the U.S. Geological Survey?s (USGS) Grand Canyon Monitoring and Research Center (GCMRC), one of the four research stations within the USGS Southwest Biological Science Center. On April 10 and 11, 2007, at the behest of Reclamation, the GCMRC convened a workshop with scientific experts to identify one or more scientifically credible, long-term experimental options for Reclamation to consider for the LTEP EIS that would be consistent with the purpose and need for the plan. Workshop participants included government, academic, and private scientists with broad experience in the Colorado River in Grand Canyon and regulated rivers around the world. Resource managers and GCDAMP participants were also present on the second day of the workshop. In advance of the workshop, Reclamation and LTEP EIS cooperating agencies identified 14 core scientific questions. Workshop participants were asked to consider how proposed options would address these questions, which fall primarily into four areas: (1) conservation of endangered humpback chub (Gila cypha) and other high-priority biological resources, (2) conservation of sediment resources, (3) enhancement of recreational resources, and (4) preservation of cultural resources. A secondary objective of the workshop was the evaluation of four long-term experimental options developed by the GCDAMP Science Planning Group (SPG) (appendix B). The flow and nonflow treatments called for in the four experimental options were an important starting point for workshop discussions. At the beginning of the workshop, participants were provided with the final LTEP EIS scoping report prepared by Reclamation. Participants were also advised that Reclamation had committed to ?make every effortEto ensure that a new population of humpback chub is established in the mainstem or one or more of the tributaries within Grand Canyon? in the 1995 Operation of Glen Canyon Dam Final Environmental Impact Statement (U.S. Department of the Interior, 1995). This decision was consistent with the U.S. Fish and Wildlife Service?s 1995 bi

  3. Highlights of the Midwest and Eastern Regional Conferences on Childhood Lead Poisoning; Chicago, Illinois, May 10-11, 1972 and Wilmington, Delaware, June 2-3, 1972.

    ERIC Educational Resources Information Center

    McCabe, Edward B., Ed.; Challop, Roger S., Ed.

    Various aspects of lead poisoning and its control are the focus of this document which consists of edited speeches presented at childhood lead poisoning conferences in Wilmington, Delaware and Chicago, Illinois. Among the topics discussed are a) the role of Federal and State governments in lead poison control; b) the local government role,…

  4. Proceedings of the Particle Beam Research Workshop, Held at US Air Force Academy, Colorado, Springs, CO on 10-11 January 1980

    DTIC Science & Technology

    1980-05-01

    gas (solid, liquid, gas, vacuum) 2) saturable reactors 3) cross-field 4) ignitrons 5) thyratrons 6) solid state 7) mechanical 8) surface flashover o...phenomena/processes 1) breakdown 18 PULSED POWER 2.5 Switching (Cont.) - gas - vacuum 2) flashover ( surface ) - gas-solid interfaces - vacuum-solid...computer models 8) electrode erosion 9) gas flow dynamics 10) surface physics 11) emission mechanisms 12) e-beam energy recovery/perfeance o low

  5. Comment on "Indication from Pioneer 10/11, Galileo, and Ulysses Data, of an Apparent Anomalous, Weak, Long-Range Acceleration"

    SciTech Connect

    Humphreys, D.R.

    1998-10-27

    In a recent Letter Anderson et al. report some very intriguing radio observations flom various interplanetary spaceprobes over the past 18 years. They interpret this data as an anomalous deceleration of the spaceprobes. Here I offer a different interpretation: that the anomaly is related to the cosmological red shift.

  6. Proceedings of the Meeting of the Coordinating Group on Modern Control Theory (2nd) 10-11 December 1980, Aberdeen Proving Ground, Maryland. Part 1

    DTIC Science & Technology

    1981-04-01

    ki , k 2 and k3 are optimal gain constants, and K is the positive-definite sol - ution of the algebraic Riccati equation ATK + KA + Q - KBr-lBTK - 0. (9...parameters for these cases are given in Table, 3, ’note that the last three digits only of tho Identifier are used here). SoL - parapmeters are quite...response shown in Figure t0. For this case the same MMAC used in the previous examples was employed, but the vign of the radome boresight error model was

  7. Effects of a 12-Month Complex Proprioceptive-Coordinative Training Program on Soccer Performance in Prepubertal Boys Aged 10-11 Years.

    PubMed

    Boraczyński, Michał; Sozański, Henryk; Boraczyński, Tomasz

    2017-03-31

    The aim was to examine the effects of a series of on-field proprioceptive-coordinative (P-C) exercises on motor performance (MP) in prepubertal soccer players. Fifty-three male soccer players aged 10.1-11.8 years were randomized among two experimental programs receiving P-C training (P-CT; n = 26) or regular training (RT; n = 27). A control group (C; n = 22) consisted of age-matched (10.3-11.9 years) cohorts not involved in any regular physical activity. Both experimental groups completed an identical 12-month comprehensive soccer program except training in P-CT was modified to substitute small-sided conditioning games with 24 multi-mode P-C exercises with modulated exercise intensity (every 8-9 weeks based on predicted HRmax). Pre-, peri-, and post-training measures included anthropometry and five tests assessing soccer-specific MP: movement rhythm (turning the ball backwards - T1), motor adaptation (running with the ball around poles - T2), spatial orientation (running to sequentially numbered balls - T3), balance (single-leg static balance - T4), and kinesthetic differentiation of movement (landing the ball on a 2 × 2 m sector - T5). Repeated measures ANOVA revealed no significant between-group differences for age, anthropometry and BF% at baseline. Significant main effects for group (P-CT vs. RT) were found in all tests (T1-T5) and main effects for time (group P-CT) in T3-T5, while a significant group × time interaction was observed only in T4 (F = 2.98, p = 0.0204). Post-hoc tests indicated that P-CT attained significantly better results than RT at peri-training (by 26.4%; p < 0.01) and post-training (by 31.9%, p < 0.01). Modulated exercise intensity had little effect on soccer performance (T1-T3, T5). Based on the results, it is recommended that the training of young soccer players be supplemented with the bilateral balance exercises and games employed in the study. Furthermore, the suitability of monitoring HR in P-C exercises targeting the analyzed MP skills is questionable.

  8. Minutes of the Explosives Safety Seminar (19th) Held at Los Angeles, California, 9-10-11 September 1980. Volume 1

    DTIC Science & Technology

    1980-01-01

    3: 1 u2 cbmk 1.0 1.72 z 10 3 9 Surface 3: Size of rebar 0.04 6.89 z 101 spacing 10 Sumface•4: ••ole penal 253.3 4.98 x 105 11 Surface 4;. /2 panel...Criteria and Design and Construction Details - Design Examples, by T. Takayanagi and A. Derecho , Skokie, Ill., May 1980. 8. University of Illinois, DASA

  9. From Early Child Development to Human Development: Investing in Our Children's Future. Proceedings of a World Bank Conference (Washington, D.C., April 10-11, 2000).

    ERIC Educational Resources Information Center

    Young, Mary Eming, Ed.

    In April 2000, the World Bank hosted a global conference that addressed the benefits and challenges of investing in early child development (ECD). The landmark conference brought together the world's leading experts, academicians, practitioners, and policymakers to focus on various aspects of ECD. This volume contains the proceedings of the…

  10. Educational Strategies for Social Change. Papers and Proceedings of the Annual Convention, Lutheran Educational Conference of North America (56th, Houston, January 10-11, 1970).

    ERIC Educational Resources Information Center

    Holcomb, Howard E., Ed.

    The purpose of the Lutheran Educational Conference of North America is to explore problems in higher education, especially those related to Lutheran higher education. It also seeks to share information, suggest strategies, and assist member institutions in their programs. This volume contains the papers and proceedings of the 56th annual meeting.…

  11. The Development of Extraversion and Ability: Analysis of Data from a Large-Scale Longitudinal Study of Children Tested at 10-11 and 14-15 Years.

    ERIC Educational Resources Information Center

    Anthony, W. S.

    1983-01-01

    Results of analysis of correlations collected by Cookson, following Eysenck and Cookson's study of personality and ability in young people, confirm the finding from previous Cattellian test data that the more intelligent children decline in relative extraversion scores and cast doubt on Eysenck's suggestion that introverts gradually show higher…

  12. Behavioral responses of the invasive Halyomorpha halys (Stal) to traps baited with stereoisomeric mixtures of 10,11-Epoxy-1-bisabolen-3-OL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The brown marmorated stink bug, Halyomorpha halys, is an invasive insect in the United States that is capable of inflicting significant yield losses for fruit, vegetable, and soybean growers. Recently, a male-produced aggregation pheromone of H. halys was identified as a 3.5:1 mixture of (3S,6S,7R,...

  13. SECTAM XII - Proceedings of the Twelfth Southeastern Conference on Theoretical and Applied Mechanics, Pine Mountain, GA, May 10, 11, 1984. Volume 1

    NASA Astrophysics Data System (ADS)

    Turbulence-related investigations are discussed, taking into account the formulation of three-dimensional boundary-layer equations for viscid/inviscid interacting flow, a theory for generating turbulent flow, numerical experiments in open-channel turbulence, the application of the K-E turbulence model to a boundary layer solution for flow about a spinning yawed projectile at Mach 3, and the simulation of late transition in plane channel flow. Other topics explored are related to wave propagation, nonlinear structural dynamics, computational methods, geomechanics, continuum mechanics, experimental methods, fluid mechanics, biofluid mechanics, vibrations of plates and shells, composite materials, fracture mechanics, interdisciplinary/applied problems, hydraulics, fluid-structure interaction, solid mechanics, and the theory of shells. Attention is given to an analysis of a superplastically formed and diffusion bonded sandwich panel, the composite repair of a cracked aluminum alloy aircraft structure, and the determination of turbomachinery blade characteristics for vibration analysis.

  14. Selected Works from the Proceedings of the Annual Communications Research Symposium (9th, Knoxville, Tennessee, April 10-11, 1986). Vol. 9.

    ERIC Educational Resources Information Center

    Singletary, Michael W., Ed.

    Featuring 11 articles of original research, this collection presents selected works from the proceedings of the ninth Annual Communications Research Symposium. Following are the titles and authors of the articles included: (1) "Issues in Inferring Media Effects from Surveys" (S. H. Chaffee); (2) "Expectancy Value Theory and…

  15. Reading: A Literary Feast: Proceedings of the Claremont Reading Conference (56th, Claremont, CA, March 10-11, 1989). Fifty-Third Yearbook.

    ERIC Educational Resources Information Center

    Douglass, Malcolm P., Ed.

    Articles in this yearbook address the issue of emphasizing the basics in reading development, and also focus on the literary experience. Articles, listed by their authors, include: (1) "A Second Helping" (Myra Cohn Livingston); (2) "Not Only a New Curriculum but a New Teacher" (Marilyn Hanf Buckley); (3) "Reading--A…

  16. Moving from Reader Response to Critical Reading: Developing 10-11-Year-Olds' Ability as Analytical Readers of Literary Texts

    ERIC Educational Resources Information Center

    McDonald, Lorraine

    2004-01-01

    This article presents aspects of a research study into how a group of ten- and eleven-year-old students (in 5th Grade in Sydney, Australia) were apprenticed to view a literary text from critical reading positions. These ways of reading were an alternative to their more typical reader response interpretations of texts. The article contrasts…

  17. Proceedings of the Annual Midwest Research-to-Practice Conference in Adult and Continuing Education (4th, Ann Arbor, Michigan, October 10-11, 1985).

    ERIC Educational Resources Information Center

    Berlin, L. S., Ed.

    This document contains the following papers on practical applications of research on adult and continuing education: "Elderly Criminal Behavior: Linking Research to Practice," by Donald J. Bachand and Carl I. Brahce; "Father? Teacher? Friend? Instructor-Student Relationships in a Refugee Class," by Gary J. Bekker; "The Small Group: Understanding…

  18. A Computational Analysis of ATP Binding of SV40 Large Tumor Antigen Helicase Motor

    PubMed Central

    Shi, Yemin; Liu, Hanbin; Gai, Dahai; Ma, Jianpeng; Chen, Xiaojiang S.

    2009-01-01

    Simian Virus 40 Large Tumor Antigen (LTag) is an efficient helicase motor that unwinds and translocates DNA. The DNA unwinding and translocation of LTag is powered by ATP binding and hydrolysis at the nucleotide pocket between two adjacent subunits of an LTag hexamer. Based on the set of high-resolution hexameric structures of LTag helicase in different nucleotide binding states, we simulated a conformational transition pathway of the ATP binding process using the targeted molecular dynamics method and calculated the corresponding energy profile using the linear response approximation (LRA) version of the semi-macroscopic Protein Dipoles Langevin Dipoles method (PDLD/S). The simulation results suggest a three-step process for the ATP binding from the initial interaction to the final tight binding at the nucleotide pocket, in which ATP is eventually “locked” by three pairs of charge-charge interactions across the pocket. Such a “cross-locking” ATP binding process is similar to the binding zipper model reported for the F1-ATPase hexameric motor. The simulation also shows a transition mechanism of Mg2+ coordination to form the Mg-ATP complex during ATP binding, which is accompanied by the large conformational changes of LTag. This simulation study of the ATP binding process to an LTag and the accompanying conformational changes in the context of a hexamer leads to a refined cooperative iris model that has been proposed previously. PMID:19779548

  19. Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects

    PubMed Central

    Tognon, Mauro; Corallini, Alfredo; Manfrini, Marco; Taronna, Angelo; Butel, Janet S.; Pietrobon, Silvia; Trevisiol, Lorenzo; Bononi, Ilaria; Vaccher, Emanuela; Barbanti-Brodano, Giuseppe; Martini, Fernanda; Mazzoni, Elisa

    2016-01-01

    Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA tumor virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18–65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses. PMID:26731525

  20. SvO2 Trigger in Transfusion Strategy After Cardiac Surgery

    ClinicalTrials.gov

    2016-05-18

    Undergoing Nonemergent Cardiac Surgery; Central Venous Catheter on the Superior Vena Cava (to Perform ScVO2 Measure); Anemia (<9g/dL) Requiring Blood Transfusion; Hemodynamic and Respiratory Stability; Bleeding Graded as Insignificant, Mild, Moderate of Universal Definition of Perioperative Bleeding

  1. Investigation Spectral Image the Upper Atmosphere over Regions with Thunderstorm Using Data from the Sv

    NASA Astrophysics Data System (ADS)

    Grichshenko, Valentina

    2016-07-01

    The results of the two-level experiment, including registration of the electric field in the surface layer during thunderstorm on TSCRS (Almaty) and synchronous image the top of the cloud cover over the test range from satellite "Terra / MODIS" are presented. Spectral image of the upper atmosphere over of the thunderstorm related to lighting discharge has been created. As a result of the processing of satellite images Terra / MODIS created a new index of "lightning discharge," which will be used to search for and investigation of optical phenomena (such as Sprites, Elves, Blue Jet) over the regions with thunderstorm activity. The developed technique of space picture processing will be used for studying optical phenomena above other regions too.

  2. Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen.

    SciTech Connect

    Li, D.; Zhao, R.; Lilyestrom, W.; Gai, D.; Zhang, R.; DeCaprio, J. A.; Fanning, E.; Joachimiak, A.; Szakonyi, G.; Chen, X. S.; Univ. of Colorado Health Science Center; Dana-Farber Cancer Ins.; Vanderbilt Univ.

    2003-05-29

    The oncoprotein large tumour antigen (LTag) is encoded by the DNA tumour virus simian virus 40. LTag transforms cells and induces tumours in animals by altering the functions of tumour suppressors (including pRB and p53) and other key cellular proteins. LTag is also a molecular machine that distorts/melts the replication origin of the viral genome and unwinds duplex DNA. LTag therefore seems to be a functional homologue of the eukaryotic minichromosome maintenance (MCM) complex. Here we present the X-ray structure of a hexameric LTag with DNA helicase activity. The structure identifies the p53-binding surface and reveals the structural basis of hexamerization. The hexamer contains a long, positively charged channel with an unusually large central chamber that binds both single-stranded and double-stranded DNA. The hexamer organizes into two tiers that can potentially rotate relative to each other through connecting alpha-helices to expand/constrict the channel, producing an 'iris' effect that could be used for distorting or melting the origin and unwinding DNA at the replication fork.

  3. Analysis of skeletal muscle function in the C57BL6/SV129 syncoilin knockout mouse

    PubMed Central

    McCullagh, Karl J. A.; Edwards, Ben; Kemp, Matthew W.; Giles, Laura C.; Burgess, Matthew

    2008-01-01

    Syncoilin is a 64-kDa intermediate filament protein expressed in skeletal muscle and enriched at the perinucleus, sarcolemma, and myotendinous and neuromuscular junctions. Due to its pattern of cellular localization and binding partners, syncoilin is an ideal candidate to be both an important structural component of myocytes and a potential mediator of inherited myopathies. Here we present a report of a knockout mouse model for syncoilin and the results of an investigation into the effect of a syncoilin null state on striated muscle function in 6–8-week-old mice. An analysis of proteins known to associate with syncoilin showed that ablation of syncoilin had no effect on absolute expression or spatial localization of desmin or alpha dystrobrevin. Our syncoilin-null animal exhibited no differences in cardiotoxin-induced muscle regeneration, voluntary wheel running, or enforced treadmill exercise capacity, relative to wild-type controls. Finally, a mechanical investigation of isolated soleus and extensor digitorum longus indicated a potential differential reduction in muscle strength and resilience. We are the first to present data identifying an increased susceptibility to muscle damage in response to an extended forced exercise regime in syncoilin-deficient muscle. This study establishes a second viable syncoilin knockout model and highlights the importance of further investigations to determine the role of syncoilin in skeletal muscle. PMID:18594912

  4. Joint measurement of lensing-galaxy correlations using SPT and DES SV data

    SciTech Connect

    Baxter, E. J.

    2016-07-04

    We measure the correlation of galaxy lensing and cosmic microwave background lensing with a set of galaxies expected to trace the matter density field. The measurements are performed using pre-survey Dark Energy Survey (DES) Science Verification optical imaging data and millimeter-wave data from the 2500 square degree South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. The two lensing-galaxy correlations are jointly fit to extract constraints on cosmological parameters, constraints on the redshift distribution of the lens galaxies, and constraints on the absolute shear calibration of DES galaxy lensing measurements. We show that an attractive feature of these fits is that they are fairly insensitive to the clustering bias of the galaxies used as matter tracers. The measurement presented in this work confirms that DES and SPT data are consistent with each other and with the currently favored $\\Lambda$CDM cosmological model. In conclusion, it also demonstrates that joint lensing-galaxy correlation measurement considered here contains a wealth of information that can be extracted using current and future surveys.

  5. Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects.

    PubMed

    Tognon, Mauro; Corallini, Alfredo; Manfrini, Marco; Taronna, Angelo; Butel, Janet S; Pietrobon, Silvia; Trevisiol, Lorenzo; Bononi, Ilaria; Vaccher, Emanuela; Barbanti-Brodano, Giuseppe; Martini, Fernanda; Mazzoni, Elisa

    2016-01-01

    Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA tumor virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18-65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses.

  6. Joint measurement of lensing-galaxy correlations using SPT and DES SV data

    DOE PAGES

    Baxter, E. J.

    2016-07-04

    We measure the correlation of galaxy lensing and cosmic microwave background lensing with a set of galaxies expected to trace the matter density field. The measurements are performed using pre-survey Dark Energy Survey (DES) Science Verification optical imaging data and millimeter-wave data from the 2500 square degree South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. The two lensing-galaxy correlations are jointly fit to extract constraints on cosmological parameters, constraints on the redshift distribution of the lens galaxies, and constraints on the absolute shear calibration of DES galaxy lensing measurements. We show that an attractive feature of these fits is that they are fairly insensitive to the clustering bias of the galaxies used as matter tracers. The measurement presented in this work confirms that DES and SPT data are consistent with each other and with the currently favoredmore » $$\\Lambda$$CDM cosmological model. In conclusion, it also demonstrates that joint lensing-galaxy correlation measurement considered here contains a wealth of information that can be extracted using current and future surveys.« less

  7. Cyber Security Indications and Warning System (SV): CRADA 1573.94 Project Accomplishments Summary

    SciTech Connect

    Hu, Tan Chang; Robinson, David G.

    2011-09-08

    As the national focus on cyber security increases, there is an evolving need for a capability to provide for high-speed sensing of events, correlation of events, and decision-making based on the adverse events seen across multiple independent large-scale network environments. The purpose of this Shared Vision project, Cyber Security Indications and Warning System, was to combine both Sandia's and LMC's expertise to discover new solutions to the challenge of protecting our nation's infrastructure assets. The objectives and scope of the proposal was limited to algorithm and High Performance Computing (HPC) model assessment in the unclassified environment within funding and schedule constraints. The interest is the identification, scalability assessment, and applicability of current utilized cyber security algorithms as applied in an HPC environment.

  8. Joint measurement of lensing-galaxy correlations using SPT and DES SV data

    NASA Astrophysics Data System (ADS)

    Baxter, E.; Clampitt, J.; Giannantonio, T.; Dodelson, S.; Jain, B.; Huterer, D.; Bleem, L.; Crawford, T.; Efstathiou, G.; Fosalba, P.; Kirk, D.; Kwan, J.; Sánchez, C.; Story, K.; Troxel, M. A.; Abbott, T. M. C.; Abdalla, F. B.; Armstrong, R.; Benoit-Lévy, A.; Benson, B.; Bernstein, G. M.; Bernstein, R. A.; Bertin, E.; Brooks, D.; Carlstrom, J.; Rosell, A. Carnero; Carrasco Kind, M.; Carretero, J.; Chown, R.; Crocce, M.; Cunha, C. E.; da Costa, L. N.; Desai, S.; Diehl, H. T.; Dietrich, J. P.; Doel, P.; Evrard, A. E.; Fausti Neto, A.; Flaugher, B.; Frieman, J.; Gruen, D.; Gruendl, R. A.; Gutierrez, G.; de Haan, T.; Holder, G.; Honscheid, K.; Hou, Z.; James, D. J.; Kuehn, K.; Kuropatkin, N.; Lima, M.; March, M.; Marshall, J. L.; Martini, P.; Melchior, P.; Miller, C. J.; Miquel, R.; Mohr, J. J.; Nord, B.; Omori, Y.; Plazas, A. A.; Reichardt, C.; Romer, A. K.; Rykoff, E. S.; Sanchez, E.; Sevilla-Noarbe, I.; Sheldon, E.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Suchyta, E.; Stark, A.; Swanson, M. E. C.; Tarle, G.; Thomas, D.; Walker, A. R.; Wechsler, R. H.

    2016-10-01

    We measure the correlation of galaxy lensing and cosmic microwave background lensing with a set of galaxies expected to trace the matter density field. The measurements are performed using pre-survey Dark Energy Survey (DES) Science Verification optical imaging data and millimetre-wave data from the 2500 sq. deg. South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. The two lensing-galaxy correlations are jointly fit to extract constraints on cosmological parameters, constraints on the redshift distribution of the lens galaxies, and constraints on the absolute shear calibration of DES galaxy-lensing measurements. We show that an attractive feature of these fits is that they are fairly insensitive to the clustering bias of the galaxies used as matter tracers. The measurement presented in this work confirms that DES and SPT data are consistent with each other and with the currently favoured Λ cold dark matter cosmological model. It also demonstrates that joint lensing-galaxy correlation measurement considered here contains a wealth of information that can be extracted using current and future surveys.

  9. Definition of a novel symbiovar (sv. retamae) within Bradyrhizobium retamae sp. nov., nodulating Retama sphaerocarpa and Retama monosperma.

    PubMed

    Guerrouj, Kamal; Ruíz-Díez, Beatriz; Chahboune, Rajaa; Ramírez-Bahena, Martha-Helena; Abdelmoumen, Hanaa; Quiñones, Miguel A; El Idrissi, Mustapha Missbah; Velázquez, Encarna; Fernández-Pascual, Mercedes; Bedmar, Eulogio J; Peix, Alvaro

    2013-06-01

    In this paper we analyze through a polyphasic approach several Bradyrhizobium strains isolated in Spain and Morocco from root nodules of Retama sphaerocarpa and Retama monosperma. All the strains have identical 16S rRNA genes and their closest relative species is Bradyrhizobium lablabi CCBAU 23086(T), with 99.41% identity with respect to the strain Ro19(T). Despite the closeness of the 16S rRNA genes, the housekeeping genes recA, atpD and glnII were divergent in Ro19(T) and B. lablabi CCBAU 23086(T), with identity values of 95.71%, 93.75% and 93.11%, respectively. These differences were congruent with DNA-DNA hybridization analysis that revealed an average of 35% relatedness between the novel species and B. lablabi CCBAU 23086(T). Also, differential phenotypic characteristics of the new species were found with respect to the already described species of Bradyrhizobium. Based on the genotypic and phenotypic data obtained in this study, we propose to classify the group of strains isolated from R. sphaerocarpa and R. monosperma as a novel species named Bradyrhizobium retamae sp. nov. (type strain Ro19(T)=LMG 27393(T)=CECT 8261(T)). The analysis of symbiotic genes revealed that some of these strains constitute a new symbiovar within genus Bradyrhizobium for which we propose the name "retamae", that mainly contains nodulating strains isolated from Retama species in different continents.

  10. Predicting Future Reconviction in Offenders with Intellectual Disabilities: The Predictive Efficacy of VRAG, PCL-SV, and the HCR-20

    ERIC Educational Resources Information Center

    Gray, Nicola S.; Fitzgerald, Suzanne; Taylor, John; MacCulloch, Malcolm J.; Snowden, Robert J.

    2007-01-01

    Accurate predictions of future reconviction, including those for violent crimes, have been shown to be greatly aided by the use of formal risk assessment instruments. However, it is unclear as to whether these instruments would also be predictive in a sample of offenders with intellectual disabilities. In this study, the authors have shown that…

  11. Quantitative and molecular analyses of mutation in a pSV2gpt transformed CHO cell line

    SciTech Connect

    Stankowski, L.F. Jr.; Tindall, K.R.; Hsie, A.W.

    1983-01-01

    Following NDA-mediated gene transfer we have isolated a cell line useful for studying gene mutation at the molecular level. This line, AS52, derived from a hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficient Chinese hamster ovary (CHO) cell line, carries a single copy of the E. coli xanthine-guanine phosphoribosyl transferase (XGPRT) gene (gpt) and exhibits a spontaneous mutant frequency of 20 TG/sup r/ mutants/10/sup 6/ clonable cells. As with HGPRT/sup -/ mutants, XGPRT/sup -/ mutants can be selected in 6-thioguanine. AS52 (XGPRT/sup +/) and wild type CHO (HGPRT/sup +/) cell exhibit almost identical cytotoxic responses to various agents. We observed significant differences in mutation induction by UV light and ethyl methanesulfonate (EMS). Ratios of XGPRT/sup -/ to HGPRT/sup -/ mutants induced per unit dose (J/m/sup 2/ for UV light and ..mu..g/ml for EMS) are 1.4 and 0.70, respectively. Preliminary Southern blot hybridization analyses has been performed on 30 XGPRT/sup -/ AS52 mutants. A majority of spontaneous mutants have deletions ranging in size from 1 to 4 kilobases (9/19) to complete loss of gpt sequences (4/19); the remainder have no detectable (5/19) or only minor (1/19) alterations. 5/5 UV-induced and 5/6 EMS-induced mutants do not show a detectable change. Similar analyses are underway for mutations induced by x-irradiation and ICR 191 treatment.

  12. Genome-Wide Detection of SNP and SV Variations to Reveal Early Ripening-Related Genes in Grape.

    PubMed

    Xu, Yanshuai; Gao, Zhihong; Tao, Jianmin; Jiang, Weihua; Zhang, Shijie; Wang, Qiunan; Qu, Shenchun

    2016-01-01

    Early ripening in grape (Vitis vinifera L.) is a crucial agronomic trait. The fruits of the grape line 'Summer Black' (SBBM), which contains a bud mutation, can be harvested approximately one week earlier than the 'Summer Black' (SBC)control. To investigate the molecular mechanism of the bud mutation related to early ripening, we detected genome-wide genetic variations based on re-sequencing. In total, 3,692,777 single nucleotide polymorphisms (SNPs) and 81,223 structure variations (SVs) in the SBC genome and 3,823,464 SNPs and 85,801 SVs in the SBBM genome were detected compared with the reference grape sequence. Of these, 635 SBC-specific genes and 665 SBBM-specific genes were screened. Ripening and colour-associated unigenes with non-synonymous mutations (NS), SVs or frame-shift mutations (F) were analysed. The results showed that 90 unigenes in SBC, 76 unigenes in SBBM and 13 genes that mapped to large fragment indels were filtered. The expression patterns of eight genes were confirmed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).The re-sequencing data showed that 635 SBC-specific genes and 665 SBBM-specific genes associated with early ripening were screened. Among these, NCED6 expression appears to be related to NCED1 and is involved in ABA biosynthesis in grape, which might play a role in the onset of anthocyanin accumulation. The SEP and ERF genes probably play roles in ethylene response.

  13. 76 FR 74779 - SV Hydro LLC; Coffeeville LLC; FFP Project 99 LLC; Lock Hydro Friends Fund XIV; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-01

    ...- river utilizing surplus water from the Coffeeville Lock & Dam, as directed by the Corps. Applicant....0 GWh, and operate run-of-river utilizing surplus water from the Coffeeville Lock & Dam, as directed... preliminary permit applications, pursuant to section 4(f) of the Federal Power Act, proposing to study...

  14. BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol.

    PubMed

    Geiger, Roger; Andritschke, Daniel; Friebe, Sarah; Herzog, Fabian; Luisoni, Stefania; Heger, Thomas; Helenius, Ari

    2011-09-25

    How non-enveloped viruses overcome host cell membranes is poorly understood. Here, we show that after endocytosis and transport to the endoplasmic reticulum (ER), but before crossing the ER membrane to the cytosol, incoming simian virus 40 particles are structurally remodelled leading to exposure of the amino-terminal sequence of the minor viral protein VP2. These hydrophobic sequences anchor the virus to membranes. A negatively charged residue, Glu 17, in the α-helical, membrane-embedded peptide is essential for infection, most likely by introducing an 'irregularity' recognized by the ER-associated degradation (ERAD) system for membrane proteins. Using a siRNA-mediated screen, the lumenal chaperone BiP and the ER-membrane protein BAP31 (both involved in ERAD) were identified as being essential for infection. They co-localized with the virus in discrete foci and promoted its ER-to-cytosol dislocation. Virus-like particles devoid of VP2 failed to cross the membrane. The results demonstrated that ERAD-factors assist virus transport across the ER membrane.

  15. Genome-Wide Detection of SNP and SV Variations to Reveal Early Ripening-Related Genes in Grape

    PubMed Central

    Tao, Jianmin; Jiang, Weihua; Zhang, Shijie; Wang, Qiunan; Qu, Shenchun

    2016-01-01

    Early ripening in grape (Vitis vinifera L.) is a crucial agronomic trait. The fruits of the grape line ‘Summer Black’ (SBBM), which contains a bud mutation, can be harvested approximately one week earlier than the ‘Summer Black’ (SBC)control. To investigate the molecular mechanism of the bud mutation related to early ripening, we detected genome-wide genetic variations based on re-sequencing. In total, 3,692,777 single nucleotide polymorphisms (SNPs) and 81,223 structure variations (SVs) in the SBC genome and 3,823,464 SNPs and 85,801 SVs in the SBBM genome were detected compared with the reference grape sequence. Of these, 635 SBC-specific genes and 665 SBBM-specific genes were screened. Ripening and colour-associated unigenes with non-synonymous mutations (NS), SVs or frame-shift mutations (F) were analysed. The results showed that 90 unigenes in SBC, 76 unigenes in SBBM and 13 genes that mapped to large fragment indels were filtered. The expression patterns of eight genes were confirmed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).The re-sequencing data showed that 635 SBC-specific genes and 665 SBBM-specific genes associated with early ripening were screened. Among these, NCED6 expression appears to be related to NCED1 and is involved in ABA biosynthesis in grape, which might play a role in the onset of anthocyanin accumulation. The SEP and ERF genes probably play roles in ethylene response. PMID:26840449

  16. Education and Science in Africa: Possible Ways of Improvement in the Next Decade. International Commission on Education for the Twenty-First Century, Working Group on Education and Science (Paris, France, January 10-11, 1994).

    ERIC Educational Resources Information Center

    Wandiga, Shem O.

    This paper analyzed the evolution of formal education in Africa with emphasis on the weaknesses and strengths of the system identified. Although the roots of modern education can be found in the early institutions of learning and libraries of Alexandria and Timbuktu in Africa, the continent today lags behind in all the fields of formal education.…

  17. Planning and Designing Effective Defence and Related Information Services: Conference Proceedings of the Technical Information Panel Specialists’ Meeting Held in Ankara, Turkey on 10-11 September 1986.

    DTIC Science & Technology

    1987-04-01

    papers were of interest to the audience. The discussion of Paper 1 highlighted problem areas common to many of the NATO Nations: financing , identifying a...Personnel - (4) Finance . This subdivision can be found in every larger or smaller part of the Ministry of Defence where it defines the user needs of that... financing recurring expenditures for staff, equipment and material. It is presumed a priori that these funds are employed in accordance with the

  18. Defining Competencies for Associate Degree Nursing Education and Practice. Proceedings of the Midwest Regional Conference on "The Associate Degree Nursing--Facilitating Competency Development" Project (Chicago, Illinois, March 10-11, 1983).

    ERIC Educational Resources Information Center

    Minckley, Barbara B., Ed.; Walters, Mary Dale, Ed.

    Focusing on "Associate Degree Nursing--Facilitating Competency Development," a 3-year project sponsored by the Midwest Alliance in Nursing (MAIN) to explore and recommend ways of strengthening Associate Degree Nursing (ADN) education and service, these proceedings contain papers by individuals involved with the development of the project and those…

  19. 2,4-Dialkyl-8,9,10,11-tetrahydrobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraones as new leads against Mycobacterium tuberculosis.

    PubMed

    Claes, Pieter; Cappoen, Davie; Uythethofken, Cynthia; Jacobs, Jan; Mertens, Birgit; Mathys, Vanessa; Verschaeve, Luc; Huygen, Kris; De Kimpe, Norbert

    2014-04-22

    Given the re-emergence of tuberculosis in Europe and beyond, the search for novel bio-active compound classes against this disease is of utmost importance. As a result of a high intrinsic tolerance of the etiological agent, Mycobacterium tuberculosis, towards most antibiotics and xenobiotics, the search for such new compounds is far from trivial. Further exacerbated by the rapid generation and spread of drug resistant M. tuberculosis and fuelled by the HIV/AIDS pandemic, halting the tuberculosis epidemic is of paramount importance. As part of our program to design new 2-aza-anthraquinones with anti-mycobacterial activity, various dialkyltetrahydrobenzo[g]pyrimido[4,5-c]isoquinolinetetraones were designed and synthesised. The compounds were submitted to a biological evaluation in which the activity against M.tb H37Rv(lux) was observed, as well as the acute toxicity towards J774 A.1 macrophages. From these results, the selectivity index was calculated. Furthermore, the activity of the most promising compounds was further studied against a multi-drug resistant LAM-1 strain and against intracellular replicating M.tb. The study was further extended with a comet assay and a VITOTOX™ assay to investigate the possibility of observable genotoxic effects caused by these compounds.

  20. 11-(4-Methyl­phen­yl)-8,9-dihydro-7H-benzo[f]cyclo­penta­[b]quinolin-10(11H)-one

    PubMed Central

    Yang, Cao

    2012-01-01

    In the title compound, C23H19NO, the naphthalene ring system and the cyclo­pent-2-enone ring exhibit planar conformations with maximum deviations of 0.034 (1) and 0.02 (1) Å, respectively. The 1,4-dihydro­pyridine ring adopts an envelope conformation with the C atom bearing the p-tolyl ring as the flap atom. Inter­molecular N—H⋯O hydrogen bonds and C—H⋯π inter­actions stabilize the crystal packing. PMID:22969629

  1. Our Town and Country Society Looks at Itself. Proceedings of the Conference of the American Country Life Association, Inc., National 4-H Club Center (41st, Washington, D.C., July 10-11, 1962).

    ERIC Educational Resources Information Center

    American Country Life Association, Sioux Falls, SD.

    The theme for this conference was "Our Town and Country Society Looks at Itself." The following papers were presented at this conference: (1) "The Miracle of Production--Can We Keep It" (Aubrey D. Gates); (2) "Recent U.S. Population Trends and Their Causes" (Calvin L. Beale and Donald J. Bogue); (3) "Commercial…

  2. Proceedings of the Electronic Test Equipment Division’s Annual Program Review of ’Electronic Test Equipment Industry Response to Emerging Defense Requirements’ Held in Arlington, VA on 10-11 May 1984

    DTIC Science & Technology

    1984-01-01

    SEND ONLY FAILED ITEMS TO THE REAR ECHELONS FOR REPAIR. TM SURE YOU CAN APPRECIATE WHAT EFFECT THIS HAS ON OUR LOGISTICS PIPELINE . 14 AN EXAMPLE...EVIDENCE OF FAILURE" RETURNS TO THE DEPOT WENT FROM 41 PERCENT TO LESS THAN 10 PERCENT; AND THE COST OF PIPELINE SPARES WAS REDUCED BY $450,000. DUE TO...and management processes, CTE offered NAVAIR some significant advantages. We provided a conceptual description of these processes -- the keystone of

  3. The Life, Influence and the Role of the Chinese in the United States, 1776-1960. Proceedings of the National Conference Held at the University of San Francisco July 10, 11, 12, 1975.

    ERIC Educational Resources Information Center

    Chinese Historical Society of America, San Francisco, CA.

    This volume contains the proceedings and the papers of the first national conference on the life, influence, and the role of the Chinese in the U.S. The proceedings include papers, films, slide presentations, and addresses. Among the topics covered by the papers presented are the following: (1) contributions of Chinese art to Fresno culture, (2)…

  4. 2-Hy­droxy-2,3,5,10,11,11a-hexa­hydro-1H-pyrrolo­[2,1-c][1,4]benzodiazepine-5,11-dione

    PubMed Central

    Ourahou, Sarah; Zouihri, Hafid; Massoui, Mohamed; Essassi, El Mokhtar; Ng, Seik Weng

    2011-01-01

    The seven-membered ring of the title compound, C12H12N2O3, which is fused with the phenyl­ene ring, adopts a boat-shaped conformation (with the methine C atom as the prow and the phenyl­ene C atoms as the stern); the H atom on the methine linkage exists in an axial position. The five-membered ring that is fused with the seven-membered ring adopts an envelope conformation (with the C atom bearing the hy­droxy substituent representing the flap) [the deviation from the plane defined by the other four atoms is 0.200 (7) Å in one mol­ecule and 0.627 (5) Å in the other]. The two independent mol­ecules are disposed about a pseudo center of inversion and are connected by a pair of N—H⋯O hydrogen bonds. Adjacent dimers are linked by a pair of O—H⋯O hydrogen bonds, generating a chain running along the b axis. PMID:22090956

  5. New Economic Realities: The Role of Women Entrepreneurs. Hearings before the Committee on Small Business. House of Representatives, One Hundredth Congress, Second Session (April 26-27, May 10, 11, 17, and 19, 1988).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Small Business.

    This document contains transcripts of oral and written testimony given at six days of Congressional hearings on women entrepreneurs, held in April and May 1988. Many of the witnesses were women who run successful companies that they started by themselves, in a variety of fields, from service industries to construction and manufacturing. Other…

  6. Report on Phase 2 Archaeological Testing at 21 AK 11, Big Sandy Lake, Aitkin County, Minnesota (June 10-11 and August 1-5 and 20-21, 1985)

    DTIC Science & Technology

    1987-10-05

    4.3.1 Area B; a rather narrow ridge which extends east as a peninsula between the south side of Sandy River and the northwestern part of the...excavated around and east of the comfort stations, all along the crest of a narrow peninsula between the south side of Sandy River and the...periodic, natural ground fires (Heinselman 1974) . Logging during the late 19th and early 20th centuries (mostly of the east and south

  7. Occupational Employment Projections for Program Planning Purposes: Issues and Examples. Proceedings of a National Workshop-Conference (TWA Breech Training Academy, Overland Park, Kansas, July 10-11, 1975).

    ERIC Educational Resources Information Center

    Stevens, David W., Ed.

    These conference proceedings (from tape transcription) cover eight major presentations plus roundtable and small-group discussions and workshop sessions and two background papers from a conference attended by producers and consumers of employment projections (Federal, State and local level administrators and technicians). Topics included are…

  8. FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007.

    PubMed

    Eichelberger, Maryna; Golding, Hana; Hess, Maureen; Weir, Jerry; Subbarao, Kanta; Luke, Catherine J; Friede, Martin; Wood, David

    2008-08-12

    The goals of the workshop were to identify gaps in our knowledge and abilities to address the unique challenges encountered in the development of vaccines intended to protect against pandemic influenza and to facilitate implementation of a global research agenda to improve efficacy assessment of pandemic influenza vaccines. This workshop included discussions on: (i) current knowledge regarding immune correlates of protection against seasonal influenza; (ii) human immune responses to avian influenza infection and vaccines for novel influenza viruses; (iii) limitations of currently available assays to evaluate vaccine immunogenicity; and (iv) potential insights from animal models for correlates of protection against avian influenza.

  9. Lecture Series on Electromagnetic Interference and Electromagnetic Compatibility Presented on 10-11 June 1991 in Kjeller, Norway, 13-14 June 1991 in Konigswinter, Germany and 17-18 June 1991 in Lisbon, Portugal.

    DTIC Science & Technology

    1991-06-01

    Hqs) Route Tout Vent Dr A.C. Marvin Sainte Foy des Vignes Dept of Electronics 24100 Bergerac University of York France Heslington York YOI 5DD Dr G.H...between sol - 6 REFERENCES utlons. The majorky of the problem can be solved once and stod and further modifications require only a solution for [1] MIL-E

  10. Ramjet and Ramrocket Propulsion Systems for Missiles Held at Monterey, California, London (United Kingdom), and Neubiberg (Germany F. R.) on 5-6; 10-11 and 13-14 September 1984

    DTIC Science & Technology

    1984-10-01

    Margin of Inlet:, 3et Htrs H 0kkm C, 0.0.5 0.0 10 20 30c. p I -dIv~ 1-13 12 R2T Fig. 16 10 RAMJETS Regions of Application of Ram-Po’R %• RA ROCKE...attack or sideslip) and the rate of heat addition in the combustor. The matching of inlet and thrust nozzle is illustrated by fig. 10 . Some simplifications...1- 0 2 1. 6 8 10 12 14 1 Mo ---- Fig. 3 En’gine Inte~ration and Booster Instalkptlon 2. GEDRATION SOOSTEft SOVAC ?5O K6 U4 Fg42 TALOS GMEF

  11. MATCHE: Management Approach to Teaching Consumer and Homemaking Education. Proceedings: MATCHE I Workshop (San Francisco, California, April 7-8, 1975; Los Angeles, California, April 10-11, 1975).

    ERIC Educational Resources Information Center

    Burrows, Ann, Ed.

    Workshop proceedings in San Francisco and Los Angeles concerning the development of the Management Approach to Teaching Consumer and Homemaking Education (MATCHE) are examined in this report. Basic information gleaned from presentations, reports, and transcripts of taped lectures of both workshops are included. Subjects contained in the report are…

  12. Upper Mississippi River Restoration (UMRR) Project Tier 3 Topobathy Data for Mississippi River Navigation Pools 5a, 6, 10, 11, 12, 14, 15-28, 20, 22, and 24

    USGS Publications Warehouse

    Stone, Jayme M.; Rogala, James T.; Sattler, Stephanie R.; Hanson, Jenny L.

    2016-01-01

    These data are associated with the U.S. Army Corps of Engineers’ Upper Mississippi River Restoration (UMRR) Program project to generate high resolution elevation datasets for the Upper Mississippi River floodplain, between Minneapolis, MN, and Cairo, IL and the Illinois River. The Tier 1 data sets were designed to make the lidar data publicly available as soon as possible. The Tier 2 data have undergone quality assurance testing, water-masking, contour-smoothing, and point-reclassification where necessary, and have been approved for release by the USGS. The Tier 3 data are product of bathymetry merged with terrestrial lidar. UMESC is the lead office for the final processing of these data, which includes additional quality control and serving the data on the UMRR Long Term Resource Monitoring (LTRM) element’s website.

  13. Brown v. Board of Education of Topeka: An Assessment Thirty Years Later. A Series of Lectures and Discussions, Proceedings (Institute, West Virginia, February 10-11 and April 11-13, 1984).

    ERIC Educational Resources Information Center

    West Virginia State Coll., Institute.

    Papers presented at a 1984 lecture series and symposium on the impact of the 1954 Brown v. Board of Education of Topeka Supreme Court decision case are collected in this report. The papers (and their authors) are: (1) "Legal Aspects of the Brown Decision" (Robert L. Carter); (2) "Desegregation/Integration and the Media: Fallout from…

  14. Variability in the high energy gamma ray emission from Cyg X-3 over a two-year period (1983 - 1984) at E 4 x 10(11) eV

    NASA Technical Reports Server (NTRS)

    Cawley, M. F.; Fegan, D. J.; Gibbs, K.; Gorham, P. W.; Lamb, R. C.; Liebing, D. F.; Porter, N. A.; Stenger, V. J.; Weekes, T. C.; Williams, R. J.

    1985-01-01

    Cygnus X-3 is observed to emit gamma rays with energies in excess of 4 x 10 to the 11th power eV during two out of 9 observational categories over an 18 month time span. The emissions are observed at the 0.6 phase of the characteristic 4.8 hr light curve for this binary system. We estimate a peak flux at phase 0.6 of 5 x 10 to the minus 10th power photons cm-2s-1 at a software threshold of 8 x 10 to the 11th power eV for Oct/Nov 1983. A flux for the June 84 effect cannot be reliably calculated at present due to lack of Monte Carlo simulations for the energy range and spectral region. For the other 7 observational categories the observations are consistent with zero source emission. The light curve would appear to be variable on a time scale of a couple of weeks at these categories. Selection of compact images in accordance with Monte Carlo simulations combined with empirical optimization techniques have led to an enriched gamma ray light curve for the Oct/Nov 1983 data. Selection on the basis of shower orientation, however, has not led to any notable enhancement of the gamma ray content. Individual Cherenko images can be reliably sorted on an event by event basis into either proton-induced or photon-induced showers.

  15. Teacher Shortage in Science and Mathematics: Myths, Realities, and Research. Proceedings of a Conference Sponsored by the National Institute of Education (Washington, District of Columbia, February 10-11, 1983).

    ERIC Educational Resources Information Center

    Taylor, John L., Ed.

    This conference was designed to identify salient elements of the national science/mathematics teacher shortage, add corollary data to the existing body of knowledge, and to influence and guide future NIE research in the area. The proceedings include: welcoming and keynote addresses by, respectively, Manuel J. Justiz and T. H. Bell; five…

  16. Paris Peace Conference: Writing a Treaty To End World War I. Grade 10/11 Lesson. Schools of California Online Resources for Education (SCORE): Connecting California's Classrooms to the World.

    ERIC Educational Resources Information Center

    Niles, Georgette Wilbur

    This problem-based learning unit asks students to assume roles as experts from countries that participated in World War I. These experts will meet both in expert groups and with their respective country representatives to determine what terms, in four specific areas, should be included in the treaty that will formally end the war. Next, they must…

  17. Galbahe C1 y C2 Tests de Lengua (Castellano. Escalas 1 y 2). Medida del nivel de Castellano para ninos de 7-8 y 10-11 anos. Manual de Aplicacion. Glotodidaktika-Lanak 27. (Galbahe Language Tests C1 and C2--Spanish, Scales 1 and 2. Measure of Level of Spanish for Children 7-8 and 10-11 years. Test administration Manual. Glotodidaktika-Lanak Series Number 27).

    ERIC Educational Resources Information Center

    Sierra, Josu; Olaziregi, Ibon

    The Galbahe Language Tests C1 and C2 measure the Spanish language proficiency of children aged 7 to 8 years (C1) and those aged 10 to 11 years (C2). Equivalent tests E1 and E2 measure the Basque language achievement of the same age groups, respectively. Both tests were designed as part of a study of teaching of the Basque language in parts of…

  18. ECAT ART - a continuously rotating PET camera: performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department.

    PubMed

    Bailey, D L; Young, H; Bloomfield, P M; Meikle, S R; Glass, D; Myers, M J; Spinks, T J; Watson, C C; Luk, P; Peters, A M; Jones, T

    1997-01-01

    Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameterx20 cm long cylindrical phantom, no scatter correction) is 11400 cps.kBq-1.ml-1. This compares with 5800 and 40500 cps.kBq-1.ml-1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350-650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of approximately 15 kBq.ml-1 in the cylinder. Spatial resolution is approximately 6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 microSv. h-1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

  19. The absorbed dose to blood from blood-borne activity

    NASA Astrophysics Data System (ADS)

    Hänscheid, H.; Fernández, M.; Lassmann, M.

    2015-01-01

    The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics. The results were deduced from published data for vessel radius-dependent dose rate coefficients and reasonable assumptions on the blood-volume distribution as a function of the vessel radius. Different parts of the circulatory system were analyzed separately. Vessel size information for heart chambers, aorta, vena cava, pulmonary artery, and capillaries was taken from published results of morphometric measurements. The remaining blood not contained in the mentioned vessels was assumed to reside in fractal-like vascular trees, the smallest branches of which are the arterioles or venules. The applied vessel size distribution is consistent with recommendations of the ICRP on the blood-volume distribution in the human. The resulting average absorbed dose rates to the blood per nuclear disintegration per milliliter (ml) of blood are (in 10-11 Gy·s-1·Bq-1·ml) Y-90: 5.58, I-131: 2.49, Lu-177: 1.72, Sm-153: 2.97, Tc-99m: 0.366, C-11: 4.56, F-18: 3.61, Ga-68: 5.94, I-124: 2.55. Photon radiation contributes 1.1-1.2·10-11 Gy·s-1·Bq-1·ml to the total dose rate for positron emitters but significantly less for the other nuclides. Blood self-absorption of the energy emitted by ß-particles in the whole blood ranges from 37% for Y-90 to 80% for Tc-99m. The correspondent values in vascular trees, which are important for the absorbed dose to organs, range from 30% for Y-90 to 82% for Tc-99m.

  20. Development of derived investigation levels for use in internal dosimetry at the West Valley Demonstration Project

    SciTech Connect

    Johnson, P.

    1991-12-31

    The objective was to determine if the routine intemal dosimetry program at the West Valley Demonstration Project is capable of meeting the performance objective of 1 mSv annual effective dose equivalent due to internal contamination. With the use of the computer code REMedy the annual effective dose equivalent is calculated. Some of the radionuclides of concern result in an annual effective dose equivalent that exceeds the performance objective. Although the results exceed the performance objective, in all but two cases they do not exceed the US DOE regulatory limits. In these instances the Th-232 and Am-241 were determined to exceed the committed dose equivalent limit to their limiting tissue. In order to document the potential missed dose for regulatory compliance, Sr-90 is used as an indicator for Th-232. For Am-241 an investigation as to whether or not the minimum detectable amount can be lowered is performed. The derived investigation levels as a result of this project are 4.9E3 Bq/lung count for Co-60, 2.2E4 Bq/lung count for Cs-137, 1.9 Bq/1 for Sr-90 and for radionuclides other than Sr-90 any value greater than or equal to three standard deviations above their net count is considered to require further investigation.

  1. Bacterial 16S diversity of basal ice, sediment, and the forefront of Svínafellsjökull glacier via isolation chips and classical culturing techniques

    NASA Astrophysics Data System (ADS)

    Toubes-Rodrigo, Mario; Cook, Simon; Elliott, David; Sen, Robin

    2016-04-01

    Sub-glacial microbes are receiving increased attention due to their central roles in storage and release of greenhouse gases, such as methane and CO2. Climate change driven warming and resulting glacier retreat exposes bedrock that can contribute to soil formation in which subglacial-released microorganisms may play a crucial role. Basal ice, which forms in the lowermost part of glaciers in the absence of light is characterised by a high debris concentration that can be regarded as a glacier niche that must be sustained by the utilisation of overridden organic matter or primary production based on chemolithotrophic metabolism. Compared to other glacial ecosystems, subglacial microbial ecology remains poorly understood, due to limited accessibility and difficulties associated with low microbial occupancy. In this study, different defined types of basal ice (cryofacies) were targeted, namely stratified cryofacies (highest sediment content, fine-grained), debris bands (intermediate debris content, coarse-grained) and dispersed cryofacies (low sediment content, polymodal). Debris bands have been suggested to form by the entrainment of sediment due to shearing forces near the bedrock. Internal glacial processes proceed to modify debris bands leading to the formation of dispersed cryofacies. Stratified cryofacies, result from a range of processes that confers high debris content with a characteristically layered appearance. Basal ice is involved in the creation of subglacial tills and therefore in moraine formation. Elemental analysis, using a portable X-ray fluorescence portable analyser (Olympus Delta), confirmed that debris bands and dispersed cryofacies were highly similar, and distinct from stratified cryofacies, which support the dispersed cryofacies formation hypothesis. Bacteria from basal ice, sediment and forefront soil were cultured via inserted isolation chips (ichips) and traditional extraction/dilution plating. Isolated bacteria were subsequently identified following 16S rRNA gene sequencing and phylogenetics. Basal ice communities comprised a mix of soil and glacial bacteria, with higher proportion of ice-related bacteria in dispersed cryofacies (Polaromonas sp, Flavobacterium xinjiangense) and a water (Arthrobacter agilis) and soil-related microorganisms (Pseudomonas sp) in the debris bands, similar to sub-glacial sediment. During debris band formation, microorganisms from bedrock and overridden soils can be entrained into the ice matrix and those which have adapted to icy conditions can proliferate, explaining the higher viable bacterial counts on dispersed ice as well as higher proportions of glacial isolated-related microorganisms. Once the subglacial sediment and basal ice are released from the glacier and as soil age increases, increased representation of soil-related microbiota (Arthrobacter alpinus, Stenotrophomonas rhizophila) were identified. The results in this study suggest cultivable communities shift in two directions: firstly, within the basal ice layer from subglacial sediment, dominated by soil and water communities towards dispersed ice with a high proportion of glacial communities. The other shift occurs when subglacial sediment is released into the forefront, where the composition changes towards a soil-like microbiota with increase in soil age.

  2. Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo.

    PubMed

    Zou, Yanfen; Jiang, Ziyan; Yu, Xiang; Sun, Ming; Zhang, Yuanyuan; Zuo, Qing; Zhou, Jing; Yang, Nana; Han, Ping; Ge, Zhiping; De, Wei; Sun, Lizhou

    2013-01-01

    SPRY4-IT1 has been reported to have extremely high expression in normal placenta tissues. It is a Long noncoding RNA (lncRNA), which is associated with cell growth, migration, invasion, and apoptosis in melanoma. A 2.8-fold increase of SPRY4-IT1 expression was validated by Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in severe preeclamptic placenta as compared with that of the normal ones (n=25) in this study. Furthermore, the role of SPRY4-IT1 in proliferation, migration, apoptosis, and network formation ability of trophoblast cells HTR-8/SVneo was assessed. Suppression of SPRY4-IT1 using siRNA treatment and its overexpression using plasmid targeting SPRY4-IT1 were performed in order to explore the biological function of SPRY4-IT1 in the development and progression of trophoblast cells HTR-8/SVneo, in vitro. The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. Our study showed for the first time that aberrant expression of lncRNA SPRY4-IT1 might contribute to the abnormal condition of trophoblast cells HTR-8/SVneo. Therefore, we proposed SPRY4-IT1 as a novel lncRNA molecule, which might be associated with the pathogenesis of preeclampsia and might provide a new target for its early diagnosis and treatment.

  3. Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen.

    PubMed

    Williams, Christina K; Vaithiyalingam, Sivaraja; Hammel, Michal; Pipas, James; Chazin, Walter J

    2012-02-15

    Simian Virus 40 uses the large T antigen (Tag) to bind and inactivate retinoblastoma tumor suppressor proteins (Rb), which can result in cellular transformation. Tag is a modular protein with four domains connected by flexible linkers. The N-terminal J domain of Tag is necessary for Rb inactivation. Binding of Rb is mediated by an LXCXE consensus motif immediately C-terminal to the J domain. Nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) were used to study the structural dynamics and interaction of Rb with the LXCXE motif, the J domain and a construct (N(260)) extending from the J domain through the origin binding domain (OBD). NMR and SAXS data revealed substantial flexibility between the domains in N(260). Binding of pRb to a construct containing the LXCXE motif and the J domain revealed weak interactions between pRb and the J domain. Analysis of the complex of pRb and N(260) indicated that the OBD is not involved and retains its dynamic independence from the remainder of Tag. These results support a 'chaperone' model in which the J domain of Tag changes its orientation as it acts upon different protein complexes.

  4. Relative Efficacy of Criminological, Clinical, and Personality Measures of Future Risk of Offending in Mentally Disordered Offenders: A Comparative Study of HCR-20, PCL:SV, and OGRS

    ERIC Educational Resources Information Center

    Gray, Nicola S.; Snowden, Robert J.; MacCulloch, Sophie; Phillips, Helen; Taylor, John; MacCulloch, Malcolm J.

    2004-01-01

    The authors compared the ability of 3 commonly used measures of risk of future offending in a sample of 315 mentally disordered offenders discharged from a medium-secure unit in the United Kingdom. The authors explored whether the same criminogenic factors that predict recidivism in the general population also predict recidivism in mentally…

  5. The phage shock protein PspA facilitates divalent metal transport and is required for virulence of Salmonella enterica sv. Typhimurium.

    PubMed

    Karlinsey, Joyce E; Maguire, Michael E; Becker, Lynne A; Crouch, Marie-Laure V; Fang, Ferric C

    2010-11-01

    The phage shock protein (Psp) system is induced by extracytoplasmic stress and thought to be important for the maintenance of proton motive force. We investigated the contribution of PspA to Salmonella virulence. A pspA deletion mutation significantly attenuates the virulence of Salmonella enterica serovar Typhimurium following intraperitoneal inoculation of C3H/HeN (Ity(r) ) mice. PspA was found to be specifically required for virulence in mice expressing the natural resistance-associated macrophage protein 1 (Nramp1) (Slc11a1) divalent metal transporter, which restricts microbial growth by limiting the availability of essential divalent metals within the phagosome. Salmonella competes with Nramp1 by expressing multiple metal uptake systems including the Nramp-homologue MntH, the ABC transporter SitABCD and the ZIP family transporter ZupT. PspA was found to facilitate Mn(2+) transport by MntH and SitABCD, as well as Zn(2+) and Mn(2+) transport by ZupT. In vitro uptake of (54) Mn(2+) by MntH and ZupT was reduced in the absence of PspA. Transport-deficient mutants exhibit reduced viability in the absence of PspA when grown under metal-limited conditions. Moreover, the ZupT transporter is required for Salmonella enterica serovar Typhimurium virulence in Nramp1-expressing mice. We propose that PspA promotes Salmonella virulence by maintaining proton motive force, which is required for the function of multiple transporters mediating bacterial divalent metal acquisition during infection.

  6. Biofilms promote survival and virulence of Salmonella enterica sv. Tennessee during prolonged dry storage and after passage through an in vitro digestion system.

    PubMed

    Aviles, Bryan; Klotz, Courtney; Eifert, Joseph; Williams, Robert; Ponder, Monica

    2013-04-01

    Salmonella enterica serotypes have been linked to outbreaks associated with low water activity foods. While the biofilm-forming abilities of Salmonella improve its survival during thermal processing and sanitation it is unclear whether biofilms enhance survival to desiccation and gastric stresses. The purpose of this study was to quantify the effect of physiological state (planktonic versus biofilm) and prior exposure to desiccation and storage in dry milk powder on Salmonella survival and gene expression after passage through an in vitro digestion model. Planktonic cells of Salmonella enterica serotype Tennessee were deposited onto membranes while biofilms were formed on glass beads. The cells were subsequently dried at room temperature and stored in dried milk powder (a(w)=0.3) for up to 30 days. Salmonella survival was quantified by serial dilution onto Brilliant Green Agar before desiccation, after desiccation, after 1-day storage and after 30-day storage. At each sampling period both physiological states were tested for survival through a simulated gastrointestinal system. RNA was extracted at the identical time points and Quantitative Real-Time PCR was used to determine relative expression for genes associated with stress response (rpoS, otsB), virulence (hilA, invA, sipC) and a housekeeping gene 16S rRNA. The physiological state and length of storage affected the survival and gene expression of Salmonella within the desiccated milk powder environment and after passage through an in vitro digestion system (p<0.05). Larger numbers of S. Tennessee were recovered by plate counts for biofilms compared to planktonic, however, the numbers of Salmonella genomes detected by qPCR were not significantly different suggesting entry of the planktonic cells of S. Tennessee into a viable but non-culturable state. The increased expression of stress response genes rpoS and otsB correlated with survival, indicating cross-protection to low water activity and acid stress. Increased expression of virulence-associated genes was seen in cells exposed to dry storage for short periods, however the largest amount of expression occurred in biofilm cells stored for 30 days at aw 0.3, suggesting increased virulence potential.

  7. Effects of dehydroepiandrosterone on obesity and glucose-6-phosphate dehydrogenase activity in the lethal yellow mouse (strain 129/Sv-Ay/Aw).

    PubMed

    Granholm, N H; Staber, L D; Wilkin, P J

    1987-04-01

    We investigated the anti-obesity effects of the adrenal androgen, dehydroepiandrosterone (DHEA), on genetically predisposed obese lethal yellow mice (Ay/Aw). Secondly, we tested the hypothesis that DHEA promotes its anti-obesity effects by decreasing the activity of glucose-6-phosphate dehydrogenase (G6PDH). We subjected four genotype-sex combinations of yellow and agouti (control) mice to four dietary treatments and determined weight changes, food consumption, and G6PDH activity. Although G6PDH activities of yellow mice were considerably decreased in the 0.4% DHEA treatment group, they were elevated in the 0.0 and 0.1% DHEA treatment groups. In contrast, G6PDH activities of DHEA-treated control agouti mice remained relatively constant. These studies confirm that DHEA prevents the Ay gene from promoting excess fat deposition via some mechanism(s) other than reduced dietary intake. However, the overall absence of agreement between weight change (gain or loss) and G6PDH activity suggests that the anti-obesity activity of DHEA is not mediated via G6PDH. Since yellow obese (Ay/Aw) mice were found to be more susceptible to DHEA's effects than their agouti (Aw/Aw) littermates, Ay appears to induce an altered metabolism in Ay/Aw mice which is more susceptible to the effects of DHEA than the normal metabolism of Aw/Aw mice.

  8. Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain.

    PubMed

    Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A

    2011-06-01

    The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS-PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner.

  9. Structure-based Design of a Disulfide-lined Oligomeric Form of the Simian Virus 40 (SV40) Large T Antigen DNA-Binding Domain

    SciTech Connect

    G Meinke; P Phelan; A Fradet-Turcotte; J Archambault; P Bullock

    2011-12-31

    The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS-PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 {angstrom} resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner.

  10. The Integration of Nanoscale Techniques for an Improved Battery Technology

    DTIC Science & Technology

    2012-06-08

    Journal of Polymer Science, Part B: Polymer Physics 31 (1993) (13) 1941. [110]. Y. Zheng, F. Chia, G. Ungar , P.V. Wright, Chemical Communications...2000) (16) 1459. 42 [111]. Y. Zheng, F. Chia, G. Ungar , T.H. Richardson, P.V. Wright, Electrochimica Acta 46 (2001) (10-11) 1397. [112]. Y...Zheng, F. Chia, G. Ungar , P.V. Wright, Journal of Power Sources 97-98 (2001) 641. [113]. V. Percec, G. Johansson, J. Heck, G. Ungar , S.V. Batty

  11. Crystal structure of methyl (3RS,4SR,4aRS,11aRS,11bSR)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-deca-hydro-3,11b-ep-oxy-azepino[2,1-a]iso-indole-4-carboxyl-ate.

    PubMed

    Toze, Flavien A A; Poplevin, Dmitry S; Zubkov, Fedor I; Nikitina, Eugeniya V; Porras, Ciara; Khrustalev, Victor N

    2015-10-01

    The title compound, C15H19NO4, is the a product of the esterification of the corresponding carbonic acid with methanol. The mol-ecule comprises a fused tetra-cyclic system containing three five-membered rings (2-pyrrolidinone, tetra-hydro-furan and di-hydro-furan) and one seven-membered ring (azepane). The five-membered rings have the usual envelope conformations, with the quaternary C atom being the flap atom for the 2-pyrrolidinone ring, and the ether O atom being the common flap atom for the remaining rings. The seven-membered azepane ring adopts a chair conformation with the methine and middle methyl-ene C atoms lying above and below the mean plane defined by the remaining five atoms. The carboxyl-ate substituent is rotated by 77.56 (5)° with respect to the base plane of the tetra-hydro-furan ring. In the crystal, the mol-ecules are bound by weak C-H⋯O hydrogen-bonding inter-actions into puckered layers parallel to (001).

  12. IR: A Look towards the 1980's and Institutional Research and Student Aid. Proceedings, Sixth Annual Meeting of the North Carolina Association for Institutional Research and the Drive-In Conference, Charlotte, November 1-2, 1978, and Southern Pines, August 10-11, 1978.

    ERIC Educational Resources Information Center

    Brown, Charles I., Ed.; Sanford, Timothy R., Ed.

    Highlights of the Sixth Annual Meeting of the North Carolina Association for Institutional Research (NCAIR) and of the Drive-In Conference held prior to the annual meeting are presented. The major emphasis of the annual meeting was to look toward the 1980's and project the role that institutional research might play in higher education. The…

  13. Integrating Research on Faculty: Seeking New Ways to Communicate about the Academic Life of Faculty. Results from the Forum Sponsored by the National Center for Education Statistics, the Association for Institutional Research, and the American Association of State Colleges and Universities. Conference Report (Washington, D.C., January 10-11, 1994).

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    This publication reports on a 1994 forum on integrating research on college and university faculty and presents the commissioned papers and findings of the forum along with references to relevant research on faculty. A description of the forum notes that it addressed the lack of integration in current policy discussions about college and…

  14. Seminar on Basic Documentation Practices (Les Pratiques de Base en Matiere de Documentation) Held in Ankara, Turkey on 3-4 September 1992, in Athens, Greece on 7-8 September 1982 in Lisbon, Portugal on 10-11 September 1992

    DTIC Science & Technology

    1992-08-01

    de Informagio *a bibllotecas e Documentagao - Comit6 de o sou Impacto na actividade Informagao para a Ind0stria des bibliotecas am Portugal: (FID/Il...1988, vol.3, p. Neuilly-sur-Seine: AGARD, 24-32. 1991, p.13.1-13.15. 10. BARRULAS, Maria Joaquina, 4. Portugal. Biblioteca Nacional. CORREIA, Ana Maria

  15. [μ-2,8-Dimethyl-1,4,5,6,7,10,11,12-octa­hydro­diimidazo[4,5-h;4′,5′-c][1,6]diaze­cine-5,11-diacetato]bis­[diaqua­nitrato­copper(II)] trihydrate

    PubMed Central

    Luna-Ramírez, Karen S.; Bernès, Sylvain; Gasque, Laura

    2008-01-01

    The title compound, [Cu2(C16H20N6O4)(NO3)2(H2O)4]·3H2O, crystallizes with two dinuclear CuII complex mol­ecules, each lying on an inversion center, and six solvent water mol­ecules per unit cell. The central 1,6-diazecine ring adopts the common chair conformation invariably found in the family of complexes bearing such ligands. The CuII atoms have an octa­hedral geometry, with a very strong tetra­gonal distortion due to the Jahn–Teller effect. Axial sites are occupied by a nitrate ion and a water mol­ecule. The Cu⋯Cu separations [7.3580 (9) and 7.3341 (9) Å] are compatible with a potential catecholase activity. Neighboring mol­ecules in the crystal structure are connected via O—H⋯O hydrogen bonds formed by water mol­ecules and carboxyl­ate O atoms. N—H⋯O hydrogen bonds are also present. PMID:21201593

  16. Crystal structure of methyl (3RS,4SR,4aRS,11aRS,11bSR)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-deca­hydro-3,11b-ep­oxy­azepino[2,1-a]iso­indole-4-carboxyl­ate

    PubMed Central

    Toze, Flavien A. A.; Poplevin, Dmitry S.; Zubkov, Fedor I.; Nikitina, Eugeniya V.; Porras, Ciara; Khrustalev, Victor N.

    2015-01-01

    The title compound, C15H19NO4, is the a product of the esterification of the corresponding carbonic acid with methanol. The mol­ecule comprises a fused tetra­cyclic system containing three five-membered rings (2-pyrrolidinone, tetra­hydro­furan and di­hydro­furan) and one seven-membered ring (azepane). The five-membered rings have the usual envelope conformations, with the quaternary C atom being the flap atom for the 2-pyrrolidinone ring, and the ether O atom being the common flap atom for the remaining rings. The seven-membered azepane ring adopts a chair conformation with the methine and middle methyl­ene C atoms lying above and below the mean plane defined by the remaining five atoms. The carboxyl­ate substituent is rotated by 77.56 (5)° with respect to the base plane of the tetra­hydro­furan ring. In the crystal, the mol­ecules are bound by weak C—H⋯O hydrogen-bonding inter­actions into puckered layers parallel to (001). PMID:26594446

  17. Education and Training for American Competitiveness. Hearings before the Committee on Education and Labor, House of Representatives, One Hundredth Congress, First Session on H.R. 5, School Improvement Act of 1987; and H.R. 90 Education and Training for American Competitiveness Act of 1987 (February 10, 11, 18, 25; March 4, 11, and 12, 1987).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    This congressional report contains testimony pertinent to the passage of the School Improvement Act of 1987 and the Education and Training for American Competitiveness Act of 1987. Testimony by representatives of the following agencies and organizations is included in the report: New York University; the United Steelworkers of America; the…

  18. (E)-2-{[1-(3,11-Dimethyl-4-methyl-ene-10-oxo-1-phenyl-4,5,10,11-tetra-hydro-1H-benzo[b]pyrazolo-[3,4-f][1,5]diazo-cin-5-yl)ethyl-idene]amino}-N-methyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)benzamide.

    PubMed

    Meneghetti, Fiorella; Maggio, Benedetta

    2013-01-01

    The central eight-membered ring of the title compound, C40H36N8O2, deviates from the ideal boat conformation because the bond between the exo-ethyl-ene group and the adjacent N atom is twisted by 60.0 (4)° due to steric hindrance. Its adjacent benzene and pyrazole rings are oriented almost perpendicular to each other, making a dihedral angle of 85.8 (3)°. In the crystal, the mol-ecules are linked by C(ar)-H⋯O hydrogen bonds, generating a three-dimensional network.

  19. 17-(5-Ethyl-6-methyl-heptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-deca-hydro-1H-cyclo-penta[a]phenanthrene-3,7-diol from Chisocheton tomentosus (Meliaceae).

    PubMed

    Najmuldeen, Ibrahim A; Hadi, Abdul Hamid Abdul; Awang, Khalijah; Mohamad, Khalit; Ng, Seik Weng

    2008-10-22

    The asymmetric unit of the title compound, C(29)H(50)O(2), contains two mol-ecules; one mol-ecule is linked to the other by two O-H⋯O hydrogen bonds, whereas only one of the hydr-oxy groups of the second mol-ecule is involved in hydrogen bonding. This gives rise to a chain that runs along the a axis of the monoclinic unit cell.

  20. Uncertainty analysis of doses from ingestion of plutonium and americium.

    PubMed

    Puncher, M; Harrison, J D

    2012-02-01

    Uncertainty analyses have been performed on the biokinetic model for americium currently used by the International Commission on Radiological Protection (ICRP), and the model for plutonium recently derived by Leggett, considering acute intakes by ingestion by adult members of the public. The analyses calculated distributions of doses per unit intake. Those parameters having the greatest impact on prospective doses were identified by sensitivity analysis; the most important were the fraction absorbed from the alimentary tract, f(1), and rates of uptake from blood to bone surfaces. Probability distributions were selected based on the observed distribution of plutonium and americium in human subjects where possible; the distributions for f(1) reflected uncertainty on the average value of this parameter for non-specified plutonium and americium compounds ingested by adult members of the public. The calculated distributions of effective doses for ingested (239)Pu and (241)Am were well described by log-normal distributions, with doses varying by around a factor of 3 above and below the central values; the distributions contain the current ICRP Publication 67 dose coefficients for ingestion of (239)Pu and (241)Am by adult members of the public. Uncertainty on f(1) values had the greatest impact on doses, particularly effective dose. It is concluded that: (1) more precise data on f(1) values would have a greater effect in reducing uncertainties on doses from ingested (239)Pu and (241)Am, than reducing uncertainty on other model parameter values and (2) the results support the dose coefficients (Sv Bq(-1) intake) derived by ICRP for ingestion of (239)Pu and (241)Am by adult members of the public.

  1. Radiation dose assessment of exposure to depleted uranium.

    PubMed

    Li, Wei Bo; Gerstmann, Udo C; Höllriegl, Vera; Szymczak, Wilfried; Roth, Paul; Hoeschen, Christoph; Oeh, Uwe

    2009-07-01

    Depleted uranium (DU) is claimed to contribute to human health problems, known as the Gulf War Syndrome and the Balkan Syndrome. Quantitative radiation dose is required to estimate the health risk of DU materials. The influences of the solubility parameters in the human alimentary tract and the respiratory tract systems and the aerosol particles size on the radiation dose of DU materials were evaluated. The dose conversion factor of daily urinary excretion of DU is provided. The retention and excretion of DU in the human body after a contamination at a wound site were predicted. Dose coefficients of DU after ingestion and inhalation were calculated using the solubility parameters of the DU corrosion products in simulated gastric and simulated lung fluid, which were determined in the Helmholtz Zentrum München. (238)U is the main radiation dose contributor per 1 Bq of DU materials. The dose coefficients of DU materials were estimated to be 3.5 x 10(-8) and 2.1 x 10(-6) Sv Bq(-1) after ingestion and inhalation for members of the public. The ingestion dose coefficient of DU materials is about 75% of the natural uranium value. The inhalation dose coefficient of DU material is in between those for Type M and Type S according to the category for inhaled materials defined by the International Commission on Radiological Protection. Radiation dose possibly received from DU materials can directly be estimated by using the dose conversion factor provided in this study, if daily urinary excretion of DU is measured.

  2. Factors that elevate the internal radionuclide and chemical retention, dose and health risks to infants and children in a radiological-nuclear emergency.

    PubMed

    Richardson, Richard B

    2009-06-01

    The factors that influence the dose and risk to vulnerable population groups from exposure and internal uptake of chemicals are examined and, in particular, the radionuclides released in chemical, biological, radiological, nuclear and explosive events. The paper seeks to identify the areas that would benefit from further research. The intake and body burdens of carbon and calcium were assessed as surrogates for contaminants that either act like or bind to hydrocarbons (e.g. tritium and (14)C) or bone-seeking radionuclides (e.g. (90)Sr and (239)Pu). The shortest turnover times for such materials in the whole body were evaluated for the newborn: 11 d and 0.5 y for carbon and calcium, respectively. However, their biokinetic behaviour is complicated by a particularly high percentage of the gut-absorbed dietary intake of carbon (approximately 16%) and calcium (approximately 100%) that is incorporated into the soft tissue and skeleton of the growing neonate. The International Commission on Radiological Protection dose coefficients (Sv Bq(-1)) were examined for 14 radionuclides, including 9 of concern because of their potential use in radiological dispersal devices. The dose coefficients for a 3-month-old are greater than those for adults (2-56 times more for ingestion and 2-12 times for inhalation). The age-dependent dose and exposure assessment of contaminant intakes would improve by accounting for gender and growth where it is currently neglected. Health risk is evaluated as the product of the exposure and hazard factors, the latter being about 10-fold greater in infants than in adults. The exposure factor is also approximately 10-fold higher for ingestion by infants than by adults, and unity for inhalation varying with the contaminant. Qualitative and quantitative physiological and epidemiological evidence supports infants being more vulnerable to cancer and neurological deficit than older children.

  3. Transcriptional and Post-Transcriptional Modulation of SPI1 and SPI2 Expression by ppGpp, RpoS and DksA in Salmonella enterica sv Typhimurium

    PubMed Central

    Rice, Christopher J.; Ramachandran, Vinoy K.; Shearer, Neil; Thompson, Arthur

    2015-01-01

    The expression of genes within Salmonella Pathogenicity Islands 1 and 2 (SPI1, SPI2) is required to facilitate invasion and intracellular replication respectively of S. Typhimurium in host cell lines. Control of their expression is complex and occurs via a variety of factors operating at transcriptional and post-transcriptional levels in response to the environmental stimuli found within the host. Several of the factors that modulate SPI1 and SPI2 expression are involved in the redistribution or modification of RNA polymerase (RNAP) specificity. These factors include the bacterial alarmone, ppGpp, the alternative sigma factor, RpoS, and the RNAP accessory protein, DksA. In this report we show not only how these three factors modulate SPI1 and SPI2 expression but also how they contribute to the ‘phased’ expression of SPI1 and SPI2 during progress through late-log and stationary phase in aerobic rich broth culture conditions. In addition, we demonstrate that the expression of at least one SPI1-encoded protein, SipC is subject to DksA-dependent post-transcriptional control. PMID:26039089

  4. Induction of apoptosis in the LNCaP human prostate carcinoma cell line and prostate adenocarcinomas of SV40T antigen transgenic rats by the Bowman-Birk inhibitor.

    PubMed

    Tang, MingXi; Asamoto, Makoto; Ogawa, Kumiko; Naiki-Ito, Aya; Sato, Shinya; Takahashi, Satoru; Shirai, Tomoyuki

    2009-11-01

    The soybean-derived serine protease inhibitor, Bowman-Birk inhibitor (BBI), has been reported as a potent chemoprevention agent against several types of tumors. The present study was undertaken to evaluate the effects of BBI on androgen-sensitive/dependent prostate cancers using a human prostate cancer cell (LNCaP) and the transgenic rats developing adenocarcinoma of the prostate (TRAP) model. Treatment of LNCaP prostate cancer cells with 500 microg/mL BBI resulted in inhibition of viability measured on WST-1 assays, with induction of connexin 43 (Cx43) and cleaved caspase-3 protein expression. Feeding of 3% roughly prepared BBI (BBIC) to TRAP from the age 3 weeks to 13 weeks resulted in significant reduction of the relative epithelial areas within the acinus and multiplicity of the adenocarcinomas in the lateral prostate lobes. Cx43- and terminal deoxynucleotidyl transferase mediated dUTP-biotin end labeling of fragmented DNA (TUNEL)-positive apoptotic cancer cells were more frequently observed in the lateral prostates treated with BBIC than in the controls. These in vivo and in vitro results suggest that BBI possesses chemopreventive activity associated with induction of Cx43 expression and apoptosis.

  5. Randomized pilot study and qualitative evaluation of a clinical decision support system for brain tumour diagnosis based on SV ¹H MRS: evaluation as an additional information procedure for novice radiologists.

    PubMed

    Sáez, Carlos; Martí-Bonmatí, Luis; Alberich-Bayarri, Angel; Robles, Montserrat; García-Gómez, Juan M

    2014-02-01

    The results of a randomized pilot study and qualitative evaluation of the clinical decision support system Curiam BT are reported. We evaluated the system's feasibility and potential value as a radiological information procedure complementary to magnetic resonance (MR) imaging to assist novice radiologists in diagnosing brain tumours using MR spectroscopy (1.5 and 3.0T). Fifty-five cases were analysed at three hospitals according to four non-exclusive diagnostic questions. Our results show that Curiam BT improved the diagnostic accuracy in all the four questions. Additionally, we discuss the findings of the users' feedback about the system, and the further work to optimize it for real environments and to conduct a large clinical trial.

  6. Crystal structure of (S)-2-[(3S,8S,9S,10R,13S,14S,17R)-3-hy-droxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-deca-hydro-1H-cyclo-penta[a]phenanthren-17-yl]-N-meth-oxy-N-methyl-pro-pan-amide (Fernholz Weinreb amide).

    PubMed

    Viktorsson, Elvar Ørn; Åstrand, Ove Alexander Høgmoen; Haseeb, Rasha Sabah; Görbitz, Carl Henrik; Rongved, Pål

    2015-03-01

    The literature compound 3β-hy-droxy-bis-nor-5-cholenic aldehyde is an important inter-mediate for the synthesis of new modulators of the nuclear oxysterol receptor Liver X. As part of our ongoing search for new LXR antagonists, the title compound, C24H39NO3, has proven to be an important inter-mediate in our new synthetic pathway, giving the corresponding aldehyde in high yield and in only three steps from the commercially available 3β-hy-droxy-bis-nor-5-cholenic acid. The title amide crystallized with two mol-ecules in the asymmetric unit, linked into helices by O-H⋯O hydrogen bonds involving the hy-droxy and carbonyl groups.

  7. (E)-2-{[1-(3,11-Dimethyl-4-methyl­ene-10-oxo-1-phenyl-4,5,10,11-tetra­hydro-1H-benzo[b]pyrazolo­[3,4-f][1,5]diazo­cin-5-yl)ethyl­idene]amino}-N-methyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)benzamide

    PubMed Central

    Meneghetti, Fiorella; Maggio, Benedetta

    2013-01-01

    The central eight-membered ring of the title compound, C40H36N8O2, deviates from the ideal boat conformation because the bond between the exo-ethyl­ene group and the adjacent N atom is twisted by 60.0 (4)° due to steric hindrance. Its adjacent benzene and pyrazole rings are oriented almost perpendicular to each other, making a dihedral angle of 85.8 (3)°. In the crystal, the mol­ecules are linked by C(ar)—H⋯O hydrogen bonds, generating a three-dimensional network. PMID:24098259

  8. Implementation of iodine biokinetic model for interpreting I-131 contamination in breast milk after the Fukushima nuclear disaster

    NASA Astrophysics Data System (ADS)

    Tani, Kotaro; Kurihara, Osamu; Kim, Eunjoo; Yoshida, Satoshi; Sakai, Kazuo; Akashi, Makoto

    2015-07-01

    After the accident at the Fukushima Daiichi Nuclear Power Plant run by Tokyo Electric Power Company in 2011, breast milk samples obtained from volunteers living in Fukushima and neighboring prefectures were examined and small amounts of I-131 (2.2-36.3 Bq/kg) were detected in some samples. In this work, the I-131 concentrations in breast milk from nursing mothers in Ibaraki prefecture were calculated based on the iodine biokinetic model during lactation together with time-variable intake scenarios by inhalation of ambient air and ingestion of tap water, using the authors’ code. The calculated I-131 concentrations in breast milk generally agreed with those measured for the volunteers. Based on the results, thyroid equivalent doses to breast-fed infants were estimated for each place of residence of the volunteers on the assumption that these infants consumed 800 ml of breast milk every day, resulting in 10-11 mSv for Mito and Kasama cities and 1.1-1.8 mSv for Tsukuba and Moriya cities. It was suggested that breast milk consumption could be a major contributor to internal dose of breast-fed infants in areas with mild I-131 pollution; however, further studies considering personal behavior surveys would be necessary to estimate individual doses.

  9. Uranium estimation in drinking water samples from some areas of Punjab and Himachal Pradesh, India using ICP-MS.

    PubMed

    Rani, Asha; Singh, Surinder; Duggal, Vikas; Balaram, V

    2013-11-01

    The uranium concentration in drinking water samples collected from areas of Punjab and Himachal Pradesh has been measured using inductively coupled plasma mass spectrometry. The sources of water comprise hand pumps and tube wells. The uranium concentration lies in the range of 1.24-45.42 µg l(-1) with a mean value of 14.91 µg l(-1) in drinking water samples from Punjab and 0.56-10.11 µg l(-1) with a mean value of 2.17 µg l(-1) in Himachal Pradesh. The measured uranium content in 4 % water samples from Punjab has been found to be higher than the limit of 30 µg l(-1) recommended by the World Health Organization (WHO) and US Environmental Protection Agency. However, the uranium concentration in all the water samples from Himachal Pradesh is well below the recommended limit. The annual effective dose associated with drinking water due to uranium concentration is estimated from its annual intake using dosimetric information based on International Commission on Radiological Protection 72. The resulting value of the annual effective dose from drinking water sources is in the range of 0.33-37.78 µSv, which is well within the limit of 100 µSv recommended by the WHO.

  10. Potentiometric stripping analysis of antimony based on carbon paste electrode modified with hexathia crown ether and rice husk.

    PubMed

    Gadhari, Nayan S; Sanghavi, Bankim J; Srivastava, Ashwini K

    2011-10-03

    An electrochemical method based on potentiometric stripping analysis (PSA) employing a hexathia 18C6 (HT18C6) and rice husk (RH) modified carbon paste electrode (HT18C6-RH-CPE) has been proposed for the subnanomolar determination of antimony. The characterization of the electrode surface has been carried out by means of scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy and chronocoulometry. By employing HT18C6-RH-CPE, a 12-fold enhancement in the PSA signal (dt/dE) was observed as compared to plain carbon paste electrode (PCPE). Under the optimized conditions, dt/dE (sV(-1)) was proportional to the Sb(III) concentration in the range of 1.42×10(-8) to 6.89×10(-11)M (r=0.9944) with the detection limit (S/N=3) of 2.11×10(-11)M. The practical analytical utilities of the modified electrode were demonstrated by the determination of antimony in pharmaceutical formulations, human hair, sea water, urine and blood serum samples. The prepared modified electrode showed several advantages, such as simple preparation method, high sensitivity, very low detection limit and excellent reproducibility. Moreover, the results obtained for antimony analysis in commercial and real samples using HT18C6-RH-CPE and those obtained by inductively coupled plasma-atomic emission spectrometry (ICP-AES) are in agreement at the 95% confidence level.

  11. A Nest Experiment of the Indonesian Seas

    DTIC Science & Technology

    2007-04-01

    experiment • A subset of the GLBa0.08 experiment with interannual air-sea forcing (year 2003). Makassar Strait Lifamatola Passage Halmahera -New Guinea...time Makassar Strait Lifamatola Passage Halmahera -New Guinea ITF1: -7.33 Sv ITF2: -7.85 Sv ITF3: -7.99 Sv GLB: -8.51 Sv ITF1: -1.40 Sv ITF2: -1.57 Sv

  12. Feasibility of using 236U to reconstruct close-in fallout deposition from the Hiroshima atomic bomb.

    PubMed

    Sakaguchi, A; Kawai, K; Steier, P; Imanaka, T; Hoshi, M; Endo, S; Zhumadilov, K; Yamamoto, M

    2010-10-15

    The first results on the feasibility of using (236)U to reconstruct the level and spatial distribution of close-in fallout deposition from the Hiroshima A-bomb are reported, coupled with the use of global fallout (137)Cs and (239+240)Pu. The results for global fallout (236)U in soil samples (0-30cm) from Ishikawa prefecture showed that the deposition density of (236)U from the global fallout can be accurately evaluated using AMS. All deposited (236)U, (137)Cs and (239+240)Pu appeared to have been recovered using 30-cm cores. It was also noted from the depth profiles for (236)U/(239+240)Pu and (236)U/(137)Cs ratios that the downward behavior of (236)U in the soil was apparently similar to that of (239+240)Pu, while the (137)Cs was liable to be retained in upper layers compared with (236)U and (239+240)Pu. The accumulated levels were 1.78×10(13)atomsm(-2) for (236)U, 4340Bqm(-2) for (137)Cs and 141Bqm(-2) for (239+240)Pu. The ratios of (236)U/(137)Cs and (236)U/(239+240)Pu were (4.10±0.12)×10(9) and (1.26±0.04)×10(11)atomsBq(-1), respectively. Results of (236)U, (137)Cs and (239+240)Pu measurements for the seven soil cores (0-30cm) from Hiroshima were discussed on the basis of ratios of (236)U/(137)Cs and (236)U/(239+240)Pu by comparing with those from the background area in Ishikawa, indicating that the global fallout dominates the current level of (236)U accumulation in soil in the Black-rain area around Hiroshima after the Hiroshima bomb, and the contribution of the close-in fallout (236)U produced by the Hiroshima A-bomb seems difficult to observe.

  13. Estimation of Radiation Doses in the Marshall Islands Based on Whole Body Counting of Cesium-137 (137Cs) and Plutonium Urinalysis

    SciTech Connect

    Daniels, J; Hickman, D; Kehl, S; Hamilton, T

    2007-06-11

    measurement. The amount of {sup 137}Cs detected is often reported in activity units of kilo-Becquerel (kBq), where 1 kBq equals 1000 Bq and 1 Bq = 1 nuclear transformation per second (t s{sup -1}). [However, in the United States the Curie (Ci) continues to be used as the unit of radioactivity; where 1 Ci = 3.7 x 10{sup 10} Bq.] The detection of {sup 239}Pu and {sup 240}Pu in bioassay (urine) samples indicates the presence of internally deposited (systemic) plutonium in the body. Urine samples that are collected in the Marshall Islands from volunteers participating in the RSMP are transported to LLNL, where measurements for {sup 239+240}Pu are performed using a state-of-the-art technology based on Accelerator Mass Spectrometry (AMS) (Hamilton et al., 2004, 2007; Brown et al., 2004). The urinary excretion of plutonium by RSMP volunteers is usually described in activity units, expressed as micro-Becquerel ({micro}Bq) of {sup 239+240}Pu (i.e., representing the sum of the {sup 239}Pu and {sup 240}Pu activity) excreted (lost) per day (d{sup -1}), where 1 {micro}Bq d{sup -1} = 10{sup -6} Bq d{sup -1} and 1 Bq = 1 t s{sup -1}. The systemic burden of plutonium is then estimated from biokinetic relationships as described by the International Commission on Radiological Protection (e.g., see ICRP, 1990). In general, nuclear transformations are accompanied by the emission of energy and/or particles in the form of gamma rays ({gamma}), beta particles ({beta}), and/or alpha particles ({alpha}). Tissues in the human body may adsorb these emissions, where there is a potential for any deposited energy to cause biological damage. The general term used to quantify the extent of any radiation exposure is referred to as the dose. The equivalent dose is defined by the average absorbed dose in an organ or tissue weighted by the average quality factor for the type and energy of the emission causing the dose. The effective dose equivalent (EDE; as applied to the whole body), is the sum of the average

  14. DoD Source Selection: Competencies, Deficiencies, and Remedies

    DTIC Science & Technology

    2014-04-30

    Ascending section of line) S = SV – (V – LVL )/(SV/W) S = SV – (HVL – V)/(SV/W) Where: HO = Highest observed value HR = Highest possible...subjective rating HVL = High value limit L = Lowest observed value LVL = Low value limit OV = Optimal value R = Actual subjective

  15. A Numerical Study of Diffraction in Reentrant Geologic Structure.

    DTIC Science & Technology

    1985-07-15

    Geophysics Lab ~rator,,’,, This first tech - im ln,,.Jd_ fault- sca- s and other block ;ons Approximatinc these regons of high curvature • by Perfect...SvReflected SV Incidente SV Diffrated SP RDiffracte P Reflected PV Figure 2-25. Diffractions for SV-wave incidence from below for different qcometri

  16. Prospective Effects of Method of Coercion in Sexual Victimization Across the First College Year

    PubMed Central

    Griffin, Melissa J.; Read, Jennifer P.

    2014-01-01

    Women who enter college with a sexual victimization (SV) history may be at particular risk for deleterious outcomes including maladaptive alcohol involve posttraumatic stress, and re-victimization. Further, pre-college SV may be an impediment for the achievement of academic mile and may negatively impact the transition into college. Recent work shows that the method of coercion used in SV may be an important predictor of post-victimization outcomes. As such, the identification of pathways between type of SV and outcomes can aid in early identification and intervention for those at highest risk. In a sample of newly-matriculated female college students, this study examined unique outcomes associated with two specific types of SV, (1) threats/use of physical force (Force SV) or (2) incapacitation (Incap SV). Participants completed assessments of SV, alcohol involvement, posttraumatic stress, and academic outcomes at 6 time-points over their first year of college. Results showed differential outcomes based on pre-matriculation exposure to Force SV or Incap SV. Women with Incap SV were higher on problem drinking indices whereas women with Force SV were at greater risk for re-victimization and marginally more PTSD symptoms. Having a history of either type of SV predicted attrition, but there were no differences when comparing Force SV to Incap SV. Overall, results from this study support the utility of delineating SV experiences by method of coercion, and point to the potential of highlighting different outcomes in tailored intervention programs. PMID:22279126

  17. Identification and fine mapping of quantitative trait loci for seed vigor in germination and seedling establishment in rice.

    PubMed

    Xie, Lixia; Tan, Zhengwei; Zhou, Yuan; Xu, Rongbao; Feng, Laibao; Xing, Yongzhong; Qi, Xiaoquan

    2014-08-01

    Seed vigor is an index of seed quality that is used to describe the rapid and uniform germination and the establishment of strong seedlings in any environmental conditions. Strong seed vigor in low-temperature germination conditions is particularly important in direct-sowing rice production systems. However, seed vigor has not been selected as an important breeding trait in traditional breeding programs due to its quantitative inherence. In this study, we identified and mapped eight quantitative trait loci (QTLs) for seed vigor by using a recombinant inbred population from a cross between rice (Oryza sativa L. ssp. indica) cultivars ZS97 and MH63. Conditional QTL analysis identified qSV-1, qSV-5b, qSV-6a, qSV-6b, and qSV-11 influenced seedling establishment and that qSV-5a, qSV-5c, and qSV-8 influenced only germination. Of these, qSV-1, qSV-5b, qSV-6a, qSV-6b, and qSV-8 were low-temperature-specific QTLs. Two major-effective QTLs, qSV-1, and qSV-5c were narrowed down to 1.13-Mbp and 400-kbp genomic regions, respectively. The results provide tightly linked DNA markers for the marker-assistant pyramiding of multiple positive alleles for increased seed vigor in both normal and low-temperature germination environments.

  18. Response to "Comment on "Conformational analysis of small organic molecules using NOE and RDC data: A discussion of strychnine and α-methylene-γ-butyrolactone" by I.A. Khodov, M.G. Kiselev, V.V. Klochkov, S.V. Efimov [http://dx.doi.org/10.1016/j.jmr.2016.02.009]" - Or Life is about compromises

    NASA Astrophysics Data System (ADS)

    Thiele, Christina M.; Kolmer, Andreas

    2016-05-01

    Since the very early days of the Nuclear Overhauser Effect (NOE) researchers try to obtain distance information from the NOE and correlate it with structure. It is quite accepted by now that NOE intensities and cross relaxation rates can be measured quantitatively. In terms of deducing structures from NOEs, however, structural models and approximations have to be used, especially if conformational flexibility is present. For a recent review article, see [1].

  19. 78 FR 339 - Proposed Collections; Comment Requests

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-03

    ... soliciting comments concerning the revisions of the Treasury International Capital (TIC) Forms BC, BL-1, BL-2, BQ-1, BQ-2, and BQ-3 (called the ``TIC B forms''). DATES: Written comments should be received on or... Treasury's TIC Forms Web page,...

  20. 76 FR 58087 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... are available on the Treasury's TIC Forms Web page, http://www.treasury.gov/resource-center/data-chart-center/tic/Pages/forms.aspx . Requests for additional information should be directed to Mr. Wolkow.... Abstract: Form BQ-1 is part of the Treasury International Capital (TIC) reporting system, which is...